Respiratory Diseases Roundup

Recent Clinical Findings on Long COVID Prevention and Recovery, Pediatric Risks After COVID-19, and More

Edited by:
Kate Young

Key Highlights

  • Early metformin use after SARS-CoV-2 infection was associated with a ≈64% lower 1-year risk of post–COVID-19 condition in adults with overweight or obesity versus a non-initiation cohort.
  • Receipt of a COVID-19 mRNA vaccine near initiation of immune checkpoint inhibitors was linked to longer overall survival in non-small cell lung cancer and melanoma.
  • Resistance exercise therapy improved walking distance, quality of life, and mood in adults with persistent symptoms after COVID-19 infection.
  • In nearly 14 million children, rare vascular and inflammatory events were more frequent and longer-lasting after COVID-19 infection than after vaccination.

Metformin and Risk of Post–COVID-19 Condition1

A population-based retrospective cohort study in Clinical Infectious Diseases used the UK Clinical Practice Research Datalink Aurum database to emulate target trials in adults with overweight or obesity (BMI ≥25 kg/m²) and a recent COVID-19 diagnosis between March 2020 and July 2023. After exclusions, 624,308 adults were included; 2976 initiated metformin within 90 days of infection. Early metformin initiation was associated with a ≈64% lower 1-year risk of post–COVID-19 condition (PCC) versus non-initiation (hazard ratio [HR], 0.36; 95% CI, 0.32–0.41), corresponding to an absolute risk difference of −12.6 percentage points.

The association was consistent in per-protocol analyses and across prespecified subgroups, including age, sex, BMI categories, diabetes status, and variant eras. Approximately half of metformin initiators had type 2 diabetes. The authors did not observe a signal for reduced cancer risk in a negative control analysis, supporting specificity of the PCC finding.

As an observational study, residual confounding and misclassification of PCC remain possible, and findings may not generalize to individuals with normal weight or different care settings. Nevertheless, these results extend prior randomized trial data and suggest that timely metformin initiation after SARS-CoV-2 infection may be a scalable strategy to reduce PCC risk in adults with overweight or obesity.

COVID-19 mRNA Vaccines and Immune Checkpoint Blockade2

A translational study in Nature evaluated whether SARS-CoV-2 mRNA vaccines modulate antitumor immunity and responses to immune checkpoint inhibitors (ICIs). In murine models, systemic administration of COVID-19 mRNA vaccines induced robust type I interferon responses, enhanced antigen-presenting cell priming, and promoted CD8+ T-cell responses against tumor-associated antigens. These changes converted immunologically “cold” tumors to a more inflamed phenotype but also upregulated PD-L1, making concurrent PD-1/PD-L1 blockade critical for maximal antitumor effect.

In retrospective clinical cohorts, investigators examined adults with stage III/IV non–small cell lung cancer treated at a single cancer center between 2015 and 2022. Receipt of a COVID-19 mRNA vaccine within 100 days of ICI initiation (n=180) was associated with longer median overall survival compared with no vaccination within that window (37.3 vs 20.6 months; adjusted HR, 0.51; 95% CI, 0.37–0.71), after adjustment for 39 covariables. Similar survival advantages were observed across disease stages and in an independent melanoma cohort. The authors also reported vaccine-associated increases in type I interferon, myeloid–lymphoid activation, and tumor PD-L1 expression in patients.

The study’s limitations include its observational design, potential unmeasured confounding (eg, health-seeking behaviors), and evolving viral variants and vaccine formulations. These data suggest that clinically available mRNA vaccines, even when targeting non-tumor antigens, can act as immune modulators that may sensitize tumors to ICIs, but prospective trials are needed before practice changes.

Resistance Exercise Therapy After COVID-19 Infection3

A randomized clinical trial in JAMA Network Open evaluated a 3-month, personalized resistance exercise program in adults with persisting symptoms after COVID-19 infection. The multicenter trial enrolled 233 adults (median age, 53.6 years; 62.7% women), including both community-managed and previously hospitalized patients, within 12 months of confirmed SARS-CoV-2 infection. Participants were randomized 1:1 to resistance exercise or usual care. The primary outcome was change in Incremental Shuttle Walk Test (ISWT) distance at 3 months.

