Background Inequality is rife throughout South Africa. The first wave of COVID-19 may have affected people in lower socioeconomic groups worse than the affluent. The SARS-CoV-2 seroprevalence and the specificity of anti-SARS-CoV-2 antibody tests in South Africa is not known. Methods We tested 405 volunteers representing all socioeconomic strata from the workforce of a popular shopping and tourist complex in central Cape Town with the Abbott SARS-CoV-2 IgG assay. We assessed the association between antibody positivity and COVID-19 symptom status, medical history, and sociodemographic variables. We tested 137 serum samples from healthy controls collected in Cape Town prior to the COVID-19 pandemic, to confirm the specificity of the assay in the local population. Results Of the 405 volunteers tested one month after the first peak of the epidemic in Cape Town, 96(23.7%) were SARS-CoV-2 IgG positive. Of those who tested positive, 46(47.9%) reported no symptoms of COVID-19 in the previous 6 months. Seropositivity was significantly associated with living in informal housing, residing in a subdistrict with low income-per household, and having a low-earning occupation. The specificity of the assay was 98.54%(95%CI 94.82%-99.82%) in the pre-COVID controls. Conclusions There is a high background seroprevalence in Cape Town, particularly in people of lower socioeconomic status. Almost half of cases are asymptomatic, and therefore undiagnosed by local testing strategies. These results cannot be explained by low assay specificity.

Mycobacterium tuberculosis (M.tb) is likely the most successful human pathogen, capable of evading protective host immune responses and driving metabolic changes to support its own survival and growth. Ineffective innate and adaptive immune responses inhibit effective clearance of the bacteria from the human host, resulting in the progression to active TB disease. Many regulatory mechanisms exist to prevent immunopathology, however, chronic infections result in the overproduction of regulatory myeloid cells, like myeloidderived suppressor cells (MDSC), which actively suppress protective host T lymphocyte responses among other immunosuppressive mechanisms. The mechanisms of M.tb internalization by MDSC and the involvement of host-derived lipid acquisition, have not been fully elucidated. Targeted research aimed at investigating MDSC impact on phagocytic control of M.tb, would be advantageous to our collective anti-TB arsenal. In this review we propose a mechanism by which M.tb may be internalized by MDSC and survive via the manipulation of host-derived lipid sources.

Background: South Africa has a high degree of inequality between population groups. The first wave of COVID-19 may have affected people in lower socioeconomic groups worse than the affluent. The SARS-CoV-2 seroprevalence and the specificity of anti-SARS-CoV-2 antibody tests in South Africa is not known. Methods: We tested 405 volunteers representing all socioeconomic strata from the workforce of a popular shopping and tourist complex in central Cape Town with the Abbott SARS-CoV-2 IgG assay. We assessed the association between antibody positivity and COVID-19 symptom status, medical history, and sociodemographic variables. We tested 137 serum samples from healthy controls collected in Cape Town prior to the COVID-19 pandemic, to confirm the specificity of the assay in the local population.Results: Of the 405 volunteers tested one month after the first peak of the epidemic in Cape Town, 96(23.7%) were SARS-CoV-2 IgG positive. Of those who tested positive, 46(47.9%) reported no symptoms of COVID-19 in the previous 6 months. Seropositivity was significantly associated with living in informal housing, residing in a subdistrict with low income-per household, and having a low-earning occupation. The specificity of the assay was 98.54%(95%CI 94.82%-99.82%) in the pre-COVID controls.Conclusions: There is a high background seroprevalence in Cape Town, particularly in people of lower socioeconomic status. Half of cases are asymptomatic, and therefore undiagnosed by local testing strategies. These results cannot be explained by low assay specificity.

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Despite recent advances in tuberculosis (TB) drug development and availability, successful antibiotic treatment is challenged by the parallel development of antimicrobial resistance. As a result, new approaches toward improving TB treatment have been proposed in an attempt to reduce the high TB morbidity and mortality rates. Host-directed therapies (HDTs), designed to modulate host immune components, provide an alternative approach for improving treatment outcome in both non-communicable and infectious diseases. Many candidate immunotherapeutics, designed to target regulatory myeloid immune components in cancer, have so far proven to be of value as repurposed HDT in TB. Several of these studies do however lack detailed description of the mechanism or host pathway affected by TB HDT treatment. In this review, we present an argument for greater appreciation of the role of regulatory myeloid cells, such as myeloid-derived suppressor cells (MDSC), as potential targets for the development of candidate TB HDT compounds. We discuss the role of MDSC in the context of Mycobacterium tuberculosis infection and disease, focussing primarily on their specific cellular functions and highlight the impact of HDTs on MDSC frequency and function.

Conventional anti-tuberculosis (TB) therapies comprise lengthy antibiotic treatment regimens, exacerbated by multi-drug resistant and extensively drug resistant mycobacterial strains. We assessed the ability of all-trans retinoic acid (ATRA), as repurposed compound serving as host-directed therapy (HDT), to counteract the suppressive effects of myeloid-derived suppressor cells (MDSCs) obtained from active TB cases (untreated or during week one of treatment) on T-cell responsiveness. We show for the first time that MDSCs suppress non-specific T-cell activation and production of interleukin (IL)-2, IL-4, IL-13 and GM-CSF via contact-dependent mechanisms. ATRA treatment decreases MDSC frequency, but fails to mature MDSCs to non-suppressive, terminally differentiated myeloid cells and does not restore T-cell function or cytokine production in the presence of MDSCs. The impact of ATRA treatment on improved immunity, using the concentration tested here, is likely to be minimal, but further identification and development of MDSC-targeting TB host-directed therapies are warranted.

No abstract

Successful TB treatment is hampered by increasing resistance to the two most effective first-line anti-TB drugs, namely isoniazid and rifampicin, thus innovative therapies focused on host processes, termed host-directed therapies (HDTs), are promising novel approaches for increasing treatment efficacy without inducing drug resistance. We assessed the ability of Sildenafil, a type-5 phosphodiesterase inhibitor, as a repurposed compound, to serve as HDT target, by counteracting the suppressive effects of myeloid-derived suppressor cells (MDSC) obtained from active TB cases on T-cell responsiveness. We confirm that MDSC suppress non-specific T-cell activation. We also show that Sildenafil treatment fails to reverse the MDSC-mediated suppression of T-cell functions measured here, namely activation and proliferation. The impact of Sildenafil treatment on improved immunity, using the concentration tested here, is likely to be minimal, but further identification and development of MDSC-targeting TB host-directed therapies are warranted.