Abstract
Background/Purpose
Healthcare workers (HCWs) are at risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection due to occupational exposure. We aim to investigate the prevalence and risk factors of SARS-CoV-2 infection among HCWs during epidemic outbreak of omicron variant in Taiwan.
Methods
Sequential reserved serum samples collected from our previous study during December 2021 and July 2022 were tested for antibodies against SARS-CoV-2 nucleocapsid protein (NP). Diagnosis of SARS-CoV-2 infection was defined as positive either of anti-SARS-CoV-2 nucleoprotein, rapid antigen test or polymerase chain reaction. Retrospective chart review and a questionnaire were used to access the symptoms and risk factors for SARS-CoV-2 infection.
Results
Totally 300 participants (69.3% female) with a median age of 37.9 years were enrolled. A significant increase incidence of SARS-CoV-2 infection was found before and during community outbreak (11.91 versus 230.93 per 100,000 person-days, P < 0.001), which was a trend paralleling that observed in the general population. For 61 SARS-CoV-2 infected participants, nine (14.8%) were asymptomatic. Multivariate analysis revealed recent contact with a SARS-CoV-2 infected household (odds ratio [OR], 7.01; 95% confidence interval [95% CI], 3.70–13.30; P < 0.001) and co-existed underlying autoimmune diseases (OR, 4.46; 95% CI, 1.28–15.51; P = 0.019) were significant risk factors associated with acquisition of SARS-CoV-2 infection among HCWs.
Conclusion
Community factors, such as closely contact with SARS-CoV-2 infected individuals and underlying immune suppression status, were significant factors for acquisition of SARS-CoV-2 infection among HCWs. We suggest the application of appropriate infection control measures for HCWs should be maintained to reduce risk of SARS-CoV-2 infection.
Keywords: Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), Anti-SARS-CoV-2 nucleocapsid protein antibody, Risk factors, Healthcare workers
Introduction
The threat of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection continues to have major impacts on social, economic and healthcare systems worldwide.1 Healthcare workers (HCWs) are at high risk for SARS-CoV-2 infection due to occupational exposure.2 , 3 Although the messenger RNA vaccination provide high efficacy against SARS-CoV-2 hospitalization and death, breakthrough infection still could be occurred in vaccinated HCWs.4 Epidemiological surveillance to estimate the prevalence of SARS-CoV-2 infection among HCW has been previously investigated in Taiwan.5 According to that serological prevalence study, none of 194 enrolled HCWs acquired SARS-CoV-2 infection during the first wave of coronavirus disease 2019 (COVID-19) outbreak in Taiwan.5
The emergence of the novel SARS-CoV-2 variants of concern were associated with consecutive epidemic of infections.6 , 7 A novel B.1.1.529 (omicron) variant initially reported from South Africa since November 2021, has already spread worldwide and has become the dominant SARS-CoV-2 variant till now.8 In vitro investigation revealed that omicron variant carry more than 30 mutations in the viral spike protein.9 , 10 A observational cohort indicate that omicron spreads faster and might escape from the natural or vaccine-induced protective immunity more readily than delta variant, resulting in increasing cases of reinfection or breakthrough infections in persons who had been vaccinated.11
Vaccination is still a major measure to prevent SARS-CoV-2 infection and HCWs were encouraged to complete the primary series and booster doses. A systematic literature review analyzed nine studies from the period of December 2020 to August 2021 revealed an overall low incidence of SARS-CoV-2 infections (0.011–0.001 per 100 individuals at risk) among HCWs who had fully vaccinated with mRNA vaccines.12 Therefore, Taiwan government listed the HCWs on the first priority group of SARS-CoV-2 vaccination, started the primary series of vaccination since March 2021 and follow-up booster dose (third dose) since December 2021 for HCWs in Taiwan. Studies suggested that vaccination against SARS-CoV-2 could reduce the risk of infection and adverse outcomes of SARS-CoV-2 from several SARS-CoV-2 variants, including the B.1.1.7 (alpha) and delta variants.13 , 14 The protection of vaccination decreased over time and a reduction in vaccine effectiveness against emerging SARS-CoV-2 variant, such as omicron, had been found.14 , 15
In this study, we investigate the prevalence and incidence of SARS-CoV-2 infection among HCWs who had already received three doses of COVID-19 vaccines during period of omicron variant dominant in northern Taiwan. The risk factors associated with acquisition of SARS-CoV-2 infection among HCWs were analyzed.
