Severe SARS-CoV-2 infection is associated with increased risk of De novo HLA antibody production in lung transplant recipients: Single-center study.

The Purpose: The COVID-19 pandemic has led to significant morbidity and mortality in lung transplant recipients (LTR). Respiratory viral infections may be associated with de-novo HLA donor-specific antibody (DSA) production and impact lung transplant outcomes. Since one of the immunomodulation strategies post-SARS-CoV-2 infection in LTR include decreasing or holding anti-metabolites, concerns have been raised for higher incidence of de-novo DSA production in LTR.

Methods: We performed a retrospective chart review of 63 consecutive LTR diagnosed with COVID-19 to investigate this concern. COVID-19 disease severity was divided into 3 groups: mild, moderate, and severe. Mild disease was defined as patients with COVID-19 diagnosis who were stable enough to be treated as out-patients. Moderate disease was defined as patients who required admission to the hospital and were on less than 10 l of oxygen at rest. Severe disease was identified as patients who required hospitalization and were on more than 10 l of oxygen with or without mechanical ventilation or extra corporal membrane oxygenation (ECMO). Groups were compared using the Kruskal-Wallis test. A total of 11, 43, and 9 LTR were diagnosed with mild, moderate, and severe COVID-19 respectively.

Results: We observed no significant differences in the CPRA pre-COVID-19 compared to 1 and 6 months post-COVID-19 diagnosis in 6/11 (54.5 %), 18/43 (41.8 %), and 6/9 (66.9 %) LTR with mild (p = 0.66), moderate (p = 0.74), and severe (p = 0.22) COVID-19 respectively. HLA class I and II DSA were detected pre-COVID-19 diagnosis and persisted with no significant differences in the median MFI levels at 1 and 6 months post-COVID-19 diagnosis in 2/11 (p = 0.93), 7/43 (p = 0.71), and 0/9 LTR with mild, moderate, and severe COVID-19 respectively. De-novo HLA DSA were detected within 6 months post-COVID-19 diagnosis in 0/11 (0 %), 1/43 (2.3 %), and 3/9 (33.3 %%) LTR with mild, moderate, and severe COVID-19 respectively (p = 0.001).

Conclusion: Severe COVID-19 may be associated with increased risk of de novo HLA DSA production resulting in allograft dysfunction.