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Table of Contents
ORIGINAL ARTICLE
Year : 2021  |  Volume : 9  |  Issue : 4  |  Page : 221-226

Study of factors associated with COVID-19 mortality in a rural tertiary health care center


1 Department of General Medicine, MVJ Medical College and Research Hospital, Bangalore, Karnataka, India
2 Department of Medicine, MVJ Medical College and Research Hospital, Bangalore, Karnataka, India

Date of Submission22-Mar-2021
Date of Decision12-May-2021
Date of Acceptance19-May-2021
Date of Web Publication20-Oct-2021

Correspondence Address:
Dr. Vasantha Kamath
Department of Medicine, MVJMC and RH, Hoskote, Bengaluru - 56 2114, Karnataka
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ajim.ajim_38_21

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  Abstract 


Background: COVID-19 has swiftly spread to emerge as a global pandemic with no visible signs of decline. It is imperative to identify the parameters contributing toward COVID-19 mortality to facilitate prompt evaluation and control measures. Materials and Methods: A total of 1754 patients with confirmed COVID-19 infection were admitted at MVJMC and RH, Bangalore, from July 1, 2020 to December 12, 2020. Various parameters such as demographical profile, symptomatology, risk factors, laboratory profile, and complications of 75 patients (4.27%) who succumbed were studied. Results: About 45.33% of the patients who died were older than 65 years. 77% of patients who died were males. About 61.33% had severe illness at the time of presentation. 84% of the patients who died had comorbid illnesses. Respiratory failure secondary to acute respiratory distress syndrome and bilateral pneumonia was the leading cause of mortality followed by sepsis/multiple organ dysfunction syndrome, myocarditis, coagulopathy, and acute cardiovascular event. The presence of lymphopenia elevated inflammatory markers, and comorbid conditions were identified as risk factors for the requirement of oxygen, mechanical ventilation, and death. Conclusion: Elderly patients (>65 years of age) and middle-age patients (45–65 years of age) comprised the highest and second-highest proportion of mortality respectively. The increasing proportion of deaths among the middle-aged patients and the narrowing gap of the same between these two groups are alarming. Old age, male gender, underlying chronic illnesses, and elevated inflammatory markers are some of the factors attributed to these trends. Hence, stringent preventive measures, early detection, and initiation of treatment pose a greater impact on reducing the burden of morbidity and mortality.

Keywords: Comorbidities, complications, COVID 19, risk of mortality


How to cite this article:
Teli JG, Reddy S, Kamath V, Jacob M J, Mohan D, Markanday K. Study of factors associated with COVID-19 mortality in a rural tertiary health care center. APIK J Int Med 2021;9:221-6

How to cite this URL:
Teli JG, Reddy S, Kamath V, Jacob M J, Mohan D, Markanday K. Study of factors associated with COVID-19 mortality in a rural tertiary health care center. APIK J Int Med [serial online] 2021 [cited 2021 Nov 29];9:221-6. Available from: https://www.ajim.in/text.asp?2021/9/4/221/328674




  Introduction Top


Coronavirus is a large group of medium-sized enveloped positive-stranded RNA viruses that cause illness in humans and animals. It has now spread to 223 countries worldwide. WHO subsequently declared COVID-19 a pandemic on March 11, 2020. This beta coronavirus pathogen uses the ACE-2 receptor located in many tissues for its access into the host cell.[1] This is the third coronavirus outbreak in the last 20 years after severe acute respiratory syndrome coronavirus 2 (SARS-CoV) and the Middle East respiratory syndrome CoV. COVID-19 has affected more than 122,524,424 cases worldwide with 2,703,620 deaths according to the WHO.[2] There is an unprecedented urgency to understand the vulnerable population at the highest risk for severe outcomes and hence it is imperative to identify the various factors contributing toward COVID-19 infection and mortality numbers to facilitate mitigation and control measures.

Aims

To study the various clinical and laboratory parameters associated with COVID-19 mortality.


  Materials and Methods Top


A total of 1754 patients tested positive for real-time reverse transcription-polymerase chain reaction (RT-PCR) for COVID-19 were admitted at MVJ Medical College and Research Hospital, Bangalore, from July 1, 2020 to December 12, 2020, of which 75 patients (4.27%) succumbed to death. The study design was a retrospective observational study analyzing patients who died due to COVID 19 disease. The confirmed diagnosis of COVID-19 was defined as a positive result by using real-time RT-PCR detection on the nasopharyngeal swab. Clinical data including age at the time of presentation (young <45 years, middle age 45–65 years, and elderly >65 years), demographical profile, symptomatology, risk factors, laboratory profile, and complications were recorded. All patients were subsequently categorized as mild, i.e., patients with uncomplicated upper respiratory tract infection with SpO2: >94% at room air, respiratory rate: <24 cycles per min with no evidence of hypoxemia or breathlessness; moderate, i.e., pneumonia with no signs of severe disease with SpO2: 90%–94% at room air, respiratory rate: 24–30 cycles per min; and severe, i.e., Severe pneumonia with SpO2: <90% room air with respiratory rate: >30 cycles per min and treated according to the standard treatment protocol of Ministry of Health and Family Welfare (MoHFW) 03/06/2020 guidelines.[3]

