Synthesis Summary Reports
Schools
COVID-19 and Schools
April 1, 2021
COVID-19 Literature Report Team: Brandon L. Guthrie PhD, Lorenzo Tolentino MPH, Molly Fischer MPH, Jessie Seiler MPH, Rodal Issema MPH, Emily Rowlinson MPH, Francis Slaughter BA, Mark Fajans MPH, Ashley Tseng MPH, Wenwen Jiang MPH, Julianne Meisner BVM&S MS, Diana M. Tordoff MPH, Sherrilynne Fuller PhD FACMI, Dylan Green MPH, Diana Louden MLib, Alison Drake PhD MPH, Will Hahn MD, and Jennifer M. Ross MD MPH
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. 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 intended to serve an updated resource compiling information about what is known about COVID-19 and SARS-CoV-2 in the context of schools, with a primary focus on K-12 grades. Much of the information in this synthesis report is drawn from summaries included in the daily COVID-19 Literature Situation Report. This is not intended to be a systematic or comprehensive summary, rather it is a frequently updated compilation and synthesis of evidence related to topics relevant to those making decisions about schools during the COVID-19 pandemic This synthesis report is supplemented by in-depth summaries of evidence related to COVID-19 and schools, including models of school re-openings from around the world that were release in July and October 2020.
Text marked in BLUE is new since the last version of this summary.
This is only part 1 of the synthesis report. A PDF version is available here that includes all relevant article summaries (part 2) in addition to the narrative seen below.
There is clear evidence that school-age children are susceptible to SARS-CoV-2 infection (Carsetti), can transmit to other children and adults, and on rare occasions, can have severe cases of COVID-19 disease as well as multi-system inflammatory syndrome in children (MIS-C). While severe outcomes do occur among school-age children and young people, particularly those with co-morbidities, the incidence of severe outcomes is very low (Carsetti, Hua, Stage, Somekh, and Heavey). An analysis of COVID-19 cases among school-age children found that 1.2% school-aged children with COVID-19 were hospitalized, including 0.1% who required ICU admission (Leeb). While very rare, deaths associated with SARS-CoV-2 infection have occurred in children, accounting for 0.08% of deaths attributed to COVID-19 (Bixler).
School-age children are capable of transmitting the virus to other children and adults (Szablewski, Stein-Zamir, Chu). While there is evidence that younger children (i.e., younger than 10 years old) may be less susceptible to infection and less likely to transmit to close contacts if they are infected (Park, Ladhani, Soriano-Arandes), a relatively small number of well documented outbreaks involving school-age children demonstrate the potential for widespread transmission among children, particularly when there are limited measures in place to stop transmission (Szablewski, Stein-Zamir, Chu) [See section of Impact of Control Measures to Limit Transmission in Congregate Settings with Children and Outbreaks of SARS-CoV-2 Linked to K-12 Schools].
Widespread transmission can occur among school-age children (Szablewski, Stein-Zamir). A well-documented case of widespread SARS-CoV-2 transmission among school-age children came from an overnight camp in Georgia in July 2020 (Szablewski). Additional outbreak investigations have demonstrated the involvement of school-age children in large clusters of transmission, particularly when transmission control measures have not been rigorously implemented (Pray, Schwartz). By contrast, when adherence to control measures are adhered to, the risk of transmission from a symptomatic child to a caregiver is low (Lee).
While there is clear evidence for the potential for widespread transmission of SARS-CoV-2 in a school environment, there is also direct and indirect evidence that the development of and adherence to protocols to minimize the risk of transmission through the use of face masks (van den Berg, Hershow, Bignami, Vlachos), physical distancing, and other control measure as well as identify cases, isolating infected individuals, quarantining close contacts, and maintaining cohorts or capsules with limited mixing between groups can substantially limit the spread of SARS-CoV-2 in the context of group settings with school-age children. A study of SARS-CoV-2 transmission among children and staff in summer schools in Spain during July 2020 found that the transmission rate under strict prevention measures was lower in school-like facilities than the general population (Jordan). The CDC has released guidelines for reopening schools of in-person instruction which include guiding principles for prioritize safe school reopening ahead of reopening many other activities (CDC). Outbreaks linked to recreational and social activities have been observed in some schools (Siegel).
The CDC has revised its guidelines regarding physical distancing in classrooms, recommending a change from ≥6 foot to ≥3 foot spacing in response to evidence the schools with a 3 foot spacing policy did not have higher incidence of COVID-19 compared to schools with a 6 foot spacing policy in the context of universal masking and other mitigation measures in place (van den Berg).
When schools open for in-person instruction while there is transmission of SARS-CoV-2 in the community, the identification of infected students and staff should be expected, particularly asymptomatic cases in children. There have been a relatively small number of large outbreaks linked to schools (Larosa, Stein-Zamir); however, most cases linked to schools have resulted in either no secondary cases, or only a small number of secondary cases (1 to 2 secondary cases) (Ismail, Larosa). One of the first well documented school outbreaks of SARS-CoV-2 occurred in Jerusalem, Israel in a secondary school (grades 7-12) in mid-May 2020 (Stein-Zamir).
There is increasing evidence that students participating in in-person learning have not experienced an increased risk of SARS-CoV-2 infection (Perramon, Gras-Le Guen, Ladhani, Doyle). As more evidence emerges there is increasing consensus that wide-scale transmission linked to schools has not occurred, and that while outbreaks have been observed in a number of settings (approximately 11% of schools in Florida [Doyle] have had outbreaks during the 2020-2021 school year), the size of these outbreaks has been small (median if 6 in Florida [Doyle] and median of 1 in England [Ismail]). Testing of asymptomatic students and staff in New York public schools determined that the incidence of COVID-19 was lower among the school population (341.1 cases per 100,000) compared to the citywide population (528.9 cases per 100,000) (Varma). In Florida, where most schools resumed in-person instruction sometime during August 2020, fewer than 1% of registered students were identified as having school-related COVID-19 (Doyle). Despite high community incidence and an inability to space classroom seats at least 6 feet apart, there was low SARS-CoV-2 transmission and no school-related outbreaks in 20 Salt Lake County elementary schools. Schools documented high mask adherence among students and also implemented multiple strategies to limit transmission (Hershow).
In Sweden, where schools remained open for many grades throughout the pandemic, there was a higher rate of SARS-CoV-2 infection among teachers who taught in-person for lower-secondary grade students (age 14 to 16) compared to upper-secondary teachers who taught students (age 16 to 19) remotely (Vlachos). Primary school teachers who taught in-person had a lower incidence of infection, which was comparable to remote teachers. In Swedish schools that remained open, measures to limit transmission in schools were minimal, with no quarantine of those exposed unless they showed symptoms of infection, no reductions in class-size, and face masks rarely used. In Scotland, teachers were at 1.4-times the risk for developing SARS-CoV-2 infection compared to the general population of working-age adults, but teachers and their household members were not at increased risk of COVID-19-associated hospitalization and were at lower risk of severe COVID-19 (Fenton). In the US, there has been very limited evidence of within-school transmission (Zimmerman, Falk, Fricchione, Monod). In response to this evidence, the CDC has concluded that schools can be safe if precautions are taken on campus and in the community (Honein, CDC).
Evidence from clusters of COVID-19 linked to in-person school transmission in Georgia indicate that teachers played a leading role in transmission, with teacher-to-teacher and teacher-to-student transmission far more common than student-to-teacher transmission (Gold), with similar findings in New York City (Varma). This highlights the importance of focusing COVID-19 prevention protocols on the teachers as a potential source of infection rather than focusing on students as the main source of infection. It also demonstrates the potential for vaccination of teachers to protect teachers from severe disease as well as to interrupt transmission if vaccination prevents infection (rather than just development of COVID-19 disease) and reduces the likelihood that an infected vaccinated individual transmits the infection to others. Thus vaccination of teachers may indirectly protect students even if vaccines are not available to children.
Sports and other recreational activities that occur outside and with no or limited direct contact between participants have been shown to be safe (Watson , Sasser, Watson), while some indoor sports and outdoor contact sports have been linked to outbreaks of COVID-19 (Atrubin, Atherstone, Siegel).
There is very little evidence, both in the context of low and high community transmission, that schools have been a driver of transmission (Leidman, Monod, Mensah, Doyle, Ladhani). In England (Mensah) and Florida (Doyle), incidence of COVID-19 in school children mirrors the incidence in the general population with a lag indicating that community transmission was the driver of infections in children. Another study from England found adults (≤65 years old) had a higher risk of SARS-CoV-2 infection if they lived in a household with school-age children during the second wave of the pandemic, although the role of school-based transmission was not clear (Forbes). During a period when schools had not yet re-opened, relaxation of mobility restrictions and re-opening other businesses and activities was associated with considerable increases in the prevalence of COVID-19 among adolescents and youth, indicating that exposures outside of the classroom are like more relevant to transmission in this age group than school-based transmission (Rumain).
Secondary transmission of SARS-CoV-2 from an infected student to their close contacts has been low, estimated at 2% of 102 close contacts identified in investigations of cases that occurred in K-12 schools (n=22) in Springfield and St. Louis County, Missouri (Dawson) and a secondary attack rate of 0.5% in New York City (Varma).
A small number of countries in regions with some level of community transmission of SARS-CoV-2 never imposed school closures. Sweden is notable among countries that did not close all schools, although Sweden did close schools for secondary grade students between March 18 and June 4, 2020 (Vogel). The incidence of severe COVID-19 was low among school-age children in Sweden and the risk among schoolteachers was similar to other occupations (Ludvigsson) Starting in late April and May 2020, many countries around the world started re-opening schools, many of which also sustained limits on other mobility and closures of many businesses after schools were re-opened. Since the initial re-opening, which often occurred for subsets of students or with modified schedules, schools have fully reopened for all students in many settings. While there have been examples of large-scale school closures in response to cases arising in schools soon after re-opening, particularly when school re-opening coincided with widespread relaxation of mobility restrictions and business closures (Israel, parts of the United States), many countries have been able to keep the large majority of schools open, even as cases of COVID-19 have increased in the community (Germany, France, Norway, Belgium, Scotland, South Korea).
Debates are ongoing about how to best balance the potential benefit of reducing SARS-CoV-2 transmission, by closing schools or significantly modifying the schedule of in-person learning, against the very real consequences of such measures on student learning (Tomasik), indirect harms to students (e.g., lack of access to school-based feeding programs) (Zviedrite), and the considerable burden this places on parents and caregivers (Verlenden), particularly those who need to simultaneously work. The burden of these indirect effects is likely to fall disproportionally on lower income families and people of color.
Rozhnova et al. (Mar 12, 2021). Model-Based Evaluation of School- and Non-School-Related Measures to Control the COVID-19 Pandemic. Nature Communications. https://doi.org/10.1038/s41467-021-21899-6
- An age-structured SARS-CoV-2 transmission model fitted to data from the COVID-19 pandemic in the Netherlands suggested that if methods to reduce the effective reproduction number (Re) of non-school-based contacts with non-school-based measures are exhausted or undesired and Re is still near 1, school-based prevention measures may be beneficial, particularly among older students. The authors provide examples from summer and autumn 2020 as evidence that keeping schools closed after summer of 2020 likely would not have prevented the fall wave of infections, but closing schools in November 2020 may have reduced Re.
Klein et al. (Feb 24, 2021). Stepping Back to School: A Step-by-Step Look at COVID Introduction, Spread, and Exportation. https://covid.idmod.org/data/Stepping_Back_to_School.pdf
- [Report, not peer-reviewed] Covasim, a model previously used to describe SARS-CoV-2 transmission among inter-personal contacts in King County, Washington predicted that the rate of introduction of SARS-CoV-2 into K-12 school classroom settings is proportional to the prevalence of SARS-CoV-2 in the community. The model is an agent-based model of contacts at home, school, work and in the community. According to the model, each 0.1% increase in community prevalence resulted in an increase in daily introduction rate by 3.1 per 100,000 population. In a classroom setting, if in-school transmissibility is low, potential outbreaks were predicted to be small, with additional countermeasures such as asymptomatic testing adding little value. If transmission is high, however, large outbreaks are possible with more transmissible variants or if interventions are insufficient. The model also predicted that the frequency of exports from schools to the broader community is dependent on the number of students infected in the schools.
Kaiser et al. (Dec 2, 2020). Social Network-Based Strategies for Classroom Size Reduction Can Help Limit Outbreaks of SARS-CoV-2 in High Schools. A Simulation Study in Classrooms of Four European Countries. Pre-print downloaded Dec 3 from https://doi.org/10.1101/2020.11.30.20241166
- Pre-print, not peer reviewed] A simulation study of classroom based on longitudinal survey data collected from four European countries (n=507 classrooms, 12,291 students) found that while establishing student cohorts that minimize out-of-school contact between different cohorts would be most effective in preventing spread of SARS-CoV-2, cohorting by approximation of social networks also performed well. Network-based cohorting outperformed dividing classrooms by gender. For all cohorting strategies, schedules with alternating weeks of instruction were most effective.
Naimark et al. (Nov 21, 2020). The Potential Impact of School Closure Relative to Community-Based Non-Pharmaceutical Interventions on COVID-19 Cases in Ontario Canada. Pre-print downloaded Nov 23 from https://doi.org/10.1101/2020.11.18.20234351
- [Preprint, not peer-reviewed] A modeling study based on a scenario of one million individuals in Ontario, Canada predicted that school reopening would result in a small change in COVID-19 case numbers among students and teachers in a setting with community-based prevention measures. The model showed that the increase was driven mostly by acquisition in the community, and fewer than 5% of infections among students and teachers were acquired within schools. It also indicated that implementation of community-based prevention measures would reduce 39,355 COVID-19 incident cases by October 31, 2020, while school closure vs. reopening on September 15 would reduce 2,040 cases.
