COVID

India is currently facing the devastating second wave of COVID-19 pandemic resulting in approximately 4000 deaths per day. To control this pandemic continuous mutational surveillance and genomic epidemiology of circulating strains is very important. In this study, we performed mutational analysis of the protein coding genes of SARS-CoV-2 strains (n=2000) collected during January 2021 to March 2021. Our data revealed the emergence of a new variant in West Bengal, India, which is characterized by the presence of 11 co-existing mutations including D614G, P681H and V1230L in S-glycoprotein. This new variant was identified in 70 out of 412 sequences submitted from West Bengal. Interestingly, among these 70 sequences, 16 sequences also harbored E484K in the S glycoprotein. Phylogenetic analysis revealed strains of this new variant emerged from GR clade (B.1.1) and formed a new cluster. We propose to name this variant as GRL or lineage B.1.1/S:V1230L due to the presence of V1230L in S glycoprotein along with GR clade specific mutations. Co-occurrence of P681H, previously observed in UK variant, and E484K, previously observed in South African variant and California variant, demonstrates the convergent evolution of SARS-CoV-2 mutation. V1230L, present within the transmembrane domain of S2 subunit of S glycoprotein, has not yet been reported from any country. Substitution of valine with more hydrophobic amino acid leucine at position 1230 of the transmembrane domain, having role in S protein binding to the viral envelope, could strengthen the interaction of S protein with the viral envelope and also increase the deposition of S protein to the viral envelope, and thus positively regulate virus infection. P618H and E484K mutation have already been demonstrated in favor of increased infectivity and immune invasion respectively. Therefore, the new variant having G614G, P618H, P1230L and E484K is expected to have better infectivity, transmissibility and immune invasion characteristics, which may pose additional threat along with B.1.617 in the ongoing COVID-19 pandemic in India.

India had witnessed unprecedented surge in SARS-CoV-2 infections and the dire consequences during the second wave of COVID-19, but the detailed report of the epidemiological based spatiotemporal incidences of the disease is missing. Here in, we have applied various statistical methods like correlation, hierarchical clustering to know the pattern of pathogenesis of the circulating VoCs. B.1.617.1 (Kappa) was the predominant VoC during the early phase of second wave. Delta (B.1.617.2) or Delta-like (AY.x) VoC constitutes majority (>90.17) of the cases during the peak of second wave. The correlation plot showed Delta/Delta-like lineage is inversely correlated with other lineages including B.1.617.1 (kappa), B.1.1.7, B.1, B.1.36.29 and B.1.36. Delta/Delta-like surge coincided with second wave whereas all other lineages (B.1.617.1, B.1.36.29, etc.) occurred during the prior phase of the second wave. The spatiotemporal analysis showed that most of the Indian states were affected during the peak of the second wave due to delta surge and fall under the same cluster. The second cluster populated mostly by north-eastern states and islands of India were minimally affected. The presence of signature mutations (T478K, D950N, E156G) along with L452K, D614G and P681R within the spike protein of Delta or Delta-like might cause elevation in host cell attachment, increased transmission and altered antigenicity which in due course of time has replaced the other circulating variants. The timely assessment of new VoCs will provide a rationale for updating the diagnostic, vaccine development by medical industries and decision making by various agencies including government, educational institutions, and corporate industries.

We examine available data on the number of individuals infected by the Covid-19 virus, across several different states in India, over the period January 30, 2020 to April 10, 2020. It is found that the growth of the number of infected individuals N(t) can be modeled across different states with a simple linear function N(t) ={gamma} + t beyond the date when reasonable number of individuals were tested (and when a countrywide lockdown was imposed). The slope is different for different states. Following recent work by Notari (arxiv:2003.12417), we then consider the dependency of the for different states on the average maximum and minimum temperatures, the average relative humidity and the population density in each state. It turns out that like other countries, the parameter , which determines the rate of rise of the number of infected individuals, seems to have a weak correlation with the average maximum temperature of the state. In contrast, any significant variation of with humidity or minimum temperature seems absent with almost no meaningful correlation. Expectedly, increases (slightly) with increase in the population density of the states; however, the degree of correlation here too is negligible. These results seem to barely suggest that a natural cause like a hot summer (larger maximum temperatures) may contribute towards reducing the transmission of the virus, though the role of minimum temperature, humidity and population density remains somewhat obscure from the inferences which may be drawn from presently available data.

