Vol.31 New variant, omicron (B.1.1.529) appeared
Last Updated 10 December 2021. Cellspect Co., Ltd.
Here comes a new coronavirus variant Omicron (B.1.1.529). This variant was first detected in South Africa on November 12 and in just two weeks, WHO judged that this variant had adversely changed the epidemiology, so it decided to change B. 1.1.529 into a Variant of Concern (VOC), named Omicron.
Why does the Omicron make scientists particularly worried?
It is because Omicron contains 32 mutations on the spike protein (S protein) which combines the mutation characteristics of various previous variants, including mutations related to virus entry into cells, immune escape, or increased infectivity, etc.. It carries mutations P681H and N679K which are 'rarely seen together' and could make it yet more resistant to vaccines. These two mutations, along with H655Y, may also make it easier for the virus to sneak into the body's cells. And the mutation N501Y may make the strain more transmissible and was previously seen on the Alpha and Beta among others. Two other mutations (R203K and G204R) could make the virus more infectious, while a mutation that is missing from this variant (NSP6) could increase its transmissibility. It also carries mutations K417N and E484A that are similar to those on the Beta variant that made it better able to dodge vaccines. Moreover, it also has the N440K, found on Delta, and S477N, on the New York variant — which was linked with a surge of cases in the state in March — that has been linked to antibody escape. Other mutations it has include G446S, T478K, Q493K, G496S, Q498R and Y505H, although their significance is not yet clear.
Omicron variant was first discovered in South Africa and Botswana, and the number of confirmed cases in Gauteng province in northeastern South Africa rose rapidly in the past two weeks, becoming the dominant variant now, showing that its transmission ability cannot be underestimated.
X-ray crystal structure analysis diagram of S protein and ACE2 receptor complex.
The mutation site of S protein found in the Omicron variant is indicated by purple spheres.
Can current PCR detect Omicron variant?
The current PCR test can detect this variant without problems. Several labs have indicated that for widely used PCR test, usually three main genes would be tested. For Omicron, it can be tested positive but one of genes will not be detected (called S gene dropout or S gene target failure), and this result can therefore be used as a marker for Omicron variant.
Will Omicron be more likely to cause severe disease?
The initial report in South Africa showed that the majority of cases were mild, but the virus was only detected for the first time in South Africa on November 12, and at the beginning it infected mostly young people. Therefore, it may take several weeks to accumulate more clinical information to analyze whether there is a higher risk for severe disease in the elderly or those who have not been vaccinated. Previously, it took about two months for this information in the case of Alpha or Delta variant.
Is the vaccine still useful for Omicron? How about oral drugs for monoclonal antibodies?
Almost all existing COVID-19 vaccines target against the S protein of the virus, however, there are 32 mutations on the S protein of Omicron variant. According to previous information on Beta, Delta variants, etc., the vaccine effectiveness should be affected more or less. Vaccine companies have already started laboratory research, and preliminary results should come out in about two weeks. The South African NICD estimates that there may be some immune escape, but the vaccine should still provide high protection against severe disease and death. Omicron variant has many mutations in the receptor-binding domain (RBD) that the monoclonal antibody acts on. Therefore, monoclonal antibodies may indeed decrease their effectiveness, which requires follow-up research. As for oral medicine, because its mechanism is completely different from that of vaccines, it does not act on S protein, so it is likely to be less affected. But this also needs to be confirmed by follow-up research.
Israel is to ban the entry of visitors from all countries due to the Omicron variant. The United States began restricting the entry of travelers from eight countries including South Africa on November 29, and urged the public to administer additional vaccines as soon as possible. The European Union proposes to impose travel restrictions on people from seven countries in southern Africa. And just now, prime minister Kishida has announced that all new entry to Japan will be suspended due to the worldwide expansion of the new COVID-19 variant Omicron.
