Real-world serological responses to extended-interval and heterologous COVID-19 mRNA vaccination in frail, older people (UNCoVER): an interim report from a prospective observational cohort study.

BACKGROUND: The use of COVID-19 vaccines has been prioritised to protect the most vulnerable-notably, older people. Because of fluctuations in vaccine availability, strategies such as delayed second dose and heterologous prime-boost have been used. However, the effectiveness of these strategies in frail, older people are unknown. We aimed to assess the antigenicity of mRNA-based COVID-19 vaccines in frail, older people in a real-world setting, with a rationed interval dosing of 16 weeks between the prime and boost doses. METHODS: This prospective observational cohort study was done across 12 long-term care facilities of the Montréal Centre-Sud - Integrated University Health and Social Services Centre in Montréal, Québec, Canada. Under a rationing strategy mandated by the provincial government, adults aged 65 years and older residing in long-term care facilities in Québec, Canada, with or without previously documented SARS-CoV-2 infection, were administered homologous or heterologous mRNA vaccines, with an extended 16-week interval between doses. All older residents in participating long-term care facilities who received two vaccine doses were eligible for inclusion in this study. Participants were enrolled from Dec 31, 2020, to Feb 16, 2021, and data were collected up to June 9, 2021. Clinical data and blood samples were serially collected from participants at the following timepoints: at baseline, before the first dose; 4 weeks after the first dose; 6-10 weeks after the first dose; 16 weeks after the first dose, up to 2 days before administration of the second dose; and 4 weeks after the second dose. Sera were tested for SARS-CoV-2-specific IgG antibodies (to the trimeric spike protein, the receptor-binding domain [RBD] of the spike protein, and the nucleocapsid protein) by automated chemiluminescent ELISA. Two cohorts were used in this study: a discovery cohort, for which blood samples were collected before administration of the first vaccine dose and longitudinally thereafter; and a confirmatory cohort, for which blood samples were only collected from 4 weeks after the prime dose. Analyses were done in the discovery cohort, with validation in the confirmatory cohort, when applicable. FINDINGS: The total study sample consisted of 185 participants. 65 participants received two doses of mRNA-1273 (Spikevax; Moderna), 36 received two doses of BNT162b2 (Comirnaty; Pfizer-BioNTech), and 84 received mRNA-1273 followed by BNT162b2. In the discovery cohort, after a significant increase in anti-RBD and anti-spike IgG concentrations 4 weeks after the prime dose (from 4·86 log binding antibody units [BAU]/mL to 8·53 log BAU/mL for anti-RBD IgG and from 5·21 log BAU/mL to 8·05 log BAU/mL for anti-spike IgG), there was a significant decline in anti-RBD and anti-spike IgG concentrations until the boost dose (7·10 log BAU/mL for anti-RBD IgG and 7·60 log BAU/mL for anti-spike IgG), followed by an increase 4 weeks later for both vaccines (9·58 log BAU/mL for anti-RBD IgG and 9·23 log BAU/mL for anti-spike IgG). SARS-CoV-2-naive individuals showed lower antibody responses than previously infected individuals at all timepoints tested up to 16 weeks after the prime dose, but achieved similar antibody responses to previously infected participants by 4 weeks after the second dose. Individuals primed with the BNT162b2 vaccine showed a larger decrease in mean anti-RBD and anti-spike IgG concentrations with a 16-week interval between doses (from 8·12 log BAU/mL to 4·25 log BAU/mL for anti-RBD IgG responses and from 8·18 log BAU/mL to 6·66 log BAU/mL for anti-spike IgG responses) than did those who received the mRNA-1273 vaccine (two doses of mRNA-1273: from 8·06 log BAU/mL to 7·49 log BAU/mL for anti-RBD IgG responses and from 6·82 log BAU/mL to 7·56 log BAU/mL for anti-spike IgG responses; mRNA-1273 followed by BNT162b2: from 8·83 log BAU/mL to 7·95 log BAU/mL for anti-RBD IgG responses and from 8·50 log BAU/mL to 7·97 log BAU/mL for anti-spike IgG responses). No differences in antibody responses 4 weeks after the second dose were noted between the two vaccines, in either homologous or heterologous combinations. INTERPRETATION: Interim results of this ongoing longitudinal study show that among frail, older people, previous SARS-CoV-2 infection and the type of mRNA vaccine influenced antibody responses when used with a 16-week interval between doses. In these cohorts of frail, older individuals with a similar age and comorbidity distribution, we found that serological responses were similar and clinically equivalent between the discovery and confirmatory cohorts. Homologous and heterologous use of mRNA vaccines was not associated with significant differences in antibody responses 4 weeks following the second dose, supporting their interchangeability. FUNDING: Public Health Agency of Canada, Vaccine Surveillance Reference Group; and the COVID-19 Immunity Task Force. TRANSLATION: For the French translation of the abstract see Supplementary Materials section.

