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Sep 19, 2022 · The anti-spike protein RBD ELISA (Roche) detected antibodies in all eight BA.2 convalescent sera. However, in the omicron BA.1 study cohort, only five (62%) of eight sera tested positive in the Roche anti-RBD ELISA, three (38%) of eight in the Abbott anti-spike protein ELISA, and two (25%) of eight sera in the Euroimmun anti-spike protein ELISA.
- Table of Contents
- Introduction
- Key points
- Overview of the evidence
- Risk of reinfection post Omicron infection
- Immune response markers post infection with Omicron
- Methods
- Acknowledgements
•Introduction
•Key points
•Overview of the evidence
•Risk of reinfection post Omicron infection
•Immune response markers post infection with Omicron
•Neutralizing antibody responses post Omicron infection (n=17)
What do we know about protective immunity post Omicron infection (against Omicron/other variants of concern?)
The SARS-CoV-2 variant of concern (VOC) Omicron (B.1.1.529) emerged in late 2021 and quickly displaced the Delta variant. Omicron has evolved into multiple sublineages such as BA.1, BA.2, BA.3, BA.4, and BA.5, each with additional mutations. Compared to previous variants, Omicron has a large number of mutations (>30 mutations in the spike (S) protein) - and thus, has been good at evading established immunity from prior infection or vaccinationFootnote 1. Omicron's ability to escape neutralizing antibodies that would stop the virus from entering and replicating in cells is due to the many mutations on the S-protein, particularly in key spots on the receptor binding domain (RBD)Footnote 1.
Although the literature on vaccine efficacy, role of waning immunity post vaccination, and/or previous infection with earlier variants is well established, little is known about immunity post Omicron infection. In this rapid review, real world data on reinfections post Omicron infection and post-Omicron immunogenicity studies (e.g., neutralizing/binding antibodies and memory immune markers such as T-cells and B-cells) are summarized across the different profiles of pre-Omicron immunity (vaccination and/or infection) studied. The different immune profiles as defined by the World Health Organization (WHO), include infection-induced immunity, vaccine-induced immunity and hybrid immunity. Hybrid immunity refers to immunity that comes from both vaccination with one or more doses of a COVID-19 vaccine and immunity via infection with SARS-CoV-2 before or after vaccination Footnote 2. Reinfection is defined as a previous confirmed and resolved SARS-CoV-2 case that has a subsequent infection of SARS-CoV-2 and it is confirmed as two different infections by laboratory evidence Footnote 3. The risk of reinfection and level of immune markers measured as neutralizing antibodies and cellular immunity activity against a pathogen can be indicative of protective immunity. However, it is important to note that markers of protective immunity do not necessarily or directly equate to protection. Instead, immune markers indicate that the immune system is primed to respond to a pathogen, which may result in prevention of infection or reduced morbidity.
Studies on animal models of immunity post Omicron were excluded. Studies published before July 26, 2022 were included.
Twenty-three studies were identified, including six observational studies on the risk of reinfection and 17 in vitro studies on the kinetics and durability of neutralizing antibodies and memory immune response markers (B-cell and T-cell) post infection with any of the Omicron sublineages. For the neutralization studies, results were divided into two sections: an analysis of differences in the levels of immune response markers post Omicron by individual vaccination and/or prior infection status and a comparison of the differences in level of neutralization of the different Omicron sublineages and other VOCs post Omicron infection. Out of the six observational studies on the risk of reinfection, five were pre-print articles, not yet published in full and one was a Letter to the Editor (LTE). Of the 17 in vitro studies, six were pre-print articles and three were Letters to the Editor.
Overall, the studies indicate that the risk of reinfection is lower and correlates of immunity are higher (stronger response) for:
•People with 2 or more doses of COVID-19 vaccination. There may be an additional benefit to having had the third dose, but more studies are required.
•Protection against the Omicron variant that caused the first Omicron infection is the highest. Protection against other Omicron variants was lower, but still significantly higher than compared to people who did not have an Omicron infection when matched by immunity (vaccination and infection) prior to getting Omicron.
