14. Modifiable risk factors and susceptibility to COVID-19
Several modifiable risk factors may be present in cancer patients, which can increase susceptibility to COVID-19 infection and the severity of the disease. Common risk factors include tobacco smoking, obesity, hypertension, and type 2 diabetes (77). Despite the known benefits of smoking cessation even following a cancer diagnosis (78), a large proportion of people will continue to smoke (79). Indeed, one 2017 cross-sectional study with over 26,000 individuals from the United States identified that people diagnosed with smoking-related cancers were more likely to continue smoking post-diagnosis than those diagnosed with non-smoking-related cancers (80). This is a particular concern given that ACE2 receptors are the binding site for the SARS-CoV-2 virus, as mentioned above, and this receptor is upregulated among current smokers (81). Moreover, it has been found that patients with any history of smoking are vulnerable to COVID-19 infection, and are more likely to have a severe case resulting in ICU admission, need for mechanical ventilation, and increased mortality (82).
Although some controversy exists whereby cigarette smoking has been associated with a lower population prevalence of COVID-19 (83), other studies counter these findings suggesting a slight increase in diagnosis (84). There is undoubtedly potential for nicotine to be considered as a therapeutic modality. However, more research is required (85). Nevertheless, the harms of cigarette smoking far outweigh any potential therapeutic benefits associated with continued smoking for active smokers. Therefore, encouraging smoking cessation even following cancer diagnosis will have benefits on cancer treatment and progression and may also reduce the risk of COVID-19 infection and severity.
Similarly, a prospective study of 92 patients from a hospital in Italy evaluated the severity of COVID-19 and obesity classes according to Body Mass Index (BMI), identifying an increased need for mechanical ventilation and access to intensive or semi-intensive care units compared to individuals classified as having normal BMIs (86). Meanwhile, a study of 103 consecutive patients from the United States identified that severe obesity (BMI > 35 kg/m2) was associated with more ICU admissions and invasive mechanical ventilation (87). A 2021 systematic review and meta-analysis compiling evidence across nine studies confirm these findings, with severe COVID-19 patients more likely to have a higher BMI than non-severe patients. Patients with obesity were more likely to be severely affected by the condition and have worse disease progression (88). Although ACE2 expression is higher in adipose tissue than lung tissue, no current evidence suggests that COVID-19 binds directly to adipose tissue (87). It is believed that pro-inflammatory cytokines and adipokines, synthesized by adipose tissue, can weaken the immune response and thus be contributing to this observed link between COVID-19 and obesity (89). It is well established that obesity causes changes in the physiological function of adipose tissue, also leading to insulin resistance and chronic inflammation, and these mechanisms are known to be linked to carcinogenesis and cancer progression (90). Hence, encouraging weight loss among people with obesity may be beneficial in reducing the severity of SARS-CoV-2 infections.