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

Abstract

BackgroundCD14+ monocytes present antigens to adaptive immune cells via monocytic human leukocyte antigen receptor (mHLA-DR), which is described as an immunological synapse. Reduced levels of mHLA-DR can display an acquired immune defect, which is often found in sepsis and predisposes for secondary infections and fatal outcomes. Monocytic HLA-DR expression is reliably induced by interferon- γ (IFNγ) therapy.Case ReportWe report a case of multidrug-resistant superinfected COVID-19 acute respiratory distress syndrome (ARDS) on extracorporeal membrane oxygenation (ECMO) support. The resistance profiles of the detected Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter baumannii and Citrobacter freundii isolates were equipped with resistance to all four antibiotic classes including carbapenems (4MRGN) and Cefiderocol in the case of K. pneumoniae. A causal therapeutic antibiotic strategy was not available. Therefore, we measured the immune status of the patient aiming to identify a potential acquired immune deficiency. Monocyte HLA-DR expression identified by FACS analysis revealed an expression level of 34% positive monocytes and suggested severe immunosuppression. We indicated IFNγ therapy, which resulted in a rapid increase in mHLA-DR expression (96%), rapid resolution of invasive bloodstream infection, and discharge from the hospital on day 70.DiscussionSuperinfection is a dangerous complication of COVID-19 pneumonia, and sepsis-induced immunosuppression is a risk factor for it. Immunosuppression is expressed by a disturbed antigen presentation of monocytes to cells of the adaptive immune system. The case presented here is remarkable as no validated antibiotic regimen existed against the detected bacterial pathogens causing bloodstream infection and severe pneumonia in a patient suffering from COVID-19 ARDS. Possible restoration of the patient’s own immunity by IFNγ was a plausible option to boost the patient’s immune system, eliminate the identified 4MRGNs, and allow for lung recovery. This led to the conclusion that immune status monitoring is useful in complicated COVID-19-ARDS and that concomitant IFNγ therapy may support antibiotic strategies.ConclusionAfter a compromised immune system has been detected by suppressed mHLA-DR levels, the immune system can be safely reactivated by IFNγ.

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.…”

Analysis of cytokine levels, cytological findings, and MP‐DNA level in bronchoalveolar lavage fluid of children with Mycoplasma pneumoniae pneumonia

“… 19 IFN‐γ can activate itself and nearby immune cells, which plays a vital role in the early host resistance to infection. 20 The timely recruitment of neutrophils plays a crucial role in initiating effective host immune responses. 21 Nevertheless, an excessive release of cytokines may result in the infiltration of neutrophils into the lungs, causing significant harm to target cells.…”

“…Under the synergistic effect of IL‐17A and TNF‐α, neutrophils rapidly migrate to the inflammation site and persist 19 . IFN‐γ can activate itself and nearby immune cells, which plays a vital role in the early host resistance to infection 20 . The timely recruitment of neutrophils plays a crucial role in initiating effective host immune responses 21 .…”

Decoding Immuno-Competence: A Novel Analysis of Complete Blood Cell Count Data in COVID-19 Outcomes

“…Tests that measure immuno-competence should be both informative and biologically valid. Ideally, they should also predict disease outcomes and help select personalized therapies [3,4]. To develop such methods, several biomedical and methodological concepts need to be considered and integrated into the chosen operationalizations, including (i) dynamics, (ii) non-binary (polychotomous) conditions, (iii) the risk of confounding, (iv) personalized factors, (v) biological complexity, (vi) data structuring and (vii) data analysis.…”