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Men and women often respond differently to infectious diseases and their treatments. Tuberculosis (TB) is a life-threatening communicable disease that affects more men than women globally. Whether male sex is an independent risk factor for unfavorable TB outcomes, however, has not been rigorously investigated in an African context, where individuals are likely exposed to different microbial and environmental factors. We analyzed data collected from a cohort study in Mali by focusing on newly diagnosed active pulmonary TB individuals who were treatment naive. We gathered baseline demographic, clinical, and microbiologic characteristics before treatment initiation and also at three time points during treatment. More males than females were affected with TB, as evidenced by a male-to-female ratio of 2.4:1. In addition, at baseline, males had a significantly higher bacterial count and shorter time to culture positivity as compared with females. Male sex was associated with lower smear negativity rate after 2 months of treatment also known as the intensive phase of treatment, but not at later time points. There was no relationship between patients’ sex and mortality from any cause during treatment. This study suggests that sex-based differences in TB outcomes exist, with sex-specific effects on disease outcomes being more pronounced before treatment initiation and during the intensive phase of treatment rather than at later phases of treatment.

As SARS-CoV-2 continues to evolve, a structural and genetic understanding of key viral epitopes will be essential to the development of next-generation diagnostics and vaccines. This study uses structural biology and epitope mapping to define the antigenic regions of the viral nucleocapsid protein in sera from a cohort of COVID-19 patients with diverse clinical outcomes.

Table S1: Detailed information on all CpGs of interest Table S2: Cancer-associated CpGs in TRGs by pathway at FDR < 0.05, with unspecified skin malignancies excluded Table S3: Methylation trajectory over time by cancer status Table S4: Logistic regression results for DNA methylation measured over 8 years before diagnosis/censoring Table S5: Regulatory elements enrichment analysis results Figure S1: Plots of Beta-coefficients by genomic location for all CpGs on six genes of interest Figure S2: DNA methylation by years to cancer diagnosis/censoring and cancers status with 95% confidence intervals Figure S3: DNA methylation by years to cancer diagnosis/censoring and cancer status for CpG additional sites Figure S4: Regulatory enrichment analysis results

Importance Statin use prior to hospitalization for Coronavirus Disease 2019 (COVID-19) is hypothesized to improve inpatient outcomes including mortality, but prior findings from large observational studies have been inconsistent, due in part to confounding. Recent advances in statistics, including incorporation of machine learning techniques into augmented inverse probability weighting with targeted maximum likelihood estimation, address baseline covariate imbalance while maximizing statistical efficiency. Objective To estimate the association of antecedent statin use with progression to severe inpatient outcomes among patients admitted for COVD-19. Design, setting and participants We retrospectively analyzed electronic health records (EHR) from individuals ≥ 40-years-old who were admitted between March 2020 and September 2022 for ≥ 24 h and tested positive for SARS-CoV-2 infection in the 30 days before to 7 days after admission. Exposure Antecedent statin use—statin prescription ≥ 30 days prior to COVID-19 admission. Main outcome Composite end point of in-hospital death, intubation, and intensive care unit (ICU) admission. Results Of 15,524 eligible COVID-19 patients, 4412 (20%) were antecedent statin users. Compared with non-users, statin users were older (72.9 (SD: 12.6) versus 65.6 (SD: 14.5) years) and more likely to be male (54% vs. 51%), White (76% vs. 71%), and have ≥ 1 medical comorbidity (99% vs. 86%). Unadjusted analysis demonstrated that a lower proportion of antecedent users experienced the composite outcome (14.8% vs 19.3%), ICU admission (13.9% vs 18.3%), intubation (5.1% vs 8.3%) and inpatient deaths (4.4% vs 5.2%) compared with non-users. Risk differences adjusted for labs and demographics were estimated using augmented inverse probability weighting with targeted maximum likelihood estimation using Super Learner. Statin users still had lower rates of the composite outcome (adjusted risk difference: − 3.4%; 95% CI: − 4.6% to − 2.1%), ICU admissions (− 3.3%; − 4.5% to − 2.1%), and intubation (− 1.9%; − 2.8% to − 1.0%) but comparable inpatient deaths (0.6%; − 1.3% to 0.1%). Conclusions and relevance After controlling for confounding using doubly robust methods, antecedent statin use was associated with minimally lower risk of severe COVID-19-related outcomes, ICU admission and intubation, however, we were not able to corroborate a statin-associated mortality benefit.

Background High risk human papillomaviruses (HR-HPV) have a causal role in cervical oncogenesis, and HIV-mediated immune suppression allows HR-HPV to persist. We studied whether vaginal microbiome community state types (CSTs) are associated with high-grade precancer and/or invasive cervical cancer (HSIL/ICC). Methods This was a cross-sectional study of adult women with cervical cancer screening (CCS) at the Jos University Teaching Hospital (JUTH) in Jos, Nigeria, between January 2020 and February 2022. Cervical swabs underwent HPV genotyping (AnyplexTM II HPV28). Cervico-vaginal lavage (CVL) sample was collected for 16S rRNA gene amplicon sequencing. We used multivariable logistic regression modelling to assess associations between CSTs and other factors associated with HSIL/ICC. Results We enrolled 155 eligible participants, 151 with microbiome data for this analysis. Women were median age 52 (IQR:43-58), 47.7% HIV positive, and 58.1% with HSIL/ICC. Of the 138 with HPV data, 40.6% were negative for HPV, 10.1% had low-risk HPV, 26.8% had single HR-HPV, and 22.5% had multiple HR-HPV types. The overall prevalence of any HR-HPV type (single and multiple) was 49.3%, with a higher proportion in women with HSIL/ICC (NILM 31.6%, LSIL 46.5%, HSIL 40.8%, and 81.5% ICC; p=0.007). Women with HIV were more likely to have HSIL/ICC (70.3% vs. 29.7% among women without HIV). In crude and multivariable analysis CST was not associated with cervical pathology (CST-III aOR=1.13, CST-IV aOR=1.31). However, in the presence of HR-HPV CST-III (aOR=6.7) and CST-IV (aOR=3.6) showed positive association with HSIL/ICC. Conclusion Vaginal microbiome CSTs were not significantly associated with HSIL/ICC. Our findings suggest however, that CST could be helpful in identifying women with HSIL/ICC and particularly those with HR-HPV. Characterization of CSTs using point-of-care molecular testing in women with HR-HPV should be studied as an approach to improve early detection and cervical cancer prevention. Future longitudinal research will improve our understanding of the temporal effect of non-optimal CST, HR-HPV, and other factors in cervical cancer development, prevention, and control.

