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Table of Contents
ORIGINAL ARTICLE
Year : 2021  |  Volume : 9  |  Issue : 4  |  Page : 233-238

Study of impact of comorbidities on patients with COVID-19 infection


Department of General Medicine, Bangalore Medical College and Research Institute, Bengaluru, Karnataka, India

Date of Submission02-Jul-2021
Date of Decision08-Aug-2021
Date of Acceptance11-Aug-2021
Date of Web Publication20-Oct-2021

Correspondence Address:
Dr. Avinash Hannabe Rajanna
Department of General Medicine, Bangalore Medical College and Research Institute, Bengaluru, Karnataka
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ajim.ajim_69_21

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  Abstract 


Aim: To study the impact of comorbidities on patients with COVID-19 infection. Materials and Methods: A single center, cross-sectional, observational study was conducted among SARS-CoV-2 infected patients from March 2020 to July 2020. The diagnosis was confirmed by real-time polymerase chain reaction. Various comorbidities were studied to know the treatment outcomes and mortality risk in COVID-19 positive patients. Results: A total of 1977 COVID-19 patients were studied. The mean age was 43.89 ± 15.58 years and had male preponderance of 61.56% of the total subjects. Death rates increased linearly with age in decades with highest fatality rate among those who are aged more than 70 years (21.9%). Among those who died, 73 (52.9%) had both hypertension and diabetes associated with microvascular or macrovascular complications. The overall case fatality rate (CFR) among patients with comorbidities was 12.38%. Among subgroup of comorbidities, Chronic kidney disease (CKD) patients had highest CFR (32%) followed by patients with both hypertension and diabetes (17.5%). Delayed viral clearance is seen in patients with diabetes (33.3%). Conclusion: COVID-19 infection seems to cause high mortality in older individuals (>50 years) with male preponderance. Patients with diabetes and hypertension associated with microvascular or macrovascular complications and CKD patients are at increased risk of disease severity and mortality. Recovery time is also increased in patients with comorbidities mainly diabetes mellitus.

Keywords: Case fatality rate, comorbidity, COVID-19 infection, viral clearance


How to cite this article:
Rohith M G, Monika N, Rajanna AH, Ravi K. Study of impact of comorbidities on patients with COVID-19 infection. APIK J Int Med 2021;9:233-8

How to cite this URL:
Rohith M G, Monika N, Rajanna AH, Ravi K. Study of impact of comorbidities on patients with COVID-19 infection. APIK J Int Med [serial online] 2021 [cited 2021 Nov 29];9:233-8. Available from: https://www.ajim.in/text.asp?2021/9/4/233/328680




  Introduction Top


COVID-19 infection which was first reported as a cluster of pneumonia from Wuhan, China, in December 2019, has rapidly emerged as a global pandemic and has endangered human lives.[1] During the early course of the pandemic, Italy had the highest infection burden and India remained much less affected with corresponding mortality rates of 14.24% and 3.03%.[2] However, the recent trends from the country show an exponential increase in daily spike, and the total cases have crossed 20 million mark according to the Health Ministry data published on May 15, 2021.[3] The officially confirmed deaths from the disease are around 266,207.

This condition is associated with high morbidity, leading to significant burden on health-care infrastructure and resources. The associated fatality rate is also higher than other respiratory viral infections. Hence, it is necessary to identify reliable predictors of disease severity and mortality for careful allocation of health-care resources and to enable earlier clinical intervention to improve clinical outcomes.

The immune system plays an important role in disease severity. A combination of underlying comorbidities such as hypertension, diabetes, obesity, cardiovascular, and chronic renal diseases contribute to disease severity by upregulation of angiotensin-converting enzyme (ACE-2) receptor, immune system dysfunction and also by causing alveolar and endothelial dysfunction.[4] The most common comorbidities reported till date include hypertension, cardiovascular diseases, and diabetes mellitus and these patients are most prone to develop acute respiratory distress syndrome (ARDS), severe pneumonia, and multiorgan failure.[5],[6]

Hence understanding the disease severity among patients with underlying comorbidities will help policy makers to design a better preventive plan and treatment guidelines. In this study, we assessed the impact of various comorbidities on severity and mortality among COVID-19-positive patients.


