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1.
Clin Infect Dis ; 2022 Jul 06.
Article in English | MEDLINE | ID: covidwho-2004983

ABSTRACT

BACKGROUND: Pregnancy represents a physiological state associated with increased vulnerability to severe outcomes from infectious diseases, both for the pregnant person and developing infant. The SARS-CoV-2 pandemic may have important health consequences for pregnant individuals, who may also be more reluctant than non-pregnant people to accept vaccination. METHODS: We sought to estimate the degree to which increased severity of SARS-CoV-2 outcomes can be attributed to pregnancy using a population-based SARS-CoV-2 case file from Ontario, Canada. Due to varying propensity to receive vaccination, and changes in dominant circulating viral strains over time, a time-matched cohort study was performed to evaluate the relative risk of severe illness in pregnant women with SARS-CoV-2 compared to other SARS-CoV-2 infected women of childbearing age (10 to 49 years old). Risk of severe SARS-CoV-2 outcomes was evaluated in pregnant women and time-matched non-pregnant controls using multivariable conditional logistic regression. RESULTS: Compared to the rest of the population, non-pregnant women of childbearing age had an elevated risk of infection (standardized morbidity ratio (SMR) 1.28), while risk of infection was reduced among pregnant women (SMR 0.43). After adjustment for confounding pregnant women had a markedly elevated risk of hospitalization (adjusted OR 4.96, 95% CI 3.86 to 6.37) and ICU admission (adjusted OR 6.58, 95% CI 3.29 to 13.18). The relative increase in hospitalization risk associated with pregnancy was greater in women without comorbidities than in those with comorbidities (P for heterogeneity 0.004). CONCLUSIONS: Given the safety of SARS-CoV-2 vaccines in pregnancy, risk-benefit calculus strongly favours SARS-CoV-2 vaccination in pregnant women.

2.
Clin Infect Dis ; 2022 May 25.
Article in English | MEDLINE | ID: covidwho-1927311

ABSTRACT

BACKGROUND: The rapid development of safe and effective vaccines against the SARS-CoV-2 virus has been a singular scientific achievement. Confounding due to health seeking behaviours, circulating variants, and differential testing by vaccination status may bias analyses towards an apparent increase in infection severity following vaccination. METHODS: We used data from Ontario, Canada's Case and Contact Management database, merged to a provincial vaccination dataset (COVaxON) to create a time-matched cohort of individuals who were hospitalized with SARS-CoV-2 infection. Vaccinated individuals were matched to up to five unvaccinated individuals based on test date. Risk of ICU admission and death were evaluated using conditional logistic regression. Unmatched exploratory analyses were performed to identify sources of heterogeneity in vaccine effects. RESULTS: In 20,064 individuals (3,353 vaccinated and 16,711 unvaccinated) hospitalized with infection due to SARS-CoV-2 between January 1st, 2021 and January 5th, 2022, vaccination with 1, 2, or 3 doses significantly reduced the risk of ICU admission and death. An inverse dose-response relationship was observed between vaccine doses received and both outcomes (adjusted odds ratio (aOR) per additional dose for ICU admission: 0.66, 95% CI 0.62 to 0.71; aOR for death: 0.78, 95% CI 0.72 to 0.84). Reduction in risk was greater for ICU admission than for death (P for heterogeneity <0.05). INTERPRETATION: We identified decreased virulence of SARS-CoV-2 infections in vaccinated individuals, even when vaccines failed to prevent infection sufficiently severe to cause hospitalization. Even with diminished efficacy of vaccines against infection with novel VOCs, vaccines remain an important tool for reduction of ICU admission and mortality.

