Critical illness due to infection in people living with HIV.

People living with HIV comprise a substantial number of the patients admitted to intensive care. This number varies according to geography, but all areas of the world are affected. In lower-income and middle-income countries, the majority of intensive care unit (ICU) admissions relate to infections, whereas in high-income countries, they often involve HIV-associated non-communicable diseases diagnoses. Management of infections potentially resulting in admission to the ICU in people living with HIV include sepsis, respiratory infections, COVID-19, cytomegalovirus infection, and CNS infections, both opportunistic and non-opportunistic. It is crucial to know which antiretroviral therapy (ART) is appropriate, when is the correct time to administer it, and to be aware of any safety concerns and potential drug interactions with ART. Although ART is necessary for controlling HIV infections, it can also cause difficulties relevant to the ICU such as immune reconstitution inflammatory syndrome, and issues associated with ART administration in patients with gastrointestinal dysfunction on mechanical ventilation. Managing infection in people with HIV in the ICU is complex, requiring collaboration from a multidisciplinary team knowledgeable in both the management of the specific infection and the use of ART. This team should include intensivists, infectious disease specialists, pharmacists, and microbiologists to ensure optimal outcomes for patients.

COVID-19: An evaluation of predictive scoring systems in South Africa.

Background: | The Coronavirus Disease 2019 (COVID-19) pandemic, caused by SARS-CoV-2, has resulted in more than 700 million cases worldwide. Sepsis and pneumonia severity scores assist in risk assessment of critical outcomes in patients with COVID-19. This allows healthcare workers to triage patients, by using clinical parameters and limited special investigations, thus offering the most appropriate level of care. Methods: | A retrospective cohort study of 605 adult patients hospitalised with moderate to severe COVID-19, at a tertiary state hospital in South Africa. Evaluating the utility of the CURB65, NEWS2 and ISARIC-4C Mortality Score, in predicting critical outcomes, using clinical characteristics on admission. Outcomes included in-hospital mortality, invasive mechanical ventilation, and intensive care unit admission (ICU). Performance of severity scores and risk factors was assessed by area under the receiver operator characteristics (AUROC) analysis and logistic regression. Findings |: A total of 605 records were used, 129 (21 %) non-survivors, 101 (17 %) ICU admissions and 77 (13 %) requiring invasive ventilation. Greater odds of mortality was associated with moderate and severe risk groups of the CURB65, ISARIC-4C and NEWS2 score. Mortality AUROC curve analysis for the CURB65 score was 0·76 (95 % CI: 0·71-0·8), 0·77 (95 % CI: 0·73-0·81) for the ISARIC-4C and 0·77 (95 % CI: 0·73-0·82) for the NEWS2 score. The CURB65 score had a sensitivity of 86 % with 12·8 % mortality, ISARIC-4C score a sensitivity of 87·6 % with 8 % mortality and NEWS2 score a sensitivity of 92·2 % with 8·6 % mortality. Interpretation |: In 605 hospitalised patients with moderate to severe COVID-19, predominantly infected by the ancestral strain, good performance of the NEWS2 and ISARIC-4C score in predicting in-hospital mortality was noted. The CURB65 score had a high mortality rate in its low-risk group suggesting unexplained risk factors, not accounted for in the score, thus limiting its utility in the South African setting.

An audit of adherence to cervical cancer screening guidelines in a tertiary-level HIV clinic.

Background: Cervical cancer is the most common malignancy affecting South African women aged 15-44 years, with a higher prevalence among women living with HIV (WLWH). Despite recommendations for a screening target of 70%, the reported rate of cervical cancer screening in South Africa is 19.3%. Objectives: To investigate the adherence of healthcare workers to cervical cancer screening guidelines in a tertiary-level HIV clinic. Method: A retrospective cross-sectional record audit of women attending the Charlotte Maxeke Johannesburg Academic Hospital HIV Clinic over a 1-month period. Results: Out of 403 WLWH who attended the clinic, 180 (44.7%) were screened for cervical cancer in the 3 years prior to the index consultation. Only 115 (51.6%) of those women with no record of prior screening were subsequently referred for screening. Women who had undergone screening in the previous 3 years were significantly older (47 years vs 44 years, P = 0.046) and had a longer time since diagnosis of their HIV (12 years vs 10 years, P = 0.001) compared to women who had not undergone screening. There was no significant difference in CD4 count or viral suppression between women who had and had not undergone screening. Conclusion: The rate of cervical cancer screening in our institution is below that recommended by the World Health Organization and the South African National Department of Health.