Materials and methods
Hospital setting
National Taiwan University Hospital (NTUH), one of the largest medical center with 2200-bed located in northern Taiwan, is a referral medical center for COVID-19 care. Near 10,000 employee at this hospital, including nursing staff, administrative employees, medical doctors and other paramedical profession personnel. The infection control and prevention measures for SARS-CoV-2 and medical care of COVID-19 patients at NTUH are following the regulations and treatment guideline from Taiwan Centers for Disease Control.16 The policy of patient isolation and implementation of personal protective equipment at NTUH were described previously.5 A web-based system of reporting daily condition of related symptoms for SARS-CoV-2 infection, place at work, breakthrough infection by rapid antigen test or polymerase chain reaction, was used to survey and monitor the health status of all employees at NTUH. Everyone need to report on the website daily. Diagnosis of COVID-19 was defined as positive rapid antigen test and/or SARS-CoV-2 polymerase chain reaction (PCR), according to the definition of COVID-19 from Central Epidemic Command Center (CECC) of Taiwan, and every COVID-19 cases need to be reported to Taiwan Center for Disease Control.16
Participants and procedure
The participants in our previous clinical trial of third dose mRNA COVID-19 vaccination, including healthcare workers, paramedical professional staff, medical students in clinical training, and other administration staff at NTUH, with their agreement, were eligible to participate in this study.17 In brief, adults aged 20–65 years, without underlying illness or with controlled comorbidities who had already received two doses of adenovirus vector vaccine (ChAdOx1, AstraZeneca, UK) and one booster dose of messenger RNA vaccine (mRNA-1273, Moderna, USA or BNT-162b2, BioNTech/Pfizer, Germany) were candidates for this study. A standard questionnaire was designed to collect the information of demographic characteristics, occupational factors, households contact, whether provide care for COVID-19 patients or not, results of rapid antigen test and viral polymerase chain reaction (PCR) for SARS-CoV-2, and symptoms indicative of COVID-19 during the study period by phone call or direct interview for every participants. The chart of participants who visited NTUH were reviewed retrospectively and results of SARS-CoV-2 PCR were recorded.
Serial serum samples collected from the participants of this study were tested for anti-SARS-CoV-2 nucleocapsid protein antibodies. The blood was collected at four different time point, including baseline (Visit 1, December 1, 2021 when first case enrolled to the last case enrolled on January 11, 2022), Visit 2 (4 weeks apart from baseline, duration from December 27, 2021 to February 11, 2022), Visit 3 (12 weeks apart from baseline, duration from March 2, 2022 to April 13, 2022) and Visit 4 (24 weeks apart from baseline, duration from May 19, 2022 to July 8, 2022), for every participants, according to the design of our previous study.17 The baseline was the time point immediately before the third dose of vaccination of each participant (Visit 1).
Ethics declaration
This study has been approved by the Institutional Review Boards (Ethics Committee) of National Taiwan University Hospital (IRB No. 202111038 MINC and 202207018 RINB).
