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Clinical profile and outcome of elderly COVID-19 patients

Corona viruses are non-segmented positive-stranded RNA viruses with a roughly 30 kb genome surrounded by a protein envelope. Most coronaviruses cause diseases in their particular host species. Those that can infect humans through cross-species transmission have become an important threat to public health. Two serious coronavirus disease outbreaks have happened in the past two decades: severe acute respiratory syndrome (SARS) in 2003 and Middle East respiratory syndrome (MERS) in 2012. Since December, 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been recognized as the causal factor in a series of severe cases of pneumonia originating in Wuhan in Hubei province, China.


INTRODUCTION
Corona viruses are non-segmented positive-stranded RNA viruses with a roughly 30 kb genome surrounded by a protein envelope. Most coronaviruses cause diseases in their particular host species. 1 Those that can infect humans through cross-species transmission have become an important threat to public health. Two serious coronavirus disease outbreaks have happened in the past two decades: severe acute respiratory syndrome (SARS) in 2003 and Middle East respiratory syndrome (MERS) in 2012. 2,3 Since December, 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been recognized as the causal factor in a series of severe cases of pneumonia originating in Wuhan in Hubei province, China. 4 This disease has been named coronavirus disease 2019 (COVID-19) by WHO. SARS-CoV-2 has been shown to cause disease via a mechanism analogous to the SARS coronavirus, with potential damage to vital organs such as lung, heart, liver, and kidney, and infection poses a considerable risk to patients by the high prevalence of pneumonia. 5 All age groups are generally susceptible to coronavirus, but elderly people with underlying diseases are more susceptible. The underlying diseases are diabetes, hypertension, cardiovascular disease, chronic kidney disease and cerebro-vascular disease. 6 The elderly are more susceptible to severe illness and are admitted to the HDU and intensive care unit (ICU), and the mortality of elderly patients is higher. 7 In this pandemic, the urban facilities in the country have been overwhelmed with the treatment of severe cases. Understanding risk factor and clinical feature of severe cases is critically important to improve the outcome and efficacy of treatment. Still more and more studies are required for understanding the pathology and formulating standard care of treatment.

METHODS
The prospective study was carried out between March 2020 to December 2020 at Victoria hospital, BMCRI, Bengaluru. Approval and clearance were obtained from the institutional ethics committee.
The study included patients aged ≥65 yrs of both the gender, diagnosed with COVID-19 infection by RT-PCR technique. The study excluded patients <65 yrs and those not willing to provide signed informed consent prior to the study. Case record form with follow-up chart was used to record the demographic data, duration of illness, comorbidities and clinical features of the disease. .
The demographic and clinical data collected were age, sex, clinical symptoms and comorbidities like hypertension, diabetes, renal, cardiac and respiratory disorders. Also, relevant laboratory investigation like haemoglobin, total leucocyte count, neutrophil%, lymphocyte%, neutrophil lymphocyte ratio (NLR), LDH, D-dimer, CRP, ferritin, chest X-ray and HRCT chest were done.
All the selected participants were followed up until discharge or death. 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 hrs apart were negative for SARS-CoV-2 RNA done using RT-PCR technique. If positive, test was repeated after 72 hrs. As per the revised discharge policy, patients who had mild and moderate symptoms were discharged after 10 days without throat/nasopharyngeal swab test for COVID-19 and symptom free for atleast 3 days and for severe patients, 14 th day discharge policy based on negative swab test was adopted and those who were positive, the tests were repeated every 3 rd day till obtaining a negative result. The demographics and clinical outcome were further correlated.
Statistical analysis was carried out using SPSS software. 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 continuous variables and Chi-square test for categorical data. The optimal cut points were estimated for significant continuous variables using receiver operating curve (ROC) analysis. Multiple regression analysis was carried out and odds ratio with confidence interval (CI) were estimated to determine the effect of significant factors on outcome death and survival. P value <0.05 was considered as statistically significant. Between the group biochemical parameter which showed statistical significance in predicting mortality were total leucocyte count, neutrophil%, lymphocyte%, neutrophil lymphocyte ratio (NLR), LDH, D-dimer, CRP, ferritin. These parameters were further considered for regression analysis. Since NLR is ratio neutrophil% and lymphocyte% only NLR was considered for multilogistic regression and ROC analysis. Odd ratio and CI are tabulated in Table 2  Based on saturation and severity at time of presentation patient was divided into 3 groups and comparison between the group is shown in Table 4. 30.8% were asymptomatic in group 1 and group 3 had fever (55.2%), cough (34.4%) and dyspnea (44.8%) as major symptom when compared to another group. 46.8% people has both diabetes with hypertension in group 3. Lab parameter like total leucocyte count, neutrophil lymphocyte ratio (NLR), LDH, D-dimer, CRP, ferritin showed statistical significance in predicting severity of disease.