Bracis et al. (Nov 13, 2020). Widespread Testing, Case Isolation and Contact Tracing May Allow Safe School Reopening with Continued Moderate Physical Distancing: A Modeling Analysis of King County, WA Data. Infectious Disease Modelling. https://doi.org/10.1016/j.idm.2020.11.003
- Modeling based on King County, Washington State indicates that returning to a level of 75% of pre-COVID-19 physical interactions between May 15-July 15 was projected to result in 350 daily deaths by early September 2020. Maintaining less than 45% of pre-COVID-19 physical interactions was required to ensure low levels of daily infections and deaths. A combination of increased testing, isolation of symptomatic infections, and contact tracing permitted 60% of pre-COVID-19 physical interactions and allowed opening of schools with <15 daily deaths.
Klein et al. (Nov 5, 2020). Testing the waters: is it time to go back to school? Diagnostic screening as a COVID‐19 risk‐mitigation strategy for reopening schools in King County, WA. Institute for Disease Modeling. Downloaded Nov. 5 from https://covid.idmod.org/data/Testing_the_waters_time_to_go_back_to_school.pdf
- [Pre-print, not peer-reviewed] Modeling of K-12 school reopening in King County, Washington found that if in-school countermeasures are observed, diagnostic screening either with PCR tests or rapid antigen tests may be of little benefit due to a higher rate of false positive tests in this low prevalence setting. Modeled in-school countermeasures included daily symptom screening, contact tracing, face masks, hand hygiene, improved ventilation, and physical distancing. Countermeasures could reduce the 3-month cumulative incidence to 2% or less for students, teachers, and staff. In this setting, school-based transmission was also found to be a limited driver of community spread, holding the effective reproduction number Re = 1 over 3 months.
Saad et al. (Nov 3, 2020). COVID-19 Active Surveillance Simulation Case Study – Health and Economic Impacts of Active Surveillance in a School Environment. Pre-print downloaded Nov 4 from https://doi.org/10.1101/2020.10.28.20221416
- A simulation study of a school environment concluded that daily testing can assist with maintenance of a low infection rate. The authors concluded that a reasonable daily test percentage (6%-10% with social distancing and mask wearing, or 8-10% without mitigation procedures) among the student population can achieve a low infection rate (≤10%).
Gilbert et al. (Dec 11, 2020). Racial and Ethnic Differences in Parental Attitudes and Concerns About School Reopening During the COVID-19 Pandemic — United States, July 2020. MMWR. https://doi.org/10.15585/mmwr.mm6949a2
- An internet panel survey (n=858) conducted in July 2020 found parents of school-aged children who identified as members of racial and ethnic minority groups expressed more concerns about some aspects of school re-opening than their peers who identified as non-Hispanic white. Though the majority (56.5%) strongly or somewhat agreed that schools should reopen in fall 2020, non-Hispanic white parents were significantly more likely than Black or Hispanic parents to support school reopening. Minority racial/ethnic groups were also more likely to report concerns about schools opening at full capacity, student mitigation compliance, and their child contracting COVID-19 from school and bringing it home.
- Checklist to support schools re-opening and preparation for COVID-19 resurgences or similar public health crises – WHO (Dec 10)
- Physical Distancing in Schools for SARS-CoV-2 and the Resurgence of Rhinovirus – The Lancet Respiratory Medicine (Oct 22)
- The Role of Schools and School-Aged Children in SARS-CoV-2 Transmission – The Lancet Infectious Diseases (Dec 8)
Non-Pharmaceutical Interventions
Non-Pharmaceutical Interventions
April 1, 2021
COVID-19 Literature Report Team: Brandon L. Guthrie PhD, Lorenzo Tolentino MPH, Molly Fischer MPH, Jessie Seiler MPH, Rodal Issema MPH, Emily Rowlinson MPH, Francis Slaughter BA, Mark Fajans MPH, Ashley Tseng MPH, Wenwen Jiang MPH, Julianne Meisner BVM&S MS, Diana M. Tordoff MPH,
Sherrilynne Fuller PhD FACMI, Dylan Green MPH, Diana Louden MLib, Alison Drake PhD MPH, Will Hahn MD, and Jennifer M. Ross MD MPH
Much of the information in this synthesis report is drawn from summaries included in the daily COVID-19 Literature Situation Report. This is not intended to be a systematic or comprehensive summary, rather it is a frequently updated compilation and synthesis of evidence related to topics relevant to those making decisions about policies related to non-pharmaceutical interventions and their implementation.
Text marked in BLUE is new since the last version of this summary.
This is only part 1 of the synthesis report. A PDF version is available here that includes all relevant article summaries (part 2) in addition to the narrative seen below.
Broad scale mobility restrictions (e.g., lockdowns, stay-at-home orders, shelter-in-place orders) imposed for a defined period of time have been shown to significantly reduce actual mobility to a large degree in many settings around the world (Pan, Pullano, Feehan), and these interventions have been associated with sizable reductions in the incidence of SARS-CoV-2 infections, COVID-19 cases, and deaths (Banholzer, Bendavid, Abouk, Flaxman). Longer duration of statewide closures was associated with a lower likelihood of a subsequent rapid rise in COVID-19 cases (Dasgupta). Mobility restrictions were most effective in preventing SARS-CoV-2 transmission in the initial pandemic surge compared to later surges (Nouvellet, Singh) and some evidence indicates that the most restrictive shelter-in-place orders may not have had a benefit beyond what people were already doing (Berry). Tracking surveys indicate that over time there have been declines in adherence to some non-pharmaceutical interventions (e.g., staying at home except for essential activities or exercise, having no close contact with non–household members, not having visitors, and avoiding eating at restaurants) but an increase in the use of facemasks (Crane, Hoeben). Some evidence from mathematical models suggests that it may be possible to relax some non-pharmaceutical interventions once vaccinations become widespread (Kraay, Shen), and there is some emerging evidence from Israel that increases in the proportion of the population that is vaccinated may be associated with declines in SARS-CoV-2 incidence in those not yet vaccinated (Milman).
Evidence of the effectiveness of bans on mass gathers, independent of the effect of other non-pharmaceutical interventions is relatively limited; however, there is some evidence that earlier implementation of bans on mass gatherings reduced mortality due to COVID-19. A number of well-documented “superspreading” events provides additional evidence for the potential effectiveness of mass gathering bans (Lemieux, Firestone).
Direct evidence for the effectiveness of school closures on community transmission of SARS-CoV-2 is inconclusive. In the presence of effective mitigation strategies, K-12 schools have not been shown to be important drivers of community transmission, at least in the context of relatively low community transmission (CDC). [For a more thorough examination of schools and COVID-19, refer to the COVID-19 the Synthesis Summary on COVID-19 and Schools. See section below on Mitigation Protocols – K-12 Schools].
Reopening of colleges and universities for in-person instruction has been linked to surges in cases in some communities (Pray, Vang). Much of the transmission on college and university campuses has been linked to social events and gatherings rather that in-person classes (Weil). [See section below on Mitigation Protocols – Colleges and Universities].
Multiple lines of evidence indicated that facemasks are effective in preventing both transmission and acquisition of SARS-CoV-2. Mask mandates are also effective in reducing community transmission. Each of these lines of evidence is described below.
Experiments that simulate the dissemination of aerosols and droplets as well as computer models have shown that a broad range of mask and face covering types are at least partially effective at blocking the spread of aerosols and droplets from an infected individual (Akhtar). The greatest protection was from N95 respirators, with similar protection from a cloth mask over a medical procedure mask (double masking) (Brooks, Sharma).
Leung et al. (May 2020). Respiratory Virus Shedding in Exhaled Breath and Efficacy of Face Masks. Nature Medicine. https://doi.org/10.1038/s41591-020-0843-2
- Use of a surgical mask significantly reduced the proportion of droplets and aerosols with detectable virus among children and adults with confirmed seasonal coronavirus and seasonal influenza infection. Among 17 patients with seasonal coronavirus, virus was detected in 30% of droplets and 40% of aerosols among those randomized to not wear a surgical mask compared to 0% detection in both droplets and aerosols of those randomized to wear a surgical mask.
- Similar results were found for the effect of surgical masks worn by patients with seasonal influenza, but there was no effect of wearing a surgical mask among those with a rhinovirus infection.
Wide variation has been observed across different mask/face covering types in terms of control of aerosols and droplets, protection from infection, and filtration efficiency. N95 masks offer the highest level of protection, with similar performance for cloth masks combined with a medical procedure mask. Double layer cloth masks and higher thread-count cloth masks offer intermediate control of aerosols and droplets, while most single layer masks showed limited control (Guha, Clapp). It may be possible to improve the airtight fit of masks by using adhesive strips (Pan).
Face masks have been shown to prevent acquisition of SARS-CoV-2 when worn consistently and correctly by individuals who were taking care of patients with SARS-CoV-2. This protection has been observed both for healthcare workers (Akinbami, Schneider) and for caregivers of children with COVID-19 (Yun, Lee).
The implementation of mandates to wear facemasks or face coverings in public places when physical distancing is not possible have been associated with declines in the incidence COVID-19 cases (Guy). Most evidence for the effectiveness of mask mandates has come from ecological and time series analyses, which often complicate the identification of the effect of mask mandates separate from other non-pharmaceutical interventions (Rebeiro, Van Dyke, Adjodah). One analysis estimated that statewide mask mandates resulted in a 5.5 percentage point decrease in the COVID-19 hospitalization growth rate among adults aged 18–64 years after mandate implementation, compared to the growth rates during the 4 weeks preceding implementation of the mandate (Joo). Survey results indicate that higher levels of reported mask usage and physical distancing are associated with a greater likelihood that communities are able to gain control of SARS-CoV-2 transmission (Rader).
Arvelo et al. (Feb 12, 2021). COVID-19 Stats: Percentage of Middle and High School Students Aged 13–21 Years Attending In-Person Classes Who Reported Observing Fellow Students Wearing a Mask All the Time, by School Setting and Activity — United States, October 2020. MMWR. https://doi.org/10.15585/mmwr.mm7006a5
- Among a sample of 3,953 middle and high school students participating in a Falcon-CDC Foundation cross-sectional web panel survey in October 2020, approximately 65% reported that fellow students wore a mask “all the time” in the classroom, hallways, and stairwells. Lower frequencies were reported for other indoor settings, including school buses (42%), restrooms (40%), and the cafeteria when not eating (36%). Reported mask use was lowest in outdoor settings (extracurricular activities 28%, outside school property 25%).
Basch et al. (Feb 2, 2021). Promoting Mask Use on TikTok: A Descriptive Study on Unconventional Approach to Public Health Education. JMIR Public Health and Surveillance. https://doi.org/10.2196/26392
- Videos promoting mask use posted on the social media platform TikTok with the hashtag #WearAMask (n=100) received almost 10 times as many cumulative views as videos by the World Health Organization (WHO) to promote mask use (n=32). Most of the #WearAMask videos used humor and dance to garner almost 500 million views. In contrast, the WHO videos, of which 3 included humor and none included dance, only garnered over 57 million views.
Barceló and Sheen. (Dec 1, 2020). Voluntary Adoption of Social Welfare-Enhancing Behavior: Mask-Wearing in Spain during the COVID-19 Outbreak. PloS One. https://doi.org/10.1371/journal.pone.0242764
- A nationally representative survey of 4000 citizens in Spain during early stages of the COVID-19 pandemic reported that 49% of respondents wore protective masks either occasionally or very frequently, 10% rarely wore a mask, and 41% never wore a mask. People who were young, had higher educational attainment, reported a lower concern about infection, and with an introverted personality were less likely to wear a mask.
Rennert et al. (Mar 22, 2021). Surveillance-Based Informative Testing for Detection and Containment of SARS-CoV-2 Outbreaks on a Public University Campus: An Observational and Modelling Study. The Lancet Child & Adolescent Health. https://doi.org/10.1016/S2352-4642(21)00060-2
- A novel strategy of random testing combined with follow-up targeted testing in outbreak areas (“surveillance-based informative testing”, SBIT) was associated with a 36% reduction in peak weekly COVID-19 cases at Clemson University in South Carolina over a 2-week period. The strategy helped identify outbreaks in 45 residence halls across 8 buildings. Transmission models based on testing data suggested that random surveillance testing alone without follow-up targeted testing would have resulted in 24% more cases throughout the semester, and up to 154% more cases in the absence of SBIT compared to voluntary testing alone.
Miller et al. (Mar 10, 2021). COVID-19 Case Investigation and Contact Tracing in Central Washington State, June–July 2020. Journal of Community Health. https://doi.org/10.1007/s10900-021-00974-5
- 68% of individuals contacted by public health departments reported having “no close contacts” (with anyone), according to an evaluation of case investigations and contact tracing (CICT) in 3 health districts in central Washington State. The study included the results of interviews with individuals with COVID-19 (n = 3,572). A total of 968 individuals with COVID-19 named specific contacts (27% of all COVID-19 cases interviewed), naming a total of 2,293 contacts, corresponding to a mean of 2.4 contacts per individual with COVID-19. There was no difference in reporting of contacts by ethnicity, and minimal differences by age group, sex, and employment status.
