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Introduction: While a large proportion of people with HIV (PWH) have experienced SARS-CoV-2 infections, there is uncertainty about the role of HIV disease severity on COVID-19 outcomes, especially in lower-income settings. We studied the association of mortality with characteristics of HIV severity and management, and vaccination, among adult PWH., Methods: We analysed observational cohort data on all PWH aged ≥15 years experiencing a diagnosed SARS-CoV-2 infection (until March 2022), who accessed public sector healthcare in the Western Cape province of South Africa. Logistic regression was used to study the association of mortality with evidence of antiretroviral therapy (ART) collection, time since first HIV evidence, CD4 cell count, viral load (among those with evidence of ART collection) and COVID-19 vaccination, adjusting for demographic characteristics, comorbidities, admission pressure, location and time period., Results: Mortality occurred in 5.7% (95% CI: 5.3,6.0) of 17,831 first-diagnosed infections. Higher mortality was associated with lower recent CD4, no evidence of ART collection, high or unknown recent viral load and recent first HIV evidence, differentially by age. Vaccination was protective. The burden of comorbidities was high, and tuberculosis (especially more recent episodes of tuberculosis), chronic kidney disease, diabetes and hypertension were associated with higher mortality, more strongly in younger adults., Conclusions: Mortality was strongly associated with suboptimal HIV control, and the prevalence of these risk factors increased in later COVID-19 waves. It remains a public health priority to ensure PWH are on suppressive ART and vaccinated, and manage any disruptions in care that occurred during the pandemic. The diagnosis and management of comorbidities, including for tuberculosis, should be optimized., (© 2023 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.)

Objectives: We aimed to compare the clinical severity of Omicron BA.4/BA.5 infection with BA.1 and earlier variant infections among laboratory-confirmed SARS-CoV-2 cases in the Western Cape, South Africa, using timing of infection to infer the lineage/variant causing infection., Methods: We included public sector patients aged ≥20 years with laboratory-confirmed COVID-19 between May 01-May 21, 2022 (BA.4/BA.5 wave) and equivalent previous wave periods. We compared the risk between waves of (i) death and (ii) severe hospitalization/death (all within 21 days of diagnosis) using Cox regression adjusted for demographics, comorbidities, admission pressure, vaccination, and previous infection., Results: Among 3793 patients from the BA.4/BA.5 wave and 190,836 patients from previous waves, the risk of severe hospitalization/death was similar in the BA.4/BA.5 and BA.1 waves (adjusted hazard ratio [aHR] 1.12; 95% confidence interval [CI] 0.93; 1.34). Both Omicron waves had a lower risk of severe outcomes than previous waves. Previous infection (aHR 0.29, 95% CI 0.24; 0.36) and vaccination (aHR 0.17; 95% CI 0.07; 0.40 for at least three doses vs no vaccine) were protective., Conclusion: Disease severity was similar among diagnosed COVID-19 cases in the BA.4/BA.5 and BA.1 periods in the context of growing immunity against SARS-CoV-2 due to previous infection and vaccination, both of which were strongly protective., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Over 130 million people have been diagnosed with Coronavirus disease 2019 (COVID-19), and more than one million fatalities have been reported worldwide. South Africa is unique in having a quadruple disease burden of type 2 diabetes, hypertension, human immunodeficiency virus (HIV) and tuberculosis, making COVID-19-related mortality of particular interest in the country. The aim of this study was to investigate the clinical characteristics and associated mortality of COVID-19 patients admitted to an intensive care unit (ICU) in a South African setting., Methods and Findings: We performed a prospective observational study of patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection admitted to the ICU of a South African tertiary hospital in Cape Town. The mortality and discharge rates were the primary outcomes. Demographic, clinical and laboratory data were analysed, and multivariable robust Poisson regression model was used to identify risk factors for mortality. Furthermore, Cox proportional hazards regression model was performed to assess the association between time to death and the predictor variables. Factors associated with death (time