key: cord-0966136-mmsxe4xo
authors: Hariyanto, Timotius Ivan; Kurniawan, Andree
title: Anemia is associated with severe coronavirus disease 2019 (COVID-19) infection
date: 2020-08-28
journal: Transfus Apher Sci
DOI: 10.1016/j.transci.2020.102926
sha: 506b80bfbb4ce7b520d87d6f99bc90a470986634
doc_id: 966136
cord_uid: mmsxe4xo

nan

A search of the literature was conducted on Google scholar using the keywords "anemia" OR "hematologic" OR "clinical characteristics" OR "comorbidities" OR "risk factors" AND "coronavirus disease 2019" OR "COVID-19", until July 21 st , 2020) with language restricted to English only. The title, abstract, and full text of all articles identified that matched the search criteria were assessed, and those reporting the rate of anemia in COVID-19 patients with a clinically validated definition of "severe disease" were included in this metaanalysis.

A meta-analysis was performed using Review Manager 5.4 (Cochrane Collaboration) software. Dichotomous variables were calculated using the Mantel-Haenszel formula with random-effects models. We used the I 2 statistic to assess the heterogeneity, value of < 25%, 26-50%, and > 50% considered as low, moderate, and high degrees of heterogeneity, respectively. The effect estimate was reported as odds ratio (OR) along with its 95% confidence intervals (CIs) for dichotomous variables, respectively. P-value was two-tailed, and the statistical significance set at ≤0.05.

A total of 17,200 records were obtained through systematic electronic searches and other ways. After screening titles, abstracts, and full texts, 7 studies [2] [3] [4] [5] [6] [7] [8] with a total of 9,912 COVID-19 patients were included in the meta-analysis. The essential characteristics of the included studies and the cut-off value for anemia diagnosis are summarized in Table 1 Based on a contrite meta-analysis of available data, anemia seems to be associated with an enhanced risk of severe COVID-19 infection. The possible pathophysiological link between anemia and severe COVID-19 can be explained by these reasons. Patients with anemia will have low hemoglobin levels. In the circulation system, hemoglobin serves as a carrier for oxygen to target organs in the body. When the concentration of the hemoglobin in the circulation is low, the transport of oxygen to several organs in the body will be disrupted, therefore causing hypoxia that will eventually result in multiple organ dysfunction, especially respiratory organ dysfunction. [9] Multiple organ dysfunction will contribute to the development of severe outcomes in COVID-19 infection. Moreover in COVID-19 infections, the state of anemia in the patients could be worsened. First, SARS-CoV-2 can interact with hemoglobin J o u r n a l P r e -p r o o f molecules on the erythrocyte through ACE2, CD147, and CD26 receptors. This viralhemoglobin interaction will cause the virus to attack the heme on the 1-beta chain of hemoglobin and causing hemolysis. [10] Second, SARS-CoV-2 may mimic the action of hepcidin which increases circulating and tissue ferritin (affecting liver, spleen, bone marrow, and muscles mainly), while inducing serum iron deficiency and lack of hemoglobin, by consequence. The resulting hyperferritinemia will give rise to ferroptosis, with high oxidative stress and lipoperoxidation that can precipitate the inflammatory/immune over-response (cytokine storm) and causing a severe outcome of the disease. [10] Patients with anemia should hence be advised to take extra precautions to minimize risk exposure to the virus. Physicians should be engaged in close monitoring of anemic patients with suspected COVID-19, for timely detecting signs of disease progression. Finally, the presence of anemia shall be regarded as an important factor in future risk stratification models for COVID-19. 

The prevalence of anemia and its association with 90-day mortality in hospitalized community-acquired pneumonia

Prognostic value of neutrophil-to-lymphocyte ratio, lactate dehydrogenase, D-Dimer and CT score in patients with COVID-19

Effect of Underlying Comorbidities on the Infection and Severity of COVID-19 in Korea: a Nationwide Case-Control Study

Risk factors for adverse clinical outcomes with COVID-19 in China: a multicenter, retrospective, observational study

Risk factors for disease severity, unimprovement, and mortality in COVID-19 patients in Wuhan, China

A Retrospective Analysis of the Clinical and Epidemiological Characteristics of COVID-19 Patients in Henan Provincial People's Hospital

Clinical characteristics and risk factors for severe-critically ill COVID-19 adult patients in Jiangsu, China: a multiplecentered, retrospective study

Clinical characteristics of 161 cases of corona virus disease 2019 (COVID-19) in Changsha

Daily Lowest Hemoglobin and Risk of Organ Dysfunctions in Critically Ill Patients

COVID-19: hemoglobin, iron, and hypoxia beyond inflammation. A narrative review