Is antiviral treatment at the acute phase of COVID-19 effective for decreasing the risk of long-COVID? A systematic review

Purpose Preliminary evidence suggests a potential effect of antiviral medication used during the acute COVID-19 phase for preventing long-COVID. This review investigates if having received pharmacological treatment during acute SARS-CoV-2 infection may reduce the risk of long-COVID. Methods MEDLINE, CINAHL, PubMed, EMBASE, Web of Science databases, as well as medRxiv/bioRxiv preprint servers were searched up to July 15th, 2023. Articles comparing the presence of long-COVID symptoms between individuals who received or not a specific medication, particularly antivirals, during the acute phase of SARS-CoV-2 infection were included. Methodological quality was assessed using the Newcastle–Ottawa Scale or Cochrane’s Risk of Bias (RoB) tool. Results From 517 studies identified, 6 peer-reviewed studies and one preprint met all inclusion criteria. The sample included 2683 ( n = 4) hospitalized COVID-19 survivors and 307,409 ( n = 3) non-hospitalized patients. The methodological quality was high in 71% of studies ( n = 5/7). Two studies investigating the effects of Nirmatrelvir/Ritonavir and three studies investigating the effect of Remdesivir reported conflicting results on effectiveness for preventing long-COVID. Three studies investigating the effects of other medication such as Dexamethasone ( n = 2) or Metformin ( n = 1) found positive results of these medications for preventing long-COVID. Conclusion Available evidence about the effect of medication treatment with antivirals during acute COVID-19 and reduced risk of developing long-COVID is conflicting. Heterogeneous evidence suggests that Remdesivir or Nirmatrelvir/Ritonavir could have a potential protective effect for long-COVID. A limited number of studies demonstrated a potential benefit of other medications such as Dexamethasone or Metformin, but more studies are needed.