SARS-CoV-2 Evolution and Spike-Specific CD4+ T-Cell Response in Persistent COVID-19 with Severe HIV Immune Suppression

Álvarez, Hortensia; Ruiz‐Mateos, Ezequiel; Juiz-González, Pedro Miguel; Vitallé, Joana; Viéitez, Irene; Vázquez-Friol, María Del Carmen; Torres-Beceiro, Isabel; Pérez-Gómez, Alberto; Gallego-García, Pilar; Estévez-Gómez, Nuria; Chiara, Loretta De; Poveda, Eva; Posada, David; Llibre, JM

doi:10.3390/microorganisms10010143

Cited by 12 publications

(10 citation statements)

References 48 publications

(58 reference statements)

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“…These mutations appeared to be adaptive at the within-host level due to their concentration in the spike protein, with several common to other variants of concern. Similar results have been observed in other patients with long-term infections of SARS-CoV-2 [21,22], including those who have been treated with convalescent plasma, indicating antigenic evolution within the host [23] (although some immunocompromised individuals show little to no within-host evolution of SARS-CoV-2 [24]). A study of infection in immunocompromised individuals has found that mutations accumulate in the spike gene receptor binding domain and N-terminal domains, associated with immune escape and viral packaging [25].…”

Section: Introductionsupporting

confidence: 82%

“…Specialisation on immunocompromised individuals has been observed for other pathogens (e.g. Pseudomonas aeruginosa infections in cystic fibrosis patients [47]) and longitudinal studies of prolonged SARS-CoV-2 infections reveal the rapid accumulation of many mutations [20–24], but it is unclear if and when this leads to specialisation with a reduction in fitness on immunocompetent hosts.…”

Section: Discussionmentioning

confidence: 99%

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Antigenic evolution of SARS-CoV-2 in immunocompromised hosts

Smith

Ashby

2022

Preprint

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The apparent lack of antigenic evolution by the Delta variant (B.1.617.2) of SARS-CoV-2 during the COVID-19 pandemic is puzzling. The combination of increasing immune pressure due to the rollout of vaccines and a relatively high number of infections following the relaxation of non-pharmaceutical interventions should have created perfect conditions for immune escape variants to evolve from the Delta lineage. Instead, the Omicron variant (B.1.1.529), which is hypothesised to have evolved in an immunocompromised individual, is the first major variant to exhibit significant immune escape following vaccination programmes and is set to become globally dominant in 2022. Here, we use a simple mathematical model to explore possible reasons why the Delta lineage did not exhibit antigenic evolution and to understand how and when immunocompromised individuals affect the emergence of immune escape variants. We show that when the pathogen does not have to cross a fitness valley for immune escape to occur, immunocompromised individuals have no qualitative effect on antigenic evolution (although they may accelerate immune escape if within-host evolutionary dynamics are faster in immunocompromised individuals). But if a fitness valley exists between immune escape variants at the between-host level, then persistent infections of immunocompromised individuals allow mutations to accumulate, therefore facilitating rather than simply speeding up antigenic evolution. Our results suggest that better global health equality, including improving access to vaccines and treatments for individuals who are immunocompromised (especially in lower- and middle-income countries), may be crucial to preventing the emergence of future immune escape variants of SARS-CoV-2.

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Section: Introductionsupporting

confidence: 82%

Section: Discussionmentioning

confidence: 99%

Antigenic evolution of SARS-CoV-2 in immunocompromised hosts

Smith

Ashby

2022

Preprint

View full text Add to dashboard Cite

show abstract

“…These mutations appeared to be adaptive at the within-host level due to their concentration in the spike protein, with several common to other variants of concern. Similar results have been observed in other patients with long-term infections of SARS-CoV-2 [ 21 , 22 ], including those who have been treated with convalescent plasma, indicating antigenic evolution within the host [ 23 ] (although some immunocompromised individuals show little to no within-host evolution of SARS-CoV-2 [ 24 ]). A study of infection in immunocompromised individuals has found that mutations accumulate in the spike gene receptor binding domain and N-terminal domains, associated with immune escape and viral packaging [ 25 ].…”