Statistical methods-The data were entered in Microsoft Excel 2013. The quantitative, qualitative, and categorical variables have been analyzed and the results were expressed in percentages with appropriate tables. Institute Ethical committee approval was obtained before starting the study.


  Results Top


A total of 1754 patients tested positive for real-time PCR for COVID-19 were admitted at MVJMC and RH, Bangalore, from July 1 to December 12, 2020, of which 75 patients (4.27%) succumbed.

Fifty-eight patients (77.33%) were male and 17 (22.66%) female. 11 patients (14.66%) were below the age group of 45 years, 30 patients (40%) belonged to the age group of 45–65 years and 34 patients (45.33%) were above 65 years. Clinical severity was categorized according to the MoHFW June 03, 2020 guidelines.[3] 6 patients (8%) on presentation belonged to the mild category, 23 patients (30.66%) belonged to the moderate category, whereas 46 patients (61.33%) belonged to the severe category [Table 1] and [Table 2]. 4 out of 6 patients of mild progressed to moderate, of which 2 had further progressed to severe and eventually succumbed. The remaining 2 patients died due to multiple organ dysfunction syndrome (MODS) and myocarditis.Ten out of 23 patients of the moderate category at the time of admission eventually progressed to severe and critically ill phase in an average of 5 days. Mild and moderate cases were admitted in the wards, whereas severe cases were admitted in the COVID ICU. Moderate patients were treated with nasal oxygen therapy, whereas severe patients were treated with high flow oxygen therapy and mechanical ventilation.
Table 1: Age, severity distribution among total COVID-19 admissions and fatal cases

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Table 2: Severity and age distribution among

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Symptomatology

Among 75 patients, 66 patients (88%) presented with typical symptoms and 9 (12%) with atypical symptoms, like gastrointestinal, neurological, and cardiovascular presentations. 47 patients (62.66%) presented with dyspnea, 39 (52%) with cough, 23 (30.66%) with sore throat, and 16 (21.33%) with fever. Musculoskeletal symptoms such as malaise, arthralgia, and myalgia were seen in 51 patients (68%). 9 patients (12%) presented with bleeding manifestations in the form of hematuria, dermal and mucosal bleeds. 8 (10.66%) presented with atypical GI manifestations such as nausea, vomiting, hiccups, loss of appetite, watery diarrhea, and pain abdomen. Cardiovascular manifestations such as chest pain and palpitations were seen in 3 patients (4%). Neurological manifestations such as headache, anosmia, and altered sensorium were seen in 3 patients (4%) [Table 3].
Table 3: Various patient characteristics and inflammatory parameters associated with COVID-19 mortality

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Risk factors

63 patients (84%) had comorbidities. The most common was Diabetes mellitus, seen in 42 patients (56%) which was uncontrolled in a majority with an average glycosylated hemoglobin of 9.3%, followed by systemic hypertension seen in 38 (50.66%). 21 patients (28%) had both Diabetes mellitus and systemic hypertension. Other comorbidities such as COPD were seen in 17 (22.66%), chronic kidney disease in 12 (16%), obesity in 12 (16%), cerebrovascular accidents in 9 patients (12%), bronchial asthma in 7 (9.33%), ischemic heart disease in 6 (8%), chronic liver disease in 4 (5.33%), and hypothyroidism in 4 (5.33%). Few patients had multiple comorbidities.

Maximum mortality was seen in patients with co-morbidities in all the categories at presentation. Patients with comorbidities were most commonly in the elderly followed by middle aged and least common in the young [Table 4].
Table 4: Distribution of death cases with comorbidities according to the category at presentation and various age groups

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Laboratory parameters

Anemia was seen in 25 patients (33.33%) with average hemoglobin of 11.9 mg/dl in males and 10.6 mg/dl in females. Thrombocytopenia was seen in 22 patients (29.33%) of which 12% of patients had bleeding manifestations in the form of haematuria, dermal and mucosal bleeds. Incidence was higher in patients aged above 60 years. There was raised NLR ratio with lymphopenia seen in 54 patients (72%). Total leukocyte count was raised in 21 patients (28%). Majority of them were in sepsis eventually progressing to multi-organ failure. Transaminitis was observed in around 19 patients (25.33%), which was transient in majority, lasting on an average for 4 days. Deranged prothrombin time/international normalized ratio/Activated partial thromboplastin time was observed in 14 patients (18.66%). Coagulopathy was seen in 11% of patients. Inflammatory markers were elevated in all the patients though the individual attribution to each marker varied [Table 3].

