COVID-19 Infections and Predictors of Sickness Related Absences Among Healthcare Workers: The Experience of a Tertiary Care Center With the COVID-19 Pandemic.

BACKGROUND: Little has been published on predictors of prolonged sick leaves during the COVID-19 pandemic. This study aims to determine the rate of COVID-19 infections among healthcare workers (HCWs) and to identify the predictors of longer sick leave days. METHODS: We identified predictors of longer sick leave using linear regression analysis in a cross-sectional study design. RESULTS: Thirty-three percent of the total workforce contracted COVID-19. On average, HCWs took 12.5 sick leave days after COVID-19 infection. The regression analysis revealed that older employees, nurses, and those who caught COVID-19 earlier in the pandemic were more likely to take longer sick leave. CONCLUSIONS: Age, job position, and month of infection predicted sick leave duration among HCWs in our sample. Results imply that transmission was most likely community-based. Public health interventions should consider these factors when planning for future pandemics.

Occupational Risk Factors for SARS-CoV-2 Seropositivity in Healthcare Workers: Results of a Longitudinal Cohort.

OBJECTIVE: The aim of the study is to evaluate COVID-19 risk factors among healthcare workers (HCWs) before vaccine-induced immunity. METHODS: We conducted a longitudinal cohort study of HCWs ( N = 1233) with SARS-CoV-2 immunoglobulin G quantification by ELISA and repeated surveys over 9 months. Risk factors were assessed by multivariable-adjusted logistic regression and Cox proportional hazards models. RESULTS: SARS-CoV-2 immunoglobulin G was associated with work in internal medicine (odds ratio [OR], 2.77; 95% confidence interval [CI], 1.05-8.26) and role of physician-in-training (OR, 2.55; 95% CI, 1.08-6.43), including interns (OR, 4.22; 95% CI, 1.20-14.00) and resident physicians (OR, 3.14; 95% CI, 1.24-8.33). Odds were lower among staff confident in N95 use (OR, 0.55; 95% CI, 0.31-0.96) and decreased over the follow-up. CONCLUSIONS: Excess COVID-19 risk observed among physicians-in-training early in the COVID-19 pandemic was reduced with improved occupational health interventions before vaccinations.

Changes Over Time in COVID-19 Incidence, Vaccinations, Serum Spike IgG, and Viral Neutralizing Potential Among Individuals From a North American Gaming Venue: December 2020-August 2021.

OBJECTIVE: This study aims to evaluate COVID-19 cases and vaccine responses among workers in the gaming/entertainment industry. METHODS: Participants provided detailed information on occupational risk factors, demographics, COVID-19 history, and vaccination status through questionnaire. Enzyme-linked immunosorbent assays were used to measure serum antiviral antibodies and neutralizing capacity. RESULTS: Five hundred-fifty individuals participated with n = 228 (41.5%) returning for follow-up. At least 71% of participants were fully vaccinated within 8 months of vaccine availability and COVID-19 rates declined concomitantly. Serum anti-spike IgG levels and neutralizing capacity were significantly (P < 0.001) associated COVID-19 history and vaccine type, but not occupational risk factors, and declined (on average 36%) within 5 months. Few vaccine nonresponders (n = 12) and "breakthrough" infections (n = 1) were noted. CONCLUSIONS: COVID-19 vaccination was associated with a marked decrease in infections; however, individual humoral responses varied and declined significantly over time.

Anxiety Among Healthcare Workers During COVID-19 Pandemic in Lebanon: The Importance of the Work Environment and Personal Resilience.

Background: Healthcare workers (HCWs) have been severely impacted by the COVID-19 pandemic. In addition to their risk of direct exposure to the virus, they were subjected to long working hours, scarcity of PPE, and additional stressors that impacted their psychological wellbeing. The purpose of this study was to assess anxiety and its predictors among a sample of HCWs at the American University of Beirut Medical Center (AUBMC) and to evaluate the association between resilience and anxiety. Methods: This cross-sectional study was conducted using an online survey between March and June 2021 among HCWs at AUBMC. The psychosocial scale section included the 7-item generalized anxiety disorder (GAD-7) scale and a 25-item resilience scale, validated tools used to assess anxiety and resilience respectively. Data were analyzed on SPSS version 27, and descriptive statistics were applied. Predictors were evaluated using bivariate and multivariate linear regression. Results: From a total of 92 participants, 75% were involved in direct patient care, and of those, 95% worked directly with suspected or confirmed COVID-19 patients. The majority (83%) had minimal to mild anxiety, whereas the rest had moderate to high anxiety levels. Around 41% reported moderately high to high resilience, 47% were found to be between the low end and moderate resilience scale and only 12% had very low or low resilience. More than 80% of the participants received PPE training, reported always working with adequate preventive infection control measures, and were vaccinated. Further, more than 70% of participants reported trusting the management and agreed that the safety of the workers is considered a high priority. No significant association between sociodemographic and COVID-19 work exposure factors with anxiety was found. Multivariate analysis results showed that a lower anxiety score was associated with higher resilience (p = 0.011). Conclusion: This study has shown a strong association between low anxiety levels and high resilience scores in this group of mostly vaccinated HCWs caring for COVID-19 patients. The high percentage of vaccination along with PPE availability could explain the low anxiety levels reported among the participants.

