Anti SARS-CoV-2 Antibody Kinetics up to 6 months of follow-up: Result from a Nation-wide Population-based, Age Stratified Sero-Epidemiological Prospective Cohort Study in India (preprint)

Repeated serological testing tells about the change in the overall infection in a community. This study aimed to evaluate changes in antibody prevalence and kinetics in a closed cohort over six months in different sub-populations in India. The study included 10,000 participants from rural and urban areas in five states and measured SARS-CoV-2 antibodies in serum in three follow-up rounds. The overall seroprevalence increased from 73.9% in round one to 90.7% in round two and 92.9% in round three. Among seropositive rural participants in round one, 98.2% remained positive in round two, and this percentage remained stable in urban and tribal areas in round three. The results showed high antibody prevalence that increased over time and was not different based on area, age group, or sex. Vaccinated individuals had higher antibody prevalence, and nearly all participants had antibody positivity for up to six months.

Test concordance of three serological assays for detection of anti-SARS-CoV-2 antibody: Result from a population-based sero-epidemiological study in Delhi (preprint)

Background Several methodological tests are available to detect SARS-CoV-2 antibody. Tests are mostly used in the aid of diagnosis or for serological assessment. No tests are fully confirmatory and have variable level of diagnostic ability. We aimed at assessing agreement with three serological tests: quantitative anti receptor binding domain ELISA (Q-RBD), qualitative ELISA (WANTAI SARS-CoV-2 Ab) and qualitative chemiluminiscence assays (CLIA).Methods This study was a part of a large population based sero-epidemiological cohort study. Participants aged 1 year or older were included from 25 randomly selected clusters each in Delhi urban (urban resettlement colony of South Delhi district) and Delhi rural (villages in Faridabad district, Haryana). Three type of tests were applied to all the baseline blood samples. Result of the three tests were evaluated by estimating the total agreement and kappa value.Results Total 3491 blood samples collected from March to September, 2021, out of which 1700 (48.7%) from urban and 1791 (51.3%) from rural. Overall 44.1% of participants were male. The proportion of sero-positivity were 78.1%, 74.1% and 31.8% by Wantai, QRBD and CLIA tests respectively. The total agreement between Wantai and QRBD was 94.2%, 53.1% between Wantai and CLIA, and 56.6% between QRBD and CLIA. The kappa value between these three tests were 0.84 (95% CI: 0.80–0.87), 0.22 (95% CI: 0.19–0.24) and 0.26 (95% CI: 0.23–0.28).Conclusions There was strong concordance between Wantai and QRBD test. Agreement between CLIA with other two tests was low. Wantai and QRBD may be used interchangeably.

Antibody response to SARS-CoV2 among COVID-19 confirmed cases, and correlates with neutralizing assay in a subgroup of patients in Delhi National Capital Region, India (preprint)

Background: Plaque reduction neutralization test (PRNT) is the gold standard to detect neutralizing capacity of the serum antibodies. Neutralizing antibody confers protection against further infection. The present study was done with the objective to measure the antibody level against SARS-CoV2 among laboratory confirmed COVID-19 cases and to evaluate whether the presence of anti-SARS-CoV2 antibodies indicate virus neutralizing capacity. Methods: One hundred COVID-19 confirmed cases were recruited. Sociodemographic details and history of COVID-19 vaccination, contact with positive COVID-19 cases, and symptoms were ascertained using a self-developed semi-structured interview schedule. Serum samples of the participants were collected within three months from date of the positive report of COVID-19. The presence of anti-SARS-CoV-2 antibodies (IgA, IgG and IgM antibodies), receptor binding domain antibodies (anti-RBD), and neutralizing antibodies were measured. Findings: Almost all participants had Anti-SARS-CoV2 antibodies (IgA, IgG and IgM) (99%) and Anti-RBD IgG antibodies (97%). However, only 69% had neutralizing antibodies against SARS-CoV2. Anti-RBD antibody levels were significantly higher among participants having neutralizing antibodies compared to those who did not. Interpretation: The present study highlights that presence of antibodies against SARS-CoV2, or presence of anti-RBD antibody does not necessarily imply presence of neutralizing antibodies. Funding: World Health Organisation

Neurological toll of COVID-19.

