IDSA’s Journal of Infectious Diseases provides a monthly roundup of JID papers with direct relevance to clinicians. Read on to learn more about how autoantibody screening could help identify high-risk patients early for effective treatment of COVID-19, the benefits of embedding a TNIC approach in vaccine trial designs and other research ready to inform clinical practice. (Titles and summaries are adapted from the March 2026 issue of JID.)
Post-transplant lymphoproliferative disorder is a serious complication of solid organ transplant and hematopoietic stem cell transplant recipients and is often associated with Epstein-Barr virus reactivation. The soluble Epstein-Barr Virus BZLF1 (sZEBRA, nuclear immediate-early antigen) protein plays a role in EBV reactivation and immune evasion potentially leading to post-transplant lymphoproliferative disorder. Combined with EBV PCR, elevated sZEBRA levels were strongly associated with PTLD and may serve as a biomarker to identify PTLD.
Autoantibodies have been implicated as key players in COVID-19 pathogenesis, with evidence of impacting disease severity and poor outcomes. In a well-controlled study, autoantibodies against type I interferons, MPO and ACE2 were associated with COVID-19 severity and poor outcomes (including mortality), showed increasing titers over time and correlated strongly with SARS-CoV-2 IgA/IgG in hospitalized COVID-19 patients. An important future goal is exploring the impact of autoantibodies in long-term immune dysregulation and post-acute sequelae in COVID-19 survivors.
Little is known about potential underlying immune defects that might predispose patients to developing chronic pulmonary aspergillosis. While polymorphonuclear function and several cytokines did not differ between individuals with CPA and controls, those with CPA displayed an impaired IFN-γ and (more restricted) IL-17 response, as well as increased IL-1RA responses suggesting adaptive immunity/lymphocyte defects as contributors to CPA pathogenesis.
Humoral immunity may play a key role in the immunopathogenesis of chronic hepatitis B. Discontinuation of nucleos(t)ide analogue therapy can promote HBsAg seroclearance but also carries a risk of hepatitis flare. In this multicenter prospective cohort study, serum HBsAg-immune complexes (HBsAg-ICs) were detectable in 97% of participants at the end of treatment. Low HBsAg-ICs levels at the end of treatment predicted hepatitis flare following nucleos(t)ide analogue withdrawal in HBeAg-negative chronic hepatitis B. Dynamic increases in HBsAg-IC levels during ALT flares were observed, supporting the role of humoral immunity in flare pathogenesis.
Traditional vaccine clinical trials sample blood from all participants. In contrast, the test-negative immune correlates design only samples blood from participants who develop symptoms. This study compared traditional to TNIC methods in the mRNA-1273 SARS-CoV-2 vaccine efficacy clinical trial. The authors found the TNIC design that measures antibody provides similar results to the usual immune correlates design but requires far fewer blood samples. The TNIC design is attractive for outbreak settings and may be useful for T-cell correlates.
