In-Depth Reports

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Summary of Evidence Related to COVID-19 Vaccine Effectiveness and Breakthrough Infections

May 14, 2021

COVID-19 Literature Report Team:

Brandon L. Guthrie PhD, Lorenzo Tolentino MPH, Jessie Seiler MPH,
Rodal Issema MPH, Molly Fisher MPH, Emily Rowlinson MPH,
Francis Slaughter BA, Mark Fajans MPH, Ashley Tseng MPH
Sherrilynne Fuller PhD FACMI, Dylan Green MPH, Diana Louden MLib,
Alison Drake PhD MPH, Will Hahn MD, Jennifer M. Ross MD MPH,

There are currently three COVID-19 vaccines authorized under an Emergency Use Authorization in the US and across the US, everyone 16 years or older is currently eligible for vaccination with at least one of the vaccines, with expansion of eligibility down to age 12 likely soon. The vaccine coverage among eligible individuals remains uneven, but high coverage among adults has been achieved in some settings. While all currently authorized vaccines have high or very high effectiveness to prevent both SARS-CoV-2 infection and COVID-19 disease, some vaccinated individuals do become infected with SARS-CoV-2, resulting in what is revered to as a “breakthrough infection”. This document is a brief summary of published evidence related to COVID-19 vaccine effectiveness and breakthrough infections. Included are manuscripts published in peer-reviewed journals or on pre-print servers through May 12, 2021. References summarized in this report were drawn from the COVID-19 Literature Report (Lit Rep) team database. References that appeared in the daily Lit Rep are marked with an asterisk*, and the summary is shown in the annotated bibliography below.

View the full PDF version here.

Executive Summary of Evidence Related to COVID-19 Vaccine Efficacy and Breakthrough Infections

All COVID-19 vaccines currently authorized for use under an Emergency Use Authorization in the US (Pfizer-BioNTech, Moderna, and Johnson & Johnson-Janssen) showed high vaccine efficacy (66% to 95%) to prevent COVID-19 disease in phase 3 efficacy trials.

Real-world effectiveness of the currently authorized vaccines has matched the efficacy observed in the trial results.

Effectiveness of the currently authorized vaccines has been similar across all age groups, but there is some indication that breakthrough infections are somewhat more common among older individuals and those who may be immunocompromised, including recipients of solid organ transplants.

Vaccine effectiveness has been high among residents and staff in skilled nursing facilities, with some indication that nursing home residents who have recovered from a past SARS-CoV-2 infection tend to mount more robust immune responses following vaccination. Partial vaccination has shown >60% effectiveness among nursing home residents.

Vaccinated individuals who subsequently become infected with SARS-CoV-2 are more likely to have asymptomatic or milder cases of COVID-19 and have lower viral loads compared to unvaccinated individuals who become infected. There is also direct and indirect evidence that vaccinated individuals who become infected are less likely to transmit the virus to others.

All vaccines currently authorized for use in the US have shown effectiveness against the B.1.1.7 variant of SARS-CoV-1 that is comparable to earlier viral strains.

Vaccine-induced immune responses show lower levels of neutralization against the B.1.351 and P.1 variants in laboratory tests, but the effectiveness of the currently authorized vaccines do not appear to be diminished to a substantial degree against B.1.351 or P.1, particularly for prevention of severe disease.
Similarly lower neutralization has been observed against a number of the newer variants of concern, but there is no evidence at this time that the vaccine effectiveness is reduced against any of these variants. There is not yet enough evidence to draw strong conclusions about the effectiveness of vaccines against the newest emerging variants.

Summary of Vaccine Effectiveness

Pfizer-BioNTech

The efficacy trial results used to support Emergency Use Authorization of the 2-dose mRNA Pfizer-BioNTech vaccine (BNT162b2) showed a vaccine efficacy of 95%, with 8 cases of COVID-19 (1 severe case) in the vaccine group and 162 cases (9 severe cases) in the placebo group (n=21,720 in vaccine group, and 21,728 in placebo group) (Polack*). Efficacy was similar across subgroups defined by age, sex, race, ethnicity, body-mass index, and presence of co-existing conditions.

There is consistent evidence from multiple countries and settings that the Pfizer-BioNTech vaccine has maintained high effectiveness (85% to 95%) in real-world settings (Haas*, Tang*, Vasileiou*, Hall*, Goldberg*, Bjork*, Jones*), with preliminary evidence that wide-scale immunization of the population has resulted in declines in the community incidence of infection and cases of severe disease and death (Rossman*, Salazar*). At 21-44 days after a single vaccine dose, vaccine effectiveness was 72% in a large population-based study in the UK (Menni*).

Impact of Variants of Concern on the Pfizer-BioNTech Vaccine Effectiveness

The Pfizer-BioNTech COVID-19 vaccine has shown comparable effectiveness against the B.1.1.7 variant relative to the strains circulating at the time of the original efficacy trial (Munitz*, Abu-Raddad*, Haas*). There is less direct evidence of the vaccine’s effectiveness against the B.1.351 and P.1 variants, but recent evidence indicates that the Pfizer-BioNTech vaccine is 75% effective against the B.1.351 variant 14 days after the second dose (Abu-Raddad*, Kustin*). In vitro neutralization assays show lower neutralization activity against these variants, although there is general consensus that the observed decrease in neutralization is unlikely to dramatically affect the vaccine effectiveness against these variants (Stankov*, Lustig*, Bates*, Jangra*). There is similar indirect evidence of maintained effectiveness against a number of the newer emerging variants (e.g., B.1.429, B.1.427, B.1.617, R.1).

Moderna

The efficacy trial results used to support Emergency Use Authorization of the 2-dose mRNA Moderna vaccine (mRNA-1273) showed 94% efficacy at preventing COVID-19, including severe disease (n=15,210 placebo, 15,210 vaccine) (Baden*). Efficacy was similar across key secondary analyses, including in participants who had evidence of SARS-CoV-2 infection at baseline and analyses in participants 65 years of age or older. Serious adverse events were rare, and the incidence was similar to placebo.

The Moderna vaccine has demonstrated high real-world effectiveness (Andrejko*), including evidence that partial immunization may lower the risk of hospitalization by 77% and the risk of death by 64% (Vahidy*)

Impact of Variants of Concern on the Moderna Vaccine Effectiveness

The ability of sera from individuals vaccinated with the Moderna vaccine to neutralize a number of the variants of concern, particularly B.1.351, has been shown to be lower than for early strains of SARS-CoV-2 (Edara*). However, there is currently no evidence that the effectiveness of the Moderna vaccine is substantially lower against the currently circulating variants.

Johnson & Johnson-Janssen

The efficacy trial results used to support Emergency Use Authorization of the 1-dose Johnson & Johnson-Janssen vaccine (Ad26.COV2.S) showed 66% efficacy at preventing moderate to severe–critical COVID-19 and a 77% efficacy for prevention of severe–critical COVID-19 (n=19,691 placebo, 19,630 vaccine) (Sadoff*). There is some evidence that the Johnson & Johnson-Janssen vaccine is associated with very rare but serious and sometime fatal blood clots. A review by the FDA and CDC concluded that the benefits of the vaccine outweigh the risks and have resumed authorization of the vaccine after a short pause to review the evidence of these side effects (MacNeil*)

Impact of Variants of Concern on the Johnson & Johnson-Janssen Vaccine Effectiveness

The efficacy of the Johnson & Johnson-Janssen vaccine to protect against severe to critical COVID-19 was equivalent in South Africa (82% at ≥28 days after vaccination), where the B.1.351 variants accounted for 95% of infections, compared to other regions where the B.1.351 variant was not circulating (86% in the US and 88% in Brazil) (FDA*, Sadoff*). The efficacy of the Johnson & Johnson-Janssen vaccine against moderate COVID-19 was somewhat lower in South Africa (64%) compared to the US (72%) and Brazil (82%).

Variants of Concern and Vaccine Effectiveness

A list of variants of concern is maintained by the CDC, including a summary of evidence regarding the susceptibility of each variant to the current vaccines. Overall, all vaccines currently authorized for use in the US have shown high effectiveness against all variants of concern (Lustig*, Munitz*, Stankov*, Goel*), although the effectiveness may be somewhat lower compared to earlier strains of the virus, particularly for prevention of asymptomatic or mild to moderate illness (Sadoff*). Across all of the vaccines currently authorized for use in the US, effectiveness appears to be similar against the B.1.1.7 variant compared to other viral lineages (Emary*, Abu-Raddad*). The Pfizer-BioNTech vaccine was found to be 75% effective against the B.1.351 variant 14 days after the second dose in a population-based study from Qatar (Abu-Raddad*). The AstraZeneca vaccine, which is not currently authorized for use in the US but is widely used around the world, has shown dramatically lower efficacy (~10%) against mild or moderate COVID-19 caused by the B.1.351 variant (Madhi*).

Across multiple studies, neutralization assays indicate somewhat lower neutralization activity against the B.1.1.7 variant compared to other viral lineages (Xie*, Wu*, Weisblum, Supasa*, Edara*, Chang*, Trinite*). Authors have generally concluded that these modest reductions in neutralization activity are unlikely to result in reduced vaccine efficacy. Considerably larger reductions in neutralizing activity against the B.1.351 variant have been observed (Garcia-Beltran*, Liu*, Wu*, Diamond*, Fisher*, Becker*, Chen*) and authors have expressed concerns that this could indicate lower vaccine efficacy against B.1.351. Evidence has varied regarding the susceptibility of the P.1 variant, which was first described in Brazil, to vaccine-induced neutralization, but it appears that P.1 may be more susceptible to vaccine neutralization than the B.1.351 variant (Dejnirattisai*, Wang*). Administration of a third booster dose of the Moderna vaccine 6 months after the two-dose series induced increases in antibody neutralization titers to the wild type and variant strains B.1.351 and P.1 (Wu). However, the relationship between levels of in vitro neutralization and actual vaccine effectiveness remains unclear and there is no currently accepted correlate of immunity.

Breakthrough Infections

Prevention of asymptomatic infection and effectiveness of partial vaccination

In addition to preventing symptomatic infections, there is evidence that vaccination is also effective at preventing asymptomatic infection (Tande*, Angel*). At least over a relatively short period of follow-up, partial vaccination with only one does of the Pfizer-BioNTech, Moderna, and Oxford-AstraZeneca vaccines has shown a level of effectiveness that is slightly lower but approaching the level of protection seen with full vaccination (Menni*, Bouton*, Yelin*, Britton*, Krammer*, Moustsen-Helms*, Bernal*, Saul*, Manisty*, Romero-Brufau*).

Disease severity and viral load in vaccinated individuals who become infected

While infections with SARS-C-V-2 occur among individuals who have been vaccinated with one of the vaccines authorized for use in the US (Hacisuleyman*), there is consistent evidence that such infections are more likely to be asymptomatic or of lower severity compared to unvaccinated individuals of comparable age and health status (Hollinghurst*, Moustsen-Helms*, Britton*, Gray*). Additionally, viral loads measured in vaccinated individuals who become infected with SARS-CoV-2 tend to be lower than in unvaccinated individuals, even following a single dose of the Pfizer-BioNTech vaccine (Jones*), indicating that the risk of secondary transmission from infected vaccinated individuals may be reduced (Harris*). These findings appear to be consistent across the viral variants of concern that have been widely circulating as vaccination rollout has occurred (e.g., B.1.1.7, B.1.351, P.1), but there is not yet clear direct evidence for or against protection against more severe illness or lower viral loads for newer emerging variants.

Factors associated with breakthrough infections

In the efficacy trials conducted in advance of Emergency Use Authorization, the currently authorized vaccines showed similar efficacy across all age groups. Under real-world conditions, there is some indication that breakthrough infections are somewhat more common among older individuals (Nace*, Canaday*) and those who may be immunocompromised (Chavarot*, Herishanu*, Grupper*, Simon*, Yelin, Pellini*, Monin*), including recipients of solid organ transplants (Boyarsky*, Rozen-Zvi*), although no strong associations have been observed between age and vaccine effectiveness (Vahidy*). Among those over age 65 years, mRNA vaccines were 94% effective against hospitalization for COVID-19 among fully vaccinated individuals in the US and 64% effective among partially-vaccinated individuals (Tenforde*), but antibody titers following vaccination have been observed to be lower among those older than 80 years compared to those younger than 60 (Müller*). There is some indication that antibody responses after the first vaccine dose may be lower among pregnant and lactating women but comparable to non-pregnant women after the second dose (Atyeo*, Rottenstreich*, Prabhu*). There is some indication that individuals who have previously been infected with SARS-CoV-2 and have recovered tend to mount more rapid and robust immune responses following a first vaccine dose compared to SARS-CoV-2-naïve individuals (Anichini*, Mishra*, Ebinger*), including among nursing home residents (Blain*, Van* Praet*), which may indicate more rapid protection from subsequent infection among vaccinated individuals who have recovered from a previous infection. However, there is currently no evidence to indicate whether previous infection is association with higher vaccine efficacy at ≥14 days after a second vaccine dose (or after the first dose for the Johnson & Johnson-Janssen vaccine).

Skilled nursing facilities

The widespread vaccination of residents and staff in skilled nursing facilities (SNFs) has provided direct evidence of the real-world effectiveness of the currently authorized vaccines in this population, with indication that the vaccines have remained highly effective among SNF residents and staff. In Chicago between December 2020 and March 2021, during which an estimated 7,931 SNF residents and 6,834 staff members received two doses of COVID-19 vaccine, a total of 627 SARS-CoV-2 infections in residents (n=353) and staff (n=274) were identified across 78 SNFs (Teran*). Of these infections, 71% occurred in unvaccinated individuals, 23% in partially vaccinated, 2% in those with 2 vaccine doses but within <14 days of the second dose, and 4% in fully vaccinated individuals. The rollout of vaccinations coincided with a sharp drop in the incidence of infections in this population. In a separate investigation in Kentucky among SNF residents and healthcare personnel (HCP), compared to those who were vaccinated, unvaccinated residents had a 3-fold higher risk of SARS-CoV-2 infection and unvaccinated HCPs had a 4.1-fold higher risk, indicating that vaccine effectiveness was similar among residents and HCPs (Cavanaugh*). This investigation was conducted at a time when the R.1 variant was widely circulating. Partial vaccination of nursing home residents with the Pfizer-BioNTech vaccine was found to be 63% effective at preventing infection with SARS-CoV-2 (Britton*).