Laboratory tests
Anti-SARS-CoV-2 spike IgG was determined for each serum sample collected at each visit by Abbott SARS-CoV-2 IgG II Quant assay (06S60, Abbott, IL, USA). This assay was designed to measure specific IgG antibodies to the receptor binding domain of spike protein, is a chemiluminescent microparticle immunoassays on the Architect i2000SR analyzer (Abbott, Abbott, IL, USA). Results were reported as arbitrary units (AU) per milliliter, and the cut-off value was 50.0 AU/mL. The mathematical relationship of the Abbott AU/mL unit to WHO unit (binding antibody unit per mL [BAU/mL]) would follow the equation: BAU/mL = 0.142∗AU/mL. Anti-SARS-CoV-2 nucleoprotein antibodies (Elecsys, Anti-SARS-CoV-2, Roche Diagnostics, Switzerland) was also determined for serum sample collected at last visit. If anti-SARS-CoV-2 nucleoprotein antibody tested by Elecsys was positive, we would test their serum sample of previous visit, until negative of anti-SARS-CoV-2 nucleoprotein antibody by Elecsys or the first serum of baseline.
Statistical analysis
Categorical variables were presented as numbers and percentages, were compared using the chi-square test or Fisher exact test. Continuous variables were presented as median (range) and means (standard deviations), groups were compared using the Student's t-test. All analyses were set at a 2-tailed significance level of 0.05. Multivariate analysis was performed to investigate the possible risk factors associated with SARS-CoV-2 infection among HCW. All statistics were conducted by Stata software (version 14; StataCorp, College Station, Texas, USA).
Results
Totally 300 participants, included 208 females (69.3%) and 92 (30.7%) males with a median age of 37.9 years, were enrolled in this study. The most common occupations of study participants were nurses (n = 62, 20.7%), medical students (n = 47, 15.7%), administrative staff (n = 46, 15.3%) and doctors (n = 29, 9.7%). A total of 61 participants, included 49 participants with positive anti-nucleocapsid protein antibodies, 48 with positive rapid antigen tests and 36 with positive SARS-CoV-2 PCR during the study period, were confirmed SARS-CoV-2 infection (case group). In the case group, 12 cases had negative anti-nucleocapsid protein antibody but all of them had positive rapid antigen tests and 5 of them also had positive PCR results. The other 7 did not receive PCR tests. In addition, all 12 cases had symptoms of SARS-CoV-2 infection when they received the rapid antigen testing. The median intervals between infection and the serum sampling for anti-nucleocapsid protein antibody test of the 12 participants were 11 days (range, 7 to 42 days). Six of them were tested serum anti-nucleocapsid protein antibody within 14 days after infection. The sensitivity and specificity of the anti-nucleocapsid protein antibody test for diagnosis of SARS-CoV-2 infection in this study were 80.3% and 100% (overall), 87.5% and 100% (in convalescence, that is, test ≥14 days after symptoms), respectively (Fig. 1 ).
Figure 1.
Diagnosis of 61 participants with SARS-CoV-2 infection in this study. PCR, polymerase chain reaction.
The clinical manifestations of the 61 infected participants (case group) are shown in Table 1 . Nine participants (14.8%) were reported asymptomatic during the study period. Of 52 infected participants with symptoms reported, the most common symptoms were cough (n = 39, 75%), followed by sore throat (n = 36, 69.2%), fever (n = 27, 44.3%), myalgia (n = 16, 30.8%) and rhinorrhea (n = 16, 30.8%). Of the 27 participants with fever, the median duration of fever was 2 days (range 1- 4 days) and the median body temperature of their fever peak was 38.3 °C (37.8 °C to 39.9 °C). Only four participants reported taste or smell dysfunction (7.7%). All 52 were mild to moderate in disease severity, and only 3 of 25 (12%) participants whom had received chest X-ray examination were reported to have mild pulmonary infiltrates. The medium initial cycle threshold (Ct) value of 36 participants with positive PCR was 21.2 (range, 12.5–36.3) and 16 (44.4%) of them were less than 20 (Table 1).
Table 1.