Hou et al. (Mar 8, 2021). A Rapid Method to Evaluate Pre-Travel Testing Programs for COVID-19 A Study in Hawaii. Pre-print downloaded Mar 9 from https://doi.org/10.1101/2021.03.06.21251482
- [Pre-print, not peer-reviewed] A rapid field study conducted in the Kahului main airport in Maui, Hawaii 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. 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. Participants were sampled anonymously at the time of departure to avoid interfering with travel plans, but had to have a ≤14 day stay in Hawaii to be eligible for the study.
Moreno et al. (Mar 6, 2021). SARS-CoV-2 Transmission in Intercollegiate Athletics Not Fully Mitigated with Daily Antigen Testing. Pre-print downloaded Mar 8 from https://doi.org/10.1101/2021.03.03.21252838
- [Pre-print, not peer-reviewed] Two SARS-CoV-2 outbreaks occurred among US university athletic programs during the fall 2020 despite mandatory directly observed daily antigen testing, suggesting that antigen testing alone may not be sufficient to prevent outbreaks in congregate settings. In the first outbreak, 32 confirmed cases occurred within an athletics program after the index patient attended a meeting while infectious, despite receiving a negative antigen test that day. 24 (92%) of 26 isolates from this outbreak were closely related, suggesting sustained transmission following an initial introduction event. In the second outbreak, 12 cases occurred among athletes who competed from two universities despite athletes receiving negative antigen test results on the day of the competition. Sequences from both teams were closely related and unique from strains circulating in the community, suggesting transmission during competition.
Fuchs et al. (Mar 2, 2021). Assessment of a Hotel-Based COVID-19 Isolation and Quarantine Strategy for Persons Experiencing Homelessness. JAMA Network Open. https://doi.org/10.1001/jamanetworkopen.2021.0490
- Among people who were referred to isolation and quarantine (I/Q) hotels in San Francisco from hospitals, outpatient settings, and public health surveillance, 81% completed their recommended I/Q course. The retrospective cohort study found that of the 1,009 I/Q hotel guests, 501 (50%) were persons experiencing sheltered (n=295) or unsheltered (n=206) homelessness, 33% had other medical disorders, 25% had mental health disorders, and 26% had substance use disorders. The factors that were most strongly associated with premature discontinuation were unsheltered homelessness (aOR=4.5) and quarantine status (compared to isolation) (aOR=2.6).
Rubio et al. (Feb 1, 2021). The COVID-19 Symptom to Isolation Cascade in a Latinx Community: A Call to Action. Open Forum Infectious Diseases. https://doi.org/10.1093/ofid/ofab023
- Approximately a quarter of SARS-CoV-2 infected patients at a low-barrier testing site serving a low-income Latinx community in San Francisco were already outside the 10-day window of isolation at the time they received counseling on isolation. Among symptomatic participants (n=145), 83% percent had moderate to high levels of virus (Ct <33). All participants received post-test guidance on the day of testing on how to quarantine while awaiting test results if they were experiencing symptoms or had a recent exposure to someone with COVID-19. Participants with a positive test result received counseling about isolation on a median of day 7 (out of a ten day recommended quarantine period). Access to a test site was the most common barrier to testing, and food and income loss was the most commonly reported barrier to isolation.
Nelson et al. (Feb 19, 2021). SARS-CoV-2 Positivity on or After 9 Days Among Quarantined Student Contacts of Confirmed Cases. JAMA. https://doi.org/10.1001/jama.2021.2392
- Among student contacts of confirmed COVID-19 cases in Florida between August and November 2020, a protocol requiring a negative RT-PCR test as early as day 9 of quarantine reduced the loss of instruction days compared to a conventional 14-day quarantine without testing. The number of missed days decreased by 3,649 days with the 9-day testing protocol compared with a theoretical 14-day quarantine (8,097 days vs 11,746 days). Of the 839 student contacts tested on days 9 to 14, 40 were positive for SARS-CoV-2 infection. Among the 799 students who tested negative, only 1 student became symptomatic after returning to school and received a positive test on day 14 after initially testing negative on day 9. The viral sequence identified from this participant was genetically distinct from the sequence of the case isolated from the known exposure.
Spencer et al. (Jan 22, 2021). COVID-19 Case Investigation and Contact Tracing Efforts from Health Departments — United States, June 25–July 24, 2020. MMWR. https://doi.org/10.15585/mmwr.mm7003a3
- An analysis of case investigation and contact tracing metric data reported by 56 U.S. health departments found wide variation in capacity and ability to conduct timely and effective contact tracing. A median of 57% of COVID-19 patients were interviewed within 24 hours of report of the case to a health department; a median of 1.2 contacts were identified and prioritized for interview per patient; and a median of 55% of contacts were notified within 24 hours of identification by a patient.
- When departments’ caseloads of COVID-19 were higher, the percentage of COVID-19 patients interviewed within 24 hours and the number of contacts identified per patient were both lower. The inverse relationship suggests that increases in staffing capacity might help reduce delays in interviewing patients and identify more contacts, according to the authors.
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Mancastroppa et al. (Dec 26, 2021). Stochastic Sampling Effects Favor Manual over Digital Contact Tracing. Nature Communications. https://doi.org/10.1038/s41467-021-22082-7
- A study using a stochastic model to compare manual and digital contact tracing methods found that even if the probability of tracing a contact was equal by each method, manual tracing robustly performed better than digital, after accounting for intrinsic delays and limited scalability associated with manual measures. The authors note that better performance of manual tracing is enhanced by heterogeneity in individual behavior; “superspreaders” not using digital contact tracing apps are invisible to digital contact tracing, while they can be easily traced manually due to their multiple contacts.
Ballouz et al. (Dec 23, 2020). Digital proximity tracing app notifications lead to faster quarantine in non-household contacts results from the Zurich SARS-CoV-2 Cohort Study. Pre-print downloaded Dec 28 from https://doi.org/10.1101/2020.12.21.20248619
- [pre-print; not peer-reviewed] Users of the SwissCovid digital contract tracing app who were notified of a non-household close contact with a SARS-CoV-2 quarantined a median of 1 day earlier than close contacts who were manually traced. Among a population-based sample of adult SARS-CoV-2 index cases (n=393) and close contacts (n=261) identified through manual contact tracing who were surveyed regarding use of the SwissCovid app, 88% of index cases reported receiving and uploading a notification code in the app to trigger a warning among proximity contacts. Among close contacts using the app, only 38% reported receiving an app warning due to the risk exposure. Non-household contacts notified by the app started quarantine on a median of day 2 following the exposure compared to day 3 among those not notified by the app.
Bushman et al. (Dec 18, 2020). Transmission of SARS-CoV-2 before and after Symptom Onset Impact of Nonpharmaceutical Interventions in China. Pre-print downloaded Dec 21 from https://www.medrxiv.org/content/10.1101/2020.12.16.20214106v1
- [Pre-print, not peer-reviewed] Using serial interval data from infector-infectee pairs before and after the rollout of non-pharmaceutical interventions (NPIs) in China (January and February 2020), the relative frequency of pre-symptomatic transmission increased from 34% pre-rollout to 71% post-rollout. After the rollout of NPIs, transmission post-symptom onset was reduced by 82% whereas pre-symptomatic transmission decreased by only 16%. The authors suggest that interventions that limit opportunities for transmission in the later stages of infection, such as contact tracing and isolation, may have been particularly effective at reducing transmission of SARS-CoV-2.
von Wyl et al. (Dec 16, 2020). Drivers of Acceptance of COVID-19 Proximity Tracing Apps in Switzerland: A Panel Survey Analysis (Preprint). JMIR Public Health and Surveillance. https://doi.org/10.2196/25701
- Higher monthly household income, more frequent internet use, better adherence to mask use, and being a non-smoker were associated with reported uptake of digital proximity tracing apps in Sweden (n=1,511). In a randomly selected subsample (n=711) with more detailed information, higher levels of trust in government and health authorities were associated with app uptake. Most frequent reasons for not using the app were lack of perceived benefit (36.8%), app incompatible with phone (22.8%), and privacy concerns (22.4%).
Bachtiger et al. (Nov 6, 2020). Belief of Having Had Unconfirmed Covid-19 Infection Reduces Willingness to Participate in App-Based Contact Tracing. Npj Digital Medicine. https://doi.org/10.1038/s41746-020-00357-5
- A questionnaire administered to 12,434 UK National Health Service users found that people who believe they had COVID-19 and recovered from it were 27% less likely to be willing to download a contract tracing app than people who do not believe they had COVID-19. While 60.3% were willing to participate, the authors report this proportion is insufficient for the app to be an effective intervention.
Malheiro et al. (Sept 29, 2020). Effectiveness of Contact Tracing and Quarantine on Reducing COVID-19 Transmission: A Retrospective Cohort Study. Public Health. https://doi.org/10.1016/j.puhe.2020.09.012
- A cohort study among COVID-19 patients in Portugal (n=551) from March 1 to April 30, 2020 found no significant difference in the attack rate from index cases between patients who received contact tracing, isolated and had close contacts who were quarantined and those who did not (12%, 95% CI 7–19% vs. 9%, 95% CI 8–11%, respectively). Patients who were traced had a shorter time between symptom onset and laboratory diagnosis (median 3 vs. 5 days, p=0.004) and fewer close contacts (median: 0 vs. 2 per index case, p<0.001) compared to patients who were not traced.
Close et al. (July 2, 2020). Contact Tracing for Native Americans in Rural Arizona. The New England Journal of Medicine. https://doi.org/10.1056/NEJMc2023540
- Close et al. report the development of an aggressive, integrated early-response plan that relies heavily on contact tracing to limit the spread of COVID-19 in a rural eastern Arizonan community of about 18,000 Native Americans. Since the inception of the staff-intensive program, more than 1,600 cases of COVID-19 have been diagnosed on the reservation with a case fatality of 1.1%, which is less than half of that reported for the rest of the state of Arizona.
Altmann et al. (May 4, 2020). Acceptability of App-Based Contact Tracing for COVID-19: Cross-Country Survey Evidence (Preprint). JMIR MHealth and UHealth. https://doi.org/10.2196/19857
- Altmann et al. measured support for digital contact tracing of COVID-19 infections using anonymous online surveys of 5,995 people in France, Germany, Italy, the UK, and the US. In spite of concerns about cyber-security and privacy and a lack of trust in governments, they found strong support (>68%) for installing and using a digital contact tracing app that would automatically notify users if they have been in close contact for at least 15 minutes with an infected person.
- There was little correlation between regional-level COVID-19 mortality and support for the app.
- American and German respondents reported stronger privacy and security concerns compared to other countries, but a large majority still said that they would probably or definitely install or keep the app on their phones.
Hoeben et al. (Mar 15, 2021). Social Distancing Compliance: A Video Observational Analysis. PLOS ONE. https://doi.org/10.1371/journal.pone.0248221
- Closed Circuit Television (CCTV) footage in inner-city Amsterdam, Netherlands showed short-lived adherence to physical distancing measures following implementation of “lockdown” policies. From February to May 2020, the observed number of physical distancing violations (less than 1.5 meters) decreased following announcements of physical distancing measures and full lockdown on March 23rd, but then increased onwards from April 2 until the end of the observation period.
Czeisler et al. (Mar 15, 2021). Early Public Adherence with and Support for Stay-at-Home COVID-19 Mitigation Strategies despite Adverse Life Impact: A Transnational Cross-Sectional Survey Study in the United States and Australia. BMC Public Health. https://doi.org/10.1186/s12889-021-10410-x
- Self-reported adherence to COVID-19 mitigation policies was high in both highly- and minimally-affected regions in the US around the time of the first wave in April 2020, according to representative cross-sectional surveys (n=5,573) administered to adults residing in throughout the US, in New York City and Los Angeles, and Australia. 82% reported adherence to recommended quarantine and stay-at-home policies, and 90% supported government-imposed measures.
de Vries et al. (Jan 25, 2021). Dynamic Public Perceptions of the Coronavirus Disease Crisis, the Netherlands, 2020. Emerging Infectious Diseases. https://pubmed.ncbi.nlm.nih.gov/33493429
- Monitoring of public perceptions during the first 3 months of the COVID-19 pandemic in the Netherlands found that respondents believed the risks associated with COVID-19 to be considerable, were positive about mitigation measures, trusted in information and response from authorities, and reported widespread adoption of protective measures. Differences in perception were mostly driven by factors such as respondents’ age and health condition. Respondents consisted of roughly 11,000 residents participating across 6 repeat surveys, with an oversampling of persons aged >65 years.
McAloon et al. (Jan 25, 2021). Numbers of Close Contacts of Individuals Infected with SARS-CoV-2 and Their Association with Government Intervention Strategies. Pre-print downloaded Jan 26 from https://doi.org/10.1101/2021.01.20.21250109
- [Pre-print, not peer-reviewed] Analysis of more than 140,000 contacts of over 40,000 SARS-CoV-2 positive cases in Ireland from May to December 2020 showed that the number of contacts per case varied across specific populations and trended with implementation of government interventions. The number of contacts per case was highest among those aged 18-24 years and lowest among those >65 years. The number of contacts per case increased after stay-at-home orders were lifted in May from a minimum of 2 to a peak of 6, then fell back to 2.6 at the beginning of Level 5 restrictions in October.
