Basic anti-spike IgG tests and PCR testing rates
A total of 12,541 health workers underwent measurement of basic antibodies against spikes; 11,364 (90.6%) were seronegative and 1177 (9.4%) seropositive in the first anti-spike IgG study, and seroconversion occurred in 88 workers during the studyTable 1and Figure S1A in Supplementary Appendix). Of the 1265 seropositive healthcare workers, 864 (68%) recalled having symptoms that matched the symptoms of coronavirus disease 2019 (Covid-19), including symptoms that preceded the widespread availability of PCR testing for SARS-CoV-2; 466 (37%) had a previous PCR-confirmed SARS-CoV-2 infection, of which 262 were symptomatic. Fewer seronegative health workers (2860 [25% of the 11,364 who were seronegative]) reported pre-bypass line symptoms, and 24 (all symptomatic, 0.2%) were previously PCR positive. The median age of seronegative and seropositive health workers was 38 years (interquartile range, 29 to 49). Healthcare workers were followed by a median of 200 days (interquartile range, 180 to 207) after a negative antibody test and 139 days of risk (interquartile range, 117 to 147) after a positive antibody test.
Symptoms of symptomatic PCR testing were similar in seronegative and seropositive healthcare workers: 8.7 and 8.0 tests per 10,000 days of risk (rate ratio, 0.92; 95% confidence interval [CI], 0.77 to 1.10). A total of 8,850 health workers had at least one asymptomatic screening test after the initial condition; seronegative health workers attended asymptomatic examinations more often than seropositive health workers (141 versus 108 per 10,000 risk days; rate ratio, 0.76; 95% CI, 0.73 to 0.80).
Incidence of PCR-positive results according to basal IgG status against spikes
Positive spike antibody assays were associated with lower rates of PCR positive assays. Of the 11,364 health workers with a negative IgG test against spikes, 223 had a positive PCR test (1.09 per 10,000 days of risk), 100 during asymptomatic screening, and 123 while symptomatic. Of the 1265 health workers with a positive IgG test against spikes, 2 had a positive PCR test (0.13 per 10,000 days of risk), and both workers were asymptomatic when tested. The incidence 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 workers was 0.60 per 10,000 days of risk, whereas no symptomatic infections were confirmed in seropositive health workers. There were no PCR positive results in 24 seronegative, previously PCR positive health workers; seroconversion occurred in 5 of these workers during follow-up.
The incidence of polymerase chain reaction (PCR) tests that were positive for SARS-CoV-2 infection in the period from April to November 2020 was shown at 10,000 risk days among healthcare workers according to their antibody status at baseline. In seronegative health workers, 1,775 PCR tests (8.7 per 10,000 days of risk) were performed in symptomatic individuals and 28,878 (141 per 10,000 risk days) in asymptomatic subjects; seropositive health care workers 126 (8.0 per 10,000 days of risk) were undertaken in symptomatic individuals, and 1704 (108 in 10,000 days of risk) in asymptomatic subjects. RR denotes the rate ratio.
The incidence varies according to calendar time (Figure 1), reflecting the first (March to April) and second (October and November) pandemic waves in the United Kingdom, and was consistently higher in seronegative health workers. After adjusting for age, sex, and month of testing (Table S1) or calendar time as a continuous variable (Figure S2), the incidence rate ratio in seropositive workers was 0.11 (95% CI, 0.03 to 0.44; P = 0.002). ). The results were similar in analyzes in which follow-up of both seronegative and seropositive workers began 60 days after the initial serological test; with a time of 90 days after a positive serological test or PCR test; and after random removal of PCR results for seronegative health professionals to match asymptomatic testing rates in seropositive health care workers (Tables S2 to S4). The incidence of positive PCR tests was inversely related to anti-spike antibody titers, including titers below the positive threshold (P <0.001 for trend) (Figure S3A).
Anti-nucleocapsid IgG status
With anti-nucleocapsid IgG used as a marker for previous infection in 12,666 health care workers (Figure S1B and Table S5), 226 of 11,543 (1.10 per 10,000 days at risk) seronegative health care workers were tested for PCR-positive, compared with 2 of 1172 (0.13 per 10,000 risk days) antibody-positive health workers (incidence rate adjusted for calendar time, age, and sex, 0.11; 95% CI, 0.03 to 0.45; P = 0.002) (Table S6). The incidence of PCR positive results decreased with increasing antinucleocapsid antibody titer (P <0.001 for trend) (Fig. S3B).
A total of 12,479 health workers had basic results against both spikes and nucleocapsids (Figure S1C and Tables S7 and S8); 218 of 11,182 workers (1.08 per 10,000 days of risk) with both negative immunoassays had subsequent PCR positive tests, compared with 1 of 1021 workers (0.07 per 10,000 days of risk) with both basic tests positive (incidence rate ratio 0 , 06; 95% CI, 0.01 to 0.46) and 2 of 344 workers (0.49 per 10,000 days of risk) with results of mixed antibody tests (incidence rate ratio 0.42; 95% CI, 0.10 to 1.69).
Seropositive healthcare workers with PCR positive results
Three seropositive health workers subsequently had PCR-positive tests for SARS-CoV-2 infection (one with spike IgG only, one with nucleocapsid IgG only, and one with both antibodies). The time between initial symptoms or seropositivity and positive PCR tests ranged from 160 to 199 days. Data on the clinical history of workers and the results of PCR and serological tests are presented in Table 2 and Figure S4.
Only a healthcare worker with both antibodies had a history of symptomatic PCR-confirmed infection prior to serological testing; after five negative PCR tests, this worker had one positive PCR test (low viral load: number of cycles, 21 [approximate equivalent cycle threshold, 31]) 190 days after infection, while the worker was asymptomatic, with subsequent negative PCR tests 2 and 4 days later and without a subsequent increase in antibody titer. If the individual PCR-positive result of this worker is false positive, the incidence ratio for PCR positivity if the IgG-seropositive against spike fell to 0.05 (95% CI, 0.01 to 0.39) and if the anti-nucleocapsid IgG –Seropositive dropped to 0.06 (95% CI, 0.01 to 0.40).
A fourth double-seropositive healthcare worker had a PCR positive test 231 days after the worker’s symptomatic infection index, but retesting the worker sample was twice negative, suggesting a laboratory error in the original PCR result. Subsequent serological tests showed declining anti-nucleocapsid and stable anti-spike antibodies.