Seroprevalence of SARS-CoV-2 antibodies in a national hospital and affiliated facility after the second epidemic wave of Japan.

Dear Editor,

Introduction

Healthcare workers (HCWs) are at high risk for coronavirus disease (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). , However, relative to the general population, there was no increase in the infection risk among HCWs in hospitals with adequate control measures against the infection. Studies on the source of infection among HCWs showed a stronger association with community factors than occupational factors,4, 5, 6 suggesting the importance of infection prevention outside the hospital. Although Japan recorded a relatively high number of COVID-19 cases in Asia, data on SARS-CoV-2 infection and its source among HCWs are limited.

The National Center for Global Health and Medicine (NCGM) has played a leading role in patient care and COVID-19 research since the early phase of the epidemic in Japan. Additionally, the staff were involved in screening for returnees from Wuhan, infection control on the Diamond Princess cruise ship, and running a fever clinic and local polymerase chain reaction (PCR) testing center. To estimate the cumulative SARS-CoV-2 infection rate over time, we designed a repeat seroprevalence study among the NCGM staff. Previously, we reported a very low seroprevalence of SARS-CoV-2 IgG antibody (0.16%) as of July 2020, after the first COVID-19 wave in Japan. Here, we report the seroprevalence and its related factors in a follow-up survey after the second, larger wave (Fig. 1 ).

Fig. 1

Change in the number of patients diagnosed with COVID-19 in Japan.

Methods

We invited all NCGM staff (Toyama and Kohnodai areas) and asked participants to complete a questionnaire and donate venous blood in October (Toyama) and December (Kohnodai) 2020. We collected data on demographics, occupational factors, close contact with patients with COVID-19, symptoms indicative of COVID-19, PCR testing results, use of public transportation, and adherence to infection prevention practices (IPPs). We qualitatively measured IgG (Abbott ARCHITECT®) and total antibodies (Roche Elecsys®) against the SARS-CoV-2 nucleocapsid protein, according to the manufacturers’ instructions at an in-house (Toyama) or external laboratory (Kohnodai). We performed a confirmatory analysis of seropositive samples on either test with the EUROIMMUN anti-S IgG immunoassay. If it was positive, neutralizing antibody titers were measured using the live virus (Supplemental Text). Written informed consent was obtained from each participant. This study was approved by the ethics committee of NCGM.

Seropositivity was defined as positivity of either test (sensitivity priority). Seroprevalence with 95% confidence intervals (CI) were calculated using the exact binomial technique. We performed Poisson regression with a robust variance estimator to assess the association between exposure variables and seropositivity. Participants who had both tests positive were classified as being seropositive (specificity priority).

Results

Of 2,893 staff invited, 2,563 (88.6%) participated. The major occupations included nurses (36%), doctors (16%), allied healthcare professionals (14%), and administrative staff (11%). Nearly half of the participants (47.6%) had been engaged in COVID-19-related work (Table 1 ). The adherence to the recommended IPPs was quite high (e.g., cough etiquette [99.8%], washing or sanitizing hands [99.3%], and wearing a mask [98.8%]) (Fig. S1).

Table 1.

Seroprevalence of SARS-CoV-2 antibodies by participants' characteristics.

Characteristicsa	Total participants, No.	Participants with seropositive		Prevalence Ratio (95% CI)
		No.	% (95% CI)
Total, No.	2563	18	0.70 (0.42–1.11)
Location of workplace
Tokyo	2054	16	0.79 (0.45–1.26)	1.0 [reference]
Chiba	509	2	0.39 (0.05–1.41)	0.50 (0.12-2.19)
Sex
Male	779	7	0.94 (0.38–1.93)	1.0 [reference]
Female	1784	11	0.64 (0.32–1.14)	0.68 (0.26-1.75)
Age range, year
<30	797	8	1.05 (0.46–2.07)	1.0 [reference]
30-39	633	1	0.17 (0.00–0.93)	0.16 (0.02–1.27)
40-49	596	3	0.52 (0.11–1.50)	0.49 (0.13–1.84)
≥50	537	6	1.13 (0.42–2.44)	1.07 (0.37–3.07)
Job category
Doctors	410	2	0.49 (0.06–1.75)	1.0 [reference]
Nurses	921	8	0.87 (0.38–1.70)	1.78 (0.38–8.35)
Allied healthcare professionals	362	3	0.83 (0.17–2.40)	1.70 (0.29–10.11)
Administrative staff	284	1	0.35 (0.01–1.95)	0.72 (0.07–7.93)
Others	492	4	0.81 (0.22–2.07)	1.67 (0.31–9.06)
Department
Non-medical departments	551	4	0.73 (0.20–1.85)	1.0 [reference]
The other medical departments	1619	11	0.68 (0.34–1.21)	0.91 (0.36–2.31)
COVID-19-related departments	299	3	1.00 (0.21–2.90)	0.92 (0.23–3.66)
The risk of SARS-CoV-2 infection at workb
Low	1184	12	1.01 (0.52–1.76)	1.0 [reference]
Moderate	690	3	0.43 (0.09–1.27)	0.43 (0.12–1.52)
High	595	3	0.50 (0.10–1.47)	0.50 (0.14–1.76)
Engagement in COVID-19-related work
Screening of returnees of the charter flight from Wuhan	119	0	0.00 (0.00–3.05)	NA
Infection control on the cruise ship	48	0	0.00 (0.00–7.40)	NA
COVID-19 testing center, fever consultation clinic	178	0	0.00 (0.00–2.05)	NA
Care facility for COVID-19 patients with mild symptom	34	0	0.00 (0.00–10.28)	NA
Works done within 1 m of COVID-19 patient	798	4	0.50 (0.14–1.28)	0.60 (0.20–1.81)
Works done at 1 m or more of COVID-19 patient	491	3	0.61 (0.13–1.78)	0.81 (0.23–2.77)
SARS-CoV-2 laboratory testing	147	1	0.68 (0.02–3.73)	0.93 (0.12–6.94)
Handling SARS-CoV-2 other than testing	194	2	1.03 (0.13–3.67)	1.47 (0.34–6.33)
Cleaning, laundry, sterilization, waste disposal	315	2	0.63 (0.08–2.27)	0.85 (0.20–3.70)
Fever screening of outpatient and visitors	198	0	0.00 (0.00–1.85)	NA
Others	96	1	1.04 (0.03–5.67)	1.45 (0.20–10.8)
Any of the above	1176	6	0.51 (0.19–1.11)	0.55 (0.21–1.46)
Symptom indicative of COVID-19
Common cold-like symptom lasting 4 days or longer	327	4	1.22 (0.33–3.10)	1.85 (0.61–5.60)
High fever	117	2	1.71 (0.21–6.04)	2.49 (0.58–10.70)
Severe fatigue	197	2	1.02 (0.12–3.62)	1.43 (0.33–6.17)
Dyspnea	64	1	1.56 (0.04–8.40)	2.19 (0.30–16.22)
Loss of sense of taste or smell	25	3	12.0 (2.55–31.22)	19.4 (5.98–38.4)c
History of previous PCR testing
No	2075	12	0.58 (0.30–1.01)	1.0 [reference]
Yes	393	6	1.53 (0.56–3.29)	2.64 (2.05–3.39)c
Close contact with COVID-19 cases
Contact in the hospitald	94	1	1.06 (0.03–5.79)	0.67 (0.09–5.00)
Contact at home and in the communitye	5	2	40.0 (5.27–85.34)	61.6 (18.9–200.4)c
Use of public transportation
<1 times/wk	888	9	1.01 (0.46–1.92)	1.0 [reference]
≥1 times/wk	1563	9	0.58 (0.26–1.09)	0.57 (0.23–1.43)