Crane et al. (Jan 22, 2021). Change in Reported Adherence to Nonpharmaceutical Interventions During the COVID-19 Pandemic, April-November 2020. JAMA. https://doi.org/10.1001/jama.2021.0286
- An analysis of the Coronavirus Tracking Survey completed between April 1 and November 24, 2020 found that the adherence index (range 0 [low] to 100 [high]) to non-pharmaceutical interventions decreased substantially from 70 in April to the high 50’s in June, before rising back to 60 by late November. All US Census regions experienced significant decreases in the NPI adherence index during this time. Protective behaviors that had the largest decreases in adherence were staying at home, except for essential activities or exercise, (80% to 41%), having no close contact with non–household members (64% to 38%), not having visitors (80% to 58%), and avoiding eating at restaurants (87% to 66%). Reported mask wearing showed a significant increase among participants from 39% to 89%.
Ipsen et al. (Jan 18, 2021). A Cross-Sectional Analysis of Trust of Information and COVID-19 Preventative Practices among People with Disabilities. Disability and Health Journal. https://doi.org/10.1016/j.dhjo.2021.101062
- Survey participants with disabilities who live outside of metropolitan areas had the lowest COVID-19 information trust ratings and reported significantly less trust in most information sources when compared to people with disabilities in either metropolitan or micropolitan counties. Increased compliance with CDC guidelines was associated with being over 65, identifying as female, and higher general trust scores. Decreased compliance with CDC guidelines was associated with being nonwhite, living in a nonmetropolitan area, higher trust scores in President Trump, and having a communication disability.
Bateman et al. (Jan 21, 2021). Confronting COVID-19 in under-Resourced, African American Neighborhoods: A Qualitative Study Examining Community Member and Stakeholders’ Perceptions. Ethnicity & Health. https://doi.org/10.1080/13557858.2021.1873250
- Qualitative research conducted in under-resourced communities in Alabama found that Black community members highlighted concerns about contracting COVID-19 and noted apathy, difficulty with social distancing, lack of information, mixed messages from authority figures, and lack of PPE as barriers to prevention. Facilitators to coping with the pandemic included religious faith, increased physical activity, and a sense of hope; barriers included insecurity, mental health issues, isolation, economic hardships, lack of health care access, and issues with virtual schooling and church services, which were exacerbated by Internet connectivity problems. Facilitators to testing included incentives, clear information from trusted sources, convenient testing locations, and free tests, while misunderstanding, fear, mistrust, testing restrictions, and location of testing sites were identified as barriers.
Anderson and Stockman. (Dec 29, 2020). Staying Home, Distancing, and Face Masks: COVID-19 Prevention among U.S. Women in The COPE Study. International Journal of Environmental Research and Public Health. https://doi.org/10.3390/ijerph18010180
- Findings from the cross-sectional COPE Study (n=491) of women in the United States conducted from May to June 2020 suggest that women’s prevention behaviors for SARS-CoV-2 transmission are influenced by multilevel factors. Women who lived in urban environments, had minimal formal education, or had a household annual income of USD 30,000–50,000 were less likely to practice prevention behaviors. Cultural context was noted as a potentially important factor in the decision-making process.
Hutchins et al. (Oct 27, 2020). COVID-19 Mitigation Behaviors by Age Group — United States, April–June 2020. MMWR. https://doi.org/10.15585/mmwr.mm6943e4
- A nationally representative survey (n=6,475) conducted in three waves from April to June 2020 found that self-reported mask wearing increased across survey waves, while handwashing, physical distancing, and cancelling social activities decreased. Avoiding some or all restaurants did not change significantly. While >40% of respondents reported following all recommended behaviors across all waves, engagement was lowest among adults aged 18-29 years and highest among those aged >60 years.
While there is clear evidence for the potential for widespread transmission of SARS-CoV-2 in a school environment, there is also direct and indirect evidence that the development of and adherence to protocols to minimize the risk of transmission through the use of face masks, physical distancing, and other control measure as well as identifying cases, isolating infected individuals, quarantining close contacts, and maintaining cohorts or capsules with limited mixing between groups can substantially limit the spread of SARS-CoV-2 in the context of group settings with school-age children. The role of fomite transmission remains incompletely understood, particularly in the context of high levels of mask usage (Kraay).
The CDC has revised its guidelines regarding physical distancing in classrooms, recommending a change from ≥6 foot to ≥3 foot spacing in response to evidence the schools with a 3 foot spacing policy did not have higher incidence of COVID-19 compared to schools with a 6 foot spacing policy in the context of universal masking and other mitigation measures in place (van den Berg).
There is very little evidence, both in the context of low and high community transmission, that schools have been a driver of transmission (Leidman, Monod, Mensah, Doyle, Ladhani). In England (Mensah) and Florida (Doyle), incidence of COVID-19 in school children mirrors the incidence in the general population with a lag indicating that community transmission was the driver of infections in children. Another study from England found adults (≤65 years old) had a higher risk of SARS-CoV-2 infection if they lived in a household with school-age children during the second wave of the pandemic, although the role of school-based transmission was not clear (Forbes). During a period when schools had not yet re-opened, relaxation of mobility restrictions and re-opening other businesses and activities was associated with considerable increases in the prevalence of COVID-19 among adolescents and youth, indicating that exposures outside of the classroom are like more relevant to transmission in this age group than school-based transmission (Rumain).
Secondary transmission of SARS-CoV-2 from an infected student to their close contacts has been low, estimated at 2% of 102 close contacts identified in investigations of cases that occurred in K-12 schools (n=22) in Springfield and St. Louis County, Missouri (Dawson) and a secondary attack rate of 0.5% in New York City (Varma).
A small number of countries in regions with some level of community transmission of SARS-CoV-2 never imposed school closures. Sweden is notable among countries that did not close all schools, although Sweden did close schools for secondary grade students between March 18 and June 4, 2020 (Vogel). The incidence of severe COVID-19 was low among school-age children in Sweden and the risk among schoolteachers was similar to other occupations (Ludvigsson) Starting in late April and May 2020, many countries around the world started re-opening schools, many of which also sustained limits on other mobility and closures of many businesses after schools were re-opened. Since the initial re-opening, which often occurred for subsets of students or with modified schedules, schools have fully reopened for all students in many settings. While there have been examples of large-scale school closures in response to cases arising in schools soon after re-opening, particularly when school re-opening coincided with widespread relaxation of mobility restrictions and business closures (Israel, parts of the United States), many countries have been able to keep the large majority of schools open, even as cases of COVID-19 have increased in the community (Germany, France, Norway, Belgium, Scotland, South Korea).
According to a landscape analysis, most of the largest public and private institutions of higher education provided at least some in-person teaching during the Fall 2020 semester, most of which offered a hybrid reopening structure (Freeman). Outbreaks of SARS-CoV-2 have been observed on multiple college and university campuses, with evidence that campus outbreaks have driven surges in surrounding communities in some cases. Much of the transmission linked to colleges and universities has been linked to social and extracurricular activities rather than in-person instruction (Vang, Weil). Implementation of mitigation protocols and testing programs has been shown to result in control of outbreaks (Fox, O’Donnell).
Self, J et al. (Mar 18, 2021). Shelter Characteristics, Infection Prevention Practices, and Universal Testing for SARS-CoV-2 at Homeless Shelters in 7 US Urban Areas. American Journal of Public Health. https://doi.org/10.2105/AJPH.2021.306198
- Findings from SARS-CoV-2 testing offered to clients and staff at 63 homeless shelters, irrespective of symptoms, found lower prevalence of infection at shelters that implemented head-to-toe sleeping and that excluded symptomatic staff from working. Shelters with medical services available were less likely to have very high infection prevalence (defined as >10%).
Chin et al. (Mar 8, 2021). Covid-19 in the California State Prison System An Observational Study of Decarceration Ongoing Risks and Risk Factors. Pre-print downloaded Mar 9 from https://doi.org/10.1101/2021.03.04.21252942
- [Pre-print, not peer-reviewed] In 9 California prisons that experienced major COVID-19 outbreaks, risk factors for SARS-CoV-2 infection included living in a dormitory vs. in a cell (2.5-fold risk) and living in a room with residents who participated in out-of-room labor vs. other rooms (1.6-fold). By the end of the study, 18% had high COVID-19 risk scores, among whom nearly 40% lived in dormitory settings, and 15% lived in rooms with 10 or more occupants. The observational study also found that the incarcerated population in the state decreased by 19% between March to October 2020.
Marcus et al. (Feb 25, 2021). Risk Factors Associated With COVID-19 Transmission Among US Air Force Trainees in a Congregant Setting. JAMA Network Open. https://doi.org/10.1001/jamanetworkopen.2021.0202
- A higher number of symptoms and higher viral loads were associated with subsequent clusters of SARS-CoV-2 cases among cohorts of US Air Force basic trainees. Among 10,613 US Air Force basic trainees, of whom 3% (403) received a diagnosis of COVID-19 during the study period, higher numbers of symptoms and higher viral loads (lower cycle threshold (Ct) values) were associated with subsequent development of clusters of individuals with COVID-19 infection. The authors suggest that Ct values may be useful in assessing risk of ongoing transmission in specific cohorts.
- Although individual cases of COVID-19 occurred in almost half of all training cohorts, only 11% of cohorts had an initial individual case that resulted in a cluster of 5 or more cases, a success that the authors attributed to effective non-pharmaceutical interventions among the trainees.
Kiran et al. (Jan 30, 2021). Factors Associated with SARS-CoV-2 Positivity in 20 Homeless Shelters in Toronto, Canada, from April to July 2020: A Repeated Cross-Sectional Study. CMAJ Open. https://doi.org/10.9778/cmajo.20200253
- Among 872 residents of homeless shelters in Toronto, Canada across 20 shelter locations, 504 unique individuals had a SARS-CoV-2 tests performed in outbreak settings (April 1 to July 31, 2020), of which 69 (14%) were positive. There was no association between SARS-CoV-2 positivity and medical history or symptoms. Those who tested positive for SARS-CoV-2 were significantly less likely than those who tested negative to have visited another shelter in the last 14 days (0% vs. 18%). The authors suggest that their findings support testing asymptomatic individuals in shelter settings when a positive case has been identified at the same shelter.
Shumsky et al. (Mar 16, 2021). Retail Store Customer Flow and COVID-19 Transmission. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.2019225118
- A mathematical model analyzing retail customer flow and SARS-CoV-2 transmission found that then restricting customers to one-way movement could reduce transmission rates to less than one-third of the rate with two-way movement, if all customers comply and transmission occurs primarily through close contact. The model was calibrated using published epidemiologic data and predicted that for a medium-sized retail store in an area with relatively high COVID-19 prevalence, the transmission rate (via direct and wake exposure) would be 0.33 infections per day without complete one-way flow compliance.
Nachman et al. (Mar 12, 2021). Day Camp in the Time of COVID-19: What Went Right? Pre-print downloaded Mar 15 from https://doi.org/10.1101/2021.03.11.21253309
- [Pre-print, not peer-reviewed] A survey of summer day camp directors (n = 23) in the metropolitan New York area conducted in September 2020 regarding their camps’ COVID-19 policies during the summer of 2020 found that common infection prevention policies included COVID-19 screening at entry, placing camp attendees in cohorts, maximizing outdoor activities, mandating mask use when indoors, and frequent hand sanitizing. Out of 8,480 children and 3,698 staff, six staff and one camper tested positive for COVID-19. There was no secondary transmission within camps, and infection rates were lower in camps than in the counties where the camps were located.
Watson et al. (Mar 3, 2021). COVID-19 in Youth Soccer During Summer 2020. Journal of Athletic Training. https://doi.org/10.4085/610-20
- US youth soccer clubs reported a relatively low incidence of COVID-19 among their players in a retrospective cohort study of 119 US youth soccer clubs representing 91,007 players with a median duration of 73 days since restarting group activities. Soccer players reported a 49% lower incidence than children nationally over the same time period (254 vs 477 cases per 100,000). After adjusting for local COVID-19 incidence, there was no relationship between club COVID-19 incidence and phase of return. Clubs reported using a median of 8 COVID-19 risk reduction strategies.
Lendacki et al. (Feb 24, 2021). COVID-19 Outbreak Among Attendees of an Exercise Facility — Chicago, Illinois, August–September 2020. MMWR. https://doi.org/10.15585/mmwr.mm7009e2
- A large outbreak of COVID-19 occurred among attendees of indoor high-intensity classes at a Chicago exercise facility in August, 2020, with 55 cases identified among 81 attendees (68% attack rate). All classes were held at reduced capacity (<25%), temperature checks were required upon entry, and participants were required to space mats at least 6 feet apart. 22 (40%) people with COVID-19 attended classes on or after the day symptoms began, and most attendees (76%) wore masks infrequently, including people with (84%) and without COVID-19 (60%). Overall, 43 (78%) of attendees with COVID-19 attended more than one class while they were potentially infectious.
Groves et al. (Feb 24, 2021). Community Transmission of SARS-CoV-2 at Three Fitness Facilities — Hawaii, June–July 2020. MMWR. https://doi.org/10.15585/mmwr.mm7009e1
- An outbreak of COVID-19 cases occurred that was linked to a fitness instructor resulting in cases at 3 fitness facilities, with the highest attack rate (95%) occurring in classes that were taught <1 day before the onset of symptoms in the instructor. Twenty-one cases of COVID-19 were linked to an index case fitness instructor in Hawaii in July, 2020, including a case in another fitness instructor. The aggregate attack rates in classes taught by both instructors <1 day, 1 to <2 days, and ≥2 days before symptom onset were 95% (20 of 21), 13% (one of eight), and 0% (zero of 33), respectively. Among the 21 secondary cases, 20 (95%) had symptomatic illness, two (10%) of whom were hospitalized. At the time of the outbreak, mask use was not required in the facilities.
