A Study of Clinical Profile and Neutrophil-Lymphocyte Ratio in Clinical Outcome of Covid 19 Patients: Tertiary Care Centre in Bangalore

Introduction: Corona virus disease is ongoing global pandemic, caused by severe acute respiratory distress syndrome corona virus 2 (SARS-Cov2). The virus was first identified in Wuhan, China in December 2019. The World Health Organization declared the virus a Public Health Emergency of International Concern on 30 January 2020, and later a pandemic on 11 March 2020.The severity of COVID-19 symptoms can range from asymptomatic milder forms to life-threatening. Severe illness is more likely in elderly patients and also in patients with co morbid conditions. Disease can transmit through air contaminated by droplets and small airborne particles. Aims: we aimed to know the clinical profile of covid 19 patients and also to co relate the neutrophil-lymphocyte ratio with clinical outcome of the disease. Materials and methods: This Prospective study was conducted in Patients admitted from August 2020 to October 2020. COVID-19 infection was diagnosed by RT-PCR and rapid antigen test (RAT) technique. Patients demographic data, clinical history was collected. Clinical assessment was performed. Laboratory investigations was sent. Patients were followed during the hospital stay. Appropriate statistical analysis was used Results: Males were commonly affected than females. Mean age of the patient was 61years. Diabetes was the most common co morbid condition. Fever was the most common symptom followed by cough, breathlessness. Neutrophil-lymphocyte ratio was elevated in intubated patients than in patients maintaining room air saturation, which was statistically significant (p value 0.001). Conclusion: Neutrophil-lymphocyte ratio (NLR) can be used as reliable, early marker for the disease progression of covid 19 disease.


Introduction
Corona viruses are non-segmented positive-stranded RNA viruses with a roughly 30 kb genome surrounded by a protein envelope. Most corona viruses 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 corona virus disease outbreaks have happened in the past two decades: severe acute respiratory syndrome (SARS) in 2003 [2] and Middle East respiratory syndrome (MERS) [3] in 2012. Since December, 2019, severe acute respiratory syndrome corona virus 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 corona virus disease 2019 (COVID-19) by WHO. SARS-CoV-2 has been shown to cause disease via a mechanism analogous to the SARS corona virus, 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] . The majority of cases are usually self-limiting with low-grade fever, sore throat, myalgia and cough [6] , in others, disease can be progressed to severe disease in the form of acute respiratory distress syndrome and it can be fatal [6] . SARS Cov 2 infection in patients with preexisting co-morbidities have poor outcome [7] . Physicians are searching for a reliable prognostic marker that can distinguish patients at risk of developing more severe forms of the disease and can reduce mortality. The neutrophil-to-lymphocyte ratio (NLR) in peripheral blood has been studied as a systemic inflammatory marker and various studies have shown that it is a valid prognostic factor in various solid tumours [8] . In our study, we aimed to know the neutrophil-lymphocyte ratio in milder and severe forms of covid 19 disease.
Aims and objectives of the study 1  In our study, 60%(60) of the subjects were male and 40%(40)) of the subjects were female. Male were predominantly affected by covid 19 infection. Overall, 34% of the patient were maintaining in room air saturation. 32% of the patient required oxygen support. 28% of the patient required noninvasive ventilation. 6% of the patient required intubation  (26) of the patient required noninvasive ventilation and 3.3% (3) of the patient required intubation which was statistically significant. 66 patients had sore throat, out of that,37.9% (25) patients required oxygen support, 33.3% (22) of the patient required non-invasive ventilation and 6.1%(4) of the patient required intubation, which was statistically significant. 65 patients had breathlessness, out of that, 47.7% (31) required oxygen support, 43.1% (28) of the patient required non-invasive ventilation and 9.2% (6) of the patient required intubation which was statistically significant. However, 84 patients had cough and 70 patients had myalgia which was not statistically significant with outcome of the disease.

Results
Most common symptoms was fever (91%) followed by cough (84%), myalgia (70%), sorethorat (66%) and breathlessness (65%). Among intubated patients, mean age of the patients was 61years, which was statistically significant with outcome of the disease. As we know, age is also risk factor for severity of the disease. Elderly people are more prone for developing severe disease.9 Mean CRP was 98.17 in intubated patients and 1.76 in patients with room air, which is statistically significant(p value <0.001). Mean value of d dimer in intubated patients was 11.78 and 0.57 in patients with room air which is statistically significant. Mean value of Neutrophil and lymphocyte ratio was 20.7 in intubated patients and 2.1 in patients with maintaining room air saturation, which is statistically significant. Mean value of neutrophil percentage count was 90 in intubated patients and 66.5 in patients with maintaining room air saturation, which is statistically significant. Mean value of lymphocyte percentage count was 4.67 in intubated patients and 32.35 in patients with maintaining room air saturation, which is statistically significant. However, haemoglobin, total leukocyte count was not statistically significant in our study.

