Study shows efficacy of Pfizer-BioNTech and Moderna vaccines against SARS-CoV-2 delta variant

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News-Medical.Net 02 August, 2021 - 07:55pm 61 views

The coronavirus is rife in common US deer

Nature.com 03 August, 2021 - 03:11am

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One-third of white-tailed deer in the north-eastern United States have antibodies against SARS-CoV-2 — a sign that they have been infected with the virus.

Researchers say the rapid exposure of a large number of animals to the virus is concerning, but that more studies are needed to assess whether the deer can infect each other — and other species — in the wild. “It’s an intriguing observation but still needs to be interpreted with caution,” says Aaron Irving, an infectious-diseases researcher at Zhejiang University in Haining, China.

The crucial questions are “how the virus spread to deer and if it will spread from infected deer to other wildlife or to domestic livestock such as cattle”, says Linda Saif, a virologist at the Ohio State University in Wooster.

Researchers are concerned about the emergence of new animal ‘reservoirs’ — animal populations that harbour SARS-CoV-2. A pool of infected animals could provide a refuge where the virus could evolve in ways that threaten vaccine efficacy. A reservoir could also allow the virus to spread to other species and back to people, even after the pandemic subsides. Saif has documented other coronaviruses jumping between species. “Similar spillover into wildlife may now be occurring worldwide,” she says.

The search for animals harbouring coronavirus — and why it matters

To assess that risk, Susan Shriner at the US Department of Agriculture (USDA) in Fort Collins, Colorado, and her colleagues tested 385 blood samples collected as part of regular wildlife-surveillance activities between January and March 2021 in four US states — Michigan, Pennsylvania, Illinois and New York. They found that a striking 40% of the samples contained SARS-CoV-2 antibodies, which are produced in response to infection. None of the surveyed deer showed signs of illness.

The researchers’ testing of archived samples also turned up antibodies in 3 samples from early 2020, when SARS-CoV-2 was beginning to circulate in the United States. All told, one-third of the 2020 and 2021 samples had antibodies for the virus.

“Given the percentage of samples in this study that had detectable antibodies, as well as the high numbers of white-tailed deer throughout the United States and their close contact with people, it is likely that deer in other states have also been exposed to the virus,” says a spokesperson for the USDA.

“The data strongly suggest that this deer species was infected with SARS-CoV-2 at some point in time,” Banerjee says. But the researchers did not test the animals for viral RNA, which would be needed to establish whether they are an animal reservoir, he says.

The real mystery, says Banerjee, is how the deer were exposed. It could have been through contact with people, other animals or even contaminated wastewater. “If there is a common source of exposure for the deer, then likely the same source can expose other animals.”

The results stress the importance of surveying deer, as well as their predators and other animals that have close contact with deer, for SARS-CoV-2, the researchers say.

Chandler, J. C. et al. Preprint at bioRxiv https://doi.org/10.1101/2021.07.29.454326 (2021).

Palmer, M. V. et al. J. Virol. 95, e00083-21 (2021).

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Opinion: Our children will suffer if adults can't get school Covid precautions right

CNN 03 August, 2021 - 03:11am

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Unvaccinated and vaccinated have similar viral load in communities high in SARS-CoV-2 delta

News-Medical.Net 03 August, 2021 - 03:11am

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A US-based study has recently compared the viral load in vaccinated and unvaccinated individuals who have been infected with the delta variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

The findings reveal that vaccinated and unvaccinated individuals exhibit similar viral loads following delta infection and that vaccine breakthrough cases have the potential to transmit infection to others. The study is currently available on the medRxiv* preprint server.

Viral breakthrough infections occur when vaccinated individuals become infected with the pathogen against which the vaccine was developed. Following immunization, ideally, a vaccine is expected to completely inhibiting viral replication by inducing “sterilizing immunity.” However, not all intramuscular vaccines made against respiratory viruses -- including the Coronavirus disease 2019 (COVID-19) vaccine -- result in sterilizing immunity. These vaccines are expected to provide protection against symptomatic disease, severe disease, and death. In this context, vaccine-mediated reduction in viral load is believed to play an essential role in reducing disease severity and controlling person-to-person viral transmission.

In the current study, the scientists evaluated whether COVID-19 vaccines can reduce viral loads in vaccine breakthrough cases. Specifically, they have compared the viral load in SARS-CoV-2-positive samples collected from 83 individuals in Dane County, Wisconsin, which has exceptionally high vaccine coverage compared to other populated counties in the United States.

