COVID-19 Literature Situation Report Sept. 29, 2020

• [Pre-print, not peer-reviewed] Segmented regression applied to COVID-19 and SARS-CoV-2 case counts in a number of US states was used to estimate the impact of the closures of schools, restaurants and bars, general lockdown orders, and masking mandates. The authors estimate that school closings reduced SARS-CoV-2 infection rates by half, while lockdowns reduced transmission rates by 3- to 4-fold, and other actions (such as closing bars and mandating masks) also decreased the rates. [EDITORIAL NOTE: The short amount of time between different types of closures and the lack of precision in the date of infection greatly limits the ability to attribute declines in the infection rate to any one intervention approach]

Matzinger et al. (Sept 28, 2020). Strong Impact of Closing Schools Closing Bars and Wearing Masks during the Covid-19 Pandemic Results from a Simple and Revealing Analysis. Pre-print downloaded Sept 29 from https://doi.org/10.1101/2020.09.26.20202457

• During August 2–September 5, 2020, weekly COVID-19 cases among young people ages 18–22 increased 55% nationally, with the largest regional increases in the Northeast (144%) and Midwest (123%). Increases in cases were not solely due to increased testing. The incidence in all other age groups declined during the same period. When examined by race and ethnicity nationally during this time period, the weekly incidence among non-Hispanic white individuals aged 18-22 years increased 150% (from 48 to 120 per 100,000). Incidence in those 18-22 years old in other racial/ethnic groups declined during the same period. The authors note that it is likely that some of this increase is linked to resumption of in-person attendance at some colleges and universities.

Salvatore et al. (Sept 29, 2020). Recent Increase in COVID-19 Cases Reported Among Adults Aged 18–22 Years — United States, May 31–September 5, 2020. MMWR. https://doi.org/10.15585/mmwr.mm6939e4

• Within 2 weeks of opening the campus to students (Aug 3 – Aug 25), a North Carolina university experienced 670 COVID-19 cases. Preliminary investigations suggest student gatherings and congregate living settings, both on and off campus, likely contributed to the rapid spread of COVID-19 on campus. The authors state that measures to reduce transmission on college campuses could include reducing on-campus housing density, ensuring that campus community members adhere to masking and other mitigation strategies, increasing testing, and discouraging student gatherings.

Wilson et al. (Sept 29, 2020). Multiple COVID-19 Clusters on a University Campus — North Carolina, August 2020. MMWR. https://doi.org/10.15585/mmwr.mm6939e3

• An exploratory, open-label, phase 2 randomized trial of the monoclonal antibody IFX-1 (vilobelimab) in adults with severe COVID-19 indicated that C5a inhibition with the drug appeared to be safe. Mortality estimates at 28 days were 13% for the IFX-1 group and 27% for the control group, although the authors note that this outcome is preliminary and the study lacked sufficient power for this endpoint. The frequency of serious adverse events were similar between groups, and no deaths were considered related to treatment assignment. However, a smaller proportion of patients had serious pulmonary embolisms in the IFX-1 group (13%) than in the control group (40%).

Vlaar et al. (Sept 2020). Anti-C5a Antibody IFX-1 (Vilobelimab) Treatment versus Best Supportive Care for Patients with Severe COVID-19 (PANAMO): An Exploratory, Open-Label, Phase 2 Randomised Controlled Trial. The Lancet Rheumatology. https://doi.org/10.1016/S2665-9913(20)30341-6

• A study of household transmission from people with mild COVID-19 found that SARS-CoV-2 RNA concentrations were lowest soon after symptoms appeared and increased with time since symptom onset. Viral concentrations were higher in patients under 18 years of age (p=0.01) and those reporting upper respiratory symptoms at the time of sample collection (p=0.001), and were lower among participants without symptoms (p=0.05). The authors conclude that these findings support the importance of early testing for SARS-CoV-2 among people with respiratory symptoms to identify and isolate infected individuals while their viral shedding is high.

