Fangchinoline inhibits SARS-CoV-2 and MERS-CoV entry.

The COVID-19 pandemic caused by SARS-CoV-2, lead to mild to severe respiratory illness and resulted in 6.9 million deaths worldwide. Although vaccines are effective in preventing COVID-19, they may not be sufficient to protect immunocompromised individuals from this respiratory illness. Moreover, novel emerging variants of SARS-CoV-2 pose a risk of new COVID-19 waves. Therefore, identification of effective antivirals is critical in controlling SARS and other coronaviruses, such as MERS-CoV. We show that Fangchinoline (Fcn), a bisbenzylisoquinoline alkaloid, inhibits replication of SARS-CoV, SARS-CoV-2, and MERS-CoV in a range of in vitro assays, by blocking entry. Therapeutic use of Fcn inhibited viral loads in the lungs, and suppressed associated airway inflammation in hACE2. Tg mice and Syrian hamster infected with SARS-CoV-2. Combination of Fcn with remdesivir (RDV) or an anti-leprosy drug, Clofazimine, exhibited synergistic antiviral activity. Compared to Fcn, its synthetic derivative, MK-04-003, more effectively inhibited SARS-CoV-2 and its variants B.1.617.2 and BA.5 in mice. Taken together these data demonstrate that Fcn is a pan beta coronavirus inhibitor, which possibly can be used to combat novel emerging coronavirus diseases.

COVID-19 vaccination and leprosy-A UK hospital-based retrospective cohort study.

BACKGROUND: Individuals with leprosy are at risk of leprosy reactions, T-cell mediated immunological complications, which lead to nerve function impairment. Leprosy reactions require systemic immunosuppression which is a risk factor for severe COVID-19. Vaccination for SARS-CoV-2 infection is recommended in the UK and became widely available in 2021 with individuals at increased risk of severe disease, including the immunosuppressed, prioritised. Vaccines for SARS-CoV-2 may provoke a T cell response. The latter poses a theoretical risk of provoking an immunological response to latent Mycobacterium leprae infection leading to clinical disease or in those with clinical disease triggering a leprosy reaction. BCG vaccination is associated with the development of leprosy in a small proportion of healthy contacts of people with leprosy within twelve weeks of administration. BCG causes a Th1 immune response. METHODOLOGY/PRINCIPAL FINDINGS: We performed a retrospective cohort study to determine the SARS-CoV-2 vaccination status of individuals diagnosed with leprosy attending the Leprosy Clinic in 2021 and whether any had developed leprosy or experienced a new leprosy reaction within twelve weeks of receiving a dose of a SARS-CoV-2 vaccine. The electronic patient records were used to retrieve data. Fifty-two individuals with leprosy attended the clinic in 2021 of which five people were newly diagnosed with leprosy. Thirty-seven (71%) were male and the median age was 48.5 years old (Range 27-85 years). Eight (15.4%) individuals were taking multi-drug therapy (MDT) and eight (15.4%) had completed MDT within three years of the study. Twenty-two (41.5%) individuals were prescribed a systemic immunosuppressant drug during 2021. Ten (18.9%) individuals have one or more risk factors for severe COVID-19. The SARS-CoV-2 vaccination status of fifty (96%) were recorded of which forty-nine were vaccinated (98%). One individual had declined vaccination. One individual was diagnosed with borderline tuberculoid (BT) leprosy having developed red skin lesions with reduced sensation (which increased in size and number) and thickened peripheral nerves one week after a second dose of BNT162b2 vaccine. Another individual who had completed MDT more than three years earlier developed red plaques and tender thickened nerves consistent with a leprosy Type 1 reaction eight weeks after a single dose of BNT162b2 vaccine (having received two doses of CoronaVac vaccine three months earlier). CONCLUSIONS/SIGNIFICANCE: The development of BT leprosy and a Type 1 reaction in another individual shortly after a dose of BNT162b2 vaccine may be associated with vaccine mediated T cell responses. The benefits of vaccination to reduce the risk of severe COVID-19 outweigh these unwanted events but data from leprosy endemic countries may provide further information about potential adverse effects of augmented T cell responses in individuals with leprosy or latent M. leprae infection.