•Omicron infection boosted correlates of immunity (neutralizing antibodies and cellular immune response – T-cell/B-cell activity) against all previous variants for those that had prior immunity (vaccination and/or infection), whereas those with no immunity prior to Omicron infection had limited cross protection against other variants.
Risk of reinfection post Omicron infection (six studies):
This review contains evidence from six observational studies of reinfection and 17 in vitro neutralization/immunogenicity studies. The lab-based in vitro studies had to include samples from individuals post infection with Omicron. Sub-groups of results by prior immunity (infection and/or vaccine) were compared with samples from individuals who were not infected with Omicron. Neutralization was generally tested against a panel of live or pseudo-viruses containing SARS-CoV-2 original variant and VOCs. Although several trends in immune response post Omicron infection were seen across the studies, detailed below, there was heterogeneity observed in the outcomes which can be due to differences in study participants, sample collection times post infection, clinical severity of infection, the study design and measurement methods. The results of in vitro studies provide limited indirect evidence about the potential risk of reinfection with Omicron or other variants and thus, we have low certainty in these results.
The reinfection studies included three case-control studies and three retrospective cohorts of cases infected with Omicron once or multiple times during the study. From these data, the risk of reinfection across groups with different prior immunity was examined. The retrospective cohort studies are of moderate to high risk of bias due to their retrospective designs. Confounding was not controlled for in these studies as they did not include multivariable analyses. Compared to prospective cohort studies, these studies have a greater potential for confounding and missing data as the results are limited to what has been collected in the past and the quality of these data. All three studies are large and the findings are directly answering the question about risk of reinfection, so our confidence in this outcome is low to moderate. The three test negative case-control studies assess the odds of a prior Omicron infection in cases with an Omicron BA.2 or BA.4/BA.5 reinfection and compared it to the odds in test negative controls. In this way, the findings directly answer the question about the effectiveness of a previous Omicron infection against reinfection with a different strain. These studies are at moderate to high risk of bias due to their retrospective designs, thus we have low confidence in these findings.
The following knowledge gaps exist in the current literature on immunity post Omicron infection:
•The correlation between markers of immune response post Omicron infection such as neutralizing antibodies and individual risk of reinfection or level of protection from different titers were not available.
•There is a lack of understanding on the correlation of memory immunity via B-cells and T-cells and the level of protection they offer against reinfection post infection with Omicron.
•Data on the long-term immune response after an Omicron infection are still limited to short timeframes. Studies included in this review examined immune responses 0.5-3 months after an Omicron infection which corresponds to peak immune response. Data on long-term waning immunity (i.e., >3 months) post Omicron infection have not been published.
Three large retrospective cohort studies and three test negative case-control studies report on risk of reinfection post infection with Omicron (Table 1). The three retrospective cohort studies are based on cohorts established from Qatar's national database Footnote 4, a Danish COVID-19 surveillance system Footnote 5, and an Austrian COVID-19 variant surveillance program Footnote 6. All three studies used different definitions of reinfection: a documented infection >35 days after initial infection when Omicron was predominant (Qatar study)Footnote 4, an infection that occurred within 20-60 days following initial infection with Omicron (Danish study) Footnote 5 and a reinfection that occurred >30 and <60 days after a primary PCR-confirmed Omicron infection (Austrian study) Footnote 6. Prior to Omicron, reinfection was defined as either laboratory evidence of two different infections or a documented infection >90 days after initial SARS-CoV-2 infection Footnote 3. The three case-control studies analyzed the odds of a prior primary Omicron infection in cases with a BA.2 reinfection Footnote 7, a BA.4/BA.5 reinfection Footnote 8 or a BA.5 and BA.2 reinfection Footnote 9 compared to test negative controls. The studies identified cases and controls from the Quebec, Canada provincial laboratory database Footnote 7, from Qatar's national COVID-19 database Footnote 8 and from the Danish COVID-19 surveillance system Footnote 9. All three studies used different definitions of a previous Omicron infection: a nucleic acid amplification testing (NAAT) positive test ≥30 days before a positive test during the study period (Canadian study) Footnote 7, a SARS-CoV-2-positive test ≥90 days before another positive test during the study period (Qatar study) Footnote 8, and a positive SARS-CoV-2 PCR test ≥60 days before a new infection during the study period (Danish study) Footnote 9.