Healthcare workers

Healthcare workers were among the first to be prioritized for vaccination and there is now clear evidence of high vaccine effectiveness among healthcare workers. In large cohort studies of healthcare workers, the currently authorized mRNA vaccines have shown to be 85% to greater than 95% effective in preventing PCR-confirmed SARS-CoV-2 infection following two doses, with 70% to 78% effectiveness among those who had received only one dose of the vaccine (Swift*, Hall*, Angel*, Tang*). Similarly, in the UK, an increase in vaccine coverage up to 83% with a single vaccine dose was associated with significant reductions in symptomatic and asymptomatic cases of SARS-CoV-2 (Lillie*).

Other Resources

PREVIOUS IN-DEPTH REPORTS

Summary of Evidence Related to Travel, Hospitality and Service Industries, and COVID-19 Risk

April 6, 2021

COVID-19 Literature Report Team:

Ashley Tseng MPH, Lorenzo Tolentino MPH, Jessie Seiler MPH,
Rodal Issema MPH, Molly Fisher MPH, Emily Rowlinson MPH,
Francis Slaughter BA, Mark Fajans MPH
Sherrilynne Fuller PhD FACMI, Dylan Green MPH, Diana Louden MLib,
Alison Drake PhD MPH, Will Hahn MD, Jennifer M. Ross MD MPH, Brandon L. Guthrie PhD

Prior to the COVID-19 pandemic, travel was a large part of most individuals’ lives – whether it was for work, leisure, or to visit family. Pre-departure and post-arrival testing and quarantining have become major public health surveillance components of traveling in the last year. Much of the travel industry has been affected by the pandemic, and despite many restrictions in response to the pandemic, essential workers have remained dedicated to their in-person responsibilities while individuals have continued to travel both domestically and internationally. This document is a brief summary of published evidence related to the role of travel in the transmission of SARS-CoV-2 and considerations for traveling during the pandemic. Included are manuscripts published in peer-reviewed journals or on pre-print servers through April 1, 2021. References summarized in this report were drawn from the COVID-19 Literature Report (Lit Rep) team database. References that appeared in the daily Lit Rep are marked with an asterisk*, and the summary is shown in the annotated bibliography below.

View the full PDF version here.

Executive Summary of Evidence Related to Travel in the Context of COVID-19

Pre-departure testing for SARS-CoV-2 alone may not be effective at preventing positive individuals from traveling. Addition of post-arrival screening and testing procedures may reduce the risk of travelers spreading SARS-CoV-2 at their destinations. Symptom-based screening alone has been largely ineffective and resource-intensive given its low yield and misses a large proportion of infected travelers due to asymptomatic infections.
A 10-day quarantine may be sufficient to reduce the risk of transmission. A 7-day quarantine may be feasible when coupled with a negative COVID-19 PCR test on the last day.
CDC guidance recommends that people who are fully vaccinated with an FDA-authorized vaccine can travel safely within the US. Fully vaccinated travelers do not need to get tested before or after travel unless their destination requires it, and do not need to self-quarantine.
In-flight transmission of SARS-CoV-2 can occur between passengers and crew members despite facemask use, with closer seating proximity associated with greater infection risk through aerosol and/or respiratory droplet transmission.
Air travel played a major role in importation of cases internationally early in the pandemic, though domestic US travel is responsible for much of the subsequent spread of SARS-CoV-2 throughout the US.
Workplace-related outbreaks have been reported across the US since March 2020, with bartenders, waiters, transport conductors and travel stewards at elevated risk of transmission in subsequent waves of the pandemic. In public-facing professions, transmission risk is lower when both employees and clients are wearing facemasks.

Pre-Departure & Post-Arrival COVID-19 Procedures

Pre-Departure Screening & Testing

While domestic and international travel slowed significantly during the COVID-19 pandemic, airports and airlines nonetheless continued to operate. As a result, airlines adopted new pre-departure policies including COVID-19 screening questions for travelers during flight check-in and some destinations have required a negative pre-departure SARS-CoV-2 test. A rapid field study conducted in the Kahului main airport in Maui, Hawaii showed that there is reason to be concerned that pre-departure testing will not fully eliminate importation of SARS-CoV-2 due to the delay between the time a person becomes infected and when they will have a positive test result (Hou*). This may be particularly true with self-administered home test that have a lower sensitivity in the presence of lower viral loads, which can occur early in infection.

A rapid field study conducted at the Kahului main airport identified 2 SARS-CoV-2 PCR positive participants out of 279 consecutively sampled participants boarding for departure, despite all participants having a negative PCR test 72 hours prior (Hou*). This positivity rate corresponded to 7 cases per 1,000 travelers, which corresponds to an estimated 52-70 infected travelers arriving daily to Hawaii during November to December 2020.

Pre-departure testing alone does not appear to be sufficient to prevent positive individuals from traveling and it may be beneficial to combine pre-departure testing with post-arrival screening and testing procedures. A model showed that the effectiveness of testing depended on timing and quality of the test, with the combination of a pre-travel test and a post-travel test 2 to 3 days after arrival reducing the risk of transmission by 45% to 70% (Johansson*). A different mathematical model developed to quantify the probability of post-quarantine transmission in the context of travel found that SARS-CoV-2 testing on exit could reduce the duration of a 14-day quarantine by 50%, while testing on entry shortened quarantine by at most one day (Wells*).

In terms of traveling during the holidays, an online panel survey administered to individuals from 10 US states (n = 7,905) found that planned travel over the December holidays was more common among those who tested positive for SARS-CoV-2 in the prior 2 weeks (67%) compared with 25% of those who tested negative in the prior 2 weeks and 11% among those who were not tested. (Mehta*).

Post-Arrival Screening, Testing & Quarantining

Pre-departure testing alone does not appear to be sufficient to prevent positive individuals from traveling and it may be beneficial to combine pre-departure testing with post-arrival screening and testing procedures. While the responsibility for pre-departure screening and testing has primarily been on travelers and airlines, different countries and US states have adopted various post-arrival screening, testing, and quarantining tactics. Screening and testing individuals traveling by air upon arrival, and repeated testing during quarantine, can prevent community transmission in the destination country (Murphy*; Yang*). A model showed that the effectiveness of testing depended on timing and quality of the test, with the combination of a pre-travel test and a post-travel test 2 to 3 days after arrival reducing the risk of transmission by 45% to 70% (Johansson*). A different mathematical model developed to quantify the probability of post-quarantine transmission in the context of travel found that SARS-CoV-2 testing on exit could reduce the duration of a 14-day quarantine by 50%, while testing on entry shortened quarantine by at most one day (Wells*). Another study found that testing and 7-day quarantine could prevent 88% of secondary cases while 14-day quarantine without testing could prevent 84% of secondary cases (Dickens*). In a modeling study, quarantining an infected traced contact for 10 days was estimated to prevent 75% to 99% of their onward transmission (Ashcroft*). A quarantine period of eight days for air travelers arriving to the UK with a PCR test on day-7 was concluded to reduce the number of infectious arrivals released into the community by a median 94% when compared with no quarantine; this reduction is similar to the 99% median reduction achieved by a 14-day quarantine period (Clifford*). Thus, a 10-day quarantine may be sufficient to reduce the risk of onward transmission. A 7-day quarantine may be feasible when coupled with a negative COVID-19 PCR test on the last day.

Symptom-based screening has been shown to be largely ineffective and resource-intensive (Dollard*). Post-arrival COVID-19 testing is particularly important to identify asymptomatic carriers (Wong*, Al-Qahtani*). A study from Japan found that symptom-based testing of travelers missed most prevalent cases of SARS-CoV-2 at entry. Even with universal screening, nearly half of cases would have been missed without repeated testing over a 14-day period (Arima*).

From mid-January to mid-September, a total of 766,044 travelers were screened, 298 (0.04%) of whom met criteria for public health assessment (Dollard*). 35 of those passengers (0.005%) were tested for SARS-CoV-2, and nine (0.001%) were positive. Overall, this approach yielded about one case for every 85,000 travelers screened.

In January 2020, 566 Japanese nationals were repatriated from Wuhan, China and were monitored for 14 days following their return. Universal RT-PCR testing identified 12 cases of SARS-CoV-2 infection over this period. Entry screening only detected 7 of 12 cases, 2 of whom were symptomatic and 5 of whom were asymptomatic. Subsequent testing identified 5 additional cases among individuals whose first RT-PCR test result was negative (Arima*).

In-Flight (Airplane) Transmission of SARS-CoV-2

A number of studies have documented transmission of SARS-CoV-2 occurring during commercial flights, with evidence of in-flight transmission between passengers and crew members despite face mask use (Choi*, Swadi*, Yang*). Closer seating proximity has been associated with greater infection risk through aerosol and/or respiratory droplet transmission without direct person-to-person contact (Eichler, Hoehl*, Khanh*). There is evidence that transmission took place through shared spaces on the aircraft (e.g., the toilet) (Bae*). For longer flights, it has been estimated that the average infection probability can be reduced by approximately 73% for passengers wearing high-efficiency masks compared to 32% for passengers wearing low-efficiency masks (Wang*).

Geographic Spread of SARS-CoV-2 Through Travel

Domestic US Travel

The evolution of and increased geographic range of novel SARS-CoV-2 variants has been largely attributable to the spread of SARS-CoV-2 through individuals travelling domestically. For most states in the US, domestic travel contributed to the largest proportion of imported infections (Davis*) and subsequent localized outbreaks (McNamara*, Shen*, Zeller*). California has been central to introductions of SARS-CoV-2 into the US (Deng*, Shen*). The B.1.1.7 variant, which was first detected in the UK, was introduced to the US by international travelers then likely subsequently spread from state-to-state through individuals who had traveled domestically (Firestone*, Long*). Phylogenetic analyses suggested that New York acted as a hub for B.1.1.7 importation and spread to other states, and the study found evidence for community transmission of B.1.1.7 in New York, New Jersey, Connecticut, and Illinois during January 2021 (Alpert*).

Strong dose-response relationships between frequency of movement (e.g., traveling for non-essential services) and self-reported SARS-CoV-2 positivity among Maryland residents (Clipman*). Travel using public transport such as trains and taxis are associated with a history of SARS-CoV-2 infection even after adjusting for social distancing (Clipman*; Sami*), and with longer travel duration times (Hu*). Further, more (60% vs. 32%) seropositive participants traveled by taxi after the cancellation of nonessential gatherings in Washington DC during March 2020 (Sami*). Prior to the Colorado stay-at-home order in March, the most common potential exposures of residents who tested positive for SARS-CoV-2 were gatherings of >10 people, domestic travel, working in or visiting a health care setting, and using public transportation (Marshall*).

International Travel

SARS-CoV-2 transmission through international travel has been a major topic of concern in regard to importation of novel variants. Early in the SARS-CoV-2 epidemic, most cases were linked to recent travel history from China or Europe, suggesting that air travel played a major role in importation of cases (De Salazar*), and was responsible for 90% of case importations by early February 2020 in South Africa, Algeria, and Kenya (Menkir*). The P.1 variant, which was first identified in Brazil, has been identified among travelers to Brazil upon returning to their home countries, including the US, Japan, and Italy (Firestone*, Fujino*, Maggi*). For the B.1.1.7 variant, two studies linked index cases in Minnesota and Texas to the individuals’ recent travel history to the UK (Firestone*, Ojelade*). A modeling study assessing the global impact of travel restrictions due to COVID-19 concluded that restrictions are effective primarily in countries with low numbers of cases or that have strong travel links with countries experiencing high rates of infection (Russell*).

Transmission of SARS-CoV-2 During Travel Events

Large travel events have been associated with outbreaks of SARS-CoV-2 infections, sometimes referred to as ‘superspreader’ events, occurring largely because public health guidelines (e.g., physical distancing, avoidance of large gatherings, facemask use) were not followed. A college spring break trip in 2020 resulted in SARS-CoV-2 infection in 60 (28%) college-aged travelers and their contacts who were included in the outbreak investigation, one-fifth of whom were asymptomatic at the time of testing (Lewis*). Evidence suggests that the 2020 Mardi Gras celebration in New Orleans was likely a superspreading event, based on the unusual lack of genetic diversity of SARS-CoV-2, which was similar to cruise ship outbreaks, and the markedly increased infection rate in New Orleans immediately following the event (Zeller*). Among Chinese tour groups traveling in Europe in 2020, it was observed that initial SARS-CoV-2 transmission occurred in family groups and later transmission within and across tour groups (Kong*). High COVID-19 incidence was reported on a cruise ship from Uruguay to Australia, with the majority of cases being asymptomatic (42% vs. 14%), suggesting great underestimation of SARS-CoV-2 cases by symptom-based screening only (Bailie*). This is in concordance with the findings from other studies evaluating symptom screening vs. testing (see the Post-Arrival Screening, Testing & Quarantining section).

Occupational Risk in Travel and Hospitality Industries

Workplace-related outbreaks have been reported across the US since March 2020 (Bui*; Pasco*; Rao*; Sami*). In terms of public-facing occupations, average transmission risks were lower when both employees and clients were wearing facemasks (Harrichandra*; Hendrix*). In Columbia, among a cohort of airport workers, those who used public transportation had a high perception of COVID-19 risk and risk perception of strongly influenced by practices related to work conditions and environments, and most COVID-19 cases in the cohort were asymptomatic (84%) (Malagón-Rojas*). In the Netherlands, hospitality and public transport workers, driving instructors, hairdressers and aestheticians had higher test positivity compared with a reference group of individuals without a close-contact occupation, while workers in childcare, education and healthcare showed lower test positivity (de Gier). A study in Norway showed that nurses, physicians, dentists, physiotherapists, bus/tram and taxi drivers had 1.1- to 4-times the odds of COVID-19 during the 1st wave, whereas bartenders, waiters, transport conductors and travel stewards had 1.1- to 3-times the odds of COVID-19 during the 2nd wave (when compared to everyone else) (Magnusson).

There are a variety of precautions being taken among restaurants and bars to prevent transmission of SARS-CoV-2 between patrons and employees. Among interviews with 16 restaurants in Milwaukee, Wisconsin, 81% of restaurants required employees to wear face masks, 94% had disposable gloves available for employees, 38% did temperature checks on their employees, and 15 restaurants conducted specific sanitation procedures for COVID-19 and believed they were following CDC precautions, although only 4 of the 15 were actually following all of the current guidelines (Drake). In Europe, incidence of COVID-19 among bartenders and waiters declined by similar amounts in municipalities that implemented full bans on serving of alcohol in bars and restaurants (65% reduction) compared to municipalities that implemented partial bans (68% reduction) (Methi) and observations conducted in bars identified persistent potential risks of COVID-19 in many bars, especially when customers were intoxicated (Fitzgerald).

