Clinical characteristics associated with mortality of COVID-19 patients admitted to an intensive care unit of a tertiary hospital in South Africa.

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.

Effect of HIV status and antiretroviral treatment on treatment outcomes of tuberculosis patients in a rural primary healthcare clinic in South Africa.

BACKGROUND: Tuberculosis (TB) remains the leading cause of death among human immunodeficiency virus (HIV) infected individuals in South Africa. Despite the implementation of HIV/TB integration services at primary healthcare facility level, the effect of HIV on TB treatment outcomes has not been well investigated. To provide evidence base for TB treatment outcome improvement to meet End TB Strategy goal, we assessed the effect of HIV status on treatment outcomes of TB patients at a rural clinic in the Ugu Health District, South Africa. METHODS: We reviewed medical records involving a cohort of 508 TB patients registered for treatment between 1 January 2013 and 31 December 2015 at rural public sector clinic in KwaZulu-Natal province, South Africa. Data were extracted from National TB Programme clinic cards and the TB case registers routinely maintained at study sites. The effect of HIV status on TB treatment outcomes was determined by using multinomial logistic regression. Estimates used were relative risk ratio (RRR) at 95% confidence intervals (95%CI). RESULTS: A total of 506 patients were included in the analysis. Majority of the patients (88%) were new TB cases, 70% had pulmonary TB and 59% were co-infected with HIV. Most of HIV positive patients were on antiretroviral therapy (ART) (90% (n = 268)). About 82% had successful treatment outcome (cured 39.1% (n = 198) and completed treatment (42.9% (n = 217)), 7% (n = 39) died 0.6% (n = 3) failed treatment, 3.9% (n = 20) defaulted treatment and the rest (6.6% (n = 33)) were transferred out of the facility. Furthermore, HIV positive patients had a higher mortality rate (9.67%) than HIV negative patients (2.91%)". Using completed treatment as reference, HIV positive patients not on ART relative to negative patients were more likely to have unsuccessful outcomes [RRR, 5.41; 95%CI, 2.11-13.86]. CONCLUSIONS: When compared between HIV status, HIV positive TB patients were more likely to have unsuccessful treatment outcome in rural primary care. Antiretroviral treatment seems to have had no effect on the likelihood of TB treatment success in rural primary care. The TB mortality rate in HIV positive patients, on the other hand, was higher than in HIV negative patients emphasizing the need for enhanced integrated management of HIV/TB in rural South Africa through active screening of TB among HIV positive individuals and early access to ART among HIV positive TB cases.

Clinical features and outcomes of COVID-19 admissions in a population with a high prevalence of HIV and tuberculosis: a multicentre cohort study.

BACKGROUND: There is still a paucity of evidence on the outcomes of coronavirus disease 2019 (COVID-19) among people living with human immunodeficiency virus (PWH) and those co-infected with tuberculosis (TB), particularly in areas where these conditions are common. We describe the clinical features, laboratory findings and outcome of hospitalised PWH and human immunodeficiency virus (HIV)-uninfected COVID-19 patients as well as those co-infected with tuberculosis (TB). METHODS: We conducted a multicentre cohort study across three hospitals in Cape Town, South Africa. All adults requiring hospitalisation with confirmed COVID-19 pneumonia from March to July 2020 were analysed. RESULTS: PWH comprised 270 (19%) of 1434 admissions. There were 47 patients with active tuberculosis (3.3%), of whom 29 (62%) were PWH. Three-hundred and seventy-three patients (26%) died. The mortality in PWH (n = 71, 26%) and HIV-uninfected patients (n = 296, 25%) was comparable. In patients with TB, PWH had a higher mortality than HIV-uninfected patients (n = 11, 38% vs n = 3, 20%; p = 0.001). In multivariable survival analysis a higher risk of death was associated with older age (Adjusted Hazard Ratio (AHR) 1.03 95%CI 1.02-1.03, p < 0.001), male sex (AHR1.38 (95%CI 1.12-1.72, p = 0.003) and being "overweight or obese" (AHR 1.30 95%CI 1.03-1.61 p = 0.024). HIV (AHR 1.28 95%CI 0.95-1.72, p 0.11) and active TB (AHR 1.50 95%CI 0.84-2.67, p = 0.17) were not independently associated with increased risk of COVID-19 death. Risk factors for inpatient mortality in PWH included CD4 cell count < 200 cells/mm3, higher admission oxygen requirements, absolute white cell counts, neutrophil/lymphocyte ratios, C-reactive protein, and creatinine levels. CONCLUSION: In a population with high prevalence of HIV and TB, being overweight/obese was associated with increased risk of mortality in COVID-19 hospital admissions, emphasising the need for public health interventions in this patient population.

