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

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.