N-terminal Pro B-type Natriuretic Peptide and Vitamin D Levels as Prognostic Markers in COVID-19 Pneumonia

Study Overview
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Brief Summary
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This study is designed to assess the difference between level of NT-pro-BNP, and Vitmin D in moderate cases who progressed to severe or critically ill category compared to those who did not. Assessment of any possible correlation between NT-pro-BNP and Vitamin D and the need for mechanical ventilation or mortality in COVID-19 infection.

Detailed Description
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On 30 January 2020, World Health Organization (WHO) officially declared the COVID-19 epidemic as a public health emergency of international concern. An acute respiratory disease, caused by a novel coronavirus (SARS-CoV-2, previously known as 2019-nCoV), the coronavirus disease 2019 (COVID-19) has spread throughout China and received worldwide attention (Guo et al., 2020). As an emerging acute respiratory infectious disease, COVID-19 primarily spreads through the respiratory tract, by droplets, respiratory secretions, and direct contact (Li et al., 2020). Based on current epidemiological investigation, the incubation period is 1-14 days, mostly 3-7 days and the COVID-19 is contagious during the latency period (Jin et al., 2020). The common clinical manifestations included fever (88.7%), cough (67.8%), fatigue (38.1%), sputum production (33.4%), shortness of breath (18.6%), sore throat (13.9%), and headache (13.6%) [16]. In addition, a part of patients manifested gastrointestinal symptoms, with diarrhea (3.8%) and vomiting (5.0%) (Guan et al., 2020). B-type Natriuretic Peptide (BNP) is mainly synthesized and secreted by myocytes in the left ventricle (LV) as a response to myocytes stretched by pressure overload or volume expansion of the ventricle (Cao et al., 2019). In patients with Community Acquired Peumonia (CAP), NT-pro BNP levels are powerful predictors of adverse cardiac events. For patients with systemic inflammatory response syndrome (SIRS), Chen et al found that compared with non-SIRS patients, subjects with SIRS had a markedly higher level of B-type natriuretic peptide (BNP). Additionally, BNP level of more than 113 pg/mL was independent predictor of all-cause mortality in septic patients. Additionally, in 302 CAP patients, Christ-Crain et al confirmed that BNP levels increased with rising disease severity as classified by the pulmonary severity index (PSI) (p=0.01). Li et al confirmed that BNP could be used as a biomarker for evaluating the severity of CAP. They recommended BNP level of 299.0 pg/mL in predicting in-hospital mortality (sensitivity 67.5%, specificity 81.6%) (Zhang et al., 2016). In respiratory system conditions, such as influenza, vitamin D has wide-ranging and fundamental roles, including through: gene transcription via COVID-19 relevant VDR (Vitamin D Receptor) pathways; wider immune function; and airway epithelial cell tight-junction function and integrity. Further, studies suggest vitamin D supplementation may be protective in respiratory conditions, the effect being highly significant in 'D' deficient persons. It is hypothesized by Watkins, 2020 and Grant et al., 2020 that vitamin D insufficiency may significantly compromise, respiratory immune response function, greatly increasing risk of COVID-19 severity and mortality (Brown and Sarkar, 2020). Primary outcomes: This study is designed to assess the difference between level of NT-pro-BNP, and Vitmin D in moderate cases who progressed to severe or critically ill category compared to those who did not. Secondary outcomes: Assessment of any possible correlation between NT-pro-BNP and Vitamin D and the need for mechanical ventilation or mortality in COVID-19 infection. The study will be conducted on 100 COVID-19 confirmed patients Group (1): 50 mild to moderate cases (lung shadows without hypoxia and oxygen saturation >92%) who progressed to severe illness characterized by hypoxia necessitating oxygen therapy, or critical illness characterized by respiratory failure necessitating mechanical ventilation either invasive or non-invasive within their hospital stay. Group (2): 50 mild to moderate cases who did not show clinical progression and were discharged.

Official Title
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N-terminal Pro B-type Natriuretic Peptide and Vitamin D Levels as Prognostic Markers in COVID-19 Pneumonia

Conditions
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COVID19 Pneumonia

Intervention / Treatment
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* Other: Pro BNP , Vitamin D


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All cases will be diagnosed with COVID-19 by RT-PCR • Group (1) Critically ill patients: Respiratory Rate > 30/min SaO2 < 92% at room temperature Chest radiology showing more than 50% lesion or progressive lesion within 24 to 48 hours • Group (2) moderate cases: Patients has pneumonia manifestations on radiology associated with symptoms &/or leucopenia or lymphopenia. Exclusion Criteria: Other causes of pneumonia other than infection with SARS-CoV-2. Concomitant heart failure. Hypoxic patients on hospital admission. Arrhythmia.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Moderate<br>Moderate: moderate COVID -19 pneumonia | Other: Pro BNP , Vitamin D<br>* This study is designed to assess the difference between level of NT-pro-BNP, and Vitamin D in moderate cases who progressed to severe or critically ill category compared to those who did not.<br>|
| Severe<br>_severe COVID-19 pneumonia | Other: Pro BNP , Vitamin D<br>* This study is designed to assess the difference between level of NT-pro-BNP, and Vitamin D in moderate cases who progressed to severe or critically ill category compared to those who did not.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| NT-pro-BNP and Vitamin D | level of NT-pro-BNP, and Vitamin D | 6 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of any possible correlation between NT-pro-BNP and Vitamin D and the need for mechanical ventilation or mortality in COVID-19 infection | Assessment of any possible correlation between NT-pro-BNP and Vitamin D and the need for mechanical ventilation or mortality in COVID-19 infection | 6 month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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NT-pro-BNP, Vitamin D, COVID-19 Pneumonia, HPLC/UV Diode array