Significant morbidity and mortality have occurred in the USA, Europe, and Asia due to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), whereas the numbers of infections and deaths in sub-Saharan Africa (SSA) have remained comparatively low. It has been hypothesized that exposure of the population in SSA to other coronaviruses prior to the COVID-19 pandemic resulted in some degree of cross-protection against SARS-CoV-2 infection and pathogenesis. We evaluated this hypothesis by comparing SARS-CoV-2 cross-reactive antibodies in pre-pandemic plasma samples collected from SSA and the USA. Pre-COVID-19 pandemic plasma samples from SSA and the USA were collected and tested by immunofluorescence assay against the spike and nucleocapsid proteins of all known human coronaviruses (HCoVs). The prevalence of SARS-CoV-2 serological cross-reactivity was significantly higher in samples from SSA compared with the USA. Most of these cross-reactive samples cross-recognized the SARS-CoV-2 nucleocapsid protein and the spike proteins of other HCoVs. Nucleocapsid proteins from HCoV-NL63 and HCoV-229E were detected in most samples, thereby implicating prior exposure to these two HCoVs as the likely source of cross-reactive antibodies against SARS-CoV-2. The low incidences of SARS-CoV-2 infection and disease in SSA appear to be correlated with the pre-pandemic serological cross-recognition of HCoVs, which are substantially more prevalent in SSA than the USA.

Background: COVID-19 is rapidly spreading causing extensive burdens across the world. Effective vaccines to prevent COVID-19 are urgently needed.Methods and findings: Our objective was to assess the effectiveness and safety of COVID-19 vaccines through analyses of all currently available randomized clinical trials. We searched the databases CENTRAL, MEDLINE, Embase, and other sources from inception to June 17, 2021 for randomized clinical trials assessing vaccines for COVID-19. At least two independent reviewers screened studies, extracted data, and assessed risks of bias. We conducted meta-analyses, network meta-analyses, and Trial Sequential Analyses (TSA). Our primary outcomes included all-cause mortality, vaccine efficacy, and serious adverse events. We assessed the certainty of evidence with GRADE. We identified 46 trials; 35 trials randomizing 219 864 participants could be included in our analyses. Our meta-analyses showed that mRNA vaccines (efficacy, 95% [95% confidence interval (CI), 92% to 97%]; 71 514 participants; 3 trials; moderate certainty); inactivated vaccines (efficacy, 61% [95% CI, 52% to 68%]; 48 029 participants; 3 trials; moderate certainty); protein subunit vaccines (efficacy, 77% [95% CI, −5% to 95%]; 17 737 participants; 2 trials; low certainty); and viral vector vaccines (efficacy 68% [95% CI, 61% to 74%]; 71 401 participants; 5 trials; low certainty) prevented COVID-19. Viral vector vaccines decreased mortality (risk ratio, 0.25 [95% CI 0.09 to 0.67]; 67 563 participants; 3 trials, low certainty), but comparable data on inactivated, mRNA, and protein subunit vaccines were imprecise. None of the vaccines showed evidence of a difference on serious adverse events, but observational evidence suggested rare serious adverse events. All the vaccines increased the risk of non-serious adverse events.Conclusions: The evidence suggests that all the included vaccines are effective in preventing COVID-19. The mRNA vaccines seem most effective in preventing COVID-19, but viral vector vaccines seem most effective in reducing mortality. Further trials and longer follow-up are necessary to provide better insight into the safety profile of these vaccines.

In sub-Saharan Africa, endemic Kaposi’s sarcoma (EnKS) is still prevalent despite high incidence of epidemic Kaposi’s sarcoma (EpKS) resulting from the on-going HIV-1 epidemic. While KSHV is clearly the etiologic agent of KS, the mechanisms underlying KS development are not fully understood. For example, HIV-1 co-infection and concomitant immune dysfunction have been associated with EpKS development. However, the direct or indirect role(s) of HIV-1, and therefore of immune suppression, in EpKS remains unclear. How, or whether, EpKS is mechanistically distinct from EnKS is unknown. Thus, the absence of HIV-1 co-infection in EnKS provides a unique control for investigating and deciphering whether HIV-1 plays a direct or indirect role in the EpKS tumor microenvironment. We hypothesized that HIV-1 co-infection would induce transcriptome changes that differentiate EpKS from EnKS, thereby defining the direct intra-tumor role of HIV-1 in KS. Comparison of ART-treated and -naïve patients would further define the impact of ART on the KS transcriptome. We utilized RNA-seq followed by multiparameter bioinformatics analysis to compare transcriptomes from KS lesions to uninvolved control skin. We provide the first transcriptomic comparison of EpKS versus EnKS, ART-treated vs–naïve EpKS and male vs female EpKS to define the roles of HIV-1 co-infection, the impact of ART, and gender on KS gene expression profiles. Our findings suggest that ART-use and gender have minimal impact on transcriptome profiles of KS lesions. Gene expression profiles strongly correlated between EpKS and EnKS patients (Spearman r = 0.83, p<10⁻¹⁰). A subset of genes involved in tumorigenesis and inflammation/immune responses showed higher magnitude, but not unique dysregulation in EnKS compared to EpKS. While gender and ART had no detectable contribution, the trend toward higher magnitude of gene dysregulation in EnKS coupled with the absence of HIV-1 transcripts in EpKS may suggest an indirect or systemic effect of HIV-1 to promote KS tumorigenesis. Despite improved antiretroviral therapy (ART) coverage, Kaposi’s sarcoma (KS) remains the most common cancer in people living with HIV/AIDS. KSHV is known to cause KS, but there are no preventive or curative vaccines. Our understanding of the interactions between KSHV, host cell and the microenvironment is lacking. HIV-1 co-infection has been implicated in KS pathogenesis, but its mechanistic role is unclear. We analyzed transcriptomes from lesions and uninvolved control skin from HIV-1-positive and -negative KS patients to determine the direct or indirect role of HIV-1 in KS development. Transcriptomes from the uninvolved control skin from KS subjects were indistinguishable from that of non-KS healthy individuals. This validates the use of uninvolved control skin to control for gene expression pattern in KS lesions. Despite high concordance in gene expression profiles between HIV-1-positive and -negative KS patients, a subset of genes involved in tumorigenesis and inflammation/immune responses showed higher magnitude of dysregulation in EnKS than EpKS patients. The trend toward lower magnitude of gene dysregulation in EpKS coupled with the absence of HIV-1-transcripts in EpKS suggests an indirect or systemic effect of HIV-1 to promote KS tumorigenesis and possibly explain the high KS incidence in regions with endemic KSHV and HIV-1 co-infections.

