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Archive for the ‘COVID-19’ Category

Will COVID become a disease of the young?

Reporter: Danielle Smolyar, Research Assistant 3 – Text Analysis for 2.0 LPBI Group’s TNS #1 – 2020/2021 Academic Internship in Medical Text Analysis (MTA)

An increase of infections among youth who are unvaccinated in countries with high vaccination rates is getting noticed in the role of young people in the pandemic.

On June 21 is Ross Ministry of health recommended that all individuals between the ages of 12 and 15 should be vaccinated. This makes the nation one of the few that have been approved vaccinations for younger kids. This decision came about in response too many other countries with high rates of vaccination are experiencing an increase in numbers of infections that are found to be in younger age groups.

Israel’s vaccination campaign which has reached to more than 85% of the adult population to be vaccinated noticed that case numbers are dropping around a dozen daily in the month of June. At the end of June, they have realized that the cases began to rise to more than 100 cases a day. These cases were found in kids under the age of 16 which is why the government decided to allow vaccinations.

Ran Balicer, and epidemiologists at Israel’s largest healthcare provider in Tel Aviv said that the younger profile is not surprising.

image source: https://www.nature.com/articles/d41586-021-01862-7

This trend that Israel started to notice is not just happening in Israel. The United States and the United Kingdom COVID-19, “become a disease of the unvaccinated, who are predominantly young”, says Joshua Goldstein, a demographer at the University of California, Berkeley. Stated in the article. 

This trend has been occurring in the countries where the older population were being vaccinated first. Follow the drop in age because they were vaccinating older people who are the most at risk for the disease.

This shift has shut attention to the studies of transmission in the younger age groups. Karin Magnusson immunologist said that it has come very important to understand the burden of the disease among the younger children. 

Magnusson on the impact of COVID-19 in children in Norway. On June 5 pre-print she reported that children see their doctor regularly up to six months after contracting Covid-19.

Balicer, is studying the virus spread in multi-generational households in Israel. Going beyond whether vaccinating children or not the patterns of COVID-19 infection have caused discussions about mask wearing to adolescence and kids in Israel. 

As stated in the article, “As the burden of cases shifts towards younger people, arguments for vaccinating adolescents will become slightly more compelling,” agrees Nick Bundle, an epidemiologist at the European Centre for Disease Prevention and Control in Stockholm.” However, the risk of disease in children still is low and in other countries the total number of cases have declined.

Countries also need to consider the global contacts. As stated in the article, “Are we really better off giving the vaccine to kids in rich countries than to older people [in less wealthy countries] where it might have a much bigger impact on people’s lives?” says Jennie Lavine, who studies infectious-disease dynamics at Emory University in Atlanta, Georgia. “It seems hard for me to imagine a really good argument for that.”

Oh there is a downward shift and the average age of infected with COVID-19 in countries with high COVID-19 vaccination rates it may be short-lived. There could be a few scenarios where the shift could bounce back says Henrik Salje, who is an infectious disease epidemiologist at the University of Cambridge, UK. Many of the countries could start vaccinating the adolescence just like Israel and the United States are already doing so. 

Bundle says that COVID- 19 can still be present in younger kids. “But how big a problem that is, is not a simple thing to respond to.”

SOURCE: Mallapaty, S. (2021, July 8). Will COVID become a disease of the young? Nature News. https://www.nature.com/articles/d41586-021-01862-7

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The race for a COVID-19 vaccine: What’s ahead ?

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COVID vaccines by Pfizer, AstraZeneca are probed in Europe after reports of heart inflammation, rare nerve disorder

Reporter: Dr. Premalata Pati, Ph.D., Postdoc

The NIH-funded adjuvant improves the efficacy of India’s COVID-19 vaccine.

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COVID and the brain: researchers zero in on how damage occurs

Reporter: Danielle Smolyar

Research Assistant 3 – Text Analysis for 2.0 LPBI Group’s TNS #1 – 2020/2021 Academic Internship in Medical Text Analysis (MTA)

Recent evidence has indicated that coronavirus can cause brain fog and also lead to different neurological symptoms. 

Since the beginning of the pandemic, researchers have been trying to understand how the coronavirus SARS-CoV-2 affects the brain

Image Credit: Stanislav Krasilnikov/TASS/Getty

image source:https://www.nature.com/articles/d41586-021-01693-6?utm_source=Nature+Briefing

New evidence has shown how coronavirus has caused much damage to the brain. There is a new evidence that shows that COVID-19 assault on the brain I has the power to be multipronged. What this means is that it can attack on certain Brain cells such as reduce the amount of blood flow that the brain needs to the brain tissue.

Along with brain damage COVID-19 has also caused strokes and memory loss. A neurologist at yell University Serena Spudich says, “Can we intervene early to address these abnormalities so that people don’t have long-term problems?”

We’re on 80% of the people who have been hospitalized due to COVID-19 have showed brain symptoms which seem to be correlated to coronavirus.

At the start of the pandemic a group of researchers speculated that coronavirus they can damage the brain by infecting the neurons in the cells which are important in the process of transmitting information. After further studies they found out that coronavirus has a harder time getting past the brains defense system and the brain barrier and that it does not affect the neurons in anyway.

An expert in this study indicated that a way in which SARS-CoV-2 may be able to get to the brain is by going through the olfactory mucosa which is the lining of the nasal cavity. It is found that this virus can be found in the nasal cavity which is why we swab the nose one getting tested for COVID-19.

Spudich quotes, “there’s not a tonne of virus in the brain”.

Recent studies indicate that SARS-CoV-2 have ability to infect astrocytes which is a type of cell found in the brain. Astrocytes do quite a lot that supports normal brain function,” including providing nutrients to neurons to keep them working, says Arnold Kriegstein, a neurologist at the University of California, San Francisco.

Astrocytes are star-shaped cells in the central nervous system that perform many functions, including providing nutrients to neurons.

Image Credit: David Robertson, ICR/SPL

image source: https://www.nature.com/articles/d41586-021-01693-6?utm_source=Nature+Briefing

Kriegstein and his fellow colleagues have found that SARS-CoV-2 I mostly infects the astrocytes over any of the other brain cells present. In this research they expose brain organoids which is a miniature brain that are grown from stem cells into the virus.

As quoted in the article” a group including Daniel Martins-de-Souza, head of proteomics at the University of Campinas in Brazil, reported6 in a February preprint that it had analysed brain samples from 26 people who died with COVID-19. In the five whose brain cells showed evidence of SARS-CoV-2 infection, 66% of the affected cells were astrocytes.”

The infected astrocytes could indicate the reasoning behind some of the neurological symptoms that come with COVID-19. Specifically, depression, brain fog and fatigue. Kreigstein quotes, “Those kinds of symptoms may not be reflective of neuronal damage but could be reflective of dysfunctions of some sort. That could be consistent with astrocyte vulnerability.”

A study that was published on June 21 they compared eight different brands of deceased people who did have COVID-19 along with 14 brains as the control. The results of this research were that they found that there was no trace of coronavirus Brain infected but they found that the gene expression was affected in some of the astrocytes.

As a result of doing all this research and the findings the researchers want to know more about this topic and how many brain cells need to be infected for there to be neurological symptoms says Ricardo Costa.

Further evidence has also been done on how SARS-CoV-2 can affect the brain by reducing its blood flow which impairs the neurons’ function which ends up killing them.

Pericytes can be found on the small blood vessels which are called capillaries and are found all throughout the body and in the brain. In a February pre-print there was a report about how SARS-CoV-2 can infect the pericyte in the brain organoids. 

David Atwell, a neuroscientist at the University College London, along with his other colleagues had published a pre-print which has evidence to show that SARS-CoV-2 odes In fact pericytes behavior. I researchers saw that in the different part of the hamsters brain SARS-CoV-2 blocks the function of receptors on the pericytes which ultimately causes the capillaries found inside the tissues to constrict.