Based on the self-reported vaccination status and dates of complete vaccination, the scientists divided the participants into two groups: the fully vaccinated group with 32 individuals and the unvaccinated group with 51 individuals. Then, as a “convenient proxy” of viral load estimation, they used polymerase chain reaction (PCR)-generated threshold cycle (Ct) values to compare viral loads between vaccinated and unvaccinated individuals who have been infected mostly with the SARS-CoV-2 delta variant (B.1.617.2).

The delta variant of SARS-CoV-2, first identified in India, has caused a sharp increase in COVID-19 cases globally. Compared to other viral variants, the delta variant has significantly higher infectivity and is partially resistant to antibody-mediated neutralization.

The respiratory samples used in this study to estimate viral load were collected during July 2021, when the delta variant was predominantly circulating worldwide and the number of new COVID-19 cases was increasing in the United States.

Based on the Ct values, no significant difference in viral load was observed between fully vaccinated and unvaccinated individuals. Of all collected samples, 16 were sequenced to identify viral variants. The delta variant was identified in the majority (88%) of sequenced samples, indicating a high prevalence of this variant in Dane county.

For further analysis, additional 208 samples from other Wisconsin counties were included. Of a total of 291 samples from all counties, 73 were associated with vaccine breakthrough cases. About 84% of vaccine breakthrough cases exhibited Ct values less than 30, which indicates the presence of infectious virus in respiratory samples. Similar Ct values were estimated in 83% of unvaccinated individuals with SARS-CoV-2 infection. Surprisingly, about 33% of vaccine breakthrough cases exhibited very high viral loads with Ct values less than 20.

Based on the genetic sequencing data, the delta variant was identified in 84% of all tested samples. This further indicates a high prevalence of the delta variant in Wisconsin during the study period. Based on this information, the scientists assumed that the delta variant caused almost all infections considered in the study.     

Taken together, the study findings indicate that the delta variant of SARS-CoV-2 is capable of inducing infection even in fully vaccinated individuals and that a significant proportion of vaccinated individuals with breakthrough infections are capable of transmitting the virus to others.

In Dane county, almost 68% of the population is fully vaccinated. Unfortunately, despite high vaccine coverage, a high percentage of vaccine breakthrough infections with high viral loads have been detected in this county. This finding further highlights the need for frequent testing and continuous adherence to non-pharmacological control measures to limit the community-level spread of SARS-CoV-2.

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information

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Tags: Antibody, Coronavirus, Coronavirus Disease COVID-19, CT, Genetic, immunity, Immunization, Pathogen, Polymerase, Polymerase Chain Reaction, Respiratory, SARS, SARS-CoV-2, Severe Acute Respiratory, Severe Acute Respiratory Syndrome, Syndrome, Vaccine, Virus

Dr. Sanchari Sinha Dutta is a science communicator who believes in spreading the power of science in every corner of the world. She has a Bachelor of Science (B.Sc.) degree and a Master's of Science (M.Sc.) in biology and human physiology. Following her Master's degree, Sanchari went on to study a Ph.D. in human physiology. She has authored more than 10 original research articles, all of which have been published in world renowned international journals.

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Dutta, Sanchari Sinha. "Unvaccinated and vaccinated have similar viral load in communities high in SARS-CoV-2 delta". News-Medical. https://www.news-medical.net/news/20210803/Unvaccinated-and-vaccinated-have-similar-viral-load-in-communities-high-in-SARS-CoV-2-delta.aspx. (accessed August 03, 2021).

Dutta, Sanchari Sinha. 2021. Unvaccinated and vaccinated have similar viral load in communities high in SARS-CoV-2 delta. News-Medical, viewed 03 August 2021, https://www.news-medical.net/news/20210803/Unvaccinated-and-vaccinated-have-similar-viral-load-in-communities-high-in-SARS-CoV-2-delta.aspx.

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Pfizer moves towards an oral anti-COVID-19 therapy

News-Medical.Net 03 August, 2021 - 03:11am

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Researchers in the United States have described a novel antiviral agent against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) currently being evaluated in clinical trials as a treatment for coronavirus disease 2019 (COVID-19).

