The Coronavirus disease (COVID-19) pandemic is a major global disaster that has caused more than 7 million deaths worldwide so far.1 Since the early stages of the COVID-19 pandemic, reported cases of reinfection have raised concerns. The definitions of reinfection vary in the studies. According to ECDC, reinfection is considered by laboratory confirmation of 2 infections by 2 different strains with timely separated infection episodes.2 However, laboratory tests such as whole-genome sequencing and phylogenetic analysis are not always available.Reference Yahav, Yelin and Eckerle3 According to the CDC, in settings with limited genomic testing, an interval between the first and second infection of ≥90 days might have higher suspicion for reinfection.4 In some studies, reinfection has been considered as a new PCR positive result 30-60 days after recovery from the initial infection. And in others, this period has been defined as 90 days; PCR positivity before this period has generally been considered as relapse, reactivation, and repositivity.Reference Ukwishaka, Ndayishimiye and Destine5 In clinical practice, reinfection is defined as clinical recurrence of symptoms consistent with COVID-19, supported by close contact, accompanied by a positive Polymerase chain reaction (PCR) test 90 days after the onset of the primary infection, and no evidence of another disease.Reference Yahav, Yelin and Eckerle3
After the first reinfection case was reported from Hong Kong in August 2020,Reference To, Hung and Ip6 studies from various countries have begun to be published to examine reinfection rates. The incidence of reinfection was mostly found to be below 1%Reference Qureshi, Baskett and Huang7, Reference Hansen, Michlmayr and Gubbels8 and it was more often in subjects continuously exposed to SARS-CoV2, such as health care workers; usually subjects with reinfection had mild diseases.Reference Hall, Foulkes and Charlett9, Reference Bongiovanni, Marra and Bini10 Vaccination significantly reduces reinfection risk and its severity; in a study they found that vaccination after recovery from COVID-19 reduces the risk of reinfection by approximately half.Reference Lewis, Chambers and Chu11
We designed this descriptive study to investigate the incidence and clinical characteristics of SARS-CoV-2 reinfection among patient cohorts and health care workers.
Methods
This observational, single-center descriptive study was conducted by the Departments of Pulmonary Medicine, Emergency Medicine, Infectious Diseases, Public Health, and Medical Microbiology at Ege University Faculty of Medicine Hospital, Izmir, Türkiye. Ethical approval was obtained from the Ege University Ethics Committee (28.05.2020, 20-5.1T/19) and the Ministry of Health (05.05.2020, T18-10-02) prior to the study. This study design was selected due to the retrospective retrieval of hospital records and the objective of describing the characteristics of reinfection within a defined population during the pandemic period.
All SARS-CoV-2 PCR-positive patient data from March 18-December 31, 2020 were retrieved. Adults aged ≥18 were screened in the Hospital Electronic Record System (HERS) for recurrent positivity after >90 days. Eligible patients were contacted via telemedicine, and their consent and eligibility were assessed.
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• Diagnosed with PCR-confirmed COVID-19 in our hospital
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• Meeting the criteria for reinfection as mentioned:
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◦ Cases with symptoms compatible with COVID-19 with PCR positivity for the second time at least 90 days after the first infection
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◦ Asymptomatic cases with PCR positivity for the second time at least 90 days after the first infection, with a history of contact with a COVID-19 patient
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Patients who had test positivity incidentally and were asymptomatic and had no history of contact with a COVID-19 patient and test errors were excluded.
A case report form was completed for each patient contacted via telemedicine. The form included demographic data, comorbidities, occupation, symptoms during both the initial infection and reinfection, vaccination status, socioeconomic status, and history of contact with a COVID-19-positive individual. Socioeconomic status was classified based on monthly income. Radiological imaging from the initial infection and reinfection was evaluated according to the interpretations of both the radiologist and the clinician. The patients’ symptoms and incidence of pneumonia during their first infection and reinfection were compared.
Patients who received at least 2 Sinovac/CoronaVac (0.5 ml) or 2 BioNTech/Pfizer (0.3 ml) were determined as fully vaccinated patients.
Data were presented as frequencies and percentages for categorical variables and as mean ± standard deviation or median (min-max) for continuous variables. Normality was assessed using the Shapiro-Wilk test. For non-normally distributed data, the Wilcoxon signed-rank test and the Mann-Whitney U test were used. The Chi-square and McNemar tests were applied for categorical comparisons. Analyses were conducted using SPSS version 25, with a significance level set at P < 0.05.
Results
Our study examined 5814 patients infected with COVID-19 at a single-center tertiary university hospital, serving as a regional reference hospital, from March 18, 2020 until the end of 2020. After excluding pediatric patients, 607 of the 5336 adult patients were health care workers. Their SARS-CoV-2 PCR tests were followed until the end of 2021.