As stated in the article, It’s a “really cool” study, says Spudich. “It could be something that is determining some of the permanent injury we see — some of these small- vessel strokes.”

Attwell brought to the attention that the drugs that are used to treat high blood pressure may in fact be used in some cases of COVID-19. Currently there are two clinical trials that are being done to further investigate this idea.

There is further evidence showing that the neurological symptoms and damage could in fact be happening because of the bodies on immune system reacting or misfiring after having COVID-19.

Over the past 15 years it has become evident that people’s immune system’s make auto antibodies which attack their own tissues says Harald Prüss in the article who has a Neuroimmunologist at the German Center for neurogenerative Diseases in Berlin. This may cause neuromyelitis optica which is when you can experience loss of vision or weakness in limbs. Harald Prüss summarized that the autoantibodies can pass through the blood brain barrier and ultimately impact neurological disorders such as psychosis.

Prüss and his colleagues published a study last year that focused on them isolating antibodies against SARS-CoV-2 from people. They found that one was able to protect hamsters from lung damage and other infections. The purpose of this was to come up with and create new treatments. During this research they found that some of the antibodies from people. They found that one was able to protect hamsters from lung damage and other infections. The purpose of this was to come up with and create new treatments. During this research they found that some of the antibodies can bind to the brain tissue which can ultimately damage it. Prüss states, “We’re currently trying to prove that clinically and experimentally,” says Prüss.

Was published online in December including Prüss sorry the blood and cerebrospinal fluid of 11 people who were extremely sick with COVID-19. These 11 people had neurological symptoms as well. All these people were able to produce auto antibodies which combined to neurons. There is evidence that when the patients were given intravenous immunoglobin which is a type of antibody it was successful.

Astrocytes, pericytes and autoantibodies we’re not the only  pathways. However it is likely that people with COVID-19 experience article symptoms for many reasons. As stated, In the article, Prüss says a key question is what proportion of cases is caused by each of the pathways. “That will determine treatment,” he says.

SOURCE: https://www.nature.com/articles/d41586-021-01693-6?utm_source=Nature+Briefing

Original article: 

Marshall, M. (2021, July 7). COVID and the brain: researchers zero in on how damage occurs. Nature News. https://www.nature.com/articles/d41586-021-01693-6

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Covid-19 and its implications on pregnancy

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Nir Hacohen and Marcia Goldberg, Researchers at MGH and the Broad Institute identify protein “signature” of severe COVID-19

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Identification of Novel genes in human that fight COVID-19 infection

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Comparing COVID-19 Vaccine Schedule Combinations, or “Com-COV” – First-of-its-Kind Study will explore the Impact of using eight different Combinations of Doses and Dosing Intervals for Different COVID-19 Vaccines

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Early Details of Brain Damage in COVID-19 Patients

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The NIH-funded adjuvant improves the efficacy of India’s COVID-19 vaccine.

Curator and Reporter: Dr. Premalata Pati, Ph.D., Postdoc

Anthony S. Fauci, Director of the National Institute of Allergy and Infectious Diseases (NIAID), Part of National Institute of Health (NIH) said,

Ending a global pandemic demands a global response. I am thrilled that a novel vaccine adjuvant developed in the United States with NIAID support is now included in an effective COVID-19 vaccine that is available to individuals in India.”

Adjuvants are components that are created as part of a vaccine to improve immune responses and increase the efficiency of the vaccine. COVAXIN was developed and is manufactured in India, which is currently experiencing a terrible health catastrophe as a result of COVID-19. An adjuvant designed with NIH funding has contributed to the success of the extremely effective COVAXIN-COVID-19 vaccine, which has been administered to about 25 million individuals in India and internationally.

Alhydroxiquim-II is the adjuvant utilized in COVAXIN, was discovered and validated in the laboratory by the biotech company ViroVax LLC of Lawrence, Kansas, with funding provided solely by the NIAID Adjuvant Development Program. The adjuvant is formed of a small molecule that is uniquely bonded to Alhydrogel, often known as alum and the most regularly used adjuvant in human vaccines. Alhydroxiquim-II enters lymph nodes, where it detaches from alum and triggers two cellular receptors. TLR7 and TLR8 receptors are essential in the immunological response to viruses. Alhydroxiquim-II is the first adjuvant to activate TLR7 and TLR8 in an approved vaccine against an infectious disease. Additionally, the alum in Alhydroxiquim-II activates the immune system to look for an infiltrating pathogen.

Although molecules that activate TLR receptors strongly stimulate the immune system, the adverse effects of Alhydroxiquim-II are modest. This is due to the fact that after COVAXIN is injected, the adjuvant travels directly to adjacent lymph nodes, which contain white blood cells that are crucial in recognizing pathogens and combating infections. As a result, just a minimal amount of Alhydroxiquim-II is required in each vaccination dosage, and the adjuvant does not circulate throughout the body, avoiding more widespread inflammation and unwanted side effects.

This scanning electron microscope image shows SARS-CoV-2 (round gold particles) emerging from the surface of a cell cultured in the lab. SARS-CoV-2, also known as 2019-nCoV, is the virus that causes COVID-19. Image Source: NIAID

COVAXIN is made up of a crippled version of SARS-CoV-2 that cannot replicate but yet encourages the immune system to produce antibodies against the virus. The NIH stated that COVAXIN is “safe and well tolerated,” citing the results of a phase 2 clinical investigation. COVAXIN safety results from a Phase 3 trial with 25,800 participants in India will be released later this year. Meanwhile, unpublished interim data from the Phase 3 trial show that the vaccine is 78% effective against symptomatic sickness, 100% effective against severe COVID-19, including hospitalization, and 70% effective against asymptomatic infection with SARS-CoV-2, the virus that causes COVID-19. Two tests of blood serum from persons who had received COVAXIN suggest that the vaccine creates antibodies that efficiently neutralize the SARS-CoV-2 B.1.1.7 (Alpha) and B.1.617 (Delta) variants (1) and (2), which were originally identified in the United Kingdom and India, respectively.

Since 2009, the NIAID Adjuvant Program has supported the research of ViroVax’s founder and CEO, Sunil David, M.D., Ph.D. His research has focused on the emergence of new compounds that activate innate immune receptors and their application as vaccination adjuvants.

Dr. David’s engagement with Bharat Biotech International Ltd. of Hyderabad, which manufactures COVAXIN, began during a 2019 meeting in India organized by the NIAID Office of Global Research under the auspices of the NIAID’s Indo-US Vaccine Action Program. Five NIAID-funded adjuvant investigators, including Dr. David, two representatives of the NIAID Division of Allergy, Immunology, and Transplantation, and the NIAID India representative, visited 4 top biotechnology companies to learn about their work and discuss future collaborations. The delegation also attended a consultation in New Delhi, which was co-organized by the NIAID and India’s Department of Biotechnology and hosted by the National Institute of Immunology.

Among the scientific collaborations spawned by these endeavors was a licensing deal between Bharat Biotech and Dr. David to use Alhydroxiquim-II in their candidate vaccines. During the COVID-19 outbreak, this license was expanded to cover COVAXIN, which has Emergency Use Authorization in India and more than a dozen additional countries. COVAXIN was developed by Bharat Biotech in partnership with the Indian Council of Medical Research’s National Institute of Virology. The company conducted thorough safety research on Alhydroxiquim-II and undertook the arduous process of scaling up production of the adjuvant in accordance with Good Manufacturing Practice standards. Bharat Biotech aims to generate 700 million doses of COVAXIN by the end of 2021.

NIAID conducts and supports research at the National Institutes of Health, across the United States, and across the world to better understand the causes of infectious and immune-mediated diseases and to develop better methods of preventing, detecting, and treating these illnesses. The NIAID website contains news releases, info sheets, and other NIAID-related materials.

