The Adrenal Cortex, an Underestimated Site of SARS-CoV-2 Infection.

Yanfei Mao,Lai Jiang,Rongrong Ren,Bo Xu,Yuan Gao,Dunfeng Xu,Feng Li,Xiaoyan Zhu,Wenbin Guan

doi:10.3389/fendo.2020.593179

Abstract

BackgroundThe majority of the critically ill patients may have critical illness-related corticosteroid insufficiency (CIRCI). The therapeutic effect of dexamethasone may be related to its ability to improve cortical function. Recent study showed that dexamethasone can reduce COVID-19 deaths by up to one third in critically ill patients. The aim of this article is to investigate whether SARS-CoV-2 can attack the adrenal cortex to aggravate the relative adrenal insufficiency.MethodsWe summarized the clinical features of COVID-19 reported in currently available observational studies. ACE2 and TMPRSS2 expression was examined in human adrenal glands by immunohistochemical staining. We retrospectively analyzed serum cortisol levels in critically ill patients with or without COVID-19.ResultsHigh percentage of critically ill patients with SARS-COV-2 infection in the study were treated with vasopressors. ACE2 receptor and TMPRSS2 serine protease were colocalized in adrenocortical cells in zona fasciculata and zona reticularis. We collected plasma cortisol concentrations in nine critically ill patients with COVID-19. The cortisol levels of critically ill patients with COVID-19 were lower than those in non-COVID-19 critically ill group. Six of the nine COVID-19 critically ill patients had random plasma cortisol concentrations below 10 µg/dl, which met the criteria for the diagnosis of CIRCI.ConclusionWe demonstrate that ACE2 and TMPRSS2 are colocalized in adrenocortical cells, and that the cortisol levels are lower in critically ill patients with COVID-19 as compared to those of non-COVID-19 critically ill patients. Based on our findings, we recommend measuring plasma cortisol level to guide hormonal therapy.

Highlights

In December 2019, Wuhan, the capital of Hubei province in China, became the centre of an outbreak of severe respiratory illness caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which was later designated coronavirus disease 2019 (COVID-19) by WHO [1]
Of these 5 clinical studies on critically ill COVID-19 patients, 2 articles reported both critically ill patients and mildly ill patients, and the patients were subgrouped according to the severity of their condition [5, 13]
Six of the nine COVID-19 critically ill patients had plasma cortisol concentrations below 10 μg/dl, which met the criteria for the diagnosis of corticosteroid insufficiency (CIRCI) [21]

Summary

Introduction

In December 2019, Wuhan, the capital of Hubei province in China, became the centre of an outbreak of severe respiratory illness caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which was later designated coronavirus disease 2019 (COVID-19) by WHO [1]. COVID-19 that has a high sequence similarity (~80%) with SARS-CoV, triggered a global pandemic of novel COVID19-infected pneumonia (NCIP) [2, 3]. In addition to the typical symptoms of severe viral pneumonia, critically ill patients suffer from acute kidney injury, acute cardiac injury, as well as multiple organ failure [5, 6]. ACE2 expression is not limited to the lung, and extrapulmonary expression of ACE2 is found in heart, vessels, kidney and digestive systems, which may contribute to the non-respiratory symptoms observed in NCIP patients [9]. Recent study showed that dexamethasone can reduce COVID-19 deaths by up to one third in critically ill patients. The aim of this article is to investigate whether SARS-CoV-2 can attack the adrenal cortex to aggravate the relative adrenal insufficiency

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