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.