Lung outcomes and related risk factors in patients after SARS-CoV-2 infection: a hospitalised single-centre cohort from Johannesburg, South Africa.

Background: Sequelae post-SARS-CoV-2 infection, including lung and functional impairment, pose a significant challenge post-recovery. We explored the burden and risk factors for post-COVID-19 sequelae in an African population with prevalent comorbidities including tuberculosis (TB) and HIV. Methods: We conducted an observational cohort study on hospitalised adults with confirmed SARS-CoV-2 infection from 20 March to 06 October 2021 at Chris Hani Baragwanath Academic Hospital, South Africa. We collected data on comorbidities, and COVID-19 severity using the World Health Organization (WHO) clinical progression scale. Prospectively, we followed up all participants within 40-days post-discharge to assess body mass index (BMI), COVID-19 symptoms and quality of life using St George's Respiratory Questionnaire (SGRQ), 6-min walking-test (6MWT), and spirometry. A subsequent in-depth visit assessed plethysmography, diffusing capacity for the lung for carbon monoxide (DLCO), and high-resolution chest-CT. Findings: We followed up 111 participants, where 65.8% were female, median age 50.5 years, and predominantly black-African (92.8%). Relevant comorbidities included TB disease (18.9%) and HIV infection (36%). SGRQ total scores were elevated in 78.9%, median 6MWT distance was reduced at 300 m (IQR 210-400), and nearly half (49.5%) exhibited spirometry findings below the lower limit of normal (LLN). In-depth pulmonary assessment for 61 participants revealed abnormalities in total lung capacity (31.6% <80% predicted), DLCO (53.4% <80% predicted), and chest-CT (86.7% abnormal). Significant risk factors for individual abnormal outcomes, adjusted for age and sex, were TB disease, HIV with CD4 <200 cells/mm3, BMI <18.5 kg/m2 and >35 kg/m2, and initial COVID-19 severity. Interpretation: This study demonstrates substantial lung and functional morbidity within the first weeks post-COVID-19, particularly in individuals with pre-existing comorbidities including TB, HIV, and low or high BMI. Chest-CT and DLCO show best early potential at reflecting COVID-19-related pathologies. Funding: The Bavarian State Ministry of Science and Arts.

Evaluation of the modified Wells score in predicting venous thromboembolic disease in patients with tuberculosis or HIV in a South African setting.

Background: There is paucity of data on the modified Wells score (MWS) utility on patients with venous thromboembolism (VTE) in a South African setting where there is a high burden of HIV and tuberculosis (TB). This study analyses the performance of this score in HIV/TB-infected patients compared with non-infected patients. Objectives: To assess the performance of the MWS as an additional risk factor for VTE in hospitalised patients with a high burden of HIV/TB infections. Method: This study was a retrospective cross-sectional cohort analysis of the utility of the MWS in 156 HIV/TB-infected and non-infected adult patients diagnosed with VTE on compression ultrasonography (CUS) or computed tomography pulmonary angiography (CTPA) in a medical inpatient setting over six months. Patients with HIV and/or TB were assessed as having an additional risk factor (1 point for each), and this was compared with the MWS. A McNeymar's paired sample chi-squared test was used to compare the sensitivity of this score against the MWS. Results: Of the 156 patients with VTE who were enrolled, HIV was the commonest risk factor (42.31%) with TB accounting for 10.90% of cases. When the MWS adjusted for HIV/TB was used, the sensitivity increased from 25% to 100% for the HIV-/TB+ category, it increased from 77.36% to 98.11% in the HIV+/TB- category and it increased from 84.62% to 92.95% in the HIV+/TB+ category. These differences were statistically significant at P < 0.05 in all categories. Conclusion: The MWS performs better when the infectivity of HIV/TB is included as an additional risk factor in the score.

Vitamin D status and COVID-19 severity.

