Factors associated with SARS-CoV-2 infection in unvaccinated children and young adults.

BACKGROUND AND OBJECTIVES: Pediatric COVID-19 cases are often mild or asymptomatic, which has complicated estimations of disease burden using existing testing practices. We aimed to determine the age-specific population seropositivity and risk factors of SARS-CoV-2 seropositivity among children and young adults during the pandemic in British Columbia (BC). METHODS: We conducted two cross-sectional serosurveys: phase 1 enrolled children and adults < 25 years between November 2020-May 2021 and phase 2 enrolled children < 10 years between June 2021-May 2022 in BC. Participants completed electronic surveys and self-collected finger-prick dried blood spot (DBS) samples. Samples were tested for immunoglobulin G antibodies against ancestral spike protein (S). Descriptive statistics from survey data were reported and two multivariable analyses were conducted to evaluate factors associated with seropositivity. RESULTS: A total of 2864 participants were enrolled, of which 95/2167 (4.4%) participants were S-seropositive in phase 1 across all ages, and 61/697 (8.8%) unvaccinated children aged under ten years were S-seropositive in phase 2. Overall, South Asian participants had a higher seropositivity than other ethnicities (13.5% vs. 5.2%). Of 156 seropositive participants in both phases, 120 had no prior positive SARS-CoV-2 test. Young infants and young adults had the highest reported seropositivity rates (7.0% and 7.2% respectively vs. 3.0-5.6% across other age groups). CONCLUSIONS: SARS-CoV-2 seropositivity among unvaccinated children and young adults was low in May 2022, and South Asians were disproportionately infected. This work demonstrates the need for improved diagnostics and reporting strategies that account for age-specific differences in pandemic dynamics and acceptability of testing mechanisms.

Prescribing patterns of antiretroviral treatments during pregnancy for women living with HIV in Canada 2004-2020: A surveillance study.

BACKGROUND: While treatment guidelines for HIV in adults have evolved rapidly with the advent of new antiretroviral (ARV) treatment, those for the prevention of vertical HIV transmission in pregnancy have evolved more slowly due to safety and efficacy concerns. Here we describe Canadian prescribing patterns for ARV treatments during pregnancy and compare them to perinatal HIV prescribing guidelines of the United States Department of Health and Human Services (HHS), that are commonly used in Canada and include recommendations for newly commercialized therapies. METHODS: The Canadian Perinatal HIV Surveillance Program (CPHSP) captures annual medical data on mothers living with HIV and their infants from 23 sites across Canada. Women from this cohort who received an ARV treatment during pregnancy and who gave birth between 2004 and 2020 were included in the study. ARV treatments were designated as 'preferred/alternative' as per HHS HIV perinatal guidelines, or 'other than preferred/alternative'. RESULTS: We identified 3673 pregnancies from 2720 women. The proportion of women that conceived while on ARV treatment increased from 29% in 2003 to 90% in 2020. Other than preferred/alternative ARV treatments were received in 1112 (30%) of pregnancies and this was significantly associated with having initiated ARV treatment before conception. CONCLUSION: In Canada during the study period, a high number of women were prescribed an other than preferred/alternative ARV treatment during pregnancy. Further optimization of ARV treatment in women of childbearing age living with HIV is warranted.

La réduction du risque d'infection périnatale chez les nouveau-nés de mères dont les soins prénatals étaient inappropriés.

Le risque que des infections maternelles ne soient ni décelées ni traitées augmente lorsque les soins prénatals sont inappropriés, ce qui met la santé de la mère et de son nouveau-né à risque. Lorsqu'une femme enceinte se présente tardivement pour recevoir des soins, les tests systématiques qui influent sur la prise en charge du nouveau-né devraient inclure l'antigène de surface de l'hépatite B (AgHBs), la sérologie du virus de l'hépatite C (VHC), du virus de l'immunodéficience humaine (VIH) et de la syphilis, de même que le dépistage de la Chlamydia trachomatis et de la Neisseria gonorrhoeae. Si la mère ne s'est pas soumise aux dépistages avant ou après l'accouchement et qu'elle n'est pas disponible pour s'y soumettre, il faudrait procéder au dépistage du VIH, du virus de l'hépatite B (VHB), du VHC et de la syphilis chez le nouveau-né. Le dépistage de la C. trachomatis et de la N. gonorrhoeae est toutefois réservé aux cas où le nouveau-né démontre des manifestations cliniques compatibles avec ces infections. Il est optimal d'obtenir rapidement les résultats du dépistage du VIH, du VHB et de la syphilis, car l'utilisation des traitements préventifs est circonscrite dans le temps. Il existe des interventions préventives précoces et efficaces pour les nouveau-nés à risque de VIH, de VHB, de syphilis ou de gonorrhée. Un suivi clinique étroit et des tests de suivi s'imposent auprès des nouveau-nés de mères dont les soins prénatals étaient inappropriés, car il est impossible d'exclure pleinement toutes les infections pendant la période périnatale.

