ABSTRACT
Some respiratory viruses can cause a viral interference through the activation of the interferon (IFN) pathway that reduces the replication of another virus. Epidemiological studies of coinfections between SARS-CoV-2 and other respiratory viruses have been hampered by non-pharmaceutical measures applied to mitigate the spread of SARS-CoV-2 during the COVID-19 pandemic. With the ease of these interventions, SARS-CoV-2 and influenza A viruses can now co-circulate. It is thus of prime importance to characterize their interactions. In this work, we investigated viral interference effects between an Omicron variant and a contemporary influenza A/H3N2 strain, in comparison with an ancestral SARS-CoV-2 strain and the 2009 pandemic influenza A/H1N1 virus. We infected nasal human airway epitheliums with SARS-CoV-2 and influenza, either simultaneously or 24 h apart. Viral load was measured by RT-qPCR and IFN-/{beta}/{lambda}1/{lambda}2 proteins were quantified by immunoassay. Expression of four interferon-stimulated genes (ISGs; OAS1/IFITM3/ISG15/MxA) was also measured by RT-droplet digital PCR. Additionally, susceptibility of each virus to IFN-/{beta}/{lambda}2 recombinant proteins was determined. Our results showed that influenza A, and especially A/H3N2, interfered with both SARS-CoV-2 viruses, but that SARS-CoV-2 only interfered with A/H1N1. Consistently with these results, influenza, and particularly the A/H3N2 strain, caused a higher production of IFN proteins and expression of ISGs than SARS-CoV-2. The IFN production induced by SARS-CoV-2 was marginal and its presence during coinfections with influenza was associated with a reduced IFN response. All viruses were susceptible to exogenous IFNs, with the ancestral SARS-CoV-2 and Omicron being less susceptible to type I and type III IFNs, respectively. Thus, influenza A causes a viral interference towards SARS-CoV-2 most likely through an IFN response. The opposite is not necessarily true, and a concurrent infection with both viruses leads to a lower IFN response. Taken together, these results help us to understand how SARS-CoV-2 interacts with another major respiratory pathogen.
Subject(s)
Coronavirus Infections , Severe Acute Respiratory Syndrome , COVID-19ABSTRACT
Importance: Repeated serological testing for SARS-CoV-2 allows the monitoring of antibody dynamics in populations, including detecting infections that are missed by RT-PCR or antigen testing. Understanding the factors associated with seroconversion and seroreversion as well as the duration of infection-induced antibodies can also inform public health recommendations regarding disease prevention and mitigation efforts. Objective: To use serological testing to assess the prevalence, seroconversion, and seroreversion of infection-induced SARS-CoV-2 antibodies in children and adolescents in Montreal, Canada. Design: This analysis reports on three rounds of data collection from a prospective cohort study (Enfants et COVID-19: Etude de seroprevalence [EnCORE]). The study rounds occurred as follows: Round 1 October 2020-March 2021, Round 2 May to July 2021, and Round 3 November 2021 to January 2022. Most Round 3 samples were collected prior to the spread of the Omicron BA.1 variant in Quebec. Setting: Population-based sample. Participants: Children and adolescents aged 2 to 17 years in Montreal, Canada. Exposure: Potential exposure to SARS-CoV-2. Main Outcomes and Measures: Participants provided dried blood spots (DBS) for antibody detection and parents completed online questionnaires for sociodemographics and COVID-19 symptoms and testing history. The serostatus of participants was determined by enzyme-linked immunosorbent assays (ELISAs) using the receptor-binding domain (RBD) from the spike protein and the nucleocapsid protein (N) as antigens. We estimated seroprevalence for each round of data collection and by participant and household characteristics. Seroconversion rates were calculated as were the likelihoods of remaining seropositive at six months and one year. Results: The study included DBS samples from 1 632, 936, and 723 participants in the first, second, and third rounds of data collection, respectively. The baseline seroprevalence was 5.8% (95% CI 4.8-7.1), which increased to 10.5% and 10.9% for the respective follow-ups (95% CI 8.6-12.7; 95% CI 8.8-13.5). The overall average crude rate of seroconversion over the study period was 12.7 per 100 person-years (95% CI 10.9-14.5). Adjusted hazard rates of seroconversion by child and household characteristics showed higher rates in children who were female, whose parent identified as a racial or ethnic minority, and in households with incomes less than 100K. The likelihood of remaining seropositive at six months was 67% (95% CI 59-76) and dropped to 19% (95% CI 11%-33%) at one year. Conclusions and Relevance: The data reported here provide estimates of pre-Omicron seroprevalence, seroconversion rates and time to seroreversion in a population-based cohort of children and adolescents. Serological studies continue to provide valuable contributions for infection prevalence estimates and help us better understand the dynamics of antibody levels following infection. Continued study of seroconversion and seroreversion can inform public health recommendations such as COVID-19 vaccination and booster schedules.