Background: Age, body mass index (BMI) and pre-existing comorbidities are known risk factors of severe coronavirus disease 2019 (COVID-19). In this study we explore the relationship between vitamin D status and COVID-19 severity. Methods: We conducted a prospective, cross-sectional descriptive study. We enrolled 100 COVID-19 positive patients admitted to a tertiary level hospital in Johannesburg, South Africa. Fifty had symptomatic disease (COVID-19 pneumonia) and 50 who were asymptomatic (incidental diagnosis). Following written informed consent, patients were interviewed regarding age, gender and sunlight exposure during the past week, disease severity, BMI, calcium, albumin, magnesium and alkaline phosphatase levels. Finally, blood was collected for vitamin D measurement. Results: We found an 82% prevalence rate of vitamin D deficiency or insufficiency among COVID-19 patients. Vitamin D levels were lower in the symptomatic group (18.1 ng/mL ± 8.1 ng/mL) than the asymptomatic group (25.9 ng/mL ± 7.1 ng/mL) with a p-value of 0.000. The relative risk of symptomatic COVID-19 was 2.5-fold higher among vitamin D deficient patients than vitamin D non-deficient patients (confidence interval [CI]: 1.14-3.26). Additional predictors of symptomatic disease were older age, hypocalcaemia and hypoalbuminaemia. Using multiple regression, the only independent predictors of COVID-19 severity were age and vitamin D levels. The patients exposed to less sunlight had a 2.39-fold increased risk for symptomatic disease compared to those with more sunlight exposure (CI: 1.32-4.33). Conclusion: We found a high prevalence of vitamin D deficiency and insufficiency among patients admitted to hospital with COVID-19 and an increased risk for symptomatic disease in vitamin D deficient patients.

Oxygen efficient respiratory Aid (OxEraTM) device: A safety study.

Background: Severe Coronavirus Disease 2019 (COVID-19) can develop pneumonia with severe complications. The Oxygen Efficient Respiratory Aid (OxEraTM) device has been granted SAPHRA approval for emergency COVID-19 pandemic use. The device has the potential to be used widely in the healthcare sector due to its efficient oxygen supply and adjustable wall positive expiratory pressure (PEP). Objectives: We assessed whether the OxEraTM device was safe to use in a healthy adult volunteer population. Our primary objective was to ensure there was no asphyxiation, as assessed by changes observed from baseline End Tidal Carbon Dioxide (ETCO2) exceeding 6.3 mmHg and above the 45 mmHg threshold. We also monitored changes in vital organ signs and assessed the pain and comfort of the participant at various intervals with changes in PEPs. Methods: This was an experimental safety study of the OxEraTM Device on 30 healthy participants at the ICU training centre of Chris Hani Baragwanath Academic Hospital, Johannesburg, South Africa. Each participant had basic vital-signs, ETCO2, and Oxygen saturation percentages (SpO2%) taken at baseline until the end of 2 h. In the first 20 min, the PEP was increased by 5 cmH20 until 20 min, then continued for the rest of the time on a PEP of 5 cmH20. At each interval, vital signs, subjective comfort, pain, and visual scores were measured. Results: Thirty healthy participants were enrolled. There was no significant difference in ETCO2 from baseline until 2 h. No participant experienced an increase in measured ETCO2 greater than 45 mmHg and no increase in ETCO2 from baseline was greater than 6.3 mmHg. The median increase in ETCO2 over the study period was 2 mmHg. There were no significant changes in respiratory rate and blood pressure. The heart rate decreased significantly (73-68 bpm). The VAS and comfort score had a significant increase over the 2 h from baseline of 0-2 at maximum; however, the PAS scores showed no significant increase. Conclusion: Overall the OxEraTM device achieved the safety endpoints set out. There was no sign of asphyxiation and there were appropriate physiological responses to changes in PEP once applied. The comfort of the mask did worsen over the 2 h; however, the scores were minimally worse on PEP application but improved once-off PEP. No adverse event was recorded at all.

Validation of the COVID-19 IgG/IgM Rapid Test Cassette (BNCP - 402 and BNCP402) in a South African setting.