Prevalence and Predictors of COVID-19 Long-Term Symptoms: A Cohort Study from the Amazon Basin.

It remains unclear whether a previous history of tropical infectious diseases and a second SARS-COV-2 infection may influence the likelihood of later symptoms. In this prospective cohort study, individuals infected with SARS-CoV-2 were followed up by telephone shortly after diagnosis of COVID-19 and again 12 months later. Poisson regression was used to identify the predictors of the highest number of symptoms in the post-COVID-19 syndrome. A total of 1,371 patients with COVID-19, with a mean age of 39.7 ± 11.7 years and 50% female, were followed for 12 months. Reinfection was found in 32 (2.3%) participants, and 806 (58.8%) individuals reported a previous history of dengue, malaria, Zika, chikungunya, leprosy, and visceral leishmaniasis. Eight hundred seventy-seven (63.9%) participants reported late symptoms related to COVID-19. After adjusting for multiple factors, female sex, non-White race, number of acute-phase symptoms, body mass index, and reinfection were independent predictors of higher number of symptoms in post-COVID-19 syndrome. Female sex, non-White race, number of acute-phase symptoms, body mass index, and reinfection, but not previous endemic tropical diseases, were associated with long-term symptoms.

Viral co-infections in leprosy: a scoping review.

CONTEXT: The most reported viral co-infections in leprosy are human immunodeficiency virus (HIV), human T-cell lymphotropic virus (HTLV), hepatitis B virus (HBV), hepatitis C virus (HCV), and SARS-CoV-2. In co-infections, the burden of an agent can be increased or decreased by the presence of others. To address this issue, we need to fully understand their prevalence, risk factors, immunology, clinical manifestations, and treatment. The purpose of this scoping review is to describe the clinical and epidemiological characteristics of the most reported viral co-infections in leprosy to inform clinicians and guide future research. METHODS: The authors conducted a literature search of five databases for articles on each of the aforementioned co-infections published prior to October 2022. Two independent reviewers conducted the selection process and identified 53 papers meeting the study inclusion criteria. The data extraction process and evidence synthesis were conducted by one reviewer and double-checked by a second one, consistent with best practice recommendations for scoping reviews. RESULTS: For all assessed viruses, most studies reported prevalence rates in leprosy patients higher than the general population. Studies found that HTLV, HBV, and HCV chronic infections were highest in multibacillary leprosy, whereas HIV was mostly found in paucibacillary leprosy, and SARS-Cov-2 affected leprosy subtypes equally. Overall, co-infections were also associated with higher rates of leprosy reactions, except for COVID-19. Forty-six percent of the studies discussed issues related to treatment, which led to favorable outcomes for the most part. CONCLUSIONS: This review summarizes the existing literature on viral co-infections in leprosy patients, generating valuable insights and recommending areas for future research.

Moderna COVID-19 vaccine was linked to myocarditis or myopericarditis at 28 d (4.2 events/100 000 persons).

SOURCE CITATION: Husby A, Hansen JV, Fosbøl E, et al. SARS-CoV-2 vaccination and myocarditis or myopericarditis: population based cohort study. BMJ. 2021;375:e068665. 34916207.

Coronavirus disease 2019 vaccination in patients with psoriasis: A position statement from India by SIG psoriasis (IADVL Academy).

