Virus World

India is taking urgent steps to halt the transmission of a rare but deadly virus that spreads from bats to humans. In the southern Indian state of Kerala, the bat-borne Nipah virus has infected six people — two of whom have died — since it emerged in late August. More than 700 people, including health-care workers, have been tested for infection over the past week. State authorities have closed some schools, offices and public-transport networks. The Nipah outbreak is the fourth to hit Kerala in five years — the most recent one was in 2021. Although such outbreaks usually affect a relatively small geographical area, they can be deadly, and some scientists worry that increased spread among people could lead to the virus becoming more contagious. Nipah virus has a fatality rate between 40% and 75% depending on the strain, says Rajib Ausraful Islam, a veterinary physician who specializes in bat-borne pathogens at the International Centre for Diarrhoeal Disease Research, Bangladesh, in Dhaka. “Each outbreak is a concern,” he says. “Every outbreak is giving the pathogen an opportunity to modify itself.” The virus can cause fever, vomiting, respiratory issues and inflammation in the brain. It is carried mainly by fruit bats, but can also infect domestic animals such as pigs, along with humans. It spreads through contact with bodily fluids from infected animals or people. There are no approved vaccines or treatments, but researchers are investigating candidates....

At the end of March 2023, XBB.1.16, a SARS-CoV-2 omicron XBB subvariant, emerged and was detected in various countries. Compared to XBB.1.5, XBB.1.16 has two substitutions in the S protein: E180V is in the N-terminal domain, and T478K in the receptor-binding domain (RBD). We first show that XBB.1.16 had an effective reproductive number (Re) that was 1.27- and 1.17-fold higher than the parental XBB.1 and XBB.1.5, respectively, suggesting that XBB.1.16 will spread worldwide in the near future. In fact, the WHO classified XBB.1.16 as a variant under monitoring on March 30, 2023. Neutralization assays demonstrated the robust resistance of XBB.1.16 to breakthrough infection sera of BA.2 (18-fold versus B.1.1) and BA.5 (37-fold versus B.1.1). We then used six clinically-available monoclonal antibodies and showed that only sotrovimab exhibits antiviral activity against XBB subvariants, including XBB.1.16. Our results suggest that, similar to XBB.1 and XBB.1.5, XBB.1.16 is robustly resistant to a variety of anti-SARS-CoV-2 antibodies. Our multiscale investigations suggest that XBB.1.16 that XBB.1.16 has a greater growth advantage in the human population compared to XBB.1 and XBB.1.5, while the ability of XBB.1.16 to exhibit profound immune evasion is comparable to XBB.1 and XBB.1.5. The increased fitness of XBB.1.16 may be due to (1) different antigenicity than XBB.1.5; and/or (2) the mutations in the non-S viral protein(s) that may contribute to increased viral growth efficiency.

Published in bioRxiv (april 6, 2023):

https://doi.org/10.1101/2023.04.06.535883 

New trial shows nasal spray reduces infection of covid-causing virus by 62% A new clinical trial led by Queen Mary University of London and Barts Health researchers has shown that the pHOXWELL nasal spray can reduce infection with SARS-CoV-2 - the virus that causes Covid-19 - by 62%. The trial was carried out in India between April to July 2021. It involved 556 participants - 275 used pHOXWELL and 281 used a placebo - three times a day. After 45 days, the researchers measured how many antibodies against Covid-19 each person in both groups had. The team found that the nasal spray was safe and that after 45 days, 13.1% of those in the group that used it had antibodies against the Covid-19 virus, compared to 34.5% in the group who received the placebo. This shows that using pHOXWELL dramatically reduces the chances of developing Covid-19. Researchers also found that people who used the nasal spray were less likely to experience symptoms than those given the placebo. No serious side effects were reported in either group and participants noted that the nasal spray was easy to use.

Professor Rakesh Uppal, Professor of Cardiovascular Surgery at Queen Mary University of London, Director of Barts Life Sciences said: “pHOXWELL presents a significant breakthrough in preventing people developing Covid-19. We now have an effective tool, previously missing, to fight this virus, and is designed to offer extra protection against Covid-19, in addition to vaccines, face masks and washing our hands. “I’m immensely proud of everyone involved in this trial and am extremely grateful to the participants who gave their time to be involved.” The researchers’ aim is to soon begin producing and distributing the treatment in India initially. Following this, they will look to expand into other countries. The treatment will be especially beneficial in parts of the world where uptake of the vaccine remains low and there is a shortage of personal protective equipment for those who require it.  It comes as Covid-19 infection continues to cause a huge burden on global health and a significant strain on the world economy. pHOXWELL offers 6-8 hours of protection with two sprays per nostril. It is also designed to be effective against other airborne respiratory viruses.

Scientists hope the immunizations, delivered through the nose or mouth, will prevent even mild cases of illness.  Two needle-free COVID-19 vaccines that are delivered through the nose or mouth have been approved for use in China and India. China’s new vaccine, announced on Sunday, is inhaled through the nose and mouth as an aerosolized mist, and India’s, announced on Tuesday, is administered as drops in the nose. These mucosal vaccines target thin mucous membranes that line the nose, mouth and lungs. By prompting immune responses where SARS-CoV-2 first enters the body, mucosal vaccines could, in theory, prevent even mild cases of illness and block transmission to other people — something COVID-19 shots have been unable to do. Vaccines that produce sterilizing immunity would be game changing for the pandemic.  “These approvals validate the need for mucosal vaccines,” says Marty Moore, co-founder of Meissa Vaccines in Redwood City, California, which is developing a COVID-19 immunization that is delivered through the nose. “That’s the direction we need to go globally, and the United States needs to catch up.” The regulatory nods from China and India bring the number of approved COVID-19 mucosal vaccines in the world to four, including one already approved in Iran and another in Russia. More than 100 mucosal vaccines against the disease are in development globally, and about 20 have reached clinical trials in humans, according to Airfinity, a health-analytics company in London. Delivery methods include sprays, drops, aerosols and pills.