3.
Brief Bioinform ; 23(3)2022 05 13.
Article in English | MEDLINE | ID: covidwho-1806276

ABSTRACT

T cell recognition of a cognate peptide-major histocompatibility complex (pMHC) presented on the surface of infected or malignant cells is of the utmost importance for mediating robust and long-term immune responses. Accurate predictions of cognate pMHC targets for T cell receptors would greatly facilitate identification of vaccine targets for both pathogenic diseases and personalized cancer immunotherapies. Predicting immunogenic peptides therefore has been at the center of intensive research for the past decades but has proven challenging. Although numerous models have been proposed, performance of these models has not been systematically evaluated and their success rate in predicting epitopes in the context of human pathology has not been measured and compared. In this study, we evaluated the performance of several publicly available models, in identifying immunogenic CD8+ T cell targets in the context of pathogens and cancers. We found that for predicting immunogenic peptides from an emerging virus such as severe acute respiratory syndrome coronavirus 2, none of the models perform substantially better than random or offer considerable improvement beyond HLA ligand prediction. We also observed suboptimal performance for predicting cancer neoantigens. Through investigation of potential factors associated with ill performance of models, we highlight several data- and model-associated issues. In particular, we observed that cross-HLA variation in the distribution of immunogenic and non-immunogenic peptides in the training data of the models seems to substantially confound the predictions. We additionally compared key parameters associated with immunogenicity between pathogenic peptides and cancer neoantigens and observed evidence for differences in the thresholds of binding affinity and stability, which suggested the need to modulate different features in identifying immunogenic pathogen versus cancer peptides. Overall, we demonstrate that accurate and reliable predictions of immunogenic CD8+ T cell targets remain unsolved; thus, we hope our work will guide users and model developers regarding potential pitfalls and unsettled questions in existing immunogenicity predictors.


Subject(s)
COVID-19 , Neoplasms , CD8-Positive T-Lymphocytes/metabolism , Computer Simulation , Epitopes, T-Lymphocyte , Humans , Peptides
4.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-331770

ABSTRACT

Background Vaccines to prevent SARS-CoV-2 infection and severe outcomes were approved in 2021 for adolescent and subsequently pediatric populations. With the emergence of variants of concern, it is important to continue to assess vaccine effectiveness against both infection and severe disease manifestations. Methods Using an age and time-matched nested case-control design, we estimated the vaccine effectiveness of SARS-CoV-2 vaccination at preventing hospitalization among adolescent and pediatric patients infected with SARS-CoV-2. We linked SARS-CoV-2 cases ages 4 to 17 years in Ontario’s reportable diseases database to SARS-CoV-2 vaccination records. We included 1,441 incident SARS-CoV-2 cases occurring between May 28, 2021 and January 10, 2022. We used multivariable logistic regression to estimate the effectiveness of one and two mRNA vaccine doses against hospitalization among adolescent and pediatric SARS-CoV-2 cases. We quantified and mitigated the impact of unmeasured confounding by calculating an E-value and by applying instrumental variable methods. Results We included n =131 hospitalized SARS-CoV-2 cases and n =1,310 non-hospitalized SARS-CoV-2 cases. One vaccine dose was shown to be 37% effective against hospitalization among SARS-CoV-2 cases (adjusted odds ratio [aOR] = 0.63 [95% CI: 0.33, 1.13]). In contrast, two doses were 59% (aOR = 0.41 [95% CI: 0.21, 0.77]) effective at preventing hospitalization among SARS-CoV-2 cases. Conclusions Even with immune evasion by SARS-CoV-2 variants, two vaccine doses continue to provide protection against hospitalization among adolescent and pediatric patients, even when the vaccines do not prevent infection. SARS-CoV-2 vaccines remain a safe and effective intervention to prevent severe outcomes.