In the US, essential workers are disproportionally low-income persons of color who are more likely to face socioeconomic vulnerabilities, systemic racism, and health inequities (Roberts). Occupational segregation by race may contribute to racial disparities in SARS-CoV-2 infection (Chen*; Hawkins*). A study using death records from the California Department of Public Health found that during the COVID-19 pandemic, working age adults experienced a 22% increase in mortality compared to historical periods, which varied by race/ethnicity and occupational sector and occupation (Chen*). In Utah, 73% of persons with workplace outbreak-associated COVID-19 were identified as Hispanic or nonwhite, although these ethnic/racial groups represent <24% of Utah’s workforce in the 15 affected industry sectors (Bui*). In June 2020, 46% of non-remote, non–health care workers used measures to prevent COVID-19 (e.g., physical barriers, masks, and other personal protective equipment), with higher-income workers more likely to report required use and to use preventive measures compared to lower-income workers (Billock*).

Vaccines

CDC recommends delaying travel until individuals are fully vaccinated, but released guidance that people who are fully vaccinated with an FDA-authorized vaccine can travel safely within the US (CDC). According to these guidelines, fully vaccinated travelers do not need to get tested before or after travel unless their destination requires it, and they do not need to self-quarantine. CDC recommendations are available to people who are not yet fully vaccinated and must travel. Additional information about vaccines and viral variants can be found in the synthesis summaries.

Other Resources for Travelling During COVID-19

Accommodating Individual Travel History Global Mobility and Unsampled Diversity in Phylogeography: a SARS-CoV-2 Case Study – Biorxiv (June 23)
Body Temperature Screening to Identify SARS-CoV-2 Infected Young Adult Travellers Is Ineffective – Travel Medicine and Infectious Disease (Aug 5)
Occupational Safety and Health Administration (OSHA) and Worker Safety During the COVID-19 Pandemic – JAMA (Sept 16)
In-Flight Transmission of SARS-CoV-2: A Review of the Attack Rates and Available Data on the Efficacy of Face Masks – Journal of Travel Medicine (Sept 25)
Risk of COVID-19 During Air Travel – JAMA (Oct 1)
The Hospitality Industry in the Face of the COVID-19 Pandemic: Current Topics and Research Methods – International Journal of Environmental Research and Public Health (Oct 2020)
Navigating the Risks of Flying During COVID-19: A Review for Safe Air Travel – Journal of Travel Medicine (Nov 2020)
Challenges of SARS-CoV-2 prevention in flights, suggested solutions with potential on-site diagnosis resembling cancer biomarkers and urgency of travel medicine – European Review for Medical and Pharmacological Sciences (Dec 2020)
Covid-19: Air travelers should not be considered high risk, says European guidance – BMJ (Dec 4 2020)
The International Health Regulations (2005) and the Re-Establishment of International Travel amidst the COVID-19 Pandemic – Journal of Travel Medicine (Dec 23)
Risk of Symptomatic COVID-19 Due to Aircraft Transmission: A Retrospective Cohort Study of Contact-traced Flights during England’s Containment Phase – Influenza and Other Respiratory Viruses (Mar 1)
Cabin Crew Health and Fitness-to-Fly: Opportunities for Re-Evaluation amid COVID-19 – Travel Medicine and Infectious Disease (Mar 2021)
Travel During COVID-19 – CDC (April 2021

Summary of Evidence Related to
the Risk of Other Infections in the Context of COVID-19

March 10, 2021

COVID-19 Literature Report Team:

Brandon L. Guthrie PhD, Ashley Tseng MPH, Lorenzo Tolentino MPH, Jessie Seiler MPH, Rodal Issema MPH, Molly Fisher MPH, Sherrilynne Fuller PhD FACMI, Dylan Green MPH, Diana Louden MLib, Francis Slaughter, Mark Fajans MPH, Emily Rowlinson MPH, Alison Drake PhD MPH, Jennifer M. Ross MD MPH, Will Hahn MD

Severe COVID-19 is associated with critical illness and immune dysregulation, both of which have been previously associated with increased risk of nosocomial infection. The care of COVID-19 patients has required dramatic changes to usual hospital practices and heightened concern for infection control practices. This document is a brief summary of published evidence related to the effect of the COVID-19 pandemic on non-COVID infections. Included are manuscripts published in peer-reviewed journals or on pre-print servers through March 10, 2021. This summary does not consider the second order effects of increased antibiotics associated with COVID-19 on antimicrobial resistance. References summarized in this report were drawn from the COVID-19 Literature Report (Lit Rep) team database. References that appeared in the daily Lit Rep are marked with an asterisk*, and the summary is shown in the annotated bibliography below.

View the full report, which contains an annotated bibliography:

VIEW A PDF OF THE ENTIRE SUMMARY HERE

Executive Summary

Contamination of improperly used personal protective equipment likely contributed to an outbreak of nosocomial infection with Candida auris in a COVID-19-specific healthcare setting.
Evidence is currently inconclusive regarding the risk of healthcare facility acquired (nosocomial) infections in patients with COVID-19 and whether critical illness associated with COVID-19 creates a higher risk of nosocomial infections compared to other forms of critical illness.
The literature does not support routine use of empiric antibiotics in the management of confirmed COVID-19 infection.
Successfully implemented infection control practices in response to COVID-19 have been associated with a decrease in the incidence of hospital acquired Clostridiodes difficile.
The COVID-19 pandemic has been associated with a remarkable decline in other respiratory viruses, most notably influenza.

Outbreaks of Other Infections in Clinical Units Caring for Patients with COVID-19

At this time, outbreaks of fungal and bacterial infections in clinical units caring for patients with COVID-19 do not appear to be widespread; however ongoing surveillance is warranted to prevent such outbreaks in these settings. A cluster of infections with the yeast Candida auris was reported in a specialty care ward treating COVID-19 patients (Prestel*). Multiple studies have characterized changes in the frequency of infections with the common hospital-acquired bacterium Clostridioides (formerly Clostridium) difficile in the setting of COVID-19 care and have indicated that the incidence C. difficile has decreased in many healthcare facilities during the COVID-19 pandemic, potentially due to the implementation of stronger infection control measures.

Candida auris

C. auris is an emerging multidrug-resistant yeast that can cause invasive infection. Prior to the COVID-19 pandemic, outbreaks of C. auris have occurred in healthcare settings due in part to asymptomatic carriage and its persistence on surfaces (CDC, Tsay). Prevention and control measures have included aggressive implementation of contact tracing and screening in response to the identification of new cases. During July-August 2020, a hospital in Florida experienced an outbreak of C. auris that involved three C. auris bloodstream infections and one urinary tract infection in patients with COVID-19 who were being treated in a dedicated COVID-19 ward (Prestel*). Upon identification of these cases, screening of 67 patients admitted to the COVID-19 unit found that 35 (52%) had positive test results. An investigation of the outbreak concluded that widespread C. auris transmission was likely aided by the use of multiple gown and glove layers by the healthcare providers in the COVID-19 unit, extended use of the underlayer of personal protective equipment (PPE), lapses in cleaning and disinfection of shared medical equipment, and lapses in adherence to hand hygiene (Prestel*). After the hospital put in place measures to address these concerns, no subsequent C. auris cases were detected in follow-up surveys. The authors state that “CDC does not recommend the use of more than one isolation gown or pair of gloves at a time when providing care to patients with suspected or confirmed SARS-CoV-2 infection. Such practices among HCP might be motivated by fear of becoming infected with SARS-CoV-2 but instead might increase risks for self-contamination when doffing and for transmission of other pathogens among patients and exacerbate PPE supply shortages.”

Clostridioides (previously Clostridium) difficile

C. difficile is a common hospital acquired bacterial gastrointestinal infection with spores that are resistant to the alcohol-based sanitizers commonly used for hand hygiene in COVID-19 care. Hand hygiene procedures effective against C. difficile transmission include washing hands with soap and water. Antibiotic exposure is a risk factor for C. difficile. Several studies have characterized changes in C. difficile infection patterns in settings of COVID-19 clinical care. Luo et al found no significant difference in incidence of hospital-associated C. difficile episodes in a New York hospital despite a trend toward increased high-risk antibiotic exposures. A study from a hospital in Spain observed a 70% decrease in the incidence of hospital associated C. difficile during the COVID-19 pandemic compared to a pre-pandemic control period, despite no change in antibiotic use, which the authors attribute to the implementation of control measures to prevent nosocomial transmission by healthcare workers and asymptomatic colonized patients (Ponce-Alonso). Similar declines in hospital acquired C. difficile infections during the COVID-19 pandemic have been observed elsewhere (Bentivegna, Hazel).

Nosocomial Infections in Patients with COVID-19

Bacterial co-infections have been reported in hospital settings caring for patients with COVID-19, but the frequency of bacterial infections has been low. The Infectious Disease Society of America has concluded the following:

Current data indicate that bacterial coinfections with SARS-CoV-2 infection are relatively infrequent (likely occurring in <10% of hospitalized COVID-19 patients).
The literature does not support routine use of empiric antibiotics in the management of confirmed COVID-19 infection.
Objective findings that increase the concern for bacterial superinfection include rise in leukocyte counts, lobar consolidation or evidence of necrotizing infection on chest imaging and recrudescence of fever after initial defervescence.
Fungal superinfection (with Aspergillus) is also a concern, but the true incidence has not been defined. Risk factors for fungal superinfection include steroid use, invasive catheters and prolonged mechanical ventilation.
Antimicrobial stewardship programs can help optimize antimicrobial use during the pandemic. Continued investigation into optimal antimicrobial stewardship program interventions to limit antibiotic overuse during the COVID-19 pandemic is warranted.

A multicenter analysis of the clinical microbiology usage in hospitalized patients in the US found patients with COVID-19 had similar rates of non-SARS-CoV-2 co-infections compared to patients without COVID-19, but that COVID-19 disease was associated with higher rates of hospital-onset infections, greater antimicrobial usage, and extended hospital and ICU length of stay (Puzniak). In a case series of patients with COVID-19 in the UK, bacterial co-infections were identified in 3% of patients 0-5 days after admission and in 6% of patients throughout hospital admission (Hughes). Comparable rates of bacterial co-infection were identified in a control group of patients with confirmed influenza infection. In one study of samples with a positive co-infection culture from patients hospitalized in New York City during the first COVID-19 surge, the most commonly isolated organisms in respiratory infections were Staphylococcus aureus (44%), Pseudomonas aeruginosa (16%), Klebsiella spp (10%), Enterobacter spp (8%), and Escherichia coli (4%) (Nori). The most commonly isolated organisms in bloodstream infections were S. aureus (30%), Staphylococcus epidermidis (12%), Streptococcus spp (10%), Enterococcus spp (7%), E. coli (7%), P. aeruginosa (6%), Klebsiella spp (3%), and Enterobacter spp (3%).

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Invasive Pulmonary Aspergillosis

Several studies have raised concern that COVID-19 patients may be more susceptible to invasive fungal infections, particularly invasive pulmonary aspergillosis (IPA), through multiple mechanisms, including declines in lymphocyte counts and viral damage to airway tissues (Koehler). Several case series and observational cohort studies, most of which have involved relatively small numbers of patients, have found that 20-30% of patients with severe COVID-19, particularly those receiving mechanical ventilation, have invasive pulmonary aspergillosis, with a high case fatality (~65-75%) among these patients. However, the Infectious Disease Society of America has urged caution regarding these findings, outlining the limitations in interpreting these observational studies, and has concluded that currently, the true incidence of COVID-19 associated pulmonary aspergillosis is not known.

A literature review on the topic of IPA in patients with COVID-19 with severe or critical illness concluded that the incidence of IPA in patients with COVID-19 ranged from 20% to 33% (Lai). Most studies included in the literature review involved a relatively small number of patients (~30), although one study from Jiangsu Province, China from January 22 to February 2, 2020 found IPA in 60 (23%) out of 243 patients. The case fatality among patients with COVID-19 who were co-infected with IPA was high (65% among a cohort of 34 patients). In an Italian cohort of 108 patients with confirmed COVID-19 (4 ICUs from 3 hospitals) who were receiving mechanical ventilation, 28% were found to have pulmonary aspergillosis and 18% were classified as having putative IPA (Bartoletti). The 30-day mortality was significantly higher among patients with pulmonary aspergillosis (44% vs 19%, P = 0.002) and IPA (74% vs 26%, P < .001) compared to patients without aspergillosis. A summary of reports of pulmonary aspergillosis and guidance on diagnosis is provided by Armstrong-James et al.

Other studies have not found pulmonary aspergillosis to be common in COVID-19 patients. An investigation in a single center in France of 54 patients with COVID-19 with moderate to severe acute respiratory distress syndrome (ARDS) found that two patients (3.7%) showed early putative IPA, neither of whom had prior immunosuppression or host risk factors (Versyck*). Immunosuppression was observed in two patients, neither of whom had IPA. The authors conclude that the frequency of IPA among patients with COVID-19 with ARDS was relatively low and was similar to what has been described in other populations with ARDS.

Nosocomial infections associated with immunomodulatory treatments

There are two primary immunomodulatory therapies currently in use for the treatment of severe COVID-19. These include corticosteroids (primarily dexamethasone) and IL-6 blockers (primarily tocilizumab). Since each of these medications target the immune system, it is biologically plausible that they would be associated with secondary infections.

Tocilizumab

Studies have reported mixed results regarding the risk of secondary infections associated with tocilizumab. A systematic review found five studies have reported an increased prevalence of infection whereas twelve studies have reported either no association or reduced infections in patients treated with tocilizumab (Khan). The differences between these studies that lead to such wide discrepancies in results are unclear. It is worth noting that almost all studies followed patients for only 28 days, whereas the half-life of tocilizumab is long with the doses typically used for treatment in COVID-19 (8mg/kg intravenous), leading to a half-life of 18 days (Abdallah). One hypothesis for why some studies have found an elevated risk of infection in the placebo arm is that tocilizumab is very effective at suppressing fever, suggesting that there may be fewer investigations for infections performed (Strohbehn).

A randomized, double blind trial of severe COVID-19 determined that there were fewer “serious infections” in tocilizumab patients. Details regarding the nature of these infections are unclear (Stone). Industry-sponsored randomized trials have not found a difference in the risk of “serious” secondary infections when compared to placebo. These include COVACTA and EMPACTA (Salama, Rosas). In the former study, the majority of participants received glucocorticoids (~80%) whereas in the latter only 20-30% of participants received glucocorticoids. The RECOVERY Trial (a large multicenter public sector trial) did not find differences in “excess deaths from other infections” among patients who received tocilizumab. Another randomized trial in patients with moderate-to-severe COVID who were not intubated did not find a difference in secondary infections (Hermine). In India, the COVINTOC trial (open label) recently reported no differences in infections between treatment arm and standard of care (Soin).