New arrivals

China’s inhaled vaccine, developed by CanSino Biologics in Tianjin, contains the same ingredients as the company’s COVID-19 shot that is already available in the country. A device called a nebulizer turns the liquid vaccine into an aerosol spray that is inhaled. China’s health department and National Medical Products Administration approved the vaccine to be used as a booster dose. India’s vaccine, developed by Bharat Biotech in Hyderabad, is approved as a two-dose primary inoculation, rather than a booster. Both companies have produced ‘viral vector’ vaccines that use a harmless adenovirus to deliver SARS-CoV-2 genetic material into host cells. Neither company has published phase III clinical-trial data, but both say they have completed those studies. Data from a phase II trial of CanSino’s inhaled vaccine found that, when given as a booster, the vaccine raised blood-serum antibody levels significantly more than did a boost from an injection. This suggests that the inhaled vaccine will offer protection that is as good as, or better than, that provided by the shot. Similarly, Bharat compared its intranasal vaccine to Covaxin, a COVID-19 jab available in India, by measuring antibody levels in the blood. The company did not release results of this study, but deemed the trial “successful”. Exactly how successful these vaccines will be is unclear. Expecting a vaccine to stop transmission of a virus or prevent even mild illness — achieving what is called sterilizing immunity — is a high bar. Bharat and CanSino won’t know whether their vaccines can achieve this until they have conducted further efficacy studies. Scant data are available on the efficacy of the two other mucosal COVID-19 vaccines. Iran approved a COVID-19 vaccine administered as a nasal spray and made by Razi Vaccine and Serum Research Institute in Karaj in October 2021. More than 5,000 doses have been delivered to the public. And Russia’s health ministry is reported to have approved an intranasal-spray version of Sputnik V, the country’s injected COVID-19 vaccine. Mucosal vaccines have been developed for other diseases, including polio, influenza and cholera. Most of these vaccines are taken orally, and one, against flu, is administered through the nose.

The Janssen COVID-19 vaccine has become the fifth vaccine against the pandemic to be granted emergency use approval.  Union health minister Mansukh Mandaviya tweeted today to inform that the single-dose vaccine manufactured by American pharmaceutical giant Johnson & Johnson has been given approval for Emergency Use in India.  The development comes just two days after the company had applied for Emergency Use Authorization in India. The company had said in a statement, “On August 5, 2021 Johnson & Johnson Pvt Ltd applied for EUA of its single-dose Covid-19 vaccine to the government of India.” They had submitted the application based on topline efficacy and safety data from the Phase 3 Ensemble clinical trial. The trial had shown that the single-dose vaccine is 85% effective in preventing severe Covid-19 disease across all regions studied. It had also shown protection against Covid-19 related hospitalisation and death, which begins 28 days after vaccination. Data from a clinical trial in South Africa also suggest that the vaccine is effective in preventing severe illness and death from the Delta and Beta variants of the coronavirus.

The company has tied up with Biological E for the supply of the vaccine in India. The vaccine will also be produced in India, at Biological E plant in Hyderabad. “Johnson & Johnson is working with Biological E. Limited on the manufacturing of the Johnson Covid-19 vaccine. We believe Biological E. will be an important part of our global Covid-19 vaccine supply network, where multiple manufacturing sites are involved in the production of our vaccine across different facilities, sometimes in different countries and continents, before the vaccine can be distributed”, an official statement released by Johnson and Johnson had earlier said.  The vaccine developed by Janssen Vaccines in Leiden, Netherlands, a subsidiary of J&J, is a viral vector vaccine. It is based on a human adenovirus that has been modified to contain the gene for making the spike protein of the virus that causes COVID-19. Responding to this spike protein, the immune system in the body produces antibodies that fights the virus. The four vaccines that India has already approved are Covaxin developed by Astra Zeneca and Oxford University, Covishield developed by Bharat Biotech, Sputnik V developed in Russia and the vaccine developed by Moderna in the USA.

When the first cases of the SARS-CoV-2 Delta variant were detected in the United Kingdom in mid-April, the nation was getting ready to open up. COVID-19 case numbers, hospitalizations and deaths were plummeting, thanks to months of lockdown and one of the world’s fastest vaccination programmes. Two months later, the variant, which was first detected in India, has catalysed a third UK wave and forced the government to delay the full reopening of society it had originally slated for 21 June. After observing the startlingly swift rise of the Delta variant in the United Kingdom, other countries are bracing for the variant’s impact — if they aren’t feeling it already. Nations with ample access to vaccines, such as those in Europe and North America, are hopeful that the shots can dampen the inevitable rise of Delta. But in countries without large vaccine stocks, particularly in Africa, some scientists worry that the variant could be devastating. “In my mind, it will be really hard to keep out this variant,” says Tom Wenseleers, an evolutionary biologist and biostatistician at the Catholic University of Leuven (KU Leuven) in Belgium. “It’s very likely it will take over altogether on a worldwide basis.”  Delta, also known as B.1.617.2, belongs to a viral lineage first identified in India during a ferocious wave of infections there in April and May. The lineage grew rapidly in some parts of the country, and showed signs of partial resistance to vaccines. But it was difficult for researchers to disentangle these intrinsic properties of the variant from other factors driving India’s confirmed cases past 400,000 per day, such as mass gatherings.

