INTRODUCTION

Coronavirus disease 2019 (COVID-19) is a recently-discovered infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus that has quickly become a global pandemic. As of the writing of this report, more than 3 million cases and nearly 250 000 deaths have been documented. However, the epidemiology of the disease is still being studied, and much more information is required to establish adequate measures for its prevention and control, especially among patients vulnerable to severe disease (pneumonia) or death [1].

Several studies have demonstrated higher frequencies of severe cases and mortality among COVID-19 patients with underlying comorbidities, such as diabetes, high blood pressure (HBP), obesity, and cardiovascular disease (CVD), relative to patients without comorbidities [2,3]. Although the causal mechanisms by which chronic conditions increase the risk of COVID-19 severity and mortality are still being studied, it has been postulated that patients with HBP and diabetes have an increased susceptibility of severe SARS-CoV-2 infection [4,5]. It has also been proposed that SARS-CoV-2 infection may cause or worsen endotheliitis, which can further affect the condition of people with previous endothelial dysfunction, such as those with obesity, diabetes, HBP, and other CVDs [5]. This raises the question of how multimorbidity—the presence of 2 or more chronic comorbidities—may influence disease severity and mortality in patients with SARS-CoV-2 infection.

Mexico has one of the highest COVID-19 mortality rates among Latin American countries. As of May 18, 2020, more than 20 000 confirmed cases and 2154 deaths attributed to COVID-19 had been reported in Mexico [1]. The potential associations of multimorbidity with disease severity and mortality in COVID-19 patients have received special attention in Mexico, as it is one of the Latin American countries with the highest prevalence of chronic conditions; 19.0-25.5% of Mexican adults have HBP, 10.0% have diabetes, and 28.0% are obese [6,7]. To date, only 1 peer-reviewed study, conducted in China, has reported a higher combined risk of admission to intensive care, intubation, or death in patients with multimorbidity compared to those without multimorbidity [8]. However, this association has not been studied in Latin America, and pneumonia and death have not been considered as separate outcomes.

The epidemiological surveillance system of the Secretaría de Salud de México collects information regarding the characteristics and comorbidities of diagnosed COVID-19 cases, as well as their clinical course and outcomes. The government of Mexico has released these data. In this study, we aimed to identify the chronic conditions and multimorbidity patterns present among COVID-19 patients and to examine their associations with pneumonia and death. Our results could help facilitate better understanding and decision-making regarding the identification of groups at relatively high risk of severe illness and death due to COVID-19 and the implementation of preventative measures affecting these groups.

METHODS

Study Design and Data Source

A cross-sectional study was performed to analyze the publicly available data of patients with COVID-19 diagnosed via reverse transcription-polymerase chain reaction (RT-PCR). These data were released by the Secretaría de Salud de México and covered the period ending on May 18, 2020. Socio-demographic and medical data (regarding date of disease onset, disease duration, epidemiological profile, presence of chronic conditions, molecular diagnostic test result, and vital status), were collected by physicians using an epidemiological COVID-19 case report form in suspected COVID-19 patients. These data were systematized using an epidemiological surveillance system and are available at https://www.gob.mx/salud/documentos/datos-abiertos-152127.

Study Variables

The dependent variables were pneumonia and death in patients with COVID-19. Eight comorbidities were included as independent variables: HBP, diabetes, obesity, asthma, immunosuppression, other CVDs, chronic obstructive pulmonary disease (COPD), and chronic kidney disease. The chronic conditions included in the analysis corresponded to the conditions reported as associated with COVID-19 in the literature [9-15] and the availability of the relevant information in the patient data. A simple count of the 8 comorbidities was used to classify participants into 4 categories: no comorbidity, 1 comorbidity, 2 comorbidities, or 3 or more comorbidities. Likewise, the 3 most frequent comorbidities (HBP, diabetes, and obesity) were classified into dyads. The presence of ≥2 of the 8 reported comorbidities was considered to indicate multimorbidity.

Statistical Analysis

The variables of interest were presented as frequencies and percentages for the categorical variables and as means and standard deviations for the continuous variables. The frequencies of pneumonia and death were presented according to the characteristics and comorbidities evaluated and stratified by sex. Simple logistic regression models were applied to measure the associations of the independent variables with pneumonia and death in patients with COVID-19. The chronic conditions that were found to be associated with pneumonia or death (p<0.05) in the simple logistic regression analysis were included in two adjusted logistic regression models. The covariables included in the adjusted models were age (continuous), gender (men/women), and smoking status (yes/no). The results were expressed as odds ratios (ORs) and adjusted odds ratios (aORs) with 95% confidence intervals (CIs) for both models. Based on the adjusted models, the marginal effects were estimated along with their 95% CI, and the probabilities of pneumonia and death according to the number of comorbidities for each year of age were graphed.

Statistical analysis was performed using Stata version 14 (StataCorp., College Station, TX, USA). For all analyses, a p-value <0.05 was considered statistically significant.

