Occurrence and significance of Omicron BA.1 infection followed by BA.2 reinfection

Stegger, Marc; Edslev, Sofie Marie; Sieber, Raphael N.; Ingham, Anna Cäcilia; Ng, Kim Lee; Tang, Man-Hung Eric; Alexandersen, Søren; Fonager, Jannik; Legarth, Rebecca; Utko, M.; Wilkowski, Bartłomiej; Gunalan, Vithiagaran; Bennedbæk, Marc; Bybjerg‐Grauholm, Jonas; Moeller, Camilla Holten; Christiansen, Lasse Engbo; Svarrer, Christina Wiid; Ellegaard, Kirsten; Baig, Sharmin; Johannesen, Thor Bech; Espenhain, Laura; Skov, Robert; As, Cohen; Larsen, Nicolai Balle; Soerensen, Karina Meden; White, Emeily Dibba; Lillebæk, Troels; Ullum, Henrik; Krause, Tyra Grove; Fomsgaard, Anders; Ethelberg, Steen; Rasmussen, Morten

doi:10.1101/2022.02.19.22271112

Cited by 60 publications

(64 citation statements)

References 18 publications

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“…In older patient groups, unvaccinated and patients with a basic vaccination scheme are more vulnerable to reinfections compared to patients who received a first booster vaccine. Data from Denmark (9) suggests reinfection usually results in mild disease not requiring hospitalization as is illustrated by this reported case.…”

Section: Textsupporting

confidence: 51%

Early SARS-CoV-2 reinfections within 60 days highlight the need to consider antigenic variations together with duration of immunity in defining retesting policies

Nevejan

Cuypers

Laenen

et al. 2022

Preprint

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The emergence of the SARS-CoV-2 Omicron variant, characterized by a significant antigenic diversity compared to the previous Delta variant, had led to a decrease in antibody efficacy in both convalescent and vaccinees sera resulting in high number of reinfections and breakthrough cases worldwide. However, to date, reinfections are defined by the ECDC as two positive tests >/= 60 days apart, influencing retesting policies after an initial positive test in several European countries. In our manuscript, we illustrate by a clinical case supplemental by epidemiological data that early reinfections do occur within 60 days especially in young, unvaccinated individuals. In older patient groups, unvaccinated and patients with a basic vaccination scheme are more vulnerable to reinfections compared to patients who received a first booster vaccine. For this reason, we consider that the duration of protection offered by a previous infection should be reconsidered, in particular when a shift between consecutive SARS-CoV-2 variants occurs.

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Section: Textsupporting

confidence: 51%

Early SARS-CoV-2 reinfections within 60 days highlight the need to consider antigenic variations together with duration of immunity in defining retesting policies

Nevejan

Cuypers

Laenen

et al. 2022

Preprint

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“…In Denmark, England, India, the Philippines, and South Africa, where Omicron strains were predominantly sublineage BA.1 in the early stages of the outbreak, sublineage BA.2 later became predominant [27]. Furthermore, reinfection with sublineage BA.2 after infection with sublineage BA.1 can occur, although it is rare [28]. Therefore, there is concern that the prevalence of the BA.2 sublineage may increase in the future.…”

Section: Discussionmentioning

confidence: 99%

SARS-CoV-2 Omicron sublineage BA.2 replaces BA.1.1: genomic surveillance in Japan from September 2021 to March 2022

