AIMS: In light of the recent safety concerns relating to NSAID use in COVID-19, 
we sought to evaluate cardiovascular and respiratory complications in patients 
taking NSAIDs during acute lower respiratory tract infections.
METHODS: We carried out a systematic review of randomised controlled trials and 
observational studies. Studies of adult patients with short-term NSAID use 
during acute lower respiratory tract infections, including bacterial and viral 
infections, were included. Primary outcome was all-cause mortality. Secondary 
outcomes were cardiovascular, renal and respiratory complications.
RESULTS: In total, eight studies including two randomised controlled trials, 
three retrospective and three prospective observational studies enrolling 44 140 
patients were included. Five of the studies were in patients with pneumonia, two 
in patients with influenza, and one in a patient with acute bronchitis. 
Meta-analysis was not possible due to significant heterogeneity. There was a 
trend towards a reduction in mortality and an increase in pleuro-pulmonary 
complications. However, all studies exhibited high risks of bias, primarily due 
to lack of adjustment for confounding variables. Cardiovascular outcomes were 
not reported by any of the included studies.
CONCLUSION: In this systematic review of NSAID use during acute lower 
respiratory tract infections in adults, we found that the existing evidence for 
mortality, pleuro-pulmonary complications and rates of mechanical ventilation or 
organ failure is of extremely poor quality, very low certainty and should be 
interpreted with caution. Mechanistic and clinical studies addressing the 
captioned subject are urgently needed, especially in relation to COVID-19.