Ethics Statement

As an analysis of secondary data, this study did not require the approval of an institutional ethics committee. The data are publicly available on the platform of the Secretaría de Salud de México under the Mexican open data policy intended to facilitate the access, use, reuse, and redistribution of information.

RESULTS

Complete data regarding the study variables were available for 51 053 patients with COVID-19, and these patients were included in the analysis. A total of 580 patients were excluded due to incomplete data. Of the included patients, 29 422 were men (57.6%). The overall mean age was 46.6±15.8 years (men, 47.1±15.7 years; women, 45.8±16.0 years). The mean disease duration was 4.2±3.3 days. A total of 14 684 (28.8%) patients presented with pneumonia (men, 32.5%; women, 23.7%).

Regarding the presence of chronic conditions, 27 667 (54.2%) of the participants had no comorbidities, while 13 652 (26.7%) presented 1 chronic condition. Multimorbidity was present in 9734 (19.1%) of the patients, with the presence of 2 (n=6518, 12.8%) and 3 (n=2490, 4.9%) comorbidities being the most common. The largest number of simultaneous chronic conditions was 8 (14 patients) (Table 1).

The results included 5233 (10.3%) deaths (men, 12.1%; women, 7.7%), with a mean time from disease onset to death of 10.6±6.5 days (Table 1). Regarding age group, pneumonia was reported in more than 50% of the people in the 65-74 (50.3%), 75-84 (53.7%), and 85 or older (51.4%) age groups, while the greatest frequencies of death were found in the 65- 74 (27.1%), 75-84 (29.1%), and 85 or older (31.3%) age groups (Table 2). In the adjusted logistic regression model, across the entire study population, it was found that chronic conditions such as HBP, diabetes, obesity, immunosuppression, other CVDs, COPD, and chronic kidney disease were associated with an increased risk of pneumonia. In men, other CVDs and COPD were not found to be associated with pneumonia. Likewise, across the study population, chronic conditions such as HBP, diabetes, obesity, immunosuppression, other CVDs, COPD, and chronic kidney disease were associated with an increased probability of death (Table 3).

A significant incremental gradient was observed for the association between multimorbidity and pneumonia in the general population (p<0.001), with the presence of 1 (aOR, 1.68; 95% CI, 1.60 to 1.77), 2 (aOR, 2.07; 95% CI, 1.95 to 2.20), and 3 or more chronic conditions (aOR, 2.40; 95% CI, 2.22 to 2.60) associated with a progressively increasing probability of this outcome. Likewise, across the study population, a significant incremental gradient (p<0.001) was found for the relationship between multimorbidity and death, in which the presence of 1 (aOR, 1.89; 95% CI, 1.75 to 2.04), 2 (aOR, 2.51; 95% CI, 2.30 to 2.73), and 3 or more chronic conditions (aOR, 3.49; 95% CI, 3.15 to 3.86) were associated with an increased probability of death among the patients. These gradients demonstrating higher probabilities of pneumonia and death in patients with more chronic conditions were also present in both men and women and were statistically significant (Table 4).

Figure 1 shows the marginal effects of age and number of comorbidities on the probabilities of pneumonia and death. The probabilities of both pneumonia and death increased with the number of comorbidities and age.

DISCUSSION

In this study, we sought to identify patterns of chronic conditions and multimorbidity and to evaluate their associations with pneumonia and death in Mexican patients with COVID-19. Chronic conditions such as HBP, diabetes, obesity, other CVDs, and chronic kidney disease were found to increase the likelihood of pneumonia. Likewise, HBP, diabetes, obesity, immunosuppression, COPD, and chronic kidney disease increased the probability of death in patients with COVID-19. Regarding multimorbidity, a greater number of chronic conditions was found to be associated with an increased probability of death or pneumonia among the study sample.

In the present study, an association was found between chronic conditions and pneumonia in patients with COVID-19. An early report from Wuhan, China, noted that about half of a sample of patients who were hospitalized for SARS-CoV-2 pneumonia had an additional medical condition. The most common comorbidities were HBP, diabetes, CVDs, and malignancies, which (except for malignancies) coincide with the most frequent conditions found in the Mexican population with COVID-19. Likewise, in the study from Wuhan, these conditions were associated with the presence of pneumonia [2]. Furthermore, the Centers for Disease Control and Prevention in the United States reported that people with serious medical conditions such as asthma (moderate to severe), COPD, diabetes, CVDs, kidney diseases, severe obesity, immunosuppression, and liver diseases have a greater probability of developing severe forms of COVID-19, including pneumonia [15]. It has been postulated that the development and severity of pneumonia may be influenced by the use of antihypertensive medication, commonly prescribed to patients with HBP and diabetes. These medications may lead to elevated lung tissue concentrations of angiotensin-converting enzyme 2, which acts as the receptor for the entry of SARS-CoV-2 [16,17]. However, other authors have reported that elevated angiotensinconverting enzyme 2 levels are not associated with an increased risk of pneumonia [18]. This suggests the need for further study of the influence of chronic conditions on the development of COVID-19.