WHO“Classification of Omicron (B.1.1.529): SARS-CoV-2 Variant of Concern”
27 Nov, 2021, “Why is Omicron so scary?” Mail Online News
26 Nov, 2021, “CDC Statement on B.1.1.529 (Omicron variant)”
Vol.32 「 オミクロン株、ＰＣＲ検査で発見可能 」
2021年12月24日 最終更新 セルスペクト（株）科学調査班編集
Conor Hale, Nov 29, 2021, “Thermo Fisher, Qiagen and other COVID-19 test makers prepare for oncoming omicron variant” Fierce Biotech
Radhika Anilkumar and Carl O'donnell, Nov 30, 2021, “Thermo Fisher says its COVID-19 tests accurately detects Omicron variant” Reuters
Ewen Callaway, Dec 02, 2021, “How bad is Omicron? What scientists know so far” Nature
Tom Batchelor, Dec 01, 2021, “Do lateral flow tests detect the Omicron variant? What we know so far” Independent News
Vol.33 「 感染初期に重症化を予測できる？ 」
2022年1月14日 最終更新 セルスペクト（株）科学調査班編集
Emilie Narni-Mancinelli & Eric Vivier, Oct 25, 2021,“Clues that natural killer cells help to control COVID” Nature news & views
Suchandrima Bhowmik, Aug 4, 2021, “The role of natural killer cells in the fight against coronavirus infection” News Medical Life Science
Xiaochan Xu and Kim Sneppen, Aug 3, 2021, “The timing of natural killer cell response in coronavirus infection: a concise model perspective” bioRxiv pre-print.
Vol.34 「 ワクチンで防ぎきれない「オミクロン株」に備えよ！ 」
2022年1月28日 最終更新 セルスペクト（株）科学調査班編集
Caroline Maslo, Dec 30, 2021, “Characteristics and Outcomes of Hospitalized Patients in South Africa During the COVID-19 Omicron Wave Compared with Previous Waves” JAMA
Emma Farge and Mrinalika Roy, Jan 5, 2022, “WHO sees more evidence that Omicron causes milder symptoms” Reuters
Elisabetta Cameroni et al., Dec 23, 2021, “Broadly neutralizing antibodies overcome SARS-CoV-2 Omicron antigenic shift” Nature
Delphine Planas et al., Dec 23, 2021 “Considerable escape of SARS-CoV-2 Omicron to antibody neutralization” Nature
Vol.35 「 UK announces end of all COVID-19 restrictionsLet's see how scientific data say? 」
Last Updated 10 February 2022. Cellspect Co., Ltd.
The pandemic is still raging across much of the world, but in UK, COVID-19 restrictions are becoming a thing of the past. British Prime Minister Boris Johnson announced that all COVID-19 restrictions in the UK will be scrapped as the Omicron wave seems to have peaked. Masks are no longer required anywhere, and vaccine passports have been dropped – although they were only compulsory in nightclubs and at large events such as soccer games. There is also no longer any work-from-home guidance. The government also removes the limit on the number of visitors allowed in nursing homes in England, and all testing requirements for fully vaccinated travelers will expire Feb. 11.
While many other countries, including Canada, have also begun to drop some COVID-19 measures, few have gone as far as Britain. It’s a risky move and will be watched closely by governments around the world, especially given the uncertainty surrounding the Omicron variant. Here, we would like to take a look of ending of these restrictions in a scientific way.
Many people are saying that Omicron is becoming influenza. Is it really like this? Below is a table of Omicron cases and mortality rate in the UK published by UKHSA on January 20.
Table 1. Cases and mortality rate of various variants in the UK (Data source: NHS England and Public Health England.)
It can be seen from this table that the infectious ability of Delta and Omicron is amazing, the confirmed cases are much more than Alpha variant and the Wuhan strain. The mortality rate and the death toll, however, are much less than Alpha variant and the Wuhan strain. Among them, the vaccine is definitely the most important contributor. So far, the mortality rate of Omicron patients is about 0.18%. Although it is still higher than influenza (about 0.1%), it is not too far beyond. Moreover, the mortality rate may be overestimated, because Omicron has too many mild and asymptomatic patients, so the actual number of infections should be higher and mortality rate would be less.
