COVID-19 and Preexisting Comorbidities: Risks, Synergies, and Clinical Outcomes

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its associated symptoms, named coronavirus disease 2019 (COVID-19), have rapidly spread worldwide, resulting in the declaration of a pandemic. When several countries began enacting quarantine and lockdown policies, the pandemic as it is now known truly began. While most patients have minimal symptoms, approximately 20% of verified subjects are suffering from serious medical consequences. Co-existing diseases, such as cardiovascular disease, cancer, diabetes, and others, have been shown to make patients more vulnerable to severe outcomes from COVID-19 by modulating host-viral interactions and immune responses, causing severe infection and mortality. In this review, we outline the putative signaling pathways at the interface of COVID-19 and several diseases, emphasizing the clinical and molecular implications of concurring diseases in COVID-19 clinical outcomes. As evidence is limited on co-existing diseases and COVID-19, most findings are preliminary, and further research is required for optimal management of patients with comorbidities.

Keywords: COVID-19; cancer; cardiovascular disease; coronavirus disease 2019; diabetes; immune responses; treatment implications.

Figure 1

Mechanisms that may contribute to diabetes patients’ higher sensitivity to coronavirus illness (COVID-19). Following aerosolized absorption of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), SARS-CoV-2 infects the respiratory epithelium and other target cells by attaching to angiotensin-converting enzyme 2 (ACE-2) on their surface. Higher ACE-2 expression (as an adaptive response to elevated angiotensin-II levels) may support more efficient cell attachment and entrance into cells. Diabetes mellitus impairs early neutrophil and macrophage recruiting and function. In diabetes mellitus, a delay in the onset of adaptive immunity and dysregulation of the cytokine response can involve the onset of cytokine storm. (Patients with diabetes mellitus are likely to have suppressed antiviral IFN responses, and the delayed activity of Th1/Th17 may contribute to heightened inflammatory responses).

Figure 2

(A) Adipose tissue expresses the receptors ACE-2, Dipeptidyl peptidase-4 (DPP4), and CD147, as well as protease furin, following the entrance of SARS-CoV-2. The expression of these proteins is elevated in obese adipose tissues, and ACE-2 and DPP4 production in the circulation of obese people is increased. Patterns of COVID-19 morbidity and severity may be influenced by the expression of mentioned proteins, which are meaningfully associated with body mass index (BMI). (B) The mechanism affecting clinical outcomes and leading to poor prognosis in obese COVID-19 patients. A population of three anti-inflammatory cell types associated with proper adipose activity can be found in normal adipose tissue. Negative regulators of inflammation include T helper (Th2) cells, M-2 macrophages, and regulatory T cells (Treg). Obesity is linked to changes in the number and diversity of immune cells in the adipose tissues, including a considerable drop in Th2 cells, Treg cells, and M-2 macrophages. Conversely, the number of pro-inflammatory cells, such as CD8+ T cells and M-1 macrophages, has increased significantly. More than 40% of M-1 macrophages are found in obese, inflamed adipose tissue, which produce a variety of pro-inflammatory cytokines that cause local and systemic inflammation. Other cell types that release pro-inflammatory elements, such as neutrophils, dendritic cells, and mast cells, also contribute to inflammatory process.