Communicable and non-communicable co-morbidities and the presentation of COVID-19 in an African setting of high HIV-1 and tuberculosis prevalence
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Abstract
Objectives
To describe the presentation and outcome of SARS-CoV2 infection in an African setting of high non-communicable co-morbidity and also HIV-1 and tuberculosis prevalence.
Design
Case control analysis with cases stratified by HIV-1 and tuberculosis status.
Setting
A single-centre observational case-control study of adults admitted to a South African hospital with proven SARS-CoV-2 infection or alternative diagnosis.
Participants
104 adults with RT-PCR-proven SARS-CoV2 infection of which 55 (52.9%) were male and 31 (29.8%) HIV-1 co-infected. 40 adults (35.7% male, 30.9% HIV-1 co-infected) admitted during the same period with no RT-PCR or serological evidence of SARS-CoV2 infection and assigned alternative diagnoses. Additional in vitro data from prior studies of 72 healthy controls and 118 HIV-1 uninfected and infected persons participants enrolled to a prior study with either immune evidence of tuberculosis sensitization but no symptoms or microbiologically confirmed pulmonary tuberculosis.
Results
Two or more co-morbidities were present in 57.7% of 104 RT-PCR proven COVID-19 presentations, the commonest being hypertension (48%), type 2 diabetes mellitus (39%), obesity (31%) but also HIV-1 (30%) and active tuberculosis (14%). Amongst patients dually infected by tuberculosis and SARS-CoV-2, clinical features could be dominated by either SARS-CoV-2 or tuberculosis: lymphopenia was exacerbated, and some markers of inflammation (D-dimer and ferritin) elevated in singly SARS-CoV-2 infected patients were even further elevated (p < 0.05). HIV-1 and SARS-CoV2 co-infection resulted in lower absolute number and proportion of CD4 lymphocytes, with those in the lowest peripheral CD4 percentage strata exhibiting absent or lower antibody responses against SARS-CoV2. Death occurred in 30/104 (29%) of all COVID-19 patients and in 6/15 (40%) of patients with coincident SARS-CoV-2 and tuberculosis.
Conclusions
In this South African setting, HIV-1 and tuberculosis are common co-morbidities in patients presenting with COVID-19. In environments in which tuberculosis is common, SARS-CoV-2 and tuberculosis may co-exist with clinical presentation being typical of either disease. Clinical suspicion of exacerbation of co-existent tuberculosis accompanying SARS-CoV-2 should be high.
What is already known on this topic?
It has been quite widely thought that Africa has been spared the worst effects of the COVID-19 pandemic. There are very few reported case series and no case-control studies comparing COVID-19 patients admitted to hospital to those admitted for other reasons. However several studies have indicated both HIV-1 and tuberculosis co-infection that are endemic in Africa constitute risk factors for poor outcome. In addition Africa is subject to demographic transition and the prevalence of non-communicable co-morbidities such as type 2 diabetes, hypertension and cardiovascular disease is rising rapidly. No study from Africa has described the clinical impact on the presentation of COVID-19 infection.
What this study adds
Two or more co-morbidities were present in over half COVID-19 presentations, including HIV-1 (30%) and active tuberculosis (14%). Patients dually infected by tuberculosis and SARS-CoV-2, presented as either SARS-CoV-2 or tuberculosis. HIV-1 and SARS-CoV2 co-infection resulted in lower absolute number and proportion of CD4 lymphocytes, and those with low CD4 counts had absent or lower antibody responses against SARS-CoV2. Death occurred 29% of all COVID-19 patients and in 40% of patients with coincident SARS-CoV-2 and tuberculosis. Thus in environments in which tuberculosis is common, SARS-CoV-2 and tuberculosis may co-exist with clinical presentation being typical of either disease and clinical suspicion of exacerbation of co-existent tuberculosis accompanying SARS-CoV-2 should be high.
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SciScore for 10.1101/2021.05.11.21256479: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics Consent: Between 11th June and 28th August 2020, the study team assessed suspected or confirmed SARS-CoV-2 (by nasopharyngeal or oropharyngeal aspirate) participants and expedited written electronic consent for inclusion was provided.
IRB: The WHO ordinal severity score was used to categorize participants on admission according to the following categories: The study was conducted according to the declaration of Helsinki, conformed to South African Good Clinical Practice guidelines, and was approved by the University of Cape Town’s Health Sciences Research Ethical Committee (HREC 207/2020).Sex as a biological variable not detected. Randomization not detected. Blinding Radiographic evaluation: … SciScore for 10.1101/2021.05.11.21256479: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics Consent: Between 11th June and 28th August 2020, the study team assessed suspected or confirmed SARS-CoV-2 (by nasopharyngeal or oropharyngeal aspirate) participants and expedited written electronic consent for inclusion was provided.
IRB: The WHO ordinal severity score was used to categorize participants on admission according to the following categories: The study was conducted according to the declaration of Helsinki, conformed to South African Good Clinical Practice guidelines, and was approved by the University of Cape Town’s Health Sciences Research Ethical Committee (HREC 207/2020).Sex as a biological variable not detected. Randomization not detected. Blinding Radiographic evaluation: Chest radiographs were reported blind to clinical status by an experienced radiologist (QS-H). Power Analysis not detected. Table 2: Resources
Antibodies Sentences Resources Switzerland) Anti-SARS-CoV-2 immunoassay which detects antibodies (including IgG) to SARS-CoV-2. Anti-SARS-CoV-2 immunoassay which detects antibodies ( including IgGsuggested: NoneSARS-CoV-2suggested: NoneCells were then stained with an antibody cocktail containing among others anti-CD3, -CD4 and -CD8 antibodies. anti-CD3suggested: None-CD8suggested: NoneSoftware and Algorithms Sentences Resources Data were entered directly into an electronic REDCap data entry system, hosted by the University of Cape Town 34. REDCapsuggested: (REDCap, RRID:SCR_003445)Samples were acquired on a BD LSR-II and analyzed using FlowJo (v9.9.6, FlowJo LCC, Ashland, OR, USA). FlowJosuggested: (FlowJo, RRID:SCR_008520)Analytical methods: Analyses were conducted in Prism 8 (GraphPad Software, San Diego, CA). GraphPadsuggested: (GraphPad Prism, RRID:SCR_002798)Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
Results from scite Reference Check: We found no unreliable references.
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