Reducing perinatal infection risk in newborns of mothers who received inadequate prenatal care.

Inadequate prenatal care increases risk for maternal infections going undetected and untreated, putting both the mother's health and that of her infant at risk. When pregnant women present late to care, routine testing that impacts infant management should include: hepatitis B surface antigen (HBsAg); serology for hepatitis C virus (HCV), human immunodeficiency virus (HIV), and syphilis; and testing for Chlamydia trachomatis and Neisseria gonorrhoeae. If the mother was not tested before or after delivery and is not available for testing, the infant should undergo testing for HIV, HBV, HCV, and syphilis. Testing for C. trachomatis and N. gonorrhoeae should be undertaken if the infant develops compatible clinical manifestations. Rapid turnaround of test results for HIV, HBV, and syphilis is optimal because preventive treatment decisions are time-sensitive. Early and effective preventive interventions are available for newborns at risk for HIV, HBV, syphilis, or gonorrhea. Close clinical follow-up and follow-up testing of infants born to mothers with inadequate prenatal care are warranted, as not all infections can be fully excluded perinatally.

Child transmission of SARS-CoV-2: a systematic review and meta-analysis.

BACKGROUND: Understanding of the role of children in COVID-19 transmission has significant implications for school and childcare policies, as well as appropriate targeting of vaccine campaigns. The objective of this systematic review was to identify the role of children in SARS-CoV-2 transmission to other children and adults. METHODS: MEDLINE, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials, and Web of Science were electronically searched for articles published before March 31, 2021. Studies of child-to-child and child-to-adult transmission and quantified the incidence of index and resulting secondary attack rates of children and adults in schools, households, and other congregate pediatric settings were identified. All articles describing confirmed transmission of SARS-CoV-2 from a child were included. PRISMA guidelines for data abstraction were followed, with each step conducted by two reviewers. RESULTS: 40 of 6110 articles identified met inclusion criteria. Overall, there were 0.8 secondary cases per primary index case, with a secondary attack rate of 8.4% among known contacts. The secondary attack rate was 26.4% among adult contacts versus 5.7% amongst child contacts. The pooled estimate of a contact of a pediatric index case being infected as secondary case was 0.10 (95% CI 0.03-0.25). CONCLUSIONS: Children transmit COVID-19 at a lower rate to children than to adults. Household adults are at highest risk of transmission from an infected child, more so than adults or children in other settings.

Women in the 2019 hepatitis C cascade of care: findings from the British Columbia Hepatitis Testers cohort study.

BACKGROUND: Women living with hepatitis C virus (HCV) are rarely addressed in research and may be overrepresented within key populations requiring additional support to access HCV care and treatment. We constructed the HCV care cascade among people diagnosed with HCV in British Columbia, Canada, as of 2019 to compare progress in care and treatment and to assess sex/gender gaps in HCV treatment access. METHODS: The BC Hepatitis Testers Cohort includes 1.7 million people who tested for HCV, HIV, reported cases of hepatitis B, and active tuberculosis in BC from 2000 to 2019. Test results were linked to medical visits, hospitalizations, cancers, prescription drugs, and mortality data. Six HCV care cascade stages were identified: (1) antibody diagnosed; (2) RNA tested; (3) RNA positive; (4) genotyped; (5) initiated treatment; and (6) achieved sustained virologic response (SVR). HCV care cascade results were assessed for women, and an 'inverse' cascade was created to assess gaps, including not being RNA tested, genotyped, or treatment initiated, stratified by sex. RESULTS: In 2019, 52,638 people with known sex were anti-HCV positive in BC; 37% (19,522) were women. Confirmatory RNA tests were received by 86% (16,797/19,522) of anti-HCV positive women and 83% (27,353/33,116) of men. Among people who had been genotyped, 68% (6756/10,008) of women and 67% (12,640/18,828) of men initiated treatment, with 94% (5023/5364) of women and 92% (9147/9897) of men achieving SVR. Among the 3252 women and 6188 men not yet treated, higher proportions of women compared to men were born after 1975 (30% vs. 21%), had a mental health diagnosis (42% vs. 34%) and had used injection drugs (50% vs. 45%). Among 1619 women and 2780 men who had used injection drugs and were not yet treated, higher proportions of women than men used stimulants (64% vs. 57%), and opiates (67% vs. 60%). CONCLUSIONS: Women and men appear to be equally engaged into the HCV care cascade; however, women with concurrent social and health conditions are being left behind. Treatment access may be improved with approaches that meet the needs of younger women, those with mental health diagnoses, and women who use drugs.