5.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-329808

ABSTRACT

Background: Pregnancy represents a physiological state associated with increased vulnerability to severe outcomes from infectious diseases, both for the pregnant person and developing infant. The SARS-CoV-2 pandemic may have important health consequences for pregnant individuals, who may also be more reluctant than non-pregnant people to accept vaccination. We sought to estimate the degree to which increased severity of SARS-CoV-2 outcomes can be attributed to pregnancy. Methods: Our study made use of a population-based SARS-CoV-2 case file from Ontario, Canada. Due to both varying propensity to receive vaccination, and changes in dominant circulating viral strains over time, a time-matched cohort study was performed to evaluate the relative risk of severe illness in pregnant women with SARS-CoV-2 compared to other SARS-CoV-2 infected women of childbearing age (10 to 49 years old). Risk of severe SARS-CoV-2 outcomes (hospitalization or intensive care unit (ICU) admission) was evaluated in pregnant women and time-matched non-pregnant controls using multivariable conditional logistic regression. Results: Compared to the rest of the population, non-pregnant women of childbearing age had an elevated risk of infection (standardized morbidity ratio (SMR) 1.28), while risk of infection was reduced among pregnant women (SMR 0.43). After adjustment for age, comorbidity, healthcare worker status, vaccination, and infecting viral variant, pregnant women had a markedly elevated risk of hospitalization (adjusted OR 4.96, 95% CI 3.86 to 6.37) and ICU admission (adjusted OR 6.58, 95% CI 3.29 to 13.18). The relative increase in hospitalization risk associated with pregnancy was greater in women without comorbidities than in those with comorbidities (P for heterogeneity 0.004). Interpretation: A time-matched cohort study suggests that while pregnant women may be at a decreased risk of infection relative to the rest of the population, their risk of severe illness is markedly elevated if infection occurs. Given the safety of SARS-CoV-2 vaccines in pregnancy, risk-benefit calculus strongly favours SARS-CoV-2 vaccination in pregnant women.

6.
EuropePMC;
Preprint in English | EuropePMC | ID: ppcovidwho-327709

ABSTRACT

Background The rapid development of safe and effective vaccines against the SARS-CoV-2 virus has been a singular scientific achievement. Confounding due to health seeking behaviours and differential testing by vaccination status may bias analyses towards an apparent increase in infection severity following vaccination. We sought to determine whether risks of intensive care unit (ICU) admission and death were diminished significantly by vaccination, even in individuals for whom vaccination failed to prevent hospitalization. Methods We used data from Ontario, Canada’s Case and Contact Management database, merged to a provincial vaccination dataset (COVaxON) to create a time-matched cohort of individuals who were hospitalized with SARS-CoV-2 infection. Each vaccinated individual was matched to up to five unvaccinated individuals based on test date of positive SARS-CoV-2 infection. Risk of ICU admission and death were evaluated using multivariable conditional logistic regression. Unmatched exploratory analyses were performed to identify sources of heterogeneity in vaccine effects. Results In 20,064 individuals (3,353 vaccinated and 16,711 unvaccinated) hospitalized with infection due to SARS-CoV-2 between January 1 st , 2021 and January 5 th , 2022, vaccination with 1, 2, or 3 doses significantly reduced the risk of ICU admission and death. An inverse dose-response relationship was observed between vaccine doses received and both outcomes (adjusted odds ratio (aOR) for ICU admission per additional dose: 0.66, 95% CI 0.62 to 0.71;aOR for death per additional dose: 0.78, 95% CI 0.72 to 0.84). The reduction in risk was greater for ICU admission than for death (P for heterogeneity <0.05), but no significant differences in risk were seen based on infecting variant of concern (VOC). Interpretation We identified a decrease in the risk of ICU admission and death in vaccinated individuals compared to unvaccinated, time-matched controls, even when vaccines failed to prevent infection sufficiently severe to cause hospitalization. Even with diminished efficacy of vaccines against infection with novel VOCs, vaccines remain an important tool for reduction of ICU admission and mortality.

7.
Immunology ; 166(1): 78-103, 2022 05.
Article in English | MEDLINE | ID: covidwho-1685321

ABSTRACT

The conditions and extent of cross-protective immunity between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and common-cold human coronaviruses (HCoVs) remain open despite several reports of pre-existing T cell immunity to SARS-CoV-2 in individuals without prior exposure. Using a pool of functionally evaluated SARS-CoV-2 peptides, we report a map of 126 immunogenic peptides with high similarity to 285 MHC-presented peptides from at least one HCoV. Employing this map of SARS-CoV-2-non-homologous and homologous immunogenic peptides, we observe several immunogenic peptides with high similarity to human proteins, some of which have been reported to have elevated expression in severe COVID-19 patients. After combining our map with SARS-CoV-2-specific TCR repertoire data from COVID-19 patients and healthy controls, we show that public repertoires for the majority of convalescent patients are dominated by TCRs cognate to non-homologous SARS-CoV-2 peptides. We find that for a subset of patients, >50% of their public SARS-CoV-2-specific repertoires consist of TCRs cognate to homologous SARS-CoV-2-HCoV peptides. Further analysis suggests that this skewed distribution of TCRs cognate to homologous or non-homologous peptides in COVID-19 patients is likely to be HLA-dependent. Finally, we provide 10 SARS-CoV-2 peptides with known cognate TCRs that are conserved across multiple coronaviruses and are predicted to be recognized by a high proportion of the global population. These findings may have important implications for COVID-19 heterogeneity, vaccine-induced immune responses, and robustness of immunity to SARS-CoV-2 and its variants.


