Basic IgG Anti-Spike Assays and PCR Test Rates
A total of 12,541 health professionals were tested for baseline anti-peak antibodies; 11,364 (90.6%) were seronegative and 1177 (9.4%) 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). Of the 1265 HIV-positive health professionals, 864 (68%) recalled having symptoms consistent with those of coronavirus 2019 (Covid-19), including symptoms that preceded the widespread availability of PCR tests for SARS-CoV-2; 466 (37%) had a previous SARS-CoV-2 infection confirmed by PCR, of which 262 were symptomatic. Fewer seronegative health professionals (2860 [25% of the 11,364 who were seronegative]) reported pre-baseline symptoms and 24 (all symptomatic, 0.2%) were previously PCR-positive. The median age of seronegative and seropositive health professionals was 38 years (interquartile range 29 to 49). Health care professionals were followed for an average of 200 days (interquartile range, 180 to 207) after a negative antibody test and 139 days at risk (interquartile range, 117 to 147) after a positive antibody test.
The rates of symptomatic CRP tests were similar in seronegative and seropositive health professionals: 8.7 and 8.0 tests per 10,000 days at risk, respectively (rate ratio, 0.92; 95% confidence interval [CI], 0.77 to 1.10). A total of 8,850 health professionals had at least one post-baseline asymptomatic screening test; seronegative health professionals participated in asymptomatic screening more frequently than seropositive health professionals (141 vs. 108 for 10,000 days at risk, respectively; rate ratio, 0.76; 95% CI, 0.73 to 0.80 ).
Incidence of positive CRP results according to baseline anti-peak IgG status
Positive baseline anti-spike antibody assays have been associated with lower rates of positive PCR tests. Of 11,364 health professionals with a negative anti-spike IgG assay, 223 had a positive CRP test (1.09 per 10,000 days at risk), 100 during asymptomatic screening and 123 when symptomatic. Of the 1265 health professionals with a positive IgG anti-spike 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 CRP tests in HIV-positive workers was 0.12 (95% CI, 0.03 to 0.47; P = 0.002). The incidence of symptomatic infection confirmed by PCR in seronegative health professionals was 0.60 per 10,000 days at risk, whereas there were no confirmed symptomatic infections in seropositive health professionals. No positive results for CRP occurred in 24 seronegative health professionals, previously positive for CRP; 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 during the period April to November 2020 is shown for 10,000 days at risk among healthcare professionals according to their status of antibodies at the start of the study. In seronegative health professionals, 1,775 CRP tests (8.7 per 10,000 days at risk) were performed on symptomatic people and 28,878 (141 per 10,000 days at risk) on asymptomatic people; in seropositive health professionals, 126 (8.0 per 10,000 days at risk) were performed in symptomatic persons and 1,704 (108 per 10,000 days at risk) in asymptomatic persons. RR denotes rate ratio.
The incidence varied according to the time of the calendar (figure 1), reflecting the first (March to April) and the second (October and November) pandemic waves in the United Kingdom, and was consistently higher in HIV-negative health workers. After adjusting for age, sex and month of testing (Table S1) or time on the calendar as a continuous variable (Fig. S2), the ratio of the incidence rate in HIV-positive workers was 0.11 (95% CI, 0.03 at 0.44; P = 0.002). The results were similar in analyzes in which the monitoring of seronegative and seropositive workers began 60 days after the baseline serological test; with a window of 90 days after positive serological test or PCR test; and after random removal of PCR results for seronegative health professionals to compare rates of asymptomatic testing in seropositive health professionals (Tables S2 to S4). The incidence of positive CRP tests was inversely associated with anti-peak antibody titers, including titers below the positive limit (P <0.001 for trend) (Fig. S3A).
Anti-nucleocapsid IgG status
With the anti-nucleocapsid IgG used as a marker for previous infection in 12,666 health professionals (Fig. S1B and Table S5), 226 out of 11,543 (1.10 per 10,000 days at risk) seronegative health professionals tested PCR-positive in compared to 2 out of 1172 (0.13 per 10,000 days at risk) healthcare workers with positive antibodies (ratio of the adjusted incidence rate to the time of the calendar, age and sex, 0.11; 95% CI, 0.03 at 0.45; P = 0.002) (Table S6). The incidence of positive CRP results decreased with increasing anti-nucleocapsid antibody titers (P <0.001 for trend) (Fig. S3B).
A total of 12,479 health professionals had baseline anti-peak and anti-nucleocapsid 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 subsequent positive tests for CRP, compared with 1 of 1,021 workers (0.07 per 10,000 days at risk) with both line tests. positive baseline (incidence rate ratio, 0.06; 95% CI, 0.01 to 0.46) and 2 out of 344 workers (0.49 per 10,000 days at risk) with mixed antibody test results (ratio incidence rate, 0.42; 95% CI, 0.10 to 1.69).
Seropositive health professionals with positive PCR results
Subsequently, three seropositive health professionals had PCR-positive 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 the subsequent positive PCR test ranged from 160 to 199 days. Information about the workers’ medical histories and the results of PCR and serological tests is shown in table 2 and Figure S4.
Only the health professional with both antibodies had a history of symptomatic infection confirmed by PCR that preceded the serological test; after five negative CRP tests, this worker had a positive CRP test (low viral load: cycle number, 21 [approximate equivalent cycle threshold, 31]) on day 190 after infection, while the worker was asymptomatic, with subsequent negative CRP tests 2 and 4 days later and no subsequent increase in antibody titers. If the only positive PCR result of this worker was a false positive, the incidence rate for PCR positivity if seropositive anti-spike IgG would drop to 0.05 (95% CI, 0.01 to 0.39) and if anti- seropositive IgG nucleocapsid would fall to 0.06 (95% CI, 0.01 to 0.40).
A fourth health professional with double seropositivity had a positive PCR test 231 days after the worker’s symptomatic infection index, but the worker’s sample retest was negative twice, which suggests a laboratory error in the original PCR result. Subsequent serological tests showed a decrease in the level of anti-nucleocapsid and stable antibodies.