The second follow-up RT-PCR
Among the 44 patients who tested negative in the first test and
continued their cooperation with the study, 3 patients (6.81%) tested
positive 60 days after the initial infection (one month after the first
negative RT-PCR test). These patients again were asymptomatic and the
interval between the initial infection and this positive test is not
significant enough to rule out viral shedding. Although, in case of
viral shedding and/or presence of remnant viral particles, we would have
expected to achieve a positive result in the previous test as well as
this one; but this dissonance can be explained in absence of
re-infection. Given the limited accuracy of RT-PCR, in case of a false
negative in the first follow-up test or a false positive in the second
test, continued shedding or complete recovery (respectively) can be
misdiagnosed as re-infection [35, 36]. On the other hand, studies
have shown that COVID-19 patients have a lower concentration of ACE2
monocyte expression—the endogenous entry receptor of SARS-CoV-2—and
researchers hypothesize that the virus can remain dormant in peripheral
blood mononuclear cells and cause a relapse after the respiratory system
has been cleared of the virus and patient has tested negative
[37-39].
Positive RT-PCR tests in absence of significant symptoms in a recovering
patient has also been reported in many studies [18, 40]. In some
cases, symptoms were present, although less severe than the first
episode [41]. Our findings include asymptomatic and mildly
symptomatic patients who re-tested positive for SARS-CoV-2. None of our
cases had symptoms as or more severe than the first episode of
infection. Contrasting our results, the majority of other reports have
described more severe symptoms in patients who re-tested positive
[15-17, 42] and researchers have hypothesized that a selection bias
towards testing and confirming re-infection in symptomatic patients
[43] and/or a primed/heightened immune response upon the second
episode of infection can be the reason why most cases of re-infection
pertain to patients with intense symptoms upon second exposure and
infection [15, 42].
An episode of re-infection can be proved by a positive viral culture
[21, 44] and/or genetic sequencing of the infective virus in both
episodes of infection to confirm that the second episode is caused by a
different clade of the virus. Tillett et al, reported a case of
re-infection in a 25-year-old male, who recovered from a
RT-PCR-confirmed episode of COVID-19, only to become symptomatic again
after a 30-day symptom-free period. Genetic sequencing showed distinct
genetic differences between the two specimen, indicating two separate
instances of infection with genetically different variants of the virus
[15]. Similar cases of re-infection with a genetically different
clade of the virus within 6 months of an original episode of COVID-19
have been reported [16-18].
Unfortunately, genetic sequencing is not readily available and based on
CDC recommendations in absence of genetic proof of infection with a
different clade of the virus, a positive RT-PCR test that has been
obtained after the first 90 days of the onset of the initial infection
can be considered indicative of re-infection. Although, a positive
RT-PCR test after two consecutive negative results, especially if
accompanied by typical symptoms, can be defined as re-infection even
within the first 90 days of the first episode of infection [21].