Hirotsu

Maejima

Shibusawa

et al. 2022

Preprint

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ObjectiveThe new emerging Omicron strain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently spreading worldwide. We aimed to analyze the genomic evolution of the shifting Omicron virus subtypes.MethodsThe study included 1,297 individuals diagnosed as SARS-CoV-2 positive by PCR test or antigen quantification test from September 2021 to March 2022. Samples were analyzed by whole genome sequencing analysis (n=489) or TaqMan assay (n=808).ResultsAfter the outbreak of the SARS-CoV-2 Delta strain, the Omicron strain spread rapidly in Yamanashi, Japan. BA.1.1 was the predominant sublineage of the Omicron strain from January to mid-February 2022, but the number of cases of sublineage BA.2 began to increase after mid-February, and this sublineage was shown to have replaced BA.1.1 by the end of March 2022. We observed higher viral and antigen levels of sublineage BA.2 than of sublineage BA.1.1 in nasopharyngeal swab samples. However, no difference in viral load by patient age was apparent between sublineages BA.1.1 and BA.2.ConclusionsA transition from sublineage BA.1.1 to sublineage BA.2 was clearly observed over approximately one month. Omicron sublineage BA.2 was found to be more transmissible owing to its higher viral load regardless of patient age.

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“…Moreover, mutations carried by BA.2 on the NTD largely differ from BA.1, with only one identical mutation, G142D, shared; however, G142D alone is sufficient to induce NTD neutralization antibody escape 13 . Given BA.2’s newly acquired mutations, higher transmissibility, and the ability to cause reinfections among BA.1 convalescents 15 , the immune escape capability and antigenicity of BA.2 require immediate investigation.…”

Section: Mainmentioning

confidence: 99%

Omicron BA.2 specifically evades broad sarbecovirus neutralizing antibodies

Cao

Yisimayi

Jian

et al. 2022

Preprint

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Constantly emerging SARS-CoV-2 variants, such as Omicron BA.1, BA.1.1 and BA.2, pose a severe challenge to COVID-19 control. Broad-spectrum antibody therapeutics and vaccines are needed for defending against future SARS-CoV-2 variants and sarbecovirus pandemics; however, we have yet to gain a comprehensive understanding of the epitopes capable of inducing broad sarbecovirus neutralization. Here, we report the identification of 241 anti-RBD broad sarbecovirus neutralizing antibodies isolated from 44 SARS-CoV-2 vaccinated SARS convalescents. Neutralizing efficacy of these antibodies against D614G, SARS-CoV-1, Omicron variants (BA.1, BA.1.1, BA.2), RATG13 and Pangolin-GD is tested, and their binding capability to 21 sarbecovirus RBDs is measured. High-throughput yeast-display mutational screening was further applied to determine each antibody's RBD escaping mutation profile, and unsupervised epitope clustering based on escaping mutation hotspots was performed. A total of 6 clusters of broad sarbecovirus neutralizing antibodies with diverse breadth and epitopes were identified, namely Group E1 (S309, BD55-3152 site), E3 (S2H97 site), F1 (CR3022, S304 site), F2 (DH1047, BD55-3500 site), F3 (ADG-2, BD55-3372 site) and B' (S2K146 site). Members of E1, F2 and F3 demonstrate the highest neutralization potency; yet, Omicron, especially BA.2, has evolved multiple mutations (G339D, N440K, T376A, D405N, R408S) to escape antibodies of these groups. Nevertheless, broad sarbecovirus neutralizing antibodies that survived Omicron would serve as favorable therapeutic candidates. Furthermore, structural analyses of selected drug candidates propose two non-competing antibody pairing strategies, E1-F2 and E1-F3, as broad-spectrum antibody cocktails. Together, our work provides a comprehensive epitope map of broad sarbecovirus neutralizing antibodies and offers critical instructions for designing broad-spectrum vaccines.

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Occurrence and significance of Omicron BA.1 infection followed by BA.2 reinfection

Cited by 60 publications

References 18 publications

Early SARS-CoV-2 reinfections within 60 days highlight the need to consider antigenic variations together with duration of immunity in defining retesting policies

Early SARS-CoV-2 reinfections within 60 days highlight the need to consider antigenic variations together with duration of immunity in defining retesting policies

SARS-CoV-2 Omicron sublineage BA.2 replaces BA.1.1: genomic surveillance in Japan from September 2021 to March 2022

Omicron BA.2 specifically evades broad sarbecovirus neutralizing antibodies

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