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Sperm damage and fertility problem due to COVID-19
Reporter and Curator: Dr. Sudipta Saha, Ph.D.
Many couples initially deferred attempts at pregnancy or delayed fertility care due to concerns about coronavirus disease 2019 (COVID-19). One significant fear during the COVID-19 pandemic was the possibility of sexual transmission. Many couples have since resumed fertility care while accepting the various uncertainties associated with severe acute respiratory syndrome coronavirus 2 (SARS-Cov2), including the evolving knowledge related to male reproductive health. Significant research has been conducted exploring viral shedding, tropism, sexual transmission, the impact of male reproductive hormones, and possible implications to semen quality. However, to date, limited definitive evidence exists regarding many of these aspects, creating a challenging landscape for both patients and physicians to obtain and provide the best clinical care.
According to a new study, which looked at sperm quality in patients who suffered symptomatic coronavirus (COVID-19) infections, showed that it could impact fertility for weeks after recovery from the virus. The data showed 60% COVID-19 infected men had reduction in sperm motility and 37% had drop in sperm count, but, 2 months after recovery from COVID-19 the value came down to 28% and 6% respectively. The researchers also of the view that COVID-19 could not be sexually transmitted through semen after a person had recovered from illness. Patients with mild and severe cases of COVID-19 showed similar rate of drop in sperm quality. But further work is required to establish whether or not COVID-19 could have a longer-term impact on fertility. The estimated recovery time is three months, but further follow-up studies are still required to confirm this and to determine if permanent damage occurred in a minority of men.
Some viruses like influenza are already known to damage sperm mainly by increasing body temperature. But in the case of COVID-19, the researchers found no link between the presence or severity of fever and sperm quality. Tests showed that higher concentrations of specific COVID-19 antibodies in patients’ blood serum were strongly correlated with reduced sperm function. So, it was believed the sperm quality reduction cause could be linked to the body’s immune response to the virus. While the study showed that there was no COVID-19 RNA present in the semen of patients who had got over the virus, the fact that antibodies were attacking sperm suggests the virus may cross the blood-testis barrier during the peak of an infection.
It was found in a previous report that SARS-CoV-2 can be present in the semen of patients with COVID-19, and SARS-CoV-2 may still be detected in the semen of recovering patients. Due to imperfect blood-testes/deferens/epididymis barriers, SARS-CoV-2 might be seeded to the male reproductive tract, especially in the presence of systemic local inflammation. Even if the virus cannot replicate in the male reproductive system, it may persist, possibly resulting from the privileged immunity of testes.
If it could be proved that SARS-CoV-2 can be transmitted sexually in future studies, sexual transmission might be a critical part of the prevention of transmission, especially considering the fact that SARS-CoV-2 was detected in the semen of recovering patients. Abstinence or condom use might be considered as preventive means for these patients. In addition, it is worth noting that there is a need for studies monitoring fetal development. Therefore, to avoid contact with the patient’s saliva and blood may not be enough, since the survival of SARS-CoV-2 in a recovering patient’s semen maintains the likelihood to infect others. But further studies are required with respect to the detailed information about virus shedding, survival time, and concentration in semen.
Why do some people with COVID-19 get sicker than others? Maybe exposure to a particularly high dose of the causative virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), accounts for the difference. Perhaps deficiencies in diet, exercise, or sleep contribute to worse illness. Although many factors govern how sick people become, a key driver of the severity of COVID-19 appears to be genetic, which is common for other human viruses and infectious agents (1). On page 579 of this issue, Wickenhagen et al. (2) show that susceptibility to severe COVID-19 is associated with a single-nucleotide polymorphism (SNP) in the human gene 2′-5′-oligoadenylate synthetase 1 (OAS1).The authors reasoned that SARS-CoV-2 should be inhibited by interferon-mediated antiviral responses, which are among the first cellular defense mechanisms produced in response to a viral infection. Interferons are a group of cytokines that induce the transcription of a large cadre of genes, many of which encode proteins with the potential to directly inhibit the invading virus. Wickenhagen et al. interrogated many hundreds of these putative antiviral proteins for their ability to suppress SARS-CoV-2 in cultured cells and found that OAS1 was particularly potent against SARS-CoV-2.OAS1 is an enzyme that is activated in the presence of double-stranded RNA, which is scattered along an otherwise singlestranded SARS-CoV-2 genome because of an assortment of RNA hairpins and other secondary structures. Once activated, OAS1 catalyzes the polymerization of adenosine triphosphate (ATP) into a second messenger, 2′-5′-oligoadenylate. This then triggers the conversion of ribonuclease L (RNaseL) into its active form so that it can cleave viral RNA, effectively blunting viral replication (3). Wickenhagen et al. found that OAS1 is expressed in respiratory tissues of healthy donors and COVID-19 patients and that it interacts with a region of the SARS-CoV-2 genome that contains double-stranded RNA secondary structures (see the figure).OAS1 exists predominantly as two isoforms in humans—a longer isoform (p46) and a shorter version (p42). Genetic variation dictates which isoform