The pandemic spread of novel coronavirus, (SARS-CoV-2) causing CoronaVirus Infectious Diseases (COVID-19) emerged into a global threat for human life causing serious death rates and economic crunch all over the globe. As on April 17, 2020 at 2:00am CEST, there include a total of 2,034,802 confirmed cases for Corona and 1,35,163 deaths worldwide have been reported which includes 212 countries, areas or territories reported by World Health Organization (WHO), in which USA tops 6,32,781 confirmed cases (28,221 deaths) followed by Italy 1,65,155 (21,647 deaths), Spain 1,77,633 (18,579 deaths) and China 84,149 (4,642 deaths). This study aims to compare the genomic nature of SARS-CoV-2 genome reported from Wuhan, China with two Indian isolate genome reported by ICMR-NIV, India. Further Phylogenetic studies performed with coronavirus infecting non-human species like Bats, Duck, and sparrow were compared with Indian and other country whole genome sequences of SARS-CoV2 using MegaX and traced out the association between the human coronavirus with the other species viral genome. In addition, epidemiological reports on COVID-19 among Worldwide and India centric data were compared between April 7, 2020 to April 17, 2020 global data and the number of active cases were increased dramatically in this 10 days period studied, highlighted in the current study.

COVID-19 is bringing scenes of sci-fi movies into real life, and it seems to be far from over. Infected individuals exhibit variable severity, suggesting the involvement of the genetic constitution of populations and previous cross-reactive immune contacts in the individuals disease outcome. To investigate the participation of MHC alleles in COVID-19 severity, the combined use of HLA-B*07, HLA-B*44, HLA-DRB1*03, and HLA-DRB1*04 grouped affected countries presenting similar death rates, based only on their allele frequencies. To prospect T cell targets in SARS-CoV-2, we modeled 3D structures of HLA-A*02:01 complexed with immunogenic epitopes from SAR-CoV-1 and compared them with models containing the corresponding SARS-CoV-2 peptides. It reveals molecular conservation between SARS-CoV peptides, evidencing that the corresponding current sequences are putative T cell epitopes. These structures were also compared with other HCoVs sequences, and with a panel of epitopes from unrelated viruses, looking for the triggers of cross-protection in asymptomatic and uninfected individuals. 229E, OC43, and impressively, viruses involved in endemic human infections share fingerprints of immunogenicity with SARS-CoV peptides. Wide-scale HLA genotyping in COVID-19 patients shall improve prognosis prediction. Structural identification of previous triggers paves the way for herd immunity examination and wide spectrum vaccine development.

A dramatic resurgence of COVID-19 cases and deaths in Bangladesh in March 2021 coincided with the SARS-CoV-2 B.1.351 (501Y.V2) variant of concern rapidly becoming the dominant circulating variant. Concurrently, increasing numbers of reinfections have been detected and the effective Reproductive number, Rt, has doubled, despite high levels of prior infection in Dhaka city. These data support the prediction that acquired immunity from past infection provides reduced protection against B.1.351, and highlights the major public health concern posed by immune escape variants, especially in populations where vaccination coverage remains low.

In this work we observe a number of cases supporting the possible correlation between the administration of BCG tuberculosis vaccine and the severity of Covid-19 effects in the population proposed in the earlier works [1]. Based on the early preliminary analysis of the publicly available data we propose a number of arguments and observations providing further support for the correlation hypothesis and make an observation that the effectiveness of the protection effect of BCG immunization, if confirmed, may depend to a significant extent on the age of administration, with the early age inoculation more effective for the lasting protection.