Some observational studies of tocilizumab under real-work conditions have also found no increased risk of secondary infections (Ignatius, Campochino et al., Eur J Int Med 2020), while others have found a substantially elevated risk of infection, including some autopsy proved bacterial infections (Kimmig, Guaraldi).

Corticosteroids

We identified few investigations of the potential risk of secondary infections associated with short term corticosteroid use for the treatment COVID-19. The median duration of dexamethasone in the RECOVERY trial was seven days and no increases in other infections were reported (Horby*).

Indirect Effects of the COVID-19 Pandemic on Vaccination

Stay-at-home orders intended to reduce the transmission of SARS-CoV-2 and concerns about acquiring SARS-CoV-2 in health care settings had the indirect of effect of reducing the rate of administration of routine vaccinations, at least in the early phase of the pandemic (Lassi*). Vaccination rates for bacterial pneumonia, tetanus-diphtheria-pertussis, and shingles among Medicare beneficiaries over the age of 65 declined by 25% to 62% compared with the corresponding period in 2019, reaching a low point in mid-April 2020 and recovering slowly in between May and July 2020 (Hong*). While national vaccination coverage among US kindergarteners was high for the 2019-20 school year, despite most schools shifting to virtual learning in the spring due to the COVID-19 pandemic, the CDC authors caution that disruptions caused by the pandemic are likely to reduce vaccination coverage for the 2020-21 school year (Seither*).

Indirect Effects of the COVID-19 Pandemic on Other Respiratory Viruses

Widespread implementation of measures to prevent community transmission of SARS-CoV-2, including stay-at-home orders, physical distancing, use of facemasks, and other non-pharmaceutical interventions (NPI) appears to have had broad indirect effects on the transmission of other respiratory infections. Evidence from many settings has shown dramatically lower incidence of influenza, rhinovirus, enterovirus, and respiratory syncytial virus (RSV) infections following the implementation of NPIs to prevent SARS-CoV-2 compared to the same time period in years prior to the COVID-19 pandemic (Freeman*, Partridge*, Sherman*). An examination of temporal trends in the incidence of these infections indicates that they occurred at rates similar to previous years during the period immediately prior to the COVID-19 pandemic and declined rapidly following implementation of NPIs (Partridge*, Zhang*). Evidence from children’s hospitals indicates that declines in influenza, RSV, and hospitalization for lower respiratory infections have also declined substantially in children (Trenholme*).

Summary of Evidence Related to
Recreational, Youth, and Collegiate Sports and the Risk of COVID-19

February 24, 2021

COVID-19 Literature Report Team:

Brandon L. Guthrie PhD, Ashley Tseng MPH, Lorenzo Tolentino MPH, Jessie Seiler MPH, Rodal Issema MPH, Molly Fisher MPH, Sherrilynne Fuller PhD FACMI, Dylan Green MPH, Diana Louden MLib, Alison Drake PhD MPH, Will Hahn MD, Jennifer M. Ross MD MPH

Recreational, youth, and collegiate sports are an important component of physical and psychological health for many people. Many sports activities have been affected by the COVID-19 pandemic, and despite many closures in response to the pandemic, sports have restarted or remained open in many settings. This document is a brief summary of published evidence related to the role of recreational, youth, and collegiate sports in COVID-19 and SARS-CoV-2 transmission and considerations for conducting sports during the pandemic. Included are manuscripts published in peer-reviewed journals or on pre-print servers through February 24, 2021. This summary does not consider professional sports or the role of large spectator gatherings related to sports events in driving SARS-CoV-2 transmission. References summarized in this report were drawn from the COVID-19 Literature Report (Lit Rep) team database. References that appeared in the daily Lit Rep are marked with an asterisk*, and the summary is shown in the annotated bibliography below.

View the full report, which contains an annotated bibliography:

VIEW A PDF OF THE ENTIRE SUMMARY HERE

Executive Summary of Evidence Related to Recreational, Youth, and Collegiate Sports in the Context of COVID-19

Outbreaks of SARS-CoV-2 have been observed among youth and collegiate athletes, particularly in the context of indoor and contact sports. In documented outbreaks (e.g., hockey and wrestling), a high proportion of participating athletes have become infected (30% to 80%) and secondary transmission, particularly to household contacts, has been observed.
Asymptomatic or pre-symptomatic individuals have been the source of infection in a number of SARS-CoV-2 outbreaks linked to sports events.
Large scale youth sports, including team sports (e.g., soccer), have been conducted with little evidence of SARS-CoV-2 transmission. Successful examples of reopening sports have had high levels of mask usage and other risk reduction measures. The lowest incidence of COVID-19 has been observed for outdoor and non-contact sports.
Outbreaks of SARS-CoV-2 have occurred within collegiate athletic teams. In many cases, it appears that transmission was driven more by social gatherings than directly through athletic activities.
The American Academic of Pediatrics advises that children participating in athletic activities use cloth face masks during all indoor sports, except for swimming and diving, cheerleading, gymnastics, and wrestling. Cloth masks are also recommended for persons on the sidelines, in locker rooms, and in training sessions.
There is some evidence of heart muscle inflammation following COVID-19 and SARS-CoV-2 infection among youth and collegiate athletes. The American Academy of Pediatrics has issued revised guidelines for children returning to athletic activities after COVID-19.

Recreational Sports

Participation in recreational sports ranges from children of all ages to older adults and includes both individual and team sports. Additionally, recreational sports include activities that range from necessarily close contact between participants to individual activities with minimal contact between participants and from large teams to individual participants. Thus the potential for SARS-CoV-2 transmission linked to participation in recreational sports varies considerably. There have been a number of outbreaks of SARS-CoV-2 linked to recreational team sports (Atrubin*, Kuitunen*), but there have also been examples of successful implementation of recreational team sports with little evidence of increased risk of SARS-CoV-2 infection (Watson*). No evidence in the published or pre-print literature was identified that provides generalizable estimates of the risk of SARS-CoV-2 infection associated with participation in recreational sports overall, let alone stratified by age, type of sport, or risk mitigation protocol model. Among participants in recreational sports, fear and anxiety related to COVID-19 was highest among older adults and those who participated in group sports, according to survey results from South Korea (Choi*).

There have been two COVID-19 outbreaks reported among recreational hockey leagues. The first involved a cluster of cases originating from a pre-symptomatic player (Atrubin*). The outbreak was linked to an indoor hockey game in Tampa, Florida in June 2020. The index case experienced symptoms one day after the game and subsequently had a positive antigen test. Overall, 62% (13 of 21) players experienced illness 2-5 days after the game (8 teammates, 5 members of the other team), as did one rink staff member. Thirteen of 15 people, including the index case, had positive SARS-CoV-2 tests (11 PCR, 2 antigen). The second outbreak occurred across five U-20 hockey teams in Finland resulting from a pre-symptomatic player who developed symptoms one day after the hockey game (Kuitunen*). The index player, who was pre-symptomatic at the time, infected 22 of 28 teammates. The team had returned from an away trip the day before the first players had symptoms. COVID-19 was detected in both teams a few days later. During two weeks of quarantine, a total of 24 players from the two opposing teams tested positive. Some of these players infected additional players on other teams. In total, 49 infections were detected in five ice hockey teams, and six teams were in quarantine for two weeks.
No relationship was found between participating in US youth soccer club activities in summer 2020 and COVID-19 incidence among players or staff (Watson*). Youth soccer clubs in the US involving 85,861 players that had restarted in-person activities reported 218 COVID-19 cases among their members. None of the cases resulted in hospitalization or death. The authors used these cases to estimate the incidence of COVID-19 among youth soccer athletes and concluded that it was lower than the overall national rate for children in the US (254 vs 477 cases per 100,000). No relationship was identified between club COVID-19 incidence and phase of return to soccer. Youth soccer clubs universally report implementing risk reduction procedures.

K-12 School-Associated Sports

K-12 school-associated sports, primarily at the middle and high school level were widely canceled in the early phase of the COVID-19 pandemic. Subsequently, school sports have been restarted, at least in some form, in many communities. With each school implementing their own model of virtual learning and reopening over the course of the pandemic, the landscape of returning to school sports has differed from school-to-school as well. CDC guidelines for reopening K-12 schools for in-person instruction have emphasized the importance of prioritizing in-person instruction over extracurricular activities, including sports (CDC*). Well-documented outbreaks of COVID-19 have occurred in the context of school sports (Atherstone*). At the same time, many athletes have experienced an incidence of COVID-19 that is similar to what is found in the general population (Sasser*). Outdoor and non-contact sports have been associated with a lower incidence of COVID-19 compared to indoor and contact sports (Watson*). Consideration of the risk associated with school-associated sports should consider more than just the student athletes and coaching staff, and should also include a focus on the impacts on their household contacts. In some situations, school sports have resulted in transmission of SARS-CoV-2 to household members (Atherstone*).

In Wisconsin in September 2020, among 207 high schools that reinitiated sports, there were 270 COVID-19 cases among 30,074 players (809 cases per 100,000 players and 32.6 cases per 100,000 player-days) (Sasser*). The majority (55%) of cases were attributed to household contact, and 41% were attributed to contact outside sport or school. There was no difference in incidence rates between team and individual sports. 84% of schools required face masks while playing.
A nationwide survey of 152,484 high school athletes found cumulative incidence of 1,682 COVID-19 cases per 100,000 athletes, corresponding to an incidence rate of 24.6 cases per 100,000 player-days between August and October 2020 (Watson*). Incidence was lower when sports were outdoors and non-contact; however, no differences were detected between team versus individual sports. Face mask use was associated with a decreased incidence in girls’ volleyball, boys’ basketball, and girls’ basketball.
An outbreak arising from a Florida high school wrestling tournament in December 2020 had an attack rate of at least 30% (38 of 126 tournament attendees who were tested) and a secondary attack rate of at least 9% (41 of 441 close contacts of the 38 COVID-19 patients). Among contacts, household members had the highest attack rate (at least 30%), test positivity rate (60%), and odds of receiving a positive test result (OR=2.7). The outbreak resulted in an estimated loss of 1,700 in-person school days due to isolation and quarantine of patients and contacts, and the death of one adult contact aged >50 years (Atherstone*).

College Sports

Outbreaks among Collegiate Athletes

On many college and university campuses, collegiate sports have restarted or have continued to be played, even when classes have been conducted in an online or remote format. Outbreaks of SARS-CoV-2 have been identified among college athletes, with evidence of transmission among teammates (Teran*). However, in many cases, it has been difficult to determine whether transmissions occurred during athletic activities or during other social interactions between athletes and other members of the campus community (Teran*, Atherstone*).

An outbreak of SARS-CoV-2 occurred among members of a Chicago university’s men’s and women’s soccer teams in August 2020, with 17 out of 45 (38%) players infected (Teran*). A large number of social gathers were reported by the athletes, with minimal use of masks or physical distancing, including a birthday party, dorm and apartment visits, and an outdoor lake gathering. Four out of the 17 cases were asymptomatic and were identified after universal testing of teams was conducted.
A modeling study indicated that transmission of SARS-CoV-2 among spectators attending college sporting events (either in person or remotely in groups) could be a driver of community transmission (Johnson*). The focus of the model was on transmission among spectators rather than directly due to athletic activities.

Quarantine of Exposed Athletes

Quarantine protocols have been implemented among collegiate athletes who are exposed to SARS-CoV-2. Among collegiate athletes who were quarantined following exposure to COVID-19, one quarter had a positive SARS-CoV-2 test result during quarantine with a mean of 3.8 days from quarantine start until the positive test result (Atherstone*). Among athletes who had not received a positive test result by day 5, the probability of testing positive decreased from 27% by day 5 to <5% after day 10. More athletes reported exposure to COVID-19 at social gatherings (41%) and from roommates (32%) than they did from exposures associated with athletic activities (13%). The authors concluded that shortening the quarantine period could increase adherence, but still poses a small transmission risk.

Transmission of SARS-CoV-2 in the Context of Athletic Activities

Detailed evidence of the risk of SARS-CoV-2 transmission associated with specific exposures related to athletic activities remains limited. Based on survey results of a large number of athletes, the risk of acquiring SARS-CoV-2 appears to be lower for outdoor and non-contact sports (Watson*). There is limited evidence of possible indirect transmission of COVID-19 either through contaminated objects in the changing room or squash court or aerosol transmission in a squash court in Slovenia (Brlek).

For outdoor contact sports such as football and rugby, the evidence thus far suggests minimal in-game transmission risk. Instead, transmission events appear to be the result of high-risk behavior such as unmasked meetings in confined rooms. An investigation of a cluster of 41 SARS-CoV-2 infections that occurred within the National Football League in late September 2020 identified at least 7 cases of infection where transmission likely occurred during interactions that consisted of less than 15 minutes of cumulative interaction within 6 feet of an infected individual (Mack*). Interviews revealed that some of these brief interactions included high-risk behavior, such as unmasked meetings in small rooms while eating. These findings led to a revised definition of high-risk contact and implementation of stricter prevention protocols. Similarly, an analysis of 4 professional rugby matches in which 8 players were retrospectively found to have SARS-CoV-2 suggested that risk of in-game transmission may be minimal. While video footage analysis and GPS data show the positive players were within 2 meters of other players for up to 316 seconds during 60 interactions, only 1 of 28 identified contacts and 5 of 100 players on opposing teams had positive tests, all of which were eventually linked to either internal club outbreaks or wider-community transmission (Jones*).

Recommendations for mitigation protocols

The American Academic of Pediatrics advises that children returning to athletic activities use cloth face masks during all indoor sports, except for swimming and diving, cheerleading, gymnastics, and wrestling. Cloth masks are also recommended for persons on the sidelines, in locker rooms, and in training sessions (McBride*, American Academy of Pediatrics).

Indirect impacts

The cancellation of school sports due to COVID-19 policies has had negative effects on the mental health of athletes. A cross-sectional study of adolescent student athletes during COVID-19-related school closures and sport cancellations found adolescents who identify as female reported a higher prevalence of moderate to severe anxiety symptoms than those who identify as males (44% vs. 28%) (McGuine*). Prevalence of depression symptoms was highest among those participating in team sports (74%) and lowest for individual sports (65%), and the total quality of life score was worst for athletes from counties with the highest poverty levels.

