Response to COVID-19 booster vaccinations in seronegative people with MS. (preprint)

Importance: Uncertainties remain about the benefit of a 3rd COVID-19 vaccine for people with attenuated response to earlier vaccines. This is of particular relevance for people with multiple sclerosis (pwMS) treated with anti-CD20 therapies and fingolimod, who have substantially reduced antibody responses to initial vaccine course. Objective: To report humoral and T-cell responses following COVID-19 vaccine 3 in pwMS who were seronegative after COVID-19 vaccines 1&2. Design, setting and participants: PwMS taking part in a seroprevalence study without a detectable IgG response following COVID-19 vaccines 1&2 were invited to participate. Participants provided a dried blood spot +/- venous blood sample 2-12 weeks following COVID-19 vaccine 3. Data on demographics, MS treatment, and COVID-19 infection/vaccine dates were derived from the medical notes. Methods: Humoral and T cell responses to SARS-CoV-2 spike protein and nucleocapsid antigen were measured. The relationship between evidence of prior COVID-19 infection and immune response to COVID-19 vaccine 3 was evaluated using Fishers exact test. Results: Of 81 participants, 79 provided a dried blood spot sample, of whom 38 also provided a whole blood sample; 2 provided only whole blood. Anti-SARS-CoV-2-spike IgG seroconversion post-COVID-19 vaccine 3 occurred in 26/79 (33%) participants; 26/40 (65%) had positive T-cell responses. Overall, 31/40 (78%) demonstrated either humoral or cellular immune response post-COVID-19 vaccine 3. There no association between laboratory evidence of prior COVID-19 infection and anti-spike seroconversion following COVID-19 vaccine 3. Conclusions: Approximately one third of pwMS who were seronegative after initial COVID-19 vaccination seroconverted after booster (third) vaccination, supporting the use of boosters in this group. Almost 8 out of 10 had a measurable immune response following 3rd COVID-19 vaccine.

Establishment of a Pediatric COVID-19 Biorepository: Unique Considerations and Opportunities for Studying the Impact of the COVID-19 Pandemic on Children (preprint)

Background: COVID-19, the disease caused by the highly infectious and transmissible coronavirus SARS-CoV-2, has quickly become a morbid global pandemic. Although the impact of SARS-CoV-2 infection in children is less clinically apparent, collecting high-quality biospecimens from infants, children, and adolescents in a standardized manner during the COVID-19 pandemic is essential to establish a biologic understanding of the disease in the pediatric population. This biorepository enables pediatric centers world-wide to collect samples uniformly to drive forward our understanding of COVID-19 by addressing specific pediatric and neonatal COVID-19-related questions. Methods: A COVID-19 biospecimen collection study was implemented with strategic enrollment guidelines to include patients seen in urgent care clinics and hospital settings, neonates born to SARS-CoV-2 infected mothers, and asymptomatic children. The methodology described here, details the importance of establishing collaborations between the clinical and research teams to harmonize protocols for patient recruitment and sample collection, processing and storage. It also details modifications required for biobanking during a surge of the COVID-19 pandemic.Results: Considerations and challenges facing enrollment of neonatal and pediatric cohorts are described. A roadmap is laid out for successful collection, processing, storage and database management of multiple pediatric samples such as blood, nasopharyngeal and oropharyngeal swabs, sputum, saliva, tracheal aspirates, stool, and urine. Using this methodology, we enrolled 327 participants, who provided a total of 972 biospecimens.Conclusions: Pediatric biospecimens will be key in answering questions relating to viral transmission by children, differences between pediatric and adult viral susceptibility and immune responses, the impact of maternal SARS-CoV-2 infection on fetal development, and factors driving the Multisystem Inflammatory Syndrome in Children. The specimens in this biorepository will allow necessary comparative studies between children and adults, help determine the accuracy of current pediatric viral testing techniques, in addition to, understanding neonatal exposure to SARS-CoV-2 infection and disease abnormalities. The successful establishment of a pediatric biorepository is critical to provide insight into disease pathogenesis, and subsequently, develop future treatment and vaccination strategies.