DISCUSSION
In the present study of 7259 admitted patients, 16% was elderly people and mortality rate was 26%, which was way too much higher than any other age group that is affected. This demonstrated that the survival chances are lower for patient ≥65 yrs. There are many literatures to validate this association between age related COVID-19 severity and mortality. A rapid review and meta-analysis have also showed the positive association between increased agerelated 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 meta-analysis involving 6,11,583 reported that mortality was <1.1% in age group <50 yrs and largest increase in mortality was observed in patient between age group of 60-69 yrs. 9 Current study has showed fever, cough, dyspnea, myalgia followed by sore throat as common symptom. But fever and dyspnea was the major symptom present among patient who succumbed to death. A study conducted by Zhang et al evaluated clinical characteristics of 82 laboratory confirmed SARS CoV-2 death cases, reported that fever (78%), cough (64.6%), shortness of breath (63.4%) as prominent symptom reported in the succumbed victims. 10 The study by Gupta et al conducted in tertiary care centre in India also noticed fever and cough as major symptom. 11 In this study diabetes with hypertension coexistence followed by IHD was major association with the patient who succumbed to death. In concurrence with these finding, the study conducted by Saluka et al in government medical college, Kota, Rajasthan has also observed increased male preponderance. Hypertension was common associated co-morbidity followed by diabetes. Also, noted increased occurrence of severe illness and complication in patient age >60 yrs. 12 The data from Mexico has identified obesity, CKD, hypertension, diabetes and COPD are associated with increased mortality risk of COVID-19 patient. A review focusing on developing countries has reported that presence of comorbidities is linked to poor outcome of COVID-19 patients. 13 Total leukocyte count, NLR, LDH, D-dimer, CRP and Ferritin were statistically significant as predictor of disease outcome. Among these variables the highest specificity (89%) and sensitivity (76%) was noted for D-dimer at 1mcg/ml followed by NLR ratio of 6.9 has specificity (82%), sensitivity (73%) and least for total leukocyte count. A study by Pomilla et al have assessed potential of routine infectious biomarker and haematological parameter in evaluating the disease severity in 100 adult COVID-19 patient. They suggested total leukocyte count of 8100/cumm has sensitivity 91%, specificity 62.5% and NLR ratio of 6.9 has sensitivity 91.7%, specificity 87.5% and may assist in triaging patient requiring ICU care and deciding on intervention. 14 Zhang et al studied the clinical characteristics of 82 cases of death due to COVID-19 and most of the findings are in line with the present results. The researchers noted increased incidence of mortality in male subjects (66%) and more than half of the subjects who died were >60 yrs of age. The most common comorbidity noted in patients who died were hypertension (56.1%), followed by heart disease (20.7%), diabetes (18.3%), cerebrovascular disease (12.2%), and cancer (7.3%). Lymphopenia, neutrophilia, and thrombocytopenia were the common clinical finding observed on admission. In addition, elevated NLR of >5, systemic immune-inflammation index of >500, CRP, LDH, and D-dimer were also observed in most of the patients. Respiratory failure was identified as the main cause of COVID-19 and high level of IL-6 (>10 pg/ml) was indicative of cytokine release syndrome-mediated damage to other vital organs. 10 The present study holds significant relevance, as there is very limited literature evidence available on elderly with COVID-19 infection. More ever, it sheds light on several significant finding which would assist clinician in screening, treatment decision and estimating disease prognosis. Another strength of this study is good sample size, but generalization of finding is limited as the study was carried out in single centre.

CONCLUSION
In conclusion, D-dimer of 1 mcg/ml, NLR ratio of 6.9 may assist in triaging patient requiring ICU care and deciding intervention. Also, elderly with multiple comorbidity should be treated aggressively, so that chance of survival can be increased.