Objectives To assess the prevalence of sexually transmitted infections (STIs), antimicrobial resistance and cervical lesions among women from Sikasso, Mali. Methods Women infected with human immunodeficiency virus (HIV) (n=44) and HIV-negative women (n=96) attending cervical cancer screening were included. Screening for human papillomavirus (HPV), Chlamydia trachomatis (CT), Mycoplasma genitalium (MG), Neisseria gonorrhoeae (NG) and Trichomonas vaginalis (TV) was performed using polymerase chain reaction assays, and herpes simplex virus (HSV-1/2) serological status was assessed using enzyme-linked immunosorbent assays. Antibiotic resistance tests were performed for MG- and NG-positive cases. Results A high prevalence of high-risk HPV (hrHPV) infection (63%) was found. This was associated with cervical lesions in 7.5% of cases. An unusual distribution was found, with HPV31, HPV56 and HPV52 being the most prevalent. The hrHPV distribution differed by HIV status, with HIV-positive cases having HPV35/31/51-52-56 and HIV-negative cases having HPV31/56/52. The seroprevalence of HSV-2 was 49%, and the prevalence of other STIs was as follows: CT, 4%; MG, 9%; NG, 1%; and TV, 7%. Five of nine MG-positive specimens and the NG strains obtained were resistant to fluoroquinolone. Conclusions These results showed high prevalence of hrHPV and fluoroquinolone resistance in several NG and MG strains. Further studies are required to confirm these data in Mali, and to improve prevention, screening and management of cervical cancer and other STIs in women.

BackgroundPerformance of rapid antigen tests for SARS-CoV-2 (Ag-RDT) varies over the course of an infection, and their performance in screening for SARS-CoV-2 is not well established. We aimed to evaluate performance of Ag-RDT for detection of SARS-CoV-2 for symptomatic and asymptomatic participants.MethodsParticipants >2 years old across the United States enrolled in the study between October 2021 and February 2022. Participants completed Ag-RDT and molecular testing (RT-PCR) for SARS-CoV-2 every 48 hours for 15 days. This analysis was limited to participants who were asymptomatic and tested negative on their first day of study participation. Onset of infection was defined as the day of first positive RT-PCR result. Sensitivity of Ag-RDT was measured based on testing once, twice (after 48-hours), and thrice (after 96 hours). Analysis was repeated for different Days Post Index PCR Positivity (DPIPP) and stratified based on symptom-status.ResultsIn total, 5,609 of 7,361 participants were eligible for this analysis. Among 154 participants who tested positive for SARS-CoV-2, 97 were asymptomatic and 57 had symptoms at infection onset. Serial testing with Ag-RDT twice 48-hours apart resulted in an aggregated sensitivity of 93.4% (95% CI: 89.1-96.1%) among symptomatic participants on DPIPP 0-6. Excluding singleton positives, aggregated sensitivity on DPIPP 0-6 for two-time serial-testing among asymptomatic participants was lower at 62.7% (54.7-70.0%) but improved to 79.0% (71.0-85.3%) with testing three times at 48-hour intervals.DiscussionPerformance of Ag-RDT was optimized when asymptomatic participants tested three-times at 48-hour intervals and when symptomatic participants tested two-times separated by 48-hours.

It is now recognized that to fully understand the role of host genetic variation on susceptibility to HIV-1 infection, investigations must be extended to African populations. We sought to determine...

Production of extended-spectrum beta-lactamases (ESBLs) can lead to treatment failures when the antibiotics are used. This study detected ESBLs genes on Multidrug Resistant Escherichia coli from HIV-infected individuals attending some hospitals in Jos. Eighty (80) isolates of multidrug resistant (MDR) E. coli were screened for plasmids. ESBLs genes including bla-CTX, bla-TEM and bla-SHV were detected on the plasmids using polymerase chain reaction (PCR) with 100 bp DNA ladder as DNA molecular weight marker. Out of the total 38 plasmids tested, ESBLs genes occurred in 13 (34.21%), with the bla-TEM dominating [7 (53.85%)] over the bla-CTX [4 (30.77%)]. Two (15.38%) of the isolates carried both genes. None of the isolates carried the bla-SHV gene in our study. All the strains showed resistance to SXT, AMC and CTX. Resistance was most frequently observed against SXT (13), AMC (13), CTX (13), CFM (12), F (8), NA (6), GN (5), CRO (4), OFX (2) and CIP (1). None of the ESBLs-bearing strains showed resistance to IPM. Result showed 34.21% prevalence of ESBLs and suggested the need to be more cautious with the clinical use of third generation Cephalosporins especially for the treatment of acute infections caused by E. coli due to the high resistance recorded. Key words: Extended spectrum beta-lactamase, resistance genes, antimicrobial, plasmids, Escherichia coli, HIV-infected, Jos.

Background The CD4/CD8 ratio is an indicator of immunosenescence and a predictor of all-cause mortality in HIV-infected patients. The effects of different ART regimens on CD4/CD8 ratio recovery remain unclear. Methods Clinical cohort study of ART-treated patients from the CFAR Network of Integrated Clinical Systems (CNICS). We included ART-naive adults with HIV infection who achieved undetectable HIV RNA during the first 48 weeks of treatment and had additional follow-up 48 weeks after virological suppression (VS). Primary endpoints included increase in CD4/CD8 ratio at both timepoints and secondary endpoints were CD4/CD8 ratio recovery at cut-offs of ≥0.5 or ≥1.0. Results Of 3971 subjects who met the study criteria, 1876 started ART with an NNRTI, 1804 with a PI and 291 with an integrase strand transfer inhibitor (INSTI). After adjusting for age, sex, race, year of entry, risk group, HCV serostatus, baseline viral load and baseline CD4/CD8 ratio, subjects on an NNRTI showed a significantly greater CD4/CD8 ratio gain compared with those on a PI, either 48 weeks after ART initiation or after 48 weeks of HIV RNA VS. The greater CD4/CD8 ratio improvement in the NNRTI arm was driven by a higher decline in CD8 counts. The INSTI group showed increased rates of CD4/CD8 ratio normalization at the ≥1.0 cut-off compared with the PI group. Conclusions NNRTI therapy was associated with a greater increase in the CD4/CD8 ratio compared with PIs. NNRTI- and INSTI-based first-line ART were associated with higher rates of CD4/CD8 ratio normalization at a cut-off of 1.0 than a PI-based regimen, which might have clinical implications.