Coronavirus disease 2019 (COVID-19) pandemic has affected every sphere of life including management of psoriasis. The availability of COVID-19 vaccines has given rise to hope and at the same time some apprehensions as well. With the general population becoming eligible for vaccination, there is some confusion, on the eligibility of patients with different medical conditions and patients on immunosuppressive or immunomodulating medications for COVID-19 vaccination. Dermatologists treating psoriasis patients frequently face questions from them, whether they can undergo coronavirus disease 2019 vaccination. A PUBMED search was performed using the following strategy: 'COVID-19' AND 'Vaccine' AND 'Psoriasis'. We also performed a PUBMED search using the following strategy: 'SARS-CoV-2' AND 'Vaccine' AND 'Psoriasis'. All articles irrespective of language and publication date were included to arrive at this position statement. This position statement deals with the safety, eligibility and modifications of treatment, if needed among psoriasis patients with regards to the coronavirus disease 2019 vaccines currently available in India.

Kynurenines in the Pathogenesis of Peripheral Neuropathy During Leprosy and COVID-19.

Inflammatory disorders are associated with the activation of tryptophan (TRYP) catabolism via the kynurenine pathway (KP). Several reports have demonstrated the role of KP in the immunopathophysiology of both leprosy and coronavirus disease 19 (COVID-19). The nervous system can be affected in infections caused by both Mycobacterium leprae and SARS-CoV-2, but the mechanisms involved in the peripheral neural damage induced by these infectious agents are not fully understood. In recent years KP has received greater attention due the importance of kynurenine metabolites in infectious diseases, immune dysfunction and nervous system disorders. In this review, we discuss how modulation of the KP may aid in controlling the damage to peripheral nerves and the effects of KP activation on neural damage during leprosy or COVID-19 individually and we speculate its role during co-infection.

Effectiveness of ivermectin-based multidrug therapy in severely hypoxic, ambulatory COVID-19 patients.

Aims: Ivermectin is a safe, inexpensive and effective early COVID-19 treatment validated in 20+ random, controlled trials. Having developed combination therapies for Helicobacter pylori, the authors present a highly effective COVID-19 therapeutic combination, stemming from clinical observations. Patients & methods: In 24 COVID-19 subjects refusing hospitalization with high-risk features, hypoxia and untreated moderate to severe symptoms averaging 9 days, the authors administered this novel combination of ivermectin, doxycycline, zinc and vitamins D and C. Results & conclusions: All subjects resolved symptoms (in 11 days on average), and oxygen saturation improved in 24 h (87.4% to 93.1%; p = 0.001). There were no hospitalizations or deaths, less than (p < 0.002 or 0.05, respectively) background-matched CDC database controls. Triple combination therapy is safe and effective even when used in outpatients with moderate to severe symptoms. Clinical Trial Registration: NCT04482686 (ClinicalTrial.gov).

Chemical profiling and unraveling of anti-COVID-19 biomarkers of red sage (Lantana camara L.) cultivars using UPLC-MS/MS coupled to chemometric analysis, in vitro study and molecular docking.