The first case of coronavirus illness was discovered in Wuhan, China, in January 2020 and quickly spread worldwide within the next couple of months. The condition was initially only linked with respiratory disorders. After the evolution of various variants of the SARS-CoV-2, the critical impact of the virus spread to multiple organs and soon, neurological disorder manifestations started to appear in the infected patients. The review is focused on the manifestation of various neurological disorders linked with both the central nervous system and peripheral nervous system. Disorders such as cytokine release syndrome, encephalitis, acute stroke, and Bell's palsy are given specific attention and psychological manifestations are also investigated. For a clear conclusion, cognitive impairment, drug addiction disorders, mood and anxiety disorders, and post-traumatic stress disorder are all fully examined. The association of the SARS-CoV-2 with neurological disorders and pathway is yet to be clear. For better understanding, the explanation of the possible mechanism of viral infection influencing the nervous system is also attempted in the review. While several vaccines and drugs are already involved in treating the SARS-CoV-2 condition, the disease is still considered fatal and more likely to leave permanent neurological damage, which leads to an essential requirement for more research to explore the neurological toll of the COVID-19 disease.

Maternal and Neonatal Tetanus Elimination: Where are We Now?

The maternal and neonatal tetanus elimination (MNTE) program was envisaged by the World Health Organization to overcome the mortality and morbidity caused by maternal and neonatal tetanus (MNT). Although preventable by simple cost-effective practices like universal immunization, clean delivery practices, and healthy umbilical cord care, as of date MNT is still prevalent in 12 developing countries of Asia and Africa. Definitive approaches need to be microplanned by these countries to successfully accomplish the three stages of MNTE, ie, achieving, validating, and sustaining. Once a country achieves MNTE, this status is required to be validated and sustained according to the high-risk and low-risk categorization of the districts. The three-pronged strategies for achieving and sustaining MNTE include (a) rigorous immunization of women of reproductive age with tetanus toxoid-containing vaccines, (b) strengthening of clean delivery services for pregnant women, and (c) effective surveillance for MNT. Although the deadlines for achieving MNTE globally have been missed many times, yet there has been a significant progress to date as evident by 80% reduction in countries requiring validation for MNTE (59 countries in 1999 to 12 countries in 2020). Huge strides have been made in the overall coverage of two doses of tetanus toxoid (13.79% to 65.27%), neonates being protected at birth (12% to 88%), global coverage of third-dose DPT (more than doubled), and reduction of 88% estimated deaths due to NT in the last four decades. Identification of the most vulnerable populations, systematic planning at all levels of health care, involvement of local community support, tackling the implementation gap, strong political will, good financial support, and continued robust surveillance will go a long way in achieving MNTE.

Discovery and Mechanism of SARS-CoV-2 Main Protease Inhibitors.

The emergence of a new coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), presents an urgent public health crisis. Without available targeted therapies, treatment options remain limited for COVID-19 patients. Using medicinal chemistry and rational drug design strategies, we identify a 2-phenyl-1,2-benzoselenazol-3-one class of compounds targeting the SARS-CoV-2 main protease (Mpro). FRET-based screening against recombinant SARS-CoV-2 Mpro identified six compounds that inhibit proteolysis with nanomolar IC50 values. Preincubation dilution experiments and molecular docking determined that the inhibition of SARS-CoV-2 Mpro can occur by either covalent or noncovalent mechanisms, and lead E04 was determined to inhibit Mpro competitively. Lead E24 inhibited viral replication with a nanomolar EC50 value (844 nM) in SARS-CoV-2-infected Vero E6 cells and was further confirmed to impair SARS-CoV-2 replication in human lung epithelial cells and human-induced pluripotent stem cell-derived 3D lung organoids. Altogether, these studies provide a structural framework and mechanism of Mpro inhibition that should facilitate the design of future COVID-19 treatments.

A Comprehensive Overview on the Production of Vaccines in Plant-Based Expression Systems and the Scope of Plant Biotechnology to Combat against SARS-CoV-2 Virus Pandemics.

