Defining the criteria of reinfection is important to understand the disease progress and create epidemiological and clinical control and treatment protocols. In our study with 23 participants, the median time between two infections was 106.4 days. In a guideline report by European Center for Disease Control (ECDC) about the COVID-19 infection characteristics, false PCR positivity, or decreased sensitivity due to swab methodology, contamination due to transport or analysis are shown as possible factors for wrong diagnosis. In addition, it is possible to misdiagnose the length of time between two infections that is only due to suppressed immunity or low levels of antibody as a reinfection. Genome sequencing can alleviate this issue by providing information about phylogenetic differences in infecting agent. [10] In addition, many reinfection cases are associated with false negative PCR results, continuing viral shedding or ceasing the treatment due to no symptoms in patients leading to increased viral replication. [11] PCR diagnosis, still regarded as the cornerstone of COVID-19 diagnosis, has been used for all participants in our study to confirm the episodes. Only 6 participants stayed asymptomatic after the diagnosis of COVID-19 first time while 4 participants stayed asymptomatic after the reinfection was confirmed. Most prevalent symptom during both courses were headache, fatigue and sore throat. Less commonly participants experienced chills, sweating and eye pain/ blurriness.
It is likely that the participants who were not experiencing any symptoms during testing for the first time could have only tested due to contact with a high-risk patient. In addition, only half of asymptomatic participants developed any symptoms after diagnosis.
While 6 participants were treated as inpatients in the first infection, most of them were treated as outpatients during reinfection, even though symptoms did not change between two episodes. It could be that mortality and morbidity was estimated higher due to COVID-19 being a emerging disease with a lot unknowns or using novel drugs that have higher efficacy. In addition, using any treatment during reinfection was lower. While these can be interpreted as less severe disease progression during reinfection, it is also possible that more we understand the disease, treatment and follow-up protocols change.
Majority of reinfection cases are diagnosed after being tested for having symptoms in the literature. In our study population, there were participants who were tested without any symptoms likely due to a contact with a high-risk patients or sporadic institutional screenings. For estimating the population level reinfections, testing of asymptomatic persons is important. [12]
Studies show the swab methodology plays a role in diagnosing reinfections of COVID-19 and also the sensitivity and specificity varies on the swab collector: While in nasopharyngeal samples rates were 7.3%, it went up to 21.4% in oropharyngeal and fecal samples. [11] In our study all swab samples were nasopharyngeal for PCR testing.
In a meta-analysis study, the required time elapsed between first and second positive results are accepted as 35.4 days [13]. However, there is evidence that shedding of SARS-COV-2 RNA can last until 53,65 or 83 days. [14,15 ] In our study, minimum time between two infections was 27 days while half of the patients were reinfected before day 102. Studies with larger sample sizes with phylogenetic and RNA analysis of SARS-COV-2 infections are needed to understand the underlying mechanism and discriminate between recurring infections, prolonged viral clearance and reinfections.
World Health organization recommends medical masks, surgical gloves, long sleeved gowns and eye protection (shields or glasses) for aerosol producing procedures for healthcare workers treating COVID-19 patients. [16]. The use of PPE’s was less common during the first infection than reinfection. It could mean that being infected lead to more caution in our group. However, use of disposable mask and surgical gloves stayed around 60% both before two episodes. WHO recommends use of risk appropriate PPE since 2014 with additional recommendations of N95 masks, long sleeved gowns, eye protection and surgical gloves for healthcare personnel working with COVID-19. [17,18] Using face masks are also shown to protect against infections both in healthcare workers and the population, while addition of eye protection provides extra protection. [19] Therefore, the recommendations also include non-healthcare personnel (cleaning, kitchen, security personnel) in the hospital to use the same protection protocols. [20] In our study usage of all protection equipment was below desired levels for all profession groups.
While participants were questioned about their contact with possible transmission, nature and length of these were not questioned, a risk stratification therefore cannot be made. However, it is known that physical distancing of 2 meters is very effective in preventing transmission. [21] Half of the participants had clinical duties as doctor, nurse or technician which put them into closer contact with COVID-19 patients, while others likely only shorter and more distant contact as cleaning personnel or health officer. Due to the nature of work, it is highly difficult for healthcare workers to maintain that distance.
Limitations
This study enrolled a small sample of healthcare workers, who are usually under higher risk than normal population for both COVID-19 and reinfection due to nature of their work. In addition, the questionnaire was done online, leading to multiple participants being unable to fill, decreasing the sample. Data collected were through a centralized platform, however no genome sequencing, viral culture or sub genomic RNA detection was done. Since the diagnostic criteria for reinfection are still limited, it is possible that some of the participants were having a recurrent or reactivated disease rather than a reinfection.