  Materials and Methods Top


This was an observational cross-sectional, study conducted among patients admitted under medicine department between March 2020 and July 2020 at Victoria hospital, Bangalore Medical College and Research Institute, Bangalore, Karnataka, India. Approval and clearance were obtained from the institutional ethics committee on April 18, 2020-BMCRI/PS/02/2020-21. The study included all the patients aged ≥18 years of both the gender, diagnosed with COVID-19 infection by real-time polymerase chain reaction (RT-PCR) technique using ABI/Thermofisher - TaqPath technique. The study excluded patients <18 years and those not willing to provide signed informed consent before the study.

Sample size estimation:



Where, n = no of sample size

Z(1−α)=1.96 at 95% confidence interval

p = proportion = 19.1%

q = 100 − P = 100 − 19.1 = 80%

d = absolute precision = 2%

on substitution,



n = 1545.19

Therefore the sample size is rounded up to 1600 approx.

Case record form with follow-up chart was used to record the demographic data, and duration and clinical features of the disease. Patients' data such as clinical symptoms, duration of illness, and prevalence and duration of comorbidities such as hypertension, diabetes, renal, cardiac, and respiratory disorders were collected. All the selected participants were followed up until discharge or death. A blood sample was collected from all the patients and sent for laboratory investigations which included complete blood count, renal function test, liver function test, and inflammatory markers such as C-reactive protein, lactate dehydrogenase, serum ferritin, and D-dimer levels. As per the first discharge policy released by the state government, the patients were discharged after 14 days, if 2 consecutive throat/nasopharyngeal swabs taken 24 h apart were negative for SARS-CoV-2 RNA done using RT-PCR technique. If positive, test was repeated after 72 h. As per the revised discharge policy dated May 26, 2020, all mild and asymptomatic patients were discharged only after a repeat RT-PCR technique for SARS-CoV-2 RNA was negative, conducted 7 days after the first test. If positive, test was repeated after 72 h. As per the third discharge policy dated 23 June 2020, patients who had mild and moderate symptoms were discharged after 10 days without throat/nasopharyngeal swab test for COVID-19 and for severe patients, 14th day discharge policy based on negative swab test was adopted and those who were positive, the tests were repeated every 3rd day till obtaining a negative result. The demographics and clinical outcome were further correlated.

Statistical analysis

Statistical analysis was carried out using software R version 3.6.0, 2019 Vienna, Austria. Continuous variables were expressed as means and standard deviation and categorical variables were presented as counts and percentages. Patients were grouped as survival and death. Different parameters were compared between the groups using t-test for continues and chi-square test for categorical data. The optimal cut-off points were estimated for significant continuous variables using receiver operating curve analysis. For evaluating the mean days of viral clearance, many mild and moderate cases were not considered due to the implementation of the revised third discharge policy. P < 0.05 was considered as statistically significant.


  Results Top


The study considered 2000 patients admitted to Victoria hospital, Bangalore under medicine department and was diagnosed positive for COVID-19. Thirty-three patients were referred to different hospitals due to various reasons. Remaining 1977 patients were included in the study. All the patients were categorized as 2 Groups - Group 1: survived (1839–93.02%) and Group 2: succumbed to death (138–6.98%) based on the outcome observed. Among 1977 patients, 1419 (71.78%), 128 (6.48%), and 428 (21.65%) were under 10-day asymptomatic policy, 2nd day swab discharge policy, and 7th day swab policy, respectively. The demographic and clinical characteristics of the patients were studied.

Age distribution

The average age of the patients was 43.89 ± 15.58 years and the mean age of survival and death noted were 42.74 ± 15.15 years and 59.12 ± 12.95 years, respectively [Table 1]. Among patients who succumbed, highest proportion of death was seen in patients aged >50 years, i.e., 79.72%. The mean age of death was almost 15 years higher than the mean age of survival group which was statistically significant. Death rates increased linearly with age in decades with highest fatality rate among those who are aged more than 70 years (21.9%) followed by 60–70-year age group who had case fatality rate (CFR) around 16.8%. The overall CFR for patients aged <50 years was just 2.26%. The CFR increased from 0.2% for those below 30 years to 21.9% for those above 70.
Table 1: Age distribution among the patients

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Sex distribution

Out of 1977 patients, male-to-female ratio was 1:0.62 showing male preponderance as shown in [Figure 1].
Figure 1: Sex distribution among patients