ETHNOPHARMACOLOGICAL RELEVANCE: Red sage (Lantana camara L.) (Verbenaceae) is a widely spread plant that was traditionally used in Brazil, India, Kenya, Thailand, Mexico, Nigeria, Australia and Southeast Asia for treating several ailments including rheumatism and leprosy. Despite its historical role in relieving respiratory diseases, limited studies progressed to the plant's probable inhibition to respiratory viruses especially after the striking spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. AIM OF THE STUDY: This study aimed to investigate the inhibitory activity of different L. camara cultivars to SARS-CoV-2, that was not previously inspected, and clarify their mechanisms of action in the metabolomics viewpoint, and to determine the biomarkers that are related to such activity using UPLC-MS/MS coupled to in vitro-studies and chemometric analysis. MATERIALS AND METHODS: Chemical profiling of different cultivars was accomplished via UPLC-MS/MS. Principle component analysis (PCA) and orthogonal projection to latent structures (OPLS) models were built using SIMCA® (multivariate data analysis software). Cytotoxicity and COVID-19 inhibitory activity testing were done followed by TaqMan Real-time RT-PCR (Reverse transcription polymerase chain reaction) assay that aimed to study extracts' effects on RNA-dependent RNA polymerase (RdRp) and E-genes expression levels. Detected biomarkers from OPLS analysis were docked into potential targets pockets to investigate their possible interaction patterns using Schrodinger® suite. RESULTS: UPLC-MS/MS analysis of different cultivars yielded 47 metabolites, most of them are triterpenoids and flavonoids. PCA plots revealed that inter-cultivar factor has no pronounced effect on the chemical profiles of extracts except for L. camara, cultivar Drap d'or flowers and leaves extracts as well as for L. camara cv Chelsea gem leaves extract. Among the tested extracts, flowers and leaves extracts of L. camara cv Chelsea gem, flowers extracts of L. camara cv Spreading sunset and L. camara cv Drap d'or showed the highest selectivity indices scoring 12.3, 10.1, 8.6 and 7.8, respectively, indicating their relative high safety and efficacy. Leaves and flowers extracts of L. camara cv Chelsea gem, flowers extracts of L. camara cv Spreading sunset and L. camara cv Drap d'or were the most promising inhibitors to viral plaques exhibiting IC50 values of 3.18, 3.67, 4.18 and 5.01 µg/mL, respectively. This was incremented by OPLS analysis that related their promising COVID-19 inhibitory activities to the presence of twelve biomarkers. Inhibiting the expression of RdRp gene is the major mechanism behind the antiviral activity of most extracts at almost all concentration levels. Molecular docking of the active biomarkers against RdRp revealed that isoverbascoside, luteolin-7,4'-O-diglucoside, camarolic acid and lantoic acid exhibited higher docking scores of -11.378, -10.64, -6.72 and -6.07 kcal/mol, respectively, when compared to remdesivir (-5.75 kcal/mol), thus these four compounds can serve as promising anti-COVID-19 candidates. CONCLUSION: Flowers and leaves extracts of four L. camara cultivars were recognized as rich sources of phytoconstituents possessing anti-COVID-19 activity. Combination of UPLC-MS/MS and chemometrics is a promising approach to detect chemical composition differences among the cultivars and correlate them to COVID-19 inhibitory activities allowing to pinpoint possible biomarkers. Further in-vitro and in-vivo studies are required to verify their activity.

Use of healthcare services during the COVID-19 pandemic in urban Ethiopia: evidence from retrospective health facility survey data.

OBJECTIVES: In recent years, Ethiopia has made enormous strides in enhancing access to healthcare, especially, maternal and child healthcare. With the onset and spread of COVID-19, the attention of the healthcare system has pivoted to handling the disease, potentially at the cost of other healthcare needs. This paper explores whether this shift has come at the cost of non-Covid related healthcare, especially the use of maternal and child health (MCH) services. SETTING: Data covering a 24-month period are drawn from 59 health centres and 29 public hospitals located in urban Ethiopia. PRIMARY AND SECONDARY OUTCOMES MEASURES: The primary outcome measures are the use of MCH services including family planning, antenatal and postnatal care, abortion care, delivery and immunisation. The secondary outcome measures are the use of health services by adults including antiretroviral therapy (ART), tuberculosis (TB) and leprosy and dental services RESULTS: There is a sharp reduction in the use of both inpatient (20%-27%, p<0.001) and outpatient (27%-34%, p<0.001) care, particularly in Addis Ababa, which has been most acutely affected by the virus. This decline does not come at the cost of MCH services. The use of several MCH components (skilled birth attendant deliveries, immunisation, postnatal care) remains unaffected throughout the period while others (family planning services, antenatal care) experience a decline (8%-17%) in the immediate aftermath but recover soon after. CONCLUSION: Concerns about the crowding out of MCH services due to the focus on COVID-19 are unfounded. Proactive measures taken by the government and healthcare facilities to ring-fence the use of essential healthcare services have mitigated service disruptions. The results underline the resilience and agility displayed by one of the world's most resource-constrained healthcare systems. Further research on the approaches used to mitigate disruptions is needed.

Impact of SARS-CoV-2 pandemic on dermatology residents: A nationwide French study.