will be expressed. In humans, p46 is expressed in people who have a SNP that causes alternative splicing of the OAS1 messenger RNA (mRNA). This results in the utilization of a terminal exon that is not used to translate p42. Thus, the carboxyl terminus of the p46 OAS1 protein contains a distinct four–amino acid motif that forms a prenylation site. Prenylation is a posttranslational modification that targets proteins to membranes. In cell culture experiments, Wickenhagen et al. showed that only OAS1 p46, but not p42, could inhibit SARS-CoV-2. However, when the prenylation site of p46 was engineered into p42, this chimeric p42 protein was able to inhibit SARS-CoV-2, which strongly implicates a role for OAS1 specifically at membranes.Why are membranes important? SARS-CoV-2, like all coronaviruses, co-opts cellular membranes at the endoplasmic reticulum to form double-membrane vesicles, in which the virus replicates its genome. Thus, membrane-bound OAS1 p46 may be specifically activated by RNA viruses that form membrane-bound vesicles for replication. Indeed, the unrelated cardiovirus A, which also forms vesicular membranous structures, was inhibited by OAS1. Conversely, other respiratory RNA viruses, such as human parainfluenza virus type 3 and human respiratory syncytial virus, which do not use membrane-tethered vesicles for replication, were not inhibited by p46.Wickenhagen et al. examined a cohort of 499 COVID-19 patients hospitalized in the UK. Whereas all patients expressed OAS1, 42.5% of them did not express the antiviral p46 isoform. These patients were statistically more likely to have severe COVID-19 (be admitted to the intensive care unit). This suggests that OAS1 is an important antiviral factor in the control of SARS-CoV-2 infection and that its inability to activate RNaseL results in prolonged infections and severe disease, although other factors likely contribute. The authors also examined animals known to harbor different coronaviruses. They found evidence for prenylated OAS1 proteins in mice, cows, and camels. Notably, horseshoe bats, which are considered a possible reservoir for SARS-related coronaviruses (4), lack a prenylation motif in their OAS1 because of genomic changes that eliminated the critical four-amino acid motif. A horseshoe bat (Rhinolophus ferrumequinum) OAS1 was unable to inhibit SARS-CoV-2 infection in cell culture. Conversely, the black flying fox (Pteropus alecto)—a pteropid bat that is a reservoir for the Nipah and Hendra viruses, which can also infect humans—possesses a prenylated OAS1 that can inhibit SARS-CoV-2. These findings indicate that horseshoe bats may be genetically and evolutionarily primed to be optimal reservoir hosts for certain coronaviruses, like SARS-CoV-2.Other studies have now shown that the p46 OAS1 variant, which resides in a genomic locus inherited from Neanderthals (5–7), correlates with protection from COVID-19 severity in various populations (8, 9). These findings mirror previous studies indicating that outcomes with West Nile virus (10) and hepatitis C virus (11) infection, both of which also use membrane vesicles for replication, are also associated with genetic variation at the human OAS1 locus. Another elegant functional study complements the findings of Wickenhagen et al. by also demonstrating that prenylated OAS1 inhibits multiple viruses, including SARS-CoV-2, and is associated with protection from severe COVID-19 in patients (12).There is a growing body of evidence that provides critical understanding of how human genetic variation shapes the outcome of infectious diseases like COVID-19. In addition to OAS1, genetic variation in another viral RNA sensor, Toll-like receptor 7 (TLR7), is associated with severe COVID-19 (13–15). The effects appear to be exclusive to males, because TLR7 is on the X chromosome, so inherited deleterious mutations in TLR7 therefore result in immune cells that fail to produce normal amounts of interferon, which correlates with more severe COVID-19. Our knowledge of the host cellular factors that control SARS-CoV-2 is rapidly increasing. These findings will undoubtedly open new avenues into SARS-CoV-2 antiviral immunity and may also be beneficial for the development of strategies to treat or prevent severe COVID-19.
Degrading viral RNAOnce inside a host cell, coronaviruses form double-membrane vesicles (DMVs) to replicate their RNA genome. When anchored to membranes, 2′-5′-oligoadenylate synthetase 1 (OAS1) detects double-stranded RNA (dsRNA) secondary structure and activates ribonuclease L (RNaseL), which degrades viral RNA. The OAS1 p42 isoform lacks the prenylation motif, so it is not membrane bound and RNaseL is not activated, leading to unrestrained viral replication and correlating with severe COVID-19.GRAPHIC: KELLIE HOLOSKI/SCIENCE Source: Shroggins SCIENCE
28 Oct 2021
Vol 374, Issue 6567
pp. 535-536
DOI: 10.1126/science.abm3921
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.
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.”
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.
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.
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
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 LLCof 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’sNational 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.
Other Related Articles published in this Open Access Online Scientific Journal include the following:
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 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.
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.
Study: Emergence of a new SARS-CoV-2 variant from GR clade with a novel S glycoprotein mutation V1230L in West Bengal, India
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; ornew 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.
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.
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.
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.
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