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Symptoms

Fever, dyspnea, and cough were the major symptoms prevalent among patients who succumbed to death than in patients who survived. In the mortality group, only 12% were asymptomatic, whereas it was around 50% among survived subjects, [Table 2]. Deaths among asymptomatic patients were mainly due to non-ARDS causes such as acute coronary syndrome, pulmonary thromboembolism, and acute cerebrovascular events.
Table 2: Symptoms at the time of admission among different groups

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Relation of comorbidities with clinical outcome and mortality

Out of 1977 patients admitted, 1074 (55%) patients did not have any comorbidities. 417 (21.09%) patients had diabetes and hypertension associated with microvascular or macrovascular complications such as cerebrovascular accident, end-stage renal disease, and ischemic heart disease. 118 (5.97%) and 94 (4.75%) patients had diabetes and hypertension, respectively, as the only underlying comorbidity. However, details regarding the type of diabetes and body mass index were not recorded during the patient's stay in the hospital. 25 (1.26%) patients had chronic kidney disease (CKD).

21% of the patients had more than one underlying comorbidity. Majority of the patients had both hypertension and diabetes as the underlying comorbidities. Among those who died, 73 (52.9%) had both hypertension and diabetes complicated by vascular events such as cerebrovascular accident, ischemic heart disease, and end-stage renal disease. Investigations that were done to evaluate these vascular complications included echocardiography, two-dimensional ECHO, fundoscopy, renal function test, and computed tomography in patients with cerebrovascular accidents. Patients with CKD constituted about 1.26% of the total study population and they constituted 5.8% to the total mortality. Furthermore, the mortality rate was comparatively lower (9.42%) among patients with other comorbidities such as chronic obstructive pulmonary disease, chronic liver disease, and malignancy. The overall CFR among patients with comorbidities was 12.38%, i.e., 108 patients succumbed out of 872 patients who had underlying comorbidities. Among the individual subgroups of comorbidities, the CFR was highest for patients with CKD (32%) followed by patients having both diabetes and hypertension with vascular complications (17.5%). Patients with either diabetes or hypertension alone as the underlying comorbidity had similar CFR, i.e., 6.7% and 6.3%, respectively.

Comorbidities of patients included in the study were noted as shown in [Table 3].
Table 3: Comorbidities of patients among different groups

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Based on the number of days required for viral clearance, the subjects were classified as Group 1: <14 days, Group 2: >15–28 days, and Group 3: >28 days. Out of 536 patients who had viral clearance information, 449 (83.77%), 121 (22.58%), and 6 (1.12%) patients were categorized into Groups 1, 2, and 3, respectively [Table 4]. 33.33% of the patients with diabetes took longer duration, i.e., >28 days for viral clearance as opposed to patients with no comorbidities who recovered within 14 days (69.04%) which was statistically significant with P < 0.001 [Table 4].
Table 4: Time required for viral clearance

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Course in the hospital

Out of 1977 patients admitted, 140 patients required oxygen out of which 103 survived and 37 died. Moreover, 264 patients who required ventilatory support in the form of noninvasive ventilation or mechanical ventilation were admitted to intensive care unit (ICU) who had multiple underlying comorbidities such as hypertension, diabetes, and ischemic heart disease. 126 patients survived and 138 patients succumbed to disease [Table 5].
Table 5: Course of patients in the hospital

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  Discussion Top


Age and sex preponderance

In concurrence with these findings, a study conducted by Saluja et al. in Government Medical College, Kota, Rajasthan, has also observed increased male preponderance with majority being asymptomatic.[7] In this study, male-to-female ratio was 1:0.62 showing male preponderance.

