Co-Occurrence of SARS-CoV-2 Infection and Inactivated SARS-CoV-2 Vaccination among Healthcare Workers

The presented cases describe the concurrent SARS-CoV-2 infection and inactivated SARS-CoV-2 vaccination among eight healthcare workers (HCWs). These cases highlighted the importance of broad hospital screening during the COVID-19 vaccination campaign. Further study regarding the durability of antibody response induced by infection and first-dose vaccination is required to determine the appropriate time for giving a second dose of inactivated SARS-CoV-2 vaccine among these cases.


Introduction
Since the first coronavirus disease 2019 (COVID-19) case caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was detected in China in December 2019, the disease has spread rapidly worldwide. Indonesia is one of the Southeast Asian countries with a high number of confirmed and active COVID-19 cases [1]. Although preventive measures such as physical distancing, quarantine, and isolation effectively reduced the number of people becoming infected, the risk of SARS-CoV-2 infection persisted in the population without immunity against SARS-CoV-2. erefore, the availability of the COVID-19 vaccine is essential to induce immunity and protect the population from SARS-CoV-2 infection.
In Indonesia, the COVID-19 vaccination campaign using inactivated SARS-CoV-2 vaccine (CoronaVac, Sinovac Life Sciences) started at the end of January 2021, initially prioritizing healthcare workers (HCWs). As CoronaVac is an inactivated vaccine containing a whole virus structure [2], vaccinated individuals would be expected to elicit antibodies against many SARS-CoV-2 antigens, such as antispike (anti-S) and antinucleocapsid (anti-N). e remarkable increase of neutralizing antibodies, spike-specific immunoglobulin G (IgG), and receptor-binding domain-(RBD-) specific IgG occurred on day 14 after the second dose of vaccination [3]. Although the most common adverse reaction was injection site pain, systemic reactions such as fever, fatigue, cough, myalgia, and headache have been reported after each injection [3,4]. e following presented cases, showing the co-occurrence of the first time use of CoronaVac with positive SARS-CoV-2 RNA among HCWs, are important due to it raising several considerations related to (1) the possibility for misinterpretation of COVID-19 symptoms with the systemic adverse reaction of vaccine, (2) the possibility of a false-positive RT-PCR result caused by the vaccine, and (3) the safety and the durability of the immune response during the coincidental events of vaccination and SARS-CoV-2 infection.

Case Presentation
is is an eight-case series of HCWs who received the first dose of inactivated SARS-CoV-2 vaccine (CoronaVac) at the Siloam Teaching Hospital (Indonesia) on January 26, 2021. e time elapsed between the first dose of vaccination and the onset of symptoms ranged from 4 to 9 days (median time 6 days). HCWs were confirmed for SARS-CoV-2 detection , and 3 (37%) were male. Most of the vaccinated and infected HCWs work as a nurse (63%). Five (63%) HCWs were infected in the community setting, and three (37%) were from a healthcare setting, who might have acquired it through contact with SARS-CoV-2-positive patients or coworkers.
Among these 8 HCWs, 6 (75%) were tested because they had COVID-19 symptoms. e most common COVID-19 symptoms were fever (75%), cough (25%), and headache (25%). Two (25%) asymptomatic COVID-19 HCWs were identified as a part of postexposure and regular hospital screening. Only one subject (HCW7) had preexisting medical conditions. e mean cycle threshold (Ct) values of the N gene and ORF1ab gene were 24.7 (±7.1) and 25.9 (±7.8), respectively. e total antibodies against S1-RBD protein (anti-S) were measured using Elecys anti-SARS-CoV-2 S assay and analyzed on the Cobas e601 platform (Roche Diagnostics, Switzerland). According to manufacturer's guidelines, sample values ≥ 0.8 U/mL were interpreted as positive for anti-S antibodies. e antibody measurement was performed at three time points: on days 30, 60, and 90 after the positive RT-PCR test (Figure 1). e result showed the seroconversion observed in all HCWs on day 30 after the positive RT-PCR test, and the anti-S antibody concentration continued to be stably detected until day 90. No significant difference of anti-S antibody concentration on days 30, 60, and 90 after the RT-PCR positive test was observed (p > 0.05, Figure 1). e clinical outcomes of vaccinated HCWs with COVID-19 were favourable in all cases, with no hospitalization and no mortality observed among study cases.

Discussion
Compared to the general population, HCWs have a higher risk of SARS-CoV-2 infection, and the infected HCWs possess a greater risk of transmitting and spreading the infection in hospital and community settings [5]. erefore, HCWs were prioritized to receive the vaccine in the initial COVID-19 vaccination program in Indonesia. However, in the situation where the vaccination program coincides with the high daily confirmed cases of COVID-19 like in Indonesia, more cases like described above will be expected.
Fever, the most prevalent symptom observed among COVID-19 HCWs in this study, is the common systemic reaction after vaccination with an inactivated COVID-19 vaccine [3,4]. Consequently, the misdiagnosis of COVID-19 with vaccination side effects is likely to occur. Considering HCWs represent a high-risk group for SARS-CoV-2 exposure, the presence of any symptoms after vaccination cannot be ignored as a vaccination side effect until a further diagnostic test can rule out the COVID-19 diagnosis. In addition, most HCWs acquired the infection through community settings. is result underscores the importance of the high-level awareness of reported symptoms from vaccinated HCWs, particularly in a region where daily confirmed COVID-19 cases are still high. Furthermore, two infected HCWs did not experience any symptoms, which can be a potential transmission source in hospital and community settings [6]. Altogether, these results imply that the hospital needs to be vigilant and introduce regular COVID-19 testing for all HCWs.
Although the false-positive RT-PCR result after vaccination has been reported after administrated intranasal live attenuated influenza vaccine (LAIV) [7,8], the positive RT-PCR among vaccinated HCWs is possibly not due to the COVID-19 vaccine. e vaccine administration of LAIV and specimen collection for testing were in the same site, resulting in the possibility of positive detection by RT-PCR [7,8]. In contrast, the COVID-19 vaccine was administrated intramuscularly into deltoid muscle, in which the protein antigen is taken up by antigen-presenting cells (APCs) and then trafficked to the lymph node for adaptive immune cell activation. As a result, it is possibly unlikely to find the trace of the vaccine component in the specimen collection site for RT-PCR. Furthermore, we observed the favourable clinical outcomes of COVID-19 among vaccinated HCWs, as all of them did not need hospitalization and no one succumbed.
is result may indicate that the coincidental inactivated COVID-19 vaccine administration, and SARS-CoV-2 infection seemed to be well tolerated and not causing the overregulation of the immune system. e seroconversion of anti-S was observed in all HCWs after 30 days of the RT-PCR test. Anti-S concentration was heterogeneous among HCWs (range 23.8 to 250, median 179.8), as has been widely described [9,10]. e antibody was relatively stable until 90 days after the RT-PCR test. Considering that all presented HCW cases in this study were not eligible for acquiring a second dose of the inactivated SARS-CoV-2 vaccine, the longer-term follow-up is required to investigate the durability of observed anti-S antibodies beyond this time point in order to decide the appropriate time for giving a second dose of COVID-19 vaccine among these study cases.

Data Availability
e data used to support the findings of this study are included within the article.