Background: Diabetic ketoacidosis (DKA) is one of the commonly encountered diabetes mellitus emergencies. Aim: This study aimed at describing the clinical profiles and hospitalization outcomes of DKA patients at the University Teaching Hospital (UTH) in Lusaka, Zambia and to investigate the role of coma on mortality outcome. Materials and Methods: This was a cross-sectional analytical study of hospitalized DKA patients at UTH. The data collected included clinical presentation, precipitating factors, laboratory profiles, complications, and hospitalization outcomes. Primary outcome measured was all-cause in-hospital mortality. Results: The median age was 40 years. Treatment noncompliance was the single highest identified risk factor for development of DKA, followed by new detection of diabetes, then infections. Comatose patients were significantly younger, had lower baseline blood pressure readings, and higher baseline respiratory rates compared to noncomatose patients. In addition, comatose patients had higher baseline admission random blood glucose readings. Their baseline sodium and chloride levels were also higher. The prevalences of hypokalemia, hypernatremia, and hyperchloremia were also higher among comatose patients compared to noncomatose patients. Development of aspiration during admission with DKA, pneumonia at baseline, development of renal failure, and altered mental status were associated with an increased risk of mortality. Development of renal failure was independently predictive of mortality. Conclusion: The mortality rate from DKA hospitalizations is high at UTH. Treatment noncompliance is the single highest identifiable precipitant of DKA. Aspiration, development of renal failure, altered sensorium, and pneumonia at baseline are associated with an increased risk of mortality. Development of renal failure during admission is predictive of mortality.

To longitudinally compare SARS-CoV-2-specific T cell and humoral immune responses between convalescent individuals who are HIV-positive (HIV+) and HIV-negative (HIV-). We conducted enzyme-linked immunospots to determine the SARS-CoV-2-specific T cell responses to spike and nucleocapsid, membrane protein, and other open reading frame proteins (NMO), whereas an immunofluorescence assay was used to determine the humoral responses. Participants were sampled at baseline and after 8 weeks of follow-up. Individuals who are HIV- had significantly more T cell responses to NMO and spike than individuals who are HIV+ at baseline, P-value = 0.026 and P-value = 0.029, respectively. At follow-up, T cell responses to NMO and spike in individuals who are HIV+ increased to levels comparable with individuals who are HIV-. T cell responses in the HIV- group significantly decreased from baseline levels at the time of follow-up (spike [P-value = 0.011] and NMO [P-value = 0.014]). A significantly higher number of individuals in the HIV+ group had an increase in T cell responses to spike (P-value = 0.01) and NMO (P-value = 0.026) during the follow-up period than the HIV- group. Antispike and antinucleocapsid antibody titers were high (1: 1280) and not significantly different between individuals who were HIV- and HIV+ at baseline. A significant decrease in antinucleocapsid titer was observed in the HIV- (P-value = 0.0001) and the HIV+ (P-value = 0.001) groups at follow-up. SARS-CoV-2 vaccination was more effective in boosting the T cell than antibody responses shortly after infection. There is an impairment of SARS-CoV-2-specific T cell immunity in individuals who are HIV+ with advanced immunosuppression. SARS-CoV-2-specific T cell immune responses may be delayed in individuals who are HIV+, even in those on antiretroviral therapy. There is no difference in SARS-CoV-2-specific humoral immunity between individuals who are HIV- and HIV+.

Background. Diabetes mellitus (DM) is known to be associated with active tuberculosis (TB). Zambia is a low-income sub-Saharan African country with a high TB burden and increasing numbers of newly diagnosed DM patients. Materials and Methods. This was an observational study conducted at the University Teaching Hospital in Lusaka, Zambia, from October 2014 to February 2016. Adult patients with active TB were screened for DM. Results. A total of 127 individuals were enrolled in the study. Six patients (5%) were found to have diabetes. Of these, three had a prior diagnosis of diabetes and were on medication while three were newly diagnosed. Low education level was significantly associated with DM (p=0.001; 95% CI 0.001–0.148). Conclusion. The prevalence of DM among individuals with smear positive TB in our study population was similar to that of the general population in Zambia.