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      Limited value of neutrophil-to-lymphocyte ratio and serum creatinine as point-of-care biomarkers of disease severity and infection mortality in patients hospitalized with COVID-19

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          Abstract

          Introduction

          In hospitalized COVID-19, neutrophil-to-lymphocyte ratio (NLR) and serum creatinine is sometimes measured under assumption they predict disease severity and mortality. We determined the potential value of NLR and serum creatinine as predictors of disease severity and mortality in COVID-19.

          Methods

          Prospective cohort study of COVID-19 patients admitted to premier COVID-19 treatment hospitals in Ethiopia. Predictive capability of biomarkers in progression and prognosis of COVID-19 was analyzed using receiver operating characteristics. Survival of COVID-19 patients with different biomarker levels was computed. Logistic regression assessed associations between disease severity and mortality on NLR and serum creatinine adjusted for odds ratio (AOR).

          Results

          The study enrolled 126 adults with severe (n = 68) or mild/moderate (n = 58) COVID-19, with median age 50 [interquartile range (IQR 20–86)]; 57.1% males. The NLR value was significantly higher in severe cases [6.68 (IQR 3.03–12.21)] compared to the mild/moderate [3.23 (IQR 2.09–5.39)], with the NLR value markedly associated with disease severity ( p<0. 001). Mortality was higher in severe cases [13 (19.1%)] compared to mild/moderate cases [2 (3.4%)] ( p = 0. 007). The NLR value was significantly higher in non-survivors [15.17 (IQR 5.13–22.5)] compared to survivors [4.26 (IQR 2.40–7.90)] ( p = 0. 002). Serum creatinine was significantly elevated in severe cases [34 (50%)] compared with mild/moderate [11 (19%)] ( p<0. 001). Disease severity [AOR 6.58, 95%CI (1.29–33.56), p = 0. 023] and NLR [AOR 1.07, 95%CI (1.02–1.12), p = 0. 004)] might be associated with death. NLR had a sensitivity and specificity of 69.1% and 60.3% as predictor of disease severity (cut-off >4.08), and 86.7% and 55.9% as prognostic marker of mortality (cut-off >4.63).

          Conclusion

          In COVID-19, NLR is a biomarker with only modest accuracy for predicting disease severity and mortality. Still, patients with NLR >4.63 are more likely to die. Monitoring of this biomarker at the earliest stage of the disease may predict outcome. Additionally, high creatinine seems related to disease severity and mortality.

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          Most cited references47

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          Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China

          Summary Background A recent cluster of pneumonia cases in Wuhan, China, was caused by a novel betacoronavirus, the 2019 novel coronavirus (2019-nCoV). We report the epidemiological, clinical, laboratory, and radiological characteristics and treatment and clinical outcomes of these patients. Methods All patients with suspected 2019-nCoV were admitted to a designated hospital in Wuhan. We prospectively collected and analysed data on patients with laboratory-confirmed 2019-nCoV infection by real-time RT-PCR and next-generation sequencing. Data were obtained with standardised data collection forms shared by WHO and the International Severe Acute Respiratory and Emerging Infection Consortium from electronic medical records. Researchers also directly communicated with patients or their families to ascertain epidemiological and symptom data. Outcomes were also compared between patients who had been admitted to the intensive care unit (ICU) and those who had not. Findings By Jan 2, 2020, 41 admitted hospital patients had been identified as having laboratory-confirmed 2019-nCoV infection. Most of the infected patients were men (30 [73%] of 41); less than half had underlying diseases (13 [32%]), including diabetes (eight [20%]), hypertension (six [15%]), and cardiovascular disease (six [15%]). Median age was 49·0 years (IQR 41·0–58·0). 27 (66%) of 41 patients had been exposed to Huanan seafood market. One family cluster was found. Common symptoms at onset of illness were fever (40 [98%] of 41 patients), cough (31 [76%]), and myalgia or fatigue (18 [44%]); less common symptoms were sputum production (11 [28%] of 39), headache (three [8%] of 38), haemoptysis (two [5%] of 39), and diarrhoea (one [3%] of 38). Dyspnoea developed in 22 (55%) of 40 patients (median time from illness onset to dyspnoea 8·0 days [IQR 5·0–13·0]). 26 (63%) of 41 patients had lymphopenia. All 41 patients had pneumonia with abnormal findings on chest CT. Complications included acute respiratory distress syndrome (12 [29%]), RNAaemia (six [15%]), acute cardiac injury (five [12%]) and secondary infection (four [10%]). 13 (32%) patients were admitted to an ICU and six (15%) died. Compared with non-ICU patients, ICU patients had higher plasma levels of IL2, IL7, IL10, GSCF, IP10, MCP1, MIP1A, and TNFα. Interpretation The 2019-nCoV infection caused clusters of severe respiratory illness similar to severe acute respiratory syndrome coronavirus and was associated with ICU admission and high mortality. Major gaps in our knowledge of the origin, epidemiology, duration of human transmission, and clinical spectrum of disease need fulfilment by future studies. Funding Ministry of Science and Technology, Chinese Academy of Medical Sciences, National Natural Science Foundation of China, and Beijing Municipal Science and Technology Commission.
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            OpenSAFELY: factors associated with COVID-19 death in 17 million patients