Born Under COVID-19 Pandemic Conditions: Infant Regulatory Problems and Maternal Mental Health at 7 Months Postpartum.

BACKGROUND: The SARS-COVID-19 pandemic and its associated disease control restrictions have in multiple ways affected families with young children, who may be especially vulnerable to mental health problems. Studies report an increase in perinatal parental distress as well as symptoms of anxiety or depression in children during the pandemic. Currently, little is known about the impact of the pandemic on infants and their development. Infant regulatory problems (RPs) have been identified as early indicators of child socio-emotional development, strongly associated with maternal mental health and the early parent-infant interaction. Our study investigates whether early parenthood under COVID-19 is associated with more maternal depressive symptoms and with a perception of their infants as having more RPs regarding crying/fussing, sleeping, or eating, compared to mothers assessed before the pandemic. METHODS: As part of a longitudinal study, 65 women who had given birth during the first nationwide disease control restrictions in Northern Germany, were surveyed at 7 months postpartum and compared to 97 women assessed before the pandemic. RPs and on maternal depressive symptoms were assessed by maternal report. Number of previous children, infant negative emotionality, and perceived social support were assessed as control variables. RESULTS: Compared to the control cohort, infants born during the COVID-19 pandemic and those of mothers with higher depressive symptoms were perceived as having more sleeping and crying, but not more eating problems. Regression-based analyses showed no additional moderating effect of parenthood under COVID-19 on the association of depressive symptoms with RPs. Infant negative emotionality was positively, and number of previous children was negatively associated with RPs. LIMITATIONS: Due to the small sample size and cross-sectional assessment, the possibility for more complex multivariate analysis was limited. The use of parent-report questionnaires to assess infant RPs can support but not replace clinical diagnosis. CONCLUSIONS: The pandemic conditions affecting everyday life may have a long-term influence on impaired infant self- and maternal co-regulation and on maternal mental health. This should be addressed in peripartum and pediatric care. Qualitative and longitudinal studies focusing on long-term parental and infant outcomes under ongoing pandemic conditions are encouraged.

Experience of early motherhood during the first wave of the COVID-19 pandemic in Northern Germany: a single-centre before and after comparison.

PURPOSE: To assess maternal mental health during the first weeks after birth including birth experience, postpartum adjustment to early motherhood and the perception of newborn behaviour, and how this may be influenced by the first wave of the COVID-19 pandemic. METHODS: Ninety women who gave birth after the first enforcement of nation-wide disease control restrictions in Germany between 16 March and 10 May 2020 were surveyed and compared with 101 women who had given birth before the pandemic. Information on maternal mental health and maternal perception of early motherhood and neonatal behaviour were assessed at 3-8 weeks postpartum. RESULTS: Mothers who gave birth under the COVID-19-associated disease control restrictions did not show significant differences in depression, anxiety and social support scales compared to mothers before the pandemic. Birth experience was similar, while support during birth was perceived to be higher under the COVID-19 restrictions. Confidence in caretaking of the newborn and perception of neonatal behaviour were comparable between the two groups. Mothers expressed significantly higher dissatisfaction with the maternal role during the pandemic. CONCLUSIONS: Overall, maternal mental health and the perception of the newborn and early caretaking during the first COVID-19 wave did not substantially differ from the perceptions of mothers before the pandemic. A potential influence of the pandemic on higher dissatisfaction with the maternal role may be associated with the pandemic conditions affecting everyday life and should be addressed in postpartum care and in future qualitative and longitudinal studies.