Background: Different diagnostic tools could improve early detection of coronavirus disease 2019 (COVID-19). A number of antibody-based serological point-of-care tests have been developed to supplement real-time reverse transcriptase polymerase chain reaction (RT-PCR)-based diagnosis. This study describes the validity of an antibody test, namely the immunoglobulin G (IgG)/immunoglobulin M (IgM) Rapid Test Cassette® (BNCP - 402 and BNCP402), manufactured by Spring Healthcare Services. Methods: A prospective cohort validation study was undertaken at Chris Hani Baragwanath Academic Hospital between 16 July 2020 and 12 August 2020. A total of 101 patients admitted as COVID-19 cases under investigation were included in the study. They were divided into two categories depending on time since symptom onset: testing performed within seven days (early cohort) and after seven days (late cohort). The rapid antibody test was compared to the RT-PCR. Results: Overall, the test has a sensitivity and specificity of 85.2% and 80.0%, respectively, for a combination of IgG and IgM. Sensitivity and specificity of IgG testing alone were 81.5% and 85%. Sensitivity improved for testing with increasing time from symptom onset; however, specifity was not significantly different. Conclusion: The study data adds to the body of evidence that because of relatively low sensitivity and specificity, there is a limited role for antibody-based point-of-care testing in the acute phase of COVID-19 infection, as was the case with this IgG/IgM Rapid Test Cassette (BNCP - 402 and BNCP402). There may exist a role for such testing in patients recovered from prior COVID-19 infection or in seroprevalence studies; however, additional evaluations at later timepoints from symptom onset are required.

Clinical characteristics and histopathology of COVID-19 related deaths in South African adults.

Comparisons of histopathological features and microbiological findings between decedents with respiratory symptoms due to SARS-CoV-2 infection or other causes, in settings with high prevalence of HIV and Mycobacterium tuberculosis (MTB) infections have not been reported. Deaths associated with a positive ante-mortem SARS-CoV-2 PCR test and/or respiratory disease symptoms at Chris Hani Baragwanath Academic Hospital in Soweto, South Africa from 15th April to 2nd November 2020, during the first wave of the South African COVID-19 epidemic, were investigated. Deceased adult patients had post-mortem minimally-invasive tissue sampling (MITS) performed to investigate for SARS-CoV-2 infection and molecular detection of putative pathogens on blood and lung samples, and histopathology examination of lung, liver and heart tissue. During the study period MITS were done in patients displaying symptoms of respiratory disease including 75 COVID-19-related deaths (COVID+) and 42 non-COVID-19-related deaths (COVID-). The prevalence of HIV-infection was lower in COVID+ (27%) than in the COVID- (64%), MTB detection was also less common among COVID+ (3% vs 13%). Lung histopathology findings showed differences between COVID+ and COVID- in the severity of the morphological appearance of Type-II pneumocytes, alveolar injury and repair initiated by SARS-CoV-2 infection. In the liver necrotising granulomatous inflammation was more common among COVID+. No differences were found in heart analyses. The prevalence of bacterial co-infections was higher in COVID+. Most indicators of respiratory distress syndrome were undifferentiated between COVID+ and COVID- except for Type-II pneumocytes. HIV or MTB infection does not appear in these data to have a meaningful correspondence with COVID-related deaths.

Demographic, clinical, electrocardiographic and echocardiographic characteristics of patients hospitalized with COVID-19 and cardiac disease at a tertiary hospital, South Africa.