“Alongside vaccines, antiviral therapeutics are an important part of the healthcare response to counter the ongoing threat presented by COVID-19,” says Dafydd Owen from Pfizer Worldwide Research in Cambridge, Massachusetts, and colleagues.

The team has now described an orally bioavailable inhibitor of the SARS-CoV-2 main protease (Mpro) that cleaves viral polyproteins into the shorter proteins needed for viral replication.

The inhibitor – called  PF-07321332 – also exhibits in vitro pan-human coronavirus antiviral activity and excellent in vivo safety profiles.

A pre-print version of the research paper is available on the medRxiv* server, while the article undergoes peer review.

Over the last two decades, the emergence of novel human coronaviruses, including SARS-CoV-1, Middle East Respiratory Syndrome (MERS), and SARS-CoV-2, has highlighted the significant potential threat that this class of viruses poses to global public health.

Since the COVID-19 outbreak began in late December 2019, SARS-CoV-2 has infected almost 200 million people and caused more than 4.2 million deaths globally.

The virus infects host cells when the receptor-binding domain of its surface spike protein binds to the human receptor angiotensin-converting enzyme 2 (ACE2).

While effective COVID-19 vaccines targeting this spike-ACE2 interaction have been developed and rolled out within record time, a substantial proportion of the population is either unwilling to be vaccinated or unable to due to existing medical conditions.

“Oral SARS-CoV-2 specific therapeutics that are applicable for treatment of the broad population upon COVID-19 diagnosis are urgently needed,” writes Owen and colleagues. “Such a treatment approach may prevent more severe disease, hospitalizations and deaths. Indirectly, it may also reduce further transmission from infected individuals.”

The SARS-CoV-2 genome encodes two polyproteins (pp1a and pp1ab) that are cleaved by Mpro to yield shorter proteins that are crucial for viral replication.

The coronavirus Mpro is a three-domain cysteine protease with substrates that share common features, including the presence of a P1 glutamine (Gln) residue.

“No known human equivalent cysteine protease exploits a P1 Gln as the cleavage site prompt, thus offering an intriguing selectivity hypothesis for this viral target over the human proteome,” say the researchers.

Furthermore, since the SARS-CoV-2 Mpro and the spike protein are distinct entities, the antiviral efficacy of a small-molecule Mpro inhibitor is not expected to be affected by the spike mutations that variants of concern have evolved.  

“Given the pivotal role of SARS-CoV-2 Mpro in viral replication, its potential for mechanistic safety, and expected lack of spike protein variant resistance challenges, SARS-CoV-2 Mpro inhibition represents an attractive small molecule approach for an oral antiviral therapy to treat COVID-19,” writes the team.

As part of the response to the SARS-CoV-1 outbreak in 2002, researchers attempted to identify inhibitors of the SARS-CoV-1 Mpro.

This led to the discovery of PF-00835231 (referred to hereafter as 1) as a potent inhibitor of recombinant SARS-CoV-1 Mpro in a fluorescence resonance energy transfer (FRET)-based cleavage assay.

Furthermore, PF-00835231 has also been shown to potently inhibit recombinant SARS-CoV-2 Mpro, which shares 100% sequence homology with the binding site of SARS-CoV-1 Mpro.

The phosphate prodrug form of PF-00835231 is now currently being investigated as an intravenous treatment for patients hospitalized with COVID-19.

As part of the researchers’ oral SARS-CoV-2 Mpro inhibitor program, they pursued two functional groups that precedented as covalent warheads for cysteine proteases.

These nitriles and benzothiazol-2-yl ketones replace the hydrogen bond donor of the P1’ α-hydroxymethyl ketone moiety in 1 to improve its absorptive permeability and oral absorption in animals.

The addition of the P1’ nitrile 6 led to the selection of what would ultimately become the clinical candidate PF07321332.

PF-07321332 demonstrated potent inhibition in FRET Mpro assays representing all coronaviruses known to infect humans – SARS-CoV-2, SARS-CoV-1, MERS, HKU1, OC43, 229E and NL63.

In vitro analysis of the antiviral activity in human adenocarcinoma-derived alveolar basal epithelial (A549) cells expressing ACE2 revealed that PF-07321332 inhibited SARS-CoV-2 replication with a half-maximal effective concentration (EC50) value and an EC90 value of 77.9nM and 215nM, respectively.