to death) at p-value < 0.05 were considered statistically significant. Of the 402 patients admitted to the ICU, 250 (62%) died, and another 12 (3%) died in the hospital after being discharged from the ICU. The median age of the study population was 54.1 years (IQR: 46.0-61.6). The mortality rate among those who were intubated was significantly higher at 201/221 (91%). After adjusting for confounding, multivariable robust Poisson regression analysis revealed that age more than 48 years, requiring invasive mechanical ventilation, HIV status, procalcitonin (PCT), Troponin T, Aspartate Aminotransferase (AST), and a low pH on admission all significantly predicted mortality. Three main risk factors predictive of mortality were identified in the analysis using Cox regression Cox proportional hazards regression model. HIV positive status, myalgia, and intubated in the ICU were identified as independent prognostic factors., Conclusions: In this study, the mortality rate in COVID-19 patients admitted to the ICU was high. Older age, the need for invasive mechanical ventilation, HIV status, and metabolic acidosis were found to be significant predictors of mortality in patients admitted to the ICU., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Nyasulu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Few data are available on COVID-19 outcomes among pregnant women in sub-Saharan Africa (SSA), where high-risk comorbidities are prevalent. We investigated the impact of pregnancy on SARS-CoV-2 infection and of SARS-CoV-2 infection on pregnancy to generate evidence for health policy and clinical practice., Methods: We conducted a 6-country retrospective cohort study among hospitalized women of childbearing age between 1 March 2020 and 31 March 2021. Exposures were (1) pregnancy and (2) a positive SARS-CoV-2 RT-PCR test. The primary outcome for both analyses was intensive care unit (ICU) admission. Secondary outcomes included supplemental oxygen requirement, mechanical ventilation, adverse birth outcomes, and in-hospital mortality. We used log-binomial regression to estimate the effect between pregnancy and SARS-CoV-2 infection. Factors associated with mortality were evaluated using competing-risk proportional subdistribution hazards models., Results: Our analyses included 1315 hospitalized women: 510 pregnant women with SARS-CoV-2, 403 nonpregnant women with SARS-CoV-2, and 402 pregnant women without SARS-CoV-2 infection. Among women with SARS-CoV-2 infection, pregnancy was associated with increased risk for ICU admission (adjusted risk ratio [aRR]: 2.38; 95% CI: 1.42-4.01), oxygen supplementation (aRR: 1.86; 95% CI: 1.44-2.42), and hazard of in-hospital death (adjusted sub-hazard ratio [aSHR]: 2.00; 95% CI: 1.08-3.70). Among pregnant women, SARS-CoV-2 infection increased the risk of ICU admission (aRR: 2.0; 95% CI: 1.20-3.35), oxygen supplementation (aRR: 1.57; 95% CI: 1.17-2.11), and hazard of in-hospital death (aSHR: 5.03; 95% CI: 1.79-14.13)., Conclusions: Among hospitalized women in SSA, both SARS-CoV-2 infection and pregnancy independently increased risks of ICU admission, oxygen supplementation, and death. These data support international recommendations to prioritize COVID-19 vaccination among pregnant women., Competing Interests: Potential conflicts of interest. J. B. N. is an infectious disease internist and epidemiologist and Principal Investigator (PI) of NIH/FIC grant numbers 1R25TW011217-01, 1R21TW011706-01, and 1D43TW010937-01A1; and payment to University of Pittsburgh. N. A. S.-A. is a clinician-scientist in Pediatric Infectious Diseases and implementation research; she is supported by the NIH National Institute of Child Health and Human Development (NICHD) grant number R01HD089866; by an NIH/FIC award through the Adolescent HIV Prevention and Treatment Implementation Science Alliance (AHISA) for the Central and West Africa Implementation Science Alliance (CAWISA) (payment to institution); and by NIH/FIC grant number 1D43TW012280-01. F. S., N. K. S., and A. P. are supported as PIs by NIH/FIC grant number 1R25TW011217-01. A. Z. is PIs of the Pan-African Network on Emerging and Re-Emerging Infections (PANDORA-ID-NET; https://www.pandora-id.net) funded by the European Developing Countries Clinical Trial Partnership (EDCTP) and the European Union Horizon 2020 Framework Program for Research and Innovation, paid to institution (University College London, London, UK). R. N. M. reports grants or contracts unrelated to this work, and payment to their institution: NIH/FIC1D43TW010547-01—The African Center for Biostatistical Excellence (ACBE). P. J. R. reports the following grants or contracts unrelated to this work and paid to their institution: 5R01AI075045-12, 5R01AI139179-04, and 5R01AI117001-07. E. R. S. reports a Bill and Melinda Gates Foundation grant for a prospective meta-analysis of COVID-19 in pregnancy, unrelated to this work, and payment to George Washington University. A. B. reports grants or contracts unrelated to this work—NIH: IMPAACT Vice-chair Funding for P1106; and UNITAID: Benefit KIDS funding for PETITE Study. P. A. reports grants or contracts unrelated to this work and paid to the University of Ibadan, Nigeria: NIH/FIC R25 grant number 1R25TW011217-01 to AFREhealth. J. W. N. reports grants paid to the University of Pittsburgh from the NIH to the Pitt-Ohio State Clinical Trials Unit (UM1 AI068636), the University of Pittsburgh Virology Support Laboratory (UM1 AI106701), the I4C Martin Delaney Collaboratory for an HIV Cure (UM1 AI126603), the REACH Martin Delaney Collaboratory for HIV Cure (UM1 AI164565), and from the National Cancer Institute through Leidos contract numbers HHSN261200800001E and 75N91019D00024 USAID; Gilead Sciences, Inc; and Janssen Pharmaceuticals. J. W. N. also reports consulting fees from Gilead Sciences, Inc (Scientific Advisory Board), Accelevir Diagnostics (Consulting Agreement), and Merck (Consulting Agreement); shares from Abound Bio, Inc, share options from Co-Crystal Pharma, Inc, and share options from Infectious Diseases Connect; a consulting agreement with Xi’an Yufan Biotechnologies; and employment with the University of Pittsburgh. M. S. reports grants or contracts unrelated to this work and paid to their institution (MGH-Boston, MA, USA): NIH/NIA R01AG059504-03 and NIH/NHLBI R01 HL141053-04. A.-P. K. reports research support unrelate to this work paid to their institution (South African Medical Research Council): NIH/FIC 1R21TW011706-01-Dolutegravir, Weight Gain and Metabolic Outcomes in South Africa. L. M. reports consulting fees from the World Health Organization on COVID in pregnancy and mother to child SARS-CoV-2 transmission (this contract is now completed); and payment from Virology Education for a talk on SARS-CoV-2 in pregnancy and possibility of mother-to-child SARS-CoV-2 transmission for continuing education sponsored by Virology Education. M. Y. is PI of the NIH/National Institute of Allergy and Infectious Diseases (NIH/NIAID) grant number 5U01AI096299-13 of the Central Africa-International epidemiology to Evaluate AIDS (CA-IeDEA). M. Y. also reports grants or contracts unrelated to this work and paid to their institution: NIH grant numbers 5U01AI096299 (NIAID), R01HD087993 (NICHD), U54CA254568 (National Cancer Institute), and R01HD105526 (NICHD). All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.)

Background: An increased incidence of thromboembolic events in hospitalised COVID‑19 patients has been demonstrated despite the use of low-molecular-weight heparin (LMWH). Antiplatelet therapy prior to admission and early in the disease course has been hypothesised to be protective against thrombosis., Objectives: To describe the bleeding and thrombosis outcomes in hospitalised patients with confirmed COVID‑19 receiving LMWH, with and without concomitant antiplatelet therapy. Secondary objectives were to explore predictors of bleeding and thrombosis outcomes, and dosing practices of antiplatelet therapy and LMWH., Methods: We conducted a descriptive, cross-sectional study of bleeding and thrombosis outcomes at Tygerberg Academic Hospital, Cape Town, South Africa, during the first COVID‑19 wave, in 808 hospitalised patients with confirmed COVID‑19 receiving LMWH with and without concomitant antiplatelet therapy. Multivariate logistic regression analysis was performed if predictors were deemed statistically and clinically significant., Results: Patients receiving both LMWH and antiplatelet therapy had similar bleeding outcomes compared with patients only receiving LMWH (odds ratio (OR) 1.5; 95% confidence interval (CI) 0.6 - 4.0). Patients receiving both LMWH and antiplatelet therapy had increased odds of developing thrombosis compared with patients only receiving LMWH (OR 4.8; 95% CI 2.1 - 10.7)., Conclusion: The bleeding risk in COVID‑19 patients receiving both LMWH and antiplatelet therapy was not significantly increased. A potentially higher risk of thrombosis in patients receiving LMWH and antiplatelet therapy was observed. However, this could reflect confounding by indication. Randomised studies are required to further evaluate the use of antiplatelet therapy to treat hospitalised patients with COVID‑19.