“Graying of HIV epidemic” is observed globally, as people living with HIV (PLWH) are aging, due to effectiveness of antiretrovirals. The normal aging processes and HIV-induced immune dysfunction, are potential mechanisms, driving multimorbidity (MM) in PLWH. MM is the concurrent presence of two or more diseases in a single individual. Aging PLWH, are at increased risk of acute and chronic morbidities compared with counterpart without HIV. Despite increasing concern in Nigeria, research on correlates of MM in aging PLWH is lagging. This was a comparative study, of ≥60 years of age, age-matched (±5 years) HIV-positive and HIV-negative patients. Patients were recruited, from the Infectious Disease Institute and Geriatric clinics of the University College Hospital, Ibadan, Nigeria, between April and June 2018. MM was defined as the occurrence of more than two morbidities in an individual, and it was considered acute, when within 30 days and chronic, when above 3-months duration. Data analysis was done using SPSS 23. We studied 186 individuals (62 HIV-positive and 124 HIV-negative). The PLWH had lower mean age (63.9 vs. 68.1 years, p = .00, t = 5.68), more chronic MM (2.0 vs. 1.3, p = .004, t = 2.970), which occurred earlier (4.7 vs. 9.6 years, p = .003, t = 3.05), more overall MM (3.6 vs. 2.8, p = .015, t = 2.448), and lower quality of life (82.7 vs. 86.2, p = .002, t = 3.130). Risk estimates for “any” MM revealed the odds are in favor of the older PLWH [69.4% vs. 46.8%, p = .004, odds ratio = 0.388 (95% confidence interval = 0.204–0.740)]. Logistic regression revealed, age >64 years, higher total body fat, lower nadir CD4 counts, and longer duration of HIV infection, were significantly associated with MM in aging PLWH (p = .019). Older individuals with HIV on antiretrovirals in Ibadan, had a significantly greater burden of MM compared with those without HIV. HIV treatment programs in Nigeria will need to adapt a comprehensive health care plan for aging PLWH.

OBJECTIVE: To assess differences in anal cancer incidence between racial/ethnic groups among a clinical cohort of men with HIV who have sex with men. DESIGN: Clinical cohort study METHODS: We studied men who have sex with men (MSM) in the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) who initiated antiretroviral therapy (ART) under HIV care in CNICS. We compared anal cancer incidence between Black and non-Black men and calculated hazard ratios controlling for demographic characteristics (age, CNICS site, year of ART initiation), HIV disease indicators (nadir CD4(+), peak HIV RNA), and co-infection/behavioral factors including hepatitis B virus (HBV), hepatitis C virus (HCV), tobacco smoking and alcohol abuse. RESULTS: We studied 7473 MSM with HIV who contributed 41 810 person-years of follow-up after initiating ART between 1996 and 2014 in CNICS. Forty-one individuals had an incident diagnosis of anal cancer under observation. Crude rates of anal cancer were 204 versus 61 per 100 000 person-years among Black versus non-Black MSM. The weighted hazard ratio for anal cancer in Black MSM (adjusting for demographics, HIV disease factors, and co-infection/behavioral factors) was 2.37 (95% confidence interval: 1.17, 4.82) compared to non-Black MSM. CONCLUSIONS: In this large multicenter cohort, Black MSM were at significantly increased risk for anal cancer compared to non-Black MSM. Further detailed studies evaluating factors impacting anal cancer incidence and outcomes in Black men with HIV are necessary. Inclusion of more diverse study cohorts may elucidate modifiable factors associated with increased anal cancer risk experienced by Black MSM.

Background: Based on our recently reported associations between specific dietary behaviors and the risk of COVID-19 infection in the UK Biobank (UKB) cohort, we further investigate whether these associations are specific to COVID-19 or extend to other respiratory infections. Methods: Pneumonia and influenza diagnoses were retrieved from hospital and death record data linked to the UKB. Baseline, self-reported (2006–2010) dietary behaviors included being breastfed as a baby and intakes of coffee, tea, oily fish, processed meat, red meat (unprocessed), fruit, and vegetables. Logistic regression estimated the odds of pneumonia/influenza from baseline to 31 December 2019 with each dietary component, adjusting for baseline socio-demographic factors, medical history, and other lifestyle behaviors. We considered effect modification by sex and genetic factors related to pneumonia, COVID-19, and caffeine metabolism. Results: Of 470,853 UKB participants, 4.0% had pneumonia and 0.2% had influenza during follow up. Increased consumption of coffee, tea, oily fish, and fruit at baseline were significantly and independently associated with a lower risk of future pneumonia events. Increased consumption of red meat was associated with a significantly higher risk. After multivariable adjustment, the odds of pneumonia (p ≤ 0.001 for all) were lower by 6–9% when consuming 1–3 cups of coffee/day (vs.

BACKGROUND The Omicron variant of SARS-CoV-2 is more transmissible than prior variants of concern (VOCs). It has caused the largest outbreaks in the pandemic, with increases in mortality and hospitalizations. Early data on the spread of Omicron were captured in countries with relatively low case counts, so it was unclear how the arrival of Omicron would impact the trajectory of the pandemic in countries already experiencing high levels of community transmission of Delta. OBJECTIVE The objective of this study is to quantify and explain the impact of Omicron on pandemic trajectories and how they differ between countries that were or were not in a Delta outbreak at the time Omicron occurred. METHODS We used SARS-CoV-2 surveillance and genetic sequence data to classify countries into 2 groups: those that were in a Delta outbreak (defined by at least 10 novel daily transmissions per 100,000 population) when Omicron was first sequenced in the country and those that were not. We used trend analysis, survival curves, and dynamic panel regression models to compare outbreaks in the 2 groups over the period from November 1, 2021, to February 11, 2022. We summarized the outbreaks in terms of their peak rate of SARS-CoV-2 infections and the duration of time the outbreaks took to reach the peak rate. RESULTS Countries that were already in an outbreak with predominantly Delta lineages when Omicron arrived took longer to reach their peak rate and saw greater than a twofold increase (2.04) in the average apex of the Omicron outbreak compared to countries that were not yet in an outbreak. CONCLUSIONS These results suggest that high community transmission of Delta at the time of the first detection of Omicron was not protective, but rather preluded larger outbreaks in those countries. Outbreak status may reflect a generally susceptible population, due to overlapping factors, including climate, policy, and individual behavior. In the absence of strong mitigation measures, arrival of a new, more transmissible variant in these countries is therefore more likely to lead to larger outbreaks. Alternately, countries with enhanced surveillance programs and incentives may be more likely to both exist in an outbreak status and detect more cases during an outbreak, resulting in a spurious relationship. Either way, these data argue against herd immunity mitigating future outbreaks with variants that have undergone significant antigenic shifts.