Salvatore et al. (Sept 28, 2020). Epidemiological Correlates of PCR Cycle Threshold Values in the Detection of SARS-CoV-2. Clinical Infectious Diseases. https://doi.org/10.1093/cid/ciaa1469

• A phase 1, dose escalation trial of a messenger RNA vaccine against SARS-CoV-2 conducted among adults ages 56-70 (n=20) and ages 71 or older (n=20) reported generating antibody response with mild to moderate adverse events. Serum neutralizing activity was detected in all participants and was similar in magnitude to responses previously reported among participants between the ages of 18 and 55. The authors emphasize the need to include older adults in vaccine trials due to increased risk for severe outcomes from COVID-19 in this age group.

Anderson et al. (Sept 29, 2020). Safety and Immunogenicity of SARS-CoV-2 MRNA-1273 Vaccine in Older Adults. New England Journal of Medicine. https://doi.org/10.1056/NEJMoa2028436

• An observational study of patients hospitalized with COVID-19 in Japan (n=2,638) found a lower prevalence of comorbidities and a trend toward lower mortality compared to inpatient studies from other countries. Among the study participants, the most common comorbidities were hypertension (15%) and diabetes without complications (14%). In addition, there were twice as many individuals with non-severe COVID-19 as with severe COVID-19. Overall, 67% of patients were discharged home, while 8% died.

Matsunaga et al. (Sept 28, 2020). Clinical Epidemiology of Hospitalized Patients with COVID-19 in Japan: Report of the COVID-19 REGISTRY JAPAN. Clinical Infectious Diseases. https://doi.org/10.1093/cid/ciaa1470

• An autopsy study among 21 patients who died of COVID-19 showed widespread systemic inflammation in the lungs, heart, kidney, liver, and brain, with a continued presence of inflammatory neutrophils cells even several weeks into the disease course. The lung was the organ with the most abundant SARS-CoV-2, and extensive inflammation was detected in the brain. SARS-CoV-2-infected cells were sporadically present up to 6 weeks after the onset of symptoms, and occasionally found at late stages of COVID-19. The authors note that these findings suggest a maladaptive immune response to SARS-CoV-2.

Schurink et al. (Sept 2020). Viral Presence and Immunopathology in Patients with Lethal COVID-19: A Prospective Autopsy Cohort Study. The Lancet Microbe. https://doi.org/10.1016/S2666-5247(20)30144-0

• An analysis of ACE2 expression among 229 individuals indicated that participants who were female (OR=2.3), had hypertension (OR=1.3), had a cardiocerebrovascular disease (OR=1.3), had cancer (OR=1.7), or who were over 60 years old (OR=3.1) had higher levels of ACE2 expression, which is one of the cellular entry receptors for SARS-CoV-2. The authors suggest that persons with greater ACE2 expression may be at an increased risk of SARS-CoV-2 infection due to higher expression of ACE2.

Li et al. (Aug 19, 2020). Exploring the Demographics and Clinical Characteristics Related to the Expression of Angiotensin-Converting Enzyme 2, a Receptor of SARS-CoV-2. Frontiers in Medicine. https://doi.org/10.3389/fmed.2020.00530

• Incidence of all-cause mortality among a cohort of US Medicare beneficiaries residing in assisted living settings between January to August 2020 (n=425,333) was 17% higher compared to a cohort from the same time in 2019 (n=422,262). The incidence ratio was 36% higher during the peak week in April 8-14, 2020 (3.3 vs 2.2 deaths per 1,000 residents). Among the 10 states with the highest COVID-19 community spread during the study period, the incidence of all-cause mortality was 24% higher and up to 73% higher during the peak week.

Thomas et al. (June 14, 2021). Estimation of Excess Mortality Rates Among US Assisted Living Residents During the COVID-19 Pandemic. JAMA Network Open. https://doi.org/10.1001/jamanetworkopen.2021.13411

• COVID-19 transmission was correlated with season in a manner similar to influenza-like illnesses (ILI), according to a comparison between the average annual time-series for ILIs based on incidence data from 2016 till 2019 and two COVID-19 time-series during 2020/2021 in the Netherlands. The authors suggest that the high correlation seems to imply factors driving seasonality of ILIs, such as temperature, relative humidity, and seasonal allergens may also drive COVID-19 seasonality.