Sami et al. (Feb 24, 2021). SARS-CoV-2 Infection and Mitigation Efforts among Office Workers, Washington, DC, USA. Emerging Infectious Diseases. https://doi.org/10.3201/eid2702.204529
- Two SARS-CoV-2 outbreaks in April, 2020 were identified among office workers in Washington, DC. The study identified two factors potentially associated with SARS-CoV-2 infection and transmission in the workplace: a significantly higher percentage of seropositive participants lived with someone who had a confirmed positive test result (13%) than those who were seronegative (1%), and more (60% vs. 32%) seropositive participants traveled by taxi after the cancellation of nonessential gatherings on March 11, 2020. There was no significant difference in workplace mitigation activities between seropositive and seronegative participants, including using a face covering most of the time or always, maintaining a distance of >6 feet, and washing hands or using hand sanitizer >5 times per day.
Billock et al. (Feb 19, 2021). Required and Voluntary Occupational Use of Hazard Controls for COVID-19 Prevention in Non-Health Care Workplaces – United States, June 2020. MMWR. https://doi.org/10.15585/mmwr.mm7007a5
- 46% of non-remote, non–health care workers used hazard controls to prevent COVID (e.g., physical barriers, masks, and other personal protective equipment). Although 56% of workers surveyed reported required use at work, higher-income workers were more likely to report required use and to use hazard controls than were lower-income workers. Among workers not using hazard controls, 8% were prohibited from using them, 15% could not obtain them, and 77% did not believe they were needed.
Leidman et al. (Oct 23, 2020). Adoption of Strategies to Mitigate Transmission of COVID-19 During a Statewide Primary Election — Delaware, September 2020. MMWR. https://doi.org/10.15585/mmwr.mm6943e2
- Survey responses from primary election poll workers in Delaware indicated that SARS-CoV-2 mitigation measures at polling places generally aligned with CDC guidelines and were widely adopted and feasible, but there were some gaps in infection prevention control efforts. Most poll workers surveyed had good knowledge about SARS-CoV-2 transmission and 80% had received COVID-19 mitigation training. However, masks were not always worn correctly (covering both nose and mouth), and 72% of respondents reported being within 6 feet of more than 100 people on election day.
Ronchi et al. (Dec 7, 2020). Evaluation of Rooming-in Practice for Neonates Born to Mothers With Severe Acute Respiratory Syndrome Coronavirus 2 Infection in Italy. JAMA Pediatrics. https://jamanetwork.com/journals/jamapediatrics/fullarticle/2773311
- It may be possible to effectively mitigate the risk of mother-to-infant transmission of SARS-CoV-2 infection, based on findings from a multi-cohort study of mother-infant dyads (n=62 neonates, 61 mothers) in Italy that found no positive results among neonates 24 hours after birth despite a 95% breastfeeding rate. Infected mothers observed contact precautions such as handwashing and mask use while breastfeeding. At follow-up until age 3 weeks, only 1 infant was diagnosed as having SARS-CoV-2 infection.
Pelletier et al. (Feb 12, 2021). Trends in US Pediatric Hospital Admissions in 2020 Compared With the Decade Before the COVID-19 Pandemic. JAMA Network Open. https://doi.org/10.1001/jamanetworkopen.2020.37227
- US pediatric hospital admissions in the US were lower in 2020 compared to the past 10 years, according to a cross-sectional study of over 5 million US pediatric hospital admissions at 49 hospitals in the Pediatric Health Information Systems database. There was a decrease in the number of admissions beginning in March 2020 compared with the period from 2010 to 2019, reaching a peak reduction of 45% in April 2020. Inflation-adjusted hospital charges in the second quarter of 2020 decreased 28% compared with prior years, and there were significant reductions in all examined diagnoses except for birth.
McIlveen et al. (Feb 5, 2021). Reduction in Oregon’s Medication Dosing Visits After the SARS-CoV-2 Relaxation of Restrictions on Take-Home Medication. Journal of Addiction Medicine. https://pubmed.ncbi.nlm.nih.gov/33560697
- Opioid treatment programs in Oregon saw a reduction in medication dosing visits and an increase in take-home doses dispensed following a relaxation of restrictions on take-home medication dosing that were intended to slow the spread of SARS-CoV-2. During the pre-SARS-CoV-2 period (February and early March 2020), patients made a mean of 16 visits per month to opioid treatment programs, with 6 take-home doses per patient per month. Following the policy change, medication visits declined 33% and take-home medication increased 97% with a mean of 10 visits per patient and a mean of 11 take-homes per patient.
Courtney et al. (Feb 4, 2021). Decreases in Young Children Who Received Blood Lead Level Testing During COVID-19 – 34 Jurisdictions, January-May 2020. MMWR. https://doi.org/10.15585/mmwr.mm7005a2
- 34% fewer US children aged <6 years had blood lead level (BLL) testing during January–May 2020 when compared to January–May 2019, according to data from 34 state and local health departments. The authors estimate that reduced testing due to the COVID-19 pandemic has led to missed identification of 9,603 children with elevated BLLs.
Holland et al. (Feb 3, 2021). Trends in US Emergency Department Visits for Mental Health, Overdose, and Violence Outcomes Before and During the COVID-19 Pandemic. JAMA Psychiatry. https://jamanetwork.com/journals/jamapsychiatry/fullarticle/2775991
- The median proportion of US emergency department (ED) visits that were related to mental health conditions, suicide attempts, all drug and opioid overdoses, and suspected child abuse and neglect (SCAN) were significantly higher from mid-March to October 2020 compared to the same period in 2019, based on a cross-sectional study of nearly 190 million visits using data from the CDC’s National Syndromic Surveillance Program. In contrast, the proportion of visits due to intimate partner violence (IPV) was similar in the 2019 and 2020 time periods. Median visit counts for suicide attempts, all drug and opioid overdoses, IPV, and SCAN were significantly higher in the 2020 than 2019 time periods.
Partridge et al. (Jan 25, 2021). Evaluation of Seasonal Respiratory Virus Activity Before and After the Statewide COVID-19 Shelter-in-Place Order in Northern California. JAMA Network Open. https://doi.org/10.1001/jamanetworkopen.2020.35281
- Infection rates for influenza and rhinovirus or enterovirus were significantly lower during March 25 to July 31, 2020 compared to the same time period during the past 5 years, according to a cohort study in California that included over 45,000 tests for the viral respiratory infections. This significant drop in infection rates coincided with implementation of shelter-in-place orders on March 19, 2020. Influenza infection rates decreased by 93%, while rhinovirus or enterovirus infection rates decreased by 81%. In contrast, infection rates for the portions of the 2020 respiratory virus season prior to March 25th were similar to rates for the same period over the past 5 years (30.4 vs 33.7 positive results per 100 tests).
Chang and Levy. (Jan 19, 2021). High Prevalence of Elder Abuse During the COVID-19 Pandemic: Risk and Resilience Factors. The American Journal of Geriatric Psychiatry. https://doi.org/10.1016/j.jagp.2021.01.007
- A survey of older adults (n=897) sheltering in place during the pandemic found the prevalence of self-reported elder abuse was 21.3%, an 83% increase from the pre-pandemic period. Increased risk of elder abuse was associated with greater pandemic-related financial hardship, while reduced risk was associated with having a strong sense of community (OR = 0.89) and adherence to distancing measures (OR = 0.94).
Freeman et al. (Jan 1, 2021). Effectiveness of Physical Distancing: Staying 6 Feet Over to Put Respiratory Viruses 6 Feet Under. Mayo Clinic Proceedings. https://doi.org/10.1016/j.mayocp.2020.10.040
- Results from an analysis of 13,324 nasopharyngeal swabs collected at a single hospital in Arizona between January 1, 2017, and July 31, 2020, found a significant reduction in the detection of respiratory viruses other than SARS-CoV-2, coinciding with the implementation of distancing and masking policies during the COVID-19 pandemic. The average monthly positivity rate for the months between April and July declined from 25% for 2017–2019 to 2% in the same period of 2020. However, it is not clear what proportions of the observed declines in testing and positivity were due to non-pharmaceutical interventions, since the COVID-19 pandemic may also be causing reluctance to seek medical care.
Altschul et al. (Dec 20, 2020). Face Covering Adherence Is Positively Associated with Better Mental Health and Wellbeing a Longitudinal Analysis of the CovidLife Surveys. Pre-print downloaded Dec 21 from https://www.medrxiv.org/content/10.1101/2020.12.18.20248477v1
- [Pre-print, not peer-reviewed] A longitudinal UK-wide survey found that individuals who wore face coverings “most of the time” or “always” had better mental health and wellbeing than those who did not, even after controlling for behavioral, social, and psychological factors. The odds of feeling anxious were 58% lower among individuals who “always” adhered to guidance on wearing face coverings, and the odds of having depressive symptoms were 25% lower among individuals who “always” adhered to the guidance.
Trenholme et al. (Dec 2, 2021). COVID-19 and Infant Hospitalizations for Seasonal Respiratory Virus Infections, New Zealand, 2020. Emerging Infectious Diseases. https://doi.org/10.3201/eid2702.204041
- A pediatric hospital in South Auckland, New Zealand observed a dramatic decrease in cases of influenza and respiratory syncytial virus after COVID-19 lockdown measures were implemented in March 2020, compared to prior seasons. Additionally, case reductions were sustained after gradual reopening beginning in April 2020. While annual hospitalizations for lower respiratory tract infections ranged from 1,486 to 2,046 during 2015-2019, only 268 admissions were reported in 2020, despite similar rates of clinician-directed PCR tests.
Zhang et al. (Nov 30, 2020). Rapid Disappearance of Influenza Following the Implementation of COVID-19 Mitigation Measures in Hamilton Ontario. Pre-print downloaded Dec 1 from https://doi.org/10.1101/2020.11.27.20240036
- [Pre-print, not peer reviewed] Following population-wide implementation of COVID-19 interventions in Hamilton, Ontario, the proportion of samples that tested positive for influenza A and B dropped rapidly to 0% by the week of March 15-21. During the 2010-2019 influenza seasons, the proportion of positive tests reached 0% on a median of the week of May 30-June 6. Data were collected from all nasopharyngeal swab specimens (n=57,503) submitted for routine respiratory virus testing between January 2010 and June 2020.
Sherman et al. (Nov 8, 2020). The Effect of SARS-CoV-2 Mitigation Strategies on Seasonal Respiratory Viruses: A Tale of Two Large Metropolitan Centers in the United States. Clinical Infectious Diseases. https://doi.org/10.1093/cid/ciaa1704
- Public health measures implemented to reduce SARS-CoV-2 transmission may have reduced the transmission of other seasonal respiratory viruses. In a retrospective review of medical records from health systems in Atlanta and Boston, average reproductive number (Rt) was found to remain above 1 for much longer in the past 5 seasons for influenza A, influenza B, and respiratory syncytial virus (RSV) compared to the September 2019-May 2020 season, which coincided with the COVID-19 pandemic. Declines in Rt in both locations in 2020 seemed to coincide with implementation of non-pharmaceutical interventions.
Vaccines
COVID-19 Vaccines
April 2, 2021
COVID-19 Literature Report Team:
Will Hahn MD, Lorenzo Tolentino MPH, Molly Fischer MPH,
Jessie Seiler MPH, Rodal Issema MPH, Emily Rowlinson MPH,
Francis Slaughter BA, Mark Fajans MPH Ashley Tseng MPH,
Wenwen Jiang MPH, Julianne Meisner BVM&S MS, Diana M. Tordoff MPH, Sherrilynne Fuller PhD FACMI, Dylan Green MPH, Diana Louden MLib, Alison Drake PhD MPH, Jennifer M. Ross MD MPH, and Brandon L. Guthrie PhD
Within one year of the first identification of SARS-CoV-2, several vaccines were unequivocally demonstrated to prevent clinical COVID-19. This document is a brief summary of the published evidence to date regarding the safety and efficacy of vaccines to prevent COVID-19 with a primary focus on the results of clinical trials. The document is not specifically intended to inform decisions regarding prioritization of specific populations, the cost-effectiveness of specific vaccination approaches, or other logistics surrounding vaccine implementation. For additional information regarding how emerging SARS-CoV-2 variants potentially affect vaccine efficacy, please consult the variants report. References summarized in this report were drawn from the daily COVID-19 Literature Situation Report.
Text marked in BLUE is new since the last version of this summary.
This is only part 1 of the synthesis report. A PDF version is available here that includes all relevant article summaries (part 2) in addition to the narrative seen below.
- COVID-19 is a vaccine preventable illness.
- All vaccine candidates reported to date have demonstrated a very high degree of efficacy against hospitalization and death from COVID-19.
- Vaccines have reported variable efficacy against mild-to-moderate disease. Direct comparison across different trials is hampered by different definitions of “mild,” “moderate,” and “severe” disease. The emergence of variant viruses further complicates direct cross-trial comparison.
- The most serious safety signal observed to date is anaphylaxis in response to the mRNA vaccines, which occurs at a rate of one episode per 11.1 per million doses (Pfizer-BioNTech) and one episode per 2.5 per million doses (Moderna). No deaths attributable to any vaccine have been reported to date.
- Emerging evidence suggests that currently authorized vaccines have high effectiveness in real-world settings.
- All currently authorized vaccines have shown effectiveness against the B.1.1.7 SARS-CoV-2 variant.
- Efficacy against the B.1.351 variant was very low (~10%) for the Oxford-AztraZeneca, but comparable to other variants for the Johnson & Johnson and Novavax vaccines.