Main Source:

https://www.miragenews.com/adjuvant-developed-with-nih-funding-enhances-587090/

References

  1. https://academic.oup.com/cid/advance-article-abstract/doi/10.1093/cid/ciab411/6271524?redirectedFrom=fulltext
  2. https://academic.oup.com/jtm/article/28/4/taab051/6193609

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Comparing COVID-19 Vaccine Schedule Combinations, or “Com-COV” – First-of-its-Kind Study will explore the Impact of using eight different Combinations of Doses and Dosing Intervals for Different COVID-19 Vaccines

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2021/02/08/comparing-covid-19-vaccine-schedule-combinations-or-com-cov-first-of-its-kind-study-will-explore-the-impact-of-using-eight-different-combinations-of-doses-and-dosing-intervals-for-diffe/

Thriving Vaccines and Research: Weizmann Institute Coronavirus Research Development

Reporter:Amandeep Kaur, B.Sc., M.Sc.

https://pharmaceuticalintelligence.com/2021/05/04/thriving-vaccines-and-research-weizmann-coronavirus-research-development/

National Public Radio interview with Dr. Anthony Fauci on his optimism on a COVID-19 vaccine by early 2021

Reporter: Stephen J. Williams, PhD

https://pharmaceuticalintelligence.com/2020/07/19/national-public-radio-interview-with-dr-anthony-fauci-on-his-optimism-on-a-covid-19-vaccine-by-early-2021/

Cryo-EM disclosed how the D614G mutation changes SARS-CoV-2 spike protein structure

Reporter: Dr. Premalata Pati, Ph.D., Postdoc

https://pharmaceuticalintelligence.com/2021/04/10/cryo-em-disclosed-how-the-d614g-mutation-changes-sars-cov-2-spike-protein-structure/

Updates on the Oxford, AstraZeneca COVID-19 Vaccine

Reporter: Stephen J. Williams, PhD

https://pharmaceuticalintelligence.com/2020/06/16/updates-on-the-oxford-astrazeneca-covid-19-vaccine/

Read Full Post »

Covid-19 and its implications on pregnancy

Reporter and Curator: Mr. Srinjoy Chakraborty (Junior Research Felllow) and Dr. Sudipta Saha, Ph.D.

Coronavirus disease 2019 (COVID-19), which is caused by the novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has emerged as a serious global health issue with high transmission rates affecting millions of people worldwide. The SARS-CoV-2 is known to damage cells in the respiratory system, thus causing viral pneumonia. The novel SARS-CoV-2 is a close relative to the previously identified severe acute respiratory syndrome-coronavirus (SARS-CoV) and Middle East respiratory syndrome-coronavirus (MERS-CoV) which affected several people in 2002 and 2012, respectively. Ever since the outbreak of covid-19, several reports have poured in about the impact of Covid-19 on pregnancy. A few studies have highlighted the impact of the viral infection in pregnant women and how they are more susceptible to the infection because of the various physiological changes of the cardiopulmonary and immune systems during pregnancy. It is known that SARS-CoV and MERS-CoV diseases have influenced the fatality rate among pregnant women. However, there are limited studies on the impact of the novel corona virus on the course and outcome of pregnancy.

Figure: commonly observed clinical symptoms of COVID-19 in the general population: Fever and cough, along with dyspnoea, diarrhoea, and malaise are the most commonly observed symptoms in pregnant women, which is similar to that observed in the normal population.

The WHO and the Indian Council of Medical Research (ICMR) have proposed detailed guidelines for treating pregnant women; these guidelines must be strictly followed by the pregnant individual and their families. According to the guidelines issued by the ICMR, the risk of pregnant women contracting the virus to that of the general population. However, the immune system and the body’s response to a viral infection is altered during pregnancy. This may result in the manifestation of more severe symptoms. The ICMR guidelines also state that the reported cases of COVID-19 pneumonia in pregnancy are milder and with good recovery. However, by observing the trends of the other coronavirus infection (SARS, MERS), the risks to the mother appear to increase in particular during the last trimester of pregnancy. Cases of preterm birth in women with COVID-19 have been mentioned in a few case report, but it is unclear whether the preterm birth was always iatrogenic, or whether some were spontaneous. Pregnant women with heart disease are at highest risk of acquiring the infection, which is similar to that observed in the normal population. Most importantly, the ICMR guidelines highlights the impact of the coronavirus epidemic on the mental health of pregnant women. It mentions that the since the pandemic has begun, there has been an increase in the risk of perinatal anxiety and depression, as well as domestic violence. It is critically important that support for women and families is strengthened as far as possible; that women are asked about mental health at every contact.

With the available literature available on the impact of SARS and MERS on reproductive outcome, it has been mentioned that SARS infection did increase the risk of miscarriage, preterm birth and, intrauterine foetal growth restriction. However, the same has not been demonstrated in early reports from COVID-19 infection in pregnancy. According to a study that included 8200 participants conducted by the centre for disease control and prevention, pregnant women may be at a higher risk of acquiring severe infection and need for ICU admissions as compared to their non-pregnant counterparts. However, a detailed and thorough study involving a larger proportion of the population is needed today.

References:

https://www.news-medical.net/news/20210614/COVID-19-in-pregnancy-could-be-less-severe-than-previously-thought-A-Danish-case-study.aspx

https://obgyn.onlinelibrary.wiley.com/doi/10.1111/jog.14696

https://www.nature.com/articles/s41577-021-00525-y

https://www.tandfonline.com/doi/full/10.1080/14767058.2020.1759541

https://www.cdc.gov/coronavirus/2019-ncov/cases-updates/special-populations/pregnancy-data-on-covid-19/what-cdc-is-doing.html

https://economictimes.indiatimes.com/news/india/why-is-covid-19-killing-so-many-pregnant-women-in-india/articleshow/82902194.cms?from=mdr

https://content.iospress.com/download/international-journal-of-risk-and-safety-in-medicine/jrs200060?id=international-journal-of-risk-and-safety-in-medicine%2Fjrs200060

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Emergence of a new SARS-CoV-2 variant from GR clade with a novel S glycoprotein mutation V1230L in West Bengal, India

Authors: Rakesh Sarkar, Ritubrita Saha, Pratik Mallick, Ranjana Sharma, Amandeep Kaur, Shanta Dutta, Mamta Chawla-Sarkar

Reporter and Original Article Co-Author: Amandeep Kaur, B.Sc. , M.Sc.

Abstract
Since its inception in late 2019, SARS-CoV-2 has evolved resulting in emergence of various variants in different countries. These variants have spread worldwide resulting in devastating second wave of COVID-19 pandemic in many countries including India since the beginning of 2021. 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.

Reference: Sarkar, R. et al. (2021) Emergence of a new SARS-CoV-2 variant from GR clade with a novel S glycoprotein mutation V1230L in West Bengal, India. medRxiv. https://doi.org/10.1101/2021.05.24.21257705https://www.medrxiv.org/content/10.1101/2021.05.24.21257705v1

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Mechanism of Thrombosis with AstraZeneca and J & J Vaccines: Expert Opinion by Kate Chander Chiang & Ajay Gupta, MD

Reporter & Curator: Dr. Ajay Gupta, MD

https://pharmaceuticalintelligence.com/2021/04/14/mechanism-of-thrombosis-with-astrazeneca-and-j-j-vaccines-expert-opinion-by-kate-chander-chiang-ajay-gupta-md/

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C.D.C. Reviewing Cases of Heart Problem in Youngsters After Getting Vaccinated and AHA Reassures that Benefits Overwhelm the Risks of Vaccination

Reporter: Amandeep Kaur, B.Sc. , M.Sc.

The latest article in New York times reported by Apoorva Mandavilli outlines the statement of officials that C.D.C. agency is investigating few cases of young adults and teenagers who might have developed myocarditis after getting vaccinated. It is not confirmed by the agency that whether this condition is caused by vaccine or not.

