Comparison of various tests of Covid-19

Last Updated 15 January 2021. Cellspect Co., Ltd.

Various Covid-19 tests are being used currently. Generally speaking, there are two kinds of tests are available for COVID-19: viral tests (diagnostic tests) and antibody tests. Viral tests are to detect whether a person is currently infected, including PCR and antigen tests. Antibody tests are to detect whether a person had an infection in the past. 

 

PCR test

PCR tests detect the presence of viral RNA. PCR tests are considered the most accurate and “gold standard” for diagnosing active coronavirus infection. This test is typically highly accurate. However, the testing cost is relatively high, the evaluation time is longer, and the analysis needs professional staff and equipment.

 

Antigen test

Antigen tests detect specific proteins from SARS-CoV-2, the virus that causes Covid-19. Antigen test is not as sensitive (accurate) as the standard PCR test and may have higher false negative rate. The advantages of antigen tests are the lower cost and lower demands on the expertise of the staff. So far, many rapid antigen tests have been developed and the results may be shown very quickly (15-30 minutes). The rapid antigen test reveals patients at the peak of the infection when the body has the highest concentration of these proteins. Positive results are usually highly accurate, but increased chance of false-negative can happen. Negative results may need to be confirmed with a PCR test.

 

Antibody test (serology test)

Antibody tests measure antibodies against SARS-CoV-2 virus, detecting if the immune system has responded to the SARS-CoV-2 virus in the past. Antibodies are not present at the onset of the disease. According to the U.S. CDC, antibodies against SARS-CoV-2 virus usually start developing within 1 to 3 weeks after infection. Antibody tests generally produce results in a few minutes based on a drop of blood taken from the finger; some tests may take 1-3 days if blood is drawn for testing. In some cases, antibody tests can help determine when Covid-19 illness occurred, since we know that IgM is formed before IgG and that IgM goes away before IgG. It can also help determine who qualifies to donate convalescent plasma for Covid-19 treatment. Moreover, antibody tests could be useful in measuring the durability of vaccine responses

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A negative viral test means that person was probably not infected at the time their sample was collected. However, it doesn’t mean they won’t get sick – it only means that they didn’t have COVID-19 at the time of testing. A negative antigen test means that SARS-CoV-2 viral proteins were not detected. Due to the false-negative rate of antigen test, it is recommended to do a PCR test for confirmation.

 References:

  1. HORIZON The EU Research & Innovation Magazine: https://horizon-magazine.eu/

  2. U.S. Food and drug administration: https://www.fda.gov/

  3. World Health Organization: WHO https://www.who.int/

  4. Centers for Disease Control and Prevention: https://www.cdc.gov/

  5. Texas Health and Human servicess: https://hhs.texas.gov/

  6. Kazuo.I et al, Antibody response patterns in COVID-19 patients with different levels of disease severity—Japan, preprint, doi: https://doi.org/10.1101/2020.11.20.20231696;

 

Cross-country comparison of Covid-19 testing policy

Last Updated 18 January 2021. Cellspect Co., Ltd.

The Covid-19 pandemic continues to pose a major threat to public health. Currently, Covid-19 tests fall into two types and three main categories, viral tests, including PCR and antigen test and antibody test. Viral tests are to detect whether a person is currently infected and antibody tests are to detect whether a person had an infection in the past. At present, the Covid-19 test policy in various countries differ due to the supply, test capabilities and medical capacity.

 

PCR test (RT-PCR)

PCR tests is the gold standard for diagnosing active coronavirus infection and still the most widely used and accepted method at the present. Official known cases mostly come from PCR tests. So far, most countries have open public testing (e.g., “drive through” testing) available to asymptomatic people, including US, Germany, France, Russia, South Africa, Japan, South Korea, China, Taiwan and Malaysia etc. Some countries provide testing for people showing Covid-19 symptoms, including UK, Canada, Australia, Finland, Spain, India, the Philippines and Thailand. In countries with limited medical and testing resources, testing is provided for those who both symptoms and meet specific criteria (e.g. key workers, admitted to hospital, came into contact with a known case), including Brazil, Mexico, Indonesia, and most Africa countries.

For international travelers, some countries accept only a negative PCR test performed less than 72 hrs before the flight for all travelers, such as France, Germany, Australia, China and Taiwan. 

