Severe COVID-19 associated variants linked to chemokine receptor gene control in monocytes and macrophages

Stikker, Bernard; Stik, Grégoire; Hendriks, Rudi W.; Stadhouders, Ralph

doi:10.1101/2021.01.22.427813

Cited by 8 publications

(6 citation statements)

References 49 publications

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“…CCL3 and CCL3L1 are both ligands for CCR1 and CCR5. Interestingly, CCR1 variants are linked to pulmonary macrophage infiltration in severe COVID‐19 [ 53 ] and inhibition of CCR5 in critical COVID‐19 patients has been associated with a decrease in plasma IL‐6 and SARS‐CoV‐2 RNA and an increase in CD8 + T cells [ 54 ]. Additionally, intermediate monocytes which constitutively express high levels of CCR5 have recently been suggested as playing a role in post‐acute sequelae of COVID‐19 [ 55 ] (often referred to as ‘long‐COVID’).…”

Section: Resultsmentioning

confidence: 99%

HLA‐dependent variation in SARS‐CoV‐2 CD8 ⁺ T cell cross‐reactivity with human coronaviruses

et al. 2022

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The conditions and extent of cross‐protective immunity between severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) and common‐cold human coronaviruses (HCoVs) remain open despite several reports of pre‐existing T cell immunity to SARS‐CoV‐2 in individuals without prior exposure. Using a pool of functionally evaluated SARS‐CoV‐2 peptides, we report a map of 126 immunogenic peptides with high similarity to 285 MHC‐presented peptides from at least one HCoV. Employing this map of SARS‐CoV‐2‐non‐homologous and homologous immunogenic peptides, we observe several immunogenic peptides with high similarity to human proteins, some of which have been reported to have elevated expression in severe COVID‐19 patients. After combining our map with SARS‐CoV‐2‐specific TCR repertoire data from COVID‐19 patients and healthy controls, we show that public repertoires for the majority of convalescent patients are dominated by TCRs cognate to non‐homologous SARS‐CoV‐2 peptides. We find that for a subset of patients, >50% of their public SARS‐CoV‐2‐specific repertoires consist of TCRs cognate to homologous SARS‐CoV‐2‐HCoV peptides. Further analysis suggests that this skewed distribution of TCRs cognate to homologous or non‐homologous peptides in COVID‐19 patients is likely to be HLA‐dependent. Finally, we provide 10 SARS‐CoV‐2 peptides with known cognate TCRs that are conserved across multiple coronaviruses and are predicted to be recognized by a high proportion of the global population. These findings may have important implications for COVID‐19 heterogeneity, vaccine‐induced immune responses, and robustness of immunity to SARS‐CoV‐2 and its variants.

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Section: Resultsmentioning

confidence: 99%

HLA‐dependent variation in SARS‐CoV‐2 CD8 ⁺ T cell cross‐reactivity with human coronaviruses

et al. 2022

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“…A region of chromosome 3, i.e., 3p21.31, containing 12 proteincoding genes may be involved in SARS-CoV-2 pathogenesis when it carries single nucleotide polymorphisms (SNPs) in its variant form. is variant enhances complement fixation and infiltration of lung tissues with monocytes and macrophages in infected cases (a hallmark of severe disease), resulting in severe inflammatory responses [70,71]. [72] analyzed SNP variants of TMPRSS2, which included rs2070788, rs383510, and rs12329760.…”

Section: Chromosomementioning

confidence: 99%

The Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) Pandemic: Are Africa’s Prevalence and Mortality Rates Relatively Low?

Mariam

2022

Advances in Virology

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Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the cause of coronavirus disease 19 (COVID-19), has been rapidly spreading since December 2019, and within a few months, it turned out to be a global pandemic. The disease affects primarily the lungs, but its pathogenesis spreads to other organs as well. However, its mortality rates vary, and in the majority of infected people, there are no serious consequences. Many factors including advanced age, preexisting health conditions, and genetic predispositions are believed to exacerbate outcomes of COVID-19. The virus contains several structural proteins including the spike (S) protein with subunits for binding, fusion, and internalization into host cells following interaction with host cell receptors and proteases (ACE2 and TMPRSS2, respectively) to cause the subsequent pathology. Although the pandemic has spread into all countries, most of Africa is thought of as having relatively less prevalence and mortality. Several hypotheses have been forwarded as reasons for this and include warmer weather conditions, vaccination with BCG (i.e., trained immunity), and previous malaria infection. From genetics or metabolic points of view, it has been proposed that most African populations could be protected to some degree because they lack some genetic susceptibility risk factors or have low-level expression of allelic variants, such as ACE2 and TMPRSS2 that are thought to be involved in increased infection risk or disease severity. The frequency of occurrence of α-1 antitrypsin (an inhibitor of a tissue-degrading protease, thereby protecting target host tissues including the lung) deficiency is also reported to be low in most African populations. More recently, infections in Africa appear to be on the rise. In general, there are few studies on the epidemiology and pathogenesis of the disease in African contexts, and the overall costs and human life losses due to the pandemic in Africa will be determined by all factors and conditions interacting in complex ways.

