Immunosuppressive Treatment Does Not Prevent Humoral and Cellular Virus-Specific Immunity in Heart or Lung Recipients with SARS-CoV-2 Pneumonia

PURPOSE: Clinical characteristics of SARS-CoV-2 infection and virus-specific humoral and cellular response were analyzed in 4 heart (HR) and 3 lung (LR) Tx recipients in standard triple immunosuppressive regimen. METHODS: SARS-CoV-2 infection was diagnosed by real-time PCR on naso-pharingeal swabs (NPS). T-cell response to structural antigens Spike (S), Envelope (E), Membrane (M) and Nucleocapsid (N) was evaluated by PBMC stimulation with overlapping peptides spanning the entire viral proteins and subsequent detection of cell activation markers CD137 and CD25. Serum IgG antibody to S and N, and IgA antibody to S were determined by ELISA. RESULTS: Three patients developed SARS-CoV-2 infection early (<3 months) and four patients late (>3 years) after Tx. One HR was asymptomatic, one LR presented only gastrointestinal symptoms, and five patients developed dyspnea with radiologic signs of interstitial pneumonia (in one HR ICU admittance was necessary. All patients recovered from SARS-CoV-2 infection, with viral clearance from NPS within 3 weeks. However, two HR (one early and one late HR) died at 6 and 4 months after infection because of multi-organ failure and sudden death. Both deaths were considered as unrelated to SARS-CoV2 infection. Patients who had no lung involvement did not develop specific antibody response, while all the other five patients developed IgG and IgA antibodies to S, and IgG antibody to N, within 2 months after infection. All the symptomatic patients developed a detectable CD4+ T-cell response to two or more antigens. Four patients were subsequently examined >3 months after infection, showing the persistence of IgG and IgA antibodies to S and a decline of IgG antibody to N, while CD4+ T-cell response to N was maintained. Timing of Tx did not affect the occurrence of virus specific immunity. CONCLUSION: Although this series is small, the data indicate that immunosuppression does not prevent the development of a specific humoral and cellular anti-SARS-CoV-2 response, more likely in patients who have experienced clinically relevant pneumonia. These preliminary data encourage the maintenance of regular follow-up to monitor the persistence of immune response and the potential occurrence of SARS-CoV-2-related sequelae in heart and lung recipients.