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.