Below is another table about mortality rates after vaccination according to the COVID Week 19 vaccine surveillance report published by UKHSA on 20 January. It can also be seen from the following table that after the third booster shot, the mortality rate can still be very effectively reduced, especially for patients between the ages of 40 and 80.
Table 2. Comparison of mortality rates (data source: UKHSA)
Based on the above analysis, the lifting of restrictions in the UK can indeed be supported by scientific data. Some health experts were apprehensive about the lifting of restrictions, but many experts also say removing restrictions was in line with public opinion. Many people are ready to start "living with COVID,” and so, there is a general feeling amongst many in the public that mandated measures shouldn’t be in place longer than necessary. The UK is a good object of observation for countries with a high rate of third-dose vaccination. Their future direction will also be a good reference for other countries in the world.
Karim El-Bar, Jan 19, 2021, “UK premier announces end of most COVID-19 restrictions in England” World Europe
PAUL WALDIE, Jan 27, 2022, “Britain drops most COVID-19 restrictions, including masks and vaccine passports” The Global and Mail
COVID-19 pandemic in the United Kingdom (https://en.wikipedia.org/wiki/COVID-19_pandemic_in_the_United_Kingdom )
Jan 20, 2022 “COVID-19 vaccine weekly surveillance reports” UK Health Security Agency (UKHSA)
Vol.36 「 <Nature Medicine> Heart Disease Risk Increased by 63% One Year after Recovery from Mild COVID-19」
Last Updated 25 February 2022. Cellspect Co., Ltd.
Do you think even mild cases of Covid-19 should not be a cause for concern? Now you may want to pay more attention, as new research finds that even mild cases of COVID can increase the risk of heart diseases.
A recent study published in the journal Nature Medicine found that one year after contracting covid-19, people were at higher risk of cardiovascular diseases, including cerebrovascular disease, arrhythmias, ischemic and non-ischemic Heart disease, pericarditis, myocarditis, heart failure and thromboembolic disease. Those not admitted to hospital with covid-19 are also at risk for these problems, and the risk increases with the severity of the infection, from those not admitted to those in intensive care. Even mild cases of COVID-19 can increase a person's risk of cardiovascular disease for at least one year after diagnosis.
Patients in this study consists of 153,760 U.S. veterans who had survived Covid-19 for at least 30 days beyond the initial diagnoses. Overall, those who had recovered from Covid-19 coronavirus infections were 63% more likely to have had some kind of cardiovascular problem in the ensuing year than those in the control groups. That included a 52% greater likelihood of suffering a stroke, a 63% higher likelihood of a heart attack, a 72% higher likelihood of heart failure, and a 145% higher likelihood of heart failure. Those who had had Covid-19 were also more likely to subsequently have various abnormal heart rhythms such as atrial fibrillation (71% more likely), sinus tachycardia (84%), sinus bradycardia (53%), and ventricular arrhythmias (84%).
People with covid-19 are at high risk for cardiovascular disease, the researchers said. While the best way to prevent cardiovascular problems is to prevent infections in the first place, governments and health systems must be prepared for major problems that may arise in the future. More than 72 million people have been infected with covid-19 in the US, more than 16 million in the UK, and more than 355 million globally. The cardiovascular problems found in some people with covid-19 are chronic and can have long-term effects on individuals and health systems, economic productivity and life expectancy, the researchers said.
The increased risk was evident regardless of age, race, gender and other cardiovascular risk factors, including obesity, hypertension, diabetes, chronic kidney disease and hyperlipidemia, the researchers wrote; prior to exposure to covid-19, they It was also evident in people without any cardiovascular disease, providing evidence that these risks may occur even in people with a lower risk of cardiovascular disease. However, they said, the way in which covid-19 infection may lead to cardiovascular problems remains unclear.
The authors warn that the analysis, which focuses on the first year after contracting the virus, suggests that the consequences of Covid-19 could extend "well beyond the acute phase of infection". They suggest: "Governments and health systems around the world should be prepared to deal with a potentially significant increase in the burden of cardiovascular disease." But with the high number of COVID-19 cases still straining medical resources, the authors worry that health authorities will delay a pandemic The consequences of preparing for too long.