Regarding multimorbidity and pneumonia in patients with COVID-19, the probability of developing pneumonia was found to increase as the number of chronic conditions increased. COVID-19 patients with comorbidities have been reported to exhibit a worse response to treatment than patients without comorbidities [19]. HBP and respiratory and CVDs are associated with a relatively severe presentation of COVID-19, including the development of pneumonia [20-22]. Likewise, greater patient age is associated with the development of pneumonia and the severe presentation of COVID-19 [23]. The presence of multimorbidity among adults (particularly older adults) impacts the physical and mental health of this group, particularly in lowincome and middle-income countries [24]. This affects the response capacity to treatment in these patients.

An association was found between the presence of chronic conditions and death in patients with COVID-19. In China, a higher frequency of COVID-19 infection and a greater lethality of the disease have been reported among patients with HBP [4,13,20,24]. Diabetes has also been described as one of the most common chronic conditions in patients with COVID-19, especially among those in the intensive care unit or with severe forms of the disease [12,19,25]. Obesity is another chronic condition associated with increased mortality risk due to challenges in the management of obese patients in relation to positioning, mobilization, and intubation [26,27]. Regarding immunosuppression, the host immunological response to SARSCoV-2 infection and its relationship with the pathophysiology and prognosis of the disease is still under study [28,29]. It has been reported that patients with COPD have an increased risk of developing severe forms of illness, possibly due to alterations in the inflammatory response, immunological and microbiome imbalances, and the use of corticosteroids, among other factors [30]. Chronic kidney disease has also been described as a chronic condition associated with a greater risk of severe manifestation of COVID-19 and death [8,31,32].

With respect to the relationship between multimorbidity and death in patients with COVID-19, an incrementally higher probability of death was observed among patients with more chronic conditions. The prevalence of multimorbidity increases with age [33]. In addition, it has been reported that older adults who have 2 or more comorbidities have a higher mortality rate than adults who do not [33,34]. The case series on COVID-19 published to date describe greater disease severity and a higher risk of death among older patients, particularly the most elderly [11,14]. In Mexico, the presence of multimorbidity in adults has been described as a predictor of quality of life and all-cause mortality [35]. Mexico has a significant burden of disease due to chronic diseases; in 2016, 80% of deaths were attributable to chronic conditions [6]. This high rate of deaths due to chronic diseases corresponds to the high prevalence of chronic conditions in the Mexican population, among which 25.5% of individuals have HBP [7], and 28% of adults are obese [6]. Given that multimorbidity can increase the risk of death due to COVID-19, in countries like Mexico, which have a high burden of disease due to these conditions, it is necessary to develop strategies to mitigate the spread of this disease in these population subgroups to decrease the impact of COVID-19 on health systems.

This study was not without limitations. The data analyzed were secondary in nature, and the accuracy of the data therefore, cannot be guaranteed. Additionally, the cases analyzed included only patients diagnosed with COVID-19 via RT-PCR, and thus, false-negative results of the RT-PCR test would not have been included in the analysis. In addition, bias may have been introduced insofar as the process of obtaining and handling of the sample influenced the results of the diagnostic test. Another possible source of bias stems from the fact that patients with asymptomatic or mildly symptomatic COVID-19 who did not seek medical attention would not have been included among the cases analyzed. Despite the limitations inherent to the information source, the use of a large dataset that includes all COVID-19 cases identified with molecular diagnostic tests and collected officially by the government of Mexico is useful for the initial study of the relationship between multimorbidity and COVID-19, bearing in mind the high burden of disease due to chronic conditions in Mexico.

In conclusion, several chronic conditions are associated with the development of pneumonia and death in Mexican patients with COVID-19. Additionally, an increase in the number of simultaneous chronic conditions was found to be associated with increased risk of pneumonia and death among these patients. These findings may be useful in the effort by decisionmakers to develop strategies to prevent COVID-19 in vulnerable subgroups, such as people with comorbidities. According to reports from different sources, patients with chronic conditions have a greater risk of COVID-19 than patients without such conditions. Hence, additional research is necessary to understand and deepen the study of the pathophysiological processes that determine this association, and this research is particularly important due to the high burden of chronic disease in various Latin American countries, including Mexico.

ACKNOWLEDGEMENTS

Notes

CONFLICT OF INTEREST

The authors have no conflicts of interest associated with the material presented in this paper.

FUNDING

None.

Notes

AUTHOR CONTRIBUTIONS

Conceptualization: AHV, DA. Data curation: AHV, RVF. Formal analysis: AHV, RVF. Funding acquisition: None. Methodology: AHV. Visualization: AHV. Writing – original draft: GBQ, DA, RVF, AHV. Writing – review & editing: GBQ, DA, RVF, AHV.

Figure. 1.

Marginal effects of age (in years) and number of comorbidities on the probabilities of (A) pneumonia or (B) death in the Mexican population with coronavirus disease 2019 (COVID-19).

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Figure & Data

References

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