At 3 months, the mean change in ISWT distance was 83 m in the intervention group vs 47 m in the control group, yielding an adjusted mean difference of 36.5 m (95% CI, 6.6–66.3 m; P=.02). Compared with usual care, the exercise group also had greater improvements in health-related quality of life (EQ-5D-5L utility score difference, 0.06; 95% CI, 0.01–0.11), anxiety/depression category (Patient Health Questionnaire; odds ratio for improvement, 0.5; 95% CI, 0.2–0.8), and handgrip strength (+2.6 kg; 95% CI, 0.9–4.2 kg). Median adherence was 71%, approximately 5 days per week of prescribed exercise.

The intervention was delivered pragmatically in community and posthospital settings, suggesting potential scalability. The trial was conducted in Scotland during specific pandemic phases, and participants had persisting symptoms but variable long COVID definitions, which may limit generalizability. Nonetheless, these findings indicate that structured resistance training is a feasible, safe, and potentially effective rehabilitation approach for physical and psychological sequelae after COVID-19 infection.

Vascular and Inflammatory Risks in Children After COVID-194

A retrospective, population-based cohort study in The Lancet Child & Adolescent Health linked electronic health records for nearly all children and young people in England (13.9 million individuals) to compare vascular and inflammatory outcomes after first COVID-19 diagnosis versus COVID-19 vaccination. Approximately 28.1% had a documented COVID-19 diagnosis from January 2020 to December 2022, and 3.4 million children aged 5–18 years received a first BNT162b2 mRNA vaccine dose from August 2021 to December 2022.

COVID-19 diagnosis was associated with significantly increased risks of arterial thromboembolism, venous thromboembolism, thrombocytopenia, myocarditis or pericarditis, and systemic inflammatory conditions in the first week after infection (eg, adjusted HR for myocarditis or pericarditis, 3.46). Some risks, including venous thromboembolism, thrombocytopenia, and myocarditis/pericarditis, remained modestly elevated for >12 months.

In contrast, vaccination was associated with an elevated risk of myocarditis or pericarditis only in the first month after BNT162b2, with an adjusted HR of 1.84 and no sustained excess risk thereafter. Over 6 months, COVID-19 infection resulted in an estimated 2.24 additional cases of myocarditis or pericarditis per 100,000 children, compared with 0.85 additional cases per 100,000 after vaccination. Although these events were rare in absolute terms, the findings indicate higher and longer-lasting risks following infection than vaccination.

The study’s limitations include reliance on coded diagnoses, inability to fully distinguish myocarditis from pericarditis, and evolving variants and vaccine uptake over time. The authors concluded that these data support pediatric COVID-19 vaccination strategies aimed at mitigating the more frequent and persistent vascular and inflammatory risks associated with infection.

References:

  1. Chaichana U, Man KKC, Ju C, Makaronidis J, Wei L. Effect of Metformin on the Risk of Post-coronavirus Disease 2019 Condition Among Individuals With Overweight or Obese: A Population-based Retrospective Cohort Study. Clin Infect Dis. Published online September 1, 2025. doi:10.1093/cid/ciaf429
  2. Grippin AJ, Marconi C, Copling S, et al. SARS-CoV-2 mRNA vaccines sensitize tumours to immune checkpoint blockade. Nature. 2025;647(8089):488-497. doi:10.1038/s41586-025-09655-y
  3. Berry C, McKinley G, Bayes HK, et al. Resistance Exercise Therapy After COVID-19 Infection: A Randomized Clinical Trial. JAMA Netw Open. 2025;8(11):e2534304. Published 2025 Nov 3. doi:10.1001/jamanetworkopen.2025.34304
  4. Sampri A, Shi W, Bolton T, et al. Vascular and inflammatory diseases after COVID-19 infection and vaccination in children and young people in England: a retrospective, population-based cohort study using linked electronic health records. Lancet Child Adolesc Health. 2025;9(12):837-847. doi:10.1016/S2352-4642(25)00247-0