Background: Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related deaths worldwide. In countries with high human immunodeficiency virus (HIV) prevalence, such as Nigeria, HIV-associated HCC causes a great health burden due to its early onset, late diagnosis, and poorer prognosis. HIV infection is involved in inflammation of the liver, which may determine an increased risk of hepatocyte neoplastic transformation. Inflammation-related DNA methylation signatures obtained in liquid biopsy, such as circulating cell-free DNA (ccfDNA) extracted from serum/plasma are promising minimally-invasive biomarkers that may inform HCC among people living with HIV. Methods: A total of 289 Nigerian participants with information on ccfDNA and other covariates were included. Participants were classified into three groups by their HCC/HIV status: 1) HCC+/HIV+ (n=28); 2) HCC-/HIV+ (n=185); and 3) HCC+/HIV- (n=76). We constructed ccfDNA methylation inflammation scores using 49 CpGs previously linked to circulating C-reactive protein (CRP) concentrations, and higher scores represented elevated CRP concentrations with lower methylation levels. To compare the ccfDNA methylation inflammation score across the groups, we performed multivariable logistic regression analyses adjusting for age, sex, alcohol consumption, smoking status, body mass index, study sites, and technical variables. Results: Participants with HCC+/HIV+ presented the highest ccfDNA methylation inflammation scores (mean=-0.03, standard deviation [SD] =0.01). Participants with HCC-/HIV+ presented the lowest scores (mean=-0.05, SD=0.01). In the multivariable logistic regressions, one SD increase of inflammation score was associated with 2.5 times higher odds of having HCC among HIV-infected participants (HCC+/HIV+ vs. HCC+/HIV-; OR=2.56, 95% CI=1.39-4.73, P=0.002). No evidence was found for the association between the inflammation score and HIV status among HCC patients (HCC+/HIV+ vs. HCC+/HIV-; OR=1.00, 95% CI=0.59-1.70, P=0.991). In the secondary analysis comparing HCC+ vs. HCC- adjusting for HIV status, one SD increase of inflammation score was associated with 3.2 times higher odds of having HCC (OR=3.22, 95% CI=1.39-7.46, P=0.006). Conclusions: We observed that ccfDNA methylation inflammation score is associated with HCC status among people with HIV. Our findings suggest that ccfDNA methylation-based inflammatory profiles may serve as a potential biomarker for early detection and risk stratification of HCC in resource-constrained countries with a high prevalence of HIV. Citation Format: Kyeezu Kim, Yinan Zheng, Claudia Hawkins, Edith Okeke, Olufunmilayo Lesi, Yishu Qu, Lewis R. Roberts, Demirkan Gursel, Fatimah B. Abdulkareem, Alani Akanmu, Godwin Imade, Jian-Jun Wei, Masha Kocherginsky, Kwang-Youn Kim, Wasiu L. Adeyemo, Firas Wehbe, Chad J. Achenbach, Atiene Sagay, Folasade T. Ogunsola, Robert L. Murphy, Lifang Hou. DNA methylation-based inflammation score is associated with hepatocellular carcinoma among people living with HIV. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6013.

Background: Rapid and accurate testing for SARS-CoV-2 is an essential tool in the medical and public health response to the COVID-19 pandemic. An ideal test for COVID-19 would combine the sensitivity of laboratory-based PCR combined with the speed and ease of use of point-of-care (POC) or home-based rapid antigen testing. Methods: To evaluate the performance of the Diagnostic Analyzer for Selective Hybridization (DASH) SARS-CoV-2 POC PCR (sample insertion to result time of 16 minutes), we conducted a cross-sectional study of adults with and without symptoms of COVID-19 at four clinical sites. We collected two bilateral anterior nasal swabs from each participant and information on COVID-19 symptoms, vaccination, and exposure. One swab was tested with the DASH SARS-CoV-2 POC PCR and the second in a central laboratory using Cepheid Xpert Xpress SARS-CoV-2 PCR. We assessed test concordance and calculated sensitivity, specificity, negative and positive predictive values using Xpert as the “gold standard.” Results: We enrolled 315 and analyzed 313 participants with median age 42 years; 65% were female, 62% symptomatic, 75% had received ≥2 doses of mRNA COVID-19 vaccine, and 16% currently COVID-19 positive. There were concordant results for 307 tests indicating an overall agreement for DASH of 0.98 [95% CI 0.96, 0.99] compared to Xpert. DASH performed at 0.96 [95% CI 0.86, 1.00] sensitivity and 0.98 [95% CI 0.96, 1.00] specificity, with a positive predictive value of 0.85 [95% CI 0.73, 0.96] and negative predictive value of 0.996 [95% CI 0.99, 1.00]. The six discordant tests between DASH and Xpert all had high Ct values (>30) on the respective positive assay. DASH and Xpert Ct values were highly correlated (R=0.89 [95% CI 0.81, 0.94]). Conclusions: DASH POC SARS-CoV-2 PCR was accurate, easy to use, and provided fast results in real-life clinical settings with an overall performance similar to an EUA-approved laboratory-based PCR. Its compact design and ease of use are optimal for a variety of healthcare, and potentially community settings, including areas with lack of access to central laboratory-based PCR testing., Summary: DASH is an accurate, easy to use, and fast point-of-care test with applications for diagnosis and screening of SARS-CoV-2 infection.