Clinical manifestations of 61 participants diagnosed SARS-CoV-2 infection (case group) in this study.
| Characteristics | No. of cases (%) |
|---|---|
| Asymptomatic infection | 9 (14.8) |
| With clinical symptoms | 52 (85.2) |
| Cough | 39 (75.0) |
| Sore throat | 36 (69.2) |
| Fever | 27 (44.3) |
| Myalgia | 16 (30.8) |
| Rhinorrhea | 16 (30.8) |
| Fatigue | 10 (19.2) |
| Dyspnea | 5 (9.6) |
| Nasal stuff | 5 (9.6) |
| Taste/smell dysfunction | 4 (7.7) |
| Dizziness | 4 (7.7) |
| Headache | 3 (5.8) |
| Chest tightness | 2 (3.8) |
| Epigastralgia | 2 (3.8) |
| Productive sputum | 2 (3.8) |
| Diarrhea | 1 (1.9) |
| Pulmonary infiltrates over chest plain film (n = 25) | |
| No infiltrates | 22 (88) |
| Unilateral infiltrates | 2 (8) |
| Bilateral infiltrates | 1 (4) |
| Initial Ct value of positive PCR test (n = 36) | 21.2 (12.5–36.3) |
| Initial Ct value < 20 | 16 (44.4) |
Abbreviations: Ct, cycle threshold; PCR, polymerase chain reaction.
The comparative analysis (univariate) of participants with or without SARS-CoV-2 infection is shown in Table 2 . There were no significant differences of age, sex, occupation and exposure at hospital, types of vaccine boost, and anti-SARS-CoV-2 spike protein antibody (IgG) titers between the two groups. The rate of positive anti-SARS-CoV-2 nucleoprotein antibody between workers with first-line COVID-19 contact and other staff was similar (16.8% versus 16.1%, P = 0.87) (Table 2). Compared with the control group, the case group had a significant higher proportion of contact with a household diagnosed COVID-19 within recent 4 weeks (50.8% versus 12.6%, P < 0.001) and a higher proportion of comorbidities with autoimmune diseases, such as rheumatoid arthritis, antiphospholipid syndrome, and Sjogren syndrome (9.8% versus 2.1%, P = 0.01). The results of multivariate analysis are shown in Table 3 . A history of recent SARS-CoV-2 infected household contact (odds ratio [OR], 7.01; 95% confidence interval [95% CI], 3.70–13.30; P < 0.001) and co-existed autoimmune diseases (OR, 4.46; 95% CI, 1.28–15.51; P = 0.019) were significant risk factors associated with acquisition of SARS-CoV-2 infection.
Table 2.
Comparative analysis of risk factors associated with SARS-CoV-2 infection among healthcare workers.
| Analytic factors | Case group Participants with SARS-CoV-2 infection (n = 61) |
Control group Participants without SARS-CoV-2 infection (n = 239) |
p-value |
|---|---|---|---|
| Age (mean ± SD) | 38.7 ± 11.4 | 37.6 ± 11.0 | 0.51 |
| Female, n (%) | 45 (73.8%) | 163 (68.2%) | 0.44 |
| Occupation or role at hospitals, n (%) | |||
| Nurses | 12 (19.7%) | 50 (20.9%) | 0.83 |
| Medical students | 9 (14.8%) | 38 (15.9%) | 0.83 |
| Administrative staffs | 9 (14.8%) | 37 (15.9%) | 0.89 |
| Doctors | 5 (8.2%) | 24 (10.0%) | 0.66 |
| Pharmacists | 3 (4.9%) | 11 (4.6%) | >0.99 |
