Improved Recovery and Survival with Trimethoprim or Cotrimoxazole in Patients with Severe COVID-19: A Retrospective Analysis

Abstract

Background: COVID-19 may become a life-threatening illness as a result of acute respiratory distress syndrome with the mainstay of management supportive, although dexamethasone and serum from recovered patients look helpful in reducing mortality in oxygen dependant patients. Methods: We retrospectively analysed data from 22 patients with severe COVID-19 treated with trimethoprim (TMP) or cotrimoxazole (CTX) added to standard therapy antibiotics (ST) and compared this with anonymized data from 22 patients with COVID-19 of similar severity receiving ST alone. Results: Patients receiving additional TMP or CTX showed clinical improvement within 48 hours with reduced fever (p= 0.001), C-reactive protein levels (p=0.002) and oxygen requirements (SpO2/FiO2, p<0.001). Mortality was reduced (to 5% versus 32% for ST, p=0.022) and the need for ventilatory support (3 versus 16 patients on ST, p<0.001) and hospital length of stay (mean: 9 days versus 22 days on ST p<0.001). Discussion: This benefit may be due to combined antimicrobial and immunological effects of TMP and CTX. Both drugs block stimulation of the formyl peptide receptors (FPR’s) on the surface of circulating neutrophils and monocytes. When stimulated, FPR’s cause homing of neutrophils to the lung and trigger the release of Reactive Oxygen Series driving cytokine production and therefore a possible cytokine storm. Stressed neutrophils can extrude their nuclear content as ‘external nets’ (NETosis) to trap infectious agents, these nets can block the pulmonary alveolar bed giving severe hypoxia and death as seen in post mortems from COVID-19 patients. Blocking of neutrophil FPR’s by these drugs may be the mechanism by which they protect the lung in COVID-19.