Other long COVID treatments under investigation—low-dose naltrexone, aripiprazole, sulodexide, and antivirals like nirmatrelvir-ritonavir—remain limited in evidence, with guidelines favoring supportive care.

Experts view the fluvoxamine findings as promising but not definitive, noting the trial focused on fatigue and lacked biomarker data.

Baseline depressive symptoms did not predict greater benefit from fluvoxamine, suggesting a potential mechanism beyond depression.

In a randomized trial of 399 adults with long COVID fatigue, fluvoxamine significantly reduced fatigue versus placebo at day 60 and day 90, with very high probabilities of superiority (about 99% at day 60 and 99.7% at day 90).

The REVIVE-TOGETHER study, conducted across 22 outpatient sites in Brazil from late 2023 to early 2025, used Fatigue Severity Scale and EQ-5D-5L to assess fatigue and health status.

Metformin did not show benefit for fatigue at any follow-up beyond day 30 and did not increase recovery frequency.

Experts urge cautious optimism given long COVID’s multisystem nature and the need for further research to optimize treatment strategies.

A limitation is that depression history was not assessed, leaving open whether benefits relate to fatigue relief or mood factors.

Authors and presenters stress replication and caution before broad adoption of fluvoxamine for long COVID fatigue, due to mixed prior results and unresolved mechanisms.

The study was published in the Annals of Internal Medicine, with authors noting long-term effects are unknown and replication is needed.

Generalizability may be limited since the Brazilian, predominantly female and Hispanic/Latino sample had a mid-40s average age, and follow-up beyond 90 days was not established.

An accompanying Harvard-led study outlined eight long COVID symptom groups to illustrate the condition’s diversity and progression.