With a decline of opportunities for children to participate in physical activity due to school closures and physical distancing measures, there has been a notable decrease in exercise during the pandemic. A survey of US parents indicated free play/unstructured activity (90%) and going for a walk (55%) as the two most common physical activities for children. Children engaged in about 90 min of school-related sitting and over 8 hours of leisure-related sitting per day. Parents of children ages 9-13 years were more likely to perceive a greater decrease of physical activity compared to parents of children ages 5-8 (Dunton*).

Returning to Physical Activity after COVID-19

Evidence of heart muscle inflammation following SARS-CoV-2 infection among youth and collegiate athletes

There have been multiple reports of evidence of heart muscle inflammation (myocarditis) among young people, including athletes, leading to concerns about the safety of returning to athletic activities following COVID-19. The actual risk to athletes remains unclear, but the American Academy of Pediatrics has issued revised guidelines for children returning to athletic activities after COVID-19 (McBride*). The guidelines suggest that children who have asymptomatic or mild COVID-19 (less than 4 days of fever) complete a brief cardiovascular evaluation with their primary care provider including assessment for chest pain, shortness of breath, palpitations, or fainting. Children with moderate or severe COVID-19 are recommended to see a cardiologist after symptom resolution and before resuming play.

Among 26 competitive college athletes who had tested positive for SARS-CoV-2 11-53 days earlier and had not require hospitalization, 4 (15%) had cardiac MRI findings suggestive of myocarditis (heart muscle inflammation) and 8 (31%) athletes exhibited late gadolinium enhancement (LGE) without T2 elevation, suggestive of prior myocardial injury (Rajpal*). Cardiac ventricular function was within normal ranges for all athletes, as measured by cardiac MRI and transthoracic echocardiogram. The authors suggest that cardiac MRI may be a useful tool to risk-stratify athletes for return to competitive sports participation following recovery from COVID-19.
In a cohort of 48 university student athletes who recovered from SARS-CoV-2 infection and returned to campus in July 2020 in West Virginia (30% asymptomatic), more than 1 in 3 showed signs of resolving heart inflammation on imaging studies (Brito*). Twenty-seven student athletes (56%) had cardiac abnormalities, including 19 students with late enhancement of the pericardium and associated pericardial effusion. No student athlete showed specific imaging features of ongoing myocardial inflammation.

Guidelines and recommendations for returning to sports and exercise following COVID-19 and SARS-CoV-2 infection

A Game Plan for the Resumption of Sport and Exercise After Coronavirus Disease 2019 (COVID-19) Infection – JAMA Cardiology (May 13, 2020)
Return-to-Play Guidelines for Athletes After COVID-19 Infection – JAMA Cardiology (Nov 4, 2020)
Screening of Potential Cardiac Involvement in Competitive Athletes Recovering From COVID-19: An Expert Consensus Statement – JACC. Cardiovascular Imaging (Dec 11, 2020)
Cardiopulmonary Considerations for High School Student-Athletes During the COVID-19 Pandemic: NFHS-AMSSM Guidance Statement – Sports Health (July 9, 2020)

Existing Guidelines and Other Resources

COVID-19 Interim Guidance: Return to Sports – American Academy of Pediatrics (Dec 17, 2020)
Operational Strategy for K-12 Schools through Phased Mitigation – CDC (Feb 12, 2021)
COVID-19 Guidelines for Sports and Physical Activity – Missouri Medicine (May 2020)
Playing Non-Professional Football in COVID-19 Time: A Narrative Review of Recommendations, Considerations, and Best Practices – International Journal of Environmental Research and Public Health (Jan 15, 2021)
Creating a Safe, Return-to-Sport Environment in Upstate New York during the COVID-19 Pandemic – Current Sports Medicine Reports (Jan 5, 2021)
Promoting Healthy Movement Behaviours among Children during the COVID-19 Pandemic – The Lancet Child & Adolescent Health (June 2020)
Returning Athletes Back to High School Sports in the COVID-19 Era: Preparing for the Fall – Sports Health (Aug 20, 2020)
COVID-19 Surveillance in Youth Soccer During Small Group Training: A Safe Return to Sports Activity – Sports Health

Latest In-Depth Report: Summary of SARS-CoV-2 Novel Variants

February 5, 2021

COVID-19 Literature Report Team:

Ashley Tseng MPH, Lorenzo Tolentino MPH, Jessie Seiler MPH, Rodal Issema MPH, Molly Fisher MPH, Sherrilynne Fuller PhD FACMI, Dylan Green MPH, Diana Louden MLib, Alison Drake PhD MPH, Will Hahn MD, Brandon L. Guthrie PhD, Jennifer M. Ross MD MPH

At just over one year into the COVID-19 pandemic, evolution of SARS-CoV-2 has generated viral variants that differ in their genetic sequence from the strain first detected in December 2019. Evidence is emerging about how these variants differ in their transmission characteristics, associated clinical symptoms, and vaccine efficacy. This document is a brief summary of published evidence about characteristics of SARS-CoV-2 variants that may impact the public health response, including transmission and response to vaccination. Included are manuscripts published in peer-reviewed journals or on pre-print servers through February 5, 2021. References summarized in this report were drawn from the COVID-19 Literature Report (Lit Rep) team database. References that appeared in the daily Lit Rep are marked with an asterisk*, and the summary is shown in the annotated bibliography below. This list was cross-referenced with resource pages hosted by the Centers for Disease Control and Prevention (CDC) and World Health Organization (WHO), genomics initiatives Nextstrain and GISAID, and supplemented with studies mentioned in media articles.^1–4 We encourage readers to consult these sites and the daily Lit Rep for evidence that emerges following publication of this report.

View the full report, which contains an annotated bibliography:

VIEW A PDF OF THE ENTIRE SUMMARY HERE

Executive Summary of SARS-CoV-2 novel variants

Continued evolution of SARS-CoV-2 has led to several variants with evidence or suspicion of increased transmissibility, including the B.1.1.7 variant emerging from the UK, the B.1.351 variant emerging from South Africa, and the P.1 variant emerging from Brazil.
Early evidence indicates that the B.1.1.7 variant is still neutralized by sera from people who received the Pfizer or Moderna vaccine series. Novavax reported similar efficacy of its vaccine (85% vs 89%) against the B.1.1.7 variant and non-variant strains and the AstraZeneca-Oxford vaccine was reported to have similar efficacy against the B.1.1.7 variant and non-variant strains (74% vs 84%).
In contrast, press releases containing preliminary findings from vaccine trial sites in South Africa during the emergence of B.1.351 suggest lower efficacy of the Novavax and Johnson & Johnson vaccines in this setting compared to sites in the US and the UK where B.1.351 was not the dominant strain, but full manuscripts have not been published.
Additionally, laboratory evidence indicates reduced neutralization of B.1.351 and B.1.1.7 strains by convalescent plasma and monoclonal antibodies.

Overview of naming conventions for SARS-CoV-2 variants

Multiple categorizations of the genetic diversity of SARS-CoV-2 have developed across research and public health organizations, resulting in several names for each variant. Researchers emphasize the importance of referring to variants by their scientific names instead of using geographic terms to avoid stigmatizing people and places and to reduce confusion as variants are detected globally.⁵ This report refers to variants with multiple leading naming conventions (Table). One leading convention described by Rambaut and utilized by Pangolin software assigns names based on the evolutionary relationships of viruses (e.g., B.1.1.7).⁶ Another, the Nextstrain genomics project, categorizes the genetic diversity of SARS-CoV-2 into different clades, which are groups of similar viruses based on their phylogenetic relatedness, with 11 clades named thus far: 19A, 19B, 20B, 20C, 20D, 20E (EU1), 20F, 20G, 20H/501Y.V2, 20I/501Y.V1, and 20J/501Y.V3. The Global Initiative on Sharing All Influenza Data (GISAID) also uses a clade system that differs from Nextstrain (e.g., clade 20B for Nextstrain; clade GR for GISAID). Public Health England uses the ‘VOC 202012/01’ nomenclature in which VOC stands for ‘variant of concern,’ the numbers include a reference to the year and month of discovery, and variant number (01).⁷ The ‘501Y.V2’ nomenclature refers to a substitution in the 501^st amino acid site of the SARS-CoV-2 spike protein used by the team that identified the variant.

Transmission characteristics of key SARS-CoV-2 variants

Early in the pandemic, SARS-CoV-2 genomic tracking efforts identified that a variant with an amino acid change in the spike protein (D614G) had become the dominant pandemic strain by March 2020.⁸ Attention turned to other variants during the northern hemisphere autumn 2020, as COVID-19 surged in Europe and a large-scale genomic sequencing effort in the UK identified a variant known as B.1.1.7 (a.k.a. variant 20I/501Y.V1 or VOC 202012/01) associated with increased risk of transmission.⁷ Recent publications focus on B.1.1.7, B.1.351 (a.k.a. 20H/501Y.V2) emerging from South Africa, P.1 (a.k.a. 20J/501Y.V3 or descendent from B.1.1.28) emerging from Brazil, and CAL.20C, whose emergence in southern California in autumn 2020 coincided with a substantial increase in COVID-19 cases.⁹ All of these variants have been identified in samples in the US.¹

Early emergence of spike protein mutation D614G, with evidence of increased transmissibility, becomes the dominant pandemic strain by March 2020.

A sequence analysis of 175 SARS-CoV-2 samples early in the pandemic from a southwestern US medical center from March to May 2020 indicated that 57% of samples carried the D614G substitution.¹⁰*
In an early study published in July 2020, Korber et al. found that patients infected with the SARS-CoV-2 strain carrying the D614G variant shed more viral nucleic acid compared to those without this mutation.⁸*
A study published as a pre-print in September 2020 using epidemiological data and phylogenetic data (35,377 sequences) estimated that the G614 mutant of SARS-CoV-2 is 31% more transmissible than the D614 wildtype. ¹¹*

Mink culling in Denmark in response to ‘Cluster-5’ variant12

A variant with 3 amino-acid changes and two deletions in the spike protein resulted in both human-to-mink and mink-to-human transmission in Denmark.¹³*

Danish health authorities found that some of the mutations were associated with reduced response to antibodies, as described in a letter from the Danish Chief Veterinary Officer to the World Organization for Animal Health.^12,14

Whole genome sequencing showed evidence of ongoing SARS-CoV-2 transmission in mink farms and spillover events to human in the Netherlands.¹⁵

Denmark decided to cull all farmed mink in early November 2020 due to concern that mink were acting as a viral reservoir and contributing to ongoing SARS-CoV-2 transmission, with the potential for additional mutations as viruses were transmitted between mink and humans.¹⁶

Lineage B.1.1.7 (a.k.a. variant 20I/501Y.V1 or VOC 202012/01) identified in the UK with evidence of increased transmissibility, becomes the dominant strain in the UK by December, 2020.7

90% of samples tested across England between January 18 and 24, 2021 carried S gene target failure (SGTF), with higher proportions in London, the South East, and East of England. SGTF is used as a proxy for monitoring B.1.1.7 in the UK based on the predominant assay in UK lighthouse laboratories.⁷

An analysis of contact tracing data by Public Health England found that the secondary attack rate was higher for SGTF, increasing from 10% to 13% of named contacts, yielding an estimate of 25% – 40% higher attack rate for the variant strain.⁷

The receptor binding domain (RBD) of the 501Y.V1 SARS-CoV-2 variant was reported to have around a 10-times higher binding affinity for human ACE2 than the RBD of the parent N501 strain, suggesting a potential mechanism for the higher rate of contagiousness observed with this strain.¹⁷*

An earlier mathematical modeling study for 3 regions in England estimated that VOC 202012/01 is 56% (range 50-74%) more transmissible than earlier strains using testing data and cell phone data. ¹⁸*

CDC identified 76 reported cases of B.1.1.7 variant in US through January 13, 2021. Models predicted that B.1.1.7 may become the dominant strain in the US by March, 2021.¹⁹*

Spoiler title

This variant with multiple spike protein mutations became the dominant strain by early November 2020 in the Eastern Cape and Western Cape Provinces of South Africa.⁹²⁰

It is estimated to be more transmissible than non-variant strains, though less quantified than B.1.1.7 variant.

It exhibits evidence of escape from neutralization by convalescent plasma and vaccinated donor sera, as described in detail below.

P.1 variant (a.k.a. 20J/501Y.V3, branch from B.1.1.28 lineage) in Brazil

This variant has 12 mutations to the spike protein, including three mutations of concern in common with 20H/501Y.V2 (K417N/T, E484K and N501Y) which may affect transmissibility and host immune response.¹

Using phylogenetic analysis, Voloch et al estimate that it emerged in Rio de Janiero in July 2020 and increased in frequency among sampled genomes.²¹

A new SARS-CoV-2 variant was one hypothesis raised to potentially explain the resurgence of COVID-19 cases in Manaus, Brazil despite high estimated seroprevalence of antibodies against SARS-CoV-2 of 76%.²²*

CAL.20C variant in California

A novel SARS-CoV-2 strain, CAL.20C, emerging from Southern California, was detected through genome sequence analysis. The strain’s increasing dominance coincided with an increased positivity rate in that region. While first observed in July, CAL.20C accounted for 24% of cases by December 2020. CAL.20C is characterized by multiple mutations in the spike protein, similar to variants emerging from the UK and South Africa. Though predominant in Southern California, CAL.20C has been isolated in samples from New York and Washington DC.²³*

Implications of variants for SARS-CoV-2 re-infection and vaccine efficacy

Greaney et al. identified the E484 site in the spike protein receptor binding domain (characteristic of variants B.1.351 and P.1) as a place where mutations reduce neutralization by convalescent serum by more than 10-fold.²⁴ Convalescent plasma from people recovering from COVID-19 had attenuated neutralization to the B.1.351 variant.^25,26* The SARS-CoV-2 variant B.1.1.7 was resistant to neutralization by several monoclonal antibodies (mAbs) targeting either the N-terminal domain (NTD) of the virus’s spike protein or its receptor-binding domain (RBD). The B.1.351 variant resisted neutralization by most NTD mAbs, multiple individual mAbs directed against the RBD, convalescent plasma (about 11-33 fold), and sera from vaccinated people (about 6.5-8.6 fold).²⁷* The SARS-CoV-2 B.1.1.7 variant was shown to reduce neutralizing activity of monoclonal antibodies (mAbs) targeting subdominant epitopes in the SARS-CoV-2 spike protein.²⁸* Cases of SARS-CoV-2 re-infection have been reported for the D614G mutation, B.1.1.7 variant, B.1.351 variant, and P.1 variant.^29–31 For B.1.1.7, the two infection episodes were separated by eight months and the second infection episode was with a B.1.1.7 variant.³⁰