Section: Introductionsupporting

confidence: 82%

Antigenic evolution of SARS-CoV-2 in immunocompromised hosts

Smith

Ashby

2022

Evolution, Medicine, and Public Health

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Prolonged infections of immunocompromised individuals have been proposed as a crucial source of new variants of SARS-CoV-2 during the COVID-19 pandemic. In principle, sustained within-host antigenic evolution in immunocompromised hosts could allow novel immune escape variants to emerge more rapidly, but little is known about how and when immunocompromised hosts play a critical role in pathogen evolution. Here, we use a simple mathematical model to understand the effects of immunocompromised hosts on the emergence of immune escape variants in the presence and absence of epistasis. We show that when the pathogen does not have to cross a fitness valley for immune escape to occur (no epistasis), immunocompromised individuals have no qualitative effect on antigenic evolution (although they may accelerate immune escape if within-host evolutionary dynamics are faster in immunocompromised individuals). But if a fitness valley exists between immune escape variants at the between-host level (epistasis), then persistent infections of immunocompromised individuals allow mutations to accumulate, therefore facilitating rather than simply speeding up antigenic evolution. Our results suggest that better genomic surveillance of infected immunocompromised individuals and better global health equality, including improving access to vaccines and treatments for individuals who are immunocompromised (especially in lower- and middle-income countries), may be crucial to preventing the emergence of future immune escape variants of SARS-CoV-2.

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“…According to them, ‘the virus could (1) have circulated and evolved in a population with little surveillance and sequencing; (2) it could have originated in an immuno‐compromised COVID‐19 patient or (3) it might have evolved in a nonhuman species, from which it recently followed a trajectory of secondary colonization in people’ (hereafter H1, H2 and H3). The second option appears to be the hypothesis of choice for many, especially associated with patients with human immunodeficiency virus (Healy, 2021a , 2021b ) despite recent opposing evidence (Álvarez et al., 2022 ). Empirical and theoretical analyses presented herein are also not in accordance with the origin of Omicron in immunodeficient humans (H1) nor in isolated human populations (H2).…”

Section: Revelations From Omicronmentioning

confidence: 99%

Ecological super‐spreaders drive host–range oscillations: Omicron and risk space for emerging infectious disease

Boeger

Brooks

Trivellone

et al. 2022

Transbounding Emerging Dis

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The unusual genetic diversity of the Omicron strain has led to speculation about its origin. The mathematical modelling platform developed for the Stockholm Paradigm (SP) indicates strongly that it has retro‐colonized humans from an unidentified nonhuman mammal, likely originally infected by humans. The relationship between Omicron and all other SARS‐CoV‐2 variants indicates oscillations among hosts, a core part of the SP. Such oscillations result from the emergence of novel variants following colonization of new hosts, replenishing and expanding the risk space for disease emergence. The SP predicts that pathogens colonize new hosts using pre‐existing capacities. Those events are thus predictable to a certain extent. Novel variants emerge after a colonization and are not predictable. This makes it imperative to take proactive measures for anticipating emerging infectious diseases (EID) and mitigating their impact. The SP suggests a policy protocol, DAMA, to accomplish this goal. DAMA comprises: DOCUMENT to detect pathogens before they emerge in new places or colonize new hosts; ASSESS to determine risk; MONITOR to detect changes in pathogen populations that increase the risk of outbreaks and ACT to prevent outbreaks when possible and minimize their impact when they occur.

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SARS-CoV-2 Evolution and Spike-Specific CD4+ T-Cell Response in Persistent COVID-19 with Severe HIV Immune Suppression

Cited by 12 publications

References 48 publications

Antigenic evolution of SARS-CoV-2 in immunocompromised hosts

Antigenic evolution of SARS-CoV-2 in immunocompromised hosts

Antigenic evolution of SARS-CoV-2 in immunocompromised hosts

Ecological super‐spreaders drive host–range oscillations: Omicron and risk space for emerging infectious disease

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