B-Type Natriuretic Peptide as Biomarker of COVID-19 Disease Severity—A Meta-Analysis

Up to 15% of coronavirus disease 2019 (COVID-19) patients experience severe clinical presentation, resulting in acute respiratory distress (ARDS) and finally death. N-terminal natriuretic peptide (NT-proBNP) is associated with a worse prognosis in patients with ARDS. However, whether or not this peptide can help discriminate high-risk COVID-19 patients remains unclear. Therefore, in this meta-analysis, we summarized the available evidence on NT-proBNP in patients admitted for COVID-19. Pooled mean, mean differences (MD) and standardized mean difference (SMD) were the summary metrics. Thirteen studies were finally selected for this analysis with a total of 2248 patients, of which 507 had a severe condition (n = 240) or died (n = 267). Pooled mean NT-proBNP levels on admission were 790.57 pg/mL (95% confidence intervals (CIs): 532.50 to 1048.64) in patients that experienced a severe clinical condition or died, and 160.56 pg/mL (95% CI: 118.15 to 202.96) in non-severe patients (SMD: 1.05; 95% (CI): 0.83 to 1.28; p < 0.001; I2 74%; and MD was 645.84 pg/mL (95% CI: 389.50–902.18). Results were consistent in studies categorizing patients as non-survivors versus survivors (SMD: 1.17; 95% CI 0.95 to 1.40; p < 0. 001; I2: 51%), and in those classifying populations in severe versus non-severe clinical condition (SMD: 0.94 95% CI 0.56 to 1.32; p < 0.001; I2: 81%; pinteraction = 0.30). In conclusion, our results suggest that assessing NT-proBNP may support physicians in discriminating high-risk COVID-19 patients.


Rationale 3 Describe the rationale for the review in the context of what is already known. 3
Objectives 4 Provide an explicit statement of questions being addressed with reference to participants, interventions, comparisons, outcomes, and study design (PICOS). 3

Protocol and registration 5
Indicate if a review protocol exists, if and where it can be accessed (e.g., Web address), and, if available, provide registration information including registration number. NA Eligibility criteria 6 Specify study characteristics (e.g., PICOS, length of follow-up) and report characteristics (e.g., years considered, language, publication status) used as criteria for eligibility, giving rationale. 3

Information sources 7
Describe all information sources (e.g., databases with dates of coverage, contact with study authors to identify additional studies) in the search and date last searched. 3 Search 8 Present full electronic search strategy for at least one database, including any limits used, such that it could be repeated. 3

Study selection 9
State the process for selecting studies (i.e., screening, eligibility, included in systematic review, and, if applicable, included in the meta-analysis). 3 Data collection process 10 Describe method of data extraction from reports (e.g., piloted forms, independently, in duplicate) and any processes for obtaining and confirming data from investigators.

3-4 Data items 11
List and define all variables for which data were sought (e.g., PICOS, funding sources) and any assumptions and simplifications made.

Risk of bias in individual studies
12 Describe methods used for assessing risk of bias of individual studies (including specification of whether this was done at the study or outcome level), and how this information is to be used in any data synthesis. 4

Summary measures 13
State the principal summary measures (e.g., risk ratio, difference in means). 4

Synthesis of results 14
Describe the methods of handling data and combining results of studies, if done, including measures of consistency (e.g., I 2 ) for each meta-analysis. 4

Risk of bias across studies 15
Specify any assessment of risk of bias that may affect the cumulative evidence (e.g., publication bias, selective reporting within studies). 4

Additional analyses 16
Describe methods of additional analyses (e.g., sensitivity or subgroup analyses, meta-regression), if done, indicating which were pre-specified. 4

Study selection 17
Give numbers of studies screened, assessed for eligibility, and included in the review, with reasons for exclusions at each stage, ideally with a flow diagram. 4

Study characteristics 18
For each study, present characteristics for which data were extracted (e.g., study size, PICOS, follow-up period) and provide the citations. 4  admission to the intensive care unit (ICU) for treatment

Deng Q. et al
Severe (one of the three criteria: respiratory distress and respiratory rate higher than 30 times per minute; fingertip blood oxygen saturation <93% at rest; partial arterial oxygen pressure (PaO 2 )/fraction of inspiration oxygen (FiO 2 ) < 300 mmHg) plus critical type (one of three conditions: respiratory failure, requiring mechanical ventilation; shock; multiple organ failure, requiring intensive care management)

Han H. et al
Severe cases (at least one of the following conditions: (a) shortness of breath, RR ≥ 30 times/min, (b) oxygen saturation (resting state) ≤93%, or (c) PaO2/FiO2 ≤ 300mm Hg) plus Critical cases (at least one of the extra following conditions: (a) respiratory failure that needs to receive mechanical ventilation; (b) shock; and (c) multiple organ failure that need to be transferred to the intensive care unit (ICU)

Yun L. et al
Severe Pneumonia (patients with the following severe manifestations: fever or suspected respiratory infection, plus one of a respiratory rate >30 breaths/min, severe respiratory distress, or SpO2 <90% on room air. Patients with ARDS, sepsis, or septic shock were also included.

Zhe Z. et al
Severe patients should meet at least one of the following criterions: First, shortness of breath with respiration rate (RR) ≥30 times/min. Second, oxygen saturation ≤93% in resting state. Third, partial pressure of arterial oxygen (PaO2)-to-fraction of inspired oxygen (FiO2) ratio ≤300 mm Hg. Obvious lesion progression >50% within 24-48 hours on pulmonary imaging were also recognized as severe cases. Critical cases were defined when one of the following conditions met: First, respiratory failure and require mechanical ventilation. Second, shock occurred. Third, combined with other organ failure and treated in intensive care unit. Mild and moderate cases were defined as non-severe group, while severe and critical patients were categorized as severe group in this study.