According to the vaccine safety group of the Centers for Disease Control and Prevention, the reports of heart problems experienced by youngsters is relatively very small in number. The group stated that these cases could be unlinked to vaccination. The condition of inflammation of heart muscle which can occur due to certain infections is known as myocarditis.

Moreover, the agency still has to determine any evidence related to vaccines causing the heart issues. The C.D.C. has posted on its website the updated guidance for doctors and clinicians, urging them to be alert to uncommon symptoms related to heart cases among teenagers who are vaccine recipients.

In New York, Dr. Celine Gounder, an infectious disease specialist at Bellevue Hospital Center stated that “It may simply be a coincidence that some people are developing myocarditis after vaccination. It’s more likely for something like that to happen by chance, because so many people are getting vaccinated right now.”

The article reported that the cases appeared mainly in young adults after about four days of their second shot of mRNA vaccines, made by Moderna and Pfizer-BioNTech. Such cases are more prevalent in males as compared to females.

The vaccine safety group stated “Most cases appear to be mild, and follow-up of cases is ongoing.” It is strongly recommended by C.D.C. that American young adults from the age of 12 and above should get vaccinated against COVID-19.

Dr. Yvonne Maldonado, chair of the American Academy of Pediatrics’s Committee on Infectious Diseases stated “We look forward to seeing more data about these cases, so we can better understand if they are related to the vaccine or if they are coincidental. Meanwhile, it’s important for pediatricians and other clinicians to report any health concerns that arise after vaccination.”

Experts affirmed that the potentially uncommon side effects of myocarditis get insignificant compared to the potential risks of SARS-CoV-2 infection, including the continuous syndrome known as “long Covid.” It is reported in the article that acute Covid can lead to myocarditis.

According to the data collected by A.A.P, about 16 thousand children were hospitalized and more than 3.9 million children were infected by coronavirus till the second week of May. In the United States, about 300 children died of SARS-CoV-2 infection, which makes it among the top 10 death causes in children since the start of pandemic.

Dr. Jeremy Faust, an emergency medicine physician at Brigham and Women’s Hospital in Boston stated that “And that’s in the context of all the mitigation measures taken.”

According to researchers, about 10 to 20 of every 1 lakh people each year develop myocarditis in the general population, facing symptoms from fatigue and chest pain to arrhythmias and cardiac arrest, whereas some have mild symptoms which remain undiagnosed.

Currently, the number of reports of myocarditis after vaccination is less than that reported normally in young adults, confirmed by C.D.C. The article reported that the members of vaccine safety group felt to communicate the information about upcoming cases of myocarditis to the providers.

The C.D.C. has not yet specified the ages of the patients involved in reporting. Since December 2020, the Pfizer-BioNTech vaccine was authorized for young people of age 16 and above. The Food and Drug Administration extended the authorization to children of age 12 to 15 years, by the starting of this month.

On 14th May, the clinicians have been alerted by C.D.C. regarding the probable link between myocarditis and vaccination. Within three days, the team started reviewing data on myocarditis, reports filed with the Vaccine Adverse Event Reporting System and others from the Department of Defense.

A report on seven cases has been submitted to the journal Pediatrics for review and State health departments in Washington, Oregon and California have notified emergency providers and cardiologists about the potential problem.

In an interview, Dr. Liam Yore, past president of the Washington State chapter of the American College of Emergency Physicians detailed a case of teenager with myocarditis after vaccination. The patient was provided treatment for mild inflammation of the inner lining of the heart and was discharged afterwards. Later, the young adult returned for care due to decrease in the heart’s output. Dr. Yore reported that still he had come across worse cases in youngsters with Covid, including in a 9-year-old child who arrived at the hospital after a cardiac arrest last winter.

He stated that “The relative risk is a lot in favor of getting the vaccine, especially considering how coronavirus vaccine have been administered.”

In the United States, more than 161 million people have received their first shot of vaccine in which about 4.5 million people were between the age 12 to 18 years.

Benefits Overwhelm Risks of COVID Vaccination, AHA Reassures

The latest statement of American Heart Association (AHA)/ American Stroke Association (ASA) on May 23rd states that the benefits of COVID-19 vaccination enormously outweigh the rare risk for myocarditis cases, which followed the C.D.C. report that the agency is tracking the Vaccine Adverse Events Reporting System (VAERS) and the Vaccine Safety Datalink (VSD) for myocarditis cases linked with mRNA vaccines against coronavirus.

The myocarditis cases in young adults are more often observed after the second dose of vaccine rather than the first one, and have more cases of males than females. The CDC’s COVID-19 Vaccine Safety Technical Work Group (VaST) observed such heart complications after 4 days of vaccination.

CDC reported that “Within CDC safety monitoring systems, rates of myocarditis reports in the window following COVID-19 vaccination have not differed from expected baseline rates.”

The CDC team stated that “The evidence continues to indicate that the COVID-19 vaccines are nearly 100% effective at preventing death and hospitalization due to COVID-19 infection, and Strongly urged all young adults and children 12 years and above to get vaccinated as soon as possible.”

Even though the analysis of myocarditis reports related to coronavirus vaccine is in progress, the AHA/ASA stated that “myocarditis is typically the result of an actual viral infection, and it is yet to be determined if these cases have any correlation to receiving a COVID-19 vaccine.”

Richard Besser, MD, president and CEO of the Robert Wood Johnson Foundation (RWJF) and former acting director of the CDC stated on ABC’s Good Morning America “We’ve lost hundreds of children and there have been thousands who have been hospitalized, thousands who developed an inflammatory syndrome, and one of the pieces of that can be myocarditis.” He added “still, from my perspective, the risk of COVID is so much greater than any theoretical risk from the vaccine.”

After COVID-19 vaccination the symptoms that occur include tiredness, muscle pain, headaches, chills, nausea and fever. The AHA/ASA stated that “typically appear within 24 to 48 hours and usually pass within 36-48 hours after receiving the vaccine.”

All healthcare providers are suggested to be aware of the rare adverse symptoms such as myocarditis, low platelets, blood clots, and severe inflammation. The agency stated that “Healthcare professionals should strongly consider inquiring about the timing of any recent COVID vaccination among patients presenting with these conditions, as needed, in order to provide appropriate treatment quickly.”

President Mitchell S.V. Elkind, M.D., M.S., FAHA, FAAN, Immediate Past President Robert A. Harrington, M.D., FAHA, President-Elect Donald M. Lloyd-Jones, M.D., Sc.M., FAHA, Chief Science and Medical Officer Mariell Jessup, M.D., FAHA, and Chief Medical Officer for Prevention Eduardo Sanchez, M.D, M.P.H., FAAFP are science leaders of AHA/ASA and reflected their views in the following statements:

We strongly urge all adults and children ages 12 and older in the U.S. to receive a COVID vaccine as soon as they can receive it, as recently approved by the U.S. Food and Drug Administration and the CDC. The evidence continues to indicate that the COVID-19 vaccines are nearly 100% effective at preventing death and hospitalization due to COVID-19 infection. According to the CDC as of May 22, 2021, over 283 million doses of COVID-19 vaccines have been administered in the U.S. since December 14, 2020, and more than 129 million Americans are fully vaccinated (i.e., they have received either two doses of the Pfizer-BioNTech or Moderna COVID-19 vaccine, or the single-dose Johnson & Johnson/Janssen COVID-19 vaccine).

We remain confident that the benefits of vaccination far exceed the very small, rare risks. The risks of vaccination are also far smaller than the risks of COVID-19 infection itself, including its potentially fatal consequences and the potential long-term health effects that are still revealing themselves, including myocarditis. The recommendation for vaccination specifically includes people with cardiovascular risk factors such as high blood pressure, obesity and type 2 diabetes, those with heart disease, and heart attack and stroke survivors, because they are at much greater risk of an adverse outcome from the COVID-19 virus than they are from the vaccine.