            COVID-19 has rapidly impacted on mortality worldwide. 1 There is unprecedented urgency to understand who is most at risk of severe outcomes, requiring new approaches for timely analysis of large datasets. Working on behalf of NHS England we created OpenSAFELY: a secure health analytics platform covering 40% of all patients in England, holding patient data within the existing data centre of a major primary care electronic health records vendor. Primary care records of 17,278,392 adults were pseudonymously linked to 10,926 COVID-19 related deaths. COVID-19 related death was associated with: being male (hazard ratio 1.59, 95%CI 1.53-1.65); older age and deprivation (both with a strong gradient); diabetes; severe asthma; and various other medical conditions. Compared to people with white ethnicity, black and South Asian people were at higher risk even after adjustment for other factors (HR 1.48, 1.29-1.69 and 1.45, 1.32-1.58 respectively). We have quantified a range of clinical risk factors for COVID-19 related death in the largest cohort study conducted by any country to date. OpenSAFELY is rapidly adding further patients’ records; we will update and extend results regularly.
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              A Review of Coronavirus Disease-2019 (COVID-19)

              There is a new public health crises threatening the world with the emergence and spread of 2019 novel coronavirus (2019-nCoV) or the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The virus originated in bats and was transmitted to humans through yet unknown intermediary animals in Wuhan, Hubei province, China in December 2019. There have been around 96,000 reported cases of coronavirus disease 2019 (COVID-2019) and 3300 reported deaths to date (05/03/2020). The disease is transmitted by inhalation or contact with infected droplets and the incubation period ranges from 2 to 14 d. The symptoms are usually fever, cough, sore throat, breathlessness, fatigue, malaise among others. The disease is mild in most people; in some (usually the elderly and those with comorbidities), it may progress to pneumonia, acute respiratory distress syndrome (ARDS) and multi organ dysfunction. Many people are asymptomatic. The case fatality rate is estimated to range from 2 to 3%. Diagnosis is by demonstration of the virus in respiratory secretions by special molecular tests. Common laboratory findings include normal/ low white cell counts with elevated C-reactive protein (CRP). The computerized tomographic chest scan is usually abnormal even in those with no symptoms or mild disease. Treatment is essentially supportive; role of antiviral agents is yet to be established. Prevention entails home isolation of suspected cases and those with mild illnesses and strict infection control measures at hospitals that include contact and droplet precautions. The virus spreads faster than its two ancestors the SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV), but has lower fatality. The global impact of this new epidemic is yet uncertain.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: InvestigationRole: MethodologyRole: Writing – original draft
                Role: InvestigationRole: MethodologyRole: SupervisionRole: Writing – review & editing
                Role: Funding acquisitionRole: MethodologyRole: SupervisionRole: Writing – review & editing
                Role: Formal analysisRole: InvestigationRole: Writing – review & editing
                Role: Data curationRole: Formal analysisRole: SoftwareRole: Writing – review & editing
                Role: Data curationRole: Formal analysisRole: SupervisionRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: SupervisionRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: SupervisionRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS One
                plos
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                6 October 2022
                2022
                6 October 2022
                : 17
                : 10
                : e0275391
                Affiliations
                [1 ] Department of Medical Biochemistry, School of Medicine, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia
                [2 ] Department of Internal Medicine, School of Medicine, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia
                [3 ] Centre for Innovative Drug Development and Therapeutic Trials for Africa (CDT-Africa), College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia
                [4 ] School of Public Health, Saint Paul’s Hospital Millennium Medical College, Addis Ababa, Ethiopia
                [5 ] Eka Kotebe General Hospital, Addis Ababa, Ethiopia
                [6 ] Gastroenterology and Hepatology Unit, Department of Medical Sciences, Uppsala University, Uppsala, Sweden
                Kaohsuing Medical University Hospital, TAIWAN
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Author information
                https://orcid.org/0000-0003-2196-6835
                https://orcid.org/0000-0003-4704-1435
                https://orcid.org/0000-0002-8360-7574
                https://orcid.org/0000-0001-8428-0772
                https://orcid.org/0000-0002-5433-0107
                Article
                PONE-D-22-15252
                10.1371/journal.pone.0275391
                9536552
                5e774df0-966d-49e1-9b9e-f78c9e6e6382
                © 2022 Tufa et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 26 May 2022
                : 15 September 2022
                Page count
                Figures: 3, Tables: 5, Pages: 14
                Funding
                No authors received funding for this particular study. Centre for Innovative Drug Development and Therapeutic Trials for Africa (CDT-Africa), College of Health Sciences, Addis Ababa University, Addis Ababa supported expenses associated with data and sample collection. Professor Per M. Hellström and Associate professor Dominic-Luc Webb, Gastroenterology and Hepatology Unit, Department of Medical Sciences, Uppsala University, Sweden support all expenses related to laboratory analysis. The funders have no role in the study design, data and decision to publish including preparation of the manuscript.
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