Immunogenicity, Safety and Effectiveness of COVID-19 Pfizer-BioNTech (BNT162b2) mRNA Vaccination in Immunocompromised Adolescents and Young Adults: A systematic Review and Meta-Analyses (preprint)

People with weak immune systems are more likely to develop severe COVID-19, less likely to be included in vaccine controlled studies but more likely to be under-vaccinated. We review post-marketing studies to examine the immunogenicity, safety and effectiveness of BNT162b2 vaccine in immunocompromised adolescents and young adults (AYA). We searched more than three international databases from 2020 to 30 May 2022 and used the ROBINS-I for bias assessment. Random effect model was used to estimate pooled proportion, log RR, and mean difference. Egger's regression and Begg's rank correlation were used to examine publication bias. 47 full texts were reviewed, and nine were included. Conditions studied were rheumatic diseases, diabetes mellitus, Down syndrome, solid tumours, neurodisability, and cystic fibrosis. Eight studies used cohort designs and one used cross-sectional designs. Europe led most of the investigations. Most studies had unclear risk of bias and none could rule out selection bias, ascertainment bias, or selective outcome reporting. The overall estimated proportion of combined local and systemic reactions after the first BNT162b2 vaccination was 30%[95% CI: 17-42%] and slightly rose to 32% [95% CI: 19-44%] after the second dose. Rheumatic illnesses had the highest rate of AEFI (40%[95% CI: 16-65%]), while cystic fibrosis had the lowest (27%[95% CI: 17%-38%]). Hospitalizations for AEFIs were rare. Healthy controls exhibited higher levels of neutralizing antibodies and measured IgG than immunocompromised AYA, although pooled estimations did not demonstrate a statistically significant difference after primary dose. BNT162b2 is safe and effective in immunocompromised AYA, with no significant difference to healthy controls. However, current evidence is low to moderate due to high RoB. Our research advocates for improving methodology in studies including specific AYA population.

Implementation of a Non-Invasive Helmet Ventilation Solution for the Management of Severe COVID-19 Respiratory Disease in Nigeria: The CircumVent Project (preprint)

ABSTRACT Affordable novel strategies are needed to treat COVID-19 cases complicated by respiratory compromise in resource limited settings. We report a mixed-methods pre-post assessment of 1) the useability of CPAP/O2 helmet non-invasive ventilation (NIV) to treat COVID-19, at ∼ 1% the cost of mechanical ventilation; 2) the effectiveness of a train-the-trainer practice facilitation intervention; and 3) whether use of CPAP/O2 helmet NIV was associated with increased COVID-19 infection among healthcare workers. At baseline, eight COVID-19 treatment centers in Nigeria (CircumVent network) received CPAP/O2 helmet systems, and were instructed on its use. After five months, clinicians within the CircumVent netwok participated in a 2-day train-the-trainers educational intervention. The physicians completed i) standardized forms on patient demographics, clinical course, and outcomes for patients seen in the treatment centers; ii) standardized surveys of feasibility and acceptability of use of CPAP/O2 helmet systems; and iii) in-depth-interviews to explore facilitators and barriers to implementation of CPAP/O2 helmet NIV. Physicians described the CPAP/O2 helmet ventilator as easy to use and they felt comfortable training their staff on its use. They rated CPAP/O2 helmet NIV as feasible, acceptable, and appropriate (mean score of 4.0, 3.8, and 3.9 out of 5, respectively, on standardized scales). Case report forms for 546 patients with suspected and/or confirmed COVID-19 infection were obtained between May 2020 and November 2021. Of these, 69% (n=376) were treated before the training; and 29.7% (n=162) were treated with CPAP/O2 helmet ventilation. CPAP/O2 helmet NIV was well-tolerated by patients, with 12% reporting claustrophobia, and 2% reporting loose- or tight-fitting helmets. Although patient outcomes improved among CPAP/O2 helmet users overall, this was not associated with training (P=0.2). This finding persisted after adjustment for disease severity at presentation. Serosurvey of 282 health workers across treatment centers revealed that 40% (n=112) were seropositive for SARS-CoV-2. Seropositivity was significantly associated with direct contact with COVID-19 patients and limited access to PPE and hand hygiene during aerosol generating procedures (P = 0.02), but not use of CPAP/O2 helmet (P’s ≥ 0.2). In conclusion, physicians effectively used CPAP/O2 helmet NIV systems to treat COVID-19 patients in Nigeria without need for practice facilliation of their training and without increased risk of infection among healthcare workers. The use of CPAP/O2 helmet NIV could be an important strategy for treating individuals with COVID-19 infection and other disease conditions complicated by respiratory distress, particularly in settings were resources such mechanical ventilation are limited.