We commend the CDC’s continual monitoring for adverse events related to the COVID-19 vaccines through VAERS and VSD, and the consistent meetings of ACIP’s VaST Work Group, demonstrating transparent and robust attention to any and all health events possibly related to a COVID-19 vaccine. The few cases of myocarditis that have been reported after COVID-19 vaccination are being investigated. However, myocarditis is usually the result of a viral infection, and it is yet to be determined if these cases have any correlation to receiving a COVID-19 vaccine, especially since the COVID-19 vaccines authorized in the U.S. do not contain any live virus.

We also encourage everyone to keep in touch with their primary care professionals and seek care immediately if they have any of these symptoms in the weeks after receiving the COVID-19 vaccine: chest pain including sudden, sharp, stabbing pains; difficulty breathing/shortness of breath; abnormal heartbeat; severe headache; blurry vision; fainting or loss of consciousness; weakness or sensory changes; confusion or trouble speaking; seizures; unexplained abdominal pain; or new leg pain or swelling.

We will stay up to date with the CDC’s recommendations regarding all potential complications related to COVID-19 vaccines, including myocarditis, pericarditis, central venous sinus thrombosis (CVST) and other blood clotting events, thrombosis thrombocytopenia syndrome (TTS), and vaccine-induced immune thrombosis thrombocytopenia (VITT).

The American Heart Associationrecommends all health care professionals be aware of these very rare adverse events that may be related to a COVID-19 vaccine, including myocarditis, blood clots, low platelets, or symptoms of severe inflammation. Health care professionals should strongly consider inquiring about the timing of any recent COVID vaccination among patients presenting with these conditions, as needed, in order to provide appropriate treatment quickly. As detailed in last month’s AHA/ASA statement, all suspected CVST or blood clots associated with the COVID-19 vaccine should be treated initially using non-heparin anticoagulants. Heparin products should not be administered in any dose if TTS/VITT is suspected, until appropriate testing can be done to exclude heparin-induced antibodies. In addition, health care professionals are required to report suspected vaccine-related adverse events to the Vaccine Adverse Event Reporting System, in accordance with federal regulations.

Individuals should refer to their local and state health departments for specific information about when and where they can get vaccinated. We implore everyone ages 12 and older to get vaccinated so we can return to being together, in person – enjoying life with little to no risk of severe COVID-19 infection, hospitalization or death.

We also support the CDC recommendations last week that loosen restrictions on mask wearing and social distancing for people who are fully vaccinated. For those who are unable to be vaccinated, we reiterate the importance of handwashing, social distancing and wearing masks, particularly for people at high risk of infection and/or severe COVID-19. These simple precautions remain crucial to protecting people who are not vaccinated from the virus that causes COVID-19.

Source:

Other related articles were published in this Open Access Online Scientific Journal, including the following:

Thriving Vaccines and Research: Weizmann Institute Coronavirus Research Development

Reporter: Amandeep Kaur, B.Sc., M.Sc.

https://pharmaceuticalintelligence.com/2021/05/04/thriving-vaccines-and-research-weizmann-coronavirus-research-development/

Identification of Novel genes in human that fight COVID-19 infection

Reporter: Amandeep Kaur, B.Sc., M.Sc.

https://pharmaceuticalintelligence.com/2021/04/19/identification-of-novel-genes-in-human-that-fight-covid-19-infection/

Fighting Chaos with Care, community trust, engagement must be cornerstones of pandemic response

Reporter: Amandeep Kaur, B.Sc., M.Sc. 

https://pharmaceuticalintelligence.com/2021/04/13/fighting-chaos-with-care/

T cells recognize recent SARS-CoV-2 variants

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2021/03/30/t-cells-recognize-recent-sars-cov-2-variants/

Need for Global Response to SARS-CoV-2 Viral Variants

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2021/02/12/need-for-global-response-to-sars-cov-2-viral-variants/

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Thriving Vaccines and Research: Weizmann Institute Coronavirus Research Development

Reporter: Amandeep Kaur, B.Sc., M.Sc.

In early February, Prof. Eran Segal updated in one of his tweets and mentioned that “We say with caution, the magic has started.”

The article reported that this statement by Prof. Segal was due to decreasing cases of COVID-19, severe infection cases and hospitalization of patients by rapid vaccination process throughout Israel. Prof. Segal emphasizes in another tweet to remain cautious over the country and informed that there is a long way to cover and searching for scientific solutions.

A daylong webinar entitled “COVID-19: The epidemic that rattles the world” was a great initiative by Weizmann Institute to share their scientific knowledge about the infection among the Israeli institutions and scientists. Prof. Gideon Schreiber and Dr. Ron Diskin organized the event with the support of the Weizmann Coronavirus Response Fund and Israel Society for Biochemistry and Molecular Biology. The speakers were invited from the Hebrew University of Jerusalem, Tel-Aviv University, the Israel Institute for Biological Research (IIBR), and Kaplan Medical Center who addressed the molecular structure and infection biology of the virus, treatments and medications for COVID-19, and the positive and negative effect of the pandemic.

The article reported that with the emergence of pandemic, the scientists at Weizmann started more than 60 projects to explore the virus from different range of perspectives. With the help of funds raised by communities worldwide for the Weizmann Coronavirus Response Fund supported scientists and investigators to elucidate the chemistry, physics and biology behind SARS-CoV-2 infection.

Prof. Avi Levy, the coordinator of the Weizmann Institute’s coronavirus research efforts, mentioned “The vaccines are here, and they will drastically reduce infection rates. But the coronavirus can mutate, and there are many similar infectious diseases out there to be dealt with. All of this research is critical to understanding all sorts of viruses and to preempting any future pandemics.”

The following are few important projects with recent updates reported in the article.

Mapping a hijacker’s methods

Dr. Noam Stern-Ginossar studied the virus invading strategies into the healthy cells and hijack the cell’s systems to divide and reproduce. The article reported that viruses take over the genetic translation system and mainly the ribosomes to produce viral proteins. Dr. Noam used a novel approach known as ‘ribosome profiling’ as her research objective and create a map to locate the translational events taking place inside the viral genome, which further maps the full repertoire of viral proteins produced inside the host.

She and her team members grouped together with the Weizmann’s de Botton Institute and researchers at IIBR for Protein Profiling and understanding the hijacking instructions of coronavirus and developing tools for treatment and therapies. Scientists generated a high-resolution map of the coding regions in the SARS-CoV-2 genome using ribosome-profiling techniques, which allowed researchers to quantify the expression of vital zones along the virus genome that regulates the translation of viral proteins. The study published in Nature in January, explains the hijacking process and reported that virus produces more instruction in the form of viral mRNA than the host and thus dominates the translation process of the host cell. Researchers also clarified that it is the misconception that virus forced the host cell to translate its viral mRNA more efficiently than the host’s own translation, rather high level of viral translation instructions causes hijacking. This study provides valuable insights for the development of effective vaccines and drugs against the COVID-19 infection.

Like chutzpah, some things don’t translate

Prof. Igor Ulitsky and his team worked on untranslated region of viral genome. The article reported that “Not all the parts of viral transcript is translated into protein- rather play some important role in protein production and infection which is unknown.” This region may affect the molecular environment of the translated zones. The Ulitsky group researched to characterize that how the genetic sequence of regions that do not translate into proteins directly or indirectly affect the stability and efficiency of the translating sequences.

Initially, scientists created the library of about 6,000 regions of untranslated sequences to further study their functions. In collaboration with Dr. Noam Stern-Ginossar’s lab, the researchers of Ulitsky’s team worked on Nsp1 protein and focused on the mechanism that how such regions affect the Nsp1 protein production which in turn enhances the virulence. The researchers generated a new alternative and more authentic protocol after solving some technical difficulties which included infecting cells with variants from initial library. Within few months, the researchers are expecting to obtain a more detailed map of how the stability of Nsp1 protein production is getting affected by specific sequences of the untranslated regions.

