Humoral response
Both insufficient and overactive immune responses have been reported in
COVID-19 patients [45]. Production of protective cytokines and
IFN-gamma, which is mediated by the CD4+ and CD8+ cells, plays an
important role in containing and resolution of the infection [46].
The dynamics of the antibody response in COVID-19 patients is not
completely known; and different studies have reported different rates of
seroconversion. Zhao et al [47] and Liu et al [48] reported
seroconversion in all infected patients respectively by 39 and 14 days
after the onset of infection. Liu et al also reported that by the
60th day IgM antibodies were undetectable in about
one-third of the patients and the IgG titers had decreased substantially
[48]. Based on another study, although recently discharged patients
have a high level of humoral immunity against the virus, antibodies
start to decreases within 2 to 3 months after the infection [13]. In
another study the seroconversion rate for IgG, IgM and IgA was
~90% and most patients seroreverted within 75 days;
with IgG levels remaining detectable over 90 days after the symptom
onset in more than 99% of patients [49]. Multiple studies have also
concluded that the humoral immunity against this virus could be
short-lived [50]. Contrasting these studies, our results showed that
94% of patients were positive for neutralizing antibodies (IgG) 120
days after the onset of symptoms; which is in line with the results of
an Icelandic population study that reported a 91% seropositivity four
months after the initial diagnosis of COVID-19 [6]. In evaluation of
the results of these studies, we should take into account the natural
process of the humoral response. In case of many other viral
infections—where seroconversion is sustained as seromaintenance and
immunity—we see a temporary decrease of antibody levels during the
first few months of infection/inoculation [51], and since the
emergence of COVID-19 is recent, we cannot judge the humoral response to
this virus in long term and a rebound increase in antibody levels can be
expected [50].
In our study, the four patients who had a positive result in RT-PCR
screening 120 days after the initial diagnosis of COVID-19, were also
positive for neutralizing antibodies; and although they theoretically
may have prevented a severe episode of re-infection and caused a lack of
any symptoms in one RT-PCR-positive patient, we cannot know for sure if
those levels are high enough to be completely protective [21]. In a
similar study Zhang et.al reported re-infection in 6 recovered patients
that was caused by viruses from lineages different from the first
infection. All these patients had varied levels of antibodies and they
concluded that presence and even maintenance of the humoral response
cannot rule out the possibility of re-infection [52]. We also
believe that the two patients who did not have sufficient levels of IgG
(<1.1 g/L), have been protected from an episode of
re-infection by a strong cellular immune response, even within an
epidemic situation.
Genetic sequencing can rule out a false positive in RT-PCR testing and
determine if the infection is caused by a different subclass of the
virus. In cases of re-infection with a different clade of the virus,
even protective levels of IgG may not be effective [21]. We
hypothesize that high levels of neutralizing antibodies do not make the
diagnosis of re-infection unlikely, unless there is genetic proof that
the positive RT-PCR results are related to the same strain of the virus
from the first episode; in which case re-activation/relapse would be a
more likely diagnosis.