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<b><i>Aim:</i></b> Several studies reported the accompaniment of severe COVID-19 with comorbidities. However, there is not a systematic evaluation of all aspects of this association. Therefore, this meta-analysis aimed to assess the association between all underlying comorbidities in COVID-19 infection severity. <b><i>Methods:</i></b> Electronic literature search was performed via scientific search engines. After the removal of duplicates and selection of articles of interest, 28 studies were included. A fixed-effects model was used; however, if heterogeneity was high (<i>I</i>² &#x3e; 50%) a random-effects model was applied to combine the data. <b><i>Results:</i></b> A total of 6,270 individuals were assessed (1,615 severe and 4,655 non-severe patients). The median age was 63 (95% confidence interval [CI]: 49–74) and 47 (95% CI: 19–63) years in the severe and non-severe groups, respectively. Moreover, about 41% of patients had comorbidities. Severity was higher in patients with a history of cerebrovascular disease: OR 4.85 (95% CI: 3.11–7.57). The odds of being in a severe group increase by 4.81 (95% CI: 3.43–6.74) for a history of cardiovascular disease (CVD). This was 4.19 (95% CI: 2.84–6.19) for chronic lung disease and 3.18, 95% CI: 2.09–4.82 for cancer. The odds ratios of diabetes and hypertension were 2.61 (95% CI: 2.02–3.3) and 2.37 (95% CI: 1.80–3.13), respectively. <b><i>Conclusions:</i></b> The presence of comorbidities is associated with severity of COVID-19 infection. The strongest association was observed for cerebrovascular disease, followed by CVD, chronic lung disease, cancer, diabetes, and hypertension.

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Cancer is the second cause of death. Association of diabetes as a growing and costly disease with cancer is a major health concern. Meanwhile, preexisting diabetes is associated with an increased risk of all-cause and cancer-specific mortalities. Presence of diabetes related comorbidities, poorer response to cancer treatment, and excess mortality related to diabetes are among the most important explanations. Although diabetes appear to be a risk factor for cancer and is associated with the mortality risk in cancer patients, several factors such as diabetes duration, multiple drug therapy, and the presence of diabetes comorbidities make the assessment of the effect of diabetes treatment on cancer risk and mortality difficult. Metformin is the drug of choice for the treatment of type 2 diabetes. The available evidence from basic science, clinical, and population-based research supports the anticancer effect of metformin. However, randomized controlled clinical trials do not provide enough evidence for a strong protective effect of metformin on cancer incidence or mortality. One of the most important limitations of these trials is the short duration of the followup. Further long-term randomized controlled clinical trials specifically designed to determine metformin effect on cancer risk are needed to provide the best answer to this challenge.