Group A streptococcal pharyngitis: A practical guide to diagnosis and treatment.

Group A Streptococcus (GAS) pharyngitis is a common clinical syndrome in primary care, yet controversy remains regarding the best approach to diagnosis and treatment, including the benefits of antibiotics. Children who are likely to have GAS pharyngitis based on history or physical examination should have a throat swab and, when positive, be treated with amoxicillin or penicillin. The disproportionate burden of acute rheumatic fever in Indigenous populations in Canada and special considerations for testing and treatment are discussed.

Clinical Correlates of Human Immunodeficiency Virus-1 (HIV-1) DNA and Inducible HIV-1 RNA Reservoirs in Peripheral Blood in Children With Perinatally Acquired HIV-1 Infection With Sustained Virologic Suppression for at Least 5 Years.

BACKGROUND: The Early Pediatric Initiation Canada Child Cure Cohort (EPIC4) study is a prospective, multicenter, Canadian cohort study investigating human immunodeficiency virus-1 (HIV-1) reservoirs, chronic inflammation, and immune responses in children with perinatally acquired HIV-1 infection. The focus of this report is HIV-1 reservoirs and correlates in the peripheral blood of children who achieved sustained virologic suppression (SVS) for ≥5 years. METHODS: HIV-1 reservoirs were determined by measuring HIV-1 DNA in peripheral blood mononuclear cells and inducible cell-free HIV-1 RNA in CD4+ T-cells by a prostratin analogue stimulation assay. HIV serology was quantified by signal-to-cutoff ratio (S/CO). RESULTS: Of 228 enrolled participants, 69 achieved SVS for ≥5 years. HIV-1 DNA, inducible cell-free HIV-1 RNA, and S/COs correlated directly with the age of effective combination antiretroviral therapy (cART) initiation (P < .001, P = .036, and P < .001, respectively) and age when SVS was achieved (P = .002, P = .038, and P < .001, respectively) and inversely with the proportion of life spent on effective cART (P < .001, P = .01, and P < .001, respectively) and proportion of life spent with SVS (P < .001, P = .079, and P < .001, respectively). Inducible cell-free HIV-1 RNA correlated with HIV-1 DNA, most particularly in children with SVS, without virologic blips, that was achieved with the first cART regimen initiated prior to 6 months of age (rho = 0.74; P = .037) or later (rho = 0.87; P < .001). S/COs correlated with HIV-1 DNA (P = .003), but less so with inducible cell-free HIV-1 RNA (P = .09). CONCLUSIONS: The prostratin analogue stimulation assay, with its lower blood volume requirement, could be a valuable method for evaluating inducible HIV-1 reservoirs in children. Standard commercial HIV serology may be a practical initial indirect measure of reservoir size in the peripheral blood of children with perinatally acquired HIV-1 infection.

Retrospective Cohort Study on the Impact of the COVID-19 Pandemic on Pregnancy Outcomes for Women Living With HIV in British Columbia.

BACKGROUND: For pregnant women living with HIV (WLWH), engagement in care is crucial to maternal health and reducing the risk of perinatal transmission. To date, there have been no studies in Canada examining the impact of the COVID-19 pandemic on pregnant WLWH. METHODS: This was a retrospective cohort study assessing the impact of the pandemic on perinatal outcomes for pregnant WLWH using data from the Perinatal HIV Surveillance Program in British Columbia, Canada. We compared maternal characteristics, pregnancy outcomes, and clinical indicators related to engagement with care between a prepandemic (January 2017-March 2020) and pandemic cohort (March 2020-December 2022). We investigated preterm birth rates with explanatory variables using logistic regression analysis. RESULTS: The prepandemic cohort (n = 87) had a significantly (P < 0.05) lower gestational age at the first antenatal encounter (9.0 vs 11.8) and lower rates of preterm births compared with the pandemic cohort (n = 56; 15% vs 37%). Adjusted odds of preterm birth increased with the presence of substance use in pregnancy (aOR = 10.45, 95% confidence interval: 2.19 to 49.94) in WLWH. There were 2 cases of perinatal transmission of HIV in the pandemic cohort, whereas the prepandemic cohort had none. CONCLUSIONS: The pandemic had pronounced effects on pregnant WLWH and their infants in British Columbia including higher rates of preterm birth and higher gestational age at the first antenatal encounter. The nonstatistically significant increase in perinatal transmission rates is of high clinical importance.