The Critical Need for Pooled Data on Coronavirus Disease 2019 in African Children: An AFREhealth Call for Action Through Multicountry Research Collaboration.

Globally, there are prevailing knowledge gaps in the epidemiology, clinical manifestations, and outcomes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among children and adolescents; and these gaps are especially wide in African countries. The availability of robust age-disaggregated data is a critical first step in improving knowledge on disease burden and manifestations of coronavirus disease 2019 (COVID-19) among children. Furthermore, it is essential to improve understanding of SARS-CoV-2 interactions with comorbidities and coinfections such as human immunodeficiency virus (HIV), tuberculosis, malaria, sickle cell disease, and malnutrition, which are highly prevalent among children in sub-Saharan Africa. The African Forum for Research and Education in Health (AFREhealth) COVID-19 Research Collaboration on Children and Adolescents is conducting studies across Western, Central, Eastern, and Southern Africa to address existing knowledge gaps. This consortium is expected to generate key evidence to inform clinical practice and public health policy-making for COVID-19 while concurrently addressing other major diseases affecting children in African countries.

Characteristics and outcome profile of hospitalized African patients with COVID-19: The Ethiopian context.

BACKGROUND: The COVID-19 pandemic seems to have a different picture in Africa; the first case was identified in the continent after it had already caused a significant loss to the rest of the world and the reported number of cases and mortality rate has been low. Understanding the characteristics and outcome of the pandemic in the African setup is therefore crucial. AIM: To assess the characteristics and outcome of Patients with COVID-19 and to identify determinants of the disease outcome among patients admitted to Millennium COVID-19 Care Center in Ethiopia. METHODS: A prospective cohort study was conducted among 1345 consecutively admitted RT-PCR confirmed Patients with COVID-19 from July to September, 2020. Frequency tables, KM plots, median survival times and Log-rank test were used to describe the data and compare survival distribution between groups. Cox proportional hazard survival model was used to identify determinants of time to clinical recovery and the independent variables, where adjusted hazard ratio, P-value and 95% CI for adjusted hazard ratio were used for testing significance and interpretation of results. Binary logistic regression model was used to assess the presence of a statistically significant association between disease outcome and the independent variables, where adjusted odds ratio, P-value and 95% CI for adjusted odds ratio were used for testing significance and interpretation of results. RESULTS: Among the study population, 71 (5.3%) died, 72 (5.4%) were transferred and the rest 1202 (89.4%) were clinically improved. The median time to clinical recovery was 14 days. On the multivariable Cox proportional hazard model; temperature (AHR = 1.135, 95% CI = 1.011, 1.274, p-value = 0.032), COVID-19 severity (AHR = 0.660, 95% CI = 0.501, 0.869, p-value = 0.003), and cough (AHR = 0.705, 95% CI = 0.519, 0.959, p-value = 0.026) were found to be significant determinants of time to clinical recovery. On the binary logistic regression, the following factors were found to be significantly associated with disease outcome; SPO2 (AOR = 0.302, 95% CI = 0.193, 0.474, p-value = 0.0001), shortness of breath (AOR = 0.354, 95% CI = 0.213, 0.590, p-value = 0.0001) and diabetes mellitus (AOR = 0.549, 95% CI = 0.337, 0.894, p-value = 0.016). CONCLUSIONS: The average duration of time to clinical recovery was 14 days and 89.4% of the patients achieved clinical recovery. The mortality rate of the studied population is lower than reports from other countries including those in Africa. Having severe COVID-19 disease severity and presenting with cough were found to be associated with delayed clinical recovery of the disease. On the other hand, being hyperthermic is associated with shorter disease duration (faster time to clinical recovery). In addition, lower oxygen saturation, subjective complaint of shortness of breath and being diabetic were associated with unfavorable disease outcome. Therefore, patients with these factors should be followed cautiously for a better outcome.