Background Coronavirus disease 2019 (COVID-19) has changed the practice of all health-care professionals. Determining the impact could prevent repercussions in future crisis. Objectives The objectives of the study were to assess the impact of the COVID-19 pandemic on dermatology residents' professional practice, working conditions, academic training and mental health. Methods An online questionnaire was sent to all French dermatology residents. We compared the activity of residents working in areas heavily impacted by COVID-19 to others. Logistic multivariate regressions were done, using as outcome variables the negative impact of the COVID crisis on residents' possibility to practice dermatology during the crisis, supervision, academic training and working more than 50 h/week. The last part of the questionnaire was the burnout questionnaire of Maslach. Results A total of 246 residents filled the questionnaire. Residents working in highly impacted COVID areas (odds ratio, OR 0.34 confidence interval, CI [0.18, 0.61], P ≤ 0.001), first-year postgraduate (PGY-1) residents (OR 0.46 CI [0.23, 0.91], P = 0.023) and those in private practice (OR 0.10 CI [0.01, 0.57], P = 0.032) were significantly less able to maintain dermatology activities. Worse supervision was significantly more frequent with non-PGY-1 residents (OR 3.24 CI [1.65, 6.65], P < 0.001). One hundred and eighty one residents claimed the pandemic to have a negative effect on their dermatology curriculum with no difference according to their regions' affection by COVID-19. This was mostly attributed to the cancelation of courses and congresses. PGY-1 residents (OR 2.09 CI [1.09, 4.04], P = 0.029) and residents in highly affected areas (OR 1.79 CI [1.01, 3.18], P = 0.049) were more at risk of working above the maximal legal working time. None of the residents was free of burnout symptoms. Conclusion Dermatology residents have been highly affected by COVID-19. It might be important to have a more integrated healthcare system to fight times of crisis with the least repercussions on residents.

Tuberculosis vaccine BCG: the magical effect of the old vaccine in the fight against the COVID-19 pandemic.

Bacillus Calmette-Guérin (BCG) is a live attenuated M. bovis vaccine that was developed about 100 years ago by Albert Calmette and Camille Guérin. Many countries have been using the vaccine for decades against tuberculosis (TB). The World Health Organization (WHO) recommends a single dose of BCG for infants in TB endemic as well as leprosy high risk countries, and globally almost 130 million infants are vaccinated yearly. The role of BCG is well known in reducing neonatal and childhood death rates. Epidemiological and retrospective cross-sectional studies demonstrated that the BCG vaccination protects the children against respiratory tract infections and lowers the risk of malaria in children. In addition, BCG enhances IFN-γ and IL-10 levels, thus providing immunity against respiratory tract infection even in elderly people. The BCG is also known to provide nonspecific innate immunity against viruses and parasites, through an innate immune mechanism termed 'trained immunity' and is defined as the immunological recall of the innate immune system by epigenetic reprogramming. Based on these studies it is suggested that the BCG has the potential to act as a protective agent against COVID-19. Further proven safety records of BCG in humans, its adjuvant activity and low-cost manufacturing make it an attractive option to stop the pandemic and reduce the COVID-19 related mortality. In this review we discuss the heterologous effects of BCG, induction of trained immunity and its implication in development of a potential vaccine against COVID-19 pandemic.

Tuberculosis treatment within differentiated service delivery models in global HIV/TB programming.

