Original Article

Multimorbidity raises the odds of decease in COVID-19 patients: An Iranian prospective study

Introduction

Coronavirus disease 2019 (COVID-19) is a contagious illness that was proclaimed as a pandemic in March 2020.¹ The new disease had a high infection and mortality rate² and among Asian countries, the infection rate in Iran was high.²

COVID-19 can vary from a mild disease with minor symptoms to serious pneumonia and multiorgan failure that cause death. Different comorbidities have been suggested as a factor contributing to severe disease and death from COVID-19.³ Several investigations have illustrated the higher chance of severe disease and pneumonia leading to intensive care, multi-organ failure, and death in patients with underlying comorbidities compared to patients without this situation. The list of common comorbidities in patients resulting in severe disease and hospitalization mainly includes hypertension, high blood sugar, heart disease, respiratory diseases, hepatic diseases, and anemia.^3-8 However, little information is available regarding multimorbidity (patients with two or more underlying diseases) and COVID-19 intensity. In Italy, a higher mortality rate in patients with higher comorbidity scores was reported.⁹ In another study in Mexico, a significant positive relationship was reported between multimorbidity and death.¹⁰ Considering that the rate of noncommunicable diseases was high in Iran,¹¹ we postulated that multimorbidity may affect the rate of death from COVID-19. Thus, we assessed the outcome of multimorbid patients infected with COVID-19 disease so that our results may help to identify the groups that are at high risk of severe illness and death and take preventative actions in this group of patients.

Materials and Methods

We used the East Azar COVID-19 Registry data for this prospective study. The criteria for registering patients in this registry were affirmative reverse transcription-polymerase chain reaction (RT-PCR) test results or lung imaging characteristics. Each patient provided informed consent.

Questionnaires were used to gather demographic and lifestyle-related characteristics. Medical reports were used for collecting clinical laboratory data. On admission, during Obtaining the medical history, the nurses asked the patients or primary next of kin, about the known diagnosis of cardiovascular-related diseases such as high blood pressure, heart attack, coronary revascularization, heart failure, high blood sugar, chronic kidney diseases, chronic pulmonary disease, higher body mass index than 30 kg/m², history of cancers, and hepatic disease.

The participants were followed up until discharged from the hospital or deceased. All information was gathered by expert nurses, and quality was checked by one of the investigators.

The main outcome of this study was studying the relationship between multimorbid conditions and death in patients suffering from COVID-19.

Statistical analysis

We analyzed the collected data by SPSS version 25 (IBM Corporation, NY, USA). We applied the Kolmogorov-Smirnov test the normality of variables. The quantitative variable was stated as the mean (SD), and the qualitative data were shown as frequency (%). The between-group comparisons for constant data were done by independent t-test and for nominal and rank data by chi-square test, with Fisher’s exact test as needed. For examination of the relationship between comorbidities and multimorbidity with mortality from COVID-19, logistic regression was used. Demographic, lifestyle, and on-admission clinical factors that had a significant relationship in the univariate model were entered into the multivariate model. As a result, the odds ratios estimated by the logistic regression were adjusted for age, smoking, and dyspnea. The significant level was considered as a P value < 0.05.

Results

Totally 1842 patients with COVID-19 with a mean age of 63.07 ± 17.22 years were involved. In this investigation, 17.75% (327) of patients were deceased.

Comparison of the baseline characteristics

As presented in Table 1, in contrast to the survivors, the non-survivors were older (P < 0.001) and heavier smokers (P = 0.03). The two groups were almost comparable in terms of the frequency of comorbidities (P > 0.05). Regarding the presence of symptoms on admission, the frequency of hypoxia was significantly higher in non-survivors (52.59%) compared to survivors (30.16%) (P < 0.001).

As can be seen in Table 2, 688 participants (37.40%) had multimorbidity. Cardiometabolic disorders predominantly accounted for the highest number of multimorbidity combinations observed: cardiovascular disease (CVD) and diabetes (287 patients), respiratory diseases and CVD (158 patients), CVD and kidney disease (124 patients), and diabetes and obesity (114 patients).

As depicted in Figure 1, the number of multi-morbidities was higher in older patients (P < 0.05).

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Figure 1.

The multimorbidity status according to age

Figure 1.