The landscape of elimination

The article reported that the body’s immune system consists of two main factors- HLA (Human Leukocyte antigen) molecules and T cells for identifying and fighting infections. HLA molecules are protein molecules present on the cell surface and bring fragments of peptide to the surface from inside the infected cell. These peptide fragments are recognized and destroyed by the T cells of the immune system. Samuels’ group tried to find out the answer to the question that how does the body’s surveillance system recognizes the appropriate peptide derived from virus and destroy it. They isolated and analyzed the ‘HLA peptidome’- the complete set of peptides bound to the HLA proteins from inside the SARS-CoV-2 infected cells.

After the analysis of infected cells, they found 26 class-I and 36 class-II HLA peptides, which are present in 99% of the population around the world. Two peptides from HLA class-I were commonly present on the cell surface and two other peptides were derived from coronavirus rare proteins- which mean that these specific coronavirus peptides were marked for easy detection. Among the identified peptides, two peptides were novel discoveries and seven others were shown to induce an immune response earlier. These results from the study will help to develop new vaccines against new coronavirus mutation variants.

Gearing up ‘chain terminators’ to battle the coronavirus

Prof. Rotem Sorek and his lab discovered a family of enzymes within bacteria that produce novel antiviral molecules. These small molecules manufactured by bacteria act as ‘chain terminators’ to fight against the virus invading the bacteria. The study published in Nature in January which reported that these molecules cause a chemical reaction that halts the virus’s replication ability. These new molecules are modified derivates of nucleotide which integrates at the molecular level in the virus and obstruct the works.

Prof. Sorek and his group hypothesize that these new particles could serve as a potential antiviral drug based on the mechanism of chain termination utilized in antiviral drugs used recently in the clinical treatments. Yeda Research and Development has certified these small novel molecules to a company for testing its antiviral mechanism against SARS-CoV-2 infection. Such novel discoveries provide evidences that bacterial immune system is a potential repository of many natural antiviral particles.

Resolving borderline diagnoses

Currently, Real-time Polymerase chain reaction (RT-PCR) is the only choice and extensively used for diagnosis of COVID-19 patients around the globe. Beside its benefits, there are problems associated with RT-PCR, false negative and false positive results and its limitation in detecting new mutations in the virus and emerging variants in the population worldwide. Prof. Eran Elinavs’ lab and Prof. Ido Amits’ lab are working collaboratively to develop a massively parallel, next-generation sequencing technique that tests more effectively and precisely as compared to RT-PCR. This technique can characterize the emerging mutations in SARS-CoV-2, co-occurring viral, bacterial and fungal infections and response patterns in human.

The scientists identified viral variants and distinctive host signatures that help to differentiate infected individuals from non-infected individuals and patients with mild symptoms and severe symptoms.

In Hadassah-Hebrew University Medical Center, Profs. Elinav and Amit are performing trails of the pipeline to test the accuracy in borderline cases, where RT-PCR shows ambiguous or incorrect results. For proper diagnosis and patient stratification, researchers calibrated their severity-prediction matrix. Collectively, scientists are putting efforts to develop a reliable system that resolves borderline cases of RT-PCR and identify new virus variants with known and new mutations, and uses data from human host to classify patients who are needed of close observation and extensive treatment from those who have mild complications and can be managed conservatively.

Moon shot consortium refining drug options

The ‘Moon shot’ consortium was launched almost a year ago with an initiative to develop a novel antiviral drug against SARS-CoV-2 and was led by Dr. Nir London of the Department of Chemical and Structural Biology at Weizmann, Prof. Frank von Delft of Oxford University and the UK’s Diamond Light Source synchroton facility.

To advance the series of novel molecules from conception to evidence of antiviral activity, the scientists have gathered support, guidance, expertise and resources from researchers around the world within a year. The article reported that researchers have built an alternative template for drug-discovery, full transparency process, which avoids the hindrance of intellectual property and red tape.

The new molecules discovered by scientists inhibit a protease, a SARS-CoV-2 protein playing important role in virus replication. The team collaborated with the Israel Institute of Biological Research and other several labs across the globe to demonstrate the efficacy of molecules not only in-vitro as well as in analysis against live virus.

Further research is performed including assaying of safety and efficacy of these potential drugs in living models. The first trial on mice has been started in March. Beside this, additional drugs are optimized and nominated for preclinical testing as candidate drug.

Source: https://www.weizmann.ac.il/WeizmannCompass/sections/features/the-vaccines-are-here-and-research-abounds

Other related articles were published in this Open Access Online Scientific Journal, including the following:

Identification of Novel genes in human that fight COVID-19 infection

Reporter: Amandeep Kaur, B.Sc., M.Sc. (ept. 5/2021)

https://pharmaceuticalintelligence.com/2021/04/19/identification-of-novel-genes-in-human-that-fight-covid-19-infection/

Fighting Chaos with Care, community trust, engagement must be cornerstones of pandemic response

Reporter: Amandeep Kaur, B.Sc., M.Sc. (ept. 5/2021)

https://pharmaceuticalintelligence.com/2021/04/13/fighting-chaos-with-care/

T cells recognize recent SARS-CoV-2 variants

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2021/03/30/t-cells-recognize-recent-sars-cov-2-variants/

Need for Global Response to SARS-CoV-2 Viral Variants

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2021/02/12/need-for-global-response-to-sars-cov-2-viral-variants/

Mechanistic link between SARS-CoV-2 infection and increased risk of stroke using 3D printed models and human endothelial cells

Reporter: Adina Hazan, PhD

https://pharmaceuticalintelligence.com/2020/12/28/mechanistic-link-between-sars-cov-2-infection-and-increased-risk-of-stroke-using-3d-printed-models-and-human-endothelial-cells/

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Identification of Novel genes in human that fight COVID-19 infection

Reporter: Amandeep Kaur, B.Sc., M.Sc. (ept. 5/2021)

Scientists have recognized human genes that fight against the SARS-CoV-2 viral infection. The information about genes and their function can help to control infection and aids the understanding of crucial factors that causes severe infection. These novel genes are related to interferons, the frontline fighter in our body’s defense system and provide options for therapeutic strategies.

The research was published in the journal Molecular Cell.

Sumit K. Chanda, Ph.D., professor and director of the Immunity and Pathogenesis Program at Sanford Burnham Prebys reported in the article that they focused on better understanding of the cellular response and downstream mechanism in cells to SARS-CoV-2, including the factors which causes strong or weak response to viral infection. He is the lead author of the study and explained that in this study they have gained new insights into how the human cells are exploited by invading virus and are still working towards finding any weak point of virus to develop new antivirals against SARS-CoV-2.

With the surge of pandemic, researchers and scientists found that in severe cases of COVID-19, the response of interferons to SARS-CoV-2 viral infection is low. This information led Chanda and other collaborators to search for interferon-stimulated genes (ISGs), are genes in human which are triggered by interferons and play important role in confining COVID-19 infection by controlling their viral replication in host.

The investigators have developed laboratory experiments to identify ISGs based on the previous knowledge gathered by the outbreak of SARS-CoV-1 from 2002-2004 which was similar to COVID-19 pandemic caused by SARS-CoV-2 virus.

The article reports that Chanda mentioned “we found that 65 ISGs controlled SAR-CoV-2 infection, including some that inhibited the virus’ ability to enter cells, some that suppressed manufacture of the RNA that is the virus’s lifeblood, and a cluster of genes that inhibited assembly of the virus.” They also found an interesting fact about ISGs that some of these genes revealed control over unrelated viruses, such as HIV, West Nile and seasonal flu.