The variant of Concern(VOC), Omicron is the predominant variant circulating throughout the world of the SARS COV2 pandemic during the third wave including India. The World Health Organisation has designated this highly mutated variant as a VOC due to its high transmissibility and risk of reinfection. Whole-genome sequencing and analysis were performed for SARS-CoV2 PCR positive samples between Dec21 to Jan22. From the 133 omicron variants detected, genomic analysis was carried out by contextualizing them with 1586 complete genomes of Omicron from India obtained from GISAID. The Omicron variant prevalence in India has increased in a log phase within 3 months in most of the metropolitan cities. The sublineage BA.1 was first observed in the country, while the BA.2 sublineage was introduced to Delhi in the mid of December 2021. The two outbreaks observed were of BA.2 variant and were observed to spread to multiple cities in a short time. The rapid spread and specific mutations in the outbreak samples of Omicron indicate that the variant is highly transmissible when compared to previous variants. The study shows the importance of genomic sequence to identify the emergence of clusters and take actions to prevent further spreading events.

Seroepidemiology and genomics are valuable tools to investigate the transmission of COVID-19. We utilized qRT-PCR, serum antibody immunoassays, and whole genome sequencing to examine the spread of SARS-CoV-2 infections in North East (NE) region of India during the first and second pandemic waves (June 2020 to September 2021). qRT-PCR analysis was performed on a selected population from NE India during June 2020 to July 2021, and metadata were collected for the region. Seroprevalence and neutralizing antibody immunoassay were studied on selected individuals (n=2026) at three time points (August 2020, February 2021 and June 2021), as well as in a cohort (n=35) for a year (August 2020 to August 2021). SARS-CoV-2 genomes of 914 qRT-PCR positive samples (June 2020 to September 2021) were sequenced and assembled, and those obtained from the sequence databases were analyzed. Test positivity rates in first and second waves were 6.34% and 6.64% in the state of Assam, respectively, and a similar pattern was observed in other NE states. Seropositivity in August 2020, February 2021, and June 2021 were 10.63%, 40.3% and 46.33% respectively, and neutralizing antibody prevalence were 90.91%, 52.14%, and 69.30% respectively. The cohort group showed the presence of stable neutralizing antibody throughout the year. Normal variants dominated the first wave, while the variant of concerns (VOCs) B.1.617.2 and AY-sublineages dominated the second wave, and identified mostly among vaccinated individuals. All eight states of NE India reported numerous incidences of SARS-CoV-2 VOCs, especially B.1.617.2 and AY sublineages, and their prevalence co-related well with high TPR and seropositivity rate in the region. High infection and seroprevalence of COVID-19 in NE India during the second wave was associated with the emergence of VOCs. Natural infection prior to vaccination provided higher neutralizing activity than vaccination alone.

While emergence of new SAS-COV-2 variants is posing grave challenge to efforts to deal with the COVID-19 pandemic, the structural and molecular basis of their fitness remain poorly understood. We performed in silico analysis of structures of two most frequent SARS-COV-2 mutations, namely, N501Y and E484K, to identify plausible basis of their fitness over the original strain. The analysis suggested that the N501Y mutation is associated with strengthening of intra- as well as intermolecular H-bond in the hACE2 receptor-spike protein complex, which could result in increased affinity and, therefore, higher infectivity. While E484K mutation did not seem to directly affect the binding with hACE2 receptor, it disrupted H-bonding and salt-bridge interaction associated with binding with neutralizing antibody, which could affect chance of re-infection, disease outcome. Survey of several other mutations showing reduction in antibody-mediated neutralization also revealed that similar disruption of H-bonding or salt-bridge or Van der Waals interaction might explain their phenotype. Analysis of GESS database indicated that N501Y, EK484 as well as these other mutations existed since March-April, 2020, might have evolved independently across the world and may keep accumulating, which could affect efficacy of vaccination and antibody-based therapies. Our analysis also indicated that these may spread in spite of current travel restrictions focused on few countries and evolve indigenously warranting intensification of surveillance for emerging mutations among all travellers as well as people in their dwelling zones. Meta-analysis of existing literature showed that repeat testing of travellers, contacts and others under scrutiny 7-11 days after the initial RT-PCR test may significantly help to contain the spread of emerging variants by catching false negative results. In addition, existing evidence calls for development of strain-specific tests, escalated sequencing and broadening the scope of surveillance including in hospitals and animal farms to contain the threat of emerging variants.

