ABSTRACT
Due to chronic immunosuppression and frequent comorbidities, severe infection with Covid-19 is common among heart transplant recipients. Heart transplant recipients with Covid-19 have a short-term mortality rate as high as 25% and hospitalization rates as high as 77%. These patients generally have a severe course of infection and present with right ventricular dysfunction, arrhythmias, and thromboembolic events. We present the case of a heart transplant recipient who presented with Covid-19 infection who, despite initial improvement, eventually passed from severe coronary vasculopathy. The incidence of vasculopathy six months post-transplant without coexisting infection is extremely uncommon. A 45-year-old male with end stage heart failure due to non ischemic cardiomyopathy underwent heart transplant in July 2021. Post-transplant, the patient was clinically stable with LVEF of 60-65%. In January 2022, the patient was admitted for cardiogenic shock with multi-organ failure and tested positive for Covid-19. His echo showed an LVEF of 20-25%. Inotrope therapy was initiated and an intra-aortic balloon pump was placed. Hemodialysis was begun due to oliguria and acute renal failure. RV biopsy indicated moderate acute T-cell mediated rejection and was treated appropriately. Prior to discharge following his six week hospitalization, pathology was negative for rejection and his LVEF increased to 50%. 3 weeks later, he was found unresponsive at home and pronounced dead by EMS. Autopsy determined that the cause of death was sudden cardiac death due to Covid-19. Autopsy Report: " The cause of death is sudden cardiac death secondary to a rapidly progressive graft vasculopathy with concomitant endothelitis and positive staining of endothelium for SARS-CoV-2 viral nucleoprotein, with consequent diffuse myocardial necrosis." The kidneys were enlarged with findings indicating Acute Tubular Necrosis. Our patient presented six months post-transplant with severe Covid-19 induced coronary vasculopathy which progressed to sudden cardiac death. This case demonstrates the importance of preventing Covid-19 infection among heart transplant recipients and the need to assess these patients for coronary vasculopathy prior to progression to sudden cardiac death. [ABSTRACT FROM AUTHOR] Copyright of Journal of Heart & Lung Transplantation is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
ABSTRACT
BACKGROUND: How cigarette smoke (CS) and chronic obstructive pulmonary disease (COPD) affect severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection and severity is controversial. We investigated the effects of COPD and CS on the expression of SARS-CoV-2 entry receptor ACE2 in vivo in COPD patients and controls and in CS-exposed mice, and the effects of CS on SARS-CoV-2 infection in human bronchial epithelial cells in vitro. METHODS: We quantified: (1) pulmonary ACE2 protein levels by immunostaining and ELISA, and both ACE2 and/or TMPRSS2 mRNA levels by RT-qPCR in two independent human cohorts; and (2) pulmonary ACE2 protein levels by immunostaining and ELISA in C57BL/6 WT mice exposed to air or CS for up to 6 months. The effects of CS exposure on SARS-CoV-2 infection were evaluated after in vitro infection of Calu-3 cells and differentiated human bronchial epithelial cells (HBECs), respectively. RESULTS: ACE2 protein and mRNA levels were decreased in peripheral airways from COPD patients versus controls but similar in central airways. Mice exposed to CS had decreased ACE2 protein levels in their bronchial and alveolar epithelia versus air-exposed mice. CS treatment decreased viral replication in Calu-3 cells, as determined by immunofluorescence staining for replicative double-stranded RNA (dsRNA) and western blot for viral N protein. Acute CS exposure decreased in vitro SARS-CoV-2 replication in HBECs, as determined by plaque assay and RT-qPCR. CONCLUSIONS: ACE2 levels were decreased in both bronchial and alveolar epithelial cells from COPD patients versus controls, and from CS-exposed versus air-exposed mice. CS-pre-exposure potently inhibited SARS-CoV-2 replication in vitro. These findings urge to investigate further the controversial effects of CS and COPD on SARS-CoV-2 infection.