 

Antigen test

Antigen test is not as sensitive (accurate) as PCR test and may have higher false negative rate, however, as rapid antigen tests have been developed and optimized, more and more countries have started accepting antigen test results. The WHO published on 11 September 2020 interim guidance on the use of rapid antigen tests for COVID-19 and recommends the use of rapid antigen tests that meet the minimum performance requirements of > 80% sensitivity and > 97% specificity. Now, when the availability of PCR testing is temporarily restricted (such as at airport), antigen testing is used. In the US, antigen tests now serve equally to PCR tests and is available in hospitals and public test stations. For other countries, antigen tests are used mostly in the airports for boarder control.

As a general rule, Japan tests all immigrants in the airports for Covid-19 and from the end of last July, the test method was changed from PCR test to saliva antigen test. From last October, Singapore have begun the use of antigen rapid tests to more quickly detect Covid-19 among migrant workers who undergo rostered routine testing. Travelers into most Europe countries (UK, Italy, Norway, Austria etc.), New Zealand and Africa are required to undergo antigen testing at the airports if they don't have a negative Covid-19 viral test without 72-hour. Beginning Jan. 26, the US CDC also require all people who plan to enter the US to show proof of a negative Covid-19 viral test (either a PCR test or an antigen test) prior to boarding. Apparently, due to the advantages of rapid tests, more and more countries and are using antigen tests on transportation and routine tests.

 

Antibody test (serology test)

Antibody tests determine whether a person has infection in the past but not suited for diagnosis of new infections. Therefore, antibody tests are mostly used for research or monitoring and not suited particular regulation policy so far. While there is a lot of uncertainty with this new virus, it is also possible that, over time, broad use of antibody tests and clinical follow-up will provide the medical community with more information on whether or not, and how long, a person who has recovered from the virus is at lower risk of infection if they are exposed to the virus again. Antibody tests can play a critical role in the fight against Covid-19 by helping healthcare professionals identify individuals who have antibodies to SARS-CoV-2 virus and have developed an adaptive immune response. In the future, this may potentially be used to help determine, together with other clinical data, whether these individuals may be less susceptible to infection. At this time, it is unknown for how long antibodies persist following infection and if the presence of antibodies confers protective immunity.

 References:

  1. U.S. Food and drug administration: https://www.fda.gov/

  2. World Health Organization: WHO https://www.who.int/

  3. Centers for Disease Control and Prevention: https://www.cdc.gov/

  4. Our world in Data:https://ourworldindata.org/

  5. OECD Policy Responses to Coronavirus (COVID-19):http://www.oecd.org/coronavirus/en/

 

Comparison of Covid-19 vaccine

Last Updated 3 February 2021. Cellspect Co., Ltd.

After suffering a terribly awful 2020 of Covid-19 pandemic, scientists embarked on a race to produce safe and effective coronavirus vaccines in record time. People now finally see some hope of returning to normal life as good news of Covid-19 vaccine gradually coming out. Up to date, several Covid-19 vaccines have been authorized for emergency use in various countries. Vaccines work by exposing healthy people to parts of a pathogen, allowing human immune system to develop the cells and proteins necessary for fighting off the pathogen when they come across the real disease. The Covid-19 vaccines currently administered globally can be roughly divided into three categories: 

1. RNA vaccines (Pfizer/BioNtech and Modena)

2. adenovirus vaccines (Oxford-AstraZeneca and Gamaleya)

3. inactived/dead coronavirus (Sinopharm)

 

Below is a quick guide to the COVID-19 vaccines now mainly in use around the world. 

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RNA vaccines

An RNA vaccine contains mRNA which, when introduced into a tissue to cause the cells to build the foreign protein and stimulate an adaptive immune response. The delivery of mRNA is achieved by a co-formulation of the molecule into lipid nanoparticles which protect the RNA strands and helps their absorption into the cells. RNA vaccines are a relatively new type of vaccines and draw public interests because they can be developed in a laboratory using readily available materials. Advantages of RNA vaccines include good safety (since there are no live components, there’s no risk of the vaccine triggering disease), reliability, and that it’s relatively simple to manufacture. Actually, mRNA vaccines have been studied before for flu, Zika, rabies, and cytomegalovirus (CMV). However, mRNA is extremely fragile and if not handled properly it can fall apart. The storage and long-distance shipping will be a big problem for RNA vaccines. Another fact is that this type of vaccine has never previously been licensed for humans.