BACKGROUND Variants of the SARS-CoV-2 virus carry differential risks to public health. The Omicron (B.1.1.529) variant, first identified in Botswana on November 11, 2021, has spread globally faster than any previous variant of concern. Understanding the transmissibility of Omicron is vital in the development of public health policy. OBJECTIVE The aim of this study is to compare SARS-CoV-2 outbreaks driven by Omicron to those driven by prior variants of concern in terms of both the speed and magnitude of an outbreak. METHODS We analyzed trends in outbreaks by variant of concern with validated surveillance metrics in several southern African countries. The region offers an ideal setting for a natural experiment given that most outbreaks thus far have been driven primarily by a single variant at a time. With a daily longitudinal data set of new infections, total vaccinations, and cumulative infections in countries in sub-Saharan Africa, we estimated how the emergence of Omicron has altered the trajectory of SARS-CoV-2 outbreaks. We used the Arellano-Bond method to estimate regression coefficients from a dynamic panel model, in which new infections are a function of infections yesterday and last week. We controlled for vaccinations and prior infections in the population. To test whether Omicron has changed the average trajectory of a SARS-CoV-2 outbreak, we included an interaction between an indicator variable for the emergence of Omicron and lagged infections. RESULTS The observed Omicron outbreaks in this study reach the outbreak threshold within 5-10 days after first detection, whereas other variants of concern have taken at least 14 days and up to as many as 35 days. The Omicron outbreaks also reach peak rates of new cases that are roughly 1.5-2 times those of prior variants of concern. Dynamic panel regression estimates confirm Omicron has created a statistically significant shift in viral spread. CONCLUSIONS The transmissibility of Omicron is markedly higher than prior variants of concern. At the population level, the Omicron outbreaks occurred more quickly and with larger magnitude, despite substantial increases in vaccinations and prior infections, which should have otherwise reduced susceptibility to new infections. Unless public health policies are substantially altered, Omicron outbreaks in other countries are likely to occur with little warning.

BackgroundInvasive cervical cancer (ICC) is a serious public health burden in Nigeria, where human immunodeficiency virus (HIV) remains highly prevalent. Previous research suggested that epigenetic age acceleration (EAA) could play a role in detection of HIV-associated ICC. However, little research has been conducted on this topic in Africa where the population is most severely affected by HIV-associated ICC. Here, we investigated the association between ICC and EAA using cervical tissues of ICC-diagnosed Nigerian women living with HIV.MethodsWe included 116 cervical tissue samples from three groups of Nigerian women in this study: (1) HIV+/ICC+ (n = 39); (2) HIV+/ICC- (n = 53); and (3) HIV-/ICC + (n = 24). We utilized four DNA methylation-based EAA estimators; IEAA, EEAA, GrimAA, and PhenoAA. We compared EAA measurements across the 3 HIV/ICC groups using multiple linear regression models. We also compared EAA between 26 tumor tissues and their surrounding normal tissues using paired t-tests. We additionally performed a receiver operating characteristics (ROC) curve analysis to illustrate the area under the curve (AUC) of EAA in ICC.ResultsWe found the most striking associations between HIV/ICC status and PhenoAge acceleration (PhenoAA). Among HIV-positive women, PhenoAA was on average 13.4 years higher in women with ICC compared to cancer-free women (P = 0.005). PhenoAA was 20.7 and 7.1 years higher in tumor tissues compared to surrounding normal tissues among HIV-positive women (P = 0.009) and HIV-negative women (P = 0.284), respectively. We did not find substantial differences in PhenoAA between HIV-positive and HIV-negative women with ICC.ConclusionPhenoAA is associated with ICC in HIV-infected women in our study. Our findings suggest that PhenoAA may serve as a potential biomarker for further risk stratification of HIV-associated ICC in Nigeria and similar resource-constrained settings.

OBJECTIVES: We assessed incidence of extrahepatic cancer among people with HIV/HCV coinfection and the potential impact of direct-acting antivirals (DAAs) on extrahepatic cancer risk among people with HIV/HCV coinfection. DESIGN: Our study cohort included adults who initiated HIV care at a CNICS site in the U.S. during 1995-2017, excluding those with previous cancer and without HCV testing. METHODS: We used Cox regression to estimate hazard ratios for extrahepatic cancer incidence among patients with HIV/HCV coinfection compared with those with HIV monoinfection. Standardized morbidity ratio (SMR) weights were used to create a “pseudopopulation” in which all patients were treated with antiretroviral therapy (ART), and to compare extrahepatic cancer incidence among patients with untreated HIV/HCV coinfection with the incidence that would have been observed if they had been successfully treated for HCV. RESULTS: Of 18,422 adults, 1,775 (10%) had HCV RNA and 10,899 (59%) were on ART at baseline. Incidence rates of any extrahepatic cancer among patients with HIV/HCV coinfection and HIV monoinfection were 1,027 and 771 per 100,000 person-years, respectively. In SMR-weighted analyses, the risk of any extrahepatic cancer among patients with untreated HCV coinfection at baseline was similar to the risk if they had been successfully treated for HCV. Patients with untreated HCV coinfection at baseline had higher incidence of kidney, lung, and inflammation-related cancers than if their HCV had been successfully treated, but these associations were not statistically significant. CONCLUSIONS: We did not find evidence that treating HCV coinfection with DAAs would reduce incidence of extrahepatic cancers among people with HIV receiving ART.

Background While several demographic and clinical correlates of coronavirus disease 2019 (COVID-19) outcome have been identified, their relationship to virological and immunological parameters remains poorly defined. Methods To address this, we performed longitudinal collection of nasopharyngeal swabs and blood samples from a cohort of 58 hospitalized adults with COVID-19. Samples were assessed for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load, viral genotype, viral diversity, and antibody titer. Demographic and clinical information, including patient blood tests and several composite measures of disease severity, was extracted from electronic health records. Results Several factors, including male sex, higher age, higher body mass index, higher 4C Mortality score, and elevated lactate dehydrogenase levels, were associated with intensive care unit admission. Of all measured parameters, only the retrospectively calculated median Deterioration Index score was significantly associated with death. While quantitative polymerase chain reaction cycle threshold (Ct) values and genotype of SARS-CoV-2 were not significantly associated with outcome, Ct value did correlate positively with C-reactive protein levels and negatively with D-dimer, lymphocyte count, and antibody titer. Intrahost viral genetic diversity remained constant through the disease course and resulted in changes in viral genotype in some participants. Conclusions Ultimately, these results suggest that worse outcomes are driven by immune dysfunction rather than by viral load and that SARS-CoV-2 evolution in hospital settings is relatively constant over time.

