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Background: The objective of this analysis was to compare the performance sensitivity and specificity of manufacturer-recommended signal-to-cutoff (S/Co) thresholds with modified S/Co values to estimate the prevalence of SARS-CoV-2-specific antibodies in a cohort of firefighters with a known infection history., Methods: Plasma venipuncture samples were used for serologic analysis of firefighters in Los Angeles, CA, USA, in October 2020. Seropositivity was assessed using the manufacturer's recommended S/Co (≥1.4 IgG) and modified S/Co thresholds based on measured antibody levels in 178 negative control patients who had blood drawn prior to the emergence of COVID-19. Optimal S/Co threshold was determined by receiver operating characteristic (ROC) curve analysis., Results: Of 585 firefighters included in the study, 52 (8.9%) reported having a PCR-positive test history prior to antibody testing. Thirty-five (67.3%) firefighters with a previous PCR-positive test were seropositive based on the manufacturer S/Co thresholds, consistent with an estimated 67.3% sensitivity and 100% specificity. After evaluating multiple modified S/Co thresholds based on pre-pandemic negative samples, a modified S/Co of 0.36 was found to yield optimal sensitivity (88.5%) and specificity (99.4%) by ROC curve analysis. This modified threshold improved serostatus classification accuracy by 21.2%., Conclusions: S/Co thresholds based on known negative samples significantly increase seropositivity and more accurately estimate cumulative incidence of disease compared to manufacturer-based thresholds., Competing Interests: Authors’ Disclosures or Potential Conflicts of Interest: Upon manuscript submission, all authors completed the author disclosure form. Disclosures and/or potential conflicts of interest: Employment or Leadership: None declared. Consultant or Advisory Role: N. Sood, Payssurance and American Medical Association. Stock Ownership: None declared. Honoraria: None declared. Research Funding: O. Toubat is supported in part by the National Heart, Lung, and Blood Institute of the National Institutes of Health under award number F30HL154324 outside of the submitted work. A.H. Berg is supported in part by grants from the National Institutes of Health outside of the submitted work. J. Bhattacharya is supported in part by grants from the National Institutes of Health outside of the submitted work. N. Sood received funding and in-kind support from the Burns and Allen Research Institute at Cedars-Sinai Medical Center, Mayor’s Office City of Los Angeles, Rockefeller Foundation, Abbott Diagnostics, and the Conrad R. Hilton Foundation for the study, and grants from the Agency for Healthcare Research and Quality, the National Institutes of Health, Health Care Services Corporation, and the Patient-Centered Outcomes Research Institute outside the submitted work. Expert Testimony: None declared. Patents: None declared. Other Remuneration: K. Mulligan, personal fees from Precision Health Economics; N. Sood, personal fees from the China Development Research Foundation, PhRMA, MDL law firms, Precision Health Economics, and H&H Wholesale; J. Bhattacharya, personal fees from Acumen LLC., (© American Association for Clinical Chemistry 2022. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: We estimate the seroprevalence of SARS-CoV-2 antibodies among a sample of firefighters in the Los Angeles (LA), California fire department in October 2020 and compare demographic and contextual factors for seropositivity., Methods: We conducted a serological survey of firefighters in LA, California, USA, in October 2020. Individuals were classified as seropositive for SARS-CoV-2 if they tested positive for IgG, IgM or both. We compared demographic and contextual factors for seropositivity., Results: All firefighters in LA, California, USA were invited to participate in our study, but only roughly 21% participated. Of 713 participants with valid serological data, 8.8% tested positive for SARS-CoV-2 antibodies, and among the 686 with complete survey data 8.9% tested positive for antibodies. Seropositivity was not associated with gender, age or race/ethnicity. Seropositivity was highest among firefighters who reported working in the vicinity of LA International Airport, which had a known outbreak in July 2020., Conclusions: Seroprevalence among firefighters in our sample was 8.8%, however, we lack a full workplace seroprevalence estimate to compare the relative magnitude against general population seroprevalence (15%). Workplace safety protocols, such as access to personal protective equipment and testing, can mitigate