Discussion
Patients treated with corticosteroids were associated with significantly
lower incidences of post-COVID-19 syndrome. While patients treated with
anticoagulants were also observed benefitting from a protective effect
from developing post-COVID-19 syndrome, this effect was not significant.
Antibiotic treatment on the other hand seemed to increase incidences of
post-COVID-19 syndrome, although not
significantly.
Although information regarding
post-COVID-19 syndrome disease pathophysiology is scarce,
corticosteroids’ effect on this disease may be explained by the
hyperactivation of (chronic) inflammatory and immunological pathways
post-COVID-19 syndrome induces and the anti-inflammatory and
immunomodulating mechanism of action of corticosteroids. Among others,
Corticosteroids decrease the production of pro-inflammatory cytokines
and chemokines, stimulate the release of anti-inflammatory cytokines,
and suppress lymphocyte activation and production of immunoglobulins,
which play important roles in the disease progression
[15,28].
Patients infected with COVID-19 have been
observed developing micro clots which in turn obstruct capillaries,
hinder oxygen exchange, and could cause post-COVID-19 related symptoms.
This in turn may be a potential explanation for the seemingly protective
effect against post-COVID-19 syndrome of anticoagulants [6]. In
contrast to corticosteroids and anticoagulants, antibiotics seemed to
increase the chances of developing post-COVID-19 syndrome. As
antibiotics are not part of Medisch Spectrum Twente’s COVID-19 treatment
protocol, we can infer that patients who had received antibiotics were
primarily treated for secondary infections which in turn suggests a
graver patient health state. This is in line with our regression model
which also shows a possible trend for higher chance of developing
post-COVID-19 syndrome with increasing disease severity. However, this
finding was not significant. Furthermore, some studies have better
identified the role of the gut microbiome in COVID-19 patients, which
show that antibiotics cause a dysbiosis in the gut microbiome which is
closely involved in immune system regulation through the gut–lung axis
and gut-brain axis amongst others. An imbalance can lead to more
pro-inflammatory mediators and immune cell activation which in turn
perpetuates the disease [29–32].
Besides the underlying disease mechanisms, the significance of these
results may be explained by the discriminatory ability of the
aforementioned drugs. When patients are admitted to MST due to COVID-19,
anticoagulants are administered as per hospital protocol, whereas
corticosteroids are only administered when certain patient criteria are
met. These criteria, such as respiratory rate and oxygen requirement are
directly linked to disease activity and therefore have a higher
discriminatory ability.
Seeing as post-COVID-19 conditions had only just started to emerge at
the commencement of this study, no treatment or predisposing factors for
these conditions were known. We can therefore infer that the COVID-19
hospitalized patients were treated as per hospital protocol and thus
received similar medical treatment, explaining why no differences were
found in administered drug treatment among patients.
The current study has several limitations. Firstly, the included sample
size was limited which has direct implications on the power of our
study. Secondly, drug class effects were measured for each drug group
without taking into account possible dose variations or treatment
duration as patients were treated as per hospital protocol. Thirdly,
comorbidities were grouped into having a direct or indirect influence on
COVID-19. Due to the relatively small sample size, it was necessary to
include limited disease groups so as to not skew the data. For this
reason, based on literature review and expert opinion it was decided to
only include a select few disease groups as these were considered to be
the most impactful on COVID-19 severity.
This study provides more insight into the effect of commonly used drug
treatments for COVID-19 hospitalized patients on the development of
post-COVID-19 syndrome. Although corticosteroids are primarily used for
the treatment of COVID-19 hospitalized patients fitting certain
respiratory criteria, this study shows corticosteroids reducing the
probability of developing post-COVID-19 syndrome related symptoms after
the acute infection. The observed protective effect is a new and
unexpected finding which may have implications for daily practice in
healthcare in relation to post COVID-19 syndrome prevention. Although
the results indicate the added value of using corticosteroids for the
prevention of post-COVID-19 syndrome, it is equally important not to
overuse these drugs given the immunosuppressive effects and the
development of infections. For this reason, more studies are needed to
not only substantiate these findings but also to find an optimal
treatment dose and length for corticosteroids.
Conclusion COVID-19 hospitalized patients in MST underwent the same treatments as
per hospital protocol. No distinction was made between patients with
predisposing factors for post-COVID-19 syndrome. Corticosteroids have
shown a significant protective effect on the development of
post-COVID-19 syndrome in this study. While anticoagulants have also
shown a similar protective effect, this effect is not significant.
Conversely, treatment with antibiotics has shown to increase
hospitalized patients’ chances of developing post-COVID-19 syndrome
while this effect is also not significant. Further research is required
to validate these findings and to yield improved prevention and
management strategies for post-COVID-19 syndrome.