Estimating vaccine confidence levels among healthcare students and staff of a tertiary institution in South Africa: protocol of a cross-sectional survey.

INTRODUCTION: The outbreak of novel COVID-19 caught the world off guard in the first quarter of 2020. To stem the tide of this pandemic, there was acceleration of the development, testing and prelicensure approval for emergency use of some COVID-19 vaccine candidates. This led to raised public concern about their safety and efficacy, compounding the challenges of vaccine hesitancy. The onus of managing and administering these vaccines to a sceptical populace when they do become available rests mostly on the shoulders of healthcare workers (HCWs). Therefore, the vaccine confidence levels of HCWs become critical to the success of vaccination endeavours. This proposed study aims to estimate the level of vaccine confidence and the intention to receive a COVID-19 vaccine among future HCWs and their trainers at a specific university in Cape Town, South Africa, and to identify any vaccination concerns early for targeted intervention. METHODS AND ANALYSIS: This proposed study is a cross-sectional survey study. An online questionnaire will be distributed to all current staff and students of the Faculty of Medicine Health Sciences of Stellenbosch University in Cape Town, South Africa. No sampling strategy will be employed. The survey questionnaire will consist of demographic questions (consisting of six items) and vaccine confidence questions (comprising six items in Likert scale format). Log binomial models will be employed to identify factors associated with vaccine confidence and intention. The strength of association will be assessed using the OR and its 95% CI. Statistical significance will be defined at a p value <0.05. ETHICS AND DISSEMINATION: Ethics approval has been obtained for the study from Stellenbosch University (Human Research Ethics Committee reference number S19/01/014 (PhD)). The results will be shared with relevant health authorities, presented at conferences and published in a peer-reviewed journal.

Laboratory biomarkers of COVID-19 disease severity and outcome: Findings from a developing country.

AIM: To identify laboratory biomarkers that predict disease severity and outcome among COVID-19 patients admitted to the Millennium COVID-19 Care Center in Ethiopia. METHODS: A retrospective cohort study was conducted among 429 COVID-19 patients who were on follow up from July to October 2020. Data was described using frequency tables. Robust Poisson regression model was used to identify predictors of COVID-19 severity where adjusted relative risk (ARR), P-value and 95 CI for ARR were used to test significance. Binary Logistic regression model was used to assess the presence of statistically significant association between the explanatory variables and COVID-19 outcome where adjusted odds ratio (AOR), P-value and 95%CI for AOR were used for testing significance. RESULTS: Among the 429 patients studied, 182 (42.4%) had Severe disease at admission and the rest 247 (57.6%) had Non-severe disease. Regarding disease outcome, 45 (10.5%) died and 384 (89.5%) were discharged alive. Age group (ARR = 1.779, 95%CI = 1.405-2.252, p-value <0.0001), Neutrophil to Lymphocyte ratio (NLR) (ARR = 4.769, 95%CI = 2.419-9.402 p-value <0.0001), Serum glutamic oxaloacetic transaminase (SGOT) (ARR = 1.358, 95%CI = 1.109-1.662 p-value = 0.003), Sodium (ARR = 1.321, 95%CI = 1.091-1.600 p-value = 0.004) and Potassium (ARR = 1.269, 95%CI = 1.059-1.521 p-value = 0.010) were found to be significant predictors of COVID-19 severity. The following factors were significantly associated with COVID-19 outcome; age group (AOR = 2.767, 95%CI = 1.099-6.067, p-value = 0.031), white blood cell count (WBC) (AOR = 4.253, 95%CI = 1.918-9.429, p-value = 0.0001) and sodium level (AOR = 3.435, 95%CI = 1.439-8.198, p-value = 0.005). CONCLUSIONS: Assessing and monitoring the laboratory markers of WBC, NLR, SGOT, sodium and potassium levels at the earliest stage of the disease could have a considerable role in halting disease progression and death.

