COVID‐19 re‐infection

Brouqui, P.; Colson, Philippe; Melenotte, Cléa; Houhamdi, Linda; Bedotto, Marielle; Devaux, Christian; Gautret, Philippe; Million, Matthieu; Parola, Philippe; Stoupan, Didier; Scola, Bernard La; Lagier, Jean-Christophe; Raoult, Didier

doi:10.1111/eci.13537

Cited by 60 publications

(88 citation statements)

References 16 publications

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“…Thus, the longevity/durability of these T cell responses should be investigated further. In essence, our results showing limited virus-specific adaptive immune responses in COVID-19-recovered patients raise concerns about reinfection in COVID19-recovered patients as well as the efficacy of protection in previously unexposed individuals following the administration of COVID-19 vaccines ( To et al, 2020 , Brouqui et al, 2021 , Kang et al, 2020 ).…”

Section: Discussionmentioning

confidence: 79%

SARS-CoV-2 specific memory T cell epitopes identified in COVID-19-recovered subjects

et al. 2021

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The COVID-19 pandemic caused by SARS-CoV-2 infection poses a serious threat to public health. An explicit investigation of COVID-19 immune responses, particularly the host immunity in recovered subjects, will lay a foundation for the rational design of therapeutics and/or vaccines against future coronaviral outbreaks. Here, we examined virus-specific T cell responses and identified T cell epitopes using peptides spanning SARS-CoV-2 structural proteins. These peptides were used to stimulate peripheral blood mononuclear cells (PBMCs) derived from COVID-19-recovered subjects, followed by an analysis of IFN-γ-secreting T cells by enzyme-linked immunosorbent spot (ELISpot). We also evaluated virus-specific CD4 or CD8 T cell activation by flow cytometry assay. By screening 52 matrix pools (comprised of 315 peptides) of the spike (S) glycoprotein and 21 matrix pools (comprised of 102 peptides) spanning the nucleocapsid (N) protein, we identified 28 peptides from S protein and 5 peptides from N protein as immunodominant epitopes. The immunogenicity of these epitopes was confirmed by a second ELISpot using single peptide stimulation in memory T cells, and they were mapped by HLA restrictions. Notably, SARS-CoV-2 specific T cell responses positively correlated with B cell IgG and neutralizing antibody responses to the receptor-binding domain (RBD) of the S protein. Our results demonstrate that defined levels of SARS-CoV-2 specific T cell responses are generated in some, but not all, COVID-19-recovered subjects, fostering hope for the protection of a proportion of COVID-19-exposed individuals against reinfection. These results also suggest that these virus-specific T cell responses may induce protective immunity in unexposed individuals upon vaccination, using vaccines generated based on the immune epitopes identified in this study. However, SARS-CoV-2 S and N peptides are not potently immunogenic, and none of the single peptides could universally induce robust T cell responses, suggesting the necessity of using a multi-epitope strategy for COVID-19 vaccine design.

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Section: Discussionmentioning

confidence: 79%

SARS-CoV-2 specific memory T cell epitopes identified in COVID-19-recovered subjects

et al. 2021

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“…We diagnosed two successive cases of COVID-19, separated by more than 4 months, in 11 patients. The first infection was diagnosed before June 2020 when Marseille-4 was not circulating in Marseille (Colson et al, 2020b;Brouqui et al, 2021), and genomic or qPCR (one and 10 patients, respectively) confirmation that the second episode was caused by the Marseille-4 variant was obtained. This suggests either short protective immunity (only a few weeks or months), as observed previously with seasonal coronaviruses (Edridge et al, 2020), or a lack of cross-immunity between different SARS-CoV-2 variants, allowing Marseille-4 to A total of 744 genomes of SARS-CoV-2 were integrated in a phylogenetic analysis.…”