Delta data

The Delta variant has been linked to a resurgence of COVID-19 in Nepal, southeast Asia and elsewhere, but its UK spread has given scientists a clear picture of the threat it poses. Delta seems to be around 60% more transmissible than the already highly infectious Alpha variant (also called B.1.1.7) identified in the United Kingdom in late 2020. Delta is moderately resistant to vaccines, particularly in people who have received just a single dose. A Public Health England study published on 22 May found that a single dose of either AstraZeneca's or Pfizer's vaccine reduced a person’s risk of developing COVID-19 symptoms caused by the Delta variant by 33%, compared to 50% for the Alpha variant. A second dose of the AstraZeneca vaccine boosted protection against Delta to 60% (compared to 66% against Alpha), while two doses of Pfizer’s jab were 88% effective (compared to 93% against Alpha). Preliminary evidence from England and Scotland suggests that people infected with Delta are about twice as likely to end up in hospital, compared with those infected with Alpha. “The data coming out of the UK is so good, that we have a really good idea about how the Delta variant is behaving,” says Mads Albertsen, a bioinformatician at Aalborg University in Denmark. “That’s been an eye-opener.” Denmark, which, like the United Kingdom, is a world leader in genomic surveillance, has also seen a steady rise in cases caused by the Delta variant — although far fewer than most other European countries. It is only a matter of time before the variant becomes dominant in Denmark, says Albertsen, but the hope is that its expansion can be slowed through vaccination, surveillance and enhanced contact tracing. “It’s going to take over,” he says, but “hopefully in a few months and not too soon.” Meanwhile, the Danish government is easing restrictions, not re-imposing them: restaurants and bars have been open for months to individuals who have been vaccinated or received a recent negative test, and, as of 14 June, masks are no longer required in most indoor settings. “It is looking good now in Denmark, and we are keeping a close eye on the Delta variant,” says Albertsen. “It can change quite fast, as it has done in the UK.” Cases of the Delta variant in the United Kingdom are doubling roughly every 11 days. But countries with ample vaccine stocks should be reassured by the slower uptick in hospital admissions, says Wenseleers. A recent Public Health England study1 found that people who have had one vaccine dose are 75% less likely to be hospitalized, compared with unvaccinated individuals, and those who are fully protected are 94% less likely to be hospitalized. 

US spread

Delta is also on the rise in the United States, particularly in the Midwest and southeast. The US Centers for Disease Control and Prevention declared it a variant of concern on 15 June. But patchy surveillance means the picture there is less clear. According to nationwide sampling conducted by the genomics company Helix in San Mateo, California, Delta is rising fast. Using a rapid genotyping test, the company has found that the proportion of cases caused by Alpha fell from more than 70% in late April to around 42% as of mid-June, with the rise of Delta driving much of the shift2. Jeremy Kamil, a virologist at Louisiana State University Health in Shreveport, expects Delta to eventually become dominant in the United States, “but to be somewhat blunted by vaccination”. However, vast disparities in vaccination rates could lead to regional and local variation in cases and hospitalizations caused by Delta, says Jennifer Surtees, a biochemist at the University at Buffalo, New York, who is conducting regional surveillance. She notes that 70% of eligible New Yorkers have received at least one dose of vaccine — a milestone that triggered the lifting of most COVID-19 restrictions last week — but that figure is below 40% in some parts of the state. Communities with high proportions of African American and Hispanic individuals, where vaccination rates tend to be low, could be especially hard hit by Delta. “These are populations that are really at risk of a localized outbreak from Delta, so I think it’s really important to still keep tracking and watch this as much as possible,” Surtees says. Data from Helix2 on nearly 20,000 samples sequenced since April suggest that the Delta variant is spreading faster in US counties where less than 30% of residents have been fully vaccinated, compared to the counties with vaccination rates above that threshold.

Africa at risk

Delta poses the biggest risk, scientists say, to countries that have limited access to vaccines, particularly those in Africa, where most nations have vaccinated less than 5% of their populations. “The vaccines will never come in time,” says Wenseleers. “If these kinds of new variant arrive, it can be very devastating.” Surveillance in African countries is extremely limited, but there are hints that the variant is already causing cases there to surge. Several sequences of the variant have been reported in the Democratic Republic of the Congo, where an outbreak in the capital city of Kinshasa has filled hospitals. The variant has also been detected in Malawi, Uganda and South Africa. Countries that have close economic links to India, such as those in East Africa, are probably at the greatest risk of seeing a surge in cases caused by Delta, says Tulio de Oliveira, a bioinformatician and director of the KwaZulu-Natal Research and Innovation Sequencing Platform in Durban, South Africa. In his country, all of the Delta cases have been detected in shipping crews at commercial ports, with no signs yet of spread in the general community. De Oliveira expects it to stay this way. South Africa is in the middle of a third wave of infections caused by the Beta variant (also known as B.1.351) identified there last year. This, combined with a lack travel from countries affected by Delta, should make it harder for a new variant to take hold. Similar factors could be keeping Delta at bay in Brazil, which is battling another immune-evading variant called P.1, or Gamma, says Gonzalo Bello, a virologist at the Oswaldo Cruz Institute in Rio de Janeiro, who is part of a team conducting national surveillance. So far, Brazil has sequenced just four cases of the Delta variant in the country. While countries gird themselves against the Delta variant — or hope that it passes them by — researchers say we need to watch for even greater threats. “What most people are concerned about are the next variants — if we start to see variants that can really challenge the vaccines,” says Albertsen.

Published in Nature (June 22, 2021):

https://doi.org/10.1038/d41586-021-01696-3

Led by surges in the two hotspots and Eastern Europe, the average number of new daily cases has exceeded 800,000 for more than a week. Worldwide, the number of new coronavirus cases has shot upward since the beginning of March, more than doubling in two months. For the past two weeks, new global cases have exceeded their previous high point in early January. The average daily rate of new cases has now been above 800,000 for more than a week. 

The increase in cases is largely being driven by the uncontrolled outbreak in India, where new cases have risen sharply for the past month and show no signs of abating. A seven-day rolling average of new daily cases in the nation exceeded 357,000 on Thursday, a more than fivefold increase since April 1. India now accounts for more than 40 percent of the world’s new cases. The country’s death rate has followed the same dramatic curve, with more than 3,000 people now dying every day. Analysts say even those grim numbers may be undercounted. The second wave of the virus in India has been devastating. In hospitals in New Delhi, the capital, a shortage of medical oxygen has reached crisis levels, and cremation grounds are working around the clock as relatives and friends continue to bring more bodies to be burned.

