Robust T cell immunity in convalescent individuals with asymptomatic or mild COVID-19

SARS-CoV-2-specific memory T cells will likely prove critical for long-term immune protection against COVID-19. Here, we systematically mapped the functional and phenotypic landscape of SARS-CoV-2-specific T cell responses in unexposed individuals, exposed family members, and individuals with acute or convalescent COVID-19. Acute-phase SARS-CoV-2-specific T cells displayed a highly activated cytotoxic phenotype that correlated with various clinical markers of disease severity, whereas convalescent-phase SARS-CoV-2-specific T cells were polyfunctional and displayed a stem-like memory phenotype. Importantly, SARS-CoV-2-specific T cells were detectable in antibody-seronegative exposed family members and convalescent individuals with a history of asymptomatic and mild COVID-19. Our collective dataset shows that SARS-CoV-2 elicits broadly directed and functionally replete memory T cell responses, suggesting that natural exposure or infection may prevent recurrent episodes of severe COVID-19

Social network, social support and the rate of decline of CD4 lymphocytes in asymptomatic HIV-positive homosexual men.

AIMS: To test a stress-disease hypothesis by investigating the influence of social network and social support factors on the course over time of the CD4 lymphocytes in an HIV-positive population of gay men. METHODS: The study is a prospective cohort study of a representative population of HIV-positive gay men, undertaken at the Department of Infectious Diseases, Malmö University Hospital. This is the only clinic providing care for HIV-positive individuals in the city of Malmö in southern Sweden (population 248,000). A total of 115 HIV-positive homosexual men, who had not received an AIDS diagnosis, were invited to take part in the study. Seventy-five men (65%) accepted to be interviewed and 64 men (56%) fulfilled the inclusion criteria for the statistical analysis. RESULTS: In a multivariate analysis adjustments were made for age, level of the first CD4 count and time since first contact with the clinic. Men with high family contact frequency had a longer half-life (20.3 years) of the CD4 lymphocyte count than men with a low family contact frequency (7.4 years) (p = 0.03). Men with high social participation also had a longer half-life of CD4 lymphocyte count (14.7 years), compared with men with low social participation (6.3 years, p = 0.10). CONCLUSIONS: The findings of this study imply the importance of social support and social network factors as modifiers of the rate of decline of the CD4 lymphocyte level, which is an important prognostic marker of survival in HIV-positive homosexual men

Clinical Predictors for Death in HIV-positive and HIV-negative Tuberculosis Patients in Guinea-Bissau.

To assess easily monitored predictors for tuberculosis mortality. Risk factors for tuberculosis mortality were assessed during the 8-month treatment in 440 men and 269 women diagnosed with confirmed or presumed intrathoracic tuberculosis included prospectively in Guinea-Bissau from May 1996 to April 2001. A civil war occurred in the study area from June 1998 to May 1999. 12% were HIV-1 positive, 16% HIV-2 positive and 7% were HIV dually infected. Case fatality rates for HIV positive were higher during (35% [22/63]) and after the war (29% [27/92]) compared to before the war (17% [15/88]). The war did not have an effect on the case fatality rate in HIV negative (10% [13/135] before the war). HIV-1-infected patients had higher mortality than HIV-2 infected, mortality rate ratio (MRR) = 2.28 (95% confidence interval 1.17-4.46). Men had higher mortality than women but only among the HIV negative (MRR = 2.09 [0.95-4.59]). Hence, the negative impact of HIV infection on mortality was stronger in women (MRR = 6.51 [2.98-14.2]) than in men (MRR = 2.64 [1.67-4.17]) (test of homogeneity, p = 0.051). Anergy to tuberculin was associated with death in HIV positive (MRR = 2.77 [1.38-5.54]) but not in HIV negative (MRR = 1.14 [0.52-2.53]). Signs of immune deficiency, such as oral candida infection or leukoplakia (MRR = 4.25 [1.92-9.44]) and diarrhea (MRR = 2.15 [1.29-3.58] was associated with mortality in HIV positive. Tendencies were similar among HIV negative. HIV-positive relapse cases were at increased risk of dying (MRR = 2.42 [1.10-5.34]). Malnutrition, measured through mid-upper arm circumference (MUAC), increased the risk of death. Easily monitored predictors for mortality in tuberculosis patients include clinical signs of immune deficiency and low MUAC

Risk factors for positive tuberculin skin test in Guinea-Bissau

Background: The tuberculin skin test is used for tracing of tuberculosis transmission and identifying individuals in need of prophylactic treatment. Methods: Using a case-control study design, we recruited 220 smear-positive tuberculosis cases and 223 randomly selected healthy community controls in Bissau, Guinea-Bissau, during 1999-2000. Tuberculin skin tests were performed on family members of cases and controls (n = 1059 and n = 92 1, respectively). Induration of 10 mm or greater was considered positive. Risk factors were calculated for children (< 15 years) and adults separately in multivariate logistic regression analysis. Results: The prevalence of positive tuberculin skin test was 41% in case-contacts compared with 22% in control-contacts, resulting in a prevalence ratio of 1.48 (95% confidence interval = 1.37-1.60). Positive skin tests among case-contacts increased with age for children, as well as with proximity to a case during the night, for both children and adults. A Bacille Calmette Guerin scar increased the likelihood of having a positive tuberculin skin test for adults in case households, but not in other categories of contacts. Among control-contacts the prevalence of positive skin test was associated with older age in children, history of tuberculosis in the family, and a positive tuberculin skin test of the control person. Conclusions: Risk factors for a positive tuberculin skin test among case- and control-contacts are closely related to tuberculosis exposure. Having a BCG scar did not increase the risk of positive skin test in unexposed individuals. Tuberculin skin testing remains a useful tool for diagnosing tuberculosis infection

