Impact of Current Malaria Infection and Previous Malaria Exposure on the Clinical Profiles and Outcome of COVID-19 in a High Malaria Transmission Setting: A Prospective Cohort Study

Achan, Josephine; Serwanga, Asadu; Wanzira, Humphrey; Kyagulanyi, Tonny; Nuwa, Anthony; Magumba, Godfrey; Kusasira, S.; Sewanyana, I; Tetteh, Kevin K. A.; Drakeley, Chris; Nakwagala, Frederick Nelson; Aanyu, Hellen T; Opigo, Jimmy; Hamade, Prudence; Marasciulo, Madeleine; Byarugaba, Baterana; Tibenderana, James

doi:10.2139/ssrn.3844848

“…Comparatively few studies have examined infectious comorbidities, and findings from this study did not suggest an association between increased COVID-19 mortality and concurrent malaria or HIV infection or history of tuberculosis. This is potentially a function of inadequate power due to low prevalence and small sample size; other research suggests that HIV/AIDS increases risk for poor outcomes whereas malaria coinfection does not [23][24][25]. To the best of our knowledge this is the first study to assess underweight as a COVID-19 risk factor and no significant association with mortality was observed, however, only eight subjects had low BMI (seven survived).…”

Section: Discussionmentioning

confidence: 84%

Clinical progression and outcomes of patients hospitalized with COVID-19 in humanitarian settings: A prospective cohort study in South Sudan and Eastern Democratic Republic of the Congo

Doocy

¹

,

Bollemeijer²,

Leidman³

et al. 2022

PLOS Glob Public Health

0

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Little information is available on COVID-19 in Africa and virtually none is from humanitarian and more resource-constrained settings. This study characterizes hospitalized patients in the African humanitarian contexts of Juba, South Sudan and North and South Kivu in Eastern Democratic Republic of the Congo. This observational cohort was conducted between December 2020 and June 2021. Patients presenting for care at five facilities or referred from home-based care by mobile medical teams were eligible for enrollment and followed until death or recovery. Disease progression was characterized for hospitalized patients using survival analysis and mixed effects regression model to estimate survival odds for patient characteristics and treatments received. 144 COVID-19 cases enrolled as hospitalized patients were followed to recovery/death. The observed mortality proportion among hospitalized patients was 16.7% (CI: 11.2–23.3%); mortality was three times higher in South Sudan, where patients presented later after symptom onset and in worse conditions. Age and diabetes history were the only patient characteristics associated with decreased survival; clinical status indicators associated with decreased survival included fever, low oxygen level, elevated respiratory and pulse rates. The only therapy associated with survival was non-invasive oxygen; invasive oxygen therapies and other specialized treatments were rarely received. Improving availability of oxygen monitoring and proven COVID-19 therapies in humanitarian and resource-poor settings is critical for health equity. Customizing training to reflect availability of specific medications, therapies and operational constraints is particularly important given the range of challenges faced by providers in these settings.

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“…63 Of interest, CD147 is the receptor malaria parasite uses to enter cells. As COVID-19 infection rate seems to be much lower in those countries where malaria is more endemic, [235][236][237] it is argued that some competition for the same receptor may likely contribute to explain the low infection rate in these African populations. Similarly, in these countries sickle cell anemia is widely diffused, which is considered a protective evolutionary mechanism.…”

Section: A) Sialic Acidmentioning

confidence: 99%

COVID-19, Cation Dysmetabolism, Sialic Acid, CD147, ACE2, Viroporins, Hepcidin and Ferroptosis: A Possible Unifying Hypothesis

Cavezzi

¹

,

Menicagli

²

,

Troiani³

et al. 2022

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Background: iron and calcium dysmetabolism, with hyperferritinemia, hypoferremia, hypocalcemia and anemia have been documented in the majority of COVID-19 patients at later/worse stages. Furthermore, complementary to ACE2, both sialic acid (SA) molecules and CD147 proved relevant host receptors for SARS-CoV-2 entry, which explains the viral attack to multiple types of cells, including erythrocytes, endothelium and neural tissue. Several authors advocated that cell ferroptosis may be the core and final cell degenerative mechanism. Methods: a literature research was performed in several scientific search engines, such as PubMed Central, Cochrane Library, Chemical Abstract Service. More than 500 articles were retrieved until mid-December 2021, to highlight the available evidence about the investigated issues. Results: based on COVID-19 literature data, we have highlighted a few pathophysiological mechanisms, associated with virus-based cation dysmetabolism, multi-organ attack, mitochondria degeneration and ferroptosis. Our suggested elucidated pathological sequence is: a) spike protein subunit S1 docking with sialylated membrane glycoproteins/receptors (ACE2, CD147), and S2 subunit fusion with the lipid layer; b) cell membrane morpho-functional changes due to the consequent electro-chemical variations and viroporin action, which induce an altered ion channel function and intracellular cation accumulation; c) additional intracellular iron concentration due to a deregulated hepcidin-ferroportin axis, with higher hepcidin levels. Viral invasion may also affect erythrocytes/erythroid precursors, endothelial cells and macrophages, through SA and CD147 receptors, with relative hemoglobin and iron/calcium dysmetabolism. AB0 blood group, hemochromatosis, or environmental elements may represent possible factors which affect individual susceptibility to COVID-19. Conclusions: our literature analysis confirms the combined role of SA molecules, ACE2, CD147, viroporins and hepcidin in determining the cation dysmetabolism and final ferroptosis in the cells infected by SARS-CoV-2. The altered ion channels and electrochemical gradients of the cell membrane have a pivotal role in the virus entry and cell dysmetabolism, with subsequent multi-organ immune-inflammatory degeneration and erythrocyte/hemoglobin alterations.

