Passive Immunotherapy Shows Promise in Treating COVID-19, but Efficacy Varies by Antibody Status and Severity of Illness

Strategic Insights -

Fresh data on Coronavirus - COVID-19 have been presented in a new report stating that anti-SARS-CoV-2 monoclonal antibodies (mAb) reduce the risk of hospitalization in outpatients with mild-to-moderate COVID-19. However, the efficacy of treatment with mAbs and other passive immunotherapies in patients hospitalized with severe COVID-19 is not clear. This study assessed the clinical effect of passive immunotherapy and its heterogeneity according to baseline endogenous neutralizing antibody status and SARS-CoV-2 antigen level in adults hospitalized with SARS-CoV-2 infection and severe COVID-19.

Key Takeaways:

  • The study included 3,079 patients hospitalized for COVID-19, with 18% having received at least one dose of an anti-SARS-CoV-2 vaccine.
  • The median plasma SARS-CoV-2 antigen level was 1,421 (IQR: 231-4,568) pg/mL, and 51% of patients were endogenous neutralizing antibody positive at study entry.
  • The overall summary estimate of sustained recovery rate ratio (RRR) of the treatment versus placebo group was 1.06 (95% CI [0.99,1.14]), but this varied significantly by antibody serostatus.
  • The RRR was 1.16 (95% CI [1.04,1.29]) among seronegative patients and 0.97 (95% CI [0.88,1.07]) in seropositive patients (p = 0.02 for interaction).
  • The summary hazard ratio (HR) for mortality comparing treatment to placebo was 0.81 (95% CI [0.64,1.03]) overall and 0.69 (95% CI [0.50,0.95]) in seronegative patients.
  • There was no evidence that the treatment effect on any outcome differed according to antigen level.
  • The study concluded that passive immunotherapy might be a useful treatment option for hospitalized patients with COVID-19, administered before the appearance of endogenous antibodies.

Statistics:

  • 3,079 patients were enrolled in the six trials.
  • 18% of patients had received at least one dose of an anti-SARS-CoV-2 vaccine.
  • The median plasma SARS-CoV-2 antigen level was 1,421 (IQR: 231-4,568) pg/mL.
  • 51% of patients were endogenous neutralizing antibody positive at study entry.
  • The overall summary estimate of sustained recovery rate ratio (RRR) was 1.06 (95% CI [0.99,1.14]).
  • The RRR was 1.16 (95% CI [1.04,1.29]) among seronegative patients and 0.97 (95% CI [0.88,1.07]) in seropositive patients.

Sources:

  • NewsRx. Studies from Intermt Medical Center Provide New Data on COVID-19 (Passive Immunotherapy for Adults Hospitalized With Covid-19: an Individual Participant Data Meta-analysis of Six Randomized Controlled Trials). Medical Letter on the CDC & FDA. August 3, 2025; p 185.
  • Passive Immunotherapy for Adults Hospitalized With Covid-19: an Individual Participant Data Meta-analysis of Six Randomized Controlled Trials. PLOS Medicine, 2025;22(7).
  • Public Library of Science. (www.plos.org)