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Reference IgG anti-spike and PCR test rates
Demographic characteristics and SARS-CoV-2 PCR tests for 12,541 healthcare workers based on SARS-CoV-2 anti-spike IgG status.
A total of 12,541 health workers underwent the measurement of the reference anti-peak antibodies; 11,364 (90.6%) were seronegative and 1177 (9.4%) were seropositive in their first anti-peak IgG assay, and seroconversion occurred in 88 workers during the study (Table 1and Fig. S1A in the Supplementary Appendix). Out of 1,265 HIV-positive healthcare workers, 864 (68%) recalled having symptoms consistent with those of coronavirus disease 2019 (Covid-19), including symptoms that preceded the wide availability of PCR testing for SARS- CoV-2; 466 (37%) had had a previous PCR-confirmed SARS-CoV-2 infection, of which 262 were symptomatic. Fewer HIV-negative health workers (2,860 [25% of the 11,364 who were seronegative]) reported symptoms prior to baseline and 24 (all symptomatic, 0.2%) were previously PCR positive. The median age of the seronegative and seropositive health workers was 38 years (interquartile range, 29 to 49). Healthcare workers were followed for a median of 200 days (interquartile range, 180 to 207) after a negative antibody test and for 139 days at risk (interquartile range, 117 to 147) after a positive antibody test.
Symptomatic CRP test rates were similar in seronegative and seropositive healthcare workers: 8.7 and 8.0 tests per 10,000 risk days, respectively (rate index, 0.92, 95% confidence interval [CI], 0.77 to 1.10). A total of 8,850 healthcare workers underwent at least one post-initiation asymptomatic screening; Seronegative healthcare workers attended asymptomatic screenings more frequently than seropositive healthcare workers (141 vs 108 per 10,000 days at risk, respectively; rate ratio 0.76, 95% CI 0.73 to 0. 80).
Incidence of positive results for PCR according to baseline anti-peak IgG
Positive baseline anti-spike antibody assays were associated with lower rates of positive PCR tests. Of the 11,364 healthcare workers with a negative anti-spike IgG assay, 223 had a positive PCR test (1.09 per 10,000 days at risk), 100 during asymptomatic detection, and 123 while presenting with symptoms. Of 1265 healthcare workers with a positive anti-spike IgG test, 2 had a positive PCR test (0.13 per 10,000 risk days) and both workers were asymptomatic when tested. The incidence rate of positive CRP tests in HIV-positive workers was 0.12 (95% CI, 0.03 to 0.47, P = 0.002). The incidence of PCR-confirmed symptomatic infection in seronegative healthcare workers was 0.60 per 10,000 days at risk, whereas there were no confirmed symptomatic infections in seropositive healthcare workers. There were no positive PCR results in 24 seronegative healthcare workers, previously PCR positive; Seroconversion occurred in 5 of these workers during follow-up.
Observed incidence of SARS-CoV-2 positive PCR results based on baseline anti-peak IgG antibodies.
The incidence of polymerase chain reaction (PCR) tests that tested positive for SARS-CoV-2 infection during the period from April to November 2020 is shown for every 10,000 days at risk among healthcare workers in according to your antibody status at the start of the study. In seronegative health workers, 1,775 CRP tests (8.7 per 10,000 days at risk) were performed in symptomatic people and 28,878 (141 per 10,000 days at risk) in asymptomatic people; In seropositive health workers, 126 (8.0 per 10,000 days at risk) were performed in symptomatic people and 1704 (108 per 10,000 days at risk) in asymptomatic people. RR denotes rate ratio.
The incidence varied according to calendar time (Figure 1), reflecting the first (March to April) and second (October and November) waves of the pandemic in the UK, and was consistently higher in HIV-negative healthcare workers. After adjusting for age, sex and month of the test (Table S1) or calendar time as continuous variable (Fig. S2), the ratio of the incidence rate in seropositive workers was 0.11 (95% CI, 0.03 to 0.44; P = 0.002). Results were similar in analyzes in which follow-up of seronegative and seropositive workers began 60 days after the initial serologic test; with a window of 90 days after a positive serological test or a PCR test; and after random elimination of PCR results for seronegative healthcare workers to equalize the rates of asymptomatic tests in seropositive healthcare workers (Tables S2 to S4). The incidence of positive PCR tests was inversely associated with anti-peak antibody titers, including titers below the positive threshold (P <0.001 for trend) (Fig. S3A).
Anti-nucleocapsid IgG status
With anti-nucleocapsid IgG used as a marker of previous infection in 12,666 healthcare workers (Fig. S1B and Table S5), 226 out of 11,543 (1.10 per 10,000 days at risk) seronegative healthcare workers tested positive in PCR, compared to 2 of 1,172 (0.13 per 10,000 risk days) antibody-positive healthcare workers (incidence rate index adjusted for calendar time, age, and sex, 0.11; 95% CI, 0.03 to 0, 45; P = 0.002) (Table S6). The incidence of positive PCR results decreased with increasing anti-nucleocapsid antibody titers (P <0.001 for trend) (Fig. S3B).
A total of 12,479 health workers had both anti-peak and anti-nucleocapsid baseline results (Fig. S1C and Tables S7 and S8); 218 of 11,182 workers (1.08 per 10,000 days at risk) with both negative immunoassays had positive subsequent PCR tests, compared to 1 of 1,021 workers (0.07 per 10,000 days at risk) with both initial tests positive (index of incidence rate, 0.06, 95% CI, 0.01 to 0.46) and 2 of 344 workers (0.49 per 10,000 days at risk) with mixed antibody assay results (incidence rate index 0.42, 95% CI 0.10 to 1.69).
HIV-positive healthcare workers with positive PCR results
Demographic, clinical and laboratory characteristics of healthcare workers with possible reinfection by SARS-CoV-2.
Subsequently, three seropositive healthcare workers had positive PCR tests for SARS-CoV-2 infection (one with anti-spike IgG only, one with anti-nucleocapsid IgG only, and one with both antibodies). The time between initial symptoms or seropositivity and subsequent positive PCR test ranged from 160 to 199 days. Information on workers’ medical records and on PCR and serological test results is displayed in Table 2 and Figure S4.
Only the healthcare worker with both antibodies had a history of PCR-confirmed symptomatic infection that preceded serological tests; After five negative PCR tests, this worker had a positive PCR test (low viral load: cycle number, 21 [approximate equivalent cycle threshold, 31]) on day 190 after infection while the worker was asymptomatic, with negative subsequent PCR tests 2 and 4 days later and no subsequent increase in antibody titers. If this worker’s single positive PCR result was a false positive, the incidence rate of positive PCR if anti-spike IgG-seropositive would drop to 0.05 (95% CI, 0.01 to 0.39) and if anti-IgG-seropositive nucleocapsid would decrease at 0.06 (95% CI, 0.01 to 0.40).
A fourth dual-seropositive healthcare worker had a positive PCR test 231 days after the worker’s symptomatic index infection, but the worker’s sample retest was negative twice, suggesting a laboratory error in the result of original PCR. Subsequent serological analyzes showed a decrease in stable anti-nucleocapsid and anti-spike antibodies.