The present study has demonstrated that the chances of survival are comparatively lower for patients >50 years of age. The mean age of death was almost 15 years higher than the mean age of survival group. Death rates increased linearly with age in decades with highest fatality rate among aged more than 70 years. There is substantial literature evidence to validate the association between age-related COVID-19 severity and mortality. A meta-analysis and rapid review by Romero Starke et al. have also reiterated the positive associated between increased age-related risk of COVID-19 disease severity, admission to ICU, and mortality. The increased risk per age year noted for disease severity was 2.7%.[8] Similarly, a meta-analysis involving 611,583 subjects has reported that the mortality was <1.1% in subjects aged <50 years, and the largest increase was observed in patients between the age group of 60 and 69 years, as opposed to 50 and 59 years.[9]

Clinical characteristics

The current study has noted fever, dyspnea, and cough as the major symptoms prevalent among patients who succumbed to death when compared to those who survived. Zhang et al. have also evaluated the clinical characteristics of 82 deaths cases, laboratory confirmed as SARS-CoV-2 infection. The researchers have reported fever (78.0%), cough (64.6%), and shortness of breath (63.4%) as the prominent symptoms reported in the succumbed victims which were statistically significant.[10] The study Gupta et al. conducted in a tertiary care center in India has also noted fever and cough (42.9%) as the most prominent symptoms, followed by headache, sore throat, and breathlessness.[11]

Comorbidities and outcome

In the current mortality group, around 53% of the subjects had diabetes and hypertension with complications. A meta-analytic review focusing on developing countries including India has reported that the presence of comorbidities is linked to poor outcomes in COVID-19 subjects. In concurrence with these findings data from Mexico has also identified CKD, hypertension, COPD, obesity, and diabetes are associated with elevated mortality risk in COVID-19 patients.[12] Zhang et al. studied the clinical characteristics of 82 cases of death due to COVID-19 which showed that most of the patients who died had comorbidities, most common being hypertension (56.1%), and more than half of them who died were >60 years old.[10]

A study done in Italy among the COVID-19 patients who died, it was observed that comorbidities such as hypertension (69%), diabetes (31%), ischemic heart disease (27%), atrial fibrillation (21%), and heart failure (16%) contributed majorly to the mortality rate. The highest percentage of association was with hypertension.[13]

The CFR was highest in CKD group (32%) in our study. Similar study done by Menon et al. showed that patients with CKD as the underlying comorbidity had worse prognosis with COVID 19 infection with CFR around 20%.[14]

Our study showed the delayed viral clearance among patients with diabetes. Study conducted by Chen et al. identified hypertension, usage of corticosteroids, male gender, and old age as the factors delaying viral clearance.[15]

Our study identified that patients with diabetes and hypertension associated with complications in the form of microvascular or macrovascular complications had greater mortality compared to the patients without any comorbidities.

Several studies have established older age, diabetes, hypertension, and obesity increase mortality in COVID-19 patients. It is unclear whether diabetes independently contributes to increased mortality and morbidity since it is associated with higher prevalence of cardiovascular diseases.[16],[17]

Possible mechanisms that may contribute to increased susceptibility to infection in patients with diabetes include (1) upregulation of ACE2 receptors resulting in higher affinity for cellular binding and viral entry, (2) delayed viral clearance, (3) impaired T-cell function, and (4) increased susceptibility to cytokine storm syndrome.[15],[16],[18] Furthermore, several hypoglycemic agents and antihypertensives such as glucagon-like peptide agonists, thiazolidinediones, statins, and ACE inhibitors upregulate ACE2 receptors increasing susceptibility to the disease.[19]

The data available regarding the relatively new virus is limited. Patients with comorbidities have more deteriorating outcomes.

Proper identification and care of the patients with comorbidities who are more likely contract disease and develop severe disease should be given importance.

The strength of our study is the availability of viral clearance data, data from very early pandemic, and beginning of first wave of India. However, as the hospitalization criteria were much different than and treatment guidelines are evolving, mortality figures may not represent the current figures. As all patients with positive RT-PCR were admitted including asymptomatic or with mild illness, mortality figures, hospitalization duration, etc., are altered and cannot be compared to data from subsequent period and or second wave. However, this study can be useful for studying and comparing pattern of hospitalization, duration of hospitality, mortality, etc., from subsequent months or year.


  Conclusion Top


COVID-19 infection seems to cause high mortality in older individuals (>50 years) with male preponderance. Patients with diabetes and hypertension associated with microvascular or macrovascular complications and CKD patients are at increased risk of disease severity and mortality. Recovery time is also increased in patients with comorbidities mainly diabetes mellitus. The knowledge of the comorbidities and their impact on the disease can better identify high-risk patients with COVID-19 infection and allow a more specific therapy and better treatment outcomes in those high-risk patients.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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    Figures

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    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]



 

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