The Impact of Pre-existing Comorbidities and Therapeutic Interventions on COVID-19

Abstract

Evidence from the global outbreak of SARS-CoV-2 has clearly demonstrated that individuals with pre-existing comorbidities are at a much greater risk of dying from COVID-19. This is of great concern for individuals living with these conditions, and a major challenge for global healthcare systems and biomedical research. Not all comorbidities confer the same risk, however, many affect the function of the immune system, which in turn directly impacts the response to COVID-19. Furthermore, the myriad of drugs prescribed for these comorbidities can also influence the progression of COVID-19 and limit additional treatment options available for COVID-19. Here, we review immune dysfunction in response to SARS-CoV-2 infection and the impact of pre-existing comorbidities on the development of COVID-19. We explore how underlying disease etiologies and common therapies used to treat these conditions exacerbate COVID-19 progression. Moreover, we discuss the long-term challenges associated with the use of both novel and repurposed therapies for the treatment of COVID-19 in patients with pre-existing comorbidities.

Keywords: COVID-19; SARS-CoV-2; comorbidities; immunology and infectious diseases; inflammation; inflammatory diseases; respiratory disease; virus immunity.

Figure 1

Prevalence of COVID-19 symptoms and complications. Data obtained from a quantitative meta-analysis of 19 studies (19). It's important to note that 87% of all cases analyzed in the meta-analysis were hospitalized cases. Therefore, the proportion of symptoms and complications are representative of this and the overall proportions with regards to all COVID-19 cases will be much lower. The prevalence of anosmia (20) and thromboembolic events (21) were obtained independently from smaller cohorts and may therefore change as more data is published.

Figure 2

Immune response in mild/moderate and severe COVID-19 cases. Mild/moderate COVID-19 is characterized by local inflammation, the recruitment of monocytes, DCs, NK cells, T and B cells, followed by resolution of the infection and inflammation. Severe COVID-19 is characterized by severe lymphopenia, T cell exhaustion, and systemic hyperinflammation that can cause the development of critical and potentially life-threatening complication such as severe pneumonia, ARDS, septic shock, and multiple organ failure (17, 30, 33).

Figure 3

Prevalence of pre-existing comorbidities among hospitalized COVID-19 patients. Prevalence of pre-existing comorbidities determined from an extensive meta-analysis of 76,993 hospitalized COVID-19 patients (1). Hypertension (16%), cardiovascular disease (12.11%), and diabetes (7.87%) were the most prevalent pre-existing co-morbidities. As this data is representative of hospitalized patients, the prevalence of these among mild/moderate cases may be different, and as more data is analyzed these may change.

Figure 4

Current COVID-19 treatment strategies. (1) Novel vaccines and convalescent plasma are being investigated to prevent viral entry. Broad-spectrum antiviral agents that inhibit (2) cell entry via endocytosis, and (3) viral replication through RNA-dependent RNA polymerase (RdRP) and protease inhibition are being repurposed to test efficacy against SARS-CoV-2. Furthermore, (4) immune modulating and anti-inflammatory treatments are being explored to prevent the development of severe COVID-19 development.