Section: In Search Of the Origin Of The Marseille-4 Variantmentioning

confidence: 92%

Emergence and outcomes of the SARS-CoV-2 ‘Marseille-4’ variant

Fournier

Colson

Levasseur

et al. 2021

International Journal of Infectious Diseases

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Introduction In Marseille, France, following a first SARS-CoV-2 outbreak in March-May 2020, a second epidemic phase occurred from June, involving ten new variants. The Marseille-4 variant caused an epidemic that started in August and is still ongoing. Materials and methods The 1,038 SARS-CoV-2 whole genome sequences obtained in our laboratory by next-generation sequencing with Illumina technology were analyzed using Nextclade and nextstrain/ncov pipelines and IQ-TREE. A Marseille-4-specific qPCR assay was implemented. Demographic and clinical features were compared between patients with Marseille-4 and earlier strains. Results Marseille-4 harbors 13 hallmark mutations. One leads to S477 N substitution in the spike receptor binding domain targeted by current vaccines. Using a specific qPCR, we observed that Marseille-4 caused 12-100% of SARS-CoV-2 infections in Marseille from September 2020, being involved in 2,106 diagnoses. This variant was more frequently associated with hypoxemia than clade 20A strains before May 2020. It caused re-infection in eleven patients SARS-CoV-2-diagnosed with different strains before June 2020, suggesting either short-term protective immunity or lack of cross-immunity. Discussion/conclusion Marseille-4 should be considered as a major SARS-CoV-2 variant. Its sudden appearance points toward an animal reservoir, possibly minks. The protective role of past-exposure and current vaccines against this variant should be evaluated.

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“…Then, 8 months later, he was reinfected with the 20I/501Y.V1 variant as documented by whole-genome sequencing, which caused a critical illness. In addition, we observed in our institute the case of several patients who had been infected in March–April 2020, then experienced clinical recovery and viral clearance as documented by qPCR negativity but were infected again during summer 2020 or later with a Marseille-4 variant that carries the S477N substitution in the spike [ 49 ]. Such clinical observation of reinfection with a Brazilian variant is corroborated by the observation that culturing in vitro, in the presence of neutralizing plasma, a SARS-CoV-2 isolate sensitive to highly-neutralizing plasma from a COVID-19 convalescent patient was associated with the occurrence of a deletion of amino acid F140 in the N-terminal domain (NTD, loop N3) of the spike after 45 days and of the E484K substitution after 73 days, followed by an insertion in the NTD, loop N5 [ 50 ].…”

Section: Mutations In the Spike Associated With A Risk Of Neutralizing Immune Response Escapementioning

confidence: 99%

A Possible Role of Remdesivir and Plasma Therapy in the Selective Sweep and Emergence of New SARS-CoV-2 Variants

Colson

Devaux

Lagier

et al. 2021

JCM

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Since summer 2020, SARS-CoV-2 strains at the origin of the COVID-19 pandemic have suddenly been replaced by new SARS-CoV-2 variants, some of which are highly transmissible and spread at a high rate. These variants include the Marseille-4 lineage (Nextclade 20A.EU2) in Europe, the 20I/501Y.V1 variant first detected in the UK, the 20H/501Y.V2 variant first detected in South Africa, and the 20J/501Y.V3 variant first detected in Brazil. These variants are characterized by multiple mutations in the viral spike protein that is targeted by neutralizing antibodies elicited in response to infection or vaccine immunization. The usual coronavirus mutation rate through genetic drift alone cannot account for such rapid changes. Recent reports of the occurrence of such mutations in immunocompromised patients who received remdesivir and/or convalescent plasma or monoclonal antibodies to treat prolonged SARS-CoV-2 infections led us to hypothesize that experimental therapies that fail to cure the patients from COVID-19 could favor the emergence of immune escape SARS-CoV-2 variants. We review here the data that support this hypothesis and urge physicians and clinical trial promoters to systematically monitor viral mutations by whole-genome sequencing for patients who are administered these treatments.

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COVID‐19 re‐infection

Cited by 60 publications

References 16 publications

SARS-CoV-2 specific memory T cell epitopes identified in COVID-19-recovered subjects

SARS-CoV-2 specific memory T cell epitopes identified in COVID-19-recovered subjects

Emergence and outcomes of the SARS-CoV-2 ‘Marseille-4’ variant

A Possible Role of Remdesivir and Plasma Therapy in the Selective Sweep and Emergence of New SARS-CoV-2 Variants

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