BackgroundSelenium forms a significant component of seleno-proteins in the body. Seleno-methionine is integrated into proteins instead of methionine and acts as a storage pool. In proteins, the active form of Selenium is seleno-cysteine.in this review we aim to prevail the results of selenium effect on thyroid status in recent clinical trials. The systemic review aims to find out the correlation between supplementation of Selenium and anti-TPO antibodies and T4 levels in Hashimotos Thyroiditis. Selenium supplementation decreases the level of anti-TPO antibodies. The supplementation of Selenium increases the level of T4 levels. MethodsThe mean and standard deviation (SD) of all 8 studies was were calculated. One of the researches had all the information in figures, and only the levels of anti-TPO antibodies and FT4 were obtained. Heterogenicity was estimated using I2. ResultsThe p-value calculated for Anti-TPO by SPSS of the eight groups had a p-value of 0.142. The p-value calculated for T4 levels by SPSS of the five groups had a p-value of 0.239. The heterogenicity test was zero after the I2 test. The studies that were included in the systematic review were assessed by Prisma diagram and selected among the articles resulted from search keywords selenium and anti tpo and hashimotho thyroiditis on different data sources. All the participants were evaluated by sex, ages, duration of the study and the levels of anti tpo ab and thyroxin (t4) and then using SPSS software to deploy metanalysis in the systematic review. Conclusionin 6 of 8 studies it was a relation of selenium and thyroid status, whereas 2 studies were not. As We ran meta analysis on the data we realized that there is not significant desired effect from selenium on thyroid antibodies against previous metanalysis done by other researchers.

IntroductionNeural tube defects (NTDs) are a folate deficiency disorder. NTDs are preventable; increasing folic acid intake through food fortification or use of supplements increases serum and red blood cell folate and reduces the risk of a woman having an NTD pregnancy. There is controversy over whether there is a blood folate level needed to achieve the full preventive effect because of discrepant conclusions from studies investigating the relationship between folate levels and NTD risk. Resolving the controversy is important in determining public health policy. MethodsData from two studies conducted in Ireland and China were used to determine the relationship between serum folate and NTD risk. The relationship from each study was compared with the observed result in a randomised trial of folic acid that increased serum folate from 5 ng/ml to 44 ng/ml among the women who took the daily folic acid supplement before and during early pregnancy. ResultsData from both studies showed a proportional (logarithmic) relationship between serum folate and NTD risk with no evidence of a folate threshold above which there is no further NTD risk reduction. Both studies accurately predicted the observed result from the randomised trial that achieved serum folate levels beyond the average levels found in the general population with an 83% preventive effect. This is higher than can be achieved with current levels of folic acid food fortification or with the recommended peri-conceptional use of 0.4mg supplements. The suggestion of a threshold is not due to discrepant data but the incorrect interpretation of the folate-NTD risk association when plotted on arithmetic scales which conceals the proportional relationship between the two. ConclusionTo achieve fully effective fortification serum folate levels need to be about 44ng/ml. Key MessagesO_ST_ABSWhat is already known on this topicC_ST_ABSNeural tube defects (NTDs), among the most common serious birth defects worldwide, are a folate deficiency disorder. Increasing folic acid (vitamin B9) intake increases serum folate and reduces the risk of an NTD pregnancy. There is a difference of opinion on the serum folate level needed for fully effective NTD prevention. What this study addsThere is no threshold above which NTD risk does not decrease and population folate levels need to be substantially increased to have the expected potential achieve effect on the prevention of NTDs. How this study might affect research, practice or policyA serum folate level of about 44ng/ml is a reasonable target to achieve an approximate 83% reduction in the prevalence of NTD pregnancies. This result can be used to help influence folic acid fortification policy.

This is the first study on omicron genomes from India to focus on phylodynamics and phylogenomics trait to provide an insight into the evolution of omicron variants. We analyzed 564 genomes deposited to GISAID database from various states of India. Pangolin COVID-19 Lineage Assigner tool was used to determine lineage assignment of all retrieved genomes. A Maximum likelihood (MLE) tree construction further confirms the separation of genomes into two distinct clades, BA. 1. and BA. 2. A very high reproduction number (R0) of 2.445 was estimated for the lineage BA.2. The highest R0 value in Telangana confirms the prevalence of lineage BA.2 in the state. Construction of the Reduced Median (RM) network shows evolution of some autochthonous haplogroups and haplotypes, which further supports the rapid evolution of omicron as compared to its previous variants. Phylogenomic analyses using maximum likelihood (ML) and RM show the potential for the emergence of sub-sublineages and novel haplogroups respectively. Due to the recombinant property and high transmissibility of omicron virus, we suggest continuous and more widespread genome sequencing in all states of India to track evolution of SARS-CoV-2 in real time.