Background: Chronic inflammatory diseases (CIDs) are considered risk enhancing factors for coronary heart disease (CHD). However, sparse data exist regarding relative CHD risks across CIDs.Objective: Determine relative differences in CHD risk across multiple CIDs: psoriasis, rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), human immunodeficiency virus (HIV), systemic sclerosis (SSc), and inflammatory bowel disease (IBD).Methods: The cohort included patients with CIDs and controls without CID in an urban medical system from 2000 to 2019. Patients with CIDs were frequency-matched with non-CID controls on demographics, hypertension, and diabetes. CHD was defined as myocardial infarction (MI), ischemic heart disease, and/or coronary revascularization based on validated administrative codes. Multivariable-adjusted Cox models were used to determine the risk of incident CHD and MI for each CID relative to non-CID controls. In secondary analyses, we compared CHD risk by disease severity within each CID.Results: Of 17,049 patients included for analysis, 619 had incident CHD (202 MI) over an average of 4.4 years of follow-up. The multivariable-adjusted risk of CHD was significantly higher for SLE [hazard ratio (HR) 1.9, 95% confidence interval (CI) 1.2, 3.2] and SSc (HR 2.1, 95% CI 1.2, 3.9). Patients with SLE also had a significantly higher risk of MI (HR 3.6, 95% CI 1.9, 6.8). When CIDs were categorized by markers of disease severity (C-reactive protein for all CIDs except HIV, for which CD4 T cell count was used), greater disease severity was associated with higher CHD risk across CIDs.Conclusions: Patients with SLE and SSc have a higher risk of CHD. CHD risk with HIV, RA, psoriasis, and IBD may only be elevated in those with greater disease severity. Clinicians should personalize CHD risk and treatment based on type and severity of CID.

Disparities in access to anti-SARS-CoV-2 monoclonal antibodies have not been well characterized.We sought to explore the impact of race/ethnicity as a social construct on monoclonal antibody delivery.Following implementation of a centralized infusion program at a large academic healthcare system, we reviewed a random sample of high-risk ambulatory adult patients with COVID-19 referred for monoclonal antibody therapy.We examined the relationship between treatment delivery, race/ethnicity, and other demographics using descriptive statistics, binary logistic regression, and spatial analysis.There was no significant difference in racial composition between patients who did (n = 25) and patients who did not (n = 378) decline treatment (p = 0.638). Of patients who did not decline treatment, 64.8% identified as White, 14.8% as Hispanic/Latinx, and 11.1% as Black. Only 44.6% of Hispanic/Latinx and 31.0% of Black patients received treatment compared to 64.1% of White patients (OR 0.45, 95% CI 0.25-0.81, p = 0.008, and OR 0.25, 95% CI 0.12-0.50, p0.001, respectively). In multivariable analysis including age, race, insurance status, non-English primary language, county Social Vulnerability Index, illness severity, and total number of comorbidities, associations between receiving treatment and Hispanic/Latinx or Black race were no longer statistically significant (AOR 1.32, 95% CI 0.69-2.53, p = 0.400, and AOR 1.34, 95% CI 0.64-2.80, p = 0.439, respectively). However, patients who were uninsured or whose primary language was not English were less likely to receive treatment (AOR 0.16, 95% CI 0.03-0.88, p = 0.035, and AOR 0.37, 95% CI 0.15-0.90, p = 0.028, respectively). Spatial analysis suggested decreased monoclonal antibody delivery to Cook County patients residing in socially vulnerable communities.High-risk ambulatory patients with COVID-19 who identified as Hispanic/Latinx or Black were less likely to receive monoclonal antibody therapy in univariate analysis, a finding not explained by patient refusal. Multivariable and spatial analyses suggested insurance status, language, and social vulnerability contributed to racial disparities.

Background The global effort to vaccinate people against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during an ongoing pandemic has raised questions about how vaccine breakthrough infections compare with infections in immunologically naive individuals and the potential for vaccinated individuals to transmit the virus. Methods We examined viral dynamics and infectious virus shedding through daily longitudinal sampling in 23 adults infected with SARS-CoV-2 at varying stages of vaccination, including 6 fully vaccinated individuals. Results The durations of both infectious virus shedding and symptoms were significantly reduced in vaccinated individuals compared with unvaccinated individuals. We also observed that breakthrough infections are associated with strong tissue compartmentalization and are only detectable in saliva in some cases. Conclusions Vaccination shortens the duration of time of high transmission potential, minimizes symptom duration, and may restrict tissue dissemination.

Mycobacterium africanum (MAF) is known to endemically cause up to 40-50% of all pulmonary TB in West Africa. The aim of this study was to compare MAF with Mycobacterium tuberculosis (MTB) with regard to time from symptom onset to TB diagnosis, and clinical and radiological characteristics. A cross-sectional study was conducted in Bamako, Mali, between August 2014 and July 2016. Seventy-seven newly diagnosed pulmonary TB patients who were naive to treatment were enrolled at Mali's University Clinical Research Center. Sputum cultures were performed to confirm the diagnosis and spoligotyping to identify the mycobacterial strain. Univariate and multivariate analyses were used to identify factors associated with disease progression. Overall, the frequency of female patients was 25% in MAF infection and only 10.0% in MTB infection (OR = 2.9), and MAF was more represented in patients aged ≥ 30 years (57.1% versus 36.7% [OR = 2.3]). More MAF- than MTB-infected patients had a history of a prior TB contact (32.1% versus 14.3% [OR = 2.8]). The mean duration between cough onset and TB diagnosis was 111 days (∼3.7 months) for MAF and 72 days (∼2.4 months) for MTB (P = 0.007). In a multivariate regression, weight loss (body mass index [BMI] 4 months) were strongly associated with MAF infection (OR = 5.20 [1.49-18.26], P = 0.010, and 4.74 [1.2-18.58], P = 0.02), respectively. Our data show that MAF infection was significantly associated with lower BMI and a longer time between symptom onset and TB diagnosis than MTB. This supports the concept that MAF infection may have slower disease progression and less severe cough symptoms than MTB.