After enacting one of the world’s strictest lockdowns last March, which kept deaths relatively low, Indian officials relaxed restrictions. Some politicians even held crowded rallies in recent weeks as the country’s infection rate picked up. The surge has left hospitals overwhelmed. “People are angry because they are not getting ventilators and oxygen,” said Dr. Rakesh Kumar, a physician in the northern Indian state of Uttar Pradesh. “They are saying, ‘We are paying for the facilities; then why are our patients dying?’” Medical professionals in India face crushing conditions. “No hospital has shut down and no doctor has retreated from the front lines,” one doctor wrote in a Facebook post. “We are fighting missiles with sticks but we are not leaving the fort.” The vaccine rollout in India has been too slow to stem the wave of cases, despite the country’s status as one of the world’s leading vaccine producers. Less than 2 percent of its residents are fully vaccinated, and less than 10 percent have received at least one dose. Other countries and regions are also seeing worrisome trends. Uruguay, currently experiencing the world’s highest cases per capita, is adding almost 3,000 cases per day — a staggering number in a country of just 3.5 million people. Indeed, much of South America is faring poorly: In addition to Uruguay, Paraguay, Brazil, Peru, Argentina and Colombia all rank among the top 20 nations in the world for Covid deaths per capita as of Thursday.

Aditi TandonTribune News ServiceNew Delhi, April 21 In a major boost to made in India Covid vaccine enterprise, indigenous shot COVAXIN has been shown to successfully neutralise the double mutant  detected in certain parts of India and the world. The Indian Council of Medical Research lab National Institute of Virology announced the development today saying the Bharat Biotech-ICMR made COVID vaccine was effective against multiple strains of the SARS-Cov2 virus.  The ICMR had earlier isolated UK and Brazil strains and shown COVAXIN was effective against these. The results of COVAXIN working against the double mutant were announced on Friday simultaneous to another major research declaration that reveals COVAXIN has 78 to 100 pc efficacy against severe COVID disease. Bharat Biotech and ICMR today jointly shared the interim results from Phase 3 trials of COVAXIN saying these “demonstrate overall interim clinical efficacy of 78 pc and 100 pc efficacy against severe COVID-19 disease”. The second interim analysis is based on more than 87 symptomatic cases of COVID-19.

The firm said due to the recent surge in cases, 127 symptomatic cases were recorded, resulting in a point estimate of vaccine efficacy of 78 pc against mild, moderate, and severe COVID-19 disease. “The efficacy against severe COVID-19 disease was 100 pc with an impact on reduction in hospitalizations. The efficacy against asymptomatic COVID-19 infection was 70 pc, suggesting decreased transmission in COVAXIN recipients,” the results said.  Safety and efficacy results from the final analysis will be available in June, and the final report will be submitted to a peer-reviewed publication, ICMR and Bharat Biotech said. The Phase 3 study enrolled 25,800 participants between 18-98 years of age, including 10 pc over the age of 60, with analysis conducted 14 days post 2nd dose. 

COVAXIN was developed with seed strains received from the National Institute of Virology and the phase 3 clinical trial was co-funded by the Indian Council of Medical Research, making it a true public, private partnership towards public health. Krishna Ella, Chairman and Managing Director, Bharat Biotech, said, “Efficacy against SARS-Cov-2 has been established. COVAXIN has demonstrated an excellent safety record in human clinical trials and in usage under emergency use. COVAXIN is now a global innovator vaccine derived from Research and development from India. The efficacy data against severe COVID-19 and asymptomatic infections is highly significant, as this helps reduce hospitalizations and disease transmission, respectively”.

Findings available in bioRxiv (April 23, 2021):

https://doi.org/10.1101/2021.04.23.441101 

The country had declined to accept the request without a small local trial on the vaccine’s safety and immunogenicity for Indians. Pfizer Inc has withdrawn an application for emergency-use authorisation of its Covid-19 vaccine in India that it has developed with Germany’s BioNTech, the company told Reuters on Friday.  The U.S. company, which was the first drugmaker to apply for emergency use authorisation of its Covid-19 vaccine in India, had a meeting with the country’s drugs regulator on Wednesday and the decision was made after that, the company said. “Based on the deliberations at the meeting and our understanding of additional information that the regulator may need, the company has decided to withdraw its application at this time,” it said in a statement to Reuters. “Pfizer will continue to engage with the authority and re-submit its approval request with additional information as it becomes available in the near future.”

Pfizer had sought authorisation for its vaccine in India late last year, but the government in January approved two much cheaper shots — one from Oxford University/AstraZeneca and another developed at home by Bharat Biotech with the Indian Council of Medical Research. Both companies had applied for approval of their vaccines after Pfizer. India’s Central Drugs Standard Control Organisation had declined to accept Pfizer’s request for approval without a small local trial on the vaccine’s safety and immunogenicity for Indians, Reuters has reported. Indian health officials say they generally ask for so-called bridging trials to determine if a vaccine is safe and generates an immune response in its citizens whose genetic makeup can be different from people in Western nations. There are, however, provisions under India’s New Drugs and Clinical Trial Rules, 2019, to waive such trials in certain conditions. Pfizer earlier told Reuters its application was supported by data from a global study that showed an overall efficacy rate of 95 per cent with no vaccine-related, serious safety concerns.

Using blood of recovered COVID-19 patients - or so-called convalescent plasma - as a potential treatment is of little benefit in helping hospitalised patients fight off the infection, according to results of a clinical trial in India. Published in the BMJ British Medical Journal on Friday, the results show that convalescent plasma, which delivers antibodies from COVID-19 survivors to infected people, failed to reduce death rates or halt progression to severe disease. The findings, from a study of more than 400 hospitalised COVID-19 patients, are a setback for a treatment that U.S. President Donald Trump touted in August as an “historic breakthrough”. The United States and India have authorised convalescent plasma for emergency use. Other countries, including Britain, are collecting donated plasma so that it could be widely rolled out if shown to be effective.

“The ... trial was able to show a small effect on the rate at which patients were able rid themselves of the virus, but this was not enough to improve their recovery from the disease,” said Simon Clarke, an expert cellular microbiology at the University of Reading. “In simple terms, there were no clinical benefits to the patients.” The Indian researchers enrolled 464 adults with confirmed moderate COVID-19 who were admitted to hospitals across India between April and July. They were randomly split into two groups - with one group receiving two transfusions of convalescent plasma, 24 hours apart, alongside best standard care, and the control group best standard care only. 

