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

Hailu Zhou, Fei Jiang+1 more|arXiv (Cornell University)|Jan 17, 2026

Long-Term Effects of COVID-190 citations

TL;DR

This study conducts a systematic review and network meta-analysis of pharmacological treatments for adults with long COVID, summarizing efficacy on mortality, hospitalization, ICU admission, mechanical ventilation, symptom recovery, and safety. It identifies several agents with potential benefits for specific symptoms and thrombotic risks.

ABSTRACT

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.

Motivation & Objective

• Assess the comparative efficacy of pharmacological interventions for adults with long COVID across key clinical outcomes.
• Evaluate safety profiles and adverse events of these pharmacological options.
• Synthesize randomized and adjusted observational evidence to guide treatment strategies.
• Highlight areas where evidence is strong or sparse to inform future research.

Proposed method

• Perform a systematic review and network meta-analysis including randomized controlled trials and adjusted observational studies.
• Use random-effects models to estimate effects on primary outcomes: all-cause mortality, hospitalization, ICU admission, and mechanical ventilation.
• Assess secondary outcomes focusing on symptom recovery across five categories and safety via adverse events.
• Quantify treatment effects using standardized mean differences for symptom outcomes and odds ratios for binary clinical events.
• Incorporate heterogeneity and bias considerations inherent to mixed study designs.

Experimental results

Research questions

• RQ1 What is the comparative efficacy of pharmacological interventions for reducing mortality, hospitalization, ICU admission, and mechanical ventilation in adults with long COVID?
• RQ2 Which pharmacological treatments show the strongest evidence for improving symptom recovery across predefined categories?
• RQ3 What are the safety profiles and adverse event risks associated with these pharmacological options, including major bleeding and thrombotic events?
• RQ4 How do therapeutic-dose anticoagulants compare to prophylactic dosing in terms of thrombotic risk and major bleeding?
• RQ5 What gaps in evidence remain to guide future research on long COVID pharmacotherapy?

Key findings

• Saline nasal irrigation significantly improved anosmia versus control (SMD 21.10; 95% CI 16.91 to 25.30).
• Nitrilotriacetic acid trisodium significantly improved anosmia versus control (SMD 7.40; 95% CI 5.79 to 9.01).
• Tetra sodium pyrophosphate significantly improved anosmia versus control (SMD 3.69; 95% CI 2.61 to 4.77).
• Sodium gluconate significantly improved anosmia versus control (SMD 3.01; 95% CI 1.92 to 4.09).
• Rivaroxaban reduced arterial thrombotic events (OR 0.33; 95% CI 0.01 to 8.19) and venous thrombotic events (OR 0.12; 95% CI 0.01 to 0.97).
• Therapeutic-dose anticoagulants lowered thrombotic risks but increased major bleeding events (OR 1.86; 95% CI 1.19 to 2.89).