INTRODUCTION: Providing more convenient and patient-centred options for service delivery is a priority within global HIV programmes. These efforts improve patient satisfaction and retention and free up time for providers to focus on new HIV diagnoses or severe illness. Recently, the coronavirus disease 2019 (COVID-19) pandemic precipitated expanded eligibility criteria for these differentiated service delivery (DSD) models to decongest clinics and protect patients and healthcare workers. This has resulted in dramatic scale-up of DSD for antiretroviral therapy, cotrimoxazole and tuberculosis (TB) preventive treatment. While TB treatment among people living with HIV (PLHIV) has traditionally involved frequent, facility-based management, TB treatment can also be adapted within DSD models. Such adaptations could include electronic tools to ensure appropriate clinical management, treatment support, adherence counselling and adverse event (AE) monitoring. In this commentary, we outline considerations for DSD of TB treatment among PLHIV, building on best practices from global DSD model implementation for HIV service delivery. DISCUSSION: In operationalizing TB treatment in DSD models, we consider the following: what activity is being done, when or how often it takes place, where it takes place, by whom and for whom. We discuss considerations for various programme elements including TB screening and diagnosis; medication dispensing; patient education, counselling and support; clinical management and monitoring; and reporting and recording. General approaches include multi-month dispensing for TB medications during intensive and continuation phases of treatment and standardized virtual adherence and AE monitoring. Lastly, we provide operational examples of TB treatment delivery through DSD models, including a conceptual model and an early implementation experience from Zambia. CONCLUSIONS: COVID-19 has catalysed the rapid expansion of differentiated patient-centred service delivery for PLHIV. Expanding DSD models to include TB treatment can capitalize on existing platforms, while providing high-quality, routine treatment, follow-up and patient education and empowerment.

Social Distance in COVID-19: Drawing the line between protective behavior and stigma manifestation.

Social stigma has long been defined by Ervin Goffman as an attribute that it is deeply discrediting and reduces the individual who bears it from a whole and usual person to a tarnished one, unfit to be included into the mainstream society.1 As stigma spans time and space and has been documented in other social species such as ants and chimpanzees, one might argue for its adaptive potential. Neuberg and colleagues2 have suggested that humans generate stigmas against threats to effective group functioning, with a notable case being infectious diseases. A similar explanation has been put forward by other researchers who consider stigma to have evolved from disease-avoidance mechanisms.3 Hence, it is not surprising that tuberculosis, HIV and leprosy have been surrounded by stigma and discrimination.4,5 More recently, people who had survived the 2013-2016 Ebola outbreak tackled social exclusion and unemployment after returning to their neighborhoods.6 Nowadays, the global community faces an unprecedented challenge of grappling with the COVID-19 pandemic. From the very outset, social distance measures were introduced in order to contain the spread of the virus, ranging from maintaining 1.5 meters physical distance to strict lockdowns. However, this may easily escalate into stigmatizing and discriminatory behaviours (desired social distance is a proxy of discrimination) against people who have suffered from COVID-19, their relatives and their caregivers, with the United Nations stating that "fear, rumours and stigma" are the key challenges surrounding COVID-19.7 Apart from the psychological distress experienced by the stigmatized individuals, due to anticipated stigma people might start concealing their illness, avoid or delay seeking medical advice or testing until they are seriously ill and be reluctant to collaborate with authorities on tracing contacts. Therefore, timely identifying stigma and addressing it is an integral part of an effective health response to the ongoing pandemic. In spite of its importance, research on COVID-19 related stigma is scarce. From the perspective of the stigmatized individuals, a study in China8 demonstrated that COVID-19 survivors faced heightened levels of overall stigma, social rejection, financial insecurity, internalized shame and social isolation, compared to healthy controls. From the perspective of the general population, a study in US9 substantiated low levels of anticipated stigma and stereotype endorsement; however, respondents who anticipated greater stigma were less likely to seek a COVID-19 test. It is therefore clear that the international literature is still on its infancy with respect to COVID-19 related stigma. In this context, in the First Department of Psychiatry, University of Athens, we conducted a survey on public attitudes to COVID-19 and to mental disorders. The study would inform the design and implementation of anti-stigma initiatives, funded by the Regional Governor of Attica. As physical distancing and social distancing are interwoven, with some researchers and practitioners using the terms interchangeably, and social distancing is also a protective public health measure against COVID-19, we enquired about attitudes and desired social distance from people who had recovered from COVID-19. Nonetheless, it merits noting that evidence from other diseases indicates that stigma may persist even after recovery.10 Moreover, rather than describing public attitudes overall, we were more interested in investigating where COVID-19 related stigma stands as compared to the most stigmatizing health condition to date, i.e., severe mental illness.11 Interestingly enough, which elements of severe mental illness render it the most stigmatized as compared to other conditions is still speculative: is it the fear of madness? the severity and the type of symptoms? the purported incurability or its chronicity? In our study, evidence from a convenience sample of 370 residents of Attica indicates that the general population holds more negative attitudes towards people who have recovered from COVID-19 than towards people with mental disorders. Nonetheless, respondents reported lower levels of desired social distance from recovered COVID-19 cases as compared to mental illness cases in social interactions of graded intimacy; however, the difference between the two groups was found to decrease as the level of intimacy decreased as well. In other words, desired social distance from COVID-19 cases is more easily discernible in transient social encounters, like talking to a stranger. It is therefore clear that social distance is still a public health protective measure rather than a stigma manifestation. For social encounters of greater intimacy, usually a sign of discriminatory behaviours, having recovered from COVID-19 is not a deterrent to interaction. Findings can be explained by the acute (non-chronic) nature of the disease, both in terms of symptoms as well as the 10-day period since symptom onset for being contagious. Nonetheless, with emerging evidence substantiating the notion of long COVID-19, defined as the persistence of symptoms for 3 weeks after infection,12 this might quickly change. Moreover, with many public health protective measures available, such as the use of mask, diagnostic testing and vaccination, people who become infected are more likely to be blamed for contracting the disease and thus deemed responsible for this, in line with the Attribution Theory.13 Specifically, overarching evidence from stigma research in many diseases/conditions indicates that when an illness or a social condition, such as economic disadvantage, is attributed to internal causes, as compared to external, lay people are more likely to hold stigmatizing attitudes.14-16 Therefore, as attitudes towards COVID-19 are worse compared to those towards people with mental illness, if tailored anti-stigma action is not undertaken, it is only a matter of time for prejudices to evolve into discriminatory behaviours, with devastating consequences on both the individuals and the course of the pandemic. Concomitantly, as severe mental illness is neither life threatening nor contagious, but COVID-19 is, it is interesting to explore how stigma is related to evolutionary mechanisms favouring adaptability and survival as well as which elements are the drivers of stigma development and establishment. Therefore, comparing and contrasting the stigma surrounding these conditions may shed light on the underpinnings of social stigma and facilitate effective interventions to reduce it and eventually eliminate it.

