SARS-CoV-2 and Plasmodium falciparum common immunodominant regions may explain low COVID-19 incidence in the malaria-endemic belt

Iesa, Mohamed A. M.; Osman, Mohamed; Hassan, Mohamed A.; Dirar, Amina Ia; Abuzeid, Nadir; Mancuso, James J.; Pandey, Ritu; Mohammed, Arwa A.; Borad, Mitesh J.; Babiker, Hani M.; Konozy, Emadeldin He

doi:10.1016/j.nmni.2020.100817

Cited by 71 publications

(89 citation statements)

References 37 publications

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“…A study by Iesa et al ( 27 ) has conducted a search of B- and T-cell immunodominant epitope as well as B- and T-cell major histocompatibility complex (MHC) restricted epitopes for shared sequences between P. falciparum and SARS-CoV-2. They reported no significantly shared homology between P. falciparum B-cell epitopes with SARS-CoV-2, suggesting that no antibodies to P. falciparum could be proposed as eliciting an immune response against infection with SARS-CoV-2 through cross-reactivity.…”

Section: Discussionmentioning

confidence: 99%

“…They reported no significantly shared homology between P. falciparum B-cell epitopes with SARS-CoV-2, suggesting that no antibodies to P. falciparum could be proposed as eliciting an immune response against infection with SARS-CoV-2 through cross-reactivity. However, Iesa et al ( 27 ) observed more than 40% of identities between SARS-CoV-2 N-protein (amino acids 215–227) and P. falciparum thrombospondin-related anonymous protein (TRAP) epitopes located at amino acids 509–523 and also between SARS-CoV-2 open reading frame 1ab (ORF1ab) and TRAP (amino acids 101–130). The immunological memory elicited following P. falciparum infection could be protective against SARS-CoV-2 infection or severe COVID-19 through the original antigenic sin theory ( 28 ), where a second antigen relies on the memory established by the first antigen to initiate response.…”

Section: Discussionmentioning

confidence: 99%

“…Iesa et al's study has revealed several conserved tetrapeptides and pentapeptides between P. falciparum and SARS-CoV-2 in the T-cell immunodominant epitope and T-cell MHC restricted epitopes. Both epitopes have been reported to stimulate CD8 + T-lymphocyte response through the HLA-A.02:01 recognition and it has been suggested that the memory of the cellular adaptive immunity mounted against the TRAP-immunodominant epitope could recognize the 219-LALLLLDRL-227–HLA-A * 02:01 complexes originating from SARS-CoV-2 infection in malaria-endemic regions and trigger an immune response ( 27 ). Much as these hypotheses need to be tested, we acknowledge that the protective effect of P. falciparum against COVID-19 infection/severity may be due to other biochemical or immunological processes that need to be elucidated.…”

Section: Discussionmentioning

confidence: 99%

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Less Severe Cases of COVID-19 in Sub-Saharan Africa: Could Co-infection or a Recent History of Plasmodium falciparum Infection Be Protective?

et al. 2021

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Sub-Saharan Africa has generally experienced few cases and deaths of coronavirus disease 2019 (COVID-19). In addition to other potential explanations for the few cases and deaths of COVID-19 such as the population socio-demographics, early lockdown measures and the possibility of under reporting, we hypothesize in this mini review that individuals with a recent history of malaria infection may be protected against infection or severe form of COVID-19. Given that both the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and Plasmodium falciparum (P. falciparum) merozoites bind to the cluster of differentiation 147 (CD147) immunoglobulin, we hypothesize that the immunological memory against P. falciparum merozoites primes SARS-CoV-2 infected cells for early phagocytosis, hence protecting individuals with a recent P. falciparum infection against COVID-19 infection or severity. This mini review therefore discusses the potential biological link between P. falciparum infection and COVID-19 infection or severity and further highlights the importance of CD147 immunoglobulin as an entry point for both SARS-CoV-2 and P. falciparum into host cells.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Less Severe Cases of COVID-19 in Sub-Saharan Africa: Could Co-infection or a Recent History of Plasmodium falciparum Infection Be Protective?