| Housekeeping workers | 2 (3.3%) | 9 (3.8%) | >0.99 |
| Dentist/assistants | 2 (3.3%) | 7 (2.9%) | >0.99 |
| Radiology staffs | 1 (1.6%) | 3 (1.3%) | >0.99 |
| Laboratory staffs | 0 (0%) | 3 (1.3%) | >0.99 |
| Other paramedical staffs | 18 (29.5%) | 57 (23.8%) | 0.36 |
| Workers with first-line COVID-19 contacta, n (%) | 17 (27.9%) | 84 (35.1%) | 0.36 |
| Workers at COVID-19 specific ICU/ward care | 11 (18.0%) | 53 (22.1%) | 0.60 |
| Household with COVID-19 recently (<4 weeks), n (%) | 31 (50.8%) | 30 (12.6%) | <0.001 |
| Types of boost vaccine, n (%) | 0.77 | ||
| mRNA-1273 full-dose | 22 (36.1%) | 78 (32.6%) | |
| BNT-162b2 | 21 (34.4%) | 79 (33.1%) | |
| mRNA-1273 half-dose | 18 (29.5%) | 82 (34.3%) | |
| Anti-spike protein IgG titers (BAU) (geometric mean ± SD) | 1054.75 ± 867.77 | 1002.25 ± 678.635 | 0.61 |
| BAU>500 | 45 (73.8%) | 186 (77.8%) | 0.50 |
| BAU>1000 | 24 (39.3%) | 91 (39.3%) | 0.88 |
| BAU>2000 | 6 (9.8%) | 18 (7.5%) | 0.60 |
| Underlying medical illness, n (%) | |||
| Diabetes mellitus | 1 (1.6%) | 4 (1.6%) | >0.99 |
| Hypertension | 4 (6.6%) | 15 (6.3%) | >0.99 |
| Chronic lung disease | 1 (1.6%) | 0 (0.0%) | 0.20 |
| Chronic liver disease | 2 (3.3%) | 4 (1.7%) | 0.35 |
| Chronic kidney disease | 1 (1.6%) | 2 (0.8%) | 0.50 |
| Thyroid diseases | 2 (3.3%) | 6 (2.5%) | 0.67 |
| Hyperthyroidism | 1 (1.6%) | 4 (1.7%) | >0.99 |
| Hypothyroidism | 1 (1.6%) | 0 (0.0%) | 0.20 |
| Autoimmune thyroiditis | 1 (1.6%) | 2 (0.8%) | >0.99 |
| Solid organ malignancy | 2 (3.3%) | 3 (1.3%) | 0.27 |
| Autoimmune diseases | 6 (9.8%) | 5 (2.1%) | 0.01 |
| Rheumatoid arthritis | 2 (3.3%) | 0 (0.0%) | 0.04 |
| Ankylosing spondylitis | 2 (3.3%) | 1 (0.4%) | 0.11 |
| Antiphospholipid syndrome | 3 (4.9%) | 1 (0.4%) | 0.03 |
| Systemic lupus erythematosus | 0 (0.0%) | 0 (0.0%) | – |
| Sjogren syndrome | 3 (4.9%) | 0 (0.0%) | 0.008 |
| Seronegative spondyloarthritis | 2 (3.3%) | 1 (0.4%) | 0.11 |
Workers with first-line COVID-19 contact included healthcare workers at emergency department, COVID-19 screen clinic, staff at COVID-19 specific ICU or wards.
Table 3.
Multivariate analysis of risk factors associated with SARS-CoV-2 infection in this study.
| Risk factors | Odds ratio | 95% confidence interval | P-value |
|---|---|---|---|
| Household with COVID-19 recently (<4 weeks) | 7.01 | 3.70–13.30 | <0.001 |
| Underlying autoimmune diseases | 4.46 | 1.28–15.51 | 0.019 |
The incidence and prevalence of SARS-CoV-2 infection are shown in Table 4 . Significant increase of SARS-CoV-2 infection were found since the endemic outbreak after early April 2022 in this study (prevalence, 0.67, 1.00, 20.40 per 100 persons at three periods, respectively, P < 0.001; incidence, 11.91, 5.97, 230.93 per 100,000 person-days, respectively, P < 0.001). The trend of incidence and prevalence among HCW were paralleling to that observed in the general population.
Table 4.
