Introduction
Severe acute respiratory syndrome (SARS)-coronavirus (CoV)-2 which
causes the Coronavirus disease (COVID-19) has taken the world by storm.
The impact this virus has had on the global economy, education, travel,
and healthcare has been astounding [1–3]. Although physicians
initially had difficulty treating this disease, a more or less
standardized treatment has been established. Corticosteroids and
anticoagulants play an important role in this treatment and target key
elements in the disease pathophysiology [4].
As higher incidences of venous thromboembolism (VTE) have been observed
for COVID-19 hospitalized patients, varying from 2.6% to 15% for
pulmonary embolisms (PE) and 4.6 to 12% for deep vein thrombosis (DVT),
researchers have been prompted to investigate the underlying mechanism
[5]. Although this mechanism has not yet been fully elucidated,
COVID-19 is thought to cause an exaggerated inflammatory response which
in turn leads to endothelial damage and activation of the coagulation
cascade. Additionally, micro clotting has been observed in COVID-19
infected patients, hindering oxygen exchange [6]. Furthermore, the
immobility of hospitalized patients further increases the risk of
thrombotic complications, hence the administration of anticoagulants
[7,8]. Aside from thrombotic complications, COVID-19 patients have
been observed with higher levels of inflammatory indices such as
C-reactive protein, neutrophils, and interleukins which in turn cause
excessive release of pro inflammatory cytokines. These cytokines cause
significant damage to the respiratory system leading to pulmonary
infections, respiratory failure, and organ damage via immune and
inflammatory mediated pathways [9,10]. Corticosteroids target these
inflammatory pathways and have played a vital role in improving clinical
outcomes and mortality in patients [11–13]. Another commonly used
drug group in the treatment of COVID-19 patients are antibiotics. These
drugs are primarily implemented to treat secondary infections and
prevent superinfections which has accounted for a significant portion of
COVID-19 deaths. That said, some COVID-19 hospitalized patients in
severe health states have also been treated empirically with
antibiotics, despite the lack of evidence for a beneficial effect
[14].
Although healthcare workers have mainly been focused on the treatment of
the acute phase, i.e., the viral infection and the associated health
symptoms of COVID-19, it has now become apparent that after the initial
infection a certain proportion of patients experience COVID-19 related
symptoms for a prolonged period [15]. Due to the lack of a
universally accepted definition among the scientific community and the
ever-changing availability of information, these post-COVID conditions
have been identified by various names. Long haul COVID, chronic COVID,
post-acute COVID-19, long COVID, and post-COVID-19 syndrome are a few of
the commonly used names. In this study, we have adopted the definitions
of COVID conditions as described in the rapid guideline on post-COVID-19
conditions developed in collaboration with the National Institute for
Health and Care Excellence (NICE), the Scottish Intercollegiate
Guidelines Network (SIGN), and the Royal College of General
Practitioners (RCGP). Post-COVID-19 syndrome is defined as “signs and
symptoms that develop during or after an infection consistent with
COVID-19, present for more than 12 weeks and are not attributable to
alternative diagnoses” [16].
As these post-COVID conditions are still in their infancy little is
known about the underlying disease pathophysiology and epidemiology. The
incidence rate of post-COVID-19 conditions varies widely per study,
ranging from more than 30% to 76% after 6 months of symptom onset
[17–21]. This variation can be attributed to differences in
follow-up length, the definition of the post COVID condition, and the
population sample [15].
While much research has
been done regarding the safety and efficacy of corticosteroids,
antibiotics, and anticoagulants on the treatment of the acute phase of
COVID-19 and its concomitant manifestations, little is known regarding
the impact these medications have on the development of post-COVID-19
syndrome. No studies were identified looking into a possible
association. Given the extent to which these drugs are prescribed, it is
therefore imperative to investigate a possible interplay between these
drugs and post-COVID-19 syndrome. Identifying the association between
pharmacotherapy and the development of post-COVID-19 syndrome allows
healthcare providers to make better-informed treatment choices and could
contribute to overall patient well-being. Therefore, the aim of this
study was to assess the effect of corticosteroids, anticoagulants, and
antibiotics on the development of post-COVID-19 syndrome.