Effect of SARS-CoV-2 Infection in Pregnancy on Maternal and Neonatal Outcomes in Africa: An AFREhealth Call for Evidence through Multicountry Research Collaboration.

In the African context, there is a paucity of data on SARS-CoV-2 infection and associated COVID-19 in pregnancy. Given the endemicity of infections such as malaria, HIV, and tuberculosis (TB) in sub-Saharan Africa (SSA), it is important to evaluate coinfections with SARS-CoV-2 and their impact on maternal/infant outcomes. Robust research is critically needed to evaluate the effects of the added burden of COVID-19 in pregnancy, to help develop evidence-based policies toward improving maternal and infant outcomes. In this perspective, we briefly review current knowledge on the clinical features of COVID-19 in pregnancy; the risks of preterm birth and cesarean delivery secondary to comorbid severity; the effects of maternal SARS-CoV-2 infection on the fetus/neonate; and in utero mother-to-child SARS-CoV-2 transmission. We further highlight the need to conduct multicountry surveillance as well as retrospective and prospective cohort studies across SSA. This will enable assessments of SARS-CoV-2 burden among pregnant African women and improve the understanding of the spectrum of COVID-19 manifestations in this population, which may be living with or without HIV, TB, and/or other coinfections/comorbidities. In addition, multicountry studies will allow a better understanding of risk factors and outcomes to be compared across countries and subregions. Such an approach will encourage and strengthen much-needed intra-African, south-to-south multidisciplinary and interprofessional research collaborations. The African Forum for Research and Education in Health's COVID-19 Research Working Group has embarked upon such a collaboration across Western, Central, Eastern and Southern Africa.

Implications of COVID-19 in high burden countries for HIV/TB: A systematic review of evidence.

BACKGROUND: The triple burden of COVID-19, tuberculosis and human immunodeficiency virus is one of the major global health challenges of the twenty-first century. In high burden HIV/TB countries, the spread of COVID-19 among people living with HIV is a well-founded concern. A thorough understanding of HIV/TB and COVID-19 pandemics is important as the three diseases interact. This may clarify HIV/TB/COVID-19 as a newly related field. However, several gaps remain in the knowledge of the burden of COVID-19 on patients with TB and HIV. This study was conducted to review different studies on SARS-CoV, MERS-CoV or COVID-19 associated with HIV/TB co-infection or only TB, to understand the interactions between HIV, TB and COVID-19 and its implications on the burden of the COVID-19 among HIV/TB co-infected or TB patients, screening algorithm and clinical management. METHODS: We conducted an electronic search of potentially eligible studies published in English in the Cochrane Controlled Register of Trials, PubMed, Medrxiv, Google scholar and Clinical Trials Registry databases. We included case studies, case series and observational studies published between January, 2002 and July, 2020 in which SARS-CoV, MERS-CoV and COVID-19 co-infected to HIV/TB or TB in adults. We screened titles, abstracts and full articles for eligibility. Descriptive and meta-analysis were done and results have been presented in graphs and tables. RESULTS: After removing 95 duplicates, 58 out of 437 articles were assessed for eligibility, of which 14 studies were included for descriptive analysis and seven studies were included in the meta-analysis. Compared to the descriptive analysis, the meta-analysis showed strong evidence that current TB exposure was high-risk COVID-19 group (OR 1.67, 95% CI 1.06-2.65, P = 0.03). The pooled of COVID-19/TB severity rate increased from OR 4.50 (95% CI 1.12-18.10, P = 0.03), the recovery rate was high among COVID-19 compared to COVID-19/TB irrespective of HIV status (OR 2.23, 95% CI 1.83-2.74, P < 0.001) and the mortality was reduced among non-TB group (P < 0.001). CONCLUSION: In summary, TB was a risk factor for COVID-19 both in terms of severity and mortality irrespective of HIV status. Structured diagnostic algorithms and clinical management are suggested to improve COVID-19/HIV/TB or COVID-19/TB co-infections outcomes.