increased risk of infection at work, and may have eliminated differences in disease burden by geography and race/ethnicity in our sample., Competing Interests: Competing interests: NS reported receiving funding and in-kind support from Burns and Allen Research Institute at Cedars-Sinai Medical Center, Mayor’s Office City of Los Angeles, Rockefeller Foundation, Abbott Diagnostics and Conrad R. Hilton Foundation for the study., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: We sought to determine the extent of SARS-CoV-2 seroprevalence and the factors associated with seroprevalence across a diverse cohort of healthcare workers., Design: Observational cohort study of healthcare workers, including SARS-CoV-2 serology testing and participant questionnaires., Settings: A multisite healthcare delivery system located in Los Angeles County., Participants: A diverse and unselected population of adults (n=6062) employed in a multisite healthcare delivery system located in Los Angeles County, including individuals with direct patient contact and others with non-patient-oriented work functions., Main Outcomes: Using Bayesian and multivariate analyses, we estimated seroprevalence and factors associated with seropositivity and antibody levels, including pre-existing demographic and clinical characteristics; potential COVID-19 illness-related exposures; and symptoms consistent with COVID-19 infection., Results: We observed a seroprevalence rate of 4.1%, with anosmia as the most prominently associated self-reported symptom (OR 11.04, p<0.001) in addition to fever (OR 2.02, p=0.002) and myalgias (OR 1.65, p=0.035). After adjusting for potential confounders, seroprevalence was also associated with Hispanic ethnicity (OR 1.98, p=0.001) and African-American race (OR 2.02, p=0.027) as well as contact with a COVID-19-diagnosed individual in the household (OR 5.73, p<0.001) or clinical work setting (OR 1.76, p=0.002). Importantly, African-American race and Hispanic ethnicity were associated with antibody positivity even after adjusting for personal COVID-19 diagnosis status, suggesting the contribution of unmeasured structural or societal factors., Conclusion and Relevance: The demographic factors associated with SARS-CoV-2 seroprevalence among our healthcare workers underscore the importance of exposure sources beyond the workplace. The size and diversity of our study population, combined with robust survey and modelling techniques, provide a vibrant picture of the demographic factors, exposures and symptoms that can identify individuals with susceptibility as well as potential to mount an immune response to COVID-19., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

BACKGROUNDSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused more than 1 million deaths worldwide; thus, there is an urgent need to develop preventive and therapeutic strategies. The antituberculosis vaccine bacillus Calmette-Guérin (BCG) demonstrates nonspecific, protective innate immune-boosting effects. Here, we determined whether a history of BCG vaccination was associated with decreased SARS-CoV-2 infection and seroconversion in a longitudinal, retrospective observational study of a diverse cohort of health care workers (HCWs).METHODSWe assessed SARS-CoV-2 seroprevalence and collected medical questionnaires, which included information on BCG vaccination status and preexisting demographic and clinical characteristics, from an observational cohort of HCWs in a multisite Los Angeles health care organization. We used multivariate analysis to determine whether a history of BCG vaccination was associated with decreased rates of SARS-CoV-2 infection and seroconversion.RESULTSOf the 6201 HCWs, 29.6% reported a history of BCG vaccination, whereas 68.9% had not received BCG vaccination. Seroprevalence of anti-SARS-CoV-2 IgG as well as the incidence of self-reported clinical symptoms associated with coronavirus disease 2019 (COVID-19) were markedly decreased among HCWs with a history of BCG vaccination compared with those without BCG vaccination. After adjusting for age and sex, we found that a history of BCG vaccination, but not meningococcal, pneumococcal, or influenza vaccination, was associated with decreased SARS-CoV-2 IgG seroconversion.CONCLUSIONSA history of BCG vaccination was associated with a decrease in the seroprevalence of anti-SARS-CoV-2 IgG and a lower number of participants who self-reported experiencing COVID-19-related clinical symptoms in this cohort of HCWs. Therefore, large randomized, prospective clinical trials of BCG vaccination are urgently needed to confirm whether BCG vaccination can confer a protective effect against SARS-CoV-2 infection.