The Center for Innovation in Point-of-Care Technologies for HIV/AIDS at Northwestern University (C-THAN) is a partner in the Point-of-Care Technologies Research Network (POCTRN) of the National Institutes of Biomedical Imaging and Bioengineering. POCTRN’s mission is to drive the development of appropriate point-of-care (POC) diagnostic technologies through collaboration that merges scientific and technological capabilities with clinical need. C-THAN develops POC technologies for improved management of HIV/AIDS in low- and middle-income countries with a focus on sub-Saharan Africa. C-THAN incorporates clinical and user needs with technology expertise and resources to address commercialization and implementation barriers through: 1) assessment of unmet clinical needs in POC testing for HIV/AIDS and its comorbidities; 2) collaborations with physicians, researchers and engineers; 3) development of technical, clinical, industrial and regulatory partnerships; 4) clinical testing of prototype devices; and 5) creation of training opportunities for technology developers, evaluators, and other stakeholders. Technologies supported include tests for detection and monitoring of HIV/AIDS and its common comorbidities including tuberculosis, non-tuberculous mycobacteria, viral hepatitis and HIV-related malignancies. CTHAN relies on collaborations established by Northwestern University in Nigeria, South Africa, Mali and Tanzania, to have impact on the prevention and clinical management of HIV/AIDS.

Background: MDR-TB is a major threat to global TB control. In 2015, 580,000 were treated for MDR-TB worldwide. The worldwide roll-out of GeneXpert MTB/RIF® has improved diagnosis of MDR-TB; however, in many countries laboratories are unable to assess drug resistance and clinical predictors of MDR-TB could help target suspected patients. In this study, we aimed to determine the clinical factors associated with MDR-TB in Bamako, Mali. Methods: We performed a cross-sectional study of 214 patients with presumed MDR-TB admitted to University of Bamako Teaching Hospital, Point-G between 2007 and 2016. We calculated crude and adjusted odds ratios for MDR-TB disease diagnosis using SPSS. Results: We found that age ≤40 years (OR = 2.56. 95% CI: 1.44–4.55), two courses of prior TB treatment (OR = 3.25, 95% CI: 1.44–7.30), TB treatment failure (OR = 3.82, 95% CI 1.82–7.79), sputum microscopy with 3+ bacilli load (OR = 1.98, 95% CI: 1.13–3.48) and a history of contact with a TB patient (OR = 2.48, 95% CI: 1.11–5.50) were significantly associated with confirmation of MDR-TB disease. HIV was not a risk factor for MDR-TB (aOR = 0.88, 95% CI: 0.34–1.94). Conclusion: We identified several risk factors that could be used to identify MDR-TB suspects and prioritize them for laboratory confirmation. Prospective studies are needed to understand factors associated with TB incidence and clinical outcomes of TB treatment and disease. Keywords: Multi-Drug Resistant Tuberculosis, Risk factors, Mali

BackgroundIndependent of CD4 cell count, low CD4/CD8 ratio in people with HIV (PWH) is associated with deleterious immune senescence, activation, and inflammation, which may contribute to carcinogenesis and excess cancer risk. We examined whether low CD4/CD8 ratios predicted cancer among PWH in the USA and Canada.MethodsWe examined all cancer-free PWH with one or more CD4/CD8 values from NA-ACCORD observational cohorts with validated cancer diagnoses between 1998-2016. We evaluated the association between time-lagged CD4/CD8 ratio and risk of specific cancers in multivariable, time-updated Cox proportional hazard models using restricted cubic spines.Models were adjusted for age, sex, race/ethnicity, hepatitis C virus, and time-updated CD4 cell count, HIV RNA, and history of AIDS-defining illness.ResultsAmong 83,893 PWH, there were 5,628 incident cancers, including lung cancer (n=755), Kaposi sarcoma (KS, n=501), non-Hodgkin lymphoma (NHL, n=497), and anal cancer (n=439). Median age at cohort entry was 43 years, 87% were male, and 43% were white. Overall median six-month lagged CD4/CD8 ratio was 0.52 (interquartile range: 0.30-0.82). Compared with six-month lagged CD4/CD8=0.80, CD4/CD8=0.30 was associated with increased risk of any incident cancer (adjusted hazard ratio = 1.24 [95% confidence interval: 1.14-1.35]). CD4/CD8 ratio was also inversely associated with NHL, KS, lung cancer, anal cancer, and colorectal cancer in adjusted analyses (all pConclusionsLow CD4/CD8 ratio up to 24 months prior to cancer diagnosis was independently associated with increased cancer risk in PWH and may serve as a clinical biomarker.

BackgroundWhile several demographic and clinical correlates of Coronavirus Disease 2019 (COVID-19) outcome have been identified, they remain imprecise tools for clinical management of disease. Furthermore, there are limited data on how these factors are associated with virological and immunological parameters over time.Methods and FindingsNasopharyngeal swabs and blood samples were longitudinally collected from a cohort of 58 hospitalized adults with COVID-19 in Chicago, Illinois between March 27 and June 9, 2020. Samples were assessed for SARS-CoV-2 viral load, viral genotype, viral diversity, and antibody titer. Demographic and clinical information, including patient blood tests and several composite measures of disease severity, were extracted from electronic health records. All parameters were assessed for association with three patient outcome groups: discharge without intensive care unit (ICU) admission (n = 23), discharge with ICU admission (n = 29), and COVID-19 related death (n = 6). Higher age, male sex, and higher body mass index (BMI) were significantly associated with ICU admission. At hospital admission, higher 4C Mortality scores and lactate dehydrogenase (LDH) levels were likewise associated with ICU admission. Longitudinal trends in Deterioration Index (DI) score, Modified Early Warning Score (MEWS), and serum neutrophil count were also associated with ICU admission, though only the retrospectively calculated median DI score was predictive of death. While viral load and genotype were not significantly associated with outcome in this study, viral load did correlate positively with C-reactive protein levels and negatively with D-dimer, lymphocyte count, and antibody titer. Intra-host viral genetic diversity resulted in changes in viral genotype in some participants over time, though intra-host evolution was not associated with outcome. A stepwise-generated multivariable model including BMI, lymphocyte count at admission, and neutrophil count at admission was sufficient to predict outcome with a 0.82 accuracy rate in this cohort.ConclusionsThese studies suggest that COVID-19 disease severity and poor outcomes among hospitalized patients are likely driven by dysfunctional host responses to infection and underlying co-morbid conditions rather than SARS-CoV-2 viral loads. Several parameters, including 4C mortality score, LDH levels, and DI score, were ultimately predictive of participant outcome and warrant further exploration in larger cohort studies for use in clinical management and risk assessment. Finally, the prevalence of intra-host diversity and viral evolution in hospitalized patients suggests a mechanism for population-level change, further emphasizing the need for effective antivirals to suppress viral replication and to avoid the emergence of new variants.