The concern about (socio-)economic consequences of collective lockdowns in the Covid-19 pandemic calls for alternative strategies. We consider a divide and conquer strategy in which a high risk group (HRG) is put on strict isolation, whereas the remainder of the population is exposed to the virus, building up immunity against Covid-19. The question is whether this strategy may suppress the effective reproduction number below the critical value of [Formula] without further lockdown once the HRG is released from isolation. While this proposal appears already rather academic, we show that [Formula] can only be obtained provided that the HRG is less than ~ 20 - 30% of the total population. Hence, this strategy is likely to fail in countries with a HRG larger than the given upper bound. In addition, we argue that the maximum infection rate occurring in this strategy is likely to exceed realistic capacities of most health care systems. While the conclusion is rather negative in this regard, we emphasise that the strategy of stopping the curve at an early stage of the Covid-19 pandemic has a chance to work out. The required duration of the lockdown is estimated to be {tau} ~ 14 days/[Formula] (up to some order one factor) for [Formula], provided a systematic tracing strategy of new infections exists for the subsequent relaxation phase. In this context we also argue why [Formula] remains the crucial parameter which needs to be accurately monitored and controlled.

New variants of SARS-COV-2 have been found in various countries. Especially, the UK has been attacked by Indias Delta Plus, and the spread of infection has been very rapid, since it is extremely infectious. Fortunately, however, the number of deaths has been stayed flat, where deaths are reported to be those who are not yet received a shot of COVID-19 vaccine. In this short not, we would like to consider why the number of deaths is so small, compared with high cases, around the infection peak, when the basic reproduction number is very large.

BackgroundWhile Bangladesh has started its mass COVID-19 vaccination drive, it is struggling to cover its huge population similar to other low- and middle-income countries due to the lack of vaccine availability. One of the major remittance sources for Bangladesh is its migrant workers who are required to receive mRNA vaccines to return to their jobs. Despite reports of higher efficacy of mRNA vaccine against COVID-19, breakthrough infection cases are arising especially with the emergence of Delta variant. It is highly important to understand the post-vaccination immune response and breakthrough infections in different populations so that the necessity of booster dosage can be assessed properly. MethodsWe observed post BNT162b2 full vaccination immune response in a small older group (mean age= 59.5{+/-}5.44 years) of migrant workers (n=10) for six months at the Sheikh Hasina National Institute of Burn and Plastic Surgery, Dhaka, Bangladesh. The plasma samples from the participants were collected after 14 days, 2 months, 3 months, 4 months, 5 months, and 6 months of receiving the 2nd dose of the BNT162b2 vaccine. Anti S1 RBD IgG responses were measured as optical density ratios using a commercially available ELISA kit. ResultsAll 10 of the participants were male migrant workers and none of them had a history of previous COVID-19 infection. The median antibody response [IQ1:IQ3] was 9.05 [7.53; 10.0] on day 14 then it increases to 13.6 [12.0; 14.0] at the second month which gradually decreased to a median of 8.63 [8.34; 9.37] on the 6th-month post-vaccination. There were two breakthrough infection cases after receiving the second dose and the antibody responses were highly increased in the following months. Two of the breakthrough cases were diagnosed with mild COVID-19 as the symptom duration was less than 3 days with no respiratory complications and no hospital admission were required. ConclusionsThe BNT162b2 mRNA vaccine produces a strong immune response that sustains at least 6 months after getting fully vaccinated. But even after getting fully vaccinated people are susceptible to breakthrough infections that are not severe and boost the immune response greatly offering a hybrid immunity from both vaccine and natural infection. Hence, it is still important to fully vaccinate a greater number of people rather than thinking of offering booster dosage to a privileged population out of the fear of breakthrough cases. If the LMICs can quickly cover at least 80% of their population with usual priority targets (healthcare workers, migrant workers, older people, etc.) then a global risk reduction and pandemic control would be possible that will allow additional variant-specific boosters for targeted populations if evidence support.