Lower Neutrophil Count Without Clinical Consequence Among Children of African Ancestry Living With HIV in Canada.

OBJECTIVE: To investigate the association between African ancestry and neutrophil counts among children living with HIV (CLWH). We also examined whether medications, clinical conditions, hospitalization, or HIV virologic control were associated with low neutrophil counts or African ancestry. DESIGN: We conducted a secondary analysis of the Early Pediatric Initiation Canada Child Cure Cohort (EPIC4) Study, a multicenter prospective cohort study of CLWH across 8 Canadian pediatric HIV care centers. METHODS: We classified CLWH according to African ancestry, defined as "African," "Caribbean," or "Black" maternal race. Longitudinal laboratory data (white blood cells, neutrophils, lymphocytes, viral load, and CD4 count) and clinical data (hospitalizations, AIDS-defining conditions, and treatments) were abstracted from medical records. RESULTS: Among 217 CLWH (median age 14, 55% female), 145 were of African ancestry and 72 were of non-African ancestry. African ancestry was associated with lower neutrophil counts, white blood cell counts, and neutrophil-lymphocyte ratios. Neutrophil count <1.5 × 109/L was detected in 60% of CLWH of African ancestry, compared with 31% of CLWH of non-African ancestry (P < 0.0001), representing a 2.0-fold higher relative frequency (95% CI: 1.4-2.9). Neutrophil count was on average 0.74 × 109/L (95% CI: 0.45 to 1.0) lower in CLWH of African ancestry (P < 0.0001). Neither neutrophil count<1.5 × 109/L nor African ancestry was associated with medications, hospitalizations, AIDS-defining conditions, or markers of virologic control (viral load, sustained viral suppression, and lifetime nadir CD4). CONCLUSIONS: In CLWH, African ancestry is associated with lower neutrophil counts, without clinical consequences. A flexible evaluation of neutrophil counts in CLWH of African ancestry may avoid unnecessary interventions.

Chronic and Latent Viral Infections and Leukocyte Telomere Length across the Lifespan of Female and Male Individuals Living with or without HIV.

BACKGROUND: Chronic/latent viral infections may accelerate immunological aging, particularly among people living with HIV (PLWH). We characterized chronic/latent virus infections across their lifespan and investigated their associations with leukocyte telomere length (LTL). METHODS: Participants enrolled in the CARMA cohort study were randomly selected to include n = 15 for each decade of age between 0 and >60 y, for each sex, and each HIV status. Cytomegalovirus (CMV), Epstein-Barr virus (EBV), human herpesvirus 8 (HHV-8), herpes simplex virus 1 (HSV-1), and HSV-2 infection were determined serologically; HIV, hepatitis C (HCV), and hepatitis B (HBV) were self-reported. LTLs were measured using monochrome multiplex qPCR. Associations between the number of viruses, LTL, and sociodemographic factors were assessed using ordinal logistic and linear regression modeling. RESULTS: The study included 187 PLWH (105 female/82 male) and 190 HIV-negative participants (105 female/84 male), ranging in age from 0.7 to 76.1 years. Living with HIV, being older, and being female were associated with harbouring a greater number of chronic/latent non-HIV viruses. Having more infections was in turn bivariately associated with a shorter LTL. In multivariable analyses, older age, living with HIV, and the female sex remained independently associated with having more infections, while having 3-4 viruses (vs. 0-2) was associated with a shorter LTL. CONCLUSIONS: Our results suggest that persistent viral infections are more prevalent in PLWH and females, and that these may contribute to immunological aging. Whether this is associated with comorbidities later in life remains an important question.

Type and timing of antiretroviral therapy during pregnancy: Impact on risk of preterm delivery and small-for-gestational age births in Canada, a retrospective cohort study.

