Risk Factors for Coronavirus Disease 2019 (COVID-19) Death in a Population Cohort Study from the Western Cape Province, South Africa

Abstract

Background Risk factors for COVID-19 death in sub-Saharan Africa and the effects of HIV and tuberculosis on COVID-19 outcomes are unknown. Methods We conducted a population cohort study using linked data from adults attending public sector health facilities in the Western Cape, South Africa. We used Cox-proportional hazards models adjusted for age, sex, location and comorbidities to examine the association between HIV, tuberculosis and COVID-19 death from 1 March-9 June 2020 among (i) public sector “active patients” (≥1 visit in the 3 years before March 2020), (ii) laboratory-diagnosed COVID-19 cases and (iii) hospitalized COVID-19 cases. We calculated the standardized mortality ratio (SMR) for COVID-19 comparing HIV positive vs. negative adults using modelled population estimates. Results Among 3,460,932 patients (16% HIV positive), 22,308 were diagnosed with COVID-19, of whom 625 died. COVID-19 death was associated with male sex, increasing age, diabetes, hypertension and chronic kidney disease. HIV was associated with COVID-19 mortality (adjusted hazard ratio [aHR] 2.14; 95% confidence interval [CI] 1.70-2.70), with similar risks across strata of viral load and immunosuppression. Current and previous tuberculosis were associated with COVID-19 death (aHR [95%CI] 2.70 [1.81-4.04] and 1.51 [1.18-1.93] respectively). The SMR for COVID-19 death associated with HIV was 2.39 (95%CI 1.96-2.86); population attributable fraction 8.5% (95%CI 6.1-11.1). Conclusion While our findings may over-estimate HIV- and tuberculosis-associated COVID-19 mortality risks due to residual confounding, both HIV and current tuberculosis were independently associated with increased COVID-19 mortality. The associations between age, sex and other comorbidities and COVID-19 mortality were similar to other settings.

Does HIV impact susceptibility to COVID-19 (SARS-CoV-2) infection and pathology? A review of the current literature

“…This increased mortality risk with HIV infection manifests itself in different parts of the patient pathway in different settings. Thus in the South African study cited above, the increased mortality risk was most apparent in non-hospitalised individuals; (19) in the NYC study, the big difference was in diagnosis and hospitalisation rates -once admitted mortality was similar to non-HIV-infected individuals; (12) in the UK study, in which hospitalisation was an entry criterion, mortality rates were found to be significantly higher in PLWH after admission. 21It does therefore appear reasonable to take HIV status into account in developing policies and practice, but do we treat all PLWH the same?…”

“…However, in the absence of better data, these papers contributed to a general consensus that HIV does not predispose to more severe disease or higher mortality; as one author put it, there is an "… under-representation of people living with HIV (PLWH) among severe COVID-19 cases". (18) More recently, four studies have been published with much larger numbers of cases that appear to overturn this relatively benign paradigm, the papers by Boulle et al, (19) Bhaskaran et al, (20) The Tesoreiro et al study, (12) summarised above also reported mortality risk. Interestingly, in their study, the mortality risk once patients were hospitalised was similar to non-HIV infected individuals, but taking increased diagnosis and admission rates into account, the standardized mortality ratio for PLWH was higher than the general population (1.23; 95% CI: 1.13-1.48).…”

Risk of adverse COVID-19 outcomes for people living with HIV: a rapid review and meta-analysis

“…In the South African study, lower CD4+ T cell counts (measured during the COVID-19 episode) were associated with mortality, but this could be a result of, rather than causing, severe disease ( Table 2). There was no difference in outcomes by HIV viral load, although viral load data was incomplete and numbers with unsuppressed viral loads were small [18]…”

“…We identified 1,908 records and included 19 studies in our final qualitative analysis ( Figure 1). Seventeen studies [10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26] were peer-reviewed and two were preprints [27,28]. Quality appraisal is included in Tables 1, S2 and S3.…”

“…We identified five cohort studies (two prospective, three retrospective) comparing related mortality between PLWH and HIV-negative people, which we pooled in a metaanalysis [10,16,18,27,28]. Four of these reported all-cause mortality among people diagnosed with COVID-19 [10,16,18,28] and one reported mortality due to COVID-19 as recorded on death certificates [27]. Of the remaining fourteen studies, seven made multiple comparisons between PLWH with COVID-19 and HIV-negative cohorts, and/or the general population, .…”