Laura Martin-Sancho, Ph.D., a senior postdoctoral associate in the Chanda lab and first author of the study reported in the article that they identified 8 different ISGs that blocked the replication of both SARS-CoV-1 and CoV-2 in the subcellular compartments responsible for packaging of proteins, which provide option to exploit these vulnerable sites to restrict infection. They are further investigating whether the genetic variability within the ISGs is associated with COVID-19 severity.

The next step for researchers will be investigating and observing the biology of variants of SARS-CoV-2 that are evolving and affecting vaccine efficacy. Martin-Sancho mentioned that their lab has already started gathering all the possible variants for further investigation.

“It’s vitally important that we don’t take our foot off the pedal of basic research efforts now that vaccines are helping control the pandemic,” reported in the article by Chanda.

“We’ve come so far so fast because of investment in fundamental research at Sanford Burnham Prebys and elsewhere, and our continued efforts will be especially important when, not if, another viral outbreak occurs,” concluded Chanda.

Source: https://medicalxpress.com/news/2021-04-covid-scientists-human-genes-infection.html

Reference: Laura Martin-Sancho et al. Functional Landscape of SARS-CoV-2 Cellular Restriction, Molecular Cell (2021). DOI: 10.1016/j.molcel.2021.04.008

Other related articles were published in this Open Access Online Scientific Journal, including the following:

Fighting Chaos with Care, community trust, engagement must be cornerstones of pandemic response

Reporter: Amandeep Kaur

https://pharmaceuticalintelligence.com/2021/04/13/fighting-chaos-with-care/

Mechanism of Thrombosis with AstraZeneca and J & J Vaccines: Expert Opinion by Kate Chander Chiang & Ajay Gupta, MD

Reporter & Curator: Dr. Ajay Gupta, MD

https://pharmaceuticalintelligence.com/2021/04/14/mechanism-of-thrombosis-with-astrazeneca-and-j-j-vaccines-expert-opinion-by-kate-chander-chiang-ajay-gupta-md/

T cells recognize recent SARS-CoV-2 variants

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2021/03/30/t-cells-recognize-recent-sars-cov-2-variants/

Need for Global Response to SARS-CoV-2 Viral Variants

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2021/02/12/need-for-global-response-to-sars-cov-2-viral-variants/

Mechanistic link between SARS-CoV-2 infection and increased risk of stroke using 3D printed models and human endothelial cells

Reporter: Adina Hazan, PhD

https://pharmaceuticalintelligence.com/2020/12/28/mechanistic-link-between-sars-cov-2-infection-and-increased-risk-of-stroke-using-3d-printed-models-and-human-endothelial-cells/

Read Full Post »

Fighting Chaos with care, community trust, engagement must be cornerstones of pandemic response

Reporter: Amandeep Kaur, BSc, MSc (Exp. 6/2021)

According to the Global Health Security Index released by Johns Hopkins University in October 2019 in collaboration with Nuclear Threat Initiative (NTI) and The Economist Intelligence Unit (EIU), the United States was announced to be the best developed country in the world to tackle any pandemic or health emergency in future.

The table turned within in one year of outbreak of the novel coronavirus COVID-19. By the end of March 2021, the country with highest COVID-19 cases and deaths in the world was United States. According to the latest numbers provided by World Health Organization (WHO), there were more than 540,000 deaths and more than 30 million confirmed cases in the United States.

Joia Mukherjee, associate professor of global health and social medicine in the Blavatnik Institute at Harvard Medical School said,

“When we think about how to balance control of an epidemic over chaos, we have to double down on care and concern for the people and communities who are hardest hit”.

She also added that U.S. possess all the necessary building blocks required for a health system to work, but it lacks trust, leadership, engagement and care to assemble it into a working system.

Mukherjee mentioned about the issues with the Index that it undervalued the organized and integrated system which is necessary to help public meet their needs for clinical care. Another necessary element for real health safety which was underestimated was conveying clear message and social support to make effective and sustainable efforts for preventive public health measures.

Mukherjee is a chief medical officer at Partners In Health, an organization focused on strengthening community-based health care delivery. She is also a core member of HMS community members who play important role in constructing a more comprehensive response to the pandemic in all over the U.S. With years of experience, they are training global health care workers, analyzing the results and constructing an integrated health system to fight against the widespread health emergency caused by coronavirus all around the world.

Mukherjee encouraged to strengthen the consensus among the community to constrain this infectious disease epidemic. She suggested that validation of the following steps are crucial such as testing of the people with symptoms of infection with coronavirus, isolation of infected individuals by providing them with necessary resources and providing clinical treatment and care to those people who are in need. Mukherjee said, that community engagement and material support are not just idealistic goal rather these are essential components for functioning of health care system during an outburst of coronavirus.

Continued alertness such as social distancing and personal contact with infected individual is important because it is not possible to rapidly replace the old-school public health approaches with new advanced technologies like smart phone applications or biomedical improvements.

Public health specialists emphasized that the infection limitation is the only and most vital strategy for controlling the outbreak in near future, even if the population is getting vaccinated. It is crucial to slowdown the spread of disease for restricting the natural modification of more dangerous variants as that could potentially escape the immune protection mechanism developed by recently generated vaccines as well as natural immune defense systems.

Making Crucial connections

The treatment is more expensive and complicated in areas with less health facilities, said Paul Farmer, the Kolokotrones University Professor at Harvard and chair of the HMS Department of Global Health and Social Medicine. He called this situation as treatment nihilism. Due to shortage of resources, the maximum energy is focused in public health care and prevention efforts. U.S. has resources to cope up with the increasing demand of hospital space and is developing vaccines, but there is a form of containment nihilism- which means prevention and infection containment are unattainable- said by many experts.

Farmer said, integration of necessary elements such as clinical care, therapies, vaccines, preventive measures and social support into a single comprehensive plan is the best approach for a better response to COVID-19 disease. He understands the importance of community trust and integrated health care system for fighting against this pandemic, as being one of the founders of Partners In Health and have years of experience along with his colleagues from HMS and PIH in fighting epidemics of HIV, Ebola, cholera, tuberculosis, other infectious and non-infectious diseases.

PIH launched the Massachusetts Community Tracing Collaborative (CTC), which is an initiative of contact tracing statewide in partnership with several other state bodies, local boards of Health system and PIH. The CTC was setup in April 2020 in U.S. by Governor Charlie Baker, with leadership from HMS faculty, to build a unified response to COVID-19 and create a foundation for a long-term movement towards a more integrated community-based health care system.

The contact tracing involves reaching out to individuals who are COVID-19 positive, then further detect people who came in close contact with infected individuals and screen out people with coronavirus symptoms and encourage them to seek testing and take necessary precautions to break the chain of infection into the community.

In the initial phase of outbreak, the CTC group comprises of contact tracers and health care coordinators who spoke 23 different languages, including social workers, public health practitioners, nurses and staff members from local board health agencies with deep links to the communities they are helping. The CTC worked with 339 out of 351 state municipalities with local public health agencies relied completely on CTC whereas some cities and towns depend occasionally on CTC backup. According to a report, CTC members reached up to 80 percent of contact tracking in hard-hit and resource deprived communities such as New Bedford.

Putting COVID-19 in context

Based on generations of experience helping people surviving some of the deadliest epidemic and endemic outbreaks in places like Haiti, Mexico, Rwanda and Peru, the staff was alert that people with bad social and economic condition have less space to get quarantined and follow other public health safety measures and are most vulnerable people at high risk in the pandemic situation.

Infected individuals or individuals at risk of getting infected by SARS-CoV-2 had many questions regarding when to seek doctor’s help and where to get tested, reported by contact tracers. People were worried about being evicted from work for two weeks and some immigrants worried about basic supplies as they were away from their family and friends.

The CTC team received more than 7,000 requests for social support assistance in the initial three months. The staff members and contact tracers were actively connecting the resourceful individuals with the needy people and filling up the gap when there was shortage in their own resources.

