key: cord-0898570-txl3it02
authors: Sarkar, P. G.; Kumar, A.; Bandyopadhyay, D.
title: CHA2DS2-VASc score on admission to predict mortality in COVID-19 patients: A meta-analysis
date: 2021-06-09
journal: nan
DOI: 10.1101/2021.06.07.21258402
sha: c3e65d6e767e54f1956d405fd9556e6000b27246
doc_id: 898570
cord_uid: txl3it02

Background: CHA2DS2-VASc score is used in non-valvular AF patients to predict thromboembolic risk. Recent studies have tried to evaluate CHA2DS2-VASc score on admission in COVID-19 patients to predict mortality. Methods: We conducted a literature search on 14 April 2021 to retrieve all published studies, pre-prints and grey literature related to the predictive power of CHA2DS2-VASc score in COVID-19 patients of admission and mortality. Screening of studies and data extraction was done by two authors independently. We used the Quality in Prognosis Studies (QUIPS) tool for the methodological quality assessment of the included studies. Results: Five studies involving 5,941 patients reported the predictive value of CHA2DS2-VASc score for mortality in COVID-19 patients. The pooled sensitivity (SEN), specificity (SPE) and area under curve were 0.72 (95% CI 0.63-0.79), 0.74 (95% CI 0.67-0.81) and 0.80 (95% CI 0.76-0.83). Conclusions: CHA2DS2-VASc score at admission has good predictive value for mortality in patients with COVID-19 infection and can help clinicians identify potentially severe cases early. Early initiation of effective management in these cases may help in reducing overall mortality due to COVID-19. Trial registry: We prospectively registered this meta-analysis on PROSPERO database (Reg number: CRD42021248398).

The ongoing COVID-19 pandemic is one of the most severe crises faced by healthcare systems worldwide. Respiratory failure is one of the most common reasons for admissions into critical care units. However, SARS-CoV-2 infection has proven to be a complex disease with multi-organ involvement in many cases.

Hypoxia and generalized endothelial dysfunction due to viral invasion leading to thromboembolic complications has been postulated as a common mechanism of multi-organ failure 1 . Mortality has been significantly higher in elderly patients with pre-existing cardiovascular risk factors 2 . Poorer outcomes in these patients may be caused by the higher incidence of endothelial dysfunction and thromboembolism leading to multi-organ failure 3 .

The CHA2DS2-VASc score is a clinical score used patients of non-valvular AF to predict the risk of thromboembolism 4 . In addition, this score has been also used to predict mortality in other cardiovascular condition without AF. This score has a prognostic significance independent of AF 5 as it is a cluster of common cardiovascular risk factors seen in clinical practice.

CHA2DS2-VASc score can be readily calculated bedside using its components C(Congestive Heart Failure), H(Hypertension), A2(Age>75 years; 2 points), D(Diabetes Mellitus), S2(Stroke, TIA or thromboembolism; 2 points), V(vascular disease), A(Age 65-74 years) and Sc(Female sex) 4 . We performed this meta-analysis to evaluate the predictive values of CHA2DS2-VASc score in . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)

The copyright holder for this preprint this version posted June 9, 2021. ; https://doi.org/10.1101/2021.06.07.21258402 doi: medRxiv preprint COVID-19 patients for mortality so as to identify potentially high risk cases early.

The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA statement) guidelines were followed to perform this meta-analysis 6 .

We prospectively registered this meta-analysis on PROSPERO database (Registration number: CRD42021248398).

We reviewed PubMed, Google scholar, Scirius, Medline, Liliacs, Cochrane, CINAHIL, Plos and SIGLE databases through April 14, 2021. The search terms were as follows: "2019 Coronavirus disease" or "Novel Coronavirus" or "SARS-CoV-2-19" or "2019-nCoV" or "COVID-19" and "CHA2DS2-VASc score".

Language restrictions were avoided. Additional citations were identified by screening the reference list of the included studies.

Twoauthors (P.G.S and D.B) independently identified the studies to be included into the final analysis. Any disagreement was resolved through discussion. In case of persistent disagreement, a third reviewer (A.K) was consulted for arbitration. Studies were selected if the following criteria were met (1) The predictive value of CHA2DS2-VASc score on mortality in patients of COVID-19 was evaluated; (2) Sufficient information was available to calculate a 2x2 table for true positive (TP), false positive (FP), true negative (TN) and false negative . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)

The copyright holder for this preprint this version posted June 9, 2021. ; https://doi.org/10.1101/2021.06.07.21258402 doi: medRxiv preprint (FN). Exclusion criteria were (1) Unable to extract 2x2 table; (2) Case reports, reviews, comment, letter, animal studies. 

We used random effects model to compute the pooled sensitivity, pooled specificity with 95% CI considering the significant heterogeneity among the studies.

Summary area under the curve was computed to determine the discriminating power of CHA2DS2-VASc score for mortality. Diagnostic odds ratio was computed to provide the accuracy of CHA2DS2-VASc score for the predicting mortality. Heterogeneity more than 50% was considered as statistically significant heterogeneity. Mete-regression analysis was done to determine the source of heterogeneity and subgroup effects. All the statistical analyses was completed using software STATA version 13.

. CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted June 9, 2021. The characteristics of each study and the predictive value of CHA2DS2-VASc score for mortality in COVID-19 patients are presented in Table 1 . Three studies have been conducted in Turkey, one in Spain and one in Italy. All the studies were retrospective in nature. The number of participants varied from 318 to 3042.

All the studies have reported SEN, SPE and AUC for CHA2DS2-VASc score for predicting mortality in COVID-19 patients.

. CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted June 9, 2021. ; https://doi.org/10.1101/2021.06.07.21258402 doi: medRxiv preprint

The methodological quality of the included studies is presented in Fig.2 and (Fig.4) . The positive likelihood ratio was 2.8 (95% CI 2.0-4.0) and the negative likelihood ratio was 0.37 (95% CI 0.26-0.54). The diagnostic odds ratio (DOR) was 8 (95% CI 4-15). The pooled AUC of CHA2DS2-VASc score for discriminating mortality was 0.80 (95% CI 0.76-0.83), indicating that it has high predicting accuracy ( Figure 5 ). Fagan normogram (Fig.6) shows that if the pre-test probability was set to 20%, the post-test probability of CHA2DS2-VASc . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted June 9, 2021. ; https://doi.org/10.1101/2021.06.07.21258402 doi: medRxiv preprint score for predicting mortality was 41% when the score was 2.5. When the CHA2DS-VASc score was below cut-off value, post-test probability was only 8%.

We did the meta-regression analysis to determine the covering factors on summary measure performance. Only four variables (hypertension, diabetes, vascular risk factor and COPD) had sufficient data to conduct meta-regression analysis. We observed that no statistically significant covariate effects of hypertension, diabetes, vascular risk factor and COPD on the pooled sensitivity and pooled specificity. Although, small number of studies limiting power of regression to detect significant effects indicating that more studies are required to detect such effects if any.

Covid-19 pandemic poses a significant stress on healthcare system of the entire world. In the present scenario, it is very important to improve triage and risk stratification and to provide clinicians with easily accessible tools to easily predict adverse clinical outcomes. Scoring systems like APACHE II (Acute physiology and chronic health evaluation), COVID-GRAM etc are being studied to predict disease progression and outcome 13 . However, both these scores are difficult to be applied in resource limited settings as they are heavily dependent . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted June 9, 2021. COVID-19 has been described as a hyper-inflammatory state leading to diffuse pulmonary intravascular coagulopathy 15 . Excess mortality in these patients is often related to progressive respiratory failure and thromboembolism. The CHA2DS2-VASc score is widely used to stratify thromboembolic risk in AF patients. In addition, they also predict all-cause mortality among a wide spectrum . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted June 9, 2021. ; https://doi.org/10.1101/2021.06.07.21258402 doi: medRxiv preprint of cardiovascular disorders without AF. CHA2DS2-VASc score has been used to predict mortality in COVID19 patients too. Most of the variables of the CHA2DS2-VASc score such as elderly age, diabetes, and hypertension are also confirmed prognostic risk factors in patients hospitalized with COVID-19.

Because CHA2DS2-VASc score clubs common risk factors predicting a prothrombotic, we can expect higher mortality in COVID-19 cases with higher CHA2DS2-VASc score. Therefore, this is the first reported meta-analyses to report that a simple bedside clinical score, CHA2DS2-VASc score, can be used to predict mortality in COVID-19 patients with high prognostic value.

This meta-analysis has the following shortcomings. First, all the studies are retrospective in nature, hence prone to confounding factors. Second, prognosis of the disease may be affected by other factors not directly included in the score.

Third, as only five studies were available for meta-analysis, publication bias and sub-group analyses could not be performed. Additional high-quality studies may be required to further shed light on the prognostic significance of this score in COVID-19 patients.

Evaluating CHA2DS2-VASc score can help clinicians identify severe cases early. Initiation aggressive and timely management in these high risk patients can help in reducing mortality due to COVID-19.

. CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted June 9, 2021. ; https://doi.org/10.1101/2021.06.07.21258402 doi: medRxiv preprint and prognosis evaluation of COVID-19: a retrospective cohort study.

Lancet Haematol2020. For more information, visit www.prisma-statement.org.

Records identified through database searching (n = 26 )

Additional records identified through other sources (n = 11 )

Records after duplicates removed (n = 9 )

Records screened (n = 28 )

Full-text articles assessed for eligibility (n = 9 )

Full-text articles excluded, with reasons (n = 4 ) 3 studies reported CHA2DS score 1 study reported mChA2DS2-VASc score Studies included in qualitative synthesis (n = 5 )

Studies included in quantitative synthesis (metaanalysis) (n = 5 ) 5 studies reported the predictive value on mortality . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted June 9, 2021. ; https://doi.org/10.1101/2021.06.07.21258402 doi: medRxiv preprint . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted June 9, 2021. ; . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)

The copyright holder for this preprint this version posted June 9, 2021. ; https://doi.org/10.1101/2021.06.07.21258402 doi: medRxiv preprint . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)

The copyright holder for this preprint this version posted June 9, 2021. ; https://doi.org/10.1101/2021.06.07.21258402 doi: medRxiv preprint Table 1 : Characteristics of the included studies and diagnostic test performance of CHA2DS2-VASc score in predicting mortality in COVID-19

. CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)

The copyright holder for this preprint this version posted June 9, 2021. ; https://doi.org/10.1101/2021.06.07.21258402 doi: medRxiv preprint

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