Antigenic sites in SARS-CoV-2 spike RBD show molecular similarity with pathogenic antigenic determinants and harbors peptides for vaccine development.

The spike protein of coronavirus is key target for drug development and other pharmacological interventions. In current study, we performed an integrative approach to predict antigenic sites in SARS-CoV-2 spike receptor binding domain and found nine potential antigenic sites. The predicted antigenic sites were then assessed for possible molecular similarity with other known antigens in different organisms. Out of nine sites, seven sites showed molecular similarity with 54 antigenic determinants found in twelve pathogenic bacterial species (Mycobacterium tuberculosis, Mycobacterium leprae, Bacillus anthracis, Borrelia burgdorferi, Clostridium perfringens, Clostridium tetani, Helicobacter Pylori, Listeria monocytogenes, Staphylococcus aureus, Streptococcus pyogenes, Vibrio cholera and Yersinia pestis), two malarial parasites (Plasmodium falciparum and Plasmodium knowlesi) and influenza virus A. Most of the bacterial antigens that displayed molecular similarity with antigenic sites in SARS-CoV-2 RBD (receptor binding domain) were toxins and virulent factors. Antigens from Mycobacterium that showed similarity were mainly involved in modulating host cell immune response and ensuring persistence and survival of pathogen in host cells. Presence of a large number of antigenic determinants, similar to those in highly pathogenic microorganisms, not merely accounts for complex etiology of the disease but also provides an explanation for observed pathophysiological complications, such as deregulated immune response, unleashed or dysregulated cytokine secretion (cytokine storm), multiple organ failure etc., that are more evident in aged and immune-compromised patients. Over-representation of antigenic determinants from Plasmodium and Mycobacterium in all antigenic sites suggests that anti-malarial and anti-TB drugs can prove to be clinical beneficial for COVID-19 treatment. Besides this, anti-leprosy, anti-lyme, anti-plague, anti-anthrax drugs/vaccine etc. are also expected to be beneficial in COVID-19 treatment. Moreover, individuals previously immunized/vaccinated or had previous history of malaria, tuberculosis or other disease caused by fifteen microorganisms are expected to display a considerable degree of resistance against SARS-CoV-2 infection. Out of the seven antigenic sites predicted in SARS-CoV-2, a part of two antigenic sites were also predicted as potent T-cell epitopes (KVGGNYNYL444-452 and SVLYNSASF366-374) against MHC class I and three (KRISNCVADYSVLYN356-370, DLCFTNVYADSFVI389-402, and YRVVVLSFELLHA508-520) against MHC class II. All epitopes possessed significantly lower predicted IC50 value which is a prerequisite for a preferred vaccine candidate for COVID-19.