- The currently authorized vaccines prevent asymptomatic infection and reduce the risk of transmission among those who become infected following vaccination.
Within 9 months of the first description of SARS-CoV-2 associated respiratory disease in Wuhan, efficacy trials established unequivocally that COVID-19 is a vaccine-preventable disease. The rapid development schedule has prompted questions regarding the mechanism for rapid approval of vaccines for COVID-19 and whether safety or data quality have been compromised. For reference, the shortest development cycle under modern approval mechanisms was ~5 years for Ebola, and a typical vaccine approval cycle takes 10-15 years (Wolf). Time savings over traditional vaccine development strategies largely was achieved with the following strategies: (1) immediately starting efficacy trials after establishing that vaccines were safe and immunogenic (rather than waiting for information regarding the durability of the immune response); (2) the large size of the populations enrolled; and (3) a “time-to-analysis” trial design whereby pre-specified interim reviews were based upon a specific number of observed infections (rather than a predefined observation period). The allocation of unprecedented resources on an international scale also undoubtedly increased the pace of development.
The current regulatory landscape is rapidly evolving and as of April 2, 2021, three vaccines have achieved emergency use authorization (EUA) in the United States:
- BNT162b2 from Pfizer-BioNTech (2 doses),
- mRNA-1273 from Moderna (2 doses)
- Ad26.COV2.S from Johnson & Johnson-Janssen (1 dose)
Another candidate vaccine currently undergoing phase III trials to support licensure in the United States is from Novovax (a two-dose regimen) (Shinde). Some sponsors also undertook additional trials that were conducted in parallel to the US trials to support licensure in other countries. For example, there is an ongoing trial of the University of Oxford-AztraZeneca product intended to support licensure in the United States whereas this product has already been approved by the UK and other international regulators on the basis of trials conducted in these countries. Other vaccines have achieved international licensure and are not, to date, conducting trials to support licensure in the United States. These include products from Sinovac in China (Coronavac), Gamaleya Research Institute in Russia (Sputnik V), and Bharat Biotech. All vaccines to date target the spike protein of the SARS-CoV-2 virus, but use a variety of platforms to deliver the spike antigen, including mRNA (Pfizer-BioNTech and Moderna), replication incompetent viruses (Oxford-AstraZeneca, Johnson & Johnson-Janssen, Gamaleya–Sputnik V), recombinant proteins (Novovax), and inactivated virus (Coronavac). There are at least 50 candidate vaccines in various stages of early clinical testing using a variety of approaches; the specific details of these products are beyond the scope of this review.
All trials thus far are randomized, placebo-controlled trials with laboratory confirmed SARS-CoV-2 infection combined with COVID-19 disease considered to be the primary endpoint. It is important to note that there are differences in how each trial has defined clinical disease, specifically with respect to the “mild”, “moderate” and “severe” categories. Furthermore, there are minor differences in the populations enrolled and the time period in which the trials were conducted, making direct cross protocol comparison complex. The pre-specified statistical analysis plan of each trial to date conducted in the US included a minimum number of clinical endpoints (e.g., PCR-confirmed SARS-CoV-2 infection plus clinical signs or symptoms defining mild, moderate, or severe COVID-19) that triggered an interim analysis (typically around 100-150 cases). The definitions of the primary endpoints used in each trial are outline below the sections describing each vaccine. In general, the protocols were designed assuming a much lower rate of community transmission than was actually observed (an assumption of ~1% of placebo recipients per year becoming infected versus an observed rate of ~5-10% per year); the high rate of community transmission, therefore, contributed to the rapid pace of determining whether a vaccine was effective because of the “case-based” design of the trials.
Trials of vaccines authorized for use in the US for those 16 years of age and older are now undergoing trials in younger people. Preliminary results from a trial of the Pfizer-BioNTech vaccine showed 100% efficacy against COVID-19 among adolescents (n=2,260) aged 12 to 15 years old in the US without prior history of infection.
The high trial efficacy (85% to 95%) of vaccines currently approved for use in the US, as well as the Oxford-AstraZeneca vaccine authorized in Europe, the UK, and elsewhere, has been mirrored by similarly high real-world effectiveness, including against the B.1.1.7 variant (Thompson, Benenson, Lumley, Rinott, Dagan). Vaccination as appears to be effective at preventing asymptomatic infection (Tande). At least over a relatively short period of follow-up, partial vaccination with only one does of the Pfizer-BioNTech, Moderna, and Oxford-AstraZeneca has shown a level of effectiveness that is slightly lower but approaching the level of protection seen with full vaccination (Bouton, Yelin, Britton, Krammer, Moustsen-Helms, Bernal, Saul, Manisty, Romero-Brufau). The authorized vaccines have performed well across various patient populations, including residents of nursing homes (Hollinghurst, Moustsen-Helms, Britton) and pregnant and breastfeeding women (Gray), although there has been some evidence of lower immune responses among nursing home residents (Canaday, ), among older individuals (Müller), those who have received solid organ transplants, and others with chronic medical conditions (Simon, Yelin, Pellini). Vaccine-induced antibodies been detected in cord blood and in breastmilk (Gray, Baird). Vaccination also results in a lower viral load among those who have been vaccinated and have subsequently become infected, including those who have been infected following first dose, and before the they have received their second dose (McEllistrem, ). Vaccine responses following a first vaccine dose have been stronger among those who have been previously infected with SARS-CoV-2 compared those with not prior infection history (Eyre, Bradley, Demonbreun, Prendecki). This high level of vaccine effectiveness, including against asymptomatic infection, lead the CDC to release recommendations that fully vaccinated individuals can now safely gather indoors with other fully vaccinated individuals without wearing a mask (CDC).
Although it is somewhat counter-intuitive given the rapid pace of vaccine approval, the COVID-19 vaccine trials have generated substantially more short-term safety data than would be available during a typical vaccine approval process. For example, each of the efficacy trials intended for licensure in the United States have enrolled (or plan to enroll) >30,000 participants, with between 15,000 and 20,000 administered study product. For comparison, the RESOLVE trial, which was intended to support licensure of a vaccine against lower respiratory tract infection caused by respiratory syncytial virus (RSV) only enrolled 11,856 participants with 1:1 randomization, meaning only 5,921 participants were administered study product (https://clinicaltrials.gov/ct2/show/NCT02608502). Additionally, the generally consistent vaccination strategy between products (e.g., using similar inserts of the spike protein of the SARS-CoV-2 virus) offers an unprecedented capacity for comparing the safety profile and performance across various platforms. The fact that multiple trials were conducted in parallel allows for a high degree of confidence that targeting the spike protein via a variety of vaccination strategies is both safe and effective. An important technical note is the conceptual differentiation in safety outcomes between reactogenicity (e.g., transient symptoms such as malaise, for example) and serious adverse events attributable to the vaccine (e.g., Guillain-Barre syndrome, anaphylaxis). The former is quite common with all vaccines, whereas the latter are extremely rare. The CDC is aggressively monitoring vaccines implemented using an EUA with a post-marketing surveillance program.
Notable safety findings:
- Both mRNA vaccines currently authorized for use in the US under an EUA (Pfizer-BioNTech and Moderna) have been associated with low rates of anaphylaxis in post-marketing surveillance (Shimabukuro, Blumenthal)
- Symptoms consistent with “reactogenicity” occurring soon after vaccination have been frequent but transient (Baden, Gee)
- Delayed late local reactions at the injection site (erythema, swelling, pain) have been reported to occur with the Moderna vaccine at a rate of 0.5-1% (Baden, Blumenthal). Such reactions have been less frequently reported with the Pfizer vaccine. If these delayed injection site reactions occur with the first dose, the CDC states that they are not a contraindication for a second dose of the vaccine (CDC).
The durability of clinical immunity generated by the various vaccines is currently unknowable given that the epidemic is only a year old, so major questions remain regarding the potential need for booster vaccinations. Evidence regarding the durability of vaccine-induced immunity will be added here has it becomes available.
Evidence is still emerging regarding the effect that widespread vaccination can have on community transmission of SARS-CoV-2, incidence of COVID-19 cases, and rates of hospitalization and death due to COVID-19. However, there is emerging evidence that increases in the proportion of the population that is immunized is associated with decreases in the incidence of SARS-CoV-2 in unvaccinated people (Milman), and vaccination is associated in a lower viral load among those who subsequently become infected, including those infected 12-37 days after the first vaccine dose (Levine-Tiefenbrun, Saad-Roy). In most settings where vaccination efforts have started, the proportion of the population that has been fully vaccinated is low and therefore the impact of widespread vaccination cannot yet be assessed. However, a small number of countries have vaccinated a large proportion of their population, most notably Israel and the UK. In Israel, where 2-dose vaccination coverage with the Pfizer-BioNTech mRNA vaccine reached 84% among persons aged ≥70 years and 10% among those aged <50 years by February 2021, there was a 67% decline in the ratio of COVID-19 patients aged ≥70 years requiring mechanical ventilation to those aged <50 years (Rinott). The authors conclude that this is preliminary evidence of the effectiveness of vaccines in preventing severe cases of COVID-19 at the national level. Other evidence from Israel indicates that a single dose of the Pfizer-BioNTech vaccine reduced the rate of SARS-CoV-2 infections among health care workers at 15-28 days after the first dose (Amit). Similarly, early evidence from Scotland indicates that under real-world conditions, with approximately 35% of the population vaccinated, there was a peak vaccine efficacy of 85% (95% CI: 76-91%) to prevent COVID-19-related hospitalization following a first dose of for the Pfizer-BioNTech vaccine and 94% (95%CI: 73-99%) efficacy for the Oxford-AstraZeneca vaccine, with the peak occurring at 28-34 days post-vaccination (Vasileiou).
While it is incontrovertible that clinical COVID-19 can be prevented by vaccination, there are major outstanding questions about how SARS-CoV-2 evolution in response to immune pressure from both natural and vaccine-induced immunity will affect the efficacy of the current generation of SARS-CoV-2 vaccines. The most direct evidence of the impact of viral mutations on vaccine efficacy come from countries where variants were circulating at the time of ongoing efficacy trials. The variant of currently of greatest concern regarding vaccine efficacy is the B.1.351 variant (first described in South Africa). There were ongoing trials of the Oxford-AstraZeneca and Johnson & Johnson-Janssen vaccines in South Africa at a time when the B.1.1.351 variant was the dominant circulating strain. For the Oxford-AstraZeneca SARS-CoV-2 vaccine, efficacy against mild or moderate COVID-19 due to infection with the B.1.351 variant was estimated to be 10% (Madhi). The authors were unable to make conclusions about protection from severe COVID-19 since no cases of severe disease or hospitalization were reported in either the vaccinated or placebo group. By contrast, the efficacy of the Johnson & Johnson-Janssen vaccine to protect against severe/critical COVID-19 was equivalent in South Africa (81.7%), where the B.1.351 variants accounted for 95% of infections, compared to other regions where the B.1.351 variant was not circulating (85.9% in the US and 87.6% in Brazil) (FDA). The efficacy of the Johnson & Johnson-Janssen vaccine against moderate COVID-19 was somewhat lower in South Africa compared to the US and Brazil. The Novavax vaccine, which is pending authorization, showed 50% efficacy overall and 60% efficacy in people who were HIV-negative in trials in South Africa, where the B.1.351 variant accounting for vast majority of infections in participants in both the placebo and vaccine arms (Shinde). Across all of the currently authorized vaccines, efficacy appears to be similar against the B.1.1.7 variant (first described in the UK) compared to other viral lineages (Emary).
Indirect evidence for the effect of viral mutations on vaccine efficacy comes from studies using serum derived from blood samples drawn from individuals who had received one of the COVID-19 vaccines. 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). However, the relationship between levels of in vitro neutralization and actual vaccine efficacy remains unclear and there is no currently accepted correlate of immunity.
The evidence presented below represent publicly available information either released by companies or published in peer-reviewed literature. Additional information has certainly accrued since these data were made available and are likely available to regulators such as the FDA. All trials use PCR to confirm active SARS-CoV-2 infection and have used various clinical definitions for the primary outcomes measured for each trial.
Type: mRNA
Doses: 2 doses 28 days apart
Handling requirements: (per EUA package insert) Store -25 °C to -15 °C. Can be refrigerated up to 30 days at 2 °C to 8 °C prior to use (cannot refreeze).
Level of evidence for efficacy: Phase III placebo-controlled efficacy trial
Regulatory status:
US: Approved for use under an Emergency Use Authorization
- Results from a phase 3 randomized, observer-blinded, placebo-controlled trial of the Moderna SARS-CoV-2 vaccine candidate (mRNA-1273) indicated that the vaccine showed 94.1% efficacy at preventing COVID-19, including severe disease. 30,420 volunteers were enrolled (15,210 placebo, 15,210 vaccine).
- 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.
- Reactogenicity after one dose was less than that observed for the recombinant adjuvanted herpes zoster (shingles) vaccine and after the second mRNA-1273 dose was similar to that of the herpes zoster vaccine (Cunningham).
Primary Endpoints by arm
Group | Total enrolled | Any COVID-19 | Mild COVID-19 | Severe COVID-19 |
Placebo | 15,210 | 185 | 155 | 30 |
Vaccine | 15,210 | 11 | 11 | 0 |
Definition of primary endpoints
PCR+ with approved test PLUS:
Mild COVID-19 | Moderate COVID-19 | Severe COVID-19 |
Any fever
OR >48 hours of any of the following:
|
Not defined | Any of the following:
· Respiratory rate >30 breaths/minute · Heart rate >125 beats per minutes · Blood oxygen (SpO2) less than 93% · Respiratory failure or acute respiratory distress syndrome (ARDS) · Shock · Acute renal, hepatic, or neurologic dysfunction · ICU admission or death |
Type: mRNA
Doses: 2 doses, 21 days apart
Handling requirements: -80 °C to -60 °C storage. Once thawed, can store undiluted vials for up to five days (120 hours) at 2C-8C.
