key: cord-0711983-h86cufyp authors: Sahu, Bikash R; Kishor Kampa, Raj; Padhi, Archana; Panda, Aditya K. title: C-reactive protein: a promising biomarker for poor prognosis in COVID-19 infection date: 2020-06-05 journal: Clin Chim Acta DOI: 10.1016/j.cca.2020.06.013 sha: a710aaa7b61576ed26b3e18cf8627675f3ca3387 doc_id: 711983 cord_uid: h86cufyp BACKGROUND: The novel coronavirus disease 2019 (COVID-19) break out from Wuhan, China, spread over 227 countries and caused approximately 0.3 million death worldwide. Several biomolecules have been explored for possible biomarkers for prognosis outcome. Although increased C reactive protein (CRP) has been associated with death due to COVID-19 infections, results from different populations remain inconsistent. For a conclusive result, the present meta-analysis was performed. METHODS: We conducted a literature survey in PubMed and Scopus database for the association of CRP concentration with COVID-19 disease outcomes. A total of 16 eligible studies were enrolled in the present analysis comprising of 1896 survivors and 849 non-survivors cases. Concentrations of CRP were compared and analyzed by a meta-analysis. RESULTS: Egger’s regression analysis (intercept=0.04, P=0.98, 95%CI=-5.48 to 5.58) and funnel plot revealed an absence of publication bias in the included studies. Due to the presence of significant heterogeneity across the studies (Q=252.03, P(heterogeneity)= 0.000, I(2)=93.65) random model was used for the analysis of the present study. The results of the meta-analysis demonstrated a significant role of CRP in COVID-19 infection outcome (Standard difference in means= 1.371, P=0.000). CONCLUSIONS: Concentrations of CRP remained increased in patients who died in COVID-19 infection and could be a promising biomarker for accessing disease lethality. The first case of Novel coronavirus disease 2019 was detected in Wuhan, China, in late December, that broke out worldwide, affecting over 227 countries and caused approximately three lakhs deaths till date (https://www.worldometers.info/coronavirus/ accessed on 13/05/2020). The mortality rate remained 14.50% worldwide (https://www.worldometers.info/coronavirus/ accessed on 13/05/2020). World Health Organisation had declared COVID-19 as pandemic disease (http://www.euro.who.int/en/health-topics/health-emergencies/coronavirus-covid-19/news/news/2020/3/who-announces-covid-19-outbreak-a-pandemic). As of today (13/05/2020), the United States of America contributed the highest number of infected cases and death due to COVID-19 in comparison to other populations (https://www.worldometers.info/coronavirus/ accessed on 13/05/2020). COVID-19 infection displays a wide range of clinical manifestations. A recent study [1] highlighted cough, sputum production, diarrhoea, nausea/vomiting, and shortness of breath as more frequent clinical phenotypes in critical/non-survived COVID-19 patients, and in contrast, fever and headache were less prevalent. Furthermore, the pathogenesis of the diseases is regulated by several host factors. Various biomolecules such as aspartate aminotransferase, creatinine, high-sensitive cardiac troponin, procalcitonin, lactate dehydrogenase, and D-dimer has been increased in COVID-19 critical patients in comparison to those with non-severe infected cases [1] . The upregulation of C reactive protein (CRP) has been reported during severe acute respiratory syndrome (SARS) outbreak in 2002 and associated with respiratory dysfunctions and death of the patients [2] . Based on these observations, various studies were carried out in COVID-19 patients hypothesizing CRP as one of the possible biomolecules linked with the death of the infected patients. However, the observations of the reports remained contradictory. Two authors, RKP and BRP searched various databases (Medline, ScienceDirect, and Scopus) to trace eligible studies for the present meta-analysis. The keywords used for the search were "COVID-19, coronavirus 2019, 2019-nCoV, SARS-CoV-2, CRP, C-reactive protein, survivors, non-survivors, death, (till 10 th May 2020). The title and abstracts of the articles obtained were screened, and apposite papers were downloaded. Furthermore, various preprint servers (bioRxiv, medRxiv and SSRN) were also screened with the above-mentioned keywords. Various inclusion and exclusion criteria were considered in the present investigation. Inclusion of a report in the current meta-analysis must have a) added analysis for death and survivors, b) plasma/serum CRP concentrations, c) data must be presented in mean± standard deviation (S.D) or median (interquartile range). Exclusion of the articles was based on the following conditions: a) duplicate articles, b) research articles including only survivors or death cases, c) lack of CRP concentrations data d) review article, summaries, or case report. Two authors BRS and AP extracted data such as authors' details, years of publication, population, number of COVID-19 infected subjects, death and survivors, CRP concentrations in mean± S.D. or median (interquartile range), significance value. Details are shown in Table-1 The meta-analysis was performed by comprehensive meta-analysis V3.1 software (Biostat). Begg's funnel plot and Eggers linear regression analysis were employed to test publication bias. CRP data was available in the median (interquartile range) format in most of the included reports, and those were converted into mean ± standard deviation according to an earlier report [3] . Association of CRP concentrations with COVID-19 disease prognosis was analyzed, and the combined standard difference in means and P-values were calculated. The Q test and I 2 statistics evaluated heterogeneity among included reports. Based on the results of heterogeneity statistics, random (heterogeneous), or fixed model (nonheterogenous) were deployed for analysis. Furthermore, a sensitivity analysis was performed to test the robustness of the meta-analysis. A total of 122 and 153 articles were obtained after searching PubMed and Scopus, respectively. After screening the titles, abstracts, and full text based on inclusion and exclusion criterias, 14 articles including data of 15 different cohorts were enrolled for the present analysis. Further, we found two articles related to our searched norms from preprint servers. Baseline data from all eligible publications were extracted and presented in Table-1. CRP data in median (interquartile range) were converted into the required format of CMA V3.1 software (mean ± S.D and sample number) [3] . infected patients include acute respiratory distress syndrome, acute cardiac injury, acute kidney injury, shock, disseminated intravascular coagulation, and a significant alterations in CRP level have been observed in these subjects [4] . A positive correlation between CRP concentrations with the lung lesion in COVID-19 infected patients has been demonstrated [2] . Furthermore, the induction of acute kidney damage [5] and the extent of the cardiac injury [6] has been directly linked with the CRP concentrations. 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The present meta-analysis revealed significant association of CRP with poor prognosis of COVID-19 infection