Hoogeveen and Hoogeveen. (June 8, 2021). Comparable Seasonal Pattern for COVID-19 and Flu-like Illnesses. One Health. https://doi.org/10.1016/j.onehlt.2021.100277

• Texas clinics in medically underserved areas (MUAs) were less likely to conduct greater than half of their visits via telehealth compared to non-MUA clinics, according to an analysis of 1,344 pooled responses from Texas primary care providers between March 27 and May 22, 2020. Restricting the analysis to responses obtained after May 1, 2020 showed that the association had attenuated, suggesting that initial telehealth barriers among MUA clinics may have resolved over time.

Adepoju et al. (May 2021). COVID-19 and Telehealth Operations in Texas Primary Care Clinics: Disparities in Medically Underserved Area Clinics. Journal of Health Care for the Poor and Underserved. https://doi.org/10.1353/hpu.2021.0073

• Emergency department (ED) visits resulting in a diagnosis for diabetic ketoacidosis (DKA) during early COVID-19 pandemic period of March to May 2020 were 70% higher than in the same period in 2019 in New York City (214 vs 106 diagnoses) according to an analysis of ED data extracted for routine quality review. By contrast, Total volume of ED visits declined by 27% from 2019 to 2020 (93,218 vs 59,009 visits).

Ditkowsky et al. (June 9, 2021). SARS-CoV-2 Infection and Associated Rates of Diabetic Ketoacidosis in a New York City Emergency Department. Western Journal of Emergency Medicine. https://doi.org/10.5811/westjem.2021.2.49634

• Nearly 1 in 4 individuals hospitalized for COVID-19 had 3 or more persistent symptoms 6 months after hospital admission in a cohort study in France (n=1,137). Presence of 3 or more symptoms at 6 months was more common among women, those with 3 or more symptoms at admission, and those who were admitted to the ICU, but was not associated with age or having two or more comorbidities. At least one symptom was present in 68% of patients at 3-months and 60% at 6-month of follow-up, with fatigue, shortness of breath, joint pain, and muscle pain being the most common symptoms.

Ghosn et al. (May 10, 2021). Persistent COVID-19 Symptoms Are Highly Prevalent 6 Months after Hospitalization: Results from a Large Prospective Cohort. Clinical Microbiology and Infection. https://doi.org/10.1016/j.cmi.2021.03.012

• In solid organ transplant recipients, a third dose of a COVID-19 vaccine was not able to elicit detectable anti-SARS-CoV-2 antibody responses in 53% of participants in a cohort study (n=30). Prior to receiving the third dose, 80% of patients did not have detectable antibody responses. All patients were fully vaccinated with mRNA vaccines (57% Pfizer-BioNTech, 43% Moderna), and received the third dose after a median of 67 days (50% Johnson & Johnson-Janssen, 30% Moderna, 20% Pfizer-BioNTech). Participants were assessed for an antibody response after a median of 14 days after the third vaccination.

Werbel et al. (June 15, 2021). Safety and Immunogenicity of a Third Dose of SARS-CoV-2 Vaccine in Solid Organ Transplant Recipients: A Case Series. Annals of Internal Medicine. https://doi.org/10.7326/L21-0282

• 82% of individuals recovered from COVID-19 maintained RBD-specific IgG titers, RBD-specific B cells, and neutralizing activities between 6-12 months after infection, according to analysis of 68 recovered individuals, suggesting long-lived immunity to COVID-19. In 41% of participants who received an mRNA vaccine, vaccination increased IgG responses by 30-fold, neutralizing activity by 50-fold, and circulating number of memory B cells by 9-fold. Sera from vaccinated individuals also showed robust neutralizing activity against variants of concern and neutralization breadth (the ability to neutralize a diverse panel of viruses) increased over time.