et al. 2021

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“…These correlations were also found between immunodominant sequences [N protein from SARS-CoV-2/SARS-CoV and thrombospondin-anonymous-related protein (TRAP) from P. falciparum] and [S protein-SARS-CoV-2/SARS-CoV and predicted epitope in sporozoite surface protein -2 (SSP-2) from P. falciparum]. Individually, both epitopes could induce the response of CD8+ CTL by HLA-A*02:01 presentation ( 1 , 2 ). Lesa et al.…”

Section: Is Oas Harmful?mentioning

confidence: 95%

“…presumed that the memory of adaptive immunity elevated against the described TRAP immunodominant epitope could recognize peptide-HLA-A*02:01 complexes originating from SARS-CoV-2 infection in malaria-endemic regions, particularly in Africa, and modify the host immune system response. Of course, such an assumption needs further empirical testing to prove its validity and ascertain the strength of the primed response ( 1 ).…”

Section: Is Oas Harmful?mentioning

confidence: 99%

HLA, Immune Response, and Susceptibility to COVID-19

et al. 2021

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The severe acute respiratory syndrome caused by Coronavirus 2 (SARS-CoV-2) that appeared in December 2019 has precipitated the global pandemic Coronavirus Disease 2019 (COVID-19). However, in many parts of Africa fewer than expected cases of COVID-19, with lower rates of mortality, have been reported. Individual human leukocyte antigen (HLA) alleles can affect both the susceptibility and the severity of viral infections. In the case of COVID-19 such an analysis may contribute to identifying individuals at higher risk of the disease and the epidemiological level to understanding the differences between countries in the epidemic patterns. It is also recognized that first antigen exposure influences the consequence of subsequent exposure. We thus propose a theory incorporating HLA antigens, the “original antigenic sin (OAS)” effect, and presentation of viral peptides which could explain with differential susceptibility or resistance to SARS-CoV-2 infections.

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Humoral Immunity Profiling to Pandemic and Bat‐Derived Coronavirus Variants: A Geographical Comparison

Fathi,

Alfonso,

Yek

et al. 2024

Advanced Science

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Dynamic pathogen exposure may impact the immunological response to SARS‐CoV‐2 (SCV2). One potential explanation for the lack of severe SCV2‐related morbidity and mortality in Southeast Asia is prior exposure to related betacoronaviruses. Recent discoveries of SCV2‐related betacoronaviruses from horseshoe bats (Rhinolophus sinicus) in Thailand, Laos, and Cambodia suggest the potential for bat‐to‐human spillover exposures in the region. In this work, serum antibodies to protein constructs from SCV2 and a representative bat coronavirus isolated in Cambodia (RshSTT182) are measured in pre‐pandemic Cambodian human sera using ELISA assays. Of 293 Cambodian samples tested (N = 131 with acute malaria, n = 162 with acute undifferentiated febrile illness), 32 (10.9%) are seropositive for SCV2 based on established Spike and receptor‐binding domain (RBD) cutoffs. Within SCV2 seropositive samples, 16 (50%) have higher antibody levels to antigens from the representative virus RshSTT182 versus SCV2 antigens; competitive binding ELISA assays demonstrate inhibition of reactivity to SCV2 Spike after pre‐incubation with RshSTT182 Spike. Surrogate virus neutralization tests demonstrate that 8/30 (26.7%) SCV2 ELISA positive pre‐pandemic Cambodian samples have neutralizing activity against SCV2, while 14/30 (46.7%) have activity against other SCV2‐related betacoronaviruses. These data suggest that exposure to related betacoronaviruses may elicit cross‐reactive immunity to SCV2 prior to the global pandemic.

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SARS-CoV-2 and Plasmodium falciparum common immunodominant regions may explain low COVID-19 incidence in the malaria-endemic belt

Cited by 71 publications

References 37 publications

Less Severe Cases of COVID-19 in Sub-Saharan Africa: Could Co-infection or a Recent History of Plasmodium falciparum Infection Be Protective?

Less Severe Cases of COVID-19 in Sub-Saharan Africa: Could Co-infection or a Recent History of Plasmodium falciparum Infection Be Protective?

HLA, Immune Response, and Susceptibility to COVID-19

Humoral Immunity Profiling to Pandemic and Bat‐Derived Coronavirus Variants: A Geographical Comparison

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