An analytical model for calculating the spread of the COVID-19 epidemic is described, and it is shown that the main patterns of epidemic development are determined by three dimensionless complexes representing the ratios of transmission rates, contact limitation due to lockdown, and population vaccination. A comparison of statistical data on the growth of the epidemic in Germany, Berlin and its various neighbourhoods shows that the development of the epidemic depends to a large extent on the ethnic composition of the population. In the same way as it is accepted in some sections of physics, it is proposed to use the methods of similarity theory to investigate the regularities of the emergence and development of the epidemic.

Recently a number of publications looked at the association between COVID-19 morbidity and mortality on one hand and countries policies with respect to BCG vaccination on the other. This connection arises from differences in the rates of infection in countries where BCG vaccination is mandatory compared to countries where mandatory vaccination no longer exists or was never implemented in the first place. In at least 2 preprint publications the authors expressed the view that the "known immunological benefits" of BCG vaccination may be behind the biological mechanism of such observation. One study accounted for different income levels in different groups. Another study did not attempted to do so, instead exploring the differences between countries where a booster shot is given vs others where no such practice exists (finding no connection). Both of these studies did not explore other potential confounding factors. Meanwhile the press has focused on these headlines and pushed the narrative that BCG vaccination is causally linked to infection and mortality rates. This poses a serious challenge, demonstrated by the recently initiated clinical trials on BCG vaccination within the COVID19 context. This study shows that population age is a very significant confounding factor that explains the rates of infections much better and has a solid biology mechanism which explains this correlation. It suggests that BCG vaccination may have little or no causal link to infection rates and advises that any follow up studies should control for several confounding factors, such as population age, ethnicity, rates of certain chronic diseases, time from community spread start date, major public policy decisions and income levels.

This is an analysis of the features of the COVID-19 pandemic the population of the Republic of Belarus from February 2020 to January 2022, the characteristics of sanitary and anti-epidemic measures carried out in the country, assessment of study the safety (tolerance) of the vaccines used the epidemiological efficacy of the vaccination. A retrospective analysis of COVID-19 cases in the Republic of Belarus from the beginning of registration (February 28, 2020) to January, 3, 2022 was performed. Vaccine safety (tolerance) and efficacy were assessed in an observational study. Safety (tolerance) was assessed by presence/absence of adverse reactions: general (fever, malaise, headache, muscle pain, runny nose, nausea, vomiting, sore throat, etc) and local ones (redness, swelling, soreness at the injection place). The COVID-19 pandemic in the Republic of Belarus is characterized by successive development stages: from no cases in early 2020 to detected cases where most individuals had no history of contact with COVID-19 patients; periods of rising and falling incidence Vaccines against COVID-19 (Gam-COVID-Vac (Russia), inactivated vaccine against SARS-CoV-2 (Vero Cell) Sinopharm / BIBP (China) demonstrated a high safety profile in mass vaccination of the population of the Republic of Belarus.

AO_SCPLOWBSTRACTC_SCPLOWIn an earlier paper we proposed a recursive model for epidemics; in the present paper we generalize this model to include the asymptomatic or unrecorded symptomatic people, which we call dark people (dark sector). We call this the SEPARd-model. A delay differential equation version of the model is added; it allows a better comparison to other models. We carry this out by a comparison with the classical SIR model and indicate why we believe that the SEPARd model may work better for Covid-19 than other approaches. In the second part of the paper we explain how to deal with the data provided by the JHU, in particular we explain how to derive central model parameters from the data. Other parameters, like the size of the dark sector, are less accessible and have to be estimated more roughly, at best by results of representative serological studies which are accessible, however, only for a few countries. We start our country studies with Switzerland where such data are available. Then we apply the model to a collection of other countries, three European ones (Germany, France, Sweden), the three most stricken countries from three other continents (USA, Brazil, India). Finally we show that even the aggregated world data can be well represented by our approach. At the end of the paper we discuss the use of the model. Perhaps the most striking application is that it allows a quantitative analysis of the influence of the time until people are sent to quarantine or hospital. This suggests that imposing means to shorten this time is a powerful tool to flatten the curves.