A Review of Coronavirus Disease 2019 in Pregnancy.

Pregnancy is an independent risk factor for morbidity and mortality in coronavirus disease 2019 (COVID-19) with increased rates of operative delivery, intensive care unit admission, and mechanical ventilation as well as a possible increased risk of death, independent of other risk factors, compared with nonpregnant women with COVID-19. Furthermore, pregnancy outcomes are worse in those with COVID-19 with increased risk for preeclampsia, venous thromboembolism, preterm birth, miscarriage, and stillbirth compared with pregnant women without COVID-19. Importantly, pregnant women of nonwhite ethnicity appear to be at greater risk of severe COVID-19, necessitating improved access to care and closer monitoring in these women. The management of COVID-19 in pregnancy is largely similar to that in nonpregnant people; however, there is an important emphasis on multidisciplinary team involvement to ensure favorable outcomes in both mother and baby. Similarly, vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is safe in pregnancy and improves maternal and neonatal outcomes.

A study of the chest imaging findings of adult patients with COVID-19 on admission to a tertiary hospital in Johannesburg, South Africa.

Background: South Africa has experienced multiple waves of the coronavirus disease 2019 (COVID-19) with little research documenting chest imaging features in an human immunodeficiency virus (HIV) and tuberculosis (TB) endemic region. Objectives: Describe the chest imaging features, demographics and clinical characteristics of COVID-19 in an urban population. Method: Retrospective, cross-sectional, review of chest radiographs and computed tomographies (CTs) of adults admitted to a tertiary hospital with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, between 01 May 2020 and 30 June 2020. Imaging was reviewed by three radiologists. Clinical parameters and laboratory data were analysed. Results: A total of 113 adult patients with a mean age of 46 years and 10 months were included. A total of 113 chest radiographs and six CTs were read. Nineteen patients were HIV-positive (16.8%), 40 were hypertensive and diabetic (35.4%), respectively, and one had TB (0.9%). Common symptoms included cough (n = 69; 61.6%), dyspnoea (n = 60; 53.1%) and fever (n = 46; 40.7%). Lower zone predominant ground glass opacities (58.4%) and consolidation (29.2%) were most frequent on chest radiographs. The right lower lobe was most involved (46.9% ground glass opacities and 17.7% consolidation), with relative sparing of the left upper lobe. Bilateral ground glass opacities (66.7%) were most common on CT. Among the HIV-positive, ground glass opacities and consolidation were less common than in HIV-negative or unknown patients (p = 0.037 and p = 0.05, respectively). Conclusion: COVID-19 in South Africa has similar chest imaging findings to those documented globally, with some differences between HIV-positive and HIV-negative or unknown patients. The authors corroborate relative sparing of the left upper lobe; however, further research is required to validate this currently unique local finding.

Competence of medical and obstetric registrars in the management of systemic lupus erythematosus in pregnancy.

INTRODUCTION: Systemic lupus erythematosus has a predilection for women of childbearing age. Globally a shortage of rheumatologists exists resulting in general physicians and obstetricians treating systemic lupus erythematosus in pregnancy. METHODS: We conducted a survey amongst medical and obstetric registrars in South Africa to assess their subjective and objective competence in managing pregnant women with systemic lupus erythematosus. RESULTS: The pass rate for the objective section was 70.8% with no statistically significant difference in the pass rate between medical and obstetric registrars. Participants felt unprepared to manage pregnant women with systemic lupus erythematosus, with a mean overall score of 3.4 out of 7 for the subjective section, based on four Likert scale type questions. CONCLUSION: Trainees are not able to accurately assess their own levels of competence in order to identify their learning needs. Due to the shortage of rheumatologists and lack of obstetric physicians in South Africa, general physicians and obstetricians must be equipped to provide adequate care to pregnant women with systemic lupus erythematosus.

