Case Report: Interferon-γ Restores Monocytic Human Leukocyte Antigen Receptor (mHLA-DR) in Severe COVID-19 With Acquired Immunosuppression Syndrome

Abstract

BackgroundThe major histocompatibility complex (MHC) class II characterized by monocytes CD14+ expression of human leukocyte antigen receptors (HLA-DR), is essential for the synapse between innate and adaptive immune response in infectious disease. Its reduced expression is associated with a high risk of secondary infections in septic patients and can be safely corrected by Interferon-y (IFNy) injection. Coronavirus disease (COVID-19) induces an alteration of Interferon (IFN) genes expression potentially responsible for the observed low HLA-DR expression in circulating monocytes (mHLA-DR).MethodsWe report a case of one-time INFy injection (100 mcg s.c.) in a superinfected 61-year-old man with COVID-19–associated acute respiratory distress syndrome (ARDS), with monitoring of mHLA-DR expression and clinical tolerance.ObservationsLow mHLA-DR pretreatment expression (26.7%) was observed. IFNy therapy leading to a rapid increase in mHLA-DR expression (83.1%).ConclusionsSevere ARDS in a COVID-19 patient has a deep reduction in mHLA-DR expression concomitantly with secondary infections. The unique IFNy injection was safe and led to a sharp increase in the expression of mHLA-DR. Based on immune and infection monitoring, more cases of severe COVID-19 patients with low mHLA-DR should be treated by IFNy to test the clinical effectiveness.

Case Report: Interferon- γ Rescues Monocytic Human Leukocyte Antigen Receptor (mHLA-DR) Function in a COVID-19 Patient With ARDS and Superinfection With Multiple MDR 4MRGN Bacterial Strains

“…Immune stimulation by IFNγ in our case was similar to that reported previously in another infectious context and appears to be efficient in severe COVID-19 ( 9 – 11 ). AIS has been described in COVID-19 patients in the ICU, but few data on immunostimulation have been reported to date.…”

“…The resistance profiles of the detected invasive bacterial species Klebsiella pneumoniae (three different pulsed-field gel electrophoresis (PFGE) types), Pseudomonas aeruginosa , Acinetobacter baumannii , and Citrobacter freundii left very limited antimicrobial options, warranting an investigation of the potential for immunomodulation by IFNγ. The observed AIS with low expression of HLA-DR in circulating monocytes prompted us to apply IFNγ therapy as in previously described cases ( 9 – 11 ). This resulted in a significant increase in mHLA-DR levels.…”

“…Several case series have shown that administration of IFNγ results in a significant increase in mHLA-DR expression, improves the ability to eliminate invasive bacterial pathogens, and in most cases results in rapid clinical improvement ( 9 – 11 ). These previous reports were convincing enough to motivate randomized clinical trials, which have not yet been reported.…”

Monocyte HLADR and Immune Dysregulation Index as Biomarkers for COVID-19 Severity and Mortality

“…With the increasing understanding of COVID-19 associated immune dysregulation, immune modulation therapy appears to be the next step forward. Dickel S et al reported a single case of superinfected COVID-19 patient with ARDS treated with a single dose of interferon-gamma (IFN-Y) with measurement of mHLA-DR pre and post-therapy; a sharp increase in mHLA-DR was reported [ 36 ]. Another case of immunostimulation with IFN-Y in protracted SARS-Cov-2 pneumonia resulted in recovery and discharge in a patient with several comorbid conditions.…”

Case report: Kinetics of human leukocyte antigen receptor HLA-DR during liver injury induced by potassium para-aminobenzoate as assessed for causality using the updated RUCAM

“…Updated RUCAM is a standardized and validated method specific to hepatotoxicity and has long been well-established in hepatological practice, studies, registries, and case reports ( Benichou et al, 1993 ; Danan and Benichou, 1993 ). The expression of HLA-DR on CD14 + monocytes and CD3 + T lymphocytes was analyzed using flow cytometry, as previously described ( Dickel et al, 2021 ; Grimm et al, 2021 ; Baier et al, 2022 ; Tampe et al, 2022 ). Antibody staining followed standard protocols for antibody staining of cells in suspension.…”