Deranged renal function parameters were seen in 19 patients, in which 12 patients had baseline derangement, i.e., in chronic kidney disease patients, whereas 7 patients developed during the hospital stay due to acute kidney injury (AKI), among which 3 patients developed acute on chronic kidney disease.

Radiological profile

Baseline chest X-ray of 59 patients (78.66%) was abnormal; majority showing bilateral peripheral nonhomogeneous opacities. 53 patients later developed diffuse pulmonary infiltrates consistent with acute respiratory distress syndrome (ARDS).

High-resolution computed tomography (CT) thorax was performed in 66 patients. The most common finding was ground-glass opacities followed by consolidation. CT severity score was more than 15 out of 25[7] in 42 patients (63.63%), of which 29 patients (69.04%) belonged to the severe category at presentation. Out of the above 29 patients, 17 (58.62%) aged more than 65 years. Higher CT severity scores were associated with increasing age and severity of the illness.

Complications

Type 1 respiratory failure secondary to ARDS and lobar pneumonia (70.66%) remained the leading cause of death followed by sepsis/septic shock and MODS (18.66%). Other complications seen were coagulopathy, AKI, myocarditis, acute cerebrovascular accident, and acute coronary syndrome [Table 3].

Forty-nine out of 53 patients who developed ARDS, 3 patients with acute hemorrhagic stroke and 4 patients with MODS were assisted on ventilator support and 3 out of 7 patients who developed AKI, were initiated on hemodialysis. The average duration of stay on ventilator support was around 7 days, of which 3 patients were successively extubated, but later succumbed due to other complications.

Duration of stay varied from 1 to 29 days with a median of 13 days (The interquartile range = 22 − 10 = 12). Severe category of presentation had a lesser duration of stay comparatively due to early mortality attributed to advanced disease at admission, reduced pulmonary residue/compliance, and increased complications.


  Discussion Top


The high case fatality and symptomatic infection rate among the elderly seen globally were reflected in our study as the maximum proportion of deaths (45.33%) were seen in the elderly age group (>65 years) and 40% in 45–65 years age group. However, the percentages were in contrast to the 80% and 90% of deaths being reported in the elderly in several studies done in Korea and Italy, respectively.[8]

Union Health Ministry of India's October analysis of COVID 19 also noted a similar trend with a percentage distribution of deaths being 53% in those aged above 60 years, 35% in 45–60 years age group, 10% in the age group of 26–44 years and 1% each in the age group of 18–25 and below 17 years.

According to a Dartmouth-led study, COVID-19 is dangerous not only for the elderly but for middle-aged adults with nearly 40% of U.S. COVID-19 deaths occurring among those aged 45–74 years.[9]

Several studies associate the poor disease outcome and vulnerability to an infection in the elderly to poor viral clearance secondary to immunosenescence and inflammaging which alters the innate immunity.[10],[11],[12]

Hence, factors like the higher expression of ACE2 by the ACE2 gene reduced immunity, changes in lung architecture and muscle atrophy, changes in the physiological function, reduction of lung reserve, airway clearance, weak defense barrier function, low organ function, or coexisting comorbidities may account for a greater increase in mortality with age.[13],[14],[15]

Our study showed increased mortality associated with the male gender which was similar to findings of a similar study by Mohitosh Biswas et al.[16] Several studies attribute this gender preponderance of susceptibility to a higher expression of the X-linked ACE2 gene which may be regulated by male sex hormones. Thus, the heterogeneous females have lower susceptibility than homogenous men.[17]

In our study, typical respiratory presentations varying from upper respiratory tract symptoms to ARDS necessitating ventilator care were more commonly seen than atypical presentations which were alike similar to studies done globally.[18]

84% of mortality in our study was associated with a variety of underlying comorbidities as evident in large cohorts which attribute increased disease susceptibility and poor disease outcomes to comorbidities such as obesity, diabetes, severe asthma and other respiratory diseases, chronic heart disease, liver disease, stroke, and reduced kidney function.[19]