Development and utilization of a surrogate SARS-CoV-2 viral neutralization assay to assess mRNA vaccine responses.

BACKGROUND: Tests for SARS-CoV-2 immunity are needed to help assess responses to vaccination, which can be heterogeneous and may wane over time. The plaque reduction neutralization test (PRNT) is considered the gold standard for measuring serum neutralizing antibodies but requires high level biosafety, live viral cultures and days to complete. We hypothesized that competitive enzyme linked immunoassays (ELISAs) based on SARS-CoV-2 spike protein's receptor binding domain (RBD) attachment to its host receptor, the angiotensin converting enzyme 2 receptor (ACE2r), would correlate with PRNT, given the central role of RBD-ACE2r interactions in infection and published studies to date, and enable evaluation of vaccine responses. METHODS AND RESULTS: Configuration and development of a competitive ELISA with plate-bound RBD and soluble biotinylated ACE2r was accomplished using pairs of pre/post vaccine serum. When the competitive ELISA was used to evaluate N = 32 samples from COVID-19 patients previously tested by PRNT, excellent correlation in IC50 results were observed (rs = .83, p < 0.0001). When the competitive ELISA was used to evaluate N = 42 vaccinated individuals and an additional N = 13 unvaccinated recovered COVID-19 patients, significant differences in RBD-ACE2r inhibitory activity were associated with prior history of COVID-19 and type of vaccine received. In longitudinal analyses pre and up to 200 days post vaccine, surrogate neutralizing activity increased markedly after primary and booster vaccine doses, but fell substantially, up to <12% maximal levels within 6 months. CONCLUSIONS: A competitive ELISA based on inhibition of RBD-ACE2r attachment correlates well with PRNT, quantifies significantly higher activity among vaccine recipients with prior COVID (vs. those without), and highlights marked declines in surrogate neutralizing activity over a 6 month period post vaccination. The findings raise concern about the duration of vaccine responses and potential need for booster shots.

Immunogenic amino acid motifs and linear epitopes of COVID-19 mRNA vaccines.

Reverse vaccinology is an evolving approach for improving vaccine effectiveness and minimizing adverse responses by limiting immunizations to critical epitopes. Towards this goal, we sought to identify immunogenic amino acid motifs and linear epitopes of the SARS-CoV-2 spike protein that elicit IgG in COVID-19 mRNA vaccine recipients. Paired pre/post vaccination samples from N = 20 healthy adults, and post-vaccine samples from an additional N = 13 individuals were used to immunoprecipitate IgG targets expressed by a bacterial display random peptide library, and preferentially recognized peptides were mapped to the spike primary sequence. The data identify several distinct amino acid motifs recognized by vaccine-induced IgG, a subset of those targeted by IgG from natural infection, which may mimic 3-dimensional conformation (mimotopes). Dominant linear epitopes were identified in the C-terminal domains of the S1 and S2 subunits (aa 558-569, 627-638, and 1148-1159) which have been previously associated with SARS-CoV-2 neutralization in vitro and demonstrate identity to bat coronavirus and SARS-CoV, but limited homology to non-pathogenic human coronavirus. The identified COVID-19 mRNA vaccine epitopes should be considered in the context of variants, immune escape and vaccine and therapy design moving forward.

Associations of SARS-CoV-2 serum IgG with occupation and demographics of military personnel.

BACKGROUND: Countries across the globe have mobilized their armed forces in response to COVID-19, placing them at increased risk for viral exposure. Humoral responses to SARS-CoV-2 among military personnel serve as biomarkers of infection and provide a basis for disease surveillance and recognition of work-related risk factors. METHODS: Enzyme-linked immunosorbent assays (ELISA) were used to measure SARS-CoV-2 spike antigen-specific IgG in serum obtained from N = 988 US National Guard soldiers between April-June 2020. Occupational information, e.g. military operating specialty (MOS) codes, and demographic data were obtained via questionnaire. Plaque assays with live SARS-CoV-2 were used to assess serum neutralizing capacity for limited subjects (N = 12). RESULTS: The SARS-CoV-2 IgG seropositivity rate among the study population was 10.3% and significantly associated with occupation and demographics. Odds ratios were highest for those working in MOS 2T-Transportation (3.6; 95% CI 0.7-18) and 92F-Fuel specialist/ground and aircraft (6.8; 95% CI 1.5-30), as well as black race (2.2; 95% CI 1.2-4.1), household size ≥6 (2.5; 95% CI 1.3-4.6) and known COVID-19 exposure (2.0; 95% CI 1.2-3.3). Seropositivity tracked along major interstate highways and clustered near the international airport and the New York City border. SARS-CoV-2 spike IgG+ serum exhibited low to moderate SARS-CoV-2 neutralizing capacity with IC50s ranging from 1:15 to 1:280. In limited follow-up testing SARS-CoV-2 serum IgG levels remained elevated up to 7 months. CONCLUSIONS: The data highlight increased SARS-CoV-2 seroprevalence among National Guard vs. the local civilian population in association with transportation-related occupations and specific demographics.