No cytotoxicity was detected at concentrations as high as 3µM.

Furthermore, PF-07321332 demonstrated potent antiviral activity against SARS-CoV-1 (EC90 = 317nM), MERS (EC90 = 351nM) and 229E (EC90 = 620nM) in cytopathic effect assays.

Next, the team evaluated the in vivo antiviral activity of PF-07321332 using a mouse-adapted model of SARS-CoV-2 infection. Following intranasal infection, twice daily (BID) oral administration of PF-07321332 protected BALB/c mice from weight loss, compared with mice that received a placebo.

The researchers also performed in vitro studies of the enzymes involved in PF-07321332 metabolism, which established a predominant role for CYP3A4.

A potent inactivator of CYP3A4 called ritonavir (RTV) is already used as a pharmacokinetic enhancer of several marketed protease inhibitors that are subject to metabolic clearance via CYP3A4.

Owen and colleagues say the safety, tolerability, and pharmacokinetics of PF-07321332 as a single agent and in combination with RTV are currently under investigation in a randomized, double-blind, placebo-controlled trial.

The administration of two oral PF-07321332 doses has already been shown to be safe, well-tolerated, and to exhibit a significant boost in plasma concentrations when co-administered with RTV.

Next, “the efficacy of PF-07321332 in COVID-19 patients will be assessed with a BID dosing paradigm with the potential to increase the dose of PF-07321332 as a single agent and/or co-administration with RTV,” says the team.

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

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In this interview, News-Medical speaks to Professor Dana Crawford about her research efforts during the COVID-19 pandemic.

In this interview, News-Medical speaks to Dr. Neeraj Narula about ultra-processed food and how this can increase your risk of developing inflammatory bowel disease(IBD).

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Summer Campers Spread COVID at Home, Follow-Up Finds

WebMD 02 August, 2021 - 01:28pm

August 2, 2021 -- After SARS-CoV-2 spread at a sleepaway camp in Georgia last summer, researchers described the efficient spread and high attack rates at camp.

In a report published online in The New England Journal of Medicine, researchers found that campers spread COVID to household members after returning home ― but transmission was more likely from some than others. Distancing and masking helped reduce the risk.

Victoria T. Chu, MD, with the CDC in Atlanta, Georgia, and colleagues with the agency and the Georgia Department of Health followed up with 224 camp attendees, aged 7 to 19 years, who had evidence of SARS-CoV-2 infection on laboratory testing.

These index patients — 88% of whom had symptoms — had 526 household contacts, mainly parents and siblings. Of 377 household contacts who underwent testing, 46 (12%) tested positive. Another two cases in household contacts were identified using clinical and epidemiologic criteria.

Of the 41 adult household contacts who were infected, four (about 10%) were hospitalized. Their hospital stays ranged from 5 to 11 days. Of the seven infected household contacts who were younger than 18 years, none were hospitalized.

The four hospitalized adults were parents and grandparents aged 45 to 80 years, Chu said. Two of the four had underlying conditions. None of the household contacts died.

In an adjusted analysis, campers who had practiced physical distancing were less likely to transmit the virus at home, compared with those who had not practiced physical distancing. Household members who had had close or direct contact with the index patients were more than 5 times more likely to become infected, compared with family members with minimal or no contact, analyses showed.

"This retrospective study showed that the efficient transmission of SARS-CoV-2 from school-age children and adolescents to household members led to the hospitalization of adults with secondary cases of Covid-19," the researchers wrote. "In households in which transmission occurred, half the household contacts were infected."

The secondary attack rates in this report may be an underestimate because testing was voluntary and participants reported the results themselves, the authors noted. It is possible that infected household contacts spread the virus further, but this study did not address that question, Chu said.

For the study, investigators interviewed all camp attendees and their parents or guardians by phone between July 17, 2020, and August 24, 2020, to collect information about demographic and clinical characteristics, SARS-CoV-2 testing, and preventive measures. The researchers' analysis excluded households in which illness onset in a household contact occurred before or less than 2 days after a camper became sick.

About a third of the index patients began to have symptoms while still at camp. These campers may have been less infectious by the time they got home, compared with those whose symptoms started after they returned.

Two thirds of the index patients adopted physical distancing at home, which "probably reduced the transmission of SARS-CoV-2 in the household," Chu and colleagues wrote.