 

Adenovirus vector vaccines

These vaccines are examples of non-replicating viral vector vaccines, using an adenovirus shell containing DNA that encodes a SARS-CoV-2 protein. Adenovirus-vectored vaccines are the other technology that has been close behind the mRNA-based vaccines in clinical testing. The biggest advantage of Adenovirus vaccines is that scientists have been using this technology in the lab for decades. The process of inserting genes into the adenovirus vectors is well developed so it can also be done pretty quickly. Moreover, the storage condition for adenovirus vaccines is much easier than RNA vaccines. Notedly, previous exposure to the vector might reduce the effectiveness.

 

Inactivated virus vaccines

Inactivated vaccines consist of virus particles that have been grown in culture and then are killed using a method such as heat or formaldehyde to lose disease producing capacity, while still stimulating an immune response. the advantages of an inactivated virus vaccine include the fact its technology is well established, it is suitable for people with compromised immune systems, and it’s relatively simple to manufacture.

 

The US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) set a cutoff of 50% as the efficacy required to approve a COVID‑19 vaccine. Currently, most Covid-19 vaccines show better efficacy than WHO’s recommendation. Other than efficacy, safety has been a top priority. Vaccine developers report side effects that include pain at the injection site, fever, muscle aches, fatigue and headaches, mostly lasting about a day or two. These are normal side effects after inoculation. So far, none of the vaccine trials have reported any serious safety concerns and safety data are continuously reviewed by the FDA and expert panels. But according to the CDC, at this time, anyone who has a severe allergy (e.g., anaphylaxis) to any of the Pfizer/BioNTech vaccine ingredients should not receive this vaccine. One more issue is that the vaccine's side-effects are rare and usually mild, but they could include fever and nausea, which could be dangerous in very ill and frail patients. Some death after Covid-19 vaccination was reported and the new guidance says doctors should evaluate each individual patient to determine whether the benefits of vaccination outweigh the risks of any potential side effects.

 References:

  1. Coronavirus Vaccine Tracker: The New York Times: https://www.nytimes.com/interactive/2020/science/coronavirus-vaccine-tracker.html

  2. U.S. Food and drug administration: https://www.fda.gov/

  3. World Health Organization: WHO https://www.who.int/

  4. Centers for Disease Control and Prevention: https://www.cdc.gov/

  5. COVID-19 vaccine – Wikipedia: https://ourworldindata.org/

  6. BBC News: https://www.bbc.com/news 

 

Emerging of SARS-CoV-2 Variants: Are they dangerous?

Last Updated 5 February 2021. Cellspect Co., Ltd.

In just about one year, the novel coronavirus has infected more than 100 million people and took away more than 2 million lives. Before the pandemic subsided, several virus variants appeared recently, causing panic among most people.

As the Covid-19 pandemic developed, numerous groups of scientists around the world have been sequencing isolates and uploading them to the GISAID (Global Initiative on Sharing All Influenza Data) database in a global collaborative effort to compile SARS-CoV-2 genetic sequences. This enables tracking of new variants that emerge over the course of the pandemic. By January 2021 as many as 300,000 genetic variants of SARS-CoV-2 have been identified. The mutation number looks scary, but it is actually very normal in all RNA viruses because it is part of their natural life cycle. SARS-CoV-2 mutates and acquires about one new mutation in its genome every two weeks but the majority of new variations in the SARS-CoV-2 genetic code have little effect on the virus. Most variants just disappeared silently. 

However, there are some notable variants worth experts’ concerns. The virus first detected in Wuhan, China, is not the same one you will find in most corners of the world. The variant D614G, named because the amino acid aspartate (D, in biochemical shorthand) at the 614th position of the spike protein was replaced by glycine (G), emerged in Europe in February and became the globally dominant form of the virus. D614G also correlates with the symptom of loss of smell which may result from higher binding of the RBD to the ACE2 receptor and hence higher infectivity of the olfactory epithelium. Another, called A222V, spread across Europe and was linked to people's summer holidays in Spain. And now, new variants, B.1.1.7 from UK, B.1.351 from South Africa, and P.1 from Brazil emerged in the fall of 2020.