A total of 74 cases were identified in our hospital who had been diagnosed with COVID-19 and had a subsequent positive PCR test at least 90 days after the initial diagnosis; these patients were contacted via telemedicine and met the criteria for reinfection. Among the 74 reinfection cases, 42 (56.8%) were women, with a mean age of 35.8 ± 11.9 years. The interval between infections ranged from 95-646 days, with a mean of 259.3 ± 115 days. In terms of occupational distribution, 36.5% (n = 27) were health care workers, and 63.5% (n = 47) were employed in other sectors. Comorbidities were present in 47.3% (n = 35) of the patients, whereas 52.7% (n = 39) had no known comorbidities. In terms of socioeconomic status, 60.3% (n = 44) reported a good socioeconomic level, 38.4% (n = 28) reported a very good level, and 1.4% (n = 1) classified their status as moderate. Smoking status varied among the patients, with 38.9% (n = 28) being smokers and 61.1% (n = 44) being non-smokers. Education levels also showed variation; 40.3% (n = 29) had a university or college degree, 12.5% (n = 9) held a postgraduate or doctorate degree, and 23.6% (n = 17) had completed primary education and another 23.6% (n = 17) had completed high school (Table 1).
Characteristics of reinfected patients
Total number of participants was 74. However, for some variables (e.g., socioeconomic status, smoking status, and education level), the total number does not add up to 74 due to missing responses.
Among the 74 reinfected patients, reinfection was identified within the first year in 39 cases. The incidence of reinfection during the 1-year follow-up was 0.73% (95% confidence interval [CI], 0.53–0.99). Reinfection occurred in 13 of the 607 health care workers, corresponding to an incidence of 2.14% (95% CI, 1.25-3.66), which was 3.9 times higher than that observed in non-health care workers (P<0.001). Pneumonia, fever, shortness of breath, and loss of taste and smell were significantly less common during reinfection compared to the initial infection (P = 0.021, P = 0.035, P = 0.029, and P = 0.007, respectively) (Table 2). One or several symptoms, such as fever, cough, and shortness of breath, were significantly less common in fully vaccinated patients compared to the other group (34.8% vs. 58.1%, P<0.05).
Comparison of initial infection and reinfection symptoms (n = 74)
Three of 74 patients died due to reinfection, yielding a mortality rate of 4.1%. All 3 patients who died had developed COVID-19 pneumonia during both their initial infection and reinfection episodes. The first patient was a liver transplant recipient; the second had heart failure; and the third had comorbidities including COPD, coronary artery disease, and diabetes mellitus. Two of the patients had not received any COVID-19 vaccination, while 1 patient had received 2 doses of the Sinovac vaccine (Sinovac Biotech Ltd, China).
Discussion
In our study, we investigated reinfection rates in a large cohort, comparing initial infections and reinfections as well as the impact of vaccination. We found that the 1-year reinfection rate was 0.73% among patients and 2.14% among health care workers. The reinfection rate in health care workers was 3.9 times higher than that in patients (P<0.001), likely due to greater exposure to viral load and easier access to testing.
Supporting our findings, Qureshi et al. reported a 0.7% reinfection rate, and an observational study found it to be 0.65%Reference Qureshi, Baskett and Huang7, Reference Hansen, Michlmayr and Gubbels8 and in a meta-analysis the risk of reinfection approached 1% after an average follow-up of 12 months.Reference Flacco, Acuti Martellucci and Baccolini12 The reinfection incidence tends to be higher among health care workers as seen in SIREN study (155 people of 8278).Reference Hall, Foulkes and Charlett9 In a study investigating SARS-CoV-2 reinfection risk factors, it was determined that health care workers and immunosuppressed or renal patients had a higher risk of reinfection.Reference Murillo-Zamora, Trujillo and Huerta13 In a study among midwestern health care workers, reinfection was diagnosed in 5.94% of 2625 participants, and COVID-clinical employees had a 3.77 times greater risk of reinfection compared to those working in non-clinical units.Reference Rivelli, Fitzpatrick and Blair14
In our study, 3 of 74 patients died due to reinfection, yielding a mortality rate of 4.1%. Another study involving 63 reinfected patients reported a mortality rate of 3%.Reference Qureshi, Baskett and Huang7 Mensah et al reported a 61% reduced risk of death within 28 days of testing positive for SARS-CoV-2 in reinfection compared to primary infection.Reference Mensah, Lacy and Stowe15 Pneumonia and symptoms such as fever, dyspnea, and loss of taste and smell were significantly less common in reinfected patients, likely due to immune response protection. However, it should be noted that 3 of our patients—2 of whom were unvaccinated and 1 who had received 2 doses of a COVID-19 vaccine—died of COVID-19 pneumonia during their reinfection. It is well established that full vaccination reduces the risk of reinfection and persistent COVID-19, particularly in high-risk groups.Reference Flacco, Acuti Martellucci and Baccolini12, Reference Mensah, Lacy and Stowe15, Reference de Arriba Fernández, Bilbao and Francés16
As a conclusion, our study results highlight the substantially increased occupational health risk for SARS-CoV-2 reinfection faced by health care workers during the COVID-19 pandemic. Although reinfections tended to be clinically milder than initial infections, the significantly higher reinfection rate underscores the need for prioritizing vaccination and protective measures in this occupational group.
Author contribution
Concept: M.A.A, O.G, Design: M.A.A., O.G., Data Collection or Processing: M.A.A., O.G., R.D., M.E., R.S., B.A., Analysis or interpretation: M.A.A., O.G., S.O., R.D., Literature Search: M.A.A., O.G., S.O., Writing: M.A.A., O.G., S.O.
Competing interests
The authors have no conflict of interest.