Risk factors for COVID-19-related in-hospital mortality in a high HIV and tuberculosis prevalence setting in South Africa: a cohort study.

BACKGROUND: The interaction between COVID-19, non-communicable diseases, and chronic infectious diseases such as HIV and tuberculosis is unclear, particularly in low-income and middle-income countries in Africa. South Africa has a national HIV prevalence of 19% among people aged 15-49 years and a tuberculosis prevalence of 0·7% in people of all ages. Using a nationally representative hospital surveillance system in South Africa, we aimed to investigate the factors associated with in-hospital mortality among patients with COVID-19. METHODS: In this cohort study, we used data submitted to DATCOV, a national active hospital surveillance system for COVID-19 hospital admissions, for patients admitted to hospital with laboratory-confirmed SARS-CoV-2 infection between March 5, 2020, and March 27, 2021. Age, sex, race or ethnicity, and comorbidities (hypertension, diabetes, chronic cardiac disease, chronic pulmonary disease and asthma, chronic renal disease, malignancy in the past 5 years, HIV, and past and current tuberculosis) were considered as risk factors for COVID-19-related in-hospital mortality. COVID-19 in-hospital mortality, the main outcome, was defined as a death related to COVID-19 that occurred during the hospital stay and excluded deaths that occurred because of other causes or after discharge from hospital; therefore, only patients with a known in-hospital outcome (died or discharged alive) were included. Chained equation multiple imputation was used to account for missing data and random-effects multivariable logistic regression models were used to assess the role of HIV status and underlying comorbidities on COVID-19 in-hospital mortality. FINDINGS: Among the 219 265 individuals admitted to hospital with laboratory-confirmed SARS-CoV-2 infection and known in-hospital outcome data, 51 037 (23·3%) died. Most commonly observed comorbidities among individuals with available data were hypertension in 61 098 (37·4%) of 163 350, diabetes in 43 885 (27·4%) of 159 932, and HIV in 13 793 (9·1%) of 151 779. Tuberculosis was reported in 5282 (3·6%) of 146 381 individuals. Increasing age was the strongest predictor of COVID-19 in-hospital mortality. Other factors associated were HIV infection (adjusted odds ratio 1·34, 95% CI 1·27-1·43), past tuberculosis (1·26, 1·15-1·38), current tuberculosis (1·42, 1·22-1·64), and both past and current tuberculosis (1·48, 1·32-1·67) compared with never tuberculosis, as well as other described risk factors for COVID-19, such as male sex; non-White race; underlying hypertension, diabetes, chronic cardiac disease, chronic renal disease, and malignancy in the past 5 years; and treatment in the public health sector. After adjusting for other factors, people with HIV not on antiretroviral therapy (ART; adjusted odds ratio 1·45, 95% CI 1·22-1·72) were more likely to die in hospital than were people with HIV on ART. Among people with HIV, the prevalence of other comorbidities was 29·2% compared with 30·8% among HIV-uninfected individuals. Increasing number of comorbidities was associated with increased COVID-19 in-hospital mortality risk in both people with HIV and HIV-uninfected individuals. INTERPRETATION: Individuals identified as being at high risk of COVID-19 in-hospital mortality (older individuals and those with chronic comorbidities and people with HIV, particularly those not on ART) would benefit from COVID-19 prevention programmes such as vaccine prioritisation as well as early referral and treatment. FUNDING: South African National Government.

Age significantly influences the sensitivity of SARS-CoV-2 rapid antibody assays.