Level of evidence for efficacy: Phase III placebo-controlled efficacy trial
Regulatory status:
US: Approved for use under an Emergency Use Authorization
- Results of the phase 3 double-blind, randomized, placebo-controlled trial for the Pfizer-BioNTech mRNA vaccine BNT162b2 (n=21,720 in vaccine group, and 21,728 in placebo group) showed a vaccine efficacy of 95% (95% CI 90.3-97.6), with 8 cases of COVID-19 (1 severe case) in the vaccine group and 162 cases (9 severe cases) in the placebo group.
- Efficacy was similar across subgroups defined by age, sex, race, ethnicity, body-mass index, and presence of co-existing conditions.
- Mild-to-moderate reactogenicity was commonly observed and increased with the second dose. Severe fatigue was observed in approximately 4% of BNT162b2 recipients, which is lower than observed in recipients of the Shingrix vaccine (another approved viral vaccine for older adults).
- Few participants in either group had severe or serious adverse events, and the 6 deaths (2 in vaccine group, 4 in placebo group) were determined by investigators not to be related to the vaccine or placebo by investigators.
Primary Endpoints by arm
Group | Total enrolled | Any COVID-19 | Mild COVID-19 | Severe COVID-19 |
Placebo | 21,728 | 162 | 151 | 9 |
Vaccine | 21,720 | 8 | 7 | 1 |
Definition of primary endpoints
PCR+ with approved test PLUS:
Mild COVID-19 | Moderate COVID-19 | Severe COVID-19 |
At least one of the following:
· Fever, · Cough · Shortness of breath · Chills · Muscle pain · Sore throat · Diarrhea · Vomiting |
Not defined | Any of the following:
· Respiratory rate >30 breaths/minute · Heart rate >125 beats/minute · shock · acute renal, hepatic or neurologic dysfunction · ICU admission · Death |
Type: Replication incompetent adenovirus (Adenovirus 26)
Doses: 1 dose
Handling requirements: Stored at 2 °C to 8 °C.
Level of evidence for efficacy: Phase III placebo-controlled efficacy trial
Regulatory status:
US: Approved for use under an Emergency Use Authorization
- Vaccine efficacy against laboratory-confirmed moderate to severe/critical COVID-19 across all geographic areas in which the trial was conducted (including South Africa where the B.1.351 variant was circulating at the time) was 66.9% when considering cases occurring at least 14 days after the single-dose vaccination and 66.1% considering cases occurring at least 28 days after vaccination. Efficacy against severe/critical COVID-19 occurring at least 14 days and at least 28 days after vaccination was 76.7% and 85.4%, respectively.
Primary Endpoints (COVID-19 Onset at least 14 Days after vaccination) by arm
Moderate to severe/critical COVID-19 | Severe/critical COVID-19 |
||||
Group | Total Enrolled | cases | Vaccine Efficacy |
cases | Vaccine Efficacy |
Placebo (US) | 9086 | 196 | 74.4% | 18 | 78.0% |
Vaccine (US) | 9119 | 51 | 4 | ||
Placebo (South Africa) | 2496 | 90 | 52% | 30 | 73.1% |
Vaccine (South Africa) | 2473 | 43 | 8 | ||
Placebo (Brazil) | 3355 | 114 | 66.2% | 11 | 81.9% |
Vaccine (Brazil) | 3370 | 39 | 2 |
Primary Endpoints (COVID-19 Onset at least 28 Days after vaccination) by arm
Moderate to severe/critical COVID-19 | Severe/critical COVID-19 |
||||
Group | Total Enrolled | cases | Vaccine Efficacy |
cases | Vaccine Efficacy |
Placebo (US) | 8835 | 112 | 72.0% | 7 | 85.9% |
Vaccine (US) | 8958 | 32 | 1 | ||
Placebo (South Africa) | 2463 | 64 | 64.0% | 22 | 81.7% |
Vaccine (South Africa) | 2449 | 23 | 4 | ||
Placebo (Brazil) | 3312 | 74 | 81.7% | 8 | 87.6% |
Vaccine (Brazil) | 3354 | 24 | 1 |
Definition of primary endpoints
PCR+ with approved test PLUS:
Mild COVID-19 | Moderate COVID-19 | Severe COVID-19 |
One of the following symptoms:
|
· 3 or more symptoms (see mild COVID-19)
OR Any one of the following new or worsening signs/symptoms: · Respiratory rate ≥20 breaths/minute · Abnormal SpO2 but stil >93% on room air at sea level · Clinical or radiologic evidence of pneumonia · Radiologic evidence of deep vein thrombosis · Shortness of breath or difficulty breathing Any 2 of the following new or worsening signs/symptoms · Fever (≥38.0°C or ≥100.4°F) · Heart rate ≥90 beats/minute · Shaking chills or rigors · Sore throat · Cough · Malaise · Headache · Muscle pain (myalgia) · Gastrointestinal symptoms · New or changing olfactory or tase disorder · Red or bruised looking feet or toes |
Clinical signs at rest indicative of severe systemic illness:
· Respiratory rate ≥30 breaths/minute · Heart rate ≥125 beats/minute · SpO2 ≤93% on room air at sea level, or partial pressure of oxygen/fraction of inspired oxygen (PaO2/FiO2) <300 mmHg) · Respiratory failure (defined as needing high-flow oxygen, non-invasive ventilation, mechanical ventilation, or extracorporeal membrane oxygenation [ECMO]) · Evidence of shock (defined as systolic blood pressure <90 mmHg, diastolic blood pressure <60 mmHg, or requiring vasopressors) · Significant acute renal, hepatic, or neurologic dysfunction · Admission to the ICU · Death |
Type: Recombinant protein
Doses: 2 doses, 21 days apart
Handling requirements: Store at 2 °C to 8 °C.
Regulatory status:
US: Anticipated EUA application is expected soon on the basis of US trial results
- Based on a press release from Novavax, preliminary results for phase 2/3 trials for the recombinant protein-based COVID-19 vaccine NVX-CoV2373 made by Novavax showed up to 3% efficacy in the UK cohort (n= >15,000), where 56 participants in the placebo group developed COVID-19 vs 6 in the vaccine group (Novavax).
- Of note, the 1.1.7 variant (first described in the UK) was observed in 32 of the COVID-19 cases, yielding an estimate of 85.6% efficacy against the variant.
- Preliminary results from the South Africa cohort (n= >4,400) showed efficacy of 60% in the HIV-negative study population vs. 49.4% in the overall study population, with 29 COVID-19 cases observed in the placebo group vs. 15 in the vaccine group.
- In the South Africa cohort, among 27 of the 44 cases with sequence data, mutations consistent with the B.1.351 variant (first described in South Africa) were detected in 25 (93%).
- Approximately 1/3 of patients in the South Africa cohort (but not included in the preliminary results) were SARS-CoV-2 seropositive at baseline, indicating prior SARS-CoV-2 infection.
Primary Endpoints by arm (Note: US trial is ongoing)
Group | Total enrolled | Any COVID-19 | Mild COVID-19 | Severe COVID-19 |
Placebo (UK) | Approx. half of “15000” | 56 | 61 | 1 |
Vaccine (UK ) | Approx. half of “15000” | 6 | 6 | 0 |
Placebo (South Africa) | Approx. half of “Over 4400” | 29 | 29 | 0 |
Vaccine (South Africa) | Approx. half of “Over 4400” | 15 | 14 | 1 |
Definition of primary endpoints
Mild COVID-19 | Moderate COVID-19 | Severe COVID-19 |
New onset cough
OR fever OR Two or more of following: · Shortness of breath · Fatigue, · Aches · Headache · Loss of taste/smell · New onset nausea/vomiting/diarrhea |
Any of the following:
· high fever (38.4 °C for 3 or more days) · Shortness of breath with exertion · Respiratory rate 24-29 breaths/minute · SPO2 94-95% · Abnormal chest x-ray, · “Adventitious” sounds on lung exam |
Any of the following:
· Respiratory rate > 30 breaths/minute · Heart rate >125 beats/minute · SpO2 less than 93% on room air · CPAP/BIPAP/high level ventilation · Renal/hepatic/right or left heart failure/stroke/thrombotic event · ICU admission · Death |
Type: Chimpanzee adenoviral vector
Doses: 2 doses, 28 days apart
Handling requirements: Store at 2°C to 8 °C
Regulatory status:
US: Undergoing licensure trial in US (separate from trials that lead to licensure in UK)
The Oxford-AstraZeneca chimpanzee adenoviral vector vaccine (ChAdOx1 NCoV-19 Vaccine, AZD1222) has a more complex regulatory path and is currently undergoing a trial intended to facilitate licensure in the US. The results of that trial are not yet available. The trials supporting licensure in the UK are listed below. Additional complexity is added by different dosing intervals and doses used during each clinical trial conducted to date.
UK and Brazil Cohorts:
- An interim analysis of two of the four ongoing phase 2/3 trials for the Oxford–AstraZeneca chimpanzee adenovirus vectored vaccine ChAdOx1 nCoV-19 (n=7,548 in UK trial, n=4,088 in Brazil trial) showed a vaccine efficacy of 62.1% (95%CI 41.0-75.7%) among participants who received the planned two standard doses (Voysey).
- A smaller number of participants (n=1367 in the vaccine group and 1374 in the placebo group) erroneously received a low initial dose followed by a standard second dose. The observed vaccine efficacy for the low-dose/standard dose combination was 90.0% (95% CI 67.4-97.0) (3 of 1,367 in the vaccine group vs 30 of 1,374 in the placebo group) (Voysey).
- The overall vaccine efficacy against symptomatic COVID-19 was 70.4% (95.8% CI 54.8-80.6%) (Voysey).
- The majority of participants included in this interim analysis were aged 18-55 (88%), white (83%), and female (61%).
- 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 against B.1.1.7 compared to 84% efficacy against non- B.1.1.7 lineages (Emary). Vaccine-induced antibodies had an approximately nine-fold reduction in neutralization activity against the B.1.1.7 variant compared to a canonical non-B.1.1.7 lineage in a live-virus neutralization assay.
- Among those vaccinated with ChAdOx1 who subsequently became infected with SARS-CoV-2, both the duration of shedding and viral load was lower than among control participants (Emary).
- Exploratory analysis of interim data from trials of the Oxford-AstraZeneca vaccine suggested that lengthening the interval between vaccination doses was associated with increases in clinical efficacy (Voysey).
- In a subset of participants who elected not to receive the second dose, the efficacy of a single-dose was 76% and protection did not decline during the 3-month period following the initial vaccination (Voysey).
- Participants in the study also received weekly swabs to look for detectable nucleic acid in the absence of symptoms. Overall reduction in PCR+ samples was 54% (45%-62%), suggesting a potential for reduced transmissibility (Voysey).
Note: the South African study was stopped due to the apparent lack of activity against the mild disease caused by the B.1.3.5 variant. Data from this decision – including efficacy against severe disease – have not been made public to date.
Primary Endpoints by arm
Group | Total enrolled | Clinical COVID-19 | Hospitalized with COVID-19 |
Placebo (pooled) | 8,581 | 248 | 15 |
Vaccine (pooled) | 8,597 | 84 | 0 |
Type: Adenovirus viral vector
Doses: 2 doses, 21 days apart. Note: there are actually two adenoviruses used (first dose is recombinant adenovirus 26 followed by recombinant adenovirus 5).
Handling requirements: Stored at 2 °C to 8 °C
Logunov et al. (Feb 2, 2021). Articles Safety and Efficacy of an RAd26 and RAd5 Vector-Based Heterologous Prime-Boost COVID-19 Vaccine: An Interim Analysis of a Randomised Controlled Phase 3 Trial in Russia. The Lancet. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)00234-8/fulltext
- Interim analysis of the randomized, double-blind, placebo-controlled phase 3 trial for the recombinant adenovirus (rAd)-based vaccine Gam-COVID-Vac (Sputnik V) (n=19,866) showed an efficacy of 91.6% (CI: 85.6%-95.2%) by 21 days after the first dose of vaccine (the day of dose 2). 16 of 14,964 (0.1%) people in the vaccine group developed COVID-19 compared to 62 of 4,902 (1.3%) people in the placebo group. Participants were required to be IgG/IgM negative at baseline for enrollment. Rates of disease onset were similar for the vaccine and placebo groups until about 16 to 18 days after the first dose.
- The observed vaccine efficacy was >87% in all age and sex subgroups (60% male), and 91.8% in participants aged >60 years (11% of participants). 98.5% of participants were white, and the entire study was conducted in 25 hospitals and polyclinics in Moscow, Russia. 94% of reported adverse events were grade 1, with 0.3% and 0.4% of vaccine and placebo group experiencing serious adverse events, respectively.