Background COVID-19 transmission rates in South Asia initially were under control when governments implemented health policies aimed at controlling the pandemic such as quarantines, travel bans, and border, business, and school closures. Governments have since relaxed public health restrictions, which resulted in significant outbreaks, shifting the global epicenter of COVID-19 to India. Ongoing systematic public health surveillance of the COVID-19 pandemic is needed to inform disease prevention policy to re-establish control over the pandemic within South Asia. Objective This study aimed to inform public health leaders about the state of the COVID-19 pandemic, how South Asia displays differences within and among countries and other global regions, and where immediate action is needed to control the outbreaks. Methods We extracted COVID-19 data spanning 62 days from public health registries and calculated traditional and enhanced surveillance metrics. We use an empirical difference equation to measure the daily number of cases in South Asia as a function of the prior number of cases, the level of testing, and weekly shifts in variables with a dynamic panel model that was estimated using the generalized method of moments approach by implementing the Arellano–Bond estimator in R. Results Traditional surveillance metrics indicate that South Asian countries have an alarming outbreak, with India leading the region with 310,310 new daily cases in accordance with the 7-day moving average. Enhanced surveillance indicates that while Pakistan and Bangladesh still have a high daily number of new COVID-19 cases (n=4819 and n=3878, respectively), their speed of new infections declined from April 12-25, 2021, from 2.28 to 2.18 and 3.15 to 2.35 daily new infections per 100,000 population, respectively, which suggests that their outbreaks are decreasing and that these countries are headed in the right direction. In contrast, India’s speed of new infections per 100,000 population increased by 52% during the same period from 14.79 to 22.49 new cases per day per 100,000 population, which constitutes an increased outbreak. Conclusions Relaxation of public health restrictions and the spread of novel variants fueled the second wave of the COVID-19 pandemic in South Asia. Public health surveillance indicates that shifts in policy and the spread of new variants correlate with a drastic expansion in the pandemic, requiring immediate action to mitigate the spread of COVID-19. Surveillance is needed to inform leaders whether policies help control the pandemic.

Background Persons living with human immunodeficiency virus (HIV; PLWH) experience a high burden of cancer. It remains unknown which cancer types are reduced in PLWH with earlier initiation of antiretroviral therapy (ART). Methods We evaluated AIDS-free, ART-naive PLWH during 1996–2014 from 22 cohorts participating in the North American AIDS Cohort Collaboration on Research and Design. PLWH were followed from first observed CD4 of 350–500 cells/µL (baseline) until incident cancer, death, lost-to-follow-up, or December 2014. Outcomes included 6 cancer groups and 5 individual cancers that were confirmed by chart review or cancer registry linkage. We evaluated the effect of earlier (in the first 6 months after baseline) versus deferred ART initiation on cancer risk. Marginal structural models were used with inverse probability weighting to account for time-dependent confounding and informative right-censoring, with weights informed by subject’s age, sex, cohort, baseline year, race/ethnicity, HIV transmission risk, smoking, viral hepatitis, CD4, and AIDS diagnoses. Results Protective results for earlier ART were found for any cancer (adjusted hazard ratio [HR] 0.57; 95% confidence interval [CI], .37–.86), AIDS-defining cancers (HR 0.23; 95% CI, .11–.49), any virus-related cancer (HR 0.30; 95% CI, .16–.54), Kaposi sarcoma (HR 0.25; 95% CI, .10–.61), and non-Hodgkin lymphoma (HR 0.22; 95% CI, .06–.73). By 15 years, there was also an observed reduced risk with earlier ART for virus-related NADCs (0.6% vs 2.3%; adjusted risk difference −1.6; 95% CI, −2.8, −.5). Conclusions Earlier ART initiation has potential to reduce the burden of virus-related cancers in PLWH but not non-AIDS-defining cancers (NADCs) without known or suspected viral etiology.

Background: Nutritional status influences immunity but its specific association with susceptibility to COVID-19 remains unclear. We examined the association of specific dietary data and incident COVID-19 in the UK Biobank (UKB). Methods: We considered UKB participants in England with self-reported baseline (2006–2010) data and linked them to Public Health England COVID-19 test results—performed on samples from combined nose/throat swabs, using real time polymerase chain reaction (RT-PCR)—between March and November 2020. Baseline diet factors included breastfed as baby and specific consumption of coffee, tea, oily fish, processed meat, red meat, fruit, and vegetables. Individual COVID-19 exposure was estimated using the UK’s average monthly positive case rate per specific geo-populations. Logistic regression estimated the odds of COVID-19 positivity by diet status adjusting for baseline socio-demographic factors, medical history, and other lifestyle factors. Another model was further adjusted for COVID-19 exposure. Results: Eligible UKB participants (n = 37,988) were 40 to 70 years of age at baseline, 17% tested positive for COVID-19 by SAR-CoV-2 PCR. After multivariable adjustment, the odds (95% CI) of COVID-19 positivity was 0.90 (0.83, 0.96) when consuming 2–3 cups of coffee/day (vs. &lt, 1 cup/day), 0.88 (0.80, 0.98) when consuming vegetables in the third quartile of servings/day (vs. lowest quartile), 1.14 (1.01, 1.29) when consuming fourth quartile servings of processed meats (vs. lowest quartile), and 0.91 (0.85, 0.98) when having been breastfed (vs. not breastfed). Associations were attenuated when further adjusted for COVID-19 exposure, but patterns of associations remained. Conclusions: In the UK Biobank, consumption of coffee, vegetables, and being breastfed as a baby were favorably associated with incident COVID-19, intake of processed meat was adversely associated. Although these findings warrant independent confirmation, adherence to certain dietary behaviors may be an additional tool to existing COVID-19 protection guidelines to limit the spread of this virus.