Many pathogenic viral pandemics have caused threats to global health; the COVID-19 pandemic is the latest. Its transmission is growing exponentially all around the globe, putting constraints on the health system worldwide. A novel coronavirus, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), causes this pandemic. Many candidate vaccines are available at this time for COVID-19, and there is a massive international race underway to procure as many vaccines as possible for each country. However, due to heavy global demand, there are strains in global vaccine production. The use of a plant biotechnology-based expression system for vaccine production also represents one part of this international effort, which is to develop plant-based heterologous expression systems, virus-like particles (VLPs)-vaccines, antiviral drugs, and a rapid supply of antigen-antibodies for detecting kits and plant origin bioactive compounds that boost the immunity and provide tolerance to fight against the virus infection. This review will look at the plant biotechnology platform that can provide the best fight against this global pandemic.

Revealing Tissue-Specific SARS-CoV-2 Infection and Host Responses using Human Stem Cell-Derived Lung and Cerebral Organoids.

COVID-19 is a transmissible respiratory disease caused by a novel coronavirus, SARS-CoV-2, and has become a global health emergency. There is an urgent need for robust and practical in vitro model systems to investigate viral pathogenesis. Here, we generated human induced pluripotent stem cell (iPSC)-derived lung organoids (LORGs), cerebral organoids (CORGs), neural progenitor cells (NPCs), neurons, and astrocytes. LORGs containing epithelial cells, alveolar types 1 and 2, highly express ACE2 and TMPRSS2 and are permissive to SARS-CoV-2 infection. SARS-CoV-2 infection induces interferons, cytokines, and chemokines and activates critical inflammasome pathway genes. Spike protein inhibitor, EK1 peptide, and TMPRSS2 inhibitors (camostat/nafamostat) block viral entry in LORGs. Conversely, CORGs, NPCs, astrocytes, and neurons express low levels of ACE2 and TMPRSS2 and correspondingly are not highly permissive to SARS-CoV-2 infection. Infection in neuronal cells activates TLR3/7, OAS2, complement system, and apoptotic genes. These findings will aid in understanding COVID-19 pathogenesis and facilitate drug discovery.

Agricultural automation: A strategic dilemma of a rich Indian farmer

Mr. Jang Bahadur Singh Bagga, a wealthy farmer based in one of the most prosperous states in India, Punjab, was deep in thought pondering over a problem that was occupying his mind. In the face of the havoc caused by COVID-19, Prime Minister Narendra Modi on 24 March 2020 announced a 3-week unprecedented nation-wide lockdown with just 4-hour notice period. Though Bagga realized that the lockdown was a necessary step to arrest the pandemic, nonetheless he was extremely worried because it was nearly time for him to harvest his wheat crop. His worry turned to panic when the lockdown was extended further for another 15?days, and then another 2 weeks, and gradually to over 2 months. While some of the restrictions had been lifted now, the problem was far from solved as most of the migrant labor that worked in the fields had returned to their villages with no signs of them returning to work soon. With crops standing in his fields, waiting to be harvested, Bagga was faced with a dilemma?should he invest in modern machinery for his agricultural activity or stick to manual labor, as was the common practice in the country? The case is suitable to teach MBA students MS Excel, information technology concepts, and business economics. It is also well-suited for executive education. The case is in the form of a story, enabling course participants to engage in experiential learning through decision-making. The learners are also provided details of the actual process of farming in India as also the necessary data to support decision-making.

Multi-Organ Involvement in COVID-19: Beyond Pulmonary Manifestations.

Coronavirus Disease 19 (COVID-19), due to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has become an on-going global health emergency affecting over 94 million cases with more than 2 million deaths globally. Primarily identified as atypical pneumonia, it has developed into severe acute respiratory distress syndrome (ARDS), a multi-organ dysfunction with associated fatality. Ever since its emergence, COVID-19 with its plethora of clinical presentations has signalled its dynamic nature and versatility of the disease process. Being a disease with droplet transmission has now assumed the proportion of a suspected airborne nature which, once proved, poses a Herculean task to control. Because of the wide distribution of the human angiotensin-converting enzyme-2 (hACE2) receptors, known for its transmission, we envisage its multiorgan spread and extensive disease distribution. Thus, an extensive review of the extrapulmonary organotropism of SARS-CoV-2 with organ-specific pathophysiology and associated manifestations like dermatological complications, myocardial dysfunction, gastrointestinal symptoms, neurologic illnesses, hepatic and renal injury is needed urgently. The plausible mechanism of site-specific viral invasion is also discussed to give a comprehensive understanding of disease complexity, to help us to focus on research priorities and therapeutic strategies to counter the disease progression. A note on the latest advancements in vaccine research will enlighten the scientific world and equip it for better preparedness.

