Anti-prothrombin autoantibodies enriched after infection with SARS-CoV-2 and influenced by strength of antibody response against SARS-CoV-2 proteins

Antiphospholipid antibodies (aPL), assumed to cause antiphospholipid syndrome (APS), are notorious for their heterogeneity in targeting phospholipids and phospholipid-binding proteins. The persistent presence of Lupus anticoagulant and/or aPL against cardiolipin and/or β2-glycoprotein I have been shown to be independent risk factors for vascular thrombosis and pregnancy morbidity in APS. aPL production is thought to be triggered by–among other factors–viral infections, though infection-associated aPL have mostly been considered non-pathogenic. Recently, the potential pathogenicity of infection-associated aPL has gained momentum since an increasing number of patients infected with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has been described with coagulation abnormalities and hyperinflammation, together with the presence of aPL. Here, we present data from a multicentric, mixed-severity study including three cohorts of individuals who contracted SARS-CoV-2 as well as non-infected blood donors. We simultaneously measured 10 different criteria and non-criteria aPL (IgM and IgG) by using a line immunoassay. Further, IgG antibody response against three SARS-CoV-2 proteins was investigated using tripartite automated blood immunoassay technology. Our analyses revealed that selected non-criteria aPL were enriched concomitant to or after an infection with SARS-CoV-2. Linear mixed-effects models suggest an association of aPL with prothrombin (PT). The strength of the antibody response against SARS-CoV-2 was further influenced by SARS-CoV-2 disease severity and sex of the individuals. In conclusion, our study is the first to report an association between disease severity, anti-SARS-CoV-2 immunoreactivity, and aPL against PT in patients with SARS-CoV-2.     

HIV/AIDS in rural India: context and health care needs

Primary research on HIV/AIDS in India has predominantly focused on known risk groups such as sex workers, STI clinic attendees and long-distance truck drivers, and has largely been undertaken in urban areas. There is evidence of HIV spreading to rural areas but very little is known about the context of the infection or about issues relating to health and social impact on people living with HIV/AIDS. In-depth interviews with nineteen men and women infected with HIV who live in rural areas were used to collect experiences of testing and treatment, the social impacts of living with HIV and differential impacts on women and men. Eight focus group discussions with groups drawn from the general population in the four villages were used to provide an analysis of community level views about HIV/AIDS. While men reported contracting HIV from sex workers in the cities, women considered their husbands to be the source of their infection. Correct knowledge about HIV transmission co-existed with misconceptions. Men and women tested for HIV reported inadequate counselling and sought treatment from traditional healers as well as professionals. Owing to the general pattern of husbands being the first to contract HIV women faced a substantial burden, with few resources remaining for their own or their children's care after meeting the needs of sick husbands. Stigma and social isolation following widowhood were common, with an enforced return to the natal home. Implications for potential educational and service interventions are discussed within the context of gender and social relations.     

Maternal Tetanus Toxoid Vaccination and Neonatal Mortality in Rural North India

Objectives

Preventable neonatal mortality due to tetanus infection remains common. We aimed to examine antenatal vaccination impact in a context of continuing high neonatal mortality in rural northern India.

Methods and Findings

Using the third round of the Indian National Family Health Survey (NFHS) 2005–06, mortality of most recent singleton births was analysed in discrete-time logistic model with maternal tetanus vaccination, together with antenatal care utilisation and supplementation with iron and folic acid. 59% of mothers reported receiving antenatal care, 48% reported receiving iron and folic acid supplementation and 68% reported receiving two or more doses of tetanus toxoid (TT) vaccination. The odds of all-cause neonatal death were reduced following one or more antenatal dose of TT with odds ratios (OR) of 0.46 (95% CI 0.26 to 0.78) after one dose and 0.45 (95% CI 0.31 to 0.66) after two or more doses. Reported utilisation of antenatal care and iron-folic acid supplementation did not influence neonatal mortality. In the statistical model, 16% (95% CI 5% to 27%) of neonatal deaths could be attributed to a lack of at least two doses of TT vaccination during pregnancy, representing an estimated 78,632 neonatal deaths in absolute terms.

Conclusions

Substantial gains in newborn survival could be achieved in rural North India through increased coverage of antenatal TT vaccination. The apparent substantial protective effect of a single antenatal dose of TT requires further study. It may reflect greater population vaccination coverage and indicates that health programming should prioritise universal antenatal coverage with at least one dose.     

Inequalities in Advice Provided by Public Health Workers to Women during Antenatal Sessions in Rural India

Objectives

Studies have widely documented the socioeconomic inequalities in maternal and child health related outcomes in developing countries including India. However, there is limited research on the inequalities in advice provided by public health workers on maternal and child health during antenatal visits. This paper investigates the inequalities in advice provided by public health workers to women during antenatal visits in rural India.

Methods and Findings

The District Level Household Survey (2007–08) was used to compute rich-poor ratios and concentration indices. Binary logistic regressions were used to investigate inequalities in advice provided by public health workers. The dependent variables comprised the advice provided on seven essential components of maternal and child health care. A significant proportion of pregnant women who attended at least four ANC sessions were not advised on these components during their antenatal sessions. Only 51%–72% of the pregnant women were advised on at least one of the components. Moreover, socioeconomic inequalities in providing advice were significant and the provision of advice concentrated disproportionately among the rich. Inequalities were highest in the case of advice on family planning methods. Advice on breastfeeding was least unequal. Public health workers working in lower level health facilities were significantly less likely than their counterparts in the higher level health facilities to provide specific advice.

Conclusion

A significant proportion of women were not advised on recommended components of maternal and child health in rural India. Moreover, there were enormous socioeconomic inequalities. The findings of this study raise questions about the capacity of the public health care system in providing equitable services in India. The Government of India must focus on training and capacity building of the public health workers in communication skills so that they can deliver appropriate and recommended advice to all clients, irrespective of their socioeconomic status.     

Cyclic peptides with a distinct arginine-fork motif recognize the HIV trans-activation response RNA in vitro and in cells

RNA represents a potential target for new antiviral therapies, which are urgently needed to address public health threats such as the human immunodeficiency virus (HIV). We showed previously that the interaction between the viral Tat protein and the HIV-1 trans-activation response (TAR) RNA was blocked by TB-CP-6.9a. This cyclic peptide was derived from a TAR-binding loop that emerged during lab evolution of a TAR-binding protein (TBP) family. Here we synthesized and characterized a next-generation, cyclic-peptide library based on the TBP scaffold. We sought to identify conserved RNA-binding interactions and the influence of cyclization linkers on RNA binding and antiviral activity. A diverse group of cyclization linkers, encompassing disulfide bonds to bicyclic aromatic staples, was used to restrain the cyclic peptide geometry. Thermodynamic profiling revealed specific arginine-rich sequences with low to submicromolar affinity driven by enthalpic and entropic contributions. The best compounds exhibited no appreciable off-target binding to related molecules, such as BIV TAR and human 7SK RNAs. A specific arginine-to-lysine change in the highest affinity cyclic peptide reduced TAR binding by tenfold, suggesting that TBP-derived cyclic peptides use an arginine-fork motif to recognize the TAR major groove while differentiating the mode of binding from other TAR-targeting molecules. Finally, we showed that HIV infectivity in cell culture was reduced in the presence of cyclic peptides constrained by methylene or naphthalene-based linkers. Our findings provide insight into the molecular determinants required for HIV-1 TAR recognition and antiviral activity. These findings are broadly relevant to the development of antivirals that target RNA molecules.