A Southeast Asian Perspective on the COVID-19 Pandemic: Hemoglobin E (HbE)-Trait Confers Resistance Against COVID-19

Papadopoulos, Konstantinos I.; Sutheesophon, Warachaya; Manipalviratn, Somjate; Aw, Tar Choon

doi:10.12659/msmbr.929207

Cited by 13 publications

(18 citation statements)

References 45 publications

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“…In dengue virus infection, which is perennially endemic in South-East Asia, red blood cell precursors in Thai carriers of thalassemia and HbE trait were significantly less susceptible to the dengue virus compared to normal controls. [ 31 ] The hypothesized conferred protection against COVID-19 could also derive from local SE Asian HLA-class allotypes, possibly in linkage disequilibrium with the thalassemia mutations. Protection from and resistance to severe malaria has been described in association with HLA antigens in the African continent.…”

Section: Discussionmentioning

confidence: 99%

SARS-CoV-2 and dengue virus coinfection in an adult with beta-thalassemia (trait): A case report from Bangladesh with literature review

Hossain¹,

Sarmin²,

Rahman³

et al. 2021

Heliyon

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Section: Discussionmentioning

confidence: 99%

SARS-CoV-2 and dengue virus coinfection in an adult with beta-thalassemia (trait): A case report from Bangladesh with literature review

Hossain¹,

Sarmin²,

Rahman³

et al. 2021

Heliyon

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“…A study conducted by Edouard Lansiaux et al 5 showed that a higher prevalence of beta thalassemia and a higher resistance against COVID-19 were found in the areas of Italy, Cyprus and Southeast Asia. 5,6 This geographical pattern, known as the 'thalassemia belt', spans along countries from the Mediterranean Sea to the Asian continent. In Cyprus, according to data, there were 560 people with beta thalassemia major.…”

Section: Articlementioning

confidence: 99%

COVID-19 in patients with transfusion dependent thalassemia in Indonesia: characteristics of the disease and patients, and comparison between epidemiological data for COVID-19 and thalassemia in Indonesia and South-East Asia

Atmakusuma

2022

Hematol Rep

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Background: People living with transfusion dependent thalassemia have high risk of getting infected by COVID-19. This can be caused by both several factors. Chronic complications of thalassemia also render them more vulnerable to infectious diseases, including COVID-19. However, anecdotal data shows that Thalassemia patients less incidence of COVID-19 compared to the general population. Patients and methods: This research used a cross sectional design. The study was conducted at the Division of Haematology and Medical Oncology of the Cipto Mangunkusumo Hospital in Jakarta from May 2020 – August 2021. Total sampling method was used involving all Thalassemia Major patients who had been infected with COVID-19 obtained directly from medical record and through the thalassemia patients-parents foundation Results: From 10,397 patients with thalassemia, 72 (0.69%) people were infected by COVID-19 and 7 (9.7%) were deceased. Meanwhile, the incidence of COVID-19 in general population of Indonesia was 0.87%, more than in the thalassemia population. This means that thalassemia might provide protection against COVID-19 due to several mechanism. Conclusion: Indonesia and other countries with high prevalence of thalassemia have lower COVID-19 incidence than countries with low prevalence of thalassemia. Thalassemia might have protective effect against COVID-19. Well designed studies are needed to provide better evidence on the protective effect of thalassemia on COVID-19.

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“…Genetically predisposed children already enjoy protective EPO levels through sustained elevated Ang II levels, through the ACE D allele in some, the ACE2 T allele leading to lower ACE2 expression in females[ 6 , 45 ], or HbE/beta thalassemia in others, thus protecting against coronavirus disease 2019 (COVID-19), in similar ways seen in malaria and dengue fever[ 46 ] (Figure 1 ). EPO secretion augmenting genetic determinants alone or synergistically, might protect from or allow an asymptomatic and uncomplicated SARS-CoV2 infection leading to seropositivity and subsequent immunity[ 2 ]. In the 2 nd Indian serosurvey, where only 3% of the seropositive individuals reported symptoms suggestive of COVID-19[ 47 ], the highest seropositivity rate was from the state of Odisha (formerly Orissa), where almost one quarter of the malaria burden of India is found[ 48 ].…”

Section: Epo Is An Ancestral Neuroprotective Mechanism Preventing Lethal Cerebral Insults At Young Age: Implications For Covid-19mentioning

confidence: 99%

“…The COVID-19 pandemic continues to be a global threat despite increasing vaccinations[ 1 ]. We and others have recently proposed that the thalassemias and especially HbE, might confer resistance to and/or protection from SARS-CoV2 infection and severity[ 2 , 3 ]. Supporting this hypothesis, Littera et al [ 4 ] from Sardinia found none of their seriously ill COVID-19 patients were carriers of beta-thalassemia while a recent metanalysis reported a pooled incidence rate of COVID-19 in patients with beta thalassemia at 1.34 per 100000 personday, which is less than half of that observed in the general population (2.89)[ 5 ].…”

