Maternal neighbourhood-level social determinants of health and their association with paediatric hepatitis C screening among children exposed to hepatitis C in pregnancy.

BACKGROUND: Current guidelines recommend HCV screening by 18 months of age for those exposed to HCV in utero; yet, screening occurs in the minority of children. OBJECTIVES: To evaluate the association between maternal neighbourhood-level social determinants of health (SDOH) and paediatric HCV screening in the general population in a publicly funded healthcare system in Canada. METHODS: Retrospective cohort study using administrative healthcare data held at ICES. Children born to individuals positive for HCV RNA in pregnancy from 2000 to 2016 were identified and followed for 2 years. Major SDOH were identified, and the primary outcome was HCV screening in exposed children (HCV antibody and/or RNA). Associations between SDOH and HCV screening were determined using multivariate Poisson regression models adjusting for confounding. RESULTS: A total of 1780 children born to persons with +HCV RNA were identified, and 29% (n = 516) were screened for HCV by age two. Most mothers resided in the lowest income quintile (42%), and most vulnerable quintiles for material deprivation (41%), housing instability (38%) and ethnic diversity (26%) with 11% living in rural locations. After adjustment for confounding, maternal rural residence (risk ratio [RR] 0.82, 95% confidence interval [CI] 0.62, 1.07) and living in the highest dependency quintile (RR 0.83, 95% CI 0.65, 1.07) were the SDOH most associated with paediatric HCV screening. Younger maternal age (RR 0.98 per 1-year increase, 95% CI 0.97, 0.99), HIV co-infection (RR 1.69, 95% CI 1.16, 2.48) and GI specialist involvement (RR 1.18, 95% CI 1.00, 1.39) were associated with higher probabilities of screening. CONCLUSIONS: Among children exposed to HCV during pregnancy, rural residences and living in highly dependent neighbourhoods showed a potential association with a lower probability of HCV screening by the age of 2. Future work evaluating barriers to paediatric HCV screening among rural residing and dependent residents is needed to enhance the screening.

Centenarians and extremely old people living with frailty can elicit durable SARS-CoV-2 spike specific IgG antibodies with virus neutralization functions following virus infection as determined by serological study.

BACKGROUND: The SARS-CoV-2 (Severe Acute Respiratory Syndrome coronavirus 2) has led to more than 165 million COVID-19 cases and >3.4 million deaths worldwide. Epidemiological analysis has revealed that the risk of developing severe COVID-19 increases with age. Despite a disproportionate number of older individuals and long-term care facilities being affected by SARS-CoV-2 and COVID-19, very little is understood about the immune responses and development of humoral immunity in the extremely old person after SARS-CoV-2 infection. Here we conducted a serological study to investigate the development of humoral immunity in centenarians following a SARS-CoV-2 outbreak in a long-term care facility. METHODS: Extreme aged individuals and centenarians who were residents in a long-term care facility and infected with or exposed to SARS-CoV-2 were investigated between April and June 2020 for the development of antibodies to SARS-CoV-2. Blood samples were collected from positive and bystander individuals 30 and 60 days after original diagnosis of SARS-CoV-2 infection. Plasma was used to quantify IgG, IgA, and IgM isotypes and subsequent subclasses of antibodies specific for SARS-CoV-2 spike protein. The function of anti-spike was then assessed by virus neutralization assays against the native SARS-CoV-2 virus. FINDINGS: Fifteen long-term care residents were investigated for SARS-CoV-2 infection. All individuals had a Clinical Frailty scale score ≥5 and were of extreme older age or were centenarians. Six women with a median age of 98.8 years tested positive for SARS-CoV-2. Anti-spike IgG antibody titers were the highest titers observed in our cohort with all IgG positive individuals having virus neutralization ability. Additionally, 5 out of the 6 positive participants had a robust IgA anti-SARS-CoV-2 response. In all 5, antibodies were detected after 60 days from initial diagnosis.

Sex and age bias viral burden and interferon responses during SARS-CoV-2 infection in ferrets.

SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) hospitalizations and deaths disportionally affect males and older ages. Here we investigated the impact of male sex and age comparing sex-matched or age-matched ferrets infected with SARS-CoV-2. Differences in temperature regulation was identified for male ferrets which was accompanied by prolonged viral replication in the upper respiratory tract after infection. Gene expression analysis of the nasal turbinates indicated that 1-year-old female ferrets had significant increases in interferon response genes post infection which were delayed in males. These results provide insight into COVID-19 and suggests that older males may play a role in viral transmission due to decreased antiviral responses.

Male sex and age biases viral burden, viral shedding, and type 1 and 2 interferon responses during SARS-CoV-2 infection in ferrets.

SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) hospitalizations and deaths disportionally affect males and the elderly. Here we investigated the impact of male sex and age by infecting adult male, aged male, and adult female ferrets with SARS-CoV-2. Aged male ferrets had a decrease in temperature which was accompanied by prolonged viral replication with increased pathology in the upper respiratory tract after infection. Transcriptome analysis of the nasal turbinates and lungs indicated that female ferrets had significant increases in interferon response genes (OASL, MX1, ISG15, etc.) on day 2 post infection which was delayed in aged males. In addition, genes associated with taste and smell such as RTP1, CHGA, and CHGA1 at later time points were upregulated in males but not in females. These results provide insight into COVID-19 and suggests that older males may play a role in viral transmission due to decreased antiviral responses.

Historical H1N1 Influenza Virus Imprinting Increases Vaccine Protection by Influencing the Activity and Sustained Production of Antibodies Elicited at Vaccination in Ferrets.

Influenza virus imprinting is now understood to significantly influence the immune responses and clinical outcome of influenza virus infections that occur later in life. Due to the yearly cycling of influenza viruses, humans are imprinted with the circulating virus of their birth year and subsequently build a complex influenza virus immune history. Despite this knowledge, little is known about how the imprinting strain influences vaccine responses. To investigate the immune responses of the imprinted host to split-virion vaccination, we imprinted ferrets with a sublethal dose of the historical seasonal H1N1 strain A/USSR/90/1977. After a +60-day recovery period to build immune memory, ferrets were immunized and then challenged on Day 123. Antibody specificity and recall were investigated throughout the time course. At challenge, the imprinted vaccinated ferrets did not experience significant disease, while naïve-vaccinated ferrets had significant weight loss. Haemagglutination inhibition assays showed that imprinted ferrets had a more robust antibody response post vaccination and increased virus neutralization activity. Imprinted-vaccinated animals had increased virus-specific IgG antibodies compared to the other experimental groups, suggesting B-cell maturity and plasticity at vaccination. These results should be considered when designing the next generation of influenza vaccines.