COVID-19, COPD, and AECOPD: Immunological, Epidemiological, and Clinical Aspects

Abstract

The newly identified severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) causes several heterogeneous clinical conditions collectively known as Coronavirus disease-19 (COVID-19). Older patients with significant cardiovascular conditions and chronic obstructive pulmonary disease (COPD) are predisposed to a more severe disease complicated with acute respiratory distress syndrome (ARDS), which is associated with high morbidity and mortality. COPD is associated with increased susceptibility to respiratory infections, and viruses are among the top causes of acute exacerbations of COPD (AECOPD). Thus, COVID-19 could represent the ultimate cause of AECOPD. This review will examine the pathobiological processes underlying SARS-CoV-2 infection, including the effects of cigarette smoke and COPD on the immune system and vascular endothelium, and the known effects of cigarette smoke on the onset and progression of COVID-19. We will also review the epidemiological data on COVID-19 prevalence and outcome in patients with COPD and analyze the pathobiological and clinical features of SARS-CoV-2 infection in the context of other known viral causes of AECOPD. Overall, SARS-CoV-2 shares common pathobiological and clinical features with other viral agents responsible for increased morbidity, thus representing a novel cause of AECOPD with the potential for a more long-term adverse impact. Longitudinal studies aimed at COPD patients surviving COVID-19 are needed to identify therapeutic targets for SARS-CoV2 and prevent the disease's burden in this vulnerable population.

Keywords: COPD; COVID-19; SARS-CoV-2; cigarette smoke (CS); endothelium; therapy.

Figure 1

There is a gradient of ACE2 expression throughout the respiratory tract. The highest ACE2 expression is found in the nasal epithelium followed by the larger airway epithelium, waning in the more distal bronchiolar and alveolar lung regions, in particular ciliated and secretory club cells, and alveolar type II (AT-II) cells. Cigarette smoke induces a loss of club cells and AT-II cells and extensive hyperplasia of goblet cells, but whether this is associated with increased susceptibility to SARS-CoV-2 infection is unclear. Additionally, cigarette smoke induces increases in the numbers of alveolar macrophages, that are the main cells expressing proteinases, and upregulates B cells, cytotoxic CD8⁺ T cells often with an exhausted phenotype, while downregulating the T regulatory cell compartment. This chronic impairment of the innate and acquired immune responses results in delayed viral clearance, enhanced mucus production, impaired antimicrobial peptide secretion, and increased pulmonary bacterial load during virus-induced exacerbations and possibly during SARS-CoV-2 infection.