Abstract
Background: Evidence of highly effective repurposed drugs for coronavirus disease 2019 (COVID-19) is insufficient. However, empirical therapy using antiviral, antibiotic and immunomodulatory drugs is massive. Studies evaluating the clinical use of these drugs in Indonesia are sparse. Methods: We performed a retrospective study using medical records of hospitalized COVID-19 patients from July 2020 to March 2021 in Bandung, Indonesia. Data were collected at relevant timelines: age, sex, comorbid condition, peripheral oxygen saturation (SpO2), and hematology at admission; antiviral, antibiotic, and immunomodulator treatment during hospitalization; length of stay hospitalization (LOS) and death at discharge. Clinical use of the drug regimens included dose, frequency, and duration of therapy. The main outcome of hospitalization care was LOS and death. Results: Out of 249 patients, 43.3% had a comorbid condition, 74.7% had non-severe COVID-19 (SpO2 ≥ 90%), and almost all received antiviral or antibiotic agents. Remdesivir was the most frequent drug composing various antiviral regimens. Patients receiving a combination of remdesivir and favipiravir had lower SpO2 compared to those receiving oseltamivir (p=0.01). The short LOS was associated with remdesivir alone (p=0.03), the combination of favipiravir and oseltamivir (p=0.01), and the combination of intravenous levofloxacin and ceftriaxone (p<0.0001). Immunomodulatory drugs (methylprednisolone, dexamethasone, tocilizumab) were used in 47.1% of patients with low SpO2 (p=0.001). Its use was associated with prolonged LOS (p=0.0043). The increased risk of death in patients treated with the combination of remdesivir and favipiravir (OR 4.1;95%CI 1.4-12.2), and immunomodulatory drugs (OR 6.2; 95%CI 1.7-23.3) was confounded by the baseline characteristics of older age, comorbid condition, SpO2 level, and low lymphocyte number. Conclusions: Some treatment regimens were associated with short LOS, but there were drug regimens which might increase the risk of death. Further study should control the clinical conditions of COVID-19 patients at admission to confirm the outcome of death following drug therapy.
Highlights
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had caused at least 240 million cases of coronavirus disease 2019 (COVID-19) and more than 4.8 million deaths worldwide until 18 October 2021.1 At that time, Indonesia has reported 4.2 million confirmed COVID-19 cases with over 140 thousand deaths.[2]
This retrospective study aimed to investigate the clinical use of antiviral, antibiotic and immunomodulatory agents in hospitalized COVID-19 patients during the first year of the pandemic. The treatment using these drugs were considered common based on the pathogenesis of infection and inflammation on COVID-19 disease. These drugs are listed in the Indonesian national guideline for COVID-19.6,7 We evaluated the outcome of length of stay (LOS) and death following hospitalization to understand the benefit of pharmacological therapy of antiviral, antibiotic and immunomodulators
Our study found that patients who were treated with immunomodulatory drugs had a significantly lower level of SpO2 compared to those who were untreated with these drugs (p = 0.001)
Summary
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had caused at least 240 million cases of coronavirus disease 2019 (COVID-19) and more than 4.8 million deaths worldwide until 18 October 2021.1 At that time, Indonesia has reported 4.2 million confirmed COVID-19 cases with over 140 thousand deaths.[2]. A clinical trial on the most promising antiviral remdesivir showed its benefit on the clinical improvement at day 15.4 the interim report of the World Health Organization’s (WHO) Solidarity trial showed the lack of benefit of remdesivir on the reduction of mortality and hospitalization duration.[5] the Indonesian national guideline for COVID-196,7 recommends the antiviral favipiravir. This drug is not part of the recommendation from the WHO guideline based on the evidence from clinical trials evaluating remdesivir and favipiravir for COVID-19 therapy.[8] The latest version of the WHO guidelines for COVID-19 therapy provides strong recommendation for systemic corticosteroid in severe and critical COVID-19, and conditional recommendation against remdesivir in hospitalized COVID-19.9 Corticosteroid and tocilizumab are drugs modulating the immune response that plays a critical role in the pathogenesis of severe COVID-19. Its use was associated with article can be found at the end of the article
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