Periodic Reporting for period 2 - CoVICIS (EU-Africa Concerted Action on SAR-CoV-2 Virus Variant and Immunological Surveillance)
Reporting period: 2023-05-01 to 2025-04-30
CoVICIS is a multidisciplinary project addressing key questions associated with the evolution of the COVID-19 pandemic, with the ultimate goal of generating scientific data that will contribute to controlling COVID-19 and future outbreaks of this nature. The project aims to identify and characterize the emergence of virus variants of concerns (VOC) and how they affect different populations (adults vs children, healthy vs immune-compromised) in different geographies. Additionally, the project will study the impact of VOC on vaccine effectiveness. The data collected by CoVICIS will help determine how emerging VOC will influence the evolution of the COVID-19 pandemic, and how such information can be utilized in new pandemics.
Objective 1 Identification of emerging VOC through genomic surveillance: Across three large genomic surveillance programs in Europe and South Africa, CoVICIS has produced more than 100,000 sequences since the start of the program and have made them available to the community through the GISAID. CoVICIS partners identified the arrival of Omicron and its significant sublineages in different geographic regions in the world.
Objective 2 Characterization of the virologic and immunologic properties of emerging VOC: For the virological characterization, we found that spikes from successful descendant viruses contribute to a better infectivity than those from their direct parental strains, and isolated mutations which would be detrimental alone for the virus fitness can be compensated by other epistatic mutations in variants circulating worldwide, and there is still room for tolerance of new escape mutations in future variants.. For the immunological properties, our findings indicates immune escape was much lower at the mucosa compared to serum, confirming a broader neutralization at mucosa level as compared to systemic circulation. When examining T-cell cross-reactivity to Omicron sub-lineages, we observed a high degree of preservation of the T-cell responses to Omicron BA.1 BA.4/5 and XBB.1. We further observed Individuals who had been infected on multiple occasions had more broadly stronger T-cell responses compared with those only vaccinated.
Objective 3 Identification of differences in clinical and immune responses in unvaccinated children cohorts: The Swiss Ciao Corona cohort has shown that the Omicron wave and the rollout of vaccines led to almost 100% seropositivity as well as better neutralizing capacity in children and adolescents. The Italian SALISARV1 School Children cohort has shown that neutralizing antibody titres were significantly higher in vaccinated compared to unvaccinated children; while in hospitalized children about 14.8% reported long COVID syndrome with no significant differences between children of normal weight and those underweight. The South African hospitalized unvaccinated children’s cohort showed that children of underweight and having one or more comorbidity are at higher risk for severe disease.
Objective 4 Delineation of the impact of VOCs on the effectiveness of vaccine-induced immune response: A large number of cohorts of different risk, gender and age groups in different geographic regions contributed to this objective. The major finding includes: 1) Combination of vaccination and infection, i.e. hybrid immunity, confers higher anti-RBD IgG levels and higher neutralizing capacity than vaccination alone, likely providing better protection against COVID-19; 2) Boosting with updated vaccines in fragile population (immunocompromised and elderly) induced neutralizing antibody and T-cell responses, and continued vaccination confers benefit to this population, in particular against severe disease.
Objective 5 Identification of immune correlates of protection against VOCs: Using the statistical model, we were able to characterize the correlates of protection, identifying the events that led to higher uplift in antibody levels and longer durability of protection. We found generally low protection levels for the immunocompromised patient group, and the post-event uplift in antibody levels largely determines the protection durability
Objective 2 Characterization of the virologic and immunologic properties of emerging VOC: For the virological characterization, we found that spikes from successful descendant viruses contribute to a better infectivity than those from their direct parental strains, and isolated mutations which would be detrimental alone for the virus fitness can be compensated by other epistatic mutations in variants circulating worldwide, and there is still room for tolerance of new escape mutations in future variants.. For the immunological properties, our findings indicates immune escape was much lower at the mucosa compared to serum, confirming a broader neutralization at mucosa level as compared to systemic circulation. When examining T-cell cross-reactivity to Omicron sub-lineages, we observed a high degree of preservation of the T-cell responses to Omicron BA.1 BA.4/5 and XBB.1. We further observed Individuals who had been infected on multiple occasions had more broadly stronger T-cell responses compared with those only vaccinated.
Objective 3 Identification of differences in clinical and immune responses in unvaccinated children cohorts: The Swiss Ciao Corona cohort has shown that the Omicron wave and the rollout of vaccines led to almost 100% seropositivity as well as better neutralizing capacity in children and adolescents. The Italian SALISARV1 School Children cohort has shown that neutralizing antibody titres were significantly higher in vaccinated compared to unvaccinated children; while in hospitalized children about 14.8% reported long COVID syndrome with no significant differences between children of normal weight and those underweight. The South African hospitalized unvaccinated children’s cohort showed that children of underweight and having one or more comorbidity are at higher risk for severe disease.
Objective 4 Delineation of the impact of VOCs on the effectiveness of vaccine-induced immune response: A large number of cohorts of different risk, gender and age groups in different geographic regions contributed to this objective. The major finding includes: 1) Combination of vaccination and infection, i.e. hybrid immunity, confers higher anti-RBD IgG levels and higher neutralizing capacity than vaccination alone, likely providing better protection against COVID-19; 2) Boosting with updated vaccines in fragile population (immunocompromised and elderly) induced neutralizing antibody and T-cell responses, and continued vaccination confers benefit to this population, in particular against severe disease.
Objective 5 Identification of immune correlates of protection against VOCs: Using the statistical model, we were able to characterize the correlates of protection, identifying the events that led to higher uplift in antibody levels and longer durability of protection. We found generally low protection levels for the immunocompromised patient group, and the post-event uplift in antibody levels largely determines the protection durability
Research conducted under CoVICIS has made the following scientific and social impact:
• Genomic surveillance programs provided timely information to the national and international governing bodies on the emergence and evolution of SARS-CoV-2, confirmed the end of substantial regional variation: a variant would emerge in one part of the world and would quickly become the dominant variant in every part of the world, mostly following a similar pattern of Delta>Omicron BA.1> BA.2> BA.5> BQ.1 > XBB.
• Cohort studies have resulted in several findings with impact on public health policies on vaccination and disease management:
o Combination of vaccination and infection, i.e. hybrid immunity, lead to higher antibody responses than vaccination alone and therefore likely providing better protection
o Fragile population benefits from booster vaccination in particular against severe disease
o Prioritize vaccination for children with comorbidities, including living with HIV, underweight for age and younger age groups
• Genomic surveillance programs provided timely information to the national and international governing bodies on the emergence and evolution of SARS-CoV-2, confirmed the end of substantial regional variation: a variant would emerge in one part of the world and would quickly become the dominant variant in every part of the world, mostly following a similar pattern of Delta>Omicron BA.1> BA.2> BA.5> BQ.1 > XBB.
• Cohort studies have resulted in several findings with impact on public health policies on vaccination and disease management:
o Combination of vaccination and infection, i.e. hybrid immunity, lead to higher antibody responses than vaccination alone and therefore likely providing better protection
o Fragile population benefits from booster vaccination in particular against severe disease
o Prioritize vaccination for children with comorbidities, including living with HIV, underweight for age and younger age groups