Incidence and prevalence of participants with COVID-19 in this study.
| Periodsa | Incidence rateb n (per 100,000 person-days) | Prevalence rate n (per 100 persons) |
|---|---|---|
| Period 1 (n = 300) | ||
| Visit 1 to Visit 2 | 1 (11.91) | 2 (0.67) |
| Period 2 (n = 299) | ||
| Visit 2 to Visit 3 | 1 (5.97) | 3 (1.00) |
| Period 3 (n = 299) | ||
| Visit 3 to Visit 4 | 58 (230.93) | 61 (20.40) |
| P value | <0.001 | <0.001 |
Date of Visit 1 (baseline): December 1, 2021 (first case) to January 11, 2022 (last case). Date of Visit 2 (4 weeks apart from baseline): December 27, 2021 to February 11, 2022. Date of Visit 3 (12 weeks apart from baseline): March 2, 2022 to April 13, 2022. Date of Visit 4 (24 weeks apart from baseline): May 19, 2022 to July 8, 2022.
One participant tested anti-nucleoprotein antibody positive at Visit 1, she received vaccination and blood test until V4 follow-up. The other participant retried before Visit 3 follow-up and had blood test for Visit 1 and Visit 2. The observed periods of these two participants were censored at their last follow up visit.
Discussion
Our study cohort presents a longitudinal surveillance of COVID-19 among 300 HCWs before and during omicron outbreak period (December, 2021 to July, 2022) in Taiwan. We revealed a similar trend of increasing prevalence of SARS-CoV-2 infection in HCWs and general population during the surge of community outbreak of COVID-19 omicron variant in Taiwan (early April, 2022 to end of this study in July, 2022) (Supplementary Figure).18 There was no evidence of significant association with the potential occupational risk of COVID-19 exposure at the hospital and the acquisition of SARS-CoV-2 infection for the HCWs. Recent contact with a COVID-19 household and co-existed autoimmune diseases were two independent significant risk factors associated with SARS-CoV-2 infection. These results demonstrate that the HCWs probably acquired SARS-CoV-2 infection from the community exposure, rather than from the hospital exposure. Our study indicates the successful application of infection control measures leads to no increase in the infection risk in HCWs.
Other studies on the source of infection among HCWs also showed a stronger association with community factors than occupational factors,19, 20, 21, 22 suggesting the beneficial effects of infection prevention procedures at hospitals. In our present study, we found the positive rate of anti-SARS-CoV-2 nucleocapsid protein antibody was not higher among HCWs who worked at COVID-19 specific screen clinic or engaged in first line care of COVID-19 patients than those who did not. A history of close contact with family members or cohabitants who had SARS-CoV-2 infection recently, rather than exposure to coworkers or patients with COVID-19 at the hospital, were significantly associated with SARS-CoV-2 infection in these HCWs. Our study also revealed the parallel correlation between the incidence of infection in HCWs and the community incidence of infection in general population. Compatible with previous reports,19, 20, 21, 22, 23 our study supports the risk of transmission at hospitals could be controlled by implementation of effective infection control measures, including the sufficient provision of personal protective equipment, universal mask wearing, hand washing, and body temperature monitoring for staff. It is necessary to emphasize on the prevention of community-acquired infection for HCW during the community outbreak of COVID-19.
Evidence from our previous study of heterologous vaccination suggests that the combination of viral vector vaccines and mRNA vaccines produces good levels of antibodies against the SARS-CoV-2 and a higher T-cell response than using homologous viral vector vaccination and were generally well tolerated.24 In line with emerging global practice,25 , 26 our participants had received heterologous two doses of adenoviral vector vaccines and one dose of mRNA vaccine against SARS-CoV-2. However, the protection of vaccination declined over time after the vaccination14 , 15 , 27 , 28 and breakthrough infections with SARS-CoV-2 omicron occurred, despite after mRNA vaccine booster dose.4 , 27 In this study we found the breakthrough infection did not correlate to the level of anti-SARS-CoV-2 spike protein antibody. With the emergence of the novel omicron variants BA.4 and BA.5 and the possibility of acquisition of SARS-CoV-2 infection acquired from community, a booster dose of vaccine contained omicron variant should be encouraged in protecting HCWs from COVID-19.