After 7 days, use of convalescent plasma seemed to improve some symptoms, such as shortness of breath and fatigue, the researchers said, and led to higher rates of something known as “negative conversion” - a sign that the virus is being neutralised by antibodies. But this did not translate into a reduction in deaths or progression to severe disease by 28 days.

“The poor performance of convalescent plasma in this trial is disappointing but not entirely surprising,” said Ian Jones, a professor of virology, also at Reading University. He said the plasma is more likely to work if given very swiftly after someone is contracts COVID-19. He urged these and other researchers to continue to conduct trials of convalescent plasma as a potential COVID-19 treatment, but to do so in newly diagnosed patients. “We still do not have enough treatments for the early stage of disease to prevent severe disease and until this becomes an option, avoiding being infected with the virus remains the key message,” he said.

Original study published in the British Medical Journal (Oct. 22, 2020):

https://doi.org/10.1136/bmj.m3939

Thought COVID was done with the surprises? Not yet, apparently. Those itchy, red eyes you have that you assumed were just the start of allergy season? It could very well be something called “Arcturus” instead. XBB.1.16, a subvariant of the Omicron variant of the COVID-19 virus that has acquired that unusual stellar label, appears to be spreading quickly in some parts of the world. For now, the worst of it appears to be in India, where local media reported Friday that daily cases are surging - up almost 50% in just the last couple of days. But it's growing in the United States as well. The CDC's variant tracker, updated Friday, shows XBB.1.16 has nearly doubled its proportion in the last week, and is now at 7.2% of all samples sequenced, though may be as high as 11.3%. In HHS Region 2, which includes New York and New Jersey, that figure is now over 9%. The CDC estimates its prevalence could be as high as 14.9%. What's notable about Arcturus so far, besides being highly contagious, is the emergence of a possible new symptom. So far, it's mostly been seen in kids. Indian pediatrician Vipin M.

Vashishtha, a member of the World Health Organization's Vaccine Safety Net program, tweeted last week that there is a rise in cases of "itchy conjunctivitis with sticky eyes" that may be associated with the subvariant. The director of the Mayo Clinic's Clinical Virology Laboratory on Thursday also reported that experts are seeing a rise in red, itchy eyes in younger patients with this new strain, a symptom not yet seen during the three years of the pandemic. The variant does not yet appear on the city health department's tracking reports, though the page hasn't been updated since early this month. A week ago, it wasn't a blip on the CDC's variant tracker for the region, either, nor does New York state's surveillance reflect the incidence rate now reported by the federal infectious disease agency. Right now, New York City transmission is the lowest it has been in many months, though that trend mirrors a dramatic plunge in the number of people getting tested. Hospitalization and death rates have also been declining steadily.

Background: Unlike intramuscular vaccines, intranasal COVID-19 vaccines may generate mucosal immunity, which may be critical for to prevent infection and human-to-human transmission. We report interim immunogenicity and safety of an intranasal adenoviral vectored SARS-CoV-2 vaccine (BBV154, iNCOVACC®) in healthy adults compared with licensed intramuscular vaccine (Covaxin®).

Methods: In this open-label, multicentre, phase 3 clinical trial, healthy Indian adults were randomised to receive either two doses of BBV154 (n = 3,000) or Covaxin® (n = 160) 28 days apart. Primary immunogenicity outcome was geometric mean neutralisation antibody titres (PRNT50) against SARS-CoV-2 viruses; key secondary outcomes were safety and solicited adverse events, secretory-IgA and serum-IgA responses and cell-mediated immune responses.

Findings:We screened 3,209 volunteers between April 16 and June 4, 2022 and enrolled and randomised 3,160 to receive BBV154 (n = 2998) or Covaxin (n = 162). On Day 42, 14 days after the second dose, serum GMTs against ancestral (Wuhan) SARS-CoV-2 were 769 (95% CI: 665‒888) and 531 (426‒662) in BBV154 and Covaxin groups. The GMT ratio of 1·45 (95% CI: 1·11‒1·88) met the pre-defined superiority criterion for BBV154 over Covaxin. BBV154 also elicited a higher serum neutralising GMT [171 (137–213)] against Omicron BA.5 than Covaxin [82·4 (48·9–139)]. Similarly, at day 42 GMTs of secretory IgA were 12·3 (95% CI: 8·7 ‒17·4) and 6·6 (95% CI 4·6 ‒9·5) after BBV154 and Covaxin; BBV154 was superior to Covaxin with a GMT ratio of 1·9 (95% CI 1·1–3·0). BBV154 induced higher serum IgA titres and significantly higher levels of antibody-secreting plasmablasts on Day 42. Both vaccines induced equivalent T cell memory responses. Both vaccines were well tolerated, systemic adverse events were reported by 2·7% (82/2990) of BBV154 recipients and 6·2% (10/161) of Covaxin vaccinees. Nasal reactions were experienced by 4·9% (146/2990) of BBV154 participants, whereas 23·0% (37/161) of Covaxin® vaccinees experienced local injection site reactions.

Interpretation:Two intranasal doses of BBV154 were well tolerated with no safety concerns while eliciting superior humoral and mucosal immune responses compared with two intramuscular Covaxin injections. Further studies to assess the effect of BBV154 on infection and transmission are warranted.

Trial Registration: The trial was registered on the Indian Clinical Trials Registry India, CTRI/2022/02/40065, and ClinicalTrials.gov, NCT05522335.