Subject(s)
COVID-19ABSTRACT
ABSTRACT Importance Public health vaccination recommendations for COVID-19 primary series and boosters in previously infected individuals differ worldwide. As infection with SARS-CoV-2 is often asymptomatic, it remains to be determined if vaccine immunogenicity is comparable in all previously infected subjects. We present detailed immunological evidence to clarify the requirements for one-or two-dose primary vaccination series for naturally primed individuals. Objective Evaluate the immune response to COVID-19 mRNA vaccines in healthcare workers (HCWs) who recovered from a SARS-CoV-2 infection. Design Multicentric observational prospective cohort study of HCWs with a PCR-confirmed SARS-CoV-2 infection designed to evaluate the dynamics of T and B cells immune responses to primary infection and COVID-19 mRNA vaccination over 12 months. Participants Unvaccinated HCWs with PCR-confirmed SARS-CoV-2 infection were selected based on the presence or absence of symptoms at infection and serostatus at enrollment. Age- and sex-matched adults not infected with SARS-CoV-2 prior to vaccination were included as naïve controls. Exposure Vaccination with Pfizer BioNTech BNT162b2 mRNA vaccine. Main Outcome(s) and Measure(s) Immunity score (zero to three), before and after vaccination, based on anti-RBD IgG ratio, serum capacity to neutralize live virus and IFN-γ secretion capacity in response to SARS-CoV-2 peptide pools above the positivity threshold for each of the three assays. We compared the immunity score between groups based on subjects’ symptoms at diagnosis and/or serostatus prior to vaccination. Results None of the naïve participants (n=14) showed a maximal immunity score of three following one dose of vaccine compared to 84% of the previously infected participants (n=55). All recovered individuals who did not have an immunity score of three were seronegative prior to vaccination, and 67% had not reported symptoms resulting from their initial infection. Following one dose of vaccine, their immune responses were comparable to naïve individuals, with significantly weaker responses than those who were symptomatic during infection. Conclusions and Relevance Individuals who did not develop symptoms during their initial SARS-CoV-2 infection and were seronegative prior to vaccination present immune responses comparable to that of naïve individuals. These findings highlight the importance of administering the complete two-dose primary regimen and following boosters of mRNA vaccines to individuals who experienced asymptomatic SARS-CoV-2 infection. KEY POINTS Question Is a single dose of COVID-19 mRNA vaccine sufficient to induce robust immune responses in individuals with prior SARS-CoV-2 infection? Findings In this cohort of 55 health care workers previously infected with SARS-CoV-2, we show that the absence of symptoms during initial infection and negative serostatus prior to vaccination predict the strength of immune responses to COVID-19 mRNA vaccine. Lack of symptoms and a negative serostatus prior to vaccination leads to immune responses comparable to naïve individuals. Meaning Our results support a two-dose primary series requirement for any individual with prior history of asymptomatic SARS-CoV-2 infection.
Subject(s)
COVID-19ABSTRACT
Background: Montreal was one of the highest COVID-19 burdened cities in Canada during the first and second waves of the pandemic. We estimated the seroprevalence of SARS-CoV-2 in children and teenagers in four neighbourhoods of Montreal, Canada.Methods: All children attending selected schools and daycares within the four neighbourhoods were invited to participate in the study. Study participation included an online questionnaire that parents completed, followed by at-home dried blood spot (DBS) collection. Serological results were analyzed using a research-based ELISA assay. Statistical analyses included multivariable logistic regression models to calculate average marginal effects and robust standard errors to account for clustering by school or daycare. Several different sociodemographic differences were examined between the seronegative and seropositive children.Findings: There were 30 daycares, 22 primary schools, and 11 secondary schools that participated in the study with 1,632 participants having provided a DBS sample that was of sufficient quality for the serological analysis. The average seroprevalence was 5·8% (95%CI 4·6 to 7·0) but increased over time from 3·2% (95% CI 0·7 to 5·8) in October-November 2020 to 8.4% (95% CI 4·4 to 12·4) in March-April 2021. The children of visible minority parents were nearly twice as likely to be seropositive as children of non-visible minority parents (1·93, 95%CI 1·11 to 2·75). Interpretation: Our results provide a benchmark of the seroprevalence status in Canadian children and provide further evidence of COVID-19 inequities. It will be important to continue monitoring the serological status of children, particularly in the context of new COVID-19 variants of concern and in the absence of mass vaccination campaigns targeting young children.Funding Information: Public Health Agency of Canada through the COVID-19 Immunity Task Force.Declaration of Interests: All authors declare no competing interests.Ethics Approval Statement: All participants provided informed consent for the survey and ethics approval was received from the research ethics boards of the Université de Montréal and the Centre Hospitalier Universitaire Sainte-Justine.
Subject(s)
COVID-19ABSTRACT
Background: Further evidence is needed to understand the contribution of schools and daycares to the spread of COVID-19 in the context of diverse transmission dynamics and continually evolving public health interventions. The Enfants et COVID-19: Etude de seroprevalence (EnCORE) study will estimate the seroprevalence and seroconversion of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among school and daycare children and personnel. In addition, the study will examine associations between seroprevalence and socio-demographic characteristics and reported COVID-19 symptoms and tests, and investigates changes in health, lifestyle and well-being outcomes. Methods: This study includes children and personnel from 62 schools and daycares in four neighbourhoods in Montreal, Canada. All children age 2-17 years attending one of the participating schools or daycares and their parents are invited to participate, as well as a sample of personnel members. Participants respond to brief questionnaires and provide blood samples, collected via dried blood spot (DBS), at baseline (October 2020-March 2021) and follow-up (May-June 2021). Questionnaires include socio-demographic and household characteristics, reported COVID-19 symptoms and tests, potential COVID-19 risk factors and prevention efforts, and health and lifestyle information. Logistic regression using generalized estimating equations will be used to estimate seroprevalence and seroconversion, accounting for school-level clustering. Discussion: The results of the EnCORE study will contribute to our knowledge about SARS-CoV-2 transmission in schools and daycares, which is critical for decisions regarding school attendance and the management of school outbreaks through the remainder of this school year and beyond. Keywords SARS-CoV-2; COVID-19; Children; School; Serology; Protocol; Canada