Summary of vaccine efficacy by manufacturer

Pfizer-BioNTech

Neutralizing activity of participants three weeks after receiving the first dose of the Pfizer vaccine was similar against the three key spike protein mutations in the B.1.1.7 variant, compared to the wild-type SARS-CoV-2 strain. However, neutralization titers were reduced up to 6-fold (median 3.85-fold) against a pseudovirus with the full set of 8 spike protein mutations present in the B.1.1.7 variant.³²*

A subsequent analysis found sera from recipients who completed the 2-dose regimen of the Pfizer vaccine BNT162b2 (n=20) had similar neutralizing geometric mean titers (GMTs) against SARS-CoV-2 viruses engineered to contain key spike protein mutations from variants emerging from the UK (B.1.1.7) and South Africa (B.1.351) compared to GMTs against the wild-type virus. The authors note a limitation that the engineered viruses do not contain the full set of mutations present in variants B.1.1.7 and B.1.351.³³*

Moderna

Sera from human subjects or non-human primates that received the mRNA-1273 (Moderna) vaccine showed no significant reduction in neutralization activity against the SARS-CoV-2 B.1.1.7 variant emerging from the UK, but reduced activity against the B.1.351 variant emerging from South Africa.³⁴*

Using a lentivirus-based pseudovirus assay, the SARS-CoV-2 B.1.1.7 (UK) variant was shown to exhibit only modestly reduced susceptibility to neutralization from convalescent sera (1.5-fold average reduction) and sera from recipients of both the Moderna and Novavax vaccine phase 1 studies (2-fold average reduction after two inoculations).³⁵*

Novavax

Preliminary results reported on January 28 for phase 2/3 trials for the recombinant protein-based COVID-19 vaccine NVX-CoV2373 made by Novavax showed up to 89% efficacy in the UK cohort (n >15,000), with an estimated 86% efficacy against the B.1.1.7 variant.³⁶*

Preliminary Novavax results from the South Africa cohort (n >4,400) showed efficacy of 60% in the HIV-negative study population vs. 49% in the overall study population, with 29 COVID-19 cases observed in the placebo group vs. 15 in the vaccine group. Among 27 of the 44 cases with sequence data, mutations consistent with the B.1.351 variant were detected in 25 (93%).³⁶*

Johnson & Johnson

Preliminary analysis of the ENSEMBLE trial reported the efficacy of single-dose vaccination with the Johnson & Johnson vaccine was lower among trial participants in South Africa (57%) than at sites in Latin America (66%) and the US (72%) in the setting of B.1.351 emergence in South Africa.³⁷*

Oxford – AstraZeneca

The efficacy the ChAdOx1 nCoV-19 vaccine against the B.1.1.7 variant of SARS-CoV-2 was similar to the efficacy against parent lineages, with 74% efficacy (95% CI, 42-89%) against B.1.1.7 compared to 84% efficacy (95% CI, 71-91%) against non- B.1.1.7 lineages.³⁸*

Implications of variants for diagnostic testing

A potential consequence of emerging variants is the ability to evade detection by specific viral diagnostic tests. CDC reports that most commercial RT-PCR-based tests have multiple targets to detect the virus, so that even if a mutation impacts one of the targets, the other RT-PCR targets will still work.¹

There is minimal impact on the performance of antigen-based tests (including rapid lateral flow devices) and there has been no impact on the performance of serological antibody tests reported on these variants.³⁹

The World Health Organization advises laboratories using S-gene based assays to monitor for dropout and consider implementing assays specific for other genomic targets (e.g., E or RdRP genes) if not already included as part of the existing panel.⁴⁰

Lineage B.1.1.7 (a.k.a. variant 20I/501Y.V1 or VOC 202012/01):

Minimal impact on performance of molecular diagnostics (69–70 deletion causes S gene dropout).⁴¹

A UK government assessment found that all five SARS-CoV-2 rapid antigen tests evaluated (Abbott Panbio, Fortress, Innova, Roche/SD Biosensor nasal swab, and Surescreen) were able to successfully detect the variant.⁴²

Abdel-Sater et al. reported the development of a rapid molecular test to identify the SARS-CoV-2 B.1.1.7 variant using a set of RT-PCR primers that were designed to confirm the deletion mutations Δ69/Δ70 in the spike and the Δ106/Δ107/Δ108 in the NSP6 gene. The large-scale screening method may help bypass the need for widespread sequencing to confirm the presence of both the B.1.1.7 variant and variants with similar deletions.⁴³* (Summarized Jan 29)

Lineage B.1.351 (a.k.a. variant 20H/501Y.V2):

We did not find data on assay performance impact yet, but there is potential of impacting assays that target S gene sequences.

Current variants and clinical severity

The UK New and Emerging Respiratory Virus Threats Advisory Group reported on January 21, 2021 that the B.1.1.7 SARS-CoV-2 variant quickly became dominant in the UK, and it is possible that infection with this variant is associated with increased risk of death. The statement cites evidence of increased case fatality from several independent UK studies of samples with s-gene target failure, a proxy for the B.1.1.7 variant.⁴⁴*

Further evidence was published on February 3 in a pre-print by Davies et al. reporting that the B.1.1.7 variant may increase the risk of death by 30%, based on an analysis of SARS-CoV-2 community test results in the UK that identified B.1.1.7-associated infections using S gene target PCR failure.⁴⁵*

An earlier analysis found that patients with the B.1.1.7 were equally likely to be asymptomatic.⁴⁶*

An analysis found no association between the proportion of the SARS-CoV-2 variant B.1.1.7 in circulation in the UK and reported disease severity, according to data obtained from reporting of symptoms and test results via the COVID Symptom Study application.⁴⁷*

Resources for tracking

The World Health Organization (WHO) publishes weekly COVID-19 situation reports with global epidemiological and operational updates, including special coverage on novel variants. Additionally, WHO has a summary of SARS-CoV-2 variants through 12/31/2020.

In addition to providing updated COVID-19 guideline, the US Centers for Disease Control and Prevention (CDC) has a periodically updated page on emerging SARS-CoV-2 variants.

GISAID a global science initiative that provides open-access genomic data of influenza viruses and SARS-CoV-2. CoVsurver is a tool that allows users to perform mutation analyses based on input sequences compared to a reference strain.

Nextstrain is an open-source project to harness the scientific and public health potential of pathogen genome data. Nextstrain provides a continually updated view of publicly available SARS-CoV-2 data and includes SARS-CoV-2 resources as well as FAQs on COVID-19.

Table: Key characteristics of novel SARS-CoV-2 variants

Table: Key characteristics of novel SARS-CoV-2 variants

Variant Name Identification Date Locations of Emergence Key Mutations Relative Transmissibility Vaccine Efficacy

D614G spike protein substitution February 2020 China; Germany The spike protein D614G amino acid change is caused by an A-to-G nucleotide substitution at position 23,403 in the Wuhan reference strain G614 mutant of SARS-CoV-2 is 31% more transmissible than the D614 wildtype¹¹ D164G SARS-CoV-2 was the dominant pandemic strain during the Moderna and Pfizer/BioNTech trials.

‘Cluster 5’ variant November 2020 Denmark Causes 3 amino-acid changes and two deletions in the spike Not quantified.

A WHO post from December 3, 2020 suggests that there is an increased risk of COVID-19 among people involved in mink farming.¹⁶
Preliminary findings: Antibodies from some people who had recovered from COVID-19 found it more difficult to recognize the Cluster-5 variant than to spot coronaviruses that did not carry these mutations.¹²

The potential for mink to act as a reservoir for ongoing SARS-CoV-2 transmission led to a decision in early November, 2020 to cull all farmed mink in Denmark.¹⁶

Lineage B.1.1.7 (a.k.a. variant 20I/501Y.V1 or VOC 202012/01) October 2020 United Kingdom N501Y: A mutation in the receptor binding domain (RBD) of the spike protein at position 501, where the amino acid asparagine (N) has been replaced with tyrosine (Y).

69/70 deletion: Occurred spontaneously many times and likely leads to a conformational change in the spike protein.

P681H: Near the S1/S2 furin cleavage site, a site with high variability in coronaviruses. This mutation has also emerged spontaneously multiple times.
56% (range 50-74%) more transmissible than earlier strains.¹⁸ The mRNA-1273 (Moderna) vaccine showed no significant reduction in neutralization activity against the SARS-CoV-2 B.1.1.7 variant.³⁴

Novavax reported that its NVX-CoV2373 vaccine has an estimated 85.6% efficacy against the B.1.1.7 variant.³⁶

The Oxford-AstraZeneca vaccine was reported to have 74% efficacy against B.1.1.7 compared to 84% efficacy against non- B.1.1.7 lineages.³⁸

Lineage B.1.351 (a.k.a. variant 20H/501Y.V2) December 2020⁹ South Africa This variant has multiple mutations in the spike protein, including K417T, E484K, N501Y. Unlike the B.1.1.7 lineage detected in the UK, this variant does not contain the deletion at 69/70. Not quantified.

Tegally et al. 2020 report that this variant became the dominant strain in by early November 2020 in the Eastern Cape and Western Cape Provinces of South Africa. “Whilst the full significance of the mutations is not yet clear, the genomic and epidemiological data suggest increased transmissibility associated with the virus.”⁹
The mRNA-1273 (Moderna) vaccine showed reduced activity against the B.1.351 variant emerging from South Africa.³⁴

Preliminary Novavax results from the South Africa cohort showed efficacy of 60% in the HIV-negative study population vs. 49.4% in the overall study population. Among 27 of the 44 cases with sequence data, mutations consistent with the B.1.351 variant were detected in 25 (93%).³⁶

Variant P.1 (a.k.a. 20J/501Y.V3 or descendent from B.1.1.28) December 2020²¹ Brazil This variant contains three mutations in the spike protein receptor binding domain: K417T, E484K, and N501.¹ Not quantified.

CDC reports, “There is evidence to suggest that some of the mutations in the P.1 variant may affect its transmissibility and antigenic profile, which may affect the ability of antibodies generated through a previous natural infection or through vaccination to recognize and neutralize the virus.” ¹
Vaccine efficacy has not been reported for this strain as of the date of this report, but there is potential for this strain also to show reduced vaccine efficacy because it contains the same three spike protein mutations as lineage B.1.351.

CAL.20C July 2020 California Defined by five mutations: ORF1a: I4205V, ORF1b: D1183Y, S: S13I, S: W152C, S: L452R (Zhang et al., 2021) Not quantified. Not reported.

Summary of Evidence Related to Indoor Ventilation to Reduce SARS-CoV2 Transmission

Summary of Evidence Related to Indoor Ventilation to Reduce SARS-CoV-2 Transmission

December 21, 2020

This updated in-depth summary (previously version released on December 21, 2020) is issued in response to new information that we received about updated definitions of aerosol particles that show that larger respiratory particles (<100 μm) can remain airborne for extended periods, and that in enclosed areas with poor ventilation, these aerosols containing infectious SARS-CoV-2 can spread beyond 6 feet and build up in a room. We apologize for not including this information in the earlier version of this summary.”

Mitigation of SARS-CoV-2 transmission in indoor spaces is crucial, especially during the winter season when activities are mostly held in enclosed indoor environments. Understanding SARS-CoV-2 transmission mechanisms relating to ventilation of indoor air and what evidence-based environmental measures are available will be key to infection control. This document is a brief summary of published evidence on SARS-CoV-2 transmission mechanisms that relate to ventilation of indoor spaces and ventilation standards/best practices for minimizing spread. References are mainly drawn from the COVID-19 Literature Report (Lit Rep) team database and guidelines published by the CDC. References that appeared in the daily Lit Rep are marked with an asterisk*, and the summary is shown in the annotated bibliography below.

View the full report, which contains :

Table of key studies

Annotated Bibliography

VIEW A PDF OF THE ENTIRE SUMMARY HERE

Executive Summary of Ventilation and SARS-CoV-2

While evidence suggests that SARS-CoV-2 is commonly transmitted through close contact and respiratory droplets, updated definitions of aerosols show that larger respiratory particles (<100 μm) can remain airborne for extended periods. In enclosed areas with poor ventilation, these aerosols containing infectious SARS-CoV-2 can spread beyond 6 feet and build up in a room. A small number of studies have isolated viable virus from air samples in lab and clinical settings and SARS-CoV-2 airborne transmission beyond 6 feet has been observed in poorly ventilated and crowded indoor spaces.

An expert panel assembled by the National Academies of Sciences, Engineering, and Medicine concluded that aerosols represent an important potential transmission pathway for SARS-CoV-2 based on multiple lines of evidence, but concluded that additional research is needed to definitively prove and quantify the role of the aerosol transmission pathway.

While SARS-CoV-2 RNA has been detected in heating, ventilation, and air conditioning (HVAC) systems, viable virus was not isolated. There has been no documented evidence of SARS-CoV-2 transmission occurring through HVAC systems.

Ventilation standards/best practices to reduce risk of SARS-CoV-2 transmission primarily include methods to decrease concentrations of aerosols that may carry infectious virus either through filtration of indoor air or circulation of cleaner air from outside.

Ventilation standards/best practices alone are not enough to mitigate SARS-CoV-2 transmission. They should be implemented in conjunction with infection control measures that more directly address SARS-CoV-2 primary modes of transmission, such as reducing building occupancy to facilitate physical distancing, mask wearing, surface disinfection, and handwashing.

SARS-CoV-2 Transmission related to Ventilation

Note: Some of the evidence covered here can also be found in the CDC brief on SARS-CoV-2 and Potential Airborne Transmission and the proceedings of the National Academies of Sciences, Engineering, and Medicine Workshop on Airborne Transmission of SARS-CoV-2.

Aerosol Transmission

Particles ejected when an infectious person sneezes, coughs, sings, or breathes form a spectrum of respiratory droplets and aerosols.

Respiratory droplets are large droplets that settle more quickly on surrounding surfaces. They are responsible for droplet transmission, which occurs when a person in close contact (within about 6 feet) inhales these droplets or through exposure via eyes, nose, or mouth.