BACKGROUND: Point-of-care serological assays are a promising tool in COVID-19 diagnostics but do have limitations. Our study evaluated the sensitivity of five rapid antibody assays and explored factors influencing their sensitivity in detecting SARS-CoV-2-specific IgG and IgM antibodies. METHODS: Finger-prick blood samples from 102 participants, within 2-6 weeks of PCR-confirmed COVID-19 diagnosis, were tested for IgG and IgM using five rapid serological assays. The assay sensitivities were compared, and patient factors evaluated in order to investigate potential associations with assay sensitivity. RESULTS: Sensitivity ranged from 36% to 69% for IgG and 13% to 67% for IgM. Age was the only factor significantly influencing the likelihood of a detectable IgG or IgM response. Individuals aged 40 years and older had an increased likelihood of a detectable IgG or IgM antibody response by rapid antibody assay. CONCLUSION: Rapid serological assays demonstrate significant variability when used in a real-world clinical context. There may be limitations in their use for COVID-19 diagnosis among the young.

Comparison of outcomes in HIV-positive and HIV-negative patients with COVID-19.

BACKGROUND: South Africa has the highest prevalence of HIV in the world and to date has recorded the highest number of cases of COVID-19 in Africa. There is uncertainty as to what the significance of this dual infection is, and whether people living with HIV (PLWH) have worse outcomes compared to HIV-negative patients with COVID-19. This study compared the outcomes of COVID-19 in a group of HIV-positive and HIV-negative patients admitted to a tertiary referral centre in Johannesburg, South Africa. METHODS: Data was collected on all adult patients with known HIV status and COVID-19, confirmed by reverse-transcriptase polymerase chain reaction (RT-PCR), admitted to the medical wards and intensive care unit (ICU) between 6 March and 11 September 2020. The data included demographics, co-morbidities, laboratory results, severity of illness scores, complications and mortality, and comparisons were made between the HIV-positive and HIV negative groups. RESULTS: Three-hundred and eighty-four patients, 108 HIV-positive and 276 HIV-negative, were included in the study. Median 4C score was significantly higher in the HIV-positive patients compared to the HIV-negative patients, but there was no significant difference in mortality between the HIV-positive and HIV-negative groups (15% vs 20%, p = 0.31). In addition, HIV-positive patients who died were younger than their HIV-negative counterparts, but this was not statistically significant (47.5 vs 57 years, p = 0.06). CONCLUSION: Our findings suggest that HIV is not a risk factor for moderate or severe COVID-19 disease neither is it a risk factor for mortality. However, HIV-positive patients with COVID-19 requiring admission to hospital are more likely to be younger than their HIV-negative counterparts. These findings need to be confirmed in future, prospective, studies.

Fibroblast growth factor-23 in patients with homozygous familial hypercholesterolemia.

BACKGROUND: Patients with homozygous familial hypercholesterolemia (HoFH) develop significant vascular calcification early in life, the cause of which is not yet fully understood. Patients with chronic kidney disease have similar vascular calcification, with fibroblast growth factor-23 (FGF23) implicated in these patients. OBJECTIVE: To determine whether there was a difference in FGF23 between patients with HoFH and age- and gender-matched controls and whether there is a correlation between FGF23 and serum low-density lipoprotein, total cholesterol, and carotid intima-media thickness in patients with HoFH. METHODS: The study was a cross-sectional review involving 30 patients with HoFH attending the Charlotte Maxeke Johannesburg Academic Hospital Lipid Clinic in Parktown, South Africa, as well as 30 age- and gender-matched healthy controls. FGF23, fasting lipid profiles, calcium, and phosphate were measured. B-mode ultrasonography of the carotid arteries was done to assess the extent and severity of arterial calcification. RESULTS: There was no difference in mean FGF23 between the patient and control groups (62.07 ± 26.42 pg/mL vs 63.69 ± 19.84 pg/mL; P = .4621) nor was there any correlation between FGF23 and low-density lipoprotein cholesterol (P = .9483 and .8474) or total cholesterol (P = .9261 and .859). In the HoFH patients, FGF23 did not correlate significantly with any cardiovascular disease. CONCLUSIONS: Serum FGF23 is not elevated in patients with HoFH when compared to non-familial hypercholesterolemia age- and gender-matched controls, and there is no correlation between serum FGF23 and cardiovascular disease in patients with HoFH. FGF23 does not appear to be a major factor for arterial calcification in HoFH.