Background Reports suggest that some persons previously infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lack detectable IgG antibodies. We aimed to determine the proportion IgG seronegative and predictors for seronegativity among persons previously infected with SARS-CoV-2. Methods We analyzed serologic data collected from health care workers and first responders in New York City and the Detroit metropolitan area with history of a positive SARS-CoV-2 reverse transcriptase polymerase chain reaction (RT-PCR) test result and who were tested for IgG antibodies to SARS-CoV-2 spike protein at least 2 weeks after symptom onset. Results Of 2,547 persons with previous confirmed SARS-CoV-2 infection, 160 (6.3%) were seronegative. Of 2,112 previously symptomatic persons, the proportion seronegative slightly increased from 14 to 90 days post symptom onset (p=0.06). The proportion seronegative ranged from 0% among 79 persons previously hospitalized to 11.0% among 308 persons with asymptomatic infections. In a multivariable model, persons taking immunosuppressive medications were more likely to be seronegative (31.9%, 95% confidence interval [CI] 10.7%-64.7%), while participants of non-Hispanic Black race/ethnicity (versus non-Hispanic White) (2.7%, 95% CI 1.5%-4.8%), with severe obesity (versus under/normal weight) (3.9%, 95% CI 1.7%-8.6%), or with more symptoms were less likely to be seronegative. Conclusions In our population with previous RT-PCR confirmed infection, approximately one in 16 persons lacked IgG antibodies. Absence of antibodies varied independently by illness severity, race/ethnicity, obesity, and immunosuppressive drug therapy. The proportion seronegative remained relatively stable among persons tested up to 90 days post symptom onset.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), a known disruptor of B-cell differentiation and a ligand for the aryl hydrocarbon receptor (AhR), induces binding of the AhR to dioxin responsive elements (DRE) in sensitive genes. The Ig heavy chain (IgH) gene is a sensitive target of TCDD and may be transcriptionally inhibited by TCDD through inhibition of the 3′IgH transcriptional regulatory region (3′IgHRR). While the 3′IgHRR contains binding sites for several transcription factors, two DRE motifs were also identified which may be responsible for TCDD-induced inhibition of 3′IgHRR activation and may implicate the AhR as an important regulator of IgH expression. The objectives of the present study were to determine if 3′IgHRR modulation is limited to TCDD or if structurally diverse chemicals (AhR ligands and non-AhR ligands) from environmental, industrial, dietary or pharmaceutical origin are also capable of modulating the 3′IgHRR and to verify a correlation between effects on a stable 3′IgHRR reporter and the endogenous IgH protein. Utilizing a CH12.LX mouse B-cell line that stably expresses a 3′IgHRR-regulated transgene, we identified an inhibition of both 3′IgHRR activation and IgH protein expression by the non-dioxin AhR activators indolo(3,2-b)carbazole, primaquine, carbaryl, and omeprazole which followed a rank order potency for AhR activation supporting a role of the AhR in the transcriptional regulation of the 3′IgHRR and IgH expression. However, modulation of the 3′IgHRR and IgH expression was not limited to AhR activators or to suppressive effects. Hydrogen peroxide and terbutaline had an activating effect and benzyl isothiocyanate was inhibitory. These chemicals are not known to influence the AhR signaling pathway but have been previously shown to modulate humoral immunity and/or transcription factors that regulate the 3′IgHRR. Taken together these results implicate the 3′IgHRR as a sensitive immunological target and are the first to identify altered 3′IgHRR activation by a diverse range of chemicals.

We conducted a serologic survey in public service agencies in New York City, New York, USA, during May–July 2020 to determine prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among first responders. Of 22,647 participants, 22.5% tested positive for SARS-CoV-2–specific antibodies. Seroprevalence for police and firefighters was similar to overall seroprevalence; seroprevalence was highest in correctional staff (39.2%) and emergency medical technicians (38.3%) and lowest in laboratory technicians (10.1%) and medicolegal death investigators (10.8%). Adjusted analyses demonstrated association between seropositivity and exposure to SARS-CoV-2–positive household members (adjusted odds ratio [aOR] 3.52 [95% CI 3.19–3.87]), non-Hispanic Black race or ethnicity (aOR 1.50 [95% CI 1.33–1.68]), and severe obesity (aOR 1.31 [95% CI 1.05–1.65]). Consistent glove use (aOR 1.19 [95% CI 1.06–1.33]) increased likelihood of seropositivity; use of other personal protective equipment had no association. Infection control measures, including vaccination, should be prioritized for frontline workers.