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“…CCL3 and CCL3L1 are both ligands for CCR1 and CCR5. Interestingly, CCR1 variants are linked to pulmonary macrophage infiltration in severe COVID-19 34 and inhibition of CCR5 in critical COVID-19 patients has been associated with a decrease in plasma IL-6 and SARS-CoV-2 RNA and an increase in CD8+ T cells 35 . Additionally, intermediate monocytes which constitutively express high levels of CCR5 have recently been suggested as playing a role in post-acute sequelae of COVID-19 36 (often referred to as 'long-COVID').…”

Section: Identification Of Shared and Private Immunogenic Sars-cov-2 Peptidesmentioning

confidence: 99%

HLA-dependent variation in SARS-CoV-2 CD8+ T cell cross-reactivity with human coronaviruses

Buckley

Lee

Pinho

et al. 2021

Preprint

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Pre-existing T cell immunity to SARS-CoV-2 in individuals without prior exposure to SARS-CoV-2 has been reported in several studies. While emerging evidence hints toward prior exposure to common-cold human coronaviruses (HCoV), the extent of- and conditions for- cross-protective immunity between SARS-CoV-2 and HCoVs remain open. Here, by leveraging a comprehensive pool of publicly available functionally evaluated SARS-CoV-2 peptides, we report 126 immunogenic SARS-CoV-2 peptides with high sequence similarity to 285 MHC-presented target peptides from at least one of four HCoV, thus providing a map describing the landscape of SARS-CoV-2 shared and private immunogenic peptides with functionally validated T cell responses. Using this map, we show that while SARS-CoV-2 immunogenic peptides in general exhibit higher level of dissimilarity to both self-proteome and -microbiomes, there exist several SARS-CoV-2 immunogenic peptides with high similarity to various human protein coding genes, some of which have been reported to have elevated expression in severe COVID-19 patients. We then combine our map with a SARS-CoV-2-specific TCR repertoire data from COVID-19 patients and healthy controls and show that whereas the public repertoire for the majority of convalescent patients are dominated by TCRs cognate to private SARS-CoV-2 peptides, for a subset of patients, more than 50% of their public repertoires that show reactivity to SARS-CoV-2, consist of TCRs cognate to shared SARS-CoV-2-HCoV peptides. Further analyses suggest that the skewed distribution of TCRs cognate to shared and private peptides in COVID-19 patients is likely to be HLA-dependent. Finally, by utilising the global prevalence of HLA alleles, we provide 10 peptides with known cognate TCRs that are conserved across SARS-CoV-2 and multiple human coronaviruses and are predicted to be recognised by a high proportion of the global population. Overall, our work indicates the potential for HCoV-SARS-CoV-2 reactive CD8+ T cells, which is likely dependent on differences in HLA-coding genes among individuals. These findings may have important implications for COVID-19 heterogeneity and vaccine-induced immune responses as well as robustness of immunity to SARS-CoV-2 and its variants.

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Severe COVID-19 associated variants linked to chemokine receptor gene control in monocytes and macrophages

Cited by 8 publications

References 49 publications

HLA‐dependent variation in SARS‐CoV‐2 CD8 ⁺ T cell cross‐reactivity with human coronaviruses

HLA‐dependent variation in SARS‐CoV‐2 CD8 ⁺ T cell cross‐reactivity with human coronaviruses

The Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) Pandemic: Are Africa’s Prevalence and Mortality Rates Relatively Low?

HLA-dependent variation in SARS-CoV-2 CD8+ T cell cross-reactivity with human coronaviruses

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Severe COVID-19 associated variants linked to chemokine receptor gene control in monocytes and macrophages

Cited by 8 publications

References 49 publications

HLA‐dependent variation in SARS‐CoV‐2 CD8 + T cell cross‐reactivity with human coronaviruses

HLA‐dependent variation in SARS‐CoV‐2 CD8 + T cell cross‐reactivity with human coronaviruses

The Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) Pandemic: Are Africa’s Prevalence and Mortality Rates Relatively Low?

HLA-dependent variation in SARS-CoV-2 CD8+ T cell cross-reactivity with human coronaviruses

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Product

Resources

About

HLA‐dependent variation in SARS‐CoV‐2 CD8 ⁺ T cell cross‐reactivity with human coronaviruses

HLA‐dependent variation in SARS‐CoV‐2 CD8 ⁺ T cell cross‐reactivity with human coronaviruses