Clinical manifestations of infection caused by SARS-CoV-2 omicron variant differs from those of the wild strain and delta variant.11 Infection caused by the omicron variant was more likely to present with upper respiratory tract symptoms, such as sore throat and hoarse voice, and had milder symptoms and a lower hospitalization rate than that of the previous dominant delta variant.11 In this report, we found sore throat was a striking characteristic symptom present during omicron prevalence. Smell and taste disorders, the pathognomonic feature of earlier waves of SARS-CoV-2 infection, were less likely to display during omicron prevalence. All of our participants had mild or moderate COVID-19. Only three had shown infiltrations over chest X-ray films indicate less pulmonary involvement of omicron variants. Since all our participants had received a third booster dose for SARS-CoV-2, which might provide a protective benefit for severe disease. We believe the biological feature of omicron variant and fully vaccination against SARS-CoV-2 in our participants contribute to a greater reduction of disease severity during the outbreak period.
Asymptomatic infections have been widely reported in the SARS-CoV-2 infection patients.29 In a systematic review by analyzing over 350 studies, the percentage of asymptomatic infection was near 35.1% (95% CI, 30.7–39.9%).29 Elderly and patients with co-existing morbidities had significantly lower rates of asymptomatic infection.29 In contrast, our cohort consists of relative young and otherwise healthy persons, has shown a relative lower rate (15%) of asymptomatic infection among HCWs after primary vaccination series and booster dose. The differences might be due to the alert of HCWs to COVID-19 associated symptoms in our study and the meta-analysis was established via the studies prior to widespread vaccination coverage (January 2020 to April 2021), while wild virus strain and other earlier variants were dominant.29 Nevertheless, the prevalence of asymptomatic infection still high (at least 15%) and the benefits of periodical surveillance and infection control measures to block potential transmission in the hospitals still should be emphasized.
Our study had some limitations. First, the retrospective study design and symptoms recalled from participants may have bias. However, our study consists of a relatively large cohort among HCWs with sequential periodical serological survey provides important information in epidemiology and clinical care. Second, the timing of blood collection based on our previous vaccination trial may be different from the onset of SARS-CoV-2 infection. Therefore, it is difficult to compare the sensitivity and specificity of rapid antigen test, antibody for SARS-CoV-2 nucleoprotein and PCR test. Third, we could not define exactly when the exposure occurred in our participants because of endemic outbreak in the community since April 2022 and participants in this study were mostly HCWs and had continuous exposure to SARS-Co-V -2 in the hospital. Therefore, the information of interval between exposure and the last dose of vaccination between HCWs with or without SARS-CoV2 infection was not available. Finally, our cohort is limited to individuals in relatively young and otherwise healthy persons, and all infections were mild and did not require hospitalization. Thus, whether our results could be applied to other age groups and immunosuppressed populations need further investigation.
In conclusion, the breakthrough infection caused by SARS-CoV-2 omicron variant could be occurred in otherwise healthy HCWs who had already received booster doses of COVID-19 vaccines. Our study revealed close contact with COVID-19 households and underlying immune suppression status were significant factors for acquisition of SARS-CoV-2 infection among HCW during the omicron pandemic outbreak in Taiwan. The need for updated vaccines to provide better protection against emerging variant of concern and maintain non-pharmaceutical measures, such as isolation precaution, mask-wearing and hand washing against COVID-19 should be emphasized.
Funding
The funding support of this study included MOST-110-2740-B-002-006 and MOST109-2327-B-002-009 from Ministry of Science and Technology Taiwan. The funders of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the manuscript.
Declaration of competing interest
There were no conflict of interests for all authors.
Acknowledgement
We would like to acknowledge the services provided by the Biosafety Level-3 Laboratory of the First Core Laboratory from National Taiwan University College of Medicine and the Biosafety Level-3 Laboratory from National Taiwan University Hospital.
Footnotes
Supplementary data to this article can be found online at https://doi.org/10.1016/j.jfma.2022.12.003.
Appendix A. Supplementary data
The following is the Supplementary data to this article.
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