Discussion
In our study, 60% males were predominantly affected. Metaanalysis conducted by Biswas M et al concluded that males were predominantly affected, and more risk for severe form of disease [9] .
In our study, we found that, elderly patients, mean age of 61 years were more affected with severe form of the disease. Bonanad C et al concluded the largest increase in mortality risk was observed in patients aged 60 to 69 years [10] .
In our study, we found that 65% patients had diabetes, 15% patients had hypertension, 11% patients had ischemic heart disease, 4% patients had hypothyroid, 5% patients had asthma.
Diabetes was the most common co morbid conditions associated with covid 19 infection. A study conducted by Osibogun et al concluded that co-morbidities are prevalent and the associated risk of death is high among COVID-19 patient [11] . A study conducted by Gold et al concluded that hypertension (47.65%) was more prevalent followed by diabetes(24.89%) [12] .
Haemoglobin was not statistically significant in our study. A study conducted by Hariyanto et al concluded anemia seems to be associated with an enhanced risk of severe COVID-19 infection [13] . It has been suggested that neutrophils enhance antiviral defenses by interaction with other immune cell populations, virus internalization and killing mechanism, cytokines release, degranulation, oxidative burst, and neutrophil extracellular traps (NETs) [14,15] . Neutrophilia has been described as an indicator of severe respiratory symptoms and a poor outcome in patients with COVID-19 [16,17,18] . In our study, 90% of the neutrophil was found in intubated patient and 66.5% in patients with maintaining room air, which is statistically significant. Lymphopenia are prominent laboratory abnormalities reported in patients with SARS, and these conditions are more frequent in patients with severe disease compared to non-severe disease [19] . Lymphopenia is also observed in approximately 60% of patients with SARS-CoV-2 infection at initial presentation [20] . In our study, 4.67% of lymphocytes was found in patients with intubated and 32.35% in patients with maintaining room air saturation, which was statistically significant. Mean CRP was 98.17 in intubated patients and 38.40 in non-invasive ventilated patients, 16.33 in oxygen support and 1.76 in patients with maintaining room air saturation, which was statistically significant. This indicates CRP was increased in severe form of covid 19 infection than compared to milder form of disease. A study conducted by Sahu et al concluded that Concentrations of CRP remained high in patients who died of COVID-19 infection and could be a promising biomarker for assessing disease lethality [21] . A study conducted by Wang, L concluded that, in the early stage of COVID-19 CRP levels were positively correlated with lung lesions and could reflect disease severity [22] . A study conducted by chen et al concluded that, the level of plasma CRP was positively correlated to the severity of COVID-19 pneumonia [23] . In our study, we found that d dimer was 11.78 in intubated patients, 6.09 in non-invasive ventilated patients, 3.56 in patients with oxygen support and 0.57 in patients with maintaining room air saturation. This reflects d dimer level was increased in severe form of disease. A study conducted by Yao concluded that d-dimer is commonly elevated in patients with COVID-19 and d-dimer levels correlate with disease severity and are a reliable prognostic marker for in-hospital mortality in patients admitted for COVID-19 [24] . A study conducted by Yu concluded that d-dimer level is associated with the severity of COVID-19 [25] .
In our study, we found that neutrophil-lymphocyte ratio was 20.75 in intubated patients, 6.98 in non invasive ventilated patient, 4.77 in patients with oxygen support and 2.10 in patients with maintaining room air. This indicates neutrophil-lymphocyte ratio reflects disease severity, can be taken as prognostic marker for the disease. A study conducted by yang et al concluded that NLR can be considered independent biomarkers for indicating poor clinical outcomes [26] . A study conducted by iran et al, concluded that NLR can be used as an early warning signal for deteriorating severe COVID-19 infection [27] . A study conducted by Li et al, concluded that, NLR has good predictive values on disease severity and mortality in patients with COVID-19 infection [28] . A study conducted by Usul et al., concluded, NLR was was found to be significantly high in critically ill COVID-19 patients compared to the control population [29] . A study conducted by gustavo et al, concluded that high neutrophil to lymphocyte ratio as a prognostic marker in COVID-19 patients [30] .

Conclusion
Neutrophil-lymphocyte ratio is significantly increased in patients with intubated patients than in patients requiring only oxygen support and in patients maintaining room air saturation. So, this indicates that neutrophil-lymphocyte ratio can reflect the disease progression. It can used as simple, reliable, early prognostic marker for the severity of covid-19 disease. Patients with high levels of neutrophil-lymphocyte ratio has higher risk of deterioration. So, such patients may be considered for early admission to critical care unit.

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Financial or Other Competing Interests: None  Was Ethics Committee Approval obtained for this study? Yes  Was informed consent obtained from the subjects involved in the study? Yes  For any images presented appropriate consent has been obtained from the subjects. NA