Aerosols tend to be smaller, lighter particles that can remain airborne for much longer and can be carried farther by airflow and wind currents. They are responsible for airborne transmission, which occurs when a person inhales these particles. While aerosols have been traditionally defined as <5 μm in diameter, updated descriptions based on aerosol science indicate that aerosols can be up to 100 μm in diameter and remain suspended in the air for extended periods. While concentrations are highest near the source, aerosols can travel more than 6 feet from the source and build up over time, particularly in enclosed spaces with poor ventilation.^1,2

The SARS-CoV-2 virus, which is around 0.1 μm, generally does not travel through the air by itself. Potentially infectious virus (based on replication in cell culture) has been isolated from air samples as well as from surfaces on which respiratory droplets have deposited,^3,4* indicating that particles of varying size can carry infectious virus.

While other coronaviruses are more likely to be present in aerosols than in larger respiratory droplets,⁵ the exact distribution of the SARS-CoV-2 across the range of different-sized particles is unknown.

The half-life of SARS-CoV-2 in aerosol is estimated to be approximately 1.1 hours, based on experimental evidence using a Goldberg drum to keep artificially generated aerosols in suspension.³ Infectious aerosols generated under experimental conditions have been found after 16 hours.⁶

UV light greatly decreases virus stability in droplets and aerosols,⁷ while lower temperatures and humidity may increase stability.⁸

An expert panel assembled by the National Academies of Sciences, Engineering, and Medicine concluded that aerosols represent an important potential transmission pathway for SARS-CoV-2 based on multiple lines of evidence:¹

Aerosols have been shown to contain infectious SARS-CoV-2 and can remain suspended in air for hours.

Asymptomatic individuals emit mostly aerosols with sizes <10 μm and produce very few droplets.

Super-spreading events are more readily explained by aerosol transmission.⁹

Aerosols are more concentrated at close range and can spread and accumulate in a room.

Transmission in outdoor settings has been much less common than indoors.

No substantial evidence on classic long-range airborne transmission

Currently, there is no substantial evidence that SARS-CoV-2 can be transmitted efficiently over long distances through airborne transmission like other pathogens such as TB, measles, or varicella (chickenpox).¹⁰

Though aerosolized SARS-CoV-2 has been shown to be stable in aerosols for 3-16 hours in laboratory settings,^3,6 real-world factors such as UV exposure from sunlight, temperature and relative humidity affect the stability of the virus, while ventilation and exhaled viral load affect the concentration necessary to infect others.

Given the significant proportion of infections caused by persons with asymptomatic SARS-CoV-2 infection, it is estimated that global spread would have occurred much more rapidly if SARS-CoV-2 spread primarily through long-range airborne transmission.¹¹

Evidence of short-range airborne transmission in certain conditions

Several instances of “short-range” airborne transmission beyond what could be attributed to droplet transmission alone have been documented. These events are associated with enclosed, indoor settings with poor or improper ventilation, prolonged exposure to infectious persons, and activities that increase the rate of droplet and aerosol generation:

An outbreak occurred in a restaurant in which directional airflow from an air conditioner is suspected to have transmitted infected aerosols from the table of the index patient to adjacent tables.¹²*

An outbreak during a 2.5-hour choir practice with an attack rate of 53-87% occurred, with indoor transmission likely augmented by singing.¹³

An outbreak involving two 50-minute rides inside a bus with recirculating air occurred, with secondary individuals sitting closer to the index case being no more likely to get infected than those sitting farther, indicating an extended range of transmission.¹⁴*

In an outbreak in 1 out of 7 wards of a nursing home during a period of low community incidence occurred, the ward experiencing the outbreak had recently installed demand-controlled ventilation that only circulated outside air based on indoor CO₂¹⁵*

A cluster of cases were associated with a shopping mall, where possible virus aerosolization occurring in confined spaces such as elevators and restrooms and contributed to indirect transmission.¹⁶

A cluster of cases associated with a squash court occurred, with individuals who played in the same squash hall as the index case at least 45 minutes later were infected, possibly from aerosols.¹⁷

An outbreak at a nightclub occurred in which infected staff likely caused multiple infections across three different events.¹⁸

An outbreak of 112 cases occurred in 12 sports facilities over 24 days, where asymptomatic and pre-symptomatic instructors taught fitness dance classes to 5–22 students in a room approximately 60 m² for 50 minutes of intense exercise.¹⁹

Indoor Transmission through HVAC systems

We found no reported evidence of SARS-CoV-2 transmission occurring through heating, ventilation, and air conditioning (HVAC) systems. SARS-CoV-2 RNA has been detected in multiple parts of HVAC systems, though viable virus was not isolated. However, a potential limitation of available evidence is that the sampling timeframe may not have captured the virus when it was infectious.

Positive samples (swab and cell media) for SARS-CoV-2 RNA were found in the HVAC system of COVID-19 wards and in the central HVAC system, which was located 5 floors above. Viral culture was unable to detect viable virus in samples.²⁰*

Tests for SARS-CoV-2 RNA were negative for swabs and air samples collected from the Diamond Princess cruise ship in cabins with no COVID-19 cases, but that shared air circulation with COVID-19 cabins via the HVAC system.²¹*

Presence of SAR-CoV-2 RNA was detected in 25% of samples collected in 9 locations of the HVAC system of a university hospital in Oregon. These samples were not evaluated for viral infectiousness.²²

Ventilation Standards/Best Practices

Note: Some of the guidelines covered here can also be found in the Washington Department of Health ventilation guidance and CDC ventilation guidance.

As respiratory droplets and aerosols can contain SARS-CoV-2, a layered prevention approach is recommended to include ventilation measures along with personal protective equipment, mask use, surface disinfection, and personal hygiene. Implementation of some ventilation measures outlined here require technical expertise, and consultation with an HVAC specialist or professional engineer is recommended.

Ventilation measures reduce the risk of SARS-CoV-2 transmission by diluting the concentration of infectious aerosols in the environment. This is primarily achieved by filtration of indoor air or circulation of cleaner air from the outside, either through 1) a central HVAC system, or 2) non-HVAC measures. Ventilation measures affect the air exchange rate per hour (ACH), which is defined as the number of times the air occupying the volume of a given space is exchanged with cleaner air.

HVAC Measures

The CDC recommends installing filters in the HVAC system with the highest performance that the system can handle. The American Society of Heating, Refrigerating and Air-Conditioning Engineers (ASHRAE) recommends installing filters with at least Minimum Efficiency Reporting Value (MERV) of 13, provided there is no substantial impact on HVAC performance or occupant comfort.

MERV values range from 1 to 16, with higher values corresponding to better efficiency. MERV 13 filters are at least 50% efficient at capturing particles in the 0.3 µm to 1.0 µm size range and 85% efficient at capturing particles in the 1 µm to 3 µm size range (more information on MERV standards can be found here.

Higher MERV values can cause a drop in air pressure as more air is filtered, but provide cleaner air with which to exchange the existing air in an enclosed space.

Turn off demand-controlled ventilation, which automatically circulates outside air based on temperature, humidity, or CO₂ concentrations, to avoid build-up of indoor air

Allow for HVAC systems to circulate outside air. Run HVAC systems on maximum to flush indoor air 2 hours before and after occupancy.

The CDC has guidelines for how long a system performing at certain ACH must be run in order to remove the recommended 99% of airborne contaminants.

Open outdoor air dampers to reduce or eliminate HVAC indoor air recirculation (this may be difficult in hot or humid weather)

Maintain relative humidity at 40-60% and temperature within 68-78F (ASHRAE guidance for residential)

Ecological studies have found higher transmission rates in geographical regions with colder and dryer air; however, there is considerable potential for confounding in these comparisons, and the role of temperature and humidity in SARS-CoV-2 infectiousness is not clearly established.²³

Surface stability of SARS-CoV-2 has been found to decrease with increasing temperature and humidity.²⁴*

Ensure that minimum rates for outdoor air circulation are met or exceeded.

These minimum rates not only depend upon the room size, but also the number of occupants, typical activities conducted within the room, and other environmental factors. In general, doubling the occupancy will double the minimum required rate. For more comprehensive standards and calculations for a wide variety of settings, see Equation 6-1 and Table 6-1 of ASHRAE 62.1 (2019)

Non-HVAC Measures

These measures are best used to augment HVAC measures and are best implemented in settings with limited or nonexistent HVAC systems.

Place portable High Efficiency Particulate (HEPA) filter-equipped systems in critical areas.

High Efficiency Particulate (HEPA) filters are at least 99.97% efficient in capturing particles 0.3 μm in size and are even more efficient in capturing particles that are both smaller and larger.

As particles increase in size from 0.3 μm, they are more likely to be strained or blocked since they cannot pass through the tightly woven fiber mesh of the filter. As particles decrease in size from 0.3μm, their movement is increasingly dictated by random diffusional collisions with other molecules rather than the airflow, and thus have increasing probability to collide with the large combined surface area of every fiber in the filter (see page 3 and page 7 of this NASA report for a more detailed explanation).

Portable HEPA-equipped systems have a Clean Air Delivery Rate (CADR) measured in cubic feet per minute (cfm), which dictates how quickly they can remove particles in the air of a room of a given size. Bigger rooms require systems with higher CADR.

Table: Portable Air Cleaner Size for Particle Removal (<a href="https://www.epa.gov/sites/production/files/2018-07/documents/guide_to_air_cleaners_in_the_home_2nd_edition.pdf">EPA</a>)

Table: Portable Air Cleaner Size for Particle Removal (EPA)

Room area (ft2) 100 200 300 400 500 600

Minimum CADR (cfm) 65 130 195 260 325 390

For estimation purposes in a home setting. CADRs are calculated based on an 8 ft.
ceiling and an ACH of 4.875.

A study (pre-print, not peer reviewed) found that HEPA filters installed in a poorly-ventilated classroom setting with a combined ACH of 5.7 could reduce the inhaled viral dose from a super-spreader in a room by a factor of 6.²⁵*

Open windows and doors to outside air. Use caution if outdoor air quality is poorer or not ideal for occupant comfort (e.g. high pollution, colder outdoor weather).

Use indoor fans to facilitate airflow following a clean-to-less-clean air pattern and blowing away from people

Place fans near windows or doors to blow out indoor air

Reverse direction of ceiling fans to pull air up

Reduce occupancy as much as possible to allow for physical distancing, and avoid occupant activities that cause higher rates of emitting respiratory droplets and aerosols (e.g., singing, shouting, cheering)

Use faces coverings

Face masks or other face coverings function as filters that are closest to the source of infectious aerosols and can drastically reduce the concentration of viral particles in indoor environments.

Hospital rooms with unmasked COVID-19 patients, despite extensive ventilation measures, were found to contain RNA-positive surface samples²⁶ and air samples with viable virus.⁴*

Air samples collected in indoor spaces (hotel room, car) where an individual who had either confirmed influenza or suspected COVID-19 wore a cotton/surgical mask showed a substantial decrease in aerosol concentration.²⁷*

A modeling study exploring risk of transmission from super-spreaders in various indoor settings (e.g. schools, offices) found that active ventilation combined with mask use outperformed portable HEPA filtration with up to 9 ACH in all scenarios.²⁸

Ventilation Considerations for Special Settings: Schools

HVAC and non-HVAC measures summarized here can be applied to a wide variety of contexts. For example, in schools, the CDC ventilation guidance recommends increasing outdoor ventilation by opening windows and using fans, improving central air filtration, and using portable HEPA filtration systems in high-risk areas such as nurses offices.

Maintain temperature and relative humidity at 72°F and 40-50% (ASHRAE winter classroom guidelines).

Other Measures

Germicidal Ultraviolet Irradiation (GUVI)

GUVI, which employs UV-C to inactivate fungal, bacterial, and viral pathogens, can be installed in ducts or as ceiling fixtures to disinfect indoor air (see ASHRAE guidelines)

GUVI can be costly (can be upwards of $1,500) and potentially harmful to occupants, thus they are typically only used in high-risk settings such as TB wards.

A modeling study estimates that installation of safer far-UVC in populated rooms could increase SARS-CoV-2 disinfection rates by 50-85%.²⁹

Summary of Evidence Related to Schools During the COVID-19 Pandemic

Summary of Evidence Related to Schools During the COVID-19 Pandemic

October 19, 2020

Most countries world-wide implemented localized or national school closures in response to the COVID-19 pandemic, with estimates of >65% of enrolled children globally affected by school closures.1 Since the early pandemic, schools in many settings around the world have fully or partially re-opened for in-person instruction, while in other settings schools have re-opened exclusively using online learning.

This document is a brief summary of the models and implementation approaches to re-opening schools, evidence related to the infection and transmission risk among school-age children, and the role of schools in driving transmission in the community. This is not a comprehensive review of the models used in all countries that have re-opened schools. Our systematic search of the published and pre-print literature yielded some articles that address this topic directly, but this summary also relies heavily on news articles and “grey literature” sources. It includes news articles, manuscripts published in peer-reviewed journals or on pre-print servers, and other resources identified through October 19, 2020. References that appeared in the daily COVID-19 Literature Report (Lit Rep) are marked with an asterisk*, and the summary is shown in the annotated bibliography below.

View the full report, which contains :

Considerations for Closing and Re-opening Schools

Summary of School Re-opening by Country

Summary of Approaches to Re-Opening Schools and Subsequent Transmission

Evidence Regarding the Susceptibility of School-age Children to SARS-CoV-2 Infection and their Potential from Transmission

Evidence Regarding the Effectiveness of Control Measures

Country-Specific Experience with School Re-Opening

Summary of School Re-opening Plans and Guidance by State

Dashboard for Tracking School Re-opening and Cases Linked to Schools

Recommended Resources

Annotated Bibliography

VIEW A PDF OF THE ENTIRE SUMMARY HERE

Executive Summary of Models of School Re-Opening Globally

Many countries globally began re-opening schools for in-person instruction starting in April and May 2020 following closures in response to the COVID-19 pandemic. In most settings where schools were re-opened, levels of community transmission were low at the time of re-opening. While subsequent outbreaks occurred in some schools, there was little evidence that schools were main drivers of transmission.

In many settings, the initial phase of school re-opening was conducted with significant modifications to the normal school model, including providing in-person instruction for only certain grades (usually younger), reduced class sizes, and alternating or staggered schedules.

Beginning in August and September, many countries shifted to class sizes and schedules that were similar to pre-pandemic models, although many instituted measures to reduce the risk of transmission, including establishing cohorts of students that don’t mix, use of face masks, staggered start times to reduce the volume of students in hallways, and full or partial closure of schools in response to a case in the school.

A small number of well documented outbreaks of SARS-CoV-2 in schools and overnight camps have demonstrated the potential for widespread transmission among school-age children, but successful examples of the application of coordinated control measures in schools and other large gatherings of children without widespread transmission indicates that it may be possible to reduce the risk of school-based transmission, particularly when rates of SARS-CoV-2 infection are relatively low in the community.