Subject(s)
COVID-19 , SARS-CoV-2 , CD8-Positive T-Lymphocytes , Cross Reactions , Epitopes, T-Lymphocyte , Humans , Peptides , Receptors, Antigen, T-Cell , Spike Glycoprotein, Coronavirus
8.
Sci Data ; 8(1): 173, 2021 07 15.
Article in English | MEDLINE | ID: covidwho-1315604

ABSTRACT

The COVID-19 pandemic has demonstrated the need for real-time, open-access epidemiological information to inform public health decision-making and outbreak control efforts. In Canada, authority for healthcare delivery primarily lies at the provincial and territorial level; however, at the outset of the pandemic no definitive pan-Canadian COVID-19 datasets were available. The COVID-19 Canada Open Data Working Group was created to fill this crucial data gap. As a team of volunteer contributors, we collect daily COVID-19 data from a variety of governmental and non-governmental sources and curate a line-list of cases and mortality for all provinces and territories of Canada, including information on location, age, sex, travel history, and exposure, where available. We also curate time series of COVID-19 recoveries, testing, and vaccine doses administered and distributed. Data are recorded systematically at a fine sub-national scale, which can be used to support robust understanding of COVID-19 hotspots. We continue to maintain this dataset, and an accompanying online dashboard, to provide a reliable pan-Canadian COVID-19 resource to researchers, journalists, and the general public.


Subject(s)
COVID-19 , Databases, Factual , Vaccination/statistics & numerical data , COVID-19/epidemiology , COVID-19/prevention & control , Canada/epidemiology , Data Collection , Humans , Pandemics
9.
Clin Infect Dis ; 74(2): 368-370, 2022 01 29.
Article in English | MEDLINE | ID: covidwho-1227648
10.
Front Immunol ; 11: 579480, 2020.
Article in English | MEDLINE | ID: covidwho-945659

ABSTRACT

While individuals infected with coronavirus disease 2019 (COVID-19) manifested a broad range in susceptibility and severity to the disease, the pre-existing immune memory to related pathogens cross-reactive against SARS-CoV-2 can influence the disease outcome in COVID-19. Here, we investigated the potential extent of T cell cross-reactivity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that can be conferred by other coronaviruses and influenza virus, and generated an in silico map of public and private CD8+ T cell epitopes between coronaviruses. We observed 794 predicted SARS-CoV-2 epitopes of which 52% were private and 48% were public. Ninety-nine percent of the public epitopes were shared with SARS-CoV and 5.4% were shared with either one of four common coronaviruses, 229E, HKU1, NL63, and OC43. Moreover, to assess the potential risk of self-reactivity and/or diminished T cell response for peptides identical or highly similar to the host, we identified predicted epitopes with high sequence similarity with human proteome. Lastly, we compared predicted epitopes from coronaviruses with epitopes from influenza virus deposited in IEDB, and found only a small number of peptides with limited potential for cross-reactivity between the two virus families. We believe our comprehensive in silico profile of private and public epitopes across coronaviruses would facilitate design of vaccines, and provide insights into the presence of pre-existing coronavirus-specific memory CD8+ T cells that may influence immune responses against SARS-CoV-2.


Subject(s)
CD8-Positive T-Lymphocytes/immunology , Coronavirus/immunology , Cross Reactions , SARS-CoV-2/immunology , Amino Acid Sequence , COVID-19 Vaccines/immunology , Computer Simulation , Databases, Factual , Epitopes, T-Lymphocyte/immunology , Humans , Orthomyxoviridae/immunology
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