Objectives: The objective was to compare COVID-19 outcomes in the Omicron-driven fourth wave with prior waves in the Western Cape, assess the contribution of undiagnosed prior infection to differences in outcomes in a context of high seroprevalence due to prior infection and determine whether protection against severe disease conferred by prior infection and/or vaccination was maintained., Methods: In this cohort study, we included public sector patients aged ≥20 years with a laboratory-confirmed COVID-19 diagnosis between 14 November and 11 December 2021 (wave four) and equivalent prior wave periods. We compared the risk between waves of the following outcomes using Cox regression: death, severe hospitalisation or death and any hospitalisation or death (all ≤14 days after diagnosis) adjusted for age, sex, comorbidities, geography, vaccination and prior infection., Results: We included 5144 patients from wave four and 11,609 from prior waves. The risk of all outcomes was lower in wave four compared to the Delta-driven wave three (adjusted hazard ratio (aHR) [95% confidence interval (CI)] for death 0.27 [0.19; 0.38]. Risk reduction was lower when adjusting for vaccination and prior diagnosed infection (aHR: 0.41, 95% CI: 0.29; 0.59) and reduced further when accounting for unascertained prior infections (aHR: 0.72). Vaccine protection was maintained in wave four (aHR for outcome of death: 0.24; 95% CI: 0.10; 0.58)., Conclusions: In the Omicron-driven wave, severe COVID-19 outcomes were reduced mostly due to protection conferred by prior infection and/or vaccination, but intrinsically reduced virulence may account for a modest reduction in risk of severe hospitalisation or death compared to the Delta-driven wave., (© 2022 The Authors Tropical Medicine & International Health Published by John Wiley & Sons Ltd.)

Background: The impact of SARS-CoV-2 infection in pregnant women living with HIV (PLHIV) has not been described previously., Objectives: To describe the clinical presentation and outcomes of a cohort of women with high-risk pregnancies with confirmed COVID-19 to determine whether risk factors for disease severity and adverse outcomes of COVID-19 differed in pregnant women without HIV compared with PLHIV., Methods: We prospectively enrolled pregnant women with COVID-19 attending the high-risk obstetric service at Tygerberg Hospital, Cape Town, South Africa, from 1 May to 31 July 2020, with follow-up until 31 October 2020. Women were considered high risk if they required specialist care for maternal, neonatal and/or anaesthetic conditions. Common maternal or obstetric conditions included hypertensive disorders, morbid obesity (body mass index (BMI) ≥40 kg/m2) and diabetes. Information on demographics, clinical features, and maternal and neonatal outcomes was collected and compared for PLHIV v. pregnant women without HIV., Results: One hundred women (72 without HIV and 28 PLHIV) with high-risk pregnancies had laboratory-confirmed COVID-19. Among the 28 PLHIV, the median (interquartile range) CD4 count was 441 (317 - 603) cells/µL, and 19/26 (73%) were virologically suppressed. COVID-19 was diagnosed predominantly in the third trimester (81%). Obesity (BMI ≥30 in n=61/81; 75%) and hypertensive disorders were frequent comorbidities. Of the 100 women, 40% developed severe or critical COVID-19, 15% required intensive care unit admission and 6% needed invasive ventilation. Eight women died, 1 from advanced HIV disease complicated by bacteraemia and urosepsis. The crude maternal mortality rate was substantially higher in women with COVID-19 compared with all other deliveries at our institution during this period (8/91 (9%) v. 7/4 058 (0.2%); p&lt;0.001). Neonatal outcomes were favourable. No significant differences in COVID-19 risk factors, disease severity, and maternal/neonatal outcome were noted for PLHIV v. those without HIV., Conclusions: In this cohort of high-risk pregnant women, the impact of COVID-19 was severe, significantly increasing maternal mortality risk compared with baseline rates. Virally suppressed HIV infection was not associated with worse COVID-19 outcomes in pregnancy.

