Adverse effects of non-steroidal anti-inflammatory drugs (NSAIDs) in COVID-19 and other viral respiratory infections: Rapid Review

Background Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most commonly used drugs, and have a wide range of uses, including treatment of acute and chronic pain, fever, and inflammations of infectious and non-infectious etiology. NSAIDs include unselective cyclooxygenase (COX) inhibitors (such as ibuprofen, aspirin (acetylsalicylate), diclofenac and naproxen) as well as selective COX 2 inhibitors (such as Celecoxib, Rofecoxib, Etoricoxib, Lumiracoxib, and Valecoxib). Concerns have been raised that NSAIDs may be associated with an increased risk for adverse effects when used in patients with acute viral respiratory infections, including COVID-19 (caused by the virus SARS-CoV-2), Severe Acute Respiratory Syndrome (SARS, caused by SARS-CoV), Middle East Respiratory Syndrome (MERS, caused by MERS-CoV), and other coronavirus infections. These concerns apply both to the use of NSAIDs prior to the infection, and to the use of NSAID during the infection. Objectives To assess the effects of prior and current use of non-steroidal anti-inflammatory drugs (NSAIDs) in patients with acute viral respiratory infections on acute severe adverse events (including mortality, acute respiratory distress syndrome (ARDS), acute organ failure and opportunistic infections), on acute healthcare utilization (including hospitalization, intensive care unit (ICU) admission, supplemental oxygen therapy and mechanical ventilation) as well as on quality of life and long-term survival. Setting of the review question and protocol development The overall review question was set by the World Health Organization (WHO), which commissioned this review. At WHO, clinical experts and methodologists were involved in defining the review question. The protocol was developed by PvP and ER drawing on Cochrane Rapid Review guidance [1] and with input from Susan Norris (WHO), Gerald Gartlehner (Cochrane Austria) as well as AM, JB, JMS, KS, LMP and SD. Outcomes were set by WHO and refined by PvP and ER drawing on guidance from the WHO Working Group on the clinical characterization of COVID-19 infection (Annex 1) [2] and Susan Norris.