Immunization During the COVID-19 Pandemic: Recommendations From Indian Academy of Pediatrics Advisory Committee on Vaccines and Immunization Practices.

During the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, immunization practices of all age groups, especially routine childhood vaccines, have been interrupted. Immunization is considered an essential health activity, which needs to be resumed as early as possible. This pandemic has created several unique issues related to routine immunization of individual children at clinics, which needs to be addressed. In this communication, the Advisory Committee on Vaccines and Immunization Practices (ACVIP) of Indian Academy of Pediatrics addresses the common questions and issues related to SARS-CoV-2 and routine immunization services. This also includes the recommendations for routine immunization of SARS-CoV-2 suspect and positive children, and for the logistics to be followed for immunization services.

Immunization During the COVID-19 Pandemic: Recommendations from Indian Academy of Pediatrics Advisory Committee on Vaccines and Immunization.

During the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, immunization practices of all age groups, especially routine childhood vaccines, have been interrupted. Immunization is considered an essential health activity, which needs to be resumed as early as possible. This pandemic has created several unique issues related to routine immunization of individual children at clinics, which needs to be addressed. In this communication, the Advisory Committee on Vaccines and Immunization Practices (ACVIP) of Indian Academy of Pediatrics addresses the common questions and issues related to SARS-CoV-2 and routine immunization services. This also includes the recommendations for routine immunization of SARS-CoV-2 suspect and positive children, and for the logistics to be followed for immunization services.

Cholesterol 25-Hydroxylase inhibits SARS-CoV-2 and other coronaviruses by depleting membrane cholesterol.

Coronavirus disease 2019 (COVID-19) is caused by SARS-CoV-2 and has spread across the globe. SARS-CoV-2 is a highly infectious virus with no vaccine or antiviral therapy available to control the pandemic; therefore, it is crucial to understand the mechanisms of viral pathogenesis and the host immune responses to SARS-CoV-2. SARS-CoV-2 is a new member of the betacoronavirus genus like other closely related viruses including SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV). Both SARS-CoV and MERS-CoV have caused serious outbreaks and epidemics in the past eighteen years. Here, we report that one of the interferon-stimulated genes (ISGs), cholesterol 25-hydroxylase (CH25H), is induced by SARS-CoV-2 infection in vitro and in COVID-19-infected patients. CH25H converts cholesterol to 25-hydrocholesterol (25HC) and 25HC shows broad anti-coronavirus activity by blocking membrane fusion. Furthermore, 25HC inhibits USA-WA1/2020 SARS-CoV-2 infection in lung epithelial cells and viral entry in human lung organoids. Mechanistically, 25HC inhibits viral membrane fusion by activating the ER-localized acyl-CoA:cholesterol acyltransferase (ACAT) which leads to the depletion of accessible cholesterol from the plasma membrane. Altogether, our results shed light on a potentially broad antiviral mechanism by 25HC through depleting accessible cholesterol on the plasma membrane to suppress virus-cell fusion. Since 25HC is a natural product with no known toxicity at effective concentrations, it provides a potential therapeutic candidate for COVID-19 and emerging viral diseases in the future.

Clinical Features and Outcome of SARS-CoV-2 Infection in Neonates: A Systematic Review.