Background: Empirical broad-spectrum antibiotics are frequently prescribed to patients with severe COVID-19, motivated by concern about bacterial coinfection. There is no evidence of benefit from such a strategy, while the dangers of inappropriate antibiotics are well described., Objectives: To investigate the frequency, profile and related outcomes of infections by bacterial pathogens in patients admitted to an intensive care unit (ICU) with severe COVID-19 pneumonia., Methods: This was a prospective, descriptive study in a dedicated COVID-19 ICU in Cape Town, South Africa, involving all adult patients admitted to the ICU with confirmed COVID-19 pneumonia between 26 March and 31 August 2020. We collected data on patient comorbidities, laboratory results, antibiotic treatment, duration of admission and in-hospital outcome., Results: We included 363 patients, who collectively had 1 199 blood cultures, 308 tracheal aspirates and 317 urine cultures performed. We found positive cultures for pathogens in 20 patients (5.5%) within the first 48 hours of ICU admission, while 73 additional patients (20.1%) had positive cultures later during their stay. The most frequently isolated pathogens at all sites were Acinetobacter baumannii (n=54), Klebsiella species (n=13) and coagulase-negative staphylococci (n=9). Length of ICU stay (p&lt;0.001) and intubation (p&lt;0.001) were associated with positive cultures on multivariate analysis. Disease severity (p=0.5), early antibiotic use (p=0.5), diabetes mellitus (p=0.1) and HIV (p=0.9) were not associated with positive cultures. Positive cultures, particularly for tracheal aspirates (p&lt;0.05), were associated with longer ICU length of stay and mortality. Early empirical antibiotic use was not associated with mortality (odds ratio 2.5; 95% confidence interval 0.95 - 6.81)., Conclusions: Bacterial coinfection was uncommon in patients at the time of admission to the ICU with severe COVID-19. Avoiding early empirical antibiotic therapy is therefore reasonable. Strategies to avoid coinfection and outbreaks in hospital, such as infection prevention and control, as well as the strict use of personal protective equipment, are important to improve outcomes.

• The response to the COVID-19 pandemic in low- and middle-income countries is challenged by fragile health systems and poverty. • Expanded access to mobile phones will facilitate their use in the COVID-19 response. • Mobile phone technology can improve case-reporting and patient referral pathways. • We give examples of initiatives enhancing patient care and public health outcomes. • We present a checklist for helpful mobile communication to combat COVID-19. Estimates of health capacities in the context of the coronavirus disease 2019 (COVID-19) pandemic indicate that most low- and middle-income countries (LMICs) are not operationally ready to manage this health emergency. Motivated by worldwide successes in other infectious disease epidemics and our experience in Sub-Saharan Africa, we support mobile phone communication to improve data collection and reporting, communication between healthcare workers, public health institutions, and patients, and the implementation of disease tracking and subsequent risk-stratified isolation measures. Programmatic action is needed for centrally coordinated reporting and communication systems facilitating mobile phones in crisis management plans for addressing the COVID-19 pandemic in LMICs. We summarize examples of worldwide mobile phone technology initiatives that have enhanced patient care and public health outcomes in previous epidemics and the current COVID-19 pandemic. In addition, we provide an overview of baseline conditions, including transparency about privacy guarantees, necessary for the successful use of mobile phones in assisting in the fight against COVID-19 spread. [ABSTRACT FROM AUTHOR]