Baseline anti-spike IgG Aces and PCR test rates
A total of 12,541 health care workers were placed under baseline anti-spike antibody measurement; 11,364 (90.6%) were seronegative and 1177 (9.4%) were seropositive on their first anti-spike IgG assay, and serocoversion occurred in 88 workers during the study (Table 1, And the illustrations in the Supplementary Appendix. S1A). Out of 1265 seropositive health care workers, 864 (68%) were reminded that they had symptoms consistent with coronovirus disease 2019 (Kovid-19), including symptoms preceding the widespread availability of PCR testing in SARS-COV-2. ; 466 (37%) had previous PCR-confirmed SARS-CoV-2 infection, of which 262 were symptomatic. Very few health care workers (2860) [25% of the 11,364 who were seronegative]) Reported prebaseline symptoms, and 24 (all symptomatic, 0.2%) were previously PCR positive. The average age of seronegative and seropositive health care workers was 38 years (intercartile range, 29 to 49). Health care workers were followed for a median of 200 days and one day after a positive antibody test. Time of exposure following a positive antibody test (intercartile range, 117 to 147).
The rates of symptomatic PCR testing were similar in seronegative and seropositive health care workers: 8.7 and 8.0 trials at 10,000 days at risk, respectively (rate ratio, 0.92; 95% confidence interval; [CI], 0.77 to 1.10). A total of 8850 health care workers had at least one postbaseline asymptomatic screening test; seronegative health care workers participated in repeated screening for seropositive health care workers (141 vs. 108 per 10,000 days compared to risk, respectively; rate ratio, 0.76; 95% CI, 0.73 to 0.80).
Occurrence of PCR-positive results according to baseline anti-spike IgG status
Positive baseline anti-spike antibody assays were associated with lower rates of PCR-positive tests. Of the 11,364 health care workers with a negative anti-spike IgG assay, 223 had positive PCR tests (1.09 per 10,000 days at risk), 100 during asymptomatic screening, and 123 during symptomatic screening. Of the 1265 health care workers with a positive anti-spike IgG assay, 2 had a positive PCR test (0.13 per 10,000 days at risk), and both workers were asymptomatic when tested. The incidence rate ratio for positive PCR tests in seropositive workers was 0.12 (95% CI, 0.03 to 0.47; P = 0.002). The incidence of PCR-confirmed symptomatic infection in seronegative health care workers was 0.60 per 10,000 days at risk, whereas in seropositive health care workers there were no confirmed symptomatic infections. No PCR-positive results occurred in 24 seronegative, first PCR-positive health care workers; Serocoversion occurred in 5 of these workers during follow-up.
Incidence of polymerase-chain-reaction (PCR) tests that were positive for SARS-CoV-2 infection during November 2020 to April showed at risk of 10,000 days among health care workers according to their antibody status at baseline is. Among serogative health care workers, 1775 PCR tests (per 10,000 days at risk) were performed in symptomatic individuals and 28,878 (141 at risk per day) in asymptomatic individuals; In seropositive health care workers, 126 (8.0 per 10,000 days at risk) were performed in symptomatic individuals and 1704 (108 per 10,000 days at risk) in asymptomatic individuals. RR denotes the ratio.
Variance by calendar timeFigure 1), Reflecting the first (through April) and second (October and November) waves of epidemics in the United Kingdom, and was consistently higher in health care workers. After adjusting for age, sex, and month of testing (Table S1) or calendar time as a continuous variable (Fig. S2), incidence rate ratio in seropositive workers was 0.11 (95% CI, 0.03 to 0.44; P; 0.002) Was. . Results were similar in analyzes in which follow-ups of seronegative and seropositive workers began 60 days after the baseline serologist assay; With a 90-day window after a positive serological assay or PCR test; And after random removal of PCR results for seronetic health care workers to match asymptomatic test rates in serial health care workers (Tables S2 through S2 through S4). The occurrence of positive PCR tests was inversely associated with anti-spike 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 for pre-infection in 12,666 health care workers (Fig. S1B and Table S5), 226 of 22,51143 (1.10 per 10,000 days at risk) of 2 Comparison with seronegative health care workers tested PCR positive. 1172 (0.13 per 10,000 days at risk) antibody-positive health care workers (adjusted incidence rate ratio for calendar time, age, and sex; 0.11; 95% CI, 0.03 to 0.45; P = 0.002) (Table S6 ). The occurrence of PCR-positive results occurred with increasing anti-nucleocapsid antibody titers (P <0.001 for)) (Fig. S3B).
A total of 12,479 health care workers had both anti-spike and anti-nucleocapsid baseline results (Fig. S1C and Tables S7 and S8); Of the 11,182 workers with both immunoassays negative, 218 (at risk per 10,000 days) underwent subsequent PCR-positive tests, compared to 1021 workers (0.07 per day at risk) with both baseline assessments positive (incidence rate ratio, 0.06); 95% CI, 0.01 to 0.46 with mixed antibody results (incidence rate ratio, 0.42; 95% CI, 0.10 to 1.69) and 2 out of 344 workers (0.49 at 10,000 days at risk).
Seropositive health care workers with PCR-positive results
Three seropositive health care workers subsequently underwent PCR-positive testing (only with anti-spike IgG, only with anti-nucleocapsid IgG, and one with both antibodies) for SARS-CoV-2 infection. The time between initial symptoms or seropositivity and subsequent positive PCR testing ranged from 160 to 199 days. Information on the workers’ clinical history and PCR and serologic test results is shown in Table 2 And Figure S4.
Only health care workers with both antibodies had a history of PCR-confirmed symptomatic infection that preceded serologic testing; 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, subsequently tested negative PCR 2 and 4 days later and antibody titers did not increase later. If the single PCR-positive result of this worker was a false positive, the incidence rate ratio for PCR positivity would fall to 0.05 if anti-spike IgG-seropositive and 95 (CI, 0.01 to 0.39) if anti-nucleosipid IgG-seropositive. Will fall; Se 0.06 (95% CI, 0.01 to 0.40).
A fourth dual-seropositive health care worker underwent a PCR-positive test 231 days after the worker’s index symptomatic infection, but re-testing the worker’s sample was twice negative, suggesting a laboratory error in the original PCR result . Later serologic aces showed anti-nucleocapsid and stable anti-spike antibodies.