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. MethodsIn 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. FindingsAmong 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...

BACKGROUND: Oral cancer is a common and lethal malignancy. Direct contact between saliva and the oral cancer lesion makes measurement of tumour markers in saliva an attractive alternative to serum testing. METHODS: We tested 19 tongue cancer patients, measuring the levels of 8 salivary markers related to oxidative stress, DNA repair, carcinogenesis, metastasis and cellular proliferation and death. RESULTS: Five markers increased in cancer patients by 39 -246%: carbonyls, lactate dehydrogenase, metalloproteinase-9 (MMP-9), Ki67 and Cyclin D1 (CycD1) (Pp0.01). Three markers decreased by 16 -29%: 8-oxoguanine DNA glycosylase, phosphorylated-Src and mammary serine protease inhibitor (Maspin) (Pp0.01). Increase in salivary carbonyls was profound (by 246%, P ¼ 0.012); alterations in CycD1 (87% increase, P ¼ 0.000006) and Maspin (29% decrease, P ¼ 0.007) were especially significant. Sensitivity values of these eight analysed markers ranged from 58% to 100%; specificity values ranged from 42% to 100%. Both values were especially high for the CycD1 and Maspin markers, 100% for each value of each marker. These were also high for carbonyls, 90% and 80%, respectively, and for MMP-9, 100% and 79%, respectively. CONCLUSIONS: The significance of each salivary alteration is discussed. As all alterations correlated with each other, they may belong to a single carcinogenetic network. Cancer-related changes in salivary tumour markers may be used as a diagnostic tool for diagnosis, prognosis and post-operative monitoring.

Oral cancer features high rates of mortality and morbidity, and is in dire need for new approaches. In the present study we analyzed 18 kDa translocator protein (TSPO) expression in oral (tongue) cancer tumors by immunohistochemistry. We also assayed TSPO binding in human tongue cancer cell lines and in the cellular fraction of saliva from tongue cancer patients, heavy cigarette smokers, and non-smoking healthy people as controls. Concurrently, TSPO protein levels, cell viability, mitochondrial membrane potential (Deltapsi(m)), and general protein levels were analyzed. TSPO expression could be significantly enhanced in oral cancer tumors, compared to unaffected adjacent tissue. We also found that five-year survival probability dropped from 65% in patients with TSPO negative tumors to 7% in patients with highly expressed TSPO (p<0.001). TSPO binding capacity was also pronounced in the human oral cancer cell lines SCC-25 and SCC-15 (3133+/-643 fmol/mg protein and 6956+/-549 fmol/mg protein, respectively). Binding decreased by 56% and 72%, in the SCC-25 and SCC-15 cell lines, respectively (p<0.05) following CS exposure in cell culture. In the cellular fraction of saliva of heavy smokers TSPO binding was lower than in non-smokers (by 53%, p<0.05). Also the cellular fraction of saliva exposed to CS in vitro showed decreased TSPO binding compared to unexposed saliva (by 30%, p<0.001). Interestingly, oral cancer patients also displayed significantly lower TSPO binding in the cellular fraction of saliva compared to healthy controls (by 40%, p<0.01). Our results suggest that low TSPO binding found in the cellular fraction of saliva may depend on genetic background as well as result from exposure to CS. We suggest that this may be related to a predisposition for occurrence of oral cancer.

Background: The interaction between COVID-19, non-communicable diseases, and chronic infectious diseases such as HIV and tuberculosis (TB) are unclear, particularly in low- and middle-income countries (LMIC) in Africa. We investigated this interaction using a nationally representative hospital surveillance system in South Africa. Methods: A national surveillance system for laboratory-confirmed COVID-19 hospital admissions (DATCOV) was established. Using DATCOV data, we describe the demographic characteristics, clinical features, and in-hospital mortality among individuals admitted to public and private hospitals with COVID-19 during 5 March to 11 August 2020. Multivariable logistic regression models were used to compare individuals who were HIV-infected and HIV-uninfected and determine the factors associated with in-hospital mortality. Findings: Hospital admissions peaked at 1,560 admissions per day, in late July. Among the 41,877 individuals admitted with laboratory-confirmed COVID-19, 7,662 (18.3%) died. Comorbidities were documented in 27,555 (65.8%) individuals, most commonly observed were hypertension (36.8%), diabetes (29.6%), obesity (19.7%), and HIV (8.7%); TB was reported in 0.7% of individuals. Increased risk of in-hospital mortality was associated with HIV and TB, as well as other described risk factors for COVID-19, such as increasing age, male sex, non-White race (Black, mixed and Indian race), chronic underlying conditions particularly hypertension, diabetes and obesity. In addition, HIV-infected individuals with immunosuppression had increased risk of mortality (adjusted odds ratio 2.2; 95% confidence interval 1.6-3.1). Among HIV-infected individuals, the prevalence of other comorbidities associated with severe COVID-19 outcomes was 39.9%. The effect of multiple comorbidities on mortality was similar in HIV-infected and -uninfected individuals. Interpretation: These data provide a better understanding of the interaction of non-communicable diseases, chronic infectious diseases like HIV and TB and COVID-19. Increasing age and presence of chronic underlying comorbidities (particularly hypertension and diabetes) are important additional factors associated with COVID-19 mortality in a middle-income African setting and are common among HIV-infected individuals. HIV- and TB-infected individuals, particularly those with additional comorbidities, would benefit from COVID-19 prevention and treatment programmes.

Juvenile idiopathic arthritis (JIA) is the most common autoimmune inflammatory disease in children; joint inflammation is the hallmark of the disease. Thirty-five children with JIA were studied, of whom 26 had active disease and 14 were receiving anti-TNF therapy (5 with Infliximab, 9 with Etanercept). Sixteen healthy controls also were studied. Saliva samples were obtained for analysis of anti-oxidant status, metalloproteinases (MMPs) and sialochemistry. The total antioxidant status was significantly higher in the saliva of all JIA patients, whether treated (P = 0.014) or not treated (P = 0.038) with anti-TNF agents. The increase in antioxidant status (TAS) in the saliva of the active patients was nearly two times higher than that of non-active patients (P = 0.01). MMP levels were significantly lower in JIA patients than in controls. MMP-9, MMP-3 and MMP-2 were lower in JIA patients without anti-TNF treatment by 36.7% (P = 0.01), 30.0% (P = 0.0001) and 10.7% (P = 0.0001), respectively. A greater reduction in MMP levels was observed in the group of patients treated with anti-TNF drugs: MMP-9, MMP-3 and MMP-2 were lower than in controls by 51.1% (P = 0.0001), 61.5% (P = 0.0001) and 55.4% (P = 0.0001), respectively. Children with JIA exhibited a significantly higher salivary antioxidant activity and significantly lower MMP levels. Anti-TNF treatment was associated with a further decrease in MMP levels in the saliva of JIA patients while an active state of JIA was associated with a further increase in the salivary antioxidant activity. Anti-TNF treatment may modulate the degradation process during the course of arthritis by inhibition of the activity of MMP .