ABSTRACT
Background: Despite increased social vulnerability and barriers to care, there has been a paucity of data on SARS-CoV-2 incidence among key populations in sub-Saharan Africa. We seek to characterize active infections and define transmission dynamics of SARS-CoV-2 among people who inject drugs (PWID) and their sexual and injecting partners from Nairobi and the coastal region in Kenya. Method(s): This was a nested cross-sectional study of SARS-CoV-2 infection from April to July 2021 within a cohort study of assisted partner services for PWID in Kenya. A total of 1000 PWID and their partners (500 living with and 500 living without HIV) were recruited for SARS-CoV-2 antibody testing, of whom 440 were randomly selected to provide self-collected nasal swabs for real-time PCR testing. Whole genome sequencing (WGS) was completed on a limited subset of samples (N=23) with cycle threshold values 32.0. Phylogenetic tree construction and analysis was performed using the Nextstrain pipeline and compared with publicly available SARS-CoV-2 sequences from GenBank. Result(s): A total of 438 (99.5%) participants provided samples for SARS-CoV-2 PCR testing. Median age was 37 (IQR 32-42);128 (29.2%) were female;and 222 (50.7%) were living with HIV. The overall prevalence of SARS-CoV-2 infection identified by RT-PCR was 86 (19.6%). In univariate analyses, there was no increased relative risk of SARSCoV- 2 infection related to positive HIV status, frequenting an injection den, methadone treatment, unstable housing, report of any high-risk exposure, or having a sexual or injecting partner diagnosed with COVID-19 or who died from COVID-19 or flu-like illness. Eight samples were successfully sequenced via WGS and classified as WHO variants of concern: 3 Delta, 3 Alpha, and 2 Beta. Seven were classified into clades predominantly circulating in Kenya during 2021. Notably, two sequences were identical and matched identically to another Kenyan sequence, which is consistent with, though not indictive of, a transmission linkage. Conclusion(s): Overall, the risk of SARS-CoV-2 infection in this population of PWID and their partners was not significantly associated with risk factors related to injection drug use. At a genomic level, the SARS-CoV-2 strains in this study were consistent with contemporary Kenyan lineages circulating during the time and not unique to PWID. Prevention efforts, therefore, must also focus on marginalized groups for control given the substantial amount of mixing that likely occurs between populations.
ABSTRACT
Current COVID-19 vaccines prevent severe disease, but do not induce mucosal immunity or prevent infection with SARS-CoV-2, especially with recent variants. Furthermore, serum antibody responses wane soon after immunization. We assessed the immunogenicity and protective efficacy of an experimental COVID-19 vaccine based on the SARS-CoV-2 Spike trimer formulated with a novel adjuvant LP-GMP, comprising TLR2 and STING agonists. We demonstrated that immunization of mice twice by the intranasal (i.n.) route or by heterologous intramuscular (i.m.) prime and i.n. boost with the Spike-LP-GMP vaccine generated potent Spike-specific IgG, IgA and tissue-resident memory (TRM) T cells in the lungs and nasal mucosa that persisted for at least 3 months. Furthermore, Spike-LP-GMP vaccine delivered by i.n./i.n., i.m./i.n., or i.m./i.m. routes protected human ACE-2 transgenic mice against respiratory infection and COVID-19-like disease following lethal challenge with ancestral or Delta strains of SARS-CoV-2. Our findings underscore the potential for nasal vaccines in preventing infection with SARS-CoV-2 and other respiratory pathogen.
ABSTRACT
IL-17 cytokine family members have diverse biological functions, promoting protective immunity against many pathogens but also driving inflammatory pathology during infection and autoimmunity. IL-17A and IL-17F are produced by CD4+ and CD8+ T cells, γδ T cells, and various innate immune cell populations in response to IL-1ß and IL-23, and they mediate protective immunity against fungi and bacteria by promoting neutrophil recruitment, antimicrobial peptide production and enhanced barrier function. IL-17-driven inflammation is normally controlled by regulatory T cells and the anti-inflammatory cytokines IL-10, TGFß and IL-35. However, if dysregulated, IL-17 responses can promote immunopathology in the context of infection or autoimmunity. Moreover, IL-17 has been implicated in the pathogenesis of many other disorders with an inflammatory basis, including cardiovascular and neurological diseases. Consequently, the IL-17 pathway is now a key drug target in many autoimmune and chronic inflammatory disorders; therapeutic monoclonal antibodies targeting IL-17A, both IL-17A and IL-17F, the IL-17 receptor, or IL-23 are highly effective in some of these diseases. However, new approaches are needed to specifically regulate IL-17-mediated immunopathology in chronic inflammation and autoimmunity without compromising protective immunity to infection.
ABSTRACT
Background: In sub-Saharan Africa many persons who inject drugs (PWID) are living with undiagnosed or untreated HIV and experience high levels of poverty, housing instability, and co morbid conditions that contribute to worse outcomes from SARS-CoV-2. We sought to determine SARS-CoV-2 antibody prevalence and risk factors for PWID and their sexual and injecting partners in Kenya. Identifying the burden of infection in marginalized populations like PWID may contribute to controlling the pandemic in LMIC Methods: In a nested cross-sectional study, we recruited PWID living with HIV and their injecting and/or sexual partners in Nairobi, Kilifi, and Mombasa counties at needle and syringe programs (NSP). Blood samples were collected from consenting participants at enrollment to determine SARS-CoV-2 antibodies using a Platellia BioRad SARS-CoV-2 total antibody enzyme-linked immunosorbent assay. Baseline data was collected on HIV status, antiretroviral therapy (ART) and methadone adherence. Logistic regression was used to identify factors associated with antibody positivity Results: In total,1000 participants were enrolled in the study between April and July 2021, of whom 323 (32.3%) were women and 677 (67.7%) were men. Median age of participants was 36 years (Interquartile range [IQR]: 30, 42). SARS-CoV-2 positivity was reported in 309 (30.9%) of the participants. Of the participants who tested positive for SARS-CoV-2 antibodies, 39.5% did not report any symptoms at any time during the last 3 months. Men were significantly less likely than women to have SARS-CoV-2 antibodies (Odds ratio [OR] 0.70, 95% confidence interval [CI] 0.52, 0.94;p<0.016). Participants from the Coast region had lower odds of SARS-CoV-2 antibody positivity compared to the Nairobi region (OR 0.72, 95% CI, 0.54, 0.95;p<0.019) and participants who had a sexual or injecting partner diagnosed with COVID-19 were more likely to have SARS-CoV-2 antibodies detected (OR 2.12, 95% CI 1.02, 4.39;p<0.042). Living with HIV was not significantly associated with presence of SARS-CoV-2 antibodies Conclusion: SARS-CoV-2 antibody was detected in 30.9% of participants in this cohort of PWID and their partners, suggesting high transmission rates within this key population. SARS-CoV-2 seroprevalence was similar for people living with and without HIV;no increase in risk was found for those living with HIV. This cohort represents an at-risk population that should be considered for COVID-19 vaccination, surveillance and other targeted public health measures.