Results from reinfection studies (n=6):
•Across all studies, findings showed that reinfections were occurring, but at a significantly lower rate than first Omicron infections.
•The retrospective cohort from Qatar reported 0.9% (1062 cases) reinfections in February 2022, which equated to 95% protection post BA.1 and 86% post BA.2 Footnote 4.
•Similarly in Quebec, prior Omicron BA.1 infection among those with 2 doses of COVID-19 vaccination had reduced the risk of any BA.2 reinfection by 96% and of a symptomatic BA.2 reinfection by 98% Footnote 7.
•Reinfection with a heterologous Omicron strain (i.e., BA.1 to BA.2 reinfection) was more common than reinfection with a homologous strain of Omicron (i.e., BA.1 to BA.1 reinfection) Footnote 5 Footnote 6.
This section summarizes 17 studies that report on post Omicron immune responses measured ≥14 days post Omicron infection for individuals with prior vaccination and/or infection immunity and ≥30 days for individuals without prior immunity (Table 2). These sample collection thresholds were selected to isolate outcomes that correlate to maximal immune...
A daily scan of the literature (published and pre-published) is conducted by the Emerging Science Group, PHAC. The scan has compiled COVID-19 literature since the beginning of the outbreak and is updated daily. Searches to retrieve relevant COVID-19 literature are conducted in Pubmed, Scopus, BioRxiv, MedRxiv, ArXiv, SSRN, Research Square and cross-referenced with the COVID-19 information centers run by Lancet, BMJ, Elsevier, Nature and Wiley. The daily summary and full scan results are maintained in a refworks database and an excel list that can be searched. Targeted keyword searching was conducted within these databases to identify all relevant citations on post Omicron immunity. The database was filtered for "Omicron" articles and then the following immune search terms were used to isolate potentially relevant articles on post Omicron immunity: reinfect*, re-infect*, recurrent, re-positive, longitudinal, immun*, neutraliz* and neutralis*. The search netted 1721 citations up to July 26, 2022, which were screened based on title and abstract for relevance to the review. Each potentially relevant reference was examined to confirm it had relevant data and relevant data was extracted into the review. This review contains research published up to July 26, 2022.
Inclusion criteria: studies had to assess immune response and/or risk of reinfection post infection with Omicron in at least a subset of the results, otherwise they were excluded. Exclusion criteria: case reports, case series and studies with a small sample size (n<5) were excluded from this review. Animal models of post Omicron immunity were excluded. In order to assess immune response elicited by Omicron infection, studies with sample collection time <14 days post infection for individuals with prior immunity via vaccination and/or infection with an earlier variant and <30 days for individuals without prior immunity were excluded. Four studies did not report on sample collection times post infection and were also excluded.
Prepared by: Adhiba Nilormi, Tricia Corrin, and Kaitlin Young, National Microbiology Laboratory Emerging Science Group, Public Health Agency of Canada.
Editorial review, science to policy review, peer-review by a subject matter expert and knowledge mobilization of this document was coordinated by the Office of the Chief Science Officer: phac.ocsoevidence-bcscdonneesprobantes.aspc@canada.ca
Sep 17, 2022 · The most widely accepted marker of protection against a SARS-CoV-2 infection is the concentration of neutralizing antibody [ 2, 3] that prevent viral infection mostly by blocking the early step of infection, viral entry, especially in interfering with virions binding to their receptor.
- 10.3390/vaccines10091548
- 2022/09
- Vaccines (Basel). 2022 Sep; 10(9): 1548.
Jan 20, 2022 · The Omicron variant is rapidly becoming the dominant SARS-CoV-2 virus circulating globally. It is important to define reductions in virus neutralizing activity in the serum of convalescent or...
Jun 9, 2022 · These findings suggest that previous SARS-CoV-2 infection, as well as high pre-infection antibody titres, might impact omicron-induced spike-specific serological responses in triple-vaccinated individuals.
Jan 26, 2022 · Thus, we tested three different antiviral compounds (i.e., remdesivir, molnupiravir, and PF-07304814) for their efficacy against omicron. The in vitro 50% inhibitory concentration (IC 50) values...
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