RESULTS:
We enrolled 1,582 HCWs, which comprised 38.5% of eligible HCWs in participating hospitals. Three participants were excluded because no follow-up data were obtained after enrolment. Supplementary Figure 1 shows the flow of participants through study.
Of the 1582 HCWs enrolled, 1473 (93%) were female, the median age was 49 (IQR: 39-57); 408 (26%) were physicians, 591 (37%) were nurses, and 583 (37%) were other HCWs (Table 1). In all, 644 (41%) participants had at least one comorbidity, and 46 (3%) and 14 (1%) participants said they smoked currently or previously, respectively. A total of 458 (29%) HCWs had received the influenza vaccine in the 2019-2020 influenza season. Overall, 582 HCWs (37%) were from central hospitals in Baku, while 1000 (63%) HCWs were from peripheral Baku hospitals.
At enrolment, 1040 (66%) participants had received primary series CoronaVac, 121 (8%) participants had received only one dose of CoronaVac, and 421 (27%) were unvaccinated (Table 1). No participants had received other COVID-19 vaccines at enrolment. Among those vaccinated with the primary series before enrolment, the median time since receipt of the second dose was 99 days (IQR 74-112). Overall, 248 HCWs (16%) had a PCR-positive COVID-19 infection documented prior to enrolment. Compared to unvaccinated participants, participants who had received primary series vaccine before enrolment worked more commonly in central hospitals (39% vs 29%), had more chronic condition (38% vs 48%) and had less PCR-confirmed infections prior to enrolment (6% vs 40%). Differences in participants by vaccination status at enrolment have been previously reported.
In total, 963/1040 (93%) participants who had received primary series vaccine were seropositive at enrolment for either anti-nucleocapsid or the anti-spike protein antibodies; 903 (90%) were seropositive for anti-spike antibodies, while 827 (83%) were seropositive for anti-nucleocapsid antibodies. Among unvaccinated participants, 363/421 (86%) were seropositive to at least one of the two antibodies (Table 1). Of the 197 unvaccinated participants who did not report a previous PCR infection at enrolment, 136 (69%) were seropositive at enrolment by one of the two assays.
During the follow-up period, 10 (<1%) participants received primary series vaccination with vaccines other than CoronaVac (9 received Pfizer, and 1 received Sputnik) and were excluded from the analysis. At their exit from analysis, 1485 (95%) participants had received primary series CoronaVac, 41 (3%) had received one dose of CoronaVac, and 43 (3%) remained unvaccinated. Changes in the vaccination status of the enrolled population over the course of the study are illustrated in Figure 1. At study exit, participants who had received the primary series were similar to unvaccinated participants in terms of median age, sex, smoking status and self-assessed health status; however, compared to participants who had received primary series vaccine, unvaccinated participants were more commonly medical doctors (47% vs 25%) and less unvaccinated participants received influenza vaccine during the previous season (70% vs. 81%) (Supplementary Table 1).
Unvaccinated HCWs contributed a total of 24,745 person-days to the 30-week study period, while participants vaccinated with the primary series of CoronaVac contributed 172,457 person-days. During this time period, 380 participants were symptomatic, of whom 201 (53%) provided a respiratory sample that was tested for SARS-CoV-2 by PCR. Overall, 72 participants (5%) had symptomatic PCR-confirmed COVID-19, including 64 vaccinated participants and 8 unvaccinated participants. Cases peaked in August, but incidence remained high through the end of the analysis period; the trajectory of cases in the study mostly mirrored the national trends of COVID-19 incidence during the summer of 2021 in Azerbaijan (Figure 2). Of the 39 samples for which WGS data were available, 36/39 (92%) were delta variant (Supplementary Figure 2).
During the course of the analysis period, in the 30 days following their positive test, 44 participants with PCR-confirmed COVID-19 illness sought medical care (4 unvaccinated and 40 fully vaccinated), and 29 participants went to an emergency room (3 unvaccinated and 26 fully vaccinated). Three participants with PCR-confirmed COVID-19 illness were hospitalized (1 unvaccinated and 2 fully vaccinated). No deaths occurred among participants with PCR-confirmed COVID -19 illness. VE could not be calculated against these more severe outcomes because of the small number of events among unvaccinated participants.
For the overall cohort, the adjusted two-dose VE was 29% (95% CI -51% to 67%) (Table 2, Figure 3a). For the delta-predominant period, adjusted two-dose VE was 19% (95% CI -81% to 64%). VE was adjusted for previous infection only; no other potential confounders changed the VE estimates in more than 5%. For the overall cohort analysis, vaccinated participants had received their second dose a median of 90 days (IQR: 75-112) prior to the beginning of the study period, while during the period of delta circulation, vaccinated participants had received their second dose a median of 108 days (IQR: 106-132) prior to the analysis period.
When we excluded participants who had PCR-confirmed SARS-CoV-2 infection prior to enrolment, unadjusted VE was 37 (95% CI -33 to 70), and unadjusted VE during the delta-predominant period was 29 (95% CI -57 to 68).
For the overall cohort, adjusted VE was 39% (95% CI -40% to 73%) for participants who had received their second CoronaVac vaccine within 14-149 days, and 19% (95%CI -81.5 to 63.4) for participants who had received their second CoronaVac vaccine ≥150 days prior (Table 3 and Figure 3b).
In sensitivity analyses, when we decreased the period after infection that participants were considered not at risk from 90 to 60 days, results were very similar (<1% difference) to the 90-day analysis (Table 4). When we considered a participant to be fully vaccinated at 7 days instead of 14 days, VE differed by < 2% from the results of the primary analysis.