16% mortality was associated with isolated or MODS-related renal impairment in the form of acute or acute on chronic kidney disease in our study. Each comorbidity has its own pathophysiology and mechanistic link between SARS-CoV-2 infection and mortality. ACE2 receptor overexpression in the tubular cells of COVID-19 patients with kidney disease can be the cause in this scenario.[20] Similar mechanism was found in patients with heart failure leading to the terminal cardio-vascular ischemic event. This is also in line with the current study findings that the patients with cardiovascular diseases were associated with a significantly increased risk of mortality.[21]

Obesity has been associated with reduced blood oxygen saturation due to compromised ventilation of basal lung fields, which can explain the association with COVID-19 mortality as seen in our study.[22]

In our study, mortality was associated with anemia in 33.33% of patients which was also seen in a similar study done in Iran where the prevalence of preexisting anemia was seen in 48% of patients. The frequency of ICU admission, ventilator requirement, and mortality was also significantly higher in anemic patients than in nonanemic ones. This can be attributed to the evidence suggesting anemia leading to activation of the sympathetic nervous system, which increases heart rate, blood pressure, and pulmonary capillary leakage, thereby predisposing ARDS.[23]

About 29.33% of patients in our study had thrombocytopenia in which 12% had bleeding manifestations. Low platelet counts are associated with over fivefold enhanced risk of severe COVID-19.[24] The mechanism is usually multifactorial like direct viral infection and mechanical ventilation-induced endothelial damage triggering platelet activation, aggregation, thrombosis causing vast consumption, and abnormal hematopoiesis due to bone marrow involvement eventually leading to DIC.[25]

Our study showed raised NLR and lymphopenia in a majority of cases. These were also identified as significant risk factors for the requirement of oxygen, mechanical ventilation, and death in a similar study.[26]

In our study, all cases (100%) who subdued to mortality showed a rise in the inflammatory markers. Inflammatory acute phase reactants like procalcitonin, serum ferritin, erythrocyte sedimentation rate, C-reactive protein, interleukin-6, and D-dimer levels significantly highlight that an over-exuberant inflammatory response is associated with the severity of COVID-19.[27],[28]

In addition, lactate dehydrogenase, released in cytokine-mediated tissue damage indicating interstitial pneumonia evolving into ARDS and thrombotic microangiopathy leading to renal failure and myocardial injury, is also associated with elevated D-dimer levels and thrombocytopenia resulting in a hypercoagulable state, contributing to the severity of illness and mortality.[29]

There was a significant positive correlation between higher CT severity scores and increasing age according to Ammar et al. which was similarly seen in our study.[30]

ARDS with Type-I respiratory failure secondary to bilateral lobar pneumonia was the commonest complication associated with mortality which can be related to ACE2 receptor mainly being expressed in blood vessels and lung alveolar type 2 epithelial cells. Various studies have found that lungs infected with SARS-CoV-2 presenting with ARDS have diffuse pulmonary edema with hyaline membrane formation and evident desquamation of pneumocytes.[31]

Our study also found that death was associated with myocarditis in 6 patients of which 3 had elevated high sensitivity troponin-I levels. Acute Coronary Syndrome was seen separately in 3 patients.

The strain of critical illness and inflammation together results in subverting any prior cardiovascular illnesses. Vascular endothelial cell dysfunction, inflammation-associated myocardial depression, stress cardiomyopathy, direct viral infiltration or the host response results in or worsens heart failure, demand-related ischemia, and arrhythmias.[32]

These factors may underlie the observed associations between cardiovascular disease and death in COVID-19 in our study.

Several studies and case series have reported high evidence of acute cerebrovascular accidents and transient ischemic attacks in COVID 19 patients. The pathophysiology underlying the mechanism of acute stroke can be due to hypercoagulability, directly related to the infection or hypoxia.[33] This is in par with the current study where 5 patients developed stroke during their stay in the hospital of which 3 patients developed ischemic and 2 developed hemorrhagic stroke.


  Conclusion Top


Mortality was the highest in the elderly age group which was marginally followed by the middle age group. Thus, indicating toward the notion that more working-age people are dying in India due to COVID 19 than in other countries. Although the overall case fatality rate was a meager 4.27%, the proportion of deaths was higher in the elderly population, especially males with comorbidities and those who had the severe disease at the time of presentation. ARDS remains the leading killer in the COVID 19 scenario. Our data support the findings of other studies that co-morbidities, increased NLR, lymphopenia, elevated acute phase reactants and higher CT severity scorings were associated with the severity of COVID-19. Hence, with the lurking risk of an upcoming second wave of COVID 19 in India, the massive loss of people in the workforce is likely to have devastating social and economic consequences. As rightly said “It is not over till it is over” we have to learn from the past and flatten the curve of morbidity and mortality due to COVID 19 by giving more emphasis to the older age group with comorbidities.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



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



 

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