Validation of automated sepsis surveillance based on the Sepsis-3 clinical criteria against physician record review in a general hospital population : observational study using electronic health records data

Background: Surveillance of sepsis incidence is important for directing resources and evaluating quality-of-care interventions. The aim was to develop and validate a fully-automated Sepsis-3 based surveillance system in non-intensive care wards using electronic health record (EHR) data, and demonstrate utility by determining the burden of hospital-onset sepsis and variations between wards. Methods: A rule-based algorithm was developed using EHR data from a cohort of all adult patients admitted at an academic centre between July 2012 and December 2013. Time in intensive care units was censored. To validate algorithm performance, a stratified random sample of 1000 hospital admissions (674 with and 326 without suspected infection) was classified according to the Sepsis-3 clinical criteria (suspected infection defined as having any culture taken and at least two doses of antimicrobials administered, and an increase in Sequential Organ Failure Assessment (SOFA) score by &gt;2 points) and the likelihood of infection by physician medical record review. Results: In total 82 653 hospital admissions were included. The Sepsis-3 clinical criteria determined by physician review were met in 343 of 1000 episodes. Among them, 313 (91%) had possible, probable or definite infection. Based on this reference, the algorithm achieved sensitivity 0.887 (95% CI: 0.799 to 0.964), specificity 0.985 (95% CI: 0.978 to 0.991), positive predictive value 0.881 (95% CI: 0.833 to 0.926) and negative predictive value 0.986 (95% CI: 0.973 to 0.996). When applied to the total cohort taking into account the sampling proportions of those with and without suspected infection, the algorithm identified 8599 (10.4%) sepsis episodes. The burden of hospital-onset sepsis (&gt;48 hour after admission) and related in-hospital mortality varied between wards. Conclusions: A fully-automated Sepsis-3 based surveillance algorithm using EHR data performed well compared with physician medical record review in non-intensive care wards, and exposed variations in hospital-onset sepsis incidence between wards

Tuberculosis in Bissau: incidence and risk factors in an urban community in sub-Saharan Africa

Background Despite the long history of tuberculosis (TB) research, population-based studies from developing countries are rare. Methods In a prospective community study in Bissau, the capital of Guinea-Bissau, we assessed the impact of demographic, socioeconomic and cultural risk factors on active TB. A surveillance system in four districts of the capital identified 247 adult (greater than or equal to15 years) cases of intrathoracic TB between May 1996 and June 1998. Risk factors were evaluated comparing cases with the 25 189 adults living in the area in May 1997. Results The incidence of intrathoracic TB in the adult population was 471 per 100 000 person-years. Significant risk factors in a multivariate analysis were increasing age (P 2 adults in household), and poor quality of housing (OR = 1.66, 95% CI: 1.24, 2.22). Household type was important; adults living alone or with adults of their own sex only, had a higher risk of developing TB than households with husband and wife present, the adjusted OR being 1.76 (95% CI: 1.11, 2.78) for male households and 3.80 (95% CI: 1.69, 8.56) for female households. In a multivariate analysis excluding household type, child crowding was a protective factor, the OR being 0.68 (95% CI: 0.51, 0.90) for households with >2 children per household. Conclusions Bissau has a very high incidence of intrathoracic TB. Human immunodeficiency virus (HIV), increasing age, male sex, ethnicity, adult crowding, family structure, and poor housing conditions were independent risk factors for TB. Apart from HIV prevention, TB control programmes need to emphasize risk factors such as socioeconomic inequality, ethnic differences, crowding, and gender

High sexual risk taking and diverging trends of HIV-1 and HIV-2 in the military of Guinea Bissau

BACKGROUND: HIV and other sexually transmitted infections are a growing problem in the military personnel of Africa, and information about this problem in Guinea-Bissau is lacking. The aims of this study were to determine the prevalence and trends of the HIV epidemics in the military forces of Guinea Bissau and to explore possible risk factors for HIV infection. METHODOLOGY: Repeated cross-sectional surveys of HIV-1 and HIV-2 were conducted between 1992 and 2005, and knowledge, sexual behaviour and risk factors for HIV-1 and HIV-2 in military personnel in Guinea-Bissau were assessed. RESULTS: The seroprevalence of HIV-1, HIV-2 and HIV-1+HIV-2 dual reactivity was 1.1%, 8.4% and 0.1% in 1992-95, and in 2005 7.7%, 5.1% and 1.9%, respectively. Both the increase of HIV-1 and the decline of HIV-2 between 1992-95 and 2005 were significant when adjusted for age (p < 0.001 for both changes). Only a minority did not know how HIV transmits, but sexual risk taking was high. Several significant risk factors were found in univariate analyses for HIV-1 and HIV-2, but the only risk factor that remained significant after multivariate regression analysis was previous contact with a prostitute among HIV-1-positive subjects (single and dually reactive) (p < 0.01). CONCLUSION: The increasing trend of HIV-1 and the high risky sexual behavior illustrate the need for improvement in HIV/AIDS prevention efforts among military personnel in Guinea Bissau