"Children who have had a known COVID-19 exposure should quarantine and obtain testing if they develop symptoms within the 14 days of returning home," Chu advised. "If a child develops COVID-19, the child should be cared for and monitored using the proper combination of physical distancing, isolation when feasible, and mask use to prevent household transmission as much as possible. In addition, any person over the age of 12 is now eligible for vaccination in the United States. If eligible, children attending camp and their family members should get vaccinated to protect themselves and others, as vaccinations are our most effective public health prevention strategy."

Another report regarding four overnight camps in Maine — in which three campers tested positive after they arrived last summer — shows that "aggressive mitigation strategies can be effective" in limiting transmission of the virus, William T. Basco, Jr, MD, said in a commentary on Medscape Medical News.

This summer, a range of factors, including vaccination rates at the camp, may influence transmission dynamics, Chu tells Medscape Medical News. In July, the Associated Press reported outbreaks tied to summer camps in several states.

"Transmission dynamics will probably vary from summer camp to summer camp depending on many factors, such as vaccination rates of camp attendees, the mitigation measures in place, and the number of individual introductions during camp," Chu says. "We would expect that a camp with a low vaccination rate among attendees and no enforcement of mitigation measures" still may experience a large outbreak.

"On the other hand, a large proportion of vaccinated individuals and appropriate implementation of multiple mitigation measures, such as wearing masks, may be quite effective at keeping their transmission rates low," Chu says. "For camps with younger children who are not currently eligible for vaccination, implementing layered prevention strategies (eg, mask use, physical distancing, and encouraging outdoor activities when feasible) is important to prevent transmission."

Although COVID-19 transmission from children to adults, potentially leading to hospitalization, is not a new phenomenon, "data on the extent of transmission driven by children and adolescents in different settings are still quite sparse," Chu says. "A better understanding of their impact on household and community transmission to help guide public health recommendations is particularly important, as most children are still not eligible for vaccination, and in-person schools will be reopening this fall."

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Severe COVID-19: Could new findings lead to better prevention?

Medical News Today 02 August, 2021 - 09:25am

A team from Boston Children’s Hospital, the Massachusetts Institute of Technology, and the University of Mississippi Medical Center looked at cells from the nose and throat of people with SARS-CoV-2 infections and compared these with the samples from healthy individuals who formed the control group.

The researchers took nasal swabs from 35 adults with COVID-19 between April and September 2020.

They then sequenced the RNA in each cell to see which cells contained RNA from the virus — showing they were infected — and which of the cell’s genes were turned on or off in response.

The researchers found that more of the genes that respond to infection were turned on in infected cells compared with healthy cells. However, the effect on the cells with SARS-CoV-2 was different in people with severe and mild infections.

Of the 58 study participants, 35 had COVID-19, ranging from people with mild symptoms to the critically ill. The study included a control group of 15 healthy people — two of whom had previously had COVID-19 — and six intensive care patients, all of whom had tested negative for SARS-CoV-2 infections.

Although the study had only a small sample size, there were some interesting results that may help in the development of effective treatments.

Speaking to Medical News Today, Dr. Christopher Coleman, assistant professor of infection immunology at the University of Nottingham in the United Kingdom, commented: “The finding about the different immune response is especially interesting. Coronaviruses have numerous proteins that block innate immunity, including interferon, so the low response may be due to high viral protein expression.”

Some researchers think that it is extreme inflammatory responses that are responsible for the more severe symptoms of COVID-19.

“Everyone with severe COVID-19 had a blunted interferon response early on in their epithelial cells and were never able to ramp up a defense,” says Dr. Ordovás-Montañés. “Having the right amount of interferon at the right time could be at the crux of dealing with SARS-CoV-2 and other viruses.”

“This study is consistent with previous studies that have shown that a lack of good interferon response leads to more severe disease,” Dr. Jonathan Stoye, a virologist at the Francis Crick Institute in London, U.K., told MNT. “We need to discover why some people have a good interferon response and others don’t.”

“Focusing on the nasopharynx is key, as that’s where the infection starts. For me, the next step would be to look at whether these findings could be used to come up with a diagnostic test to predict whether people will develop severe COVID-19.”

The researchers now plan to investigate what is causing this difference in the interferon response and whether there are ways to enhance it in early COVID-19 infections, perhaps with a nasal spray or drops. Successful developments might also be useful for other viral infections, such as flu.

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