OBJECTIVE: The objective of this study is to systematically synthesize the currently available literature on various modes of transmission (congenital, intrapartum, and postpartum), clinical features and outcomes of SARS-CoV-2 infection in neonates. METHODS: We conducted a comprehensive literature search using PubMed, EMBASE, and Web of Science until 9 June 2020. A combination of keywords and MeSH terms, such as COVID-19, coronavirus, SARS-CoV-2, 2019-nCoV, severe acute respiratory syndrome coronavirus 2, neonates, newborn, infant, pregnancy, obstetrics, vertical transmission, maternal-foetal transmission and intrauterine transmission, were used in the search strategy. We included studies reporting neonatal outcomes of SARS-CoV-2 proven pregnancies or neonatal cases diagnosed with SARS-CoV-2 infection. RESULTS: Eighty-six publications (45 case series and 41 case reports) were included in this review. Forty-five case series reported 1992 pregnant women, of which 1125 (56.5%) gave birth to 1141 neonates. A total of 281 (25%) neonates were preterm, and caesarean section (66%) was the preferred mode of delivery. Forty-one case reports describe 43 mother-baby dyads of which 16 were preterm, 9 were low birth weight and 27 were born by caesarean section. Overall, 58 neonates were reported with SARS-CoV-2 infection (4 had a congenital infection), of which 29 (50%) were symptomatic (23 required ICU) with respiratory symptoms being the predominant manifestation (70%). No mortality was reported in SARS-CoV-2-positive neonates. CONCLUSION: The limited low-quality evidence suggests that the risk of SARS-CoV-2 infections in neonates is extremely low. Unlike children, most COVID-positive neonates were symptomatic and required intensive care. Postpartum acquisition was the commonest mode of infection in neonates, although a few cases of congenital infection have also been reported.

Risk stratification as a tool to rationalize quarantine among health care workers exposed to COVID-19 cases - Evidence from a tertiary healthcare centre in India (preprint)

BackgroundQuarantine of healthcare workers (HCWs) exposed to COVID -19 confirmed cases is a well-known strategy for limiting the transmission of infection. However, there is need of evidence-based guidelines for quarantine of HCWs in COVID -19. MethodsWe describe our experience of contact tracing and risk stratification of 3853 HCWs who were exposed to confirmed COVID-19 cases in a tertiary health care institution in India. We developed an algorithm, on the basis of risk stratification, to rationalize quarantine among HCWs. Risk stratification was based on the duration of exposure, distance from the patient, and appropriateness of personal protection equipment (PPE) usage. Only high-risk contacts were quarantined for 14 days. They underwent testing for COVID-19 after five days of exposure, while low-risk contacts continued their work with adherence to physical distancing, hand hygiene, and appropriate use of PPE. The low-risk contacts were encouraged to monitor for symptoms and report for COVID-19 screening if fever, cough, or shortness of breath occurred. We followed up all contacts for 14 days from the last exposure and observed for symptoms of COVID-19 and test positivity. Results and interpretationOut of total 3853 contacts, 560 (14.5%) were categorized as high-risk contacts, and 40 of them were detected positive for COVID-19, with a test positivity rate of 7.1% (95% CI = 5.2 - 9.6). Overall, 118 (3.1%) of all contacts tested positive. Our strategy prevented 3215 HCWs from being quarantined and saved 45,010 person-days of health workforce until June 8, 2020, in the institution. We conclude that exposure-based risk stratification and quarantine of HCWs is a viable strategy to prevent unnecessary quarantine, in a healthcare institution. SummaryO_ST_ABSWhat is already known about this subject?C_ST_ABSO_LIQuarantine of HCWs is a well-known strategy for community and HCWs to prevent the transmission of COVID-19. C_LIO_LIThough success stories of prompt contact tracing and quarantine to control COVID-19 are available from countries like South Korea, Singapore, and Hong Kong, there is a scarcity of evidence that could guide targeted quarantine of HCWs exposed to COVID -19 in India. C_LI What does this study add?O_LIOnly 14.5% HCWs exposed to COVID-19 cases were stratified "high risk" contacts, and the most common reason for high-risk contacts was non-formal workplace interactions such as having meals together. C_LIO_LIThe overall test positivity rate among the high-risk contacts was 7.1%, while it was higher in symptomatic high-risk contacts as compared to those who were asymptomatic (10.2% vs. 6.3%). C_LI How might this impact on clinical practice?O_LIContact tracing and risk stratification can be used to minimize unnecessary quarantine of COVID-19 exposed health care workers and prevent the depletion of healthcare workers amidst the pandemic to continue the healthcare services optimally. C_LI