Wang et al. (June 14, 2021). Naturally Enhanced Neutralizing Breadth against SARS-CoV-2 One Year after Infection. Nature. https://doi.org/10.1038/s41586-021-03696-9

• Self-reported allergic symptoms following the first dose of a COVID-19 mRNA vaccine was associated with a 5-fold increase in odds of not completing the second dose after adjusting for demographics, vaccine manufacturer, wave of vaccine eligibility, and other confounders in a prospective cohort of healthcare employees in Boston. Among 61,057 employees who received a first dose, incomplete vaccination occurred in 3% (43 of 1,261) of those who self-reporting allergic symptoms compared to 0.6% of those who did not report allergic symptoms. Self-reported severe allergic symptoms were rare (n=6) and associated with markedly increased odds of not completing the vaccination course (aOR=23).

Robinson et al. (June 11, 2021). Allergic Symptoms after mRNA COVID-19 Vaccination and Risk of Incomplete Vaccination. The Journal of Allergy and Clinical Immunology: In Practice. https://doi.org/10.1016/j.jaip.2021.05.031

• As of May 8, 2021, 16% (22,197 of 135,968) of pregnant women identified in CDC’s Vaccine Safety Datalink, which includes integrated health systems from 7 US states, have received ≥1 dose of a COVID-19 vaccine during pregnancy. Of those initiating vaccination 68% have completed either a 1- or 2-dose series. Vaccination during pregnancy was highest among women aged 35-49 years (23%) and lowest among those aged 18-24 years (6%), and higher among Asian (25%) and white women (20%) compared to Hispanic (12%) and Black women (6%).

Razzaghi et al. (June 15, 2021). COVID-19 Vaccination Coverage Among Pregnant Women During Pregnancy — Eight Integrated Health Care Organizations, United States, December 14, 2020–May 8, 2021. MMWR. https://doi.org/10.15585/mmwr.mm7024e2

• A study evaluating the immune responses in four infants with mild COVID-19 (median age 7 weeks old) found that compared to their parents who also had COVID-19 (n=8) and a cohort of adult controls with prior COVID-19 (n=10), infants had higher anti-SARS-CoV-2 IgG antibody levels in both sera and saliva and exhibited more robust serum neutralizing activity. Infants also had reduced production of interferon-gamma after direct ex-vivo stimulation (ELISPOT), despite a comparable frequency of SARS-specific T cells and comparable capacity for expansion with prolonged stimulation with SARS-CoV-2 antigens.

Goenka et al. (June 9, 2021). Young Infants Exhibit Robust Functional Antibody Responses and Restrained IFN-γ Production to SARS-CoV-2. Cell Reports Medicine. https://doi.org/10.1016/j.xcrm.2021.100327

• [Pre-print, not peer-reviewed] A modeling study using a stochastic compartmental model showed that in-person sporting events on college campuses could increase COVID-19 cases among the campus community. Even when COVID-19 cases were controlled both on-campus and among the larger population from which visitors to campus were drawn, such events presented a risk to the community. Depending on the scenario, and the prevalence of COVID-19, both on and off campus, the increase ranged from 25% to 822%.

Johnson et al. (Sept 28, 2020). Excess Risk of COVID-19 to University Populations Resulting from In-Person Sporting Events. Pre-print downloaded Sept 29 from https://doi.org/10.1101/2020.09.27.20202499

• [Pre-print, not peer-reviewed] Despite ongoing COVID-19 activity in Ontario, the prevalence of anti-SARS-CoV-2 antibodies did not change substantially (range 0.4% – 1.4% positive) between five surveys conducted from March to August 2020. Bolotin et al. analyzed residual clinical specimens and found that the geometric mean concentration of antibodies among the positive samples declined between June and August (p=0.015), suggesting that loss of anti-N antibodies over time may result in an underestimate of cumulative SARS-CoV-2 infections at the population level. This finding is supported further by an increase over time in the geometric mean concentration of anti-N antibodies in the samples that tested negative.

Bolotin et al. (Sept 29, 2020). COVID-19 Seroprevalence Surveys and Antibody Decline – A Note of Caution on Antibody Decline. Pre-print downloaded Sept 29 from https://doi.org/10.1101/2020.09.28.20200915