More and more studies have shown that infection with the novel coronavirus will not only affect the heart and blood circulation of patients in the short term, but also affect the heart and blood circulation in the long term. Angiography (MRI) still showed cardiac abnormalities; in addition, a study in JAMA Cardiology pointed out that asymptomatic patients with the novel coronavirus infection still develop heart damage or inflammation after recovery. Moreover, while there is evidence of long-term heart and vascular damage, similar things could be happening in the brain and other organs, resulting in symptoms characteristic of long covid, including brain fog. Therefore, doctors suggest that those who have recovered from Covid, even those with milder disease, undergo a cardiac or full check-up around six months after the infection, at least till researchers can determine who is at risk of these long Covid symptoms.
Yan Xie et al., Feb 7, 2022, “Long-term cardiovascular outcomes of COVID-19” Nature Medicine
Bruce Y. Lee, Feb 13, 2022, “Study Finds Increased Heart Disease, Stroke Risk After Surviving Even Mild Covid-19” Forbes
Sarah Newey, Feb 8, 2022, “Heart attack risk increases 63pc post-Covid, says major American study” The Telegraph
Saima May Sidik, Feb 10, 2022 “Heart-disease risk soars after COVID — even with a mild case” Nature
Curt J. Daniels et al., May 27, 2021 “Prevalence of Clinical and Subclinical Myocarditis in Competitive Athletes With Recent SARS-CoV-2 Infection” JAMA Cardiology
2022年3月11日 最終更新 セルスペクト（株）科学調査班編集
Qin Liu et al., Mar 2022, “Gut microbiota dynamics in a prospective cohort of patients with post-acute COVID-19 syndrome” Gut
Jan 26, 2022 “CU Medicine study shows distinct gut microbial profile associated with long COVID” CU Medicine Press Releases
James Kingsland, Feb 1, 2022, “Gut bacteria may play a role in the development of long COVID” Medical News Today
Shawn Radcliffe, Jan 27, 2022, “Long COVID Linked to Unbalanced Gut Microbiome: What to Know Now” healthline
Thomas R, Jan 25, 2022, “Collins Gut bacteria linked with long COVID” Internal Medicine News
Vol.38 「Indian Glenmark and Canadian SaNOtize introduce nasal spray to treat Covid-19 in India」
Last Updated 25 March 2022. Cellspect Co., Ltd.
Recently, the Nitric Oxide Nasal Spray (NONS), jointly developed by Indian company Glenmark Pharmaceuticals and Canada's SaNOtize Research & Development Corp., has been approved by the Indian Drug Regulatory Agency for COVID-19 patients at increased disease progression risk. This nasal spray will be marketed under the brand name FabiSpray.
FabiSpray is a nitric oxide spray, a small molecule gas naturally produced by the human body and has been shown to have antimicrobial properties. FabiSpray has been designed to destroy the SARS-CoV-2 virus that causes Covid-19 in the upper airways. When applied over nasal mucosa, the spray works as a physical as well as a chemical barrier against the virus, thereby averting the viral incubation and spreading to the lungs. The Phase III clinical trial of FabiSpray was conducted in India. It was a double-blind, two-arm parallel, multi-center study involving a total of 306 patients and conducted at 20 experimental sites to evaluate the use of FabiSpray in non-hospitalized adult patients with COVID-19 regarding efficacy and safety. In the trial, patients at risk of disease progression were specifically analyzed, including unvaccinated patients, middle-aged and elderly patients, and patients with other complications.
The phase III clinical data of FabiSpray showed that the virus load in confirmed patients using the drug was reduced by more than 94% within 24 hours and by more than 99% within 48 hours. This data was statistically significant and superior to the placebo group using normal saline. Dr Srikanth Krishnamurthy one of the Principal Investigators of the study said that Nitric Oxide Nasal Spray lowers the viral load and hastens RT-PCR negativity when used early in COVID 19 infection leading to recovery. Most importantly, viral load reduction with FabiSpray has the potential to reduce the chain of transmission. Moreover, FabiSpray being topical, is safe and makes this therapeutic option very attractive, he added.
