ABSTRACT
The new coronavirus was first reported in 2019 (China) and officially announced by the World Health Organization as a pandemic in March 2020. Severe acute respiratory syndrome coro-navirus 2 (SARS-CoV-2) is the causative agent of the pneumonia-associated illnesses and shares structural homology with the related Severe acute respiratory syndrome coronavirus-1 (SARS-CoV--1). One of the mechanisms for SARS-Cov-1 and-2 infection is mediated by the angiotensin-con-verting enzyme-2 (ACE2) cell receptor, enabling the virus to enter the host cells. ACE2 is an iso-form of the angiotensin-converting enzyme 1 (ACE). The actions of ACE2 counterbalance the clas-sic renin-angiotensin system (RAS) axis through the production of Ang 1-7, which promotes car-diovascular, renal, and lung-protective effects. The ACE2 is not the only route for SARS-CoV-2 to enter the host cells. However, due to its roles in the RAS and its participation in the SARS-CoV-2 virulence, ACE2 has gained attention regarding viral mechanisms of pathogenesis, effects of drugs that interfere with the RAS, and as a potential target for therapeutic strategies for the damages caused by SARS-CoV-2 infection. Among other tissues, ACE2 gene expression seems to be in-creased in the lungs upon SARS-CoV-2 infection;however, amid other variables, expression and/or activity of ACE2 is shown as a disease, sex, and age-dependent. The present review covers critical aspects for a comprehensive understanding of ACE2 and its current involvement in SARS-CoV-2 infection and the development of COVID-19.Copyright © 2021 Bentham Science Publishers.
ABSTRACT
Purpose: COVID-19 therapies have evolved over time, but little is known regarding outcomes in SOT recipients treated with newer therapeutic agents such as remdesivir, dexamethasone, and convalescent plasma. We sought to compare outcomes including mortality, rejection, and renal function in a retrospective cohort of SOT recipients with COVID-19 treated during two different eras of therapy. Methods: 40 SOT recipients hospitalized for COVID-19 at our center comprised Era 1 (Mar-May 2020, 20 patients) and Era 2 (Jun-Aug 2020, 20 patients). Data were collected on demographics, comorbidities, renal function, and mortality at time points out to 90 days after COVID-19 infection. Results: Patients in Era 1 received hydroxychloroquine (11/20, 55%), tocilizumab (5/20, 25%) and/or convalescent plasma (3/20, 15%) as targeted therapy;patients in Era 2 received primarily remdesivir (8/20, 40%), dexamethasone (6/20, 30%), and/or convalescent plasma (13/20, 65%). Mortality was 1/20 in Era 1 and 0/20 in Era 2. MMF was held in 33/35 (94%) of patients. Acute kidney injury was present on presentation in 14/40 (35%). The median (IQR) decrease in SCr (mg/dl) between admission and last followup was 0.5 (0.4-0.6) and 0.1 (0-0.4) in patients who had and had not received remdesivir, respectively (p=0.02), 0.5 (0.1-0.6) and 0.1 (0-0.3) in patients who had and had not received plasma, respectively (p=0.09). Antibodymediated rejection (AMR) occurred in 2 patients in Era 1 and 0 patients in Era 2. Acute cellular rejection (ACR) occurred in 1 patient in Era 1 and 0 patients in Era 2. Conclusions: SOT recipients treated in Era 2, when the major targeted therapies were remdesivir, dexamethasone, and convalescent plasma, were not at higher risk for renal dysfunction, ACR, or AMR in the aftermath of COVID-19;rejection was uncommon in both eras and mortality was low in both eras. While awaiting detailed safety studies, these results suggest against renal toxicity or triggering of alloimunity in those receiving newer therapies.