Definition of primary endpoints
Mild COVID-19 | Moderate COVID-19 | Severe COVID-19 | Extremely Severe COVID-19 |
· Cough, weakness, sore throat
· “No symptoms of moderate and severe course” |
· Fever over 38.5C
· Respiratory rate >28 breaths per minute · Shortness of breath during physical exertion · Pneumonia (confirmed by computed tomography of lungs) · Oxygen saturation less than 95% · C-reactive protein of blood serum more than 10mg/L |
· Respiratory Rate more than 22 breaths/minute
· Oxygen saturation level <93% · Progression of changes in the lungs according to Xray, CT, or ultrasonography · Decreased level of consciousness, agitation · Unstable hemodynamics · Arterial blood lactate >2mmol/liter · More than 2 points on the Sequential Organ Failure Score |
· Acute respiratory failure with need for invasive mechanical ventilation
· Septic Shock · Multiple organ failure · Changes in the lungs on CT typical of critical viral lesion or evidence of acute respiratory distress syndrome (ARDS) |
Type: inactivated
Doses: 2 doses, 14 days apart
Handling requirements: Stored at 2 °C to 8 °C
Note neither the underlying protocol nor the underlying data were made publicly available at present.
Press release: “As of December 16, 2020, there were 12,396 health workers over 18 years old enrolled. A total of 253 positive cases were collected during the observation period. After 14 days following vaccination with 2 doses of vaccine following a 0, 14 day schedule, the efficacy rate against diseases caused by COVID-19 was 50.65% for all cases, 83.70% for cases requiring medical treatment, and 100.00% for hospitalized, severe, and fatal cases.”
Wu et al. (Feb 3, 2021). Safety, Tolerability, and Immunogenicity of an Inactivated SARS-CoV-2 Vaccine (CoronaVac) in Healthy Adults Aged 60 Years and Older: A Randomised, Double-Blind, Placebo-Controlled, Phase 1/2 Clinical Trial. The Lancet Infectious Diseases.
https://www.thelancet.com/article/S1473-3099(20)30843-4/fulltext
- In a randomized, double-blind, placebo-controlled phase 1/2 trial of the inactivated SARS-CoV-2 vaccine CoronaVac conducted among healthy, seronegative adults aged ≥60 years (n=421), all adverse reactions were mild or moderate, with injection site pain as the most frequently reported reaction (9%). Seroconversion after two doses was reported in at least 90% of all dosage groups and none in the placebo groups.
Type: inactivated
Doses: 2 doses, 14 days apart
Ella et al. (Mar 8, 2021). Safety and Immunogenicity of an Inactivated SARS-CoV-2 Vaccine, BBV152: Interim Results from a Double-Blind, Randomised, Multicentre, Phase 2 Trial, and 3-Month Follow-up of a Double-Blind, Randomised Phase 1 Trial. The Lancet Infectious Diseases. https://doi.org/10.1016/S1473-3099(21)00070-0
- Interim results from a double-blind randomized phase 2 trial (n=380) of the Bharat Biotech whole-virion inactivated SARS-CoV-2 vaccine (BBV152) show robust neutralizing titers against wild-type SARS-CoV-2 at day 56 following two doses administered on day 0 and day 28. In a plaque-reduction neutralization test, the 6 µg dose group compared to the 3 µg dose group had higher geometric mean neutralizing titers (197 vs 100) and higher proportion of seroconversion (98% vs 93%) at day 56. No significant difference was observed in the proportion of participants who reported local or systematic adverse reactions between the dose groups (20% vs 21%), and no serious adverse events were reported in the study.
Stern et al. (Apr 2, 2021). Willingness to Receive a COVID-19 Vaccination Among Incarcerated or Detained Persons in Correctional and Detention Facilities — Four States, September–December 2020. MMWR. https://doi.org/10.15585/mmwr.mm7013a3
- The COVID-19 vaccination refusal rate was 45% among 5,110 surveyed residents of three prisons and 13 jails across four states during September to December 2020 (all three prisons and 10 jails in Washington State). The most common reason for vaccination refusal was distrust of health care, correctional, or government personnel or institutions (20%). 10% of surveyed residents expressed vaccine hesitancy; waiting for more information was the most common reason for hesitancy (55%). Willingness to be vaccinated was lowest among Black participants (37%; 510 of 1,390), participants aged 18–29 years (39%; 583 of 1,516), and those who lived in jails versus prisons (44%; 1,850 of 4,232).
Grumbach et al. (Mar 30, 2021). Association of Race/Ethnicity With Likeliness of COVID-19 Vaccine Uptake Among Health Workers and the General Population in the San Francisco Bay Area. JAMA Internal Medicine. https://doi.org/10.1001/jamainternmed.2021.1445
- Black, Latinx, and Asian employees of three large medical centers in San Francisco had lower odds of reporting that they were likely to get vaccinated against COVID-19 compared to white employees in a cross-sectional study conducted from November 2020 to January 2021 (n=1,803). Compared to white respondents, Black, Asian and Latinx had 50%, 63%, and 72% lower odds for likeliness of vaccine uptake, respectively. Similarly, ethnic minorities in a general population cohort (n=3,161) residing in counties in the San Francisco Bay Area reported lower odds for likeliness of vaccine uptake compared to white respondents. While ratings of reasons to get vaccinated were similar across racial/ethnic groups, minorities were significantly more likely than white respondents to endorse reasons not to get vaccinated, such as less confidence in vaccine efficacy, less trust in vaccine manufacturers, and more worry that government process were rushed.
Lindemer et al. (Mar 26, 2021). Counties with Lower Insurance Coverage Are Associated with Both Slower Vaccine Rollout and Higher COVID-19 Incidence across the United States. Pre-print downloaded Mar 29 from https://doi.org/10.1101/2021.03.24.21254270
- [Pre-print, not peer-reviewed] US counties with high levels of uninsured individuals had significantly lower COVID-19 vaccination rates and tended to have the highest COVID-19 incidence rates in March 2021 relative to December 2020, according to an analysis of data from over 1,500 counties (228 million individuals). Counties with higher percentages of Black and Hispanic individuals also had significantly lower vaccination rates, and smaller declines in COVID-incidence rates.
Kriss et al. (Mar 15, 2021). COVID-19 Vaccine Second-Dose Completion and Interval Between First and Second Doses Among Vaccinated Persons — United States, December 14, 2020-February 14, 2021. MMWR. https://doi.org/10.15585/mmwr.mm7011e2
- Vaccination data reported to CDC indicate that among people who received the first dose of either the Moderna or Pfizer/BioNTech vaccines as of February 14, 2021, and for whom enough time had elapsed to receive the second dose, 88.0% had completed the series and 8.6% had not received the second dose. Among all people who received 2 doses, 95.6% received the second dose within the recommended time interval (Pfizer-BioNTech 1-25 days and Moderna 24-32 days since the first dose). The percentage of people who missed the second dose varied by geographic area (range = 0.0%−9.1%).
Jain et al. (Mar 12, 2021). A Rapid Review of COVID-19 Vaccine Prioritization in the U.S. Alignment between Federal Guidance and State Practice. Pre-print downloaded Mar 15 from https://doi.org/10.1101/2021.03.11.21253411
- [Pre-print, not peer-reviewed] A study assessing variability in vaccine priority groups between state and federal guidance found that while state plans largely prioritized healthcare workers and residents of long-term care facilities (consistent with federal guidelines), essential workers were often excluded from state priority plans. Of 37 states that included frontline essential workers, 12 assigned them to a lower priority than recommended by federal guidance. Almost all states prioritized individuals ages 65-74 years, and most assigned them to a higher position than recommended in federal guidance. Some groups not considered high priority in federal guidelines, such as people living in congregate settings or with disabilities, were highly prioritized by 38 states.
Chapman et al. (Mar 8, 2021). Comparison of COVID-19 Vaccine Prioritization Strategies in the United States. Pre-print downloaded Mar 10 from https://doi.org/10.1101/2021.03.04.21251264
- [Pre-print, not peer-reviewed] A static simulation model using California as an example to compare the impact of different vaccine prioritization strategies in the United States found that prioritizing older individuals averted the highest proportion of disability-adjusted life years (DALYs, 40% for 5 million individuals vaccinated) and deaths (65%), but the lowest proportion of cases (12%). Prioritizing essential workers averted the lowest proportion of DALYs (25%) and deaths (33%). Allocating vaccines simultaneously by age and location or multiple factors (age, sex, race/ethnicity, location, occupation, and comorbidity status) averted a significantly higher proportion of DALYs (48% and 56%) than any strategy prioritizing by a single risk factor. The authors note that their approach may underestimate the impact of vaccination by not incorporating onward transmission.
Immunity
Immunity to COVID-19 and SARS-CoV-2 Infection
April 16, 2021
COVID-19 Literature Report Team:
Will Hahn MD, Lorenzo Tolentino MPH, Molly Fischer MPH,
Jessie Seiler MPH, Rodal Issema MPH, Emily Rowlinson MPH,
Francis Slaughter BA, Mark Fajans MPH, Ashley Tseng MPH,
Wenwen Jiang MPH, Julianne Meisner BVM&S MS, Diana M. Tordoff MPH,
Sherrilynne Fuller PhD FACMI, Dylan Green MPH, Diana Louden MLib,
Alison Drake PhD MPH, Jennifer M. Ross MD MPH, and Brandon L. Guthrie PhD
Much of the information in this synthesis report is drawn from summaries included in the daily COVID-19 Literature Situation Report. This is not intended to be a systematic or comprehensive summary, rather it is a frequently updated compilation and synthesis of evidence related to immunity to SARS-CoV-2 infection and protection against COVID-19 disease following recovery from an initial SARS-CoV-2 infection.
This is only part 1 of the synthesis report. A PDF version is available here that includes all relevant article summaries (part 2) in addition to the narrative seen below.
Natural infection with SARS-CoV-2 results in a robust antibody response in up to 95% of immunocompetent persons (Arkhipova-Jenkins, Van Elslande), peaking approximately 3-4 weeks after infection. Most data on the immune response comes from the detection of antibodies against the spike protein that surrounds the virus. Anti-spike IgM titers rapidly wane by approximately 12 weeks whereas IgG titers persist (Cheng, Sherina). There are also antibody responses against other portions of the SARS-CoV-2 virus. Antibodies directed against nucleocapsid are generally detected earlier (Semmler), but wane more rapidly than antibodies directed against the spike protein. Seroreversion (having a negative antibody serology test following a period of being seropositive) is relatively common; however the relevance of this waning of detectable antibodies to immunity against reinfection is unclear and there is evidence that immune activity against SARS-CoV-2 persists among individuals who serorevert to a negative antibody test.
Several clinical and demographic variables are associated with different antibody responses. Younger children and older adults have been observed to produce higher levels of antibodies (Yang). More severe infections are generally associated with higher anti-Spike antibody titers across all isotypes, including neutralization titers (Chia, Bartsch); however, antibodies are commonly detected in those with asymptomatic infections and in individuals with no suspected exposure to SARS-CoV-2 (Tsitsilonis).
There is strong evidence that infection with SARS-CoV-2 confers some level of immunity against reinfection but cases of re-infection have been reported, including cases with severe outcomes during the second infection.
- The CDC defines suspected SARS-CoV-2 reinfection as an infection that occurs >90 days after initial documented infection with SARS-CoV-2.
- The level of protection against re-infection is not fully know, but estimates of protection are as high as 80% to 95% (Sheehan, Hansen, Leidi, Letizia), although these estimates are based on observational studies that may over- or underestimate the actual level of protection.
- Immunity appears to be strongest for protection against the same strain of the virus as the initial infection, although there appears to be at least partial immunity to other viral variants (refer to the section below on the impact of variants on natural immune protection).
- Cases of reinfection with SARS-CoV-2 have been reported (Lee), including in individuals with a symptomatic initial infection (Cavanaugh). There is particular concern regarding reinfection with the P.1, P.2, and B.1.351 variants following an initial infection with an earlier strain of the virus (Fintelman-Rodrigues, Nonaka).
The emergence of several SARS-CoV-2 “variants of concern” with mutations in the spike protein has complicated the landscape for immunity through natural infection and vaccination as well as treatment using monoclonal antibodies. The literature is complex and fast moving but conceptually there are mutations that lead to enhanced viral fitness (including replication), such as the B.1.1.7 variant first identified in the UK, and mutations that lead to immune escape, such as the B.1.351 first identified in South Africa. Studies are ongoing, but it is reasonable to expect larger effects of the mutations on the efficacy of monoclonal antibodies and smaller effects on immunity from natural infection and vaccination.
- Tests of the ability of antibodies from individuals who have been infected with earlier strains of SARS-CoV-2 indicate lower levels of viral neutralization against the B.1.351, P.1, and CAL.20C variants (Jangra, McCallum, Dejnirattisai, Becker, Wang, Vogel, Widera, Li, Edara, Zhou, Planas, Collier, Redd, Diamond, Betton), but similar neutralization against the B.1.1.7 variant (Becker). The impact of lower neutralization titers on actual protection from re-infection is not yet understood.
- Antibodies produced in response to infection with the B.1.351 variant appear to be cross-reactive against other strains of the virus, including P.1 (Moyo-Gwete, Betton).
Several groups have reported that receipt of non-COVID vaccines is associated with both reduced risk of SARS-CoV-2 diagnosis and severe COVID disease. Vaccines that have been observationally associated with lower incidence of COVID-19 include the pneumococcal and influenza vaccines (Lewnard, Wilcox).
Cross-reactive immunity, presumably generated by infection with seasonal coronaviruses, is common in samples taken prior to the pandemic, but the presence of this immunity does not appear to affect clinical outcomes after infection with SARS-CoV-2 (Anderson). Similarly, virologically confirmed infection with seasonal coronavirus is not associated with protection against subsequent infection with SARS-CoV-2 (Ringlander).