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“…61 Of interest, CD147 is the receptor malaria parasite uses to enter cells. As COVID-19 infection rate seems to be much lower in those countries where malaria is more endemic, [233][234][235] it is argued that some competition for the same receptor may likely contribute to explain the low infection rate in these African populations. Similarly, in these countries sickle cell anemia is widely diffused, which is considered a protective evolutionary mechanism.…”

Section: A) Sialic Acidmentioning

confidence: 99%

COVID-19, Cation Dysmetabolism, Sialic Acid, CD147, ACE2, Viroporins, Hepcidin and Ferroptosis: A Possible Unifying Hypothesis

Cavezzi

¹

,

Menicagli

²

,

Troiani

³

et al. 2022

View full text Add to dashboard Cite

Background: iron and calcium dysmetabolism, with hyperferritinemia, hypoferremia, hypocalcemia and anemia have been documented in the majority of COVID-19 patients at later/worse stages. Furthermore, complementary to ACE2, both sialic acid (SA) molecules and CD147 proved relevant host receptors for SARS-CoV-2 entry, which explains the viral attack to multiple types of cells, including erythrocytes, endothelium and neural tissue. Several authors advocated that cell ferroptosis may be the core and final cell degenerative mechanism. Methods: a literature research was performed in several scientific search engines, such as PubMed Central, Cochrane Library, Chemical Abstract Service. More than 500 articles were retrieved until mid-December 2021, to highlight the available evidence about the investigated issues. Results: based on COVID-19 literature data, we have highlighted a few pathophysiological mechanisms, associated with virus-based cation dysmetabolism, multi-organ attack, mitochondria degeneration and ferroptosis. Our suggested elucidated pathological sequence is: a) spike protein subunit S1 docking with sialylated membrane glycoproteins/receptors (ACE2, CD147), and S2 subunit fusion with the lipid layer; b) cell membrane morpho-functional changes due to the consequent electro-chemical variations and viroporin action, which induce an altered ion channel function and intracellular cation accumulation; c) additional intracellular iron concentration due to a deregulated hepcidin-ferroportin axis, with higher hepcidin levels. Viral invasion may also affect erythrocytes/erythroid precursors, endothelial cells and macrophages, through SA and CD147 receptors, with relative hemoglobin and iron/calcium dysmetabolism. AB0 blood group, hemochromatosis, or environmental elements may represent possible factors which affect individual susceptibility to COVID-19. Conclusions: our literature analysis confirms the combined role of SA molecules, ACE2, CD147, viroporins and hepcidin in determining the cation dysmetabolism and final ferroptosis in the cells infected by SARS-CoV-2. The altered ion channels and electrochemical gradients of the cell membrane have a pivotal role in the virus entry and cell dysmetabolism, with subsequent multi-organ immune-inflammatory degeneration and erythrocyte/hemoglobin alterations.

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Impact of Current Malaria Infection and Previous Malaria Exposure on the Clinical Profiles and Outcome of COVID-19 in a High Malaria Transmission Setting: A Prospective Cohort Study

Cited by 5 publications

References 0 publications

Clinical progression and outcomes of patients hospitalized with COVID-19 in humanitarian settings: A prospective cohort study in South Sudan and Eastern Democratic Republic of the Congo

Clinical progression and outcomes of patients hospitalized with COVID-19 in humanitarian settings: A prospective cohort study in South Sudan and Eastern Democratic Republic of the Congo

COVID-19, Cation Dysmetabolism, Sialic Acid, CD147, ACE2, Viroporins, Hepcidin and Ferroptosis: A Possible Unifying Hypothesis

COVID-19, Cation Dysmetabolism, Sialic Acid, CD147, ACE2, Viroporins, Hepcidin and Ferroptosis: A Possible Unifying Hypothesis

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