Abbreviations: COVID-19, coronavirus disease 2019; NA, not applicable; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2

The number of missing data for each characteristics was as follows: job category (94), department (94), the risk of SARS-CoV-2 infection at work (94), engagement in COVID-19-related work (94), symptom indicative of COVID-19 (111), history of previous PCR testing (95), close contact with COID-19 cases (95), and use of public transportation (112).

Categorized as follows: low (those who were not engaged in COVID-19-related work), moderate (those who were engaged in COVID-19-related work without heavy exposure to the virus), and high (those who were heavily exposed to SARS-CoV-2).

P < 0.05 (2-tailed).

Close contact with COVID-19-positive patients or coworkers.

Close contact with COVID-19-positive family members, cohabitants, friends, or acquaintances.

Eighteen staff had one positive test (10 on Abbott and 13 on Roche), giving a seroprevalence of 0.70% (95% CI: 0.42–1.11). None of them belonged to the same department. Using the second definition (two positive tests), only 5 were seropositive (seroprevalence: 0.20%, 95% CI 0.06–0.45). Of the seropositive staff, 8 (44%) were positive on the EUROIMMUN assay, but none had a neutralizing antibody.

A history of loss of taste and smell and PCR testing were associated with an increased seropositivity rate. Close contact with patients with COVID-19 at home and in the community (family members, cohabitants, acquaintances, or friends), but not in the hospital (coworker or patients), was associated with seropositivity. The seropositivity rate was not high among those working in the COVID-19 ward or engaged in COVID-19-related work (Table 1).

Discussion

After the second COVID-19 wave in Japan, the seroprevalence rate among the NCGM staff remained low (0.70%), which was even lower than those of the general population in Tokyo during the same period (1.94%, recalculated according to the definition used in this study).

We found no evidence of clustering of seropositive staff in the center and no significant association between occupational factors and seropositivity. These data refute an increased risk of inpatient-to-HCW and HCW-to-HCW transmission in hospitals well prepared for COVID-19. NCGM has introduced and strengthened multiple infection control measures since the early phase of the epidemic, including the provision of personal protective equipment, universal masking, hand washing, and routine checking of staff's body temperature, and PCR testing in case of suspected infection. These results support the effectiveness of these measures against infection associated with occupational exposure.

Regarding non-occupational factors, close contact with patients with COVID-19 at home and in the community was associated with increased seropositivity. Given few seropositive staff who had close contact in these settings (n = 2, 11% of seropositive staff), it is reasonable to assume that the primary route of infection might be unrecognized contact with asymptomatic cases in the community. The NCGM is located in an epicenter of the second wave; therefore, the infection control division sends e-mails to all staff weekly to enhance their awareness of preventive behaviors, leading to high adherence to the recommended IPPs by the staff (Fig. S1). With the correlation between the infection rate of HCWs and the cumulative community incidence, , there is need for more emphasis on the prevention of community-acquired infection in preventing nosocomial infection.

This study provides more evidence on the contribution of comprehensive control measures targeting both occupational and community risk of SARS-CoV-2 infection in the protection of HCWs from infection during the epidemic.

Funding

This work was supported by the NCGM COVID-19 Gift Fund and the Japan Health Research Promotion Bureau Research Fund (2020-B-09).

Role of the funder/sponsor

The funder did not play any role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication.

Declaration of Competing Interest

Antibody test reagents were provided by Abbott and Roche Diagnostic.