OBJECTIVE: To evaluate the impact of type and timing of antiretroviral therapy (ART) on the risk of preterm delivery (PTD) and small-for-gestational age (SGA) birth among pregnant women and people living with HIV in Canada. METHODS: Data for this retrospective cohort study were analyzed from the Canadian Perinatal HIV Surveillance Program from 1990 to 2020. The association between ART and risk of PTD (<37 weeks) and SGA birth (<10th percentile) was explored using mixed effects logistic regression and time-dependent Cox proportional hazards models. RESULTS: Overall, there were 14.9% (654 of 4379) PTD and 18.5% (732 of 3947) SGA cases. A higher risk of PTD was observed with nonnucleoside reverse transcriptase inhibitor-(adjusted hazard ratio [aHR], 1.73; P = 0.019) and boosted protease inhibitor- (aHR, 186; P = 0.007) based regimens compared with integrase strand transfer inhibitor (INSTI)-based regimens. ART initiation prior to conception was associated with a lower risk of SGA birth compared with ART initiation after conception at 1 to 14 weeks (adjusted odds ratio [aOR], 0.69; P = 0.024) and > 14 weeks (aOR, 0.70; P = 0.005). CONCLUSION: INSTI-based ART regimens were associated with lower risk of PTD compared with other regimens, and ART initiation before conception was associated with a lower risk of SGA birth. These findings, with overall safety data, should be considered when providing pregnancy counseling to people living with HIV.

Higher Hospitalization Rates in Children Born HIV-exposed Uninfected in British Columbia, Canada, Between 1990 and 2012.

BACKGROUND: Compared with children who are HIV-unexposed and uninfected (CHUU), children who are HIV-exposed and uninfected (CHEU) experience more clinical complications. We investigated hospitalizations among CHEU by antenatal antiretroviral therapy (ART) exposure, in British Columbia, Canada. METHODS: This retrospective controlled cohort study used administrative health data from 1990 to 2012. CHEU and CHUU were matched 1:3 for age, sex and maternal geographical area of residence. We determined adjusted odds ratios (aORs) via conditional logistic regression, adjusting for maternal risk factors. RESULTS: A total of 446 CHEU and 1333 CHUU were included. Compared with CHUU, more CHEU experienced one or more lifetime hospitalization (47.3% vs. 29.8%), one or more neonatal hospitalization (40.4% vs. 27.6%), and any intensive care unit admission (28.5% vs. 9.2%). In adjusted analyses, CHEU experienced higher odds of any lifetime hospitalization (aOR 2.30, 95% confidence interval 1.81-2.91) and neonatal hospitalization (aOR 2.14, 95% confidence interval 1.68-2.73), compared with CHUU. There was, however, no difference in infection-related hospitalizations (9.0% vs. 7.5%), which were primarily respiratory tract infections among both CHEU and CHUU. CHEU whose mothers-initiated ART preconception showed lower odds of infection-related hospitalizations than children whose mothers initiated ART during pregnancy or received no ART. CONCLUSIONS: CHEU experienced increased odds of hospitalization relative to CHUU. A substantial number of CHEU hospitalizations occurred within the neonatal period and were ICU admissions. Initiating ART preconception may reduce the risk of infection-related hospitalizations. These findings reinforce the benefit of ART in pregnancy and the need for ongoing pediatric care to reduce hospitalizations.

Kawasaki disease following immunization reported to the Canadian Immunization Monitoring Program ACTive (IMPACT) from 2013 to 2018.

Kawasaki disease (KD) is an acute systemic vasculitis primarily affecting children younger than 5 y of age that has been reported as an adverse event following immunization (AEFI). The Canadian Immunization Monitoring Program ACTive (IMPACT) conducts active surveillance for KD following immunization across Canada. We characterized KD cases reported to IMPACT between 2013 and 2018. Cases admitted to an IMPACT hospital with a physician diagnosis of complete or incomplete KD with onset 0-42 d following vaccination were reviewed. Cases meeting the Brighton Collaboration case definition (BCCD) levels of diagnostic certainty levels 1 a/b, 2a/b or 3a-e were defined as KD cases. Demographic and vaccination characteristics were compared between KD cases and non-cases. Of 84 cases reviewed, 58 met the BCCD: 47 (81%) cases met level 1a (Complete KD), 8 (14%) met level 1b (Incomplete KD), 2 (3%) met level 2a, and 1 (2%) met level 2c (Probable KD). Median age at admission was 13 months (interquartile range 7-26 months). A median of 9.5 cases were reported per year (range 4-14). Thirty-one (53%) KD cases were temporally associated with diphtheria-tetanus acellular pertussis containing vaccinations, followed by 21 (36%) cases with pneumococcal conjugate vaccines. Symptom onset was 0-14 d after vaccination in 32 (55%) cases. Echocardiogram results were available for 43 (74%) cases with 22 reported as abnormal. Age, sex, interval to symptom onset, and vaccines received were similar between KD cases and non-cases. No safety signals were detected in these data.