Implications of COVID-19 in high burden countries for HIV/TB: A systematic review of evidence (preprint)

Background: The triple burden of COVID-19, tuberculosis and human immunodeficiency virus is one of the major global health challenges of the 21 st century. In high burden HIV/TB countries, the spread of COVID-19 among people living with HIV is a well-founded concern. A thorough understanding of HIV/TB and COVID-19 pandemics is important as the three diseases interact. This may clarify HIV/TB/COVID-19 as a newly related field and play an important role in the present and future management of the co-infections. However, several gaps are remaining in the knowledge of the burden of COVID-19 on patients with TB and HIV, the diagnosis, and management of these patients. Objectives The study was conducted to review different studies on SARS-CoV, MERS-CoV or COVID-19 associated with HIV/TB co-infection or only TB and to understand the interactions between HIV, TB and COVID-19 and its implications on the burden of the COVID-19 among HIV/TB co-infected or TB patients, screening algorithm and clinical management. Methods We conducted electronic search of potential eligible studies published in English in the Cochrane Controlled Register of Trials, PubMed, Medrxiv, Google scholar and Clinical Trials Registry databases. We included case studies, case series and observational studies published between January, 2002 and March, 2020 in which SARS-CoV, MERS-CoV and COVID-19 co-infected to HIV/TB or TB were managed in adult patients. We screened titles, abstracts and full articles for eligibility. As we anticipated heterogeneity in the literature, results were reported narratively. Main results After removing 69 duplicates, 24 out of 246 articles were assessed for eligibility, of which 9 studies were included for qualitative analysis. Among them, we included two case reports, four case series, one case-control and two retrospective observational studies. The studies have shown that TB may occur during or after SARS-CoV. In terms of severity, the proportion of severe/critical SARS, MERS and COVID cases with TB co-infection was higher than in patients with mild/moderate stages (P= 0.0008). Conclusion SARS/MERS-CoV/COVID-19 associated to HIV/TB or TB subjects had a higher risk of developing severe/critical than mild/moderate SARS/MERS-CoV/COVID-19. Diagnostic algorithms and clinical management were suggested for efficiently improving COVID-19/HIV/TB co-infections outcomes.

Clinical evolution, management and outcomes of patients with COVID-19 admitted at Tygerberg Hospital, Cape Town, South Africa: a research protocol.

INTRODUCTION: The outbreak of the SARS-CoV-2 virus causing COVID-19, declared a global pandemic by the WHO, is a novel infection with a high rate of morbidity and mortality. In South Africa, 55 421 cases have been confirmed as of 10 June 2020, with most cases in the Western Cape Province. Coronavirus leaves us in a position of uncertainty regarding the best clinical approach to successfully manage the expected high number of severely ill patients with COVID-19. This presents a unique opportunity to gather data to inform best practices in clinical approach and public health interventions to control COVID-19 locally. Furthermore, this pandemic challenges our resolve due to the high burden of HIV and tuberculosis (TB) in our country as data are scarce. This study endeavours to determine the clinical presentation, severity and prognosis of patients with COVID-19 admitted to our hospital. METHODS AND ANALYSIS: The study will use multiple approaches taking into account the evolving nature of the COVID-19 pandemic. Prospective observational design to describe specific patterns of risk predictors of poor outcomes among patients with severe COVID-19 admitted to Tygerberg Hospital. Data will be collected from medical records of patients with severe COVID-19 admitted at Tygerberg Hospital. Using the Cox proportional hazards model, we will investigate the association between the survival time of patients with COVID-19 in relation to one or more of the predictor variables including HIV and TB. ETHICS AND DISSEMINATION: The research team obtained ethical approval from the Health Research Ethics Committee of the Faculty of Medicine and Health Sciences, Stellenbosch University and Research Committee of the Tygerberg Hospital. All procedures for the ethical conduct of scientific investigation will be adhered to by the research team. The findings will be disseminated in clinical seminars, scientific forums and conferences targeting clinical care providers and policy-makers.