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Correlation of COVID-19 Biomarkers with Disease Severity: A Retrospective Study
Indian Journal of Critical Care Medicine ; 26:S84-S87, 2022.
Article in English | EMBASE | ID: covidwho-2006373
ABSTRACT

Introduction:

Many viruses through aerosols, droplets, and droplet nuclei utilize the respiratory passages to establish not only localized respiratory tract infections but also systemic disease. The coronaviruses (CoV) are no exception. The two most common illnesses that occurred in the recent past were severe acute respiratory syndrome (SARS, 2003) and the Middle East respiratory syndrome (MERS, 2012).1 The current pandemic, which broke out in late December 2019, has been a major threat to global public health due to significant morbidity and mortality, akin to snapping of Thanos' fingers. The novel coronavirus was initially named the 2019-novel CoV (2019-nCoV), but because of nearly 80% genetic homology to SARS-CoV, the Coronavirus Study Group of International Committee rechristened this virus as SARS-CoV-2.1 The disease was named coronavirus disease 2019 (COVID-19) on January 12, 2020, by the World Health Organization (WHO).2 According to the Advisory Committee on dangerous pathogens UK, COVID-19 is assigned as a hazardous group-3 organism, meaning that it can cause severe human disease.3 The novel coronavirus was named the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2, 2019-nCoV) due to its high homology (∼80%) to SARS-CoV, which caused acute respiratory distress syndrome (ARDS) and high mortality during 2002-2003.4 The outbreak of SARS-CoV-2 was considered to have originally started via a zoonotic transmission associated with the seafood market in Wuhan, China. Later it was recognized that human-to-human transmission played a major role in the subsequent outbreak.5 The most common clinical manifestations of COVID-19 include fever, cough, dyspnea, fatigue, and myalgia. A few patients have developed severe pneumonia and they may present with acute respiratory distress syndrome (ARDS), extrapulmonary organ dysfunction, or even death. SARS-CoV-2 virus primarily affects the respiratory system, although other organ systems are also involved. Lower respiratory tract infection-related symptoms including fever, dry cough, and dyspnea were reported in the initial case series.6 In addition, headache, dizziness, generalized weakness, vomiting, and diarrhea were observed.7 It is now widely recognized that respiratory symptoms of COVID-19 are extremely heterogeneous, ranging from minimal symptoms to significant hypoxia with ARDS. The heterogeneous disease course of COVID-19 is unpredictable with most patients experiencing mild self-limiting symptoms. However, up to 30% require hospitalisation, and up to 17% of these require intensive care support for acute respiratory distress syndrome (ARDS), hyperinflammation, and multiorgan failure. 8-10 A cytokine storm in patients with severe disease was identified in the early reports of Wuhan patients and is intrinsic to disease pathology. In this cohort, elevated plasma interleukin (IL)-2, IL-7, IL-10, granulocyte colony-stimulating factor (GCSF), interferon γ-induced protein 10 (IP10, monocyte chemoattractant protein-1 (MCP1), macrophage inflammatory protein 1-alpha (MIP1A), and tumor necrosis factor-alpha (TNF-α) levels in ICU patients were identified. 6 Studies have shown that severe or fatal cases of COVID-19 disease are associated with an elevated white cell count, blood urea nitrogen, creatinine, markers of liver and kidney function, C-reactive protein (CRP), interleukin-6 (IL-6), lower lymphocyte (<1000/μL) and platelet counts (<100 × 109/L) as well as albumin levels compared with milder cases in which survival is the outcome. Subsequent studies have implicated IL-6 as a valuable predictor of adverse clinical outcome and a potential therapeutic target.11,12 One or more clinical and wet biomarkers may enable early identification of high-risk cases, assisting disease stratification and effective use of limited specialist resources. Age is a strong risk factor for severe illness, complications, and death.13,14 Patients with no underlying medical comorbid conditions have an overall case fatality rate of <1%. Case fatality is higher for patients with comorbidit es. The severe cases are associated with elevated levels of inflammatory biomarkers such as serum lactate dehydrogenase, creatine kinase, C-reactive protein (CRP), d-dimer, procalcitonin, and ferritin.15 Since laboratory medicine has always supported clinical decision-making in various infectious diseases, it is important to assess the ability of laboratory-derived biomarkers to facilitate risk stratification of COVID-19 disease. This study will comprehensively explore clinical disease features and routine laboratory tests associated with COVID-19 disease and its complications, to address their association with disease severity and outcome. Hence, the present retrospective study will be done at our tertiary care centre to assess the association between different laboratory biomarkers and disease severity and outcomes in COVID-19 patients. Aims and

objectives:

