Comparative efficacy and safety of pharmacological interventions for the treatment of long COVID in adults: a systematic review and network meta-analysis

Coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, represents a major global pandemic of the 21st century, with long-term effects termed long COVID. This systematic review and network meta-analysis (NMA) evaluated pharmacological interventions for adults with long COVID, incorporating randomized controlled trials and adjusted observational studies. Primary outcomes included all-cause mortality, hospitalization, ICU admission, and mechanical ventilation; secondary outcomes covered symptom recovery across five categories, with safety assessed via adverse events. Results from random-effects models showed that saline nasal irrigation (SMD=21.10, 95% CI [16.91, 25.30]), nitrilotriacetic acid trisodium (SMD=7.40 [5.79, 9.01]), tetra sodium pyrophosphate (SMD=3.69 [2.61, 4.77]), and sodium gluconate (SMD=3.01 [1.92, 4.09]) significantly improved anosmia versus control. For thrombosis, rivaroxaban reduced arterial (OR=0.33 [0.01, 8.19]) and venous thrombotic events (OR=0.12 [0.01, 0.97]), while therapeutic-dose anticoagulants lowered thrombotic risks but increased major bleeding events (OR=1.86 [1.19, 2.89]) compared to prophylactic dosing. This NMA provides comparative evidence to guide treatment strategies for long COVID, highlighting the need for further research as new evidence emerges.