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.

Burden, Causation, and Particularities of long-COVID in African populations: A rapid systematic review (preprint)

BackgroundThe global estimated prevalence of long COVID-19 is 43%, and the most common symptoms found globally are fatigue, confusion, or lack of confusion, and dyspnea, with prevalence rates of 23%, 14%, and 13%, respectively. However, long COVID still lacks an overall review in African populations. The aim of this review was to determine the prevalence of long COVID, its most common symptoms, comorbidities, and pathophysiological mechanisms. MethodsA systematic review of long COVID in African populations was conducted. The random effects model was used to calculate the pooled prevalence rates (95% CI). If the results could not be pooled, a narrative synthesis was performed. ResultsWe included 14 studies from 7 African countries, totaling 6,030 previously SARS-CoV-2 infected participants and 2,954 long COVID patients. Long COVID had a pooled prevalence of 41% [26%-56%]. Fatigue, dyspnea, and confusion or lack of concentration were the most common symptoms, with prevalence rates (95% CI) of 41% [26%-56%], 25% [12%-38%], and 40% [12%-68%], respectively. Long COVID was associated with advanced age, being female, more than three long COVID symptoms in the acute phase, initial fatigue and dyspnea, post-recovery stress, sadness, and sleep disturbances, and loss of appetite at symptoms onset, mild, moderate, and severe, pre-existing obesity, hypertension, diabetes mellitus, and the presence of any chronic illness (P [≤]0.05). According to our review, high micro clot and platelet poor plasma (PPP) viscosity explain the pathophysiology of long COVID. ConclusionLong COVID prevalence in Africa was comparable to the global prevalence. However, the prevalence of the most common symptoms was higher in Africa. Comorbidities associated with long COVID may lead to additional complications in African populations due to hypercoagulation and thrombosis.

The interface between SARS-CoV-2 and non-communicable diseases (NCDs) in a high HIV/TB burden district level hospital setting, Cape Town, South Africa (preprint)

Background COVID-19 experiences on noncommunicable diseases (NCDs) from district-level hospital settings during waves I and II are scarcely documented. The aim of this study is to investigate the NCDs associated with COVID-19 severity and mortality in a district-level hospital with a high HIV/TB burden. Methods This was a retrospective observational study that compared COVID-19 waves I and II at Khayelitsha District Hospital in Cape Town, South Africa. COVID-19 adult patients with a confirmed SARS-CoV-2 polymerase chain reaction (PCR) or positive antigen test were included. In order to compare the inter wave period, clinical and laboratory parameters on hospital admission of noncommunicable diseases, the Student t-test or Mann-Whitney U for continuous data and the X2 test or Fishers' Exact test for categorical data were used. The role of the NCD subpopulation on COVID-19 mortality was determined using latent class analysis (LCA). Findings Among 560 patients admitted with COVID-19, patients admitted during wave II were significantly older than those admitted during wave I. The most prevalent comorbidity patterns were hypertension (87%), diabetes mellitus (65%), HIV/AIDS (30%), obesity (19%), Chronic Kidney Disease (CKD) (13%), Congestive Cardiac Failure (CCF) (8.8%), Chronic Obstructive Pulmonary Disease (COPD) (3%), cerebrovascular accidents (CVA)/stroke (3%), with similar prevalence in both waves except HIV status [(23% vs 34% waves II and I, respectively), p = 0.022], obesity [(52% vs 2.5%, waves II and I, respectively), p <0.001], previous stroke [(1% vs 4.1%, waves II and I, respectively), p = 0.046]. In terms of clinical and laboratory findings, our study found that wave I patients had higher haemoglobin and HIV viral loads. Wave II, on the other hand, had statistically significant higher chest radiography abnormalities, fraction of inspired oxygen (FiO2), and uraemia. The adjusted odds ratio for death vs discharge between waves I and II was similar (0.94, 95%CI: 0.84-1.05). Wave I had a longer average survival time (8.0 vs 6.1 days) and a shorter average length of stay among patients discharged alive (9.2 vs 10.7 days). LCA revealed that the cardiovascular phenotype had the highest mortality, followed by diabetes and CKD phenotypes. Only Diabetes and hypertension phenotypes had the lowest mortality. Conclusion Even though clinical and laboratory characteristics differed significantly between the two waves, mortality remained constant. According to LCA, the cardiovascular, diabetes, and CKD phenotypes had the highest death probability.

The epidemiological and clinical characteristics of COVID-19 in a high HIV/TB burden district level hospital setting (preprint)

Background: The coronavirus disease 2019 (COVID-19) pandemic continues to evolve. Globally, COVID-19 continues to strain even the most resilient healthcare systems, with Omicron being the latest variant. We made a thorough search for literature describing the effects of the COVID-19 in a high human immunodeficiency virus (HIV)/tuberculosis (TB) burden district-level hospital setting. We found scanty literature.Methods: A retrospective observational study was conducted at Khayelitsha District Hospital in Cape Town, South Africa (SA) over the period March 2020 – December 2021. We included confirmed COVID-19 cases with HIV infection aged from 18 years and above. Analysis was performed to identify predictors of mortality or hospital discharge among people living with HIV (PLWH). Predictors investigated include CD4 count, antiretroviral therapy (ART), TB, non-communicable diseases, haematological, and biochemical parameters.Findings: This cohort of PLWH with SARS-CoV-2 infection had a median (IQR) age of 46 (37–54) years, male sex distribution of 29.1%, and a median (IQR) CD4 count of 267 (141–457) cells/mm3. Of 255 patients, 195 (76%) patients were discharged, 60 (24%) patients died. One hundred and sixty-nine patients (88%) were on ART with 73(28%) patients having acquired immunodeficiency syndrome (AIDS). After multivariate analysis, smoking (risk ratio [RR]: 2.86 (1.75–4.69)), neutrophilia [RR]: 1.024 (1.01–1.03), and glycated haemoglobin A1 (HbA1c) [RR]: 1.01 (1.007–1.01) were associated with mortality.Conclusion: The district hospital had a high COVID-19 mortality rate among PLWH. Easy-to-access biomarkers such as CRP, neutrophilia, and HbA1c may play a significant role in informing clinical management to prevent high mortality due to COVID-19 in PLWH at the district-level hospitals.