BACKGROUND: Coronavirus associated disease 2019 (COVID-19) is associated with higher morbidity and mortality in patients with cardiovascular disease. There is a paucity of data regarding COVID-19 and cardiac disease from Africa. We aimed to describe the demographic, clinical, electrocardiographic and echocardiographic characteristics of patients with COVID-19 and cardiac disease at a tertiary hospital in South Africa. METHODS: This was a retrospective cross-sectional descriptive study (Aug 2020 to March 2021) of 200 patients with COVID-19 and confirmed cardiac disease, conducted at Chris Hani Baragwanath. Demographic, clinical, electrocardiographic and echocardiographic characteristics were systematically collected. RESULTS: Majority (86%) of patients were Africans with mean age 56.4±15.6 years (57.5% females). Fifty three percent were unemployed and 28% were pensioners. Main comorbidities were hypertension (69.5%), diabetes mellitus (31.5%) and human immunodeficiency virus (HIV) (22.5%). Majority of the patients were overweight or obese (65.5%). All except 8 patients were on chronic medication. Dyspnoea on admission was noted in 88.5% of patients. Seventy nine percent of patients had abnormal chest X-Ray. Frequently documented electrocardiography findings were sinus tachycardia (63%) and atrial fibrillation, noted in 7% of patients. The most common indication for echocardiography was heart failure (30%). Severe left ventricular dysfunction was noted in 21.5%. Features of pulmonary hypertension were present in 45.5%. The right ventricle was enlarged in 59% of patients, and functional tricuspid regurgitation was noted in 54.5%. The most common diagnoses were hypertensive heart disease with preserved ejection fraction (35.8%), cardiomyopathies (20%), cor pulmonale (15.7%), acute coronary syndrome (6.5%), infective endocarditis (5.5%) and valvular heart disease (2.5%). Echocardiography modified management in 53% of cases. An in-hospital mortality of 17.5% was noted. On multivariate logistic regression analysis sinus tachycardia was the most important independent predictor of mortality (odds ratio, OR: 2.52, 95% confidence interval, CI: 1.08-5.85, P=0.03). CONCLUSIONS: Most patients were obese females with underlying hypertension. Echocardiography altered management in about half the patients. Mortality amongst this cohort of patients was high and were predominantly males.

Prevalence and Trajectory of COVID-19-Associated Hypercoagulability Using Serial Thromboelastography in a South African Population.

INTRODUCTION: The coagulation abnormalities resulting from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been attributed to inflammation and subsequent cytokine storm. Thromboelastography (TEG) is a point-of-care test used to assess clot formation and degradation in whole blood and is an indicator of the overall real-time coagulopathic state of the patient. METHODS: A single-centre, prospective, observational cohort study was conducted in South Africa, analysing the coagulation patterns of 41 patients with hypoxia related to SARS-CoV-2 using serial thromboelastography (TEG) on admission, after 48 hours, and at resolution of hypoxia/day 10. Results: Two-thirds (n = 26) were women. The median age was 61 (IQR 50-67), and the majority (88%) were Black patients. Almost half (22) of the patients were critically ill and ventilated, with median SOFA and SAPS2 scores of 3 and 22 (IQR2-4 and 18-30), respectively. The prevalence of hypercoagulability was 0.54 (95% CI 0.46-0.62), whilst 29/41 (0.71, CI 0.64-0.78)) met the definition of hypofibrinolysis. Differences between the hypercoagulable (HC) and non-hypercoagulable groups remained apparent at 48 hours after anticoagulation. At this time point, the K time was significantly lower (p ˂ 0,01), and the α-angle (p ˂ 0,01) and maximum amplitude (MA) (p ˂ 0,01) were significantly higher in the HC cohort. At resolution of hypoxia, or day 10, only MA was significantly higher in the hypercoagulable group compared to the non-hypercoagulable group (p = 0.01). The initial impairment in fibrinolysis (Ly30), α angle, and MA were significantly associated with mortality, with p values of 0.006, 0.031, and 0.04, respectively. CONCLUSIONS: In this South African population, hypercoagulability was a highly prevalent phenomenon in COVID-19 disease. It was typified by hypofibrinolysis and a persistently elevated MA, despite anticoagulation therapy.

Classical Hodgkin Lymphoma involving the central nervous system (brain) - an unusual presentation.

KEY CLINICAL MESSAGE: Intracranial Hodgkin lymphoma (HL) is considered so atypical that an intracranial space-occupying lesion in a patient with known HL should be thoroughly investigated to rule out a second disease process.