COVID-19 Literature Situation Report Jan 29, 2021

After an outbreak of 371 cases of COVID-19 on an Indiana university campus, the university was able to rapidly decrease new cases and gradually return to in-person learning by implementing aggressive transmission mitigation policies. These included aggressive testing, tracing, and isolation program, switching to online instruction for 2 weeks, mandating masks and physical distancing, developing a communication campaign focused on mitigation measures, and increasing rapid antigen test site hours and capacity. Most cases occurred among undergraduates, with several large off-campus gatherings identified as the source of the exposure. 

Fox et al. (Jan 29, 2021). Response to a COVID-19 Outbreak on a University Campus — Indiana, August 2020. MMWR. https://doi.org/10.15585/mmwr.mm7004a3

• 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

One in five symptomatic patients admitted to the medical department who had a negative SARS-CoV-2 swab received a clinical diagnosis of COVID-19 according to a retrospective cohort study from two large London hospitals. Swab-negative clinical COVID-19 cases were defined as (a) clinical COVID-19 or high level of suspicion as defined by the treating medical team (as recorded in the medical record); and (b) RT-PCR swab-negative on both initial and any subsequent testing.  Swab-negative clinical COVID-19 patients had better outcomes, with shorter length of hospital stay, reduced need for supplementary oxygen and reduced mortality.

Middleton et al. (Jan 27, 2021). Characteristics and outcomes of clinically diagnosed RT-PCR swab negative COVID-19: a retrospective cohort study. Scientific Reports. https://doi.org/10.1038/s41598-021-81930-0

[Pre-print, not peer-reviewed] Abdel-Sater et al. reported the development of a rapid molecular test to identify the SARS-CoV-2 B.1.1.7 (UK) variant using a set of RT-PCR primers that were designed to confirm the deletion mutations Δ69/Δ70 in the spike and the Δ106/Δ107/Δ108 in the NSP6 gene. The large-scale screening method may help bypass the need for widespread sequencing to confirm the presence of both the B.1.1.7 variant and variants with similar deletions.

Abdel-Sater et al. (Jan 29, 2021). A Rapid and Low-Cost protocol for the detection of B.1.1.7 lineage of SARS-CoV-2 by using SYBR Green-Based RT-qPCR. Pre-print downloaded Jan 29 from https://doi.org/10.1101/2021.01.27.21250048

The BinaxNow Antigen Card showed low analytical sensitivity (53%) for detecting SARS-CoV-2 infection in a population of asymptomatic or pre-symptomatic individuals when compared to RT-PCR testing for SARS-CoV-2.

Okoye et al. (Jan 27, 2021). Performance Characteristics of BinaxNOW COVID-19 Antigen Card for Screening Asymptomatic Individuals in a University Setting. Journal of Clinical Microbiology. https://doi.org/10.1128/JCM.03282-20

[Pre-print, not peer-reviewed] Follow-up of 11,468 adults with mild or asymptomatic COVID-19 infection found that serological evidence of previous infection, specifically the presence of either IgG or IgM antibodies, waned quickly over time, with roughly 50% of people undergoing sero-reversion within 30 days of their initial positive test. The rate of sero-reversion was not associated with age, sex, race/ethnicity, or healthcare worker status.

Herrington et al. (Jan 29, 2021). Duration of SARS-CoV-2 Sero-Positivity in a Large Longitudinal Sero-Surveillance Cohort The COVID-19 Community Research Partnership. Pre-print downloaded Jan 29 from https://doi.org/10.1101/2021.01.27.21250615

[Pre-print, not peer-reviewed] The first dose of the BNT162b2 mRNA COVID-19 vaccine (Pfizer–BioNTech) is associated with an approximately 51% reduction in the incidence of PCR-confirmed SARS-CoV-2 infections at 13 to 24 days after immunization compared to the rate during the first 12 days. These findings are based on a retrospective cohort study in Israel (December 19 to January 15). Similar levels of effectiveness were found across age groups, sex, as well as among individuals residing in Arab or ultra-orthodox Jewish communities that have experienced an increased COVID-19 risk.

Chodcik et al. (Jan 29, 2021). The effectiveness of the first dose of BNT162 b 2 vaccine in reducing SARS-CoV-2 infection 13-24 days after immunization real-world evidence. Pre-print downloaded Jan 29 from https://doi.org/10.1101/2021.01.27.21250612

[Pre-print, not peer-reviewed] Using a lentivirus-based pseudovirus assay, the SARS-CoV-2 B.1.1.7 (UK) variant was shown to exhibit only modestly reduced susceptibility to neutralization from convalescent sera (1.5-fold average reduction) and sera from recipients of both the Moderna and Novavax vaccine phase 1 studies (2-fold average reduction after two inoculations. The authors used the prototypic D614G variant as a comparator.

Cheng et al. (Jan 28, 2021). SARS-CoV-2 variant B.1.1.7 is susceptible to neutralizing antibodies elicited by ancestral Spike vaccines. Pre-print downloaded Jan 29 from 

https://doi.org/10.1101/2021.01.27.428516

[Press release, not peer-reviewed] The Johnson and Johnson single-dose COVID-19 candidate vaccine had 66% efficacy against moderate to severe COVID-19, based on a press release describing the phase 3 clinical trial results from the ENSEMBLE trial. Among all participants including those infected with an emerging viral variant the vaccine prevented moderate to severe COVID-19 28 days after vaccination with the first evidence of protection observed as early as day 14. The level of protection against moderate to severe COVID-19 infection was 72% in the United States, 66% in Latin America, and 57% in South Africa 28 days post-vaccination. 