Approved for the treatment of adult patients with Covid, who have a high risk of disease progression, Dr Monika Tandon, Glenmark Pharma’s Senior - and Head (Clinical Development) said. The spray will be available on doctor’s prescription and priced at 12 USD for a 25 ml bottle which covers the length of one person’s treatment. FabiSpray is a useful and convenient option to fight the novel coronavirus. From a patient and community perspective, as highly contagious variants of the virus continue to emerge, reducing viral load will provide effective infection control. Moreover, according to Glenmark, the spray is not “variant-specific”, and has been proven to work against the alpha, beta, gamma and delta variants of SARS-CoV-2, as well as the Rhinovirus and H1N1 virus.
SaNOtize co-founder and CEO Gilly Regev said, "We are delighted that the company can provide patients with an affordable product that has been shown to help cure diseases faster and its safety has been proven. They look forward to the drug becoming the first line treatment and possible preventive measure for COVID-19. "
In addition to India, the drug has also obtained EU CE marking and SaNOtize is approved to market the product in the EU; the product is also under approval in Israel, Thailand, Indonesia and Bahrain under the product name enovid™ or VirX™.
PT Jyothi Datta, Feb 9 2022, “Glenmark, Canadian firm SaNOtize’s Nitric Oxide nasal spray against Covid launched in India” BussinessLine
Feb 9, 2022 “Glenmark and SaNOtize introduce nasal spray to treat Covid-19 in India” Pharmaceutical Technology
IANS, Feb 9, 2022, “Mumbai-Based Glenmark Launches Nitric Oxide Nasal Spray for COVID-19 Treatment” The Times of India
Vol.39 「Oxford Study: Even Mild Covid Can Cause Obvious Brain Damage or Cognitive Decline」
Last Updated 8 April 2022. Cellspect Co., Ltd.
Recently days, a clinical neuroscience team at the University of Oxford in the United Kingdom found that even mild COVID may still cause brain damage, including: weakening of cortex in specific areas, tissue damage and great shrinkage in brain areas related to smell, etc. The study compared the brain images of 785 patients diagnosed with COVID and healthy people and was published in the top journal "Nature".
The analysis group in this study was between 51 and 81 years old. Among them, 401 people were diagnosed with COVID between two brain scans with an average interval of 34 weeks, and only 15 cases were severe cases, the rest are mild to moderate cases without hospitalization.
The study found that "cognitive decline" was more obvious between scans in those diagnosed, and the problem appeared to be related to damage to the cerebellum. After brain scans of healthy and diagnosed patients, they found that gray matter stiffness and tissue connectivity decreased more in the orbitofrontal cortex and para hippocampal gyrus regions of the brain. In the functionally-connected regions with the primary olfactory cortex, the tissue damage was more pronounced and the volume of the whole brain was reduced more.
The study also assessed cognitive changes in the participants and found that those who had been diagnosed had more cognitive decline at the two assessment time points. In addition, if 15 critically ill patients were excluded from the analysis, the cognitive and brain changes caused by the above infections were still quite significant. This finding is particularly important because most brain-related COVID studies to date have focused on hospitalized patients with severe disease.
Separately, the authors studied people who developed pneumonia not related to COVID, showing that the changes were specific to COVID, and not due to the generic effects of contracting a respiratory illness.
The UK Biobank COVID-19 has generated a unique "repeat Imaging" resource by collecting a second set of multi-organ imaging scans from COVID patients and healthy people. These imaging enabled the only study in the world to demonstrate “before vs after” changes in the brain associated with SARS-CoV-2 infection.
This study shows that the possible damage of the COVID to the brain and nervous system is greater than everyone expected, and even patients with mild to moderate symptoms cannot ignore the correct treatment and care. From very early on in the pandemic, there has been strong evidence that COVID affects the brain and nervous system, such as symptoms like the loss of smell and taste as hallmarks of early infection. Many of the debilitating sequelae of COVID infection, including "brain fog," fatigue, memory impairment and headaches, have also been deeply linked to neurological problems caused by the virus. More research is needed to determine whether these negative effects of Covid-19 persist over time. At the same time, whether the COVID will further cause other changes in the brain structure, for example, if the limbic system of the brain may become more fragile or affect memory and emotion, etc., will also be a great concern in the future.
