Effect of SARS-CoV-2 Infection on Anti-HLA Antibodies and De Novo DSA Incidence in Lung Transplant Recipients

PURPOSE: The SARS-CoV-2 pandemic has brought many challenges into the field of transplantation. The infection itself leads to a broad activation of B-lymphocytes, which in combination with reduced immunosuppression and systemic pro-inflammatory state may possibly lead to an alloimmune response. The main objective of this retrospective single-center study was to evaluate the effect of SARS-CoV-2 infection on anti-HLA antibody dynamics and development of de novo donor specific antibodies (dnDSA) in lung transplant recipients (LTRs). We also aimed to determine the outcomes of treatment with convalescent plasma (CP) and mycophenolate mofetil (MMF) reduction. METHODS: A cohort of 27 LTRs infected by SARS-CoV-2 was retrospectively analyzed. The median age of LTRs at infection was 45.4 years (IQR 26.8-59.5) and median time between transplantation and infection was 16.8 months (IQR 8.0-56.9). The inclusion criteria were history of SARS-CoV-2 infection and screening for anti-HLA antibodies (Luminex technology, One Lambda) before and after infection (median 84, IQR 29-239 days and median 55, IQR 32-90 days resp.). RESULTS: No dnDSA were detected after SARS-CoV-2 infection. De novo class II anti-HLA antibodies with low mean fluorescence intensity (MFI) were observed in 1 patient (3.7%) treated with favipiravir and MMF discontinuation without receiving CP. The standard therapeutic regimen consisted of specific antiviral therapy (remdesivir n=15, 55.6%; favipiravir n=12, 44.4%), reduced or discontinued MMF (n=10, 37.0% and n=17, 63.0%, resp.) and administration of CP (n=18, 66.7%) (Table 1). CONCLUSION: In this retrospective study we did not observe a significant effect of SARS-CoV-2 infection, MMF reduction or CP treatment on anti-HLA antibody dynamics and dnDSA incidence in LTRs. Therefore, CP and MMF withdrawal may be considered as safe therapeutic options regarding antibody-mediated rejection in LTRs affected by SARS-CoV-2. Future studies in larger cohorts are needed to confirm the findings.