Farmer said, “COVID is a misery-seeking missile that has targeted the most vulnerable.”

The reality that infected individuals concerned about lacking primary household items, food items and access to childcare, emphasizes the urgency of rudimentary social care and community support in fighting against the pandemic. Farmer said, to break the chain of infection and resume society it is mandatory to meet all the elementary needs of people.

“What kinds of help are people asking for?” Farmer said and added “it’s important to listen to what your patients are telling you.”

An outbreak of care

The launch of Massachusetts CTC with the support from PIH, started receiving requests from all around the country to assist initiating contact tracing procedures. In May, 2020 the organization announced the launch of a U.S. public health accompaniment to cope up with the asked need.

The unit has included team members in nearly 24 states and municipal health departments in the country and work in collaboration with local organizations. The technical support on things like choosing and implementing the tools and software for contact tracing was provided by PIH. To create awareness and provide new understanding more rapidly, a learning collaboration was established with more than 200 team members from more than 100 different organizations. The team worked to meet the needs of population at higher risk of infection by advocating them for a stronger and more reliable public health response.

The PIH public health team helped to train contact trackers in the Navajo nation and operate to strengthen the coordination between SARS-CoV-2 testing, efforts for precaution, clinical health care delivery and social support in vulnerable communities around the U.S.

“For us to reopen our schools, our churches, our workplaces,” Mukherjee said, “we have to know where the virus is spreading so that we don’t just continue on this path.”

SOURCE:

https://hms.harvard.edu/news/fighting-chaos-care?utm_source=Silverpop&utm_medium=email&utm_term=field_news_item_1&utm_content=HMNews04052021

Other related articles were published in this Open Access Online Scientific Journal, including the following:

T cells recognize recent SARS-CoV-2 variants

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2021/03/30/t-cells-recognize-recent-sars-cov-2-variants/

The WHO team is expected to soon publish a 300-page final report on its investigation, after scrapping plans for an interim report on the origins of SARS-CoV-2 — the new coronavirus responsible for killing 2.7 million people globally

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2021/03/27/the-who-team-is-expected-to-soon-publish-a-300-page-final-report-on-its-investigation-after-scrapping-plans-for-an-interim-report-on-the-origins-of-sars-cov-2-the-new-coronavirus-responsibl/

Need for Global Response to SARS-CoV-2 Viral Variants

Reporter: Aviva Lev-Ari, PhD, RN

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Mechanistic link between SARS-CoV-2 infection and increased risk of stroke using 3D printed models and human endothelial cells

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Cryo-EM disclosed how the D614G mutation changes SARS-CoV-2 spike protein structure.

Reporter: Dr. Premalata Pati, Ph.D., Postdoc

SARS-CoV-2, the virus that causes COVID-19, has had a major impact on human health globally; infecting a massive quantity of people around 136,046,262 (John Hopkins University); causing severe disease and associated long-term health sequelae; resulting in death and excess mortality, especially among older and prone populations; altering routine healthcare services; disruptions to travel, trade, education, and many other societal functions; and more broadly having a negative impact on peoples physical and mental health.

It’s need of the hour to answer the questions like what allows the variants of SARS-CoV-2 first detected in the UK, South Africa, and Brazil to spread so quickly? How can current COVID-19 vaccines better protect against them?

Scientists from the Harvard Medical School and the Boston Children’s Hospital help answer these urgent questions. The team reports its findings in the journal “Science a paper entitled Structural impact on SARS-CoV-2 spike protein by D614G substitution. The mutation rate of the SARS-CoV-2 virus has rapidly evolved over the past few months, especially at the Spike (S) protein region of the virus, where the maximum number of mutations have been observed by the virologists.

Bing Chen, HMS professor of pediatrics at Boston Children’s, and colleagues analyzed the changes in the structure of the spike proteins with the genetic change by D614G mutation by all three variants. Hence they assessed the structure of the coronavirus spike protein down to the atomic level and revealed the reason for the quick spreading of these variants.


This model shows the structure of the spike protein in its closed configuration, in its original D614 form (left) and its mutant form (G614). In the mutant spike protein, the 630 loop (in red) stabilizes the spike, preventing it from flipping open prematurely and rendering SARS-CoV-2 more infectious.

Fig. 1. Cryo-EM structures of the full-length SARS-CoV-2 S protein carrying G614.

(A) Three structures of the G614 S trimer, representing a closed, three RBD-down conformation, an RBD-intermediate conformation and a one RBD-up conformation, were modeled based on corresponding cryo-EM density maps at 3.1-3.5Å resolution. Three protomers (a, b, c) are colored in red, blue and green, respectively. RBD locations are indicated. (B) Top views of superposition of three structures of the G614 S in (A) in ribbon representation with the structure of the prefusion trimer of the D614 S (PDB ID: 6XR8), shown in yellow. NTD and RBD of each protomer are indicated. Side views of the superposition are shown in fig. S8.

IMAGE SOURCE: Bing Chen, Ph.D., Boston Children’s Hospital, https://science.sciencemag.org/content/early/2021/03/16/science.abf2303

The work

The mutant spikes were imaged by Cryo-Electron microscopy (cryo-EM), which has resolution down to the atomic level. They found that the D614G mutation (substitution of in a single amino acid “letter” in the genetic code for the spike protein) makes the spike more stable as compared with the original SARS-CoV-2 virus. As a result, more functional spikes are available to bind to our cells’ ACE2 receptors, making the virus more contagious.


Fig. 2. Cryo-EM revealed how the D614G mutation changes SARS-CoV-2 spike protein structure.

IMAGE SOURCE:  Zhang J, et al., Science

Say the original virus has 100 spikes,” Chen explained. “Because of the shape instability, you may have just 50 percent of them functional. In the G614 variants, you may have 90 percent that is functional. So even though they don’t bind as well, the chances are greater and you will have an infection

Forthcoming directions by Bing Chen and Team

The findings suggest the current approved COVID-19 vaccines and any vaccines in the works should include the genetic code for this mutation. Chen has quoted:

Since most of the vaccines so far—including the Moderna, Pfizer–BioNTech, Johnson & Johnson, and AstraZeneca vaccines are based on the original spike protein, adding the D614G mutation could make the vaccines better able to elicit protective neutralizing antibodies against the viral variants

Chen proposes that redesigned vaccines incorporate the code for this mutant spike protein. He believes the more stable spike shape should make any vaccine based on the spike more likely to elicit protective antibodies. Chen also has his sights set on therapeutics. He and his colleagues are further applying structural biology to better understand how SARS-CoV-2 binds to the ACE2 receptor. That could point the way to drugs that would block the virus from gaining entry to our cells.

In January, the team showed that a structurally engineered “decoy” ACE2 protein binds to SARS-CoV-2 200 times more strongly than the body’s own ACE2. The decoy potently inhibited the virus in cell culture, suggesting it could be an anti-COVID-19 treatment. Chen is now working to advance this research into animal models.

Main Source:

Abstract

Substitution for aspartic acid by glycine at position 614 in the spike (S) protein of severe acute respiratory syndrome coronavirus 2 appears to facilitate rapid viral spread. The G614 strain and its recent variants are now the dominant circulating forms. We report here cryo-EM structures of a full-length G614 S trimer, which adopts three distinct prefusion conformations differing primarily by the position of one receptor-binding domain. A loop disordered in the D614 S trimer wedges between domains within a protomer in the G614 spike. This added interaction appears to prevent premature dissociation of the G614 trimer, effectively increasing the number of functional spikes and enhancing infectivity, and to modulate structural rearrangements for membrane fusion. These findings extend our understanding of viral entry and suggest an improved immunogen for vaccine development.

https://science.sciencemag.org/content/early/2021/03/16/science.abf2303?rss=1

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Miniproteins against the COVID-19 Spike protein may be therapeutic

Reporter: Stephen J. Williams, PhD

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