Effect of immunomodulatory therapies on mortality in adults hospitalised with COVID-19 and non-COVID-19 community-acquired pneumonia: A systematic review and meta-analysis
In brief
JAK inhibitors linked to 34% lower odds of 30-day death in COVID pneumonia
A review of 196 studies involving 89,117 patients found lower 30-day mortality with JAK inhibitors, cytokine inhibitors and corticosteroids in adults hospitalized with COVID-19 pneumonia; JAK inhibitors had the largest association, with 34% lower odds. No therapy consistently reduced mortality in non-COVID pneumonia, and evidence for benefit beyond 30 days remains uncertain.
- Journal
- Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases (Q1)
- Published
- 6 November 2026
- Study design
- Systematic review / meta-analysis of RCTs
- Evidence level
- Level 1, High (CEBM 1a)
- Authors
- Luke Flower, Joseph Newman, Martin Law, Eckart De Bie, Dominique-Laurent Couturier, Elisabeth Robinson, et al.
- PMID
- 42994614
- DOI
- 10.1016/j.cmi.2026.11.001
Why clinicians should know about it
- Picked for Pulmonary and Respiratory Medicine (paper of the day, 8 November 2026): Effect of immunomodulatory therapies on mortality in adults hospitalised with
Abstract
BACKGROUND: Community-acquired pneumonia (CAP) is the leading infectious cause of morbidity and mortality globally. Severe disease is driven by a dysregulated host inflammatory response, leading to tissue damage. Despite numerous immunomodulatory strategies studied in CAP, their effectiveness remains unclear. OBJECTIVE: To assess the effectiveness of immunomodulatory therapies on 30-day and 90-day mortality in adults hospitalised with CAP. METHODS/DATA SOURCES: Medline (via Ovid), Embase (via Ovid), Web of Science (Core Collection), Scopus, and Global Health (via Ebscohost) were searched from inception to 9 December 2025. STUDY ELIGIBILITY CRITERIA: All studies investigating the use of immunomodulatory therapies in adult patients hospitalised with CAP. PARTICIPANTS: Adult patients admitted to hospital with CAP. INTERVENTIONS: Any immunomodulatory therapy initiated for the management of CAP. ASSESSMENT OF RISK OF BIAS: RoB2 was used for RCTs and ROBINS-I for non-randomised studies of interventions. METHODS OF DATA SYNTHESIS: Treatments were grouped into pre-specified categories, then analysed in a series of pairwise random-effects meta-analyses. Pre-specified subgroup analyses were undertaken regarding severity, aetiology and individual treatments within selected categories. COVID-19 and non-COVID-19 CAP analyses were performed separately. RESULTS: 196 studies, including 89,117 patients, were included. Nine treatment categories included five or more randomised controlled trials (RCTs) reporting 30-day mortality. Among these, corticosteroids, cytokine inhibitors (predominantly IL-6), and JAK inhibitors were associated with reduced 30-day mortality in COVID-19, with odds ratios of 0.87 (95% CI 0.765-0.999), 0.84 (95% CI 0.76-0.93), and 0.66 (95% CI 0.47-0.93), respectively. The only therapies evaluated in five or more RCTs reporting 90-day mortality were cytokine inhibitors in COVID-19 CAP (OR 0.68, 95% CI 0.45-1.03). No therapies were consistently associated with reduced mortality in non-COVID-19 CAP. CONCLUSIONS: Cytokine inhibitors reduce 30-day mortality while corticosteroids and JAK inhibitors probably reduce 30-day mortality in adults hospitalised with COVID-19 CAP. Further research is needed to identify effective immunomodulatory strategies for non-COVID-19 CAP. SYSTEMATIC REVIEW REGISTRATION: PROSPERO ID - CRD42024565301.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.