The effect of BCG revaccination on all-cause mortality beyond infancy: 30-year follow-up of a population-based, double-blind, randomised placebo-controlled trial in Malawi.

BACKGROUND: Trials of BCG vaccination to prevent or reduce severity of COVID-19 are taking place in adults, some of whom have been previously vaccinated, but evidence of the beneficial, non-specific effects of BCG come largely from data on mortality in infants and young children, and from in-vitro and animal studies, after a first BCG vaccination. We assess all-cause mortality following a large BCG revaccination trial in Malawi. METHODS: The Karonga Prevention trial was a population-based, double-blind, randomised controlled in Karonga District, northern Malawi, that enrolled participants between January, 1986, and November, 1989. The trial compared BCG (Glaxo-strain) revaccination versus placebo to prevent tuberculosis and leprosy. 46 889 individuals aged 3 months to 75 years were randomly assigned to receive BCG revaccination (n=23 528) or placebo (n=23 361). Here we report mortality since vaccination as recorded during active follow-up in northern areas of the district in 1991-94, and in a demographic surveillance follow-up in the southern area in 2002-18. 7389 individuals who received BCG (n=3746) or placebo (n=3643) lived in the northern follow-up areas, and 5616 individuals who received BCG (n=2798) or placebo (n=2818) lived in the southern area. Year of death or leaving the area were recorded for those not found. We used survival analysis to estimate all-cause mortality. FINDINGS: Follow-up information was available for 3709 (99·0%) BCG recipients and 3612 (99·1%) placebo recipients in the northern areas, and 2449 (87·5%) BCG recipients and 2413 (85·6%) placebo recipients in the southern area. There was no difference in mortality between the BCG and placebo groups in either area, overall or by age group or sex. In the northern area, there were 129 deaths per 19 694 person-years at risk in the BCG group (6·6 deaths per 1000 person-years at risk [95% CI 5·5-7·8]) versus 133 deaths per 19 111 person-years at risk in the placebo group (7·0 deaths per 1000 person-years at risk [95% CI 5·9-8·2]; HR 0·94 [95% CI 0·74-1·20]; p=0·62). In the southern area, there were 241 deaths per 38 399 person-years at risk in the BCG group (6·3 deaths per 1000 person-years at risk [95% CI 5·5-7·1]) versus 230 deaths per 38 676 person-years at risk in the placebo group (5·9 deaths per 1000 person-years at risk [95% CI 5·2-6·8]; HR 1·06 [95% CI 0·88-1·27]; p=0·54). INTERPRETATION: We found little evidence of any beneficial effect of BCG revaccination on all-cause mortality. The high proportion of deaths attributable to non-infectious causes beyond infancy, and the long time interval since BCG for most deaths, might obscure any benefits. FUNDING: British Leprosy Relief Association (LEPRA); Wellcome Trust.