Preprint at the Lancet available (Jan.31, 2023):

https://papers.ssrn.com/sol3/papers.cfm?abstract_id=4342771

The study, done by researchers in India, found deposits of blood, calcium and iron at abnormal levels in key regions of the brain. The study was done using MRI scans six months after an infection. People with long Covid suffer physical alterations to their brain months after clearing the initial infection, a study has shown. MRIs of patients still suffering with symptoms six months later show clusters in parts of the brain linked to fatigue, headaches and cognition. The Indian researchers behind the study say it is the first to show that Covid causes physical changes to the brain. Other studies have found that the virus can also cause changes in other organs such as the heart and lungs. Long Covid is not a specific condition with a set diagnosis, but instead an amalgamation of different symptoms with tenuous links to one-another that have been placed in the same category.   The Centers for Disease Control and Prevention (CDC) estimates that one in five adults that are infected with Covid will suffer long Covid to varying degrees.  There is no proven treatment or cure, but experts are exploring whether an alcoholism drug has benefit after showing promise in small studies.

Researchers from the the Indian Institute of Technology, in Dehli, gathered data from 46 patents who had Covid in the last six months and 30 people that had never been infected with the virus.

They found that most of the people who had recovered from Covid had changes in the circulation of tiny blood vessels in the frontal lobe and brain stem areas. These regions are involved in higher order cognitive skills such as language expression and voluntary movements. Sapna Mishra, a PhD candidate at the institute a lead researchers of the study said 'these brain regions are linked with fatigue, insomnia, anxiety, depression, headaches and cognitive problems.' The cluster obtained in the frontal lobe primarily showed changes in white matter. White matter is found in the deepest tissues of the brain and is made up of millions of nerve fibers that connects parts of the brain and links the brain to the spinal cord Through changes in white matter, the brain finds it harder to transfer information, leading to difficulties with memory, mobility and balance. These clusters in the frontal lobe were made up of three elements. They were made up of portions of the left orbital-inferior frontal gyrus, which is a key region for language comprehension and production and the right orbital-inferior frontal gyrus. The latter is associated with functions like attention, motor inhibition, imagery, social cognitive processes, and processing speech and language. White matter was the final component of these clusters.

The researchers also found significant differences in the right ventral diencephalon region in the brain. This area is linked to many key bodily functions such as releasing hormones, sending sensory and motor signals to the outer surface of the brain. These functions are responsible for processing thought, emotion, language and memory, and the body's daily sleep and wake cycle. Researchers say that this is the first study that focuses on how the virus affects actual composition of the brain, and how it in turn causes long Covid symptoms.  'Our study highlights this new aspect of the neurological effects of Covid-19 and reports significant abnormalities in Covid survivors,' Ms Mishra said. She added: 'This study points to serious long-term complications that may be caused by the coronavirus, even months after recovery from the infection. 'The present findings are from the small temporal window. However, the longitudinal time points across a couple of years will elucidate if there exists any permanent change.' The researchers are now conducting a study on the same patient cohort to determine whether these brain abnormalities persist over a longer time frame. Long Covid has puzzled scientists and physicians since it first popped on their radar in 2020. Its causes have not been figured out, but experts believe it could be tied to the body's immune response to the virus. There have also been previously known cases of people suffering long-term symptoms after suffering more common viruses like the flu. The CDC estimates that around 7.5 per cent of American adults are suffering from long Covid symptoms. Sufferers are generally under the age of 50, and are more likely to be women. Reports of long Covid are most common in southern states like Kentucky and Alabama. 

NEW DELHI: The Drugs Controller General of India (DCGI) approved Bharat Biotech's Covid-19 recombinant nasal vaccine, health minister Mansukh Mandaviya tweeted on Tuesday. Notably, this will be India's first nasal vaccine for coronavirus. He took to Twitter, the health minister said, "Big Boost to India's Fight Against Covid-19! Bharat Biotech's ChAd36-SARS-CoV-S Covid-19 (Chimpanzee Adenovirus Vectored) recombinant nasal vaccine approved by @CDSCO_INDIA_INF for primary immunization against Covid-19 in 18+ age group for restricted use in emergency situation." "This step will further strengthen our collective fight against the pandemic. India has harnessed its science, R&D, and human resources in the fight against Covid-19 under PM @NarendraModi Ji's leadership," he added. He also said that we will defeat Covid-19 with a science-driven approach. "With the science-driven approach and Sabka Prayas, we will defeat Covid-19," he said. The regulator approved the vaccine for primary immunisation of those aged 18 years and above, for restricted use in emergency situations, Mandaviya added. The Hyderabad-based firm completed clinical trials of the nasal vaccine with about 4,000 volunteers and there is no side effect or adverse reaction reported so far, company sources had said.

Since the end of 2021, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant outcompeted other variants and took over the world. After the emergence of original Omicron BA.1, Omicron BA.2 subvariant emerged and outcompeted BA.1. As of July 2022, some BA.2 subvariants, including BA.2.12.1, BA.4 and BA.5, emerged in multiple countries and begun outcompeting original BA.2. Moreover, a novel BA.2 subvariant, BA.2.75, was detected in eight countries including India at the end of June 2022, and preliminary investigations suggest that BA.2.75 is more transmissible over the other BA.2 subvariants. On July 7, 2022, the WHO classified BA.2.75 as a variant-of-concern lineage under monitoring. We have recently demonstrated that BA.4/5 is highly resistant to a therapeutic monoclonal antibody, cilgavimab, than BA.2. The resistance of SARS-CoV-2 variants to therapeutic antibodies can be attributed to the mutations in the viral spike protein. Compared to the BA.2 spike, BA.2.12.1 and BA.4/5 respectively bear two and four mutations in their spike proteins. On the other hand, the majority of BA.2.75 spike bears nine substitutions. The fact that the mutation number in the BA.2.75 spike is larger than those in the BA.4/5 spike raises the possibility that the BA.2.75 spike significantly reduces sensitivity towards therapeutic monoclonal antibodies than BA.2 and BA.4/5. In this study, we generated pseudoviruses harboring the spike proteins of BA.2.75, BA.4/5 and BA.2 and evaluated the efficacy of ten therapeutic monoclonal antibodies and three antibody cocktails against BA.2.75.

