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Association of HScore Parameters with Severe COVID-19: A Systematic Review and Meta-Analysis
Mohammad Hossein Kazemi1,2, Bentolhoda Kuhestani Dehaghi1,3, Elham Roshandel1
1Hematopoietic Stem Cell Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Insights
Severe COVID-19 (sCOVID-19) shares features with hemophagocytic lymphohistiocytosis (HLH). This meta-analysis found HScore parameters like fever and hyperferritinemia are associated with sCOVID-19 severity, though some findings contrast with HLH criteria.
Area of Science:
- Hematology
- Infectious Diseases
- Critical Care Medicine
Background:
- Severe COVID-19 (sCOVID-19) has been linked to secondary hemophagocytic lymphohistiocytosis (sHLH).
- The hemophagocytic syndrome diagnostic score (HScore) has been proposed for evaluating sCOVID-19.
- Understanding HScore parameter associations with COVID-19 severity is crucial.
Purpose of the Study:
- To systematically review and meta-analyze the association between HScore parameters and COVID-19 severity.
- To identify key hematological and clinical markers indicative of severe disease.
Main Methods:
- Systematic search of Medline, EMBASE, and Cochrane databases for studies published in 2020.
- Inclusion of 18 studies with 2459 patients.
- Meta-analysis using random/fixed-effect models to estimate pooled mean differences and odds ratios.
Main Results:
- Significant differences in leukocyte, neutrophil, AST, ferritin, and fibrinogen levels between severe and non-severe COVID-19 patients.
- Lower levels of lymphocytes, platelets, and hemoglobin were observed in severe cases.
- Fever showed a trend towards association with increased odds of severe COVID-19 (P=0.051).
Conclusions:
- Lymphopenia, thrombocytopenia, hypohemoglobinemia, hyperferritinemia, elevated AST, and fever are common in both sCOVID-19 and HLH.
- Leukocytosis, neutrophilia, and hyperfibrinogenemia in sCOVID-19 contrast with typical HScore findings.
- HScore parameters may serve as risk factors for sCOVID-19, but require refined interpretation for this specific condition.
Background:
Several reports have associated the severe Coronavirus disease-2019 (sCOVID-19) with secondary-hemophagocytic lymphohistiocytosis (sHLH) and proposed utilizing the hemophagocytic syndrome diagnostic score (HScore) for sCOVID-19 patients. We conducted a systematic review and meta-analysis to find the possible association of HScore parameters with severity in COVID-19 patients.
Methods:
A systematic search was performed in Medline via PubMed, EMBASE, and Cochrane databases using all HScore and COVID-19 keywords. The studies were all from 2020, and the study language was limited to English. The records were screened based on inclusion/exclusion criteria. Random/fixed-effect models were employed for meta-analysis, based on the I2 index of parameters. The pooled mean differences were estimated for continuous parameters. The pooled odds-ratio was estimated for fever. The level of significance was set at 0.05.
Results:
Eighteen studies (comprising 2459 patients) out of 26151 screened studies were included in this meta-analysis. The results showed that the level of leukocyte, neutrophil, aspartate transaminase (AST), ferritin, and fibrinogen were significantly higher in sCOVID-19 patients than in non-severe ones. Significant lower levels of lymphocyte, platelet, and hemoglobin were also found in sCOVID-19 patients than non-severe patients. Fever was nearly associated with two times increased odds of sCOVID-19 (P=0.051).
Conclusion:
Lymphopenia, thrombocytopenia, hypohemoglobinemia, hyperferritinemia, high levels of AST, and fever are common features of both sCOVID-19 and HLH. However, the leukocytosis, neutrophilia, and hyperfibrinogenemia found in sCOVID-19 are in contrast with HScore. Conclusively, HScore parameters could be risk factors for sCOVID-19. However, some parameters' roles are contradictory, suggesting the need for further investigation and a new way of HScore interpretation in sCOVID-19 patients.A preprint of this study was published at https://www.researchsquare.com/article/rs-54490/v2.