Clinical correlation of biomarkers and disease severity in COVID-19 patients-a retrospective study. Review of Literature Xia et al.16 in 2020 defined disease stages and identified stages' determining factors are instructive for the definition of standards for home quarantine. The authors demonstrated pulmonary involvement on a chest CT scan in 97.9% of cases. It took 16.81 ± 8.54 (3-49) days from the appearance of the first symptom until 274 patients tested virus-negative in naso- and oropharyngeal (NP) swabs, blood, urine, and stool, and 234 (83%) patients were asymptomatic for 9.09 ± 7.82 (1-44) days. Subsequently, 131 patients were discharged. One hundred and sixty-nine remained in the hospital;these patients tested virus-free and were clinically asymptomatic because of widespread persisting or increasing pulmonary infiltrates. Hospitalization took 16.24 ± 7.57 (2-47) days;the time interval from the first symptom to discharge was 21.37 ± 7.85 (3-52) days. The authors concluded that with an asymptomatic phase, disease courses are unexpectedly long until the stage of virus negativity. NP swabs are not reliable in the later stages of COVID-19. Pneumonia outlasts virus-positive tests if sputum is not acquired. Imminent pulmonary fibrosis in high-risk groups demands follow-up examinations. Investigation of promising antiviral agents should heed the specific needs of mild and moderate COVID-19 patients. Keddie et al.17 in 2020 investigated the routine laboratory tests and cytokines implicated in COVID-19 for their potential application as biomarkers of disease severity, respiratory failure, and need for higher-level care. The authors found CRP, IL-6, IL-10, and LDH were most strongly correlated with the WHO ordinal scale of illness severity, the fraction of inspired oxygen delivery, radiological evidence of ARDS, and level of respiratory support. IL-6 levels of ≥3.27 pg/mL provide a sensitivity of 0.87 and specificity of 0.64 for a requirement of ventilation, and a CRP of ≥37 mg/L of 0.91 and 0.66. The authors concluded that reliable stratification of highrisk cases has significant implications on patient triage, resource management, and potentially the initiation of novel therapies in severe patients. Malik et al.18 in 2020 in a systematic review and meta-analysis assessed the role of biomarkers in evaluating the severity of disease and appropriate allocation of resources. Studies having biomarkers, including lymphocyte, platelets, d-dimer, lactate dehydrogenase (LDH), C-reactive protein (CRP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine, procalcitonin (PCT), and creatine kinase (CK), and describing outcomes were selected with the consensus of three independent reviewers. The authors found lymphopenia, thrombocytopenia, elevated d-dimer, elevated CRP, elevated PCT, elevated CK, elevated AST, elevated ALT, elevated creatinine, and LDH were independently associated with a higher risk of poor outcomes. The authors concluded a significant association between lymphopenia, thrombocytopenia, and elevated levels of CRP, PCT, LDH, d-dimer, and COVID-19 severity. The results have the potential to be used as an early biomarker to impro e the management of COVID-19 patients, by identification of high-risk patients and appropriate allocation of healthcare resources in the pandemic. Tjendra et al.19 in 2020 assessed specific laboratory parameters and summarized the currently available literature on the predictive role of various biomarkers in COVID-19 patients.
Keywords
alanine aminotransferase; antivirus agent; aspartate aminotransferase; biological marker; C reactive protein; creatine kinase; creatinine; cytokine; D dimer; dextro lactate dehydrogenase; dimer; endogenous compound; ferritin; gamma interferon inducible protein 10; granulocyte colony stimulating factor; interleukin 10; interleukin 2; interleukin 6; interleukin 7; lactate dehydrogenase; macrophage inflammatory protein 1alpha; monocyte chemotactic protein 1; procalcitonin; tumor necrosis factor; adult; adult respiratory distress syndrome; advisory committee; alanine aminotransferase blood level; albumin level; all cause mortality; assisted ventilation; asthenia; case fatality rate; case study; China; clinical decision making; clinical outcome; cohort analysis; communicable disease; comorbidity; complication; conference abstract; consensus; coronavirus disease 2019; coughing; cytokine storm; diagnosis; diarrhea; dizziness; dry cough; dyspnea; fatality; fatigue; feces; female; ferritin blood level; fever; follow up; fraction of inspired oxygen; gene expression; genetic susceptibility; headache; high risk patient; high risk population; home quarantine; hospital discharge; hospitalization; human; human cell; human tissue; hyperinflammation; hypoxia; intensive care; kidney function; laboratory test; lactate dehydrogenase blood level; leukocyte count; literature; liver function; lower respiratory tract infection; lung fibrosis; lung infiltrate; lymphocyte; lymphocytopenia; male; mortality; multiple organ failure; myalgia; nonhuman; organ systems; oropharyngeal swab; outcome assessment; pandemic; patient triage; platelet count; pneumonia; protein expression; resource management; respiratory failure; retrospective study; risk assessment; risk factor; SARS coronavirus; sensitivity and specificity; Severe acute respiratory syndrome coronavirus 2; sputum; survival; systematic review; tertiary care center; thorax; thrombocytopenia; urea nitrogen blood level; vomiting; World Health Organization; x-ray computed tomography; zoonotic transmission

Full text: Available Collection: Databases of international organizations Database: EMBASE Type of study: Observational study / Prognostic study Language: English Journal: Indian Journal of Critical Care Medicine Year: 2022 Document Type: Article

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Full text: Available Collection: Databases of international organizations Database: EMBASE Type of study: Observational study / Prognostic study Language: English Journal: Indian Journal of Critical Care Medicine Year: 2022 Document Type: Article