In the United States (US), there is considerable variability between states and districts in approaches to in-person instruction. As of October 2020, in some states, nearly all students are participating exclusively in online or remote education. In other states, students have returned to in-person learning, with models ranging from fully in-person learning with normal class sizes to hybrid models with a mix of in-person and online or remote learning.

Data regarding the number of cases of SARS-CoV-2 infection and COVID-19 disease linked to schools in the US is not collected and reported systematically, with variability from state-to-state in terms of requirements to report cases associated with schools. A number of dashboards are collecting available data about cases linked to schools.

Summary of COVID-19 Long-term Health Effects: Emerging Evidence and Ongoing Investigation, September 1, 2020

Summary of COVID-19 Long-term Health Effects: Emerging Evidence and Ongoing Investigation, September 1, 2020

Understanding the course of patients’ recovery from COVID-19 is critical for health system planning and for guiding public health prevention efforts. At less than one year into the COVID-19 pandemic, many long-term effects of SARS-CoV-2 infection remain unknown. However, new evidence is emerging rapidly about symptom profiles and rehabilitation needs of COVID-19 survivors in the initial months of their recovery. This document is a brief summary of published evidence about the sequelae of COVID-19 and ongoing studies of its long-term health effects. Included are manuscripts published in peer-reviewed journals or on pre-print servers through August 31, 2020. References summarized in this report were drawn from the COVID-19 Literature Report (Lit Rep) team database. References that appeared in the daily Lit Rep are marked with an asterisk*, and the summary is shown in the annotated bibliography below. This list was cross-referenced with the Infectious Disease Society of America COVID-19 Expanded Reference Center, a search of Clinicaltrials.gov for observational studies on COVID-19, and supplemented with studies mentioned in media articles.¹ We encourage readers to consult these sites and the daily Lit Rep for evidence that emerges following the date of this report.

View the full report, which contains :

Emerging evidence of COVID-19 Sequelae

Ongoing Studies of COVID-19 Clinical Outcomes and Sequelae

Table on selected COVID-19 epidemiological studies from these sites or reported on other media sites

Recommended Resources

Annotated Bibliography

VIEW A PDF OF THE ENTIRE SUMMARY HERE

Executive Summary of COVID-19 Long-term effects

Emerging evidence indicates that a majority of people who require hospitalization for COVID-19 experience sequelae such as fatigue and shortness of breath in the months following their hospital discharge.

Evidence on the long-term sequelae of COVID-19 among non-hospitalized but symptomatic individuals remains limited. Short-term follow-up indicates that recovery to usual state of health may be faster for this group than among their hospitalized counterparts.

Many epidemiologic studies are ongoing to systematically investigate the long-term effects of COVID-19.

Summary of School Re-Opening Models and Implementation
Approaches During the COVID 19 Pandemic, July 6, 2020

Summary of School Re-Opening Models and Implementation
Approaches During the COVID 19 Pandemic, July 6, 2020

Schools closed in many countries for some period of time during the COVID-19 pandemic as part of mitigation efforts to reduce transmission of SARS-CoV-2. Currently, a number of countries have fully or partially re-opened schools or are in the process of doing so.

This document is a brief summary of the models and implementation approaches to re-opening schools that focuses on the approaches used in 15 countries for which we were able to identify data. This is not a comprehensive survey of the models used in all countries that have re-opened schools. Oursystematic search of the published and pre-print literature yielded very few articles that address this topic and so this summary relies heavily on news articles and “grey literature” sources. It includes news articles, manuscripts published in peer-reviewed journals or on pre-print servers, and other resources identified through July 6, 2020. References that appeared in the daily COVID-19 Literature Report (Lit Rep) are marked with an asterisk*, and the summary is shown in the annotated bibliography.

VIEW A PDF OF THE ENTIRE SUMMARY HERE

COVID-19 Treatment Summary, June 5, 2020

COVID-19 Treatment Summary, June 5, 2020

COVID-19 treatment is rapidly evolving as public health professionals accumulate and share observations and research teams generate and disseminate their findings. This document is a brief summary of published evidence regarding medications to treat COVID-19. Included are manuscripts published in peer-reviewed journals or on pre-print servers through June 4, 2020. References summarized in this report were drawn from the COVID-19 Literature Report (Lit Rep) team database and identified with the #treatment label. References that appeared in the daily Lit Rep are marked with an asterisk*, and the summary is shown in the annotated bibliography below. This list was cross-referenced with the UW IDEA COVID-19 treatment reference site, the UW Medicine COVID-19 resource site, and the NIH treatment guidelines updated May 12, 2020 1–3. We encourage readers to consult these sites, which are updated in an ongoing manner, for evidence that emerges following the date of this report.

VIEW A PDF OF THE ENTIRE SUMMARY HERE

Executive Summary of COVID-19 Treatments

Remdesivir is the only agent currently recommended for treatment of COVID-19, for use in patients with severe disease.

Many trials of other agents are underway, but data do not support the use of other agents for treatment of COVID-19 at this time.

There are no currently recommended preventive treatment options for COVID-19, although there are ongoing trials evaluating pre- and post-exposure interventions.

Psychosocial Correlates of Outbreak Response Activities – March 18, 2020

VIEW A PDF OF THE ENTIRE SUMMARY HERE

Pandemic Preparedness and Response: Correctional Facilities – March 4, 2020

VIEW A PDF OF THE ENTIRE SUMMARY HERE

In-Depth Reports

Summary of Evidence Related to COVID-19 Vaccine Effectiveness and Breakthrough Infections

Impact of Variants of Concern on the Pfizer-BioNTech Vaccine Effectiveness

Impact of Variants of Concern on the Moderna Vaccine Effectiveness

Impact of Variants of Concern on the Johnson & Johnson-Janssen Vaccine Effectiveness

PREVIOUS IN-DEPTH REPORTS

Summary of Evidence Related to Travel, Hospitality and Service Industries, and COVID-19 Risk

Summary of Evidence Related to Travel, Hospitality and Service Industries, and COVID-19 Risk

Summary of Evidence Related to the Risk of Other Infections in the Context of COVID-19

Summary of Evidence Related to
the Risk of Other Infections in the Context of COVID-19

Summary of Evidence Related to
Recreational, Youth, and Collegiate Sports and the Risk of COVID-19

Summary of Evidence Related to
Recreational, Youth, and Collegiate Sports and the Risk of COVID-19

Summary of SARS-CoV-2 Novel Variants

Latest In-Depth Report: Summary of SARS-CoV-2 Novel Variants

Summary of Evidence Related to Indoor Ventilation to Reduce SARS-CoV2 Transmission

Summary of Evidence Related to Indoor Ventilation to Reduce SARS-CoV-2 Transmission

Summary of Evidence Related to Schools During the COVID-19 Pandemic

Summary of Evidence Related to Schools During the COVID-19 Pandemic

Executive Summary of Models of School Re-Opening Globally

Summary of COVID-19 Long-term Health Effects: Emerging Evidence and Ongoing Investigation, September 1, 2020

Summary of COVID-19 Long-term Health Effects: Emerging Evidence and Ongoing Investigation, September 1, 2020

Executive Summary of COVID-19 Long-term effects

Summary of School Re-Opening Models and Implementation
Approaches During the COVID 19 Pandemic, July 6, 2020

Summary of School Re-Opening Models and Implementation
Approaches During the COVID 19 Pandemic, July 6, 2020

COVID-19 Treatment Summary, June 5, 2020

COVID-19 Treatment Summary, June 5, 2020

Executive Summary of COVID-19 Treatments

Psychosocial Correlates of Outbreak Response Activities – March 18, 2020

Pandemic Preparedness and Response: Correctional Facilities – March 4, 2020

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Variant Name	Identification Date	Locations of Emergence	Key Mutations	Relative Transmissibility	Vaccine Efficacy
D614G spike protein substitution	February 2020	China; Germany	The spike protein D614G amino acid change is caused by an A-to-G nucleotide substitution at position 23,403 in the Wuhan reference strain	G614 mutant of SARS-CoV-2 is 31% more transmissible than the D614 wildtype¹¹	D164G SARS-CoV-2 was the dominant pandemic strain during the Moderna and Pfizer/BioNTech trials.
‘Cluster 5’ variant	November 2020	Denmark	Causes 3 amino-acid changes and two deletions in the spike	Not quantified. A WHO post from December 3, 2020 suggests that there is an increased risk of COVID-19 among people involved in mink farming.¹⁶	Preliminary findings: Antibodies from some people who had recovered from COVID-19 found it more difficult to recognize the Cluster-5 variant than to spot coronaviruses that did not carry these mutations.¹² The potential for mink to act as a reservoir for ongoing SARS-CoV-2 transmission led to a decision in early November, 2020 to cull all farmed mink in Denmark.¹⁶
Lineage B.1.1.7 (a.k.a. variant 20I/501Y.V1 or VOC 202012/01)	October 2020	United Kingdom	N501Y: A mutation in the receptor binding domain (RBD) of the spike protein at position 501, where the amino acid asparagine (N) has been replaced with tyrosine (Y). 69/70 deletion: Occurred spontaneously many times and likely leads to a conformational change in the spike protein. P681H: Near the S1/S2 furin cleavage site, a site with high variability in coronaviruses. This mutation has also emerged spontaneously multiple times.	56% (range 50-74%) more transmissible than earlier strains.¹⁸	The mRNA-1273 (Moderna) vaccine showed no significant reduction in neutralization activity against the SARS-CoV-2 B.1.1.7 variant.³⁴ Novavax reported that its NVX-CoV2373 vaccine has an estimated 85.6% efficacy against the B.1.1.7 variant.³⁶ The Oxford-AstraZeneca vaccine was reported to have 74% efficacy against B.1.1.7 compared to 84% efficacy against non- B.1.1.7 lineages.³⁸
Lineage B.1.351 (a.k.a. variant 20H/501Y.V2)	December 2020⁹	South Africa	This variant has multiple mutations in the spike protein, including K417T, E484K, N501Y. Unlike the B.1.1.7 lineage detected in the UK, this variant does not contain the deletion at 69/70.	Not quantified. Tegally et al. 2020 report that this variant became the dominant strain in by early November 2020 in the Eastern Cape and Western Cape Provinces of South Africa. “Whilst the full significance of the mutations is not yet clear, the genomic and epidemiological data suggest increased transmissibility associated with the virus.”⁹	The mRNA-1273 (Moderna) vaccine showed reduced activity against the B.1.351 variant emerging from South Africa.³⁴ Preliminary Novavax results from the South Africa cohort showed efficacy of 60% in the HIV-negative study population vs. 49.4% in the overall study population. Among 27 of the 44 cases with sequence data, mutations consistent with the B.1.351 variant were detected in 25 (93%).³⁶
Variant P.1 (a.k.a. 20J/501Y.V3 or descendent from B.1.1.28)	December 2020²¹	Brazil	This variant contains three mutations in the spike protein receptor binding domain: K417T, E484K, and N501.¹	Not quantified. CDC reports, “There is evidence to suggest that some of the mutations in the P.1 variant may affect its transmissibility and antigenic profile, which may affect the ability of antibodies generated through a previous natural infection or through vaccination to recognize and neutralize the virus.” ¹	Vaccine efficacy has not been reported for this strain as of the date of this report, but there is potential for this strain also to show reduced vaccine efficacy because it contains the same three spike protein mutations as lineage B.1.351.
CAL.20C	July 2020	California	Defined by five mutations: ORF1a: I4205V, ORF1b: D1183Y, S: S13I, S: W152C, S: L452R (Zhang et al., 2021)	Not quantified.	Not reported.

Room area (ft2)	100	200	300	400	500	600
Minimum CADR (cfm)	65	130	195	260	325	390

In-Depth Reports

Summary of Evidence Related to COVID-19 Vaccine Effectiveness and Breakthrough Infections

Impact of Variants of Concern on the Pfizer-BioNTech Vaccine Effectiveness

Impact of Variants of Concern on the Moderna Vaccine Effectiveness

Impact of Variants of Concern on the Johnson & Johnson-Janssen Vaccine Effectiveness

PREVIOUS IN-DEPTH REPORTS

Summary of Evidence Related to Travel, Hospitality and Service Industries, and COVID-19 Risk

Summary of Evidence Related to Travel, Hospitality and Service Industries, and COVID-19 Risk

Summary of Evidence Related to the Risk of Other Infections in the Context of COVID-19

Summary of Evidence Related to the Risk of Other Infections in the Context of COVID-19

Summary of Evidence Related to Recreational, Youth, and Collegiate Sports and the Risk of COVID-19

Summary of Evidence Related to Recreational, Youth, and Collegiate Sports and the Risk of COVID-19

Summary of SARS-CoV-2 Novel Variants

Latest In-Depth Report: Summary of SARS-CoV-2 Novel Variants

Summary of Evidence Related to Indoor Ventilation to Reduce SARS-CoV2 Transmission

Summary of Evidence Related to Indoor Ventilation to Reduce SARS-CoV-2 Transmission

Summary of Evidence Related to Schools During the COVID-19 Pandemic

Summary of Evidence Related to Schools During the COVID-19 Pandemic

Executive Summary of Models of School Re-Opening Globally

Summary of COVID-19 Long-term Health Effects: Emerging Evidence and Ongoing Investigation, September 1, 2020

Summary of COVID-19 Long-term Health Effects: Emerging Evidence and Ongoing Investigation, September 1, 2020

Executive Summary of COVID-19 Long-term effects

Summary of School Re-Opening Models and Implementation Approaches During the COVID 19 Pandemic, July 6, 2020

Summary of School Re-Opening Models and Implementation Approaches During the COVID 19 Pandemic, July 6, 2020

COVID-19 Treatment Summary, June 5, 2020

COVID-19 Treatment Summary, June 5, 2020

Executive Summary of COVID-19 Treatments

Psychosocial Correlates of Outbreak Response Activities – March 18, 2020

Pandemic Preparedness and Response: Correctional Facilities – March 4, 2020

Summary of Evidence Related to
the Risk of Other Infections in the Context of COVID-19

Summary of Evidence Related to
Recreational, Youth, and Collegiate Sports and the Risk of COVID-19

Summary of Evidence Related to
Recreational, Youth, and Collegiate Sports and the Risk of COVID-19

Summary of School Re-Opening Models and Implementation
Approaches During the COVID 19 Pandemic, July 6, 2020

Summary of School Re-Opening Models and Implementation
Approaches During the COVID 19 Pandemic, July 6, 2020