Section: Introductionmentioning

confidence: 99%

“…Supporting this hypothesis, Littera et al [ 4 ] from Sardinia found none of their seriously ill COVID-19 patients were carriers of beta-thalassemia while a recent metanalysis reported a pooled incidence rate of COVID-19 in patients with beta thalassemia at 1.34 per 100000 personday, which is less than half of that observed in the general population (2.89)[ 5 ]. We hypothesized that host immune system modulations engendered by malarial selection pressure via thalassemia/HbE mutations might confer this protection akin to an antimalarial effect[ 2 ]. Another genetic variant significantly associated with mild malaria vs severe malaria is the D allele of angiotensin converting enzyme (ACE) I/D polymorphism, that codes for higher ACE levels and subsequently increased angiotensin II (Ang II) production vs the I allele[ 6 - 8 ].…”

Section: Introductionmentioning

confidence: 99%

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Age and genotype dependent erythropoietin protection in COVID-19

Papadopoulos

Sutheesophon

Manipalviratn³

et al. 2021

WJSC

Self Cite

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Erythropoietin (EPO) is the main mediator of erythropoiesis and an important tissue protective hormone that appears to mediate an ancestral neuroprotective innate immune response mechanism at an early age. When the young brain is threatened-prematurity, neonatal hyperbilirubinemia, malaria- EPO is hyper-secreted disproportionately to any concurrent anemic stimuli. Under eons of severe malarial selection pressure, neuroprotective EPO augmenting genetic determinants such as the various hemoglobinopathies, and the angiotensin converting enzyme (ACE) I/D polymorphism, have been positively selected. When malarial and other cerebral threats abate and the young child survives to adulthood, EPO subsides. Sustained high ACE and angiotensin II (Ang II) levels through the ACE D allele in adulthood may then become detrimental as witnessed by epidemiological studies. The ubiquitous renin angiotensin system (RAS) influences the α-klotho/fibroblast growth factor 23 (FGF23) circuitry, and both are interconnected with EPO. Here we propose that at a young age, EPO augmenting genetic determinants through ACE D allele elevated Ang II levels in some or HbE/beta thalassemia in others would increase EPO levels and shield against coronavirus disease 2019, akin to protection from malaria and dengue fever. Human evolution may use ACE2 as a “bait” for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) to gain cellular entry in order to trigger an ACE/ACE2 imbalance and stimulate EPO hypersecretion using tissue RAS, uncoupled from hemoglobin levels. In subjects without EPO augmenting genetic determinants at any age, ACE2 binding and internalization upon SARS-CoV-2 entry would trigger an ACE/ACE2 imbalance, and Ang II oversecretion leading to protective EPO stimulation. In children, low nasal ACE2 Levels would beneficially augment this imbalance, especially for those without protective genetic determinants. On the other hand, in predisposed adults with the ACE D allele, ACE/ACE2 imbalance, may lead to uncontrolled RAS overactivity and an Ang II induced proinflammatory state and immune dysregulation, with interleukin 6 (IL-6), plasminogen activator inhibitor, and FGF23 elevations. IL-6 induced EPO suppression, aggravated through co-morbidities such as hypertension, diabetes, obesity, and RAS pharmacological interventions may potentially lead to acute respiratory distress syndrome, cytokine storm and/or autoimmunity. HbE/beta thalassemia carriers would enjoy protection at any age as their EPO stimulation is uncoupled from the RAS system. The timely use of rhEPO, EPO analogs, acetylsalicylic acid, bioactive lipids, or FGF23 antagonists in genetically predisposed individuals may counteract those detrimental effects.

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A Southeast Asian Perspective on the COVID-19 Pandemic: Hemoglobin E (HbE)-Trait Confers Resistance Against COVID-19

Cited by 13 publications

References 45 publications

SARS-CoV-2 and dengue virus coinfection in an adult with beta-thalassemia (trait): A case report from Bangladesh with literature review

SARS-CoV-2 and dengue virus coinfection in an adult with beta-thalassemia (trait): A case report from Bangladesh with literature review

COVID-19 in patients with transfusion dependent thalassemia in Indonesia: characteristics of the disease and patients, and comparison between epidemiological data for COVID-19 and thalassemia in Indonesia and South-East Asia

Age and genotype dependent erythropoietin protection in COVID-19

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