Johnson & Johnson (Jan 29, 2021). Johnson & Johnson Announces Single-Shot Janssen COVID-19 Vaccine Candidate Met Primary Endpoints in Interim Analysis of its Phase 3 ENSEMBLE Trial. Press release downloaded Jan 29 from https://www.jnj.com/johnson-johnson-announces-single-shot-janssen-covid-19-vaccine-candidate-met-primary-endpoints-in-interim-analysis-of-its-phase-3-ensemble-trial 

[Pre-print, not peer-reviewed] Eighty percent (95%CI: 65% to 92%) of persons infected with SARS-CoV-2 developed one or more long-term symptoms, according to a systematic review and meta-analysis (n=47,910 patients) assessing long-term effects of COVID-19. Follow-up time of study participants ranged from 15 to 110 days post-viral infection. The age of the study participants ranged between 17 and 87 years. The five most common symptoms were fatigue (58%), headache (44%), attention disorder (27%), hair loss (25%), and difficulty breathing (dyspnea) (24%). 

Lopez-Leon et al. (Jan 29, 2021). More than 50 Long-term effects of COVID-19: a systematic review and meta-analysis. Pre-print downloaded Jan 29 from https://doi.org/10.1101/2021.01.27.21250617

[Pre-print, not peer-reviewed] No association was found between the proportion of the UK SARS-CoV-2 variant B.1.1.7 in circulation and reported disease severity, according to data obtained from reporting of symptoms and test results via the COVID Symptom Study application. The authors controlled for both demographic characteristics (age, sex) and seasonal variables (temperature, humidity). No effects were observed based on the number of different reported symptoms, hospitalizations, frequency any of the individual symptoms, or the proportion of individuals with long symptom duration (≥28 days). The proportion of individuals with duration of symptoms ≥28 days did not change in association with the presence of the B.1.1.7 variant. The proportion of users with asymptomatic disease did not significantly change as B.1.1.7 increased in prevalence.

Graham et al. (Jan 29, 2021). The effect of SARS-CoV-2 variant B.1.1.7 on symptomatology re-infection and transmissibility. Pre-print downloaded Jan 29 from https://doi.org/10.1101/2021.01.28.21250680

Health care workers (HCWs) hospitalized with COVID-19 were less likely to require admission to an intensive care unit (aOR, 0.6; 95% CI, 0.3-0.9) and less likely to be admitted for 7 days or longer (aOR, 0.5; 95% CI, 0.3-0.8) when compared to matched non-healthcare workers in a retrospective, observational cohort involving 36 North American centers. There were no differences between matched HCWs and non-HCWs in terms of need for mechanical ventilation (aOR, 0.7; 95% CI, 0.4-1.2), death (aOR, 0.5; 95% CI, 0.2-1.3), or use of vasopressors (aOR, 0.7; 95% CI, 0.4-1.2).

Yang et al. (Jan 28, 2021). Outcomes of COVID-19 Among Hospitalized Health Care Workers in North America. JAMA Network Open. https://doi.org/10.1001/jamanetworkopen.2020.35699

Using previously collected indoor air quality data from New York City public schools, Pavilonis et al. estimated the probability of in-classroom transmission to be 5% for student-to-student transmission, 14% for student-to-teacher transmission, and 20% for teacher-to-student transmission after the introduction of one infectious person into the classroom. Consistent mask wearing by both students and teachers was associated with lower predicted transmission rates, while the probability of transmission increased during the winter due to closing windows and doors to retain heat. Classrooms with mechanical ventilation, which increases the rate of outdoor airflow in indoor classrooms, had lower predicted probabilities of infection. Older schools and schools in low-income areas had lower predicted probability of transmission, potentially due to lower airtightness compared to newer or recently renovated schools.

Pavilonis et al. (Jan 26, 2021). Estimating Aerosol Transmission Risk of SARS-CoV-2 in New York City Public Schools During Reopening. Environmental Research. https://doi.org/10.1016/j.envres.2021.110805 

[Pre-print, not peer-reviewed] Extending the interval between doses of the Moderna vaccine from 4 weeks to 9-12 weeks could prevent additional infections, hospitalizations, and deaths according to an agent-based model. However, there was no clear advantage for delaying the second dose of the Pfizer-BioNTech vaccines beyond the standard 3-week interval. This is largely attributable to the differences in efficacy used for the first dose of each vaccine (52% for the Pfizer-BioNTech versus 80% for the Moderna vaccine). The authors note uncertainty about how quickly immunity wanes following vaccination, and developed scenarios with different assumptions for this parameter.

Moghadas et al. (Jan 29, 2021). Evaluation of COVID-19 vaccination strategies with a delayed second dose. Pre-print downloaded Jan 29 from https://doi.org/10.1101/2021.01.27.21250619 

Cervical cancer screening rates decreased among 1.5 million women served by Kaiser Permanente Southern California during stay-at-home orders implemented in March 2020 in response to the COVID-19 pandemic. Compared with 2019 screening rates, 2020 screening rates among women aged 21-29 years and aged 30-65 years were 78% and 82% lower, respectively, during the stay-at-home order (March-June). After the stay-at-home orders were lifted, screening rates returned to near baseline but were still 24-29% lower compared to 2019 rates. The decline in screening rates were consistent across racial and ethnic groups. 

Miller et al. (Jan 29, 2021). Impact of COVID-19 on Cervical Cancer Screening Rates Among Women Aged 21-65 Years in a Large Integrated Health Care System – Southern California, January 1-September 30, 2019, and January 1-September 30, 2020. MMWR. https://doi.org/10.15585/mmwr.mm7004a1