Critically ill COVID-19 patients undergoing cytokine storm are believed to have a worse prognosis and increased fatality rate. Ibuprofen is a non-steroidal anti-inflammatory drug (NSAIDs) that might prove beneficial for the early management of COVID-19 due to its immunomodulatory effects. This study aimed to assess the efficacy and safety of the early use of ibuprofen to attenuate the severity of the course of COVID-19 and improve outcomes in patients diagnosed with a moderate case of COVID-19 disease.


This randomized, double-blinded prospective study was conducted from January, 2022 to May, 2022, which included a total sample size of 180 patients with moderate cases of COVID-19. The number of patients transferred to intensive care was used as a primary outcome with a proposed large effect size (0.8), alfa =0.05, and power=0.80, so 90 cases were included in each group. Secondary outcomes were inflammatory markers: C-Reactive Protein (CRP), serum ferritin, and interleukin-6 (IL-6), duration of hospital stay, and need for ICU admission.


One hundred eighty patients with moderate case of COVID-19 disease were divided in a 1: 1 ratio to receive ibuprofen (IG) or paracetamol (CG). The average age of the included patients was almost 41 years. Statistically significant differences were reported between both groups in terms of improvement in cough symptoms and lymphopenia in IG compared to CG (p= 0.034 and p= 0.044, respectively). Regarding secondary outcomes, statistically, significant differences were reported between the study’s groups in terms of the mean number of patients transferred to the ICU in IG compared to the CG (p =0.0.047) and duration of hospitalization (p =0.013), with no significant differences (p > 0.9999) in the occurrence of side effects.

Concerning the follow-up of the cytokine storm marker, there was a statistically significant reduction in serum cytokine marker compared to the baseline value (P < 0.05) in the same group. No statistically significant differences were observed when comparing both groups together in terms of serum ferritin level (p =0.570), serum IL-6 level (p =0.580), and CRP level (p =0.401).


It can be concluded that early use of ibuprofen as adjuvant therapy in COVID-19 management is effective and safe to attenuate the severity of diseases and improve outcomes.

Trial Registration:

Project manager for the Pan African Clinical Trial Registry PACTR202202880140319. Registered 9th February, 2022 - Retrospectively registered, (https://pactr.samrc.ac.za/)

Keywords: Ibuprofen, COVID-19, Immunity-cytokine storm, IL-6, ARDS, Anti-inflammatory, Patients.
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