Preprint available in medRxiv (July 15, 2022):

 https://doi.org/10.1101/2022.07.14.500041 

KENILWORTH, N.J., July 9, 2021 – Merck (NYSE: MRK), known as MSD outside the United States and Canada, affirmed its commitment to enabling global access to molnupiravir through its voluntary license agreements and ongoing clinical program. As previously announced, Merck has entered into voluntary license agreements for molnupiravir with established Indian generics manufacturers.Merck has entered into these agreements to accelerate availability of molnupiravir in India and in other low- and middle-income countries (LMICs) following approvals or emergency authorization by local regulatory agencies.  Molnupiravir is an investigational oral antiviral agent currently being studied in a Phase 3 trial for the treatment of non-hospitalized patients with confirmed COVID-19. Merck is developing molnupiravir in collaboration with Ridgeback Biotherapeutics.

One of these generics manufacturers, Hetero, has announced that it has accumulated positive data from an open label clinical study of molnupiravir and has submitted these data to the Drug Controller General of India (DCGI).  Merck is encouraged by these promising data and looks forward to continuing to work with Hetero and other generics manufacturers that Merck has agreements with as they conduct studies of generic versions of investigational molnupiravir.  Merck, in collaboration with Ridgeback Biotherapeutics, is conducting an ongoing randomized placebo-controlled phase 2/3 clinical trial of molnupiravir in non-hospitalized patients with confirmed COVID-19 at more than 100 sites worldwide. For more information on this clinical trial visit https://merckcovidresearch.com. Merck has a long track record of making our medicines and vaccines accessible and affordable globally, and we remain committed to doing the same for molnupiravir. These voluntary license agreements are part of this commitment.

About Molnupiravir

Molnupiravir (EIDD-2801/MK-4482) is an investigational, orally bioavailable form of a potent ribonucleoside analog that inhibits the replication of multiple RNA viruses including SARS-CoV-2, the causative agent of COVID-19. Molnupiravir has been shown to be active in several models of SARS-CoV-2, including for prophylaxis, treatment, and prevention of transmission, as well as SARS-CoV-1 and MERS. EIDD-2801 was invented at Drug Innovations at Emory (DRIVE), LLC, a not-for-profit biotechnology company wholly owned by Emory University and is being developed by Merck & Co., Inc. in collaboration with Ridgeback Biotherapeutics. Since licensed by Ridgeback, all funds used for the development of EIDD-2801/MK-4482 have been provided by Wayne and Wendy Holman and Merck.

About Merck

For 130 years, Merck, known as MSD outside of the United States and Canada, has been inventing for life, bringing forward medicines and vaccines for many of the world’s most challenging diseases in pursuit of our mission to save and improve lives. We demonstrate our commitment to patients and population health by increasing access to health care through far-reaching policies, programs and partnerships. Today, Merck continues to be at the forefront of research to prevent and treat diseases that threaten people and animals – including cancer, infectious diseases such as HIV and Ebola, and emerging animal diseases – as we aspire to be the premier research-intensive biopharmaceutical company in the world. For more information, visit www.merck.com and connect with us on Twitter, Facebook,  Instagram, YouTube and LinkedIn.

The Centers for Disease Control and Prevention (CDC) yesterday said that Delta, a highly transmissible COVID-19 variant first identified in India and currently sweeping through the United Kingdom, now makes up at least 10% of all US cases. On May 22, the variant had made up only 2.7% of cases.The CDC also now designated Delta as a variant of concern, which means the agency officially recognizes that the variant may carry a risk of more severe illness and transmissibility. In addition to Delta, the CDC has noted five other variants of concern. The rapid rise of the variant in the United Kingdom—where it now accounts for 90% of cases—has slowed that nation’s reopening efforts by 4 or 5 weeks.

See variant distribution in the U.S.A:

https://covid.cdc.gov/covid-data-tracker/#variant-proportions 

A study by France’s Pasteur Institute found people who had received two doses of Pfizer saw a three-fold reduction in their antibodies against the B. 1.617 variant. The co-author of the research said the findings show that ‘this variant has acquired partial resistance to antibodies’  The Pfizer vaccine is slightly less effective but appears to still protect against the more transmissible Covid-19 

The Drug Controller General of India (DCGI) on Friday granted emergency use approval for pharma major Zydus Cadila’s antiviral drug ‘Virafin’, to treat moderate COVID-19 disease in adults, company press release said. “A single dose subcutaneous regimen of the antiviral Virafin [a pegylated interferon alpha-2b (PegIFN)] will make the treatment more convenient for the patients. When administered early on during COVID, Virafin will help patients recover faster and avoid much of the complications. Virafin will be available on the prescription of a medical specialist for use in hospital/institutional setup,” the release added.  The drug’s safety profile is already well known as it is used in treating people with chronic hepatitis B and C. The drug has been repurposed for treating moderate COVID-19 disease. According to Dr. Sharvil Patel, Managing Director, Cadila Healthcare Limited, the therapy “significantly reduces viral load when given early on and can help in better disease management”.

In a multi-centre trial in 20-25 centres across India, the company found the drug reduced the need for supplemental oxygen. This clearly “indicates that the antiviral was able to control respiratory distress and failure which has been one of the major challenges in treating COVID-19”, the company said. In the phase-3 trials, the drug was able to achieve “better clinical improvement in the patients suffering from COVID-19”. A “higher proportion (91.15%) of patients administered the drug were RT-PCR negative by day seven as it ensures faster viral clearance”. According to an April 5 company press release, the drug reduced the duration for supplemental oxygen to 56 hours from 84 hours in moderate COVID-19 patients. The results of the phase-2 trial using the drug published in the International Journal of Infectious Diseases found that of the 20 participants who received the drug and standard of care, 19 (95%) achieved clinical improvement on day 15 compared to 13 of the 20 (68.42%) participants who were in the control arm and received only standard of care. The trial found that 80% and 95% of participants who received the therapy plus standard of care were RT-PCR negative on day seven and 14, respectively, compared to 63% and 68% in the control arm.

The significant improvement in clinical status on day 15 is likely due to faster viral reduction compared to the control arm. Participants with moderate disease showed a difference as early as day seven, which became significant by day 14, the authors say in the paper. Mild adverse events were reported in 11 participants in the phase-2 trial compared with eight in the control arm. According to the release, type I interferons are the body’s first line of defence against many viral infections. In old people, the ability to produce interferon alpha in response to viral infections gets reduced, which might be the reason for higher mortality. The drug when administered early during the disease can replace this deficiency and help in the recovery process.