The multimorbidity status according to age

As shown in Figure 2, 24.6% of participants with more than four comorbidities died. However, this value was approximately 17% in participants with less than four comorbidities.

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Figure 2.

The rate of mortality in patients with COVID-19 stratified by number of co-morbidities

Figure 2.

The rate of mortality in patients with COVID-19 stratified by number of co-morbidities

Relationship between comorbidities and mortality from COVID-19

Table 3 presents the association between comorbidities and death during attendance in the hospital in patients with COVID-19. The odds of death were 53% greater in patients with diabetes. Additionally, patients with comorbidities ≥ 4 had less chance of survival from COVID-19 (OR: 2.05; 95% CI: 1.21, 3.45). However, no significant correlation was observed between other comorbidities and death in this study.

Discussion

Previously, different investigations showed that comorbidities increase mortality and disease severity in patients with COVID-19.^3,6 Nevertheless, some researches have focused on the relationship between multimorbid conditions and COVID-19 outcomes. The current study result showed that 37.4% of patients with COVID-19 had multimorbidity in Iran. This value is higher than the rate of multimorbidity in Mexico (19.1%).¹⁰ However, it is lower than the reported multimorbidity rate in the UK (43.1%)¹² and the United States (88%).³ The differences in the multimorbidity rate between the studies may be due to the dissimilarities in the age groups of participants. As reported in the present study and a previous study, the rate of multimorbidity increases with age.⁹ In addition, differences in multimorbidity prevalence in the community could also affect the frequency of multimorbidity in patients with COVID-19. In addition, dissimilarities in multimorbidity definition in various studies could also be considered another justification for differences in the multimorbidity rate in various studies.

In line with previous studies, the most prevalent multi-morbidities were related to cardiometabolic conditions.⁶ According to the report of a systematic review, in different studies, high blood pressure, high normal weight, and diabetes were reported as the most prevalent comorbidities in hospitalized COVID-19 patients.¹³ This may be related to impaired immune function and inflammatory response and the type of medications used by patients. For example, most patients with cardiometabolic conditions use angiotensin-converting enzyme (ACE) inhibitors, which increase the expression of the ACE2 receptor, allowing the entrance of SARS-CoV-2 to different cells.¹⁴

Our results indicated higher chance of death in patients with multi-morbidities ≥ 4. Our result was in agreement with the earlier studies’ findings. Iaccarino et al reported a higher death rate in patients with COVID-19 who had higher comorbidity scores.⁹ In another study in Mexico, a significant positive relationship was reported between multimorbidity and death.¹⁰ Although the higher mortality rate due to multimorbidity could partly be attributed to the higher age,¹⁵ in our study, the relationship between multimorbidity and death was still significant even after adjusting the results for age. Therefore, the observed association between multimorbidity and death may be partly due to the higher psychological stress in patients with multimorbidity.¹⁶ On the other hand, COVID-19 is also associated with higher psychological stress.^17,18 Studies have shown that psychological stress is related to a higher mortality rate.¹⁹ In patients with COVID-19, the presence of multimorbidity influences physical and psychological health, mainly in developing countries.²⁰ This influence on the response to treatment in these patients.¹⁰

Higher inflammatory factors in patients with multimorbidity is another mechanism that may support our findings.²¹ Higher rates of mortality in patients with COVID-19 who had higher inflammatory cytokine levels have been reported.^22,23

The present study suffers from some limitations, including using single-center data that bring into question the generalizability. However, the center we collected our data is the focal point for COVID-19 in our region. Besides, our participants were patients who attended the hospital, and we cannot comment on the associations between multimorbidity and mortality in the community.

Conclusion

In conclusion, our finding showed the high rate of multimorbidity in patients with COVID-19 which is also associated with a higher mortality rate in these patients. Therefore, in countries with higher multimorbidity rates, such as Iran, it is essential to design efficient approaches to alleviate the spread of COVID-19 within these specific groups to diminish the influence of COVID-19 on healthcare organizations.

Competing Interests

The authors have no conflicts of interest to declare.

Ethical Approval

The research ethics committee of Tabriz University of Medical Sciences, Iran approved the study (code: IR.TBZMED.REC.1398.1274) and a written informed consent was obtained from all patients.

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