Human IgG and IgA responses to COVID-19 mRNA vaccines.

SARS-CoV-2 spike antigen-specific IgG and IgA elicited by infection mediate viral neutralization and are likely an important component of natural immunity, however, limited information exists on vaccine induced responses. We measured COVID-19 mRNA vaccine induced IgG and IgA in serum serially, up to 145 days post vaccination in 4 subjects. Spike antigen-specific IgG levels rose exponentially and plateaued 21 days after the initial vaccine dose. After the second vaccine dose IgG levels increased further, reaching a maximum approximately 7-10 days later, and remained elevated (average of 58% peak levels) during the additional >100 day follow up period. COVID-19 mRNA vaccination elicited spike antigen-specific IgA with similar kinetics of induction and time to peak levels, but more rapid decline in serum levels following both the 1st and 2nd vaccine doses (<18% peak levels within 100 days of the 2nd shot). The data demonstrate COVID-19 mRNA vaccines effectively induce spike antigen specific IgG and IgA and highlight marked differences in their persistence in serum.

SARS-CoV-2 Infection Hospitalization Rate and Infection Fatality Rate Among the Non-Congregate Population in Connecticut.

BACKGROUND: Infection fatality rate and infection hospitalization rate, defined as the proportion of deaths and hospitalizations, respectively, of the total infected individuals, can estimate the actual toll of coronavirus disease 2019 (COVID-19) on a community, as the denominator is ideally based on a representative sample of a population, which captures the full spectrum of illness, including asymptomatic and untested individuals. OBJECTIVE: To determine the COVID-19 infection hospitalization rate and infection fatality rate among the non-congregate population in Connecticut between March 1 and June 1, 2020. METHODS: The infection hospitalization rate and infection fatality rate were calculated for adults residing in non-congregate settings in Connecticut prior to June 2020. Individuals with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies were estimated using the seroprevalence estimates from the recently conducted Post-Infection Prevalence study. Information on total hospitalizations and deaths was obtained from the Connecticut Hospital Association and the Connecticut Department of Public Health, respectively. RESULTS: Prior to June 1, 2020, nearly 113,515 (90% confidence interval [CI] 56,758-170,273) individuals were estimated to have SARS-CoV-2 antibodies, and there were 7792 hospitalizations and 1079 deaths among the non-congregate population. The overall COVID-19 infection hospitalization rate and infection fatality rate were estimated to be 6.86% (90% CI, 4.58%-13.72%) and 0.95% (90% CI, 0.63%-1.90%), respectively, and there was variation in these rate estimates across subgroups; older people, men, non-Hispanic Black people, and those belonging to 2 of the counties had a higher burden of adverse outcomes, although the differences between most subgroups were not statistically significant. CONCLUSIONS: Using representative seroprevalence estimates, the overall COVID-19 infection hospitalization rate and infection fatality rate were estimated to be 6.86% and 0.95%, respectively, among community residents in Connecticut.

Seroprevalence of SARS-CoV-2-Specific IgG Antibodies Among Adults Living in Connecticut: Post-Infection Prevalence (PIP) Study.

BACKGROUND: A seroprevalence study can estimate the percentage of people with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies in the general population; however, most existing reports have used a convenience sample, which may bias their estimates. METHODS: We sought a representative sample of Connecticut residents, ages ≥18 years and residing in noncongregate settings, who completed a survey between June 4 and June 23, 2020, and underwent serology testing for SARS-CoV-2-specific immunoglobulin G (IgG) antibodies between June 10 and July 29, 2020. We also oversampled non-Hispanic black and Hispanic subpopulations. We estimated the seroprevalence of SARS-CoV-2-specific IgG antibodies and the prevalence of symptomatic illness and self-reported adherence to risk-mitigation behaviors among this population. RESULTS: Of the 567 respondents (mean age 50 [± 17] years; 53% women; 75% non-Hispanic white individuals) included at the state level, 23 respondents tested positive for SARS-CoV-2-specific antibodies, resulting in weighted seroprevalence of 4.0 (90% confidence interval [CI] 2.0-6.0). The weighted seroprevalence for the oversampled non-Hispanic black and Hispanic populations was 6.4% (90% CI 0.9-11.9) and 19.9% (90% CI 13.2-26.6), respectively. The majority of respondents at the state level reported following risk-mitigation behaviors: 73% avoided public places, 75% avoided gatherings of families or friends, and 97% wore a facemask, at least part of the time. CONCLUSIONS: These estimates indicate that the vast majority of people in Connecticut lack antibodies against SARS-CoV-2, and there is variation by race and ethnicity. There is a need for continued adherence to risk-mitigation behaviors among Connecticut residents to prevent resurgence of COVID-19 in this region.