Gwenaëlle Douaud et al., Mar 7 2022, “SARS-CoV-2 is associated with changes in brain structure in UK Biobank” Nature.
Robert Hart, Mar 8, 2022 “Even Mild Covid Can Cause Brain Damage, Study Suggests” Forbes.
Mar 7, 2022, “Brain regions related to smell show decline following mild COVID-19” University of Oxford Press
Vol.40 「New Frontier in Infectious Disease Surveillance: Wastewater Test for COVID-19」
Last Updated 22 April 2022. Cellspect Co., Ltd.
After the outbreak of Covid-19, wastewater surveillance, a new tracking system, has begun to play a critical role in the field of public health.
In a March 2020, a study published in The Lancet Gastroenterology and Hepatology confirmed that confirmed that the novel coronavirus can appear in feces within three days of infection, which is much earlier than the time required for people to develop symptoms. Other studies show that the median duration of SARS-CoV-2 presence in feces was 22 days, which was significantly longer than in respiratory (18 days; P = .002) and serum samples (16 days; P < .001). Regardless of the infectious disease, since pathogens end up in wastewater treatment facilities, wastewater testing or wastewater-based epidemiology (WBE) may be useful in understanding the actual incidence of COVID-19 in the region. Early warning of a COVID-19 outbreak is effective.
After the Covid-19 pandemic began, countries all over the world began to monitor wastewater one after another. In Japan, the novel coronavirus was detected in wastewater for the first time in June, 2020. The CDC also officially launched the National Wastewater Surveillance System (NWSS) in September 2020. What started as a civic-based effort by academic researchers and wastewater treatment agencies has quickly become a nationwide monitoring system. The NWSS provides community-level information, specifically on COVID infections in the community, to understand which communities are experiencing rising and which are declining. The NWSS has been so successful that it allows the government to identify where infection hotspots are and deploy more resources to contain the spread.
Data from wastewater surveillance are uniquely powerful because they can capture infections in both symptomatic and asymptomatic people. And they're not affected by whether a patient has access to health care or clinical testing. These advantages can inform important public health decisions, such as where to allocate mobile testing and vaccination sites. And this system has its advantages even more for the Omicron variant, which mostly infected patients are asymptomatic. For example, on December 25 last year in Texas in the United States, through the analysis of samples collected by 35 sewage plants out of 39 in the city, it was found that the positive rate of Omicron variant increased by 164%, which also timely warned the trend of the outbreak of Omicron variant.
The U.S. NWSS system was built for COVID as part of COVID prevention, but wastewater surveillance can be applied to a wide variety of epidemic problems. The United States is now expanding wastewater surveillance platforms to collect data on other pathogens. Targets include antibiotic resistance, foodborne infectious pathogens such as E. coli, Salmonella, Norwalk influenza and emerging fungal pathogens. Japan currently does not have a surveillance system similar to NWSS, but Japan also started the " Promotion Plan for Wastewater Surveillance " in November 2021. The purpose is also to speed up the verification and analysis of wastewater surveillance, and put it into practical application as soon as possible. We look forward to its future applications.
Akihiko Hata et al, June 12, 2020 “Detection of SARS-CoV-2 in wastewater in Japan by multiple molecular assays-implication for wastewater-based epidemiology (WBE)”. medRxiv
Eiji Haramoto et al., published online 2020 Jun 20. “First environmental surveillance for the presence of SARS-CoV-2 RNA in wastewater and river water in Japan”. Sci Total Environ. 2020 Oct 1; 737: 140405.
Yongjian Wu et al, published Online March 19, 2020 “Prolonged presence of SARS-CoV-2 viral RNA in faecal samples” Lancet Gastroenterol Hepatol. 2020 May;5(5):434-435.
US Centers for Disease Control and Prevention, Newstarget，CCTV2
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