Bharat Biotech's vaccine showed 81% efficacy in preventing symptomatic COVID-19 in an interim analysis of a late-stage trial in India, it said on Wednesday, a major boost for the shot shunned by some due to a lack of such data.  The positive result also brightens prospects for sales overseas, with the vaccine, India’s first successful homemade COVID-19 shot, already attracting interest from more than 40 countries, according to the firm. “COVAXIN demonstrates high clinical efficacy trend against COVID-19 but also significant immunogenicity against the rapidly emerging variants,” Bharat Biotech Chairman Krishna Ella said in a statement, referring to its vaccine. It said the analysis is based on 43 cases of COVID-19 patients who showed symptoms ranging from mild to moderate and severe, and of the total cases, 36 were from a placebo group, while seven were from those who received the vaccine. The results come as India struggles to convince its health and front-line workers to take the Bharat Biotech shot, which was approved in January without late-stage efficacy data.

Only about 11% of the more than 10 million Indians vaccinated had taken the Bharat Biotech shot as of last week, Reuters had reported. Many politicians in India, including Prime Minister Narendra Modi, have been inoculated with COVAXIN this week instead of a rival one developed by AstraZeneca Plc and Oxford University, as they seek to boost confidence in the locally developed vaccine. With more than 11 million infections so far, India is battling the world’s largest COVID-19 outbreak outside the United States. COVAXIN, which can be stored at normal refrigerator temperatures, is likely to be effective against the UK strain of the coronavirus, a study said in late January. The shot is an inactivated vaccine that introduces dead virus into the body to trigger an immune response.

Bharat Biotech is based in the southern Indian city of Hyderabad, a hub for drug and vaccine makers. It began operations in 1996, and has delivered over 3 billion doses globally of various types of vaccines, including ones for Hepatitis-B and typhoid. It is aiming to produce about 700 million doses of COVAXIN this year. The company, which signed a deal with Brazil to supply 20 million doses of the shot, said the next interim analysis will target 87 cases and the final analysis will be based on 130 cases. Its first interim analysis was based on a Phase III clinical trial involving 25,800 participants which was conducted with the Indian Council for Medical Research (ICMR), a federal government body. The trial included 2,433 participants who were older than 60, and 4,500 participants with co-morbidities. The trial results were evaluated by an independent data safety and monitoring board, the ICMR said in a separate statement.

It aims to inoculate some 300m people this year in one of the world's largest vaccination campaigns. The drugs regulatory authority gave the green light to the jabs developed by AstraZeneca with Oxford University and by local firm Bharat Biotech. Prime Minister Narendra Modi called it "a decisive turning point". India plans to inoculate some 300 million people on a priority list this year. It has recorded the second-highest number of infections in the world, with more than 10.3 million confirmed cases to date. Nearly 150,000 people have died. On Saturday India held nationwide drills to prepare more than 90,000 health care workers to administer vaccines across the country, which has a population of 1.3 billion people.  The Drugs Controller General of India said both manufacturers had submitted data showing their vaccines were safe to use. However, opposition politicians and some doctors have criticised a lack of transparency in the approval process.

The rate of death went down in patients over 65. Researchers also found that children of all ages became infected and spread the virus to others. With 1.3 billion people jostling for space, India has always been a hospitable environment for infectious diseases of every kind. And the coronavirus has proved to be no exception: The country now has more than six million cases, second only to the United States. An ambitious study of nearly 85,000 of those cases and nearly 600,000 of their contacts, published Wednesday in the journal Science, offers important insights not just for India, but for other low- and middle-income countries. Among the surprises: The median hospital stay before death from Covid-19, the illness caused by the coronavirus, was five days in India, compared with two weeks in the United States, possibly because of limited access to quality care. And the trend in increasing deaths with age seemed to drop off after age 65 — perhaps because Indians who live past that age tend to be relatively wealthy and have access to good health care. The contact tracing study also found that children of all ages can become infected with the coronavirus and spread it to others — offering compelling evidence on one of the most divisive questions about the virus. And the report confirmed, as other studies have, that a small number of people are responsible for seeding a vast majority of new infections.

An overwhelming majority of coronavirus cases globally have occurred in resource-poor countries, noted Joseph Lewnard, an epidemiologist at the University of California, Berkeley, who led the study. But most of the data has come from high-income countries. “It still surprises me that it took until this point for a lot of data to come out of a low- or middle-income country about the epidemiology of Covid,” he said. In particular, he added, few studies anywhere have done contact tracing at the scale of the study. “I think it’s some of the most important data we collect in an epidemic in order to decide what kinds of interactions are safe, and what kinds are not,” he said. And yet, “data like this has not really been published very much.” Though its overall total of cases is huge, the per capita number of cases reported daily in India — and in many other low-income countries, including in Africa — is lower than in Spain, France or even the United States. And its number of deaths has not yet topped 100,000 — which has surprised some scientists. India “is a place where you would expect a disease like this to roar through, at least in the older populations,” said Dr. Krutika Kuppalli, an infectious disease expert at the Medical University of South Carolina. “They haven’t seen that as much as you would expect.”

India recorded its first case of Covid-19 on Jan. 30 in an Indian citizen evacuated from China. The government began screening travelers from China and other countries on Feb. 7 and extended these efforts to travelers by sea and land on March 15. The country shut down on March 25 but reopened two months later, despite soaring rates of infection. The study focused on two southern Indian states, Andhra Pradesh and Tamil Nadu, which together have a population of about 128 million, and represent two of the five Indian states with the most cases. They also have among the most sophisticated health care systems in the country. Contact tracers reached more than three million contacts of the 435,539 cases in these two states, although this still did not represent the full set of contacts. The researchers analyzed data for the 575,071 contacts for whom test information was available...

Original study available in Science (Sept. 30, 2020):

https://doi.org/10.1126/science.abd7672