This retrospective study identified the type and number of comorbidities associated with a complicated hospital course and increasing risk of death in a large cohort of hospitalized Iranian patients with COVID-19. Patients with DM, HF, CKD, malignancy, and lung disease had significantly higher risks of reaching the composite end-point (ICU admission, invasive mechanical ventilation, or death). Moreover, those with DM and CKD had a significantly escalated risk of death during the hospital course. Considering the number of comorbidities, having two or more comorbidities incrementally increased the risk of death during the hospitalization in patients less than 65 years.
The most prevalent comorbidities in this large cohort of COVID-19 patients were DM, HTN, and CAD. These comorbidities remained the most common underlying diseases in the studies with different sample sizes conducted in various populations [1, 4, 17]. Moreover, meta-analyses of several studies, although most of them had been conducted in china, reported the same findings [18, 19)]. Considering the relatively large sample size, we investigated a spectrum of comorbidities including CKD, HF, CVA, COPD, asthma, chronic liver disease, HIV, and TB. Consistent with the results of previous studies [1, 4, 17], the percentage of patients with these comorbidities was relatively low. This observation could be explained by the facts that such cardio-metabolic diseases as DM, HTN, and CAD are highly prevalent across the world, and they are more likely to be reported by the patients. Furthermore, the observed frequency of comorbidities might also be representative of the transmission of disease within the particular sub-groups.
Similar to the previous studies [17, 20, 21], our findings suggested that comorbidities such as malignancy, lung disease (COPD and asthma), HF, CKD, and DM are associated with a complicated hospital course in patients with COVID-19. However, in this cohort patients with known HTN did not reach the composite end-point. While HTN was associated with a significant greater risk of the same composite end-point in a large cohort of Chinese patients with COVID-19 . This discrepancy might be explained by the fact that no adjustment for other comorbidities was made in this study while we considered all the other co-existence underlying disease such as malignancy, lung disease, HF, CKD, and DM that could confound the results. Moreover, patients in our cohort had well-controlled blood pressure (BP) at the time of admission (with median of 120/80 mmHg). This finding highlighted that poorly controlled BP might complicate the hospital course of COVID-19 patients not merely being known as a hypertensive case. Another meta-analysis that concluded HTN is associated with a greater risk of ICU admission had included studies with relatively low sample size not adjusted for other potential risk factors . Moreover, definition of HTN and the need for ICU admission were different in the included studies .
Survival analysis showed DM and CKD significantly increased the hazard of death during the hospital course. Not only did previous studies indicate DM is associated with an increase in the risk of mortality [22, 23] but also they indicated different levels of blood glucose control impose different outcomes in patients with COVID-19 and preexisting T2DM . Although some studies found an adverse association between CKD and severity of COVID-19 , few investigated the impact of CKD on the death . On the contrary to the study conducted in New York  we found a significant association between CKD and the death in the hospitalized patients, considering all the potential risk factors. This inconsistency might be explained by the fact that the previous study was a single center one that had not included a large number of patients. Moreover, a prospective study, although included a small number of patients with known CKD (2.0%), demonstrated a significant association between kidney disease and in-hospital death .
Although the coexistence of different underlying diseases has been frequently reported in the cohorts of COVID-19- patients [4, 21, 27], a few investigated the impact of coexisting comorbidities on the clinical outcome of COVID-19 . Our study confirmed the coexistence of two or more comorbidities incrementally increased the hazard of the death. However, there was no significant difference in the prognosis of those with one comorbidity compared to the ones without any comorbidity. Considering the strong independent role of age in the complicated hospital course and in-hospital death [14, 25], we performed a sensitivity analysis stratifying the patients according to the age (< 65 vs ≥ 65 years). We found the adverse impact of the coexisting comorbidities on death is considerable in patients less than 65 years. This finding provides some evidence in that fatality of COVID-19 patients more than 65 years is independent of the presence of any comorbidity.
Strengths and limitations
To the best of our knowledge, it was the first multicenter cohort study on Iranian people with COVID-19 exploring the association between a spectrum of comorbidities and a complicated hospital course. Moreover, data on comorbidities were available for more than 90% of the admitted patients. However, this study has several limitations. First, due to the urgency of data extraction, random sampling could not be applied in our study. Second, comorbidities were self-reporting. Under-reporting of comorbidities due to the lack of awareness or diagnostic testing might confound the strength of their association with the clinical outcomes.
In this cohort of Iranian people with COVID-19, the presence of malignancy, lung disease, HF, CKD, and DM were predictors of a complicated hospital course. DM and CKD were also risk factors of in-hospital mortality. Moreover, there is an incremental risk of in-patient mortality with increased burden of comorbidity in hospitalized patients less than 65 years old.