key: cord-0753076-ubkl52d0 authors: Kehinde, Tawakalitu Abosede; Osundiji, Mayowa Azeez title: Sickle cell trait and the potential risk of severe coronavirus disease 2019—A mini‐review date: 2020-07-14 journal: Eur J Haematol DOI: 10.1111/ejh.13478 sha: b3955ddb9f28dcdd8727a2c75f27bd0e37e56253 doc_id: 753076 cord_uid: ubkl52d0 Coronavirus Disease 2019 (COVID‐19) pandemic is a rapidly evolving public health problem. The severity of COVID‐19 cases reported hitherto has varied greatly from asymptomatic to severe pneumonia and thromboembolism with subsequent mortality. An improved understanding of risk factors for adverse clinical outcomes may shed some light on novel personalized approaches to optimize clinical care in vulnerable populations. Emerging trends in the United States suggest possibly higher mortality rates of COVID‐19 among African Americans, although detailed epidemiological study data is pending. Sickle cell disease (SCD) disproportionately affects Black/African Americans in the United States as well as forebearers from sub‐Saharan Africa, the Western Hemisphere (South America, the Caribbean, and Central America), and some Mediterranean countries. The carrier frequency for SCD is high among African Americans. This article underscores the putative risks that may be associated with COVID‐19 pneumonia in sickle cell trait as well as potential opportunities for individualized medical care in the burgeoning era of personalized medicine. thromboembolism to the severity of COVID-19. Increasing evidence suggests a higher risk of venous thromboembolism in COVID-19, [3] [4] [5] prompting ongoing considerations and potential applications of prophylactic anticoagulation 24 and therapeutic thrombolysis. 25 Being the carrier state for an autosomal recessive genetic disorder, sickle cell trait is frequently perceived to be a relatively benign condition; however, this remains controversial. [26] [27] [28] [29] [30] Conditions of increased oxygen demands may trigger sickle-related complications in heterozygotes. [31] [32] [33] [34] [35] [36] [37] [38] [39] [40] [41] [42] [43] [44] COVID-19 causes severe pneumonia in at-risk individuals resulting in an increased oxygen demand. Yet, the notion that COVID-19 associated pneumonia may result in poor clinical outcomes in sickle cell trait if unrecognized is less discussed. This mini-review highlights the putative risks of severe COVID-19 in SCD and sickle cell trait, with a focus on the risks associated with the heterozygous state. Sickle cell trait affects approximately 300 million people globally. 45 Owing to its protective effects against severe malaria, sickle cell trait confers an evolutionary survival advantage. 46 The highest prevalence of sickle cell trait is in Africa and among people of African descent across the world. 18, 47 In the United States, national estimates of the sickle cell trait prevalence from Newborn Screening data suggest about 1.5% with about 8% prevalence among African Americans, almost 3 million individuals. 48 About 1%-3% of the European population carries a gene mutation for hemoglobinopathy, particularly sickle cell trait. [49] [50] [51] [52] Approximately 5% of the world carry a significant hemoglobin gene variant. 52 A recent global meta-estimate of birth prevalence of SCD was approximately 112 per 100 000 live births with about 10 folds higher birth prevalence in Africa, 1125 per 100 000. 18, 47 Being the heterozygous state, red blood cells in sickle cell trait have one copy of normal adult hemoglobin (Hb) denoted as HbA and one copy of mutant Hb (HbS) resulting in Hb genotype of HbAS. 53 HbS results from a missense mutation causing amino acid substitution whereby valine replaces glutamic acid in the 6th codon of the β chain. 54, 55 The presence of HbA attenuates HbS phenotype, reducing the probability of polymer formation; hence, normal hematological parameters are observed in the majority of individuals with sickle cell trait. 54 COVID-19 course in four SCD patients, who seemed to have benefited from early risk stratification and initiation of treatment. 59 A larger case series of 10 SCD patients described 6 confirmed cases of COVID-19, one of which was fatal. 23 There are two independent case reports of patients with severe COVID-19 who responded well to tocilizumab. 21, 22 The dataset on COVID-19 in SCD patients continues to evolve. Although ACS has been reported in a few patients with sickle cell trait, 60 ,61 it appears to be exceedingly rare. 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