The new variants caused alarm because all of them involved multiple mutations including mutations in the receptor binding domain (RBD) of the spike protein. It is known that the novel coronavirus attaches to human cells through a "spike protein." After the spike protein binds to the ACE2 receptor on a human cell, the viral membrane fuses with the human cell membrane, allowing the genome of the virus to enter human cells. The RBD mutation of the virus is the reason for the higher affinity of SARS-CoV-2 and ACE2. 

Preliminary reports show that British variant B.1.1.7 is more transmissible than previous circulating viruses, with an estimated increase of between 50% and 70% in transmissibility. The mutant N501Y which is found in all three emerging variants, increase binding affinity between virus and cells thus makes the virus bind more tightly to human cells. 

More infectious doesn’t mean more dangerous. At present, there is no data that British variant increases severity of Covid-19. On January 22, British Prime Minister Boris Johnson stated that "British coronavirus variant may be more deadly", however, later the UK government revised its original view that the B.1.1.7 variant was not more dangerous. The government said that new evidence showed that on average, for 1,000 men in their 60s, 13 to 14 would die if they contracted the new variant, compared to 10 for the original strain of SARS-CoV-2. However, even if the effect of the variant on severity does not change, if it spreads much more easily, that means the quality of medical care may drop, which can lead to higher death rates than would otherwise be expected.

 

Another concern is that if vaccines and current drugs still work against the new variants. Both Pfizer and Modena stated that their laboratory tests showed their vaccine still work against the new variants. Regeneron also reported that their antibody cocktail treatment can neutralize variants, despite the mutations. Although more evidence is needed, experts generally believe that vaccines and drugs will still be effective so far. 

 

To sum up, the best way to face these variants is to stay alert but no need to panic. New variants still spread the same way as the ordinary form of the coronavirus. That means everyone should do the same things: washing hands, physical distancing, masks and good ventilation to prevent the spread of virus

 References:

  1. U.S. Food and drug administration: https://www.fda.gov/

  2. World Health Organization: WHO https://www.who.int/

  3. Centers for Disease Control and Prevention: https://www.cdc.gov/

  4. GISAID: https://www.gisaid.org/

 

For Severe COVID-19: Who Are at High Risk?

Last Updated 15 February 2021. Cellspect Co., Ltd.

COVID-19 can affect anyone, and the disease can cause symptoms ranging from mild to very severe. For some other illnesses caused by respiratory viruses (such as influenza), some people may be more likely to have severe illness than others because they have characteristics or medical conditions that increase their risk. These are commonly called “risk factors.” Examples include older age or having certain underlying medical conditions.

Severe COVID-19 means that a person with COVID-19 may require hospitalization, intensive care, or a ventilator and may even die in the worst condition. So far, age is generally considered as a biggest risk factor for severe COVID-19. According to CDC, 8 out of 10 COVID-19 deaths reported in the U.S. have been in adults 65 years old and older. Below is the table of severe COVID-19 cases by age in Japan:

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Apparently, age greatly Increases risk for severe COVID-19 Illness . Besides age, any person with the following conditions are warned by WHO that may be at increased risk to develop severe COVID-19:

  • Cancer

  • Severe Obesity (BMI ≥ 30 kg/m2)

  • Chronic kidney disease

  • Type 2 diabetes mellitus

  • COPD (chronic obstructive pulmonary disease)

  • Heart conditions, such as heart failure, coronary artery disease, or cardiomyopathies

  • Smoking

  • Pregnancy

  • Down Syndrome

  • Sickle cell disease

 

Not all these risk factors have clear explanations, however, scientists do have several speculations for these risk factors. As for age, aging (i.e., internal physiological deterioration) is absent in children and minimal in young adults. It accelerates, however, in later years, resulting in a generalized, progressive decline in somatic function. Decreased resilience to all manner of insults, including infection, inevitably follows. Moreover, aging is known to impair both cardiac function and damage-repair capabilities, and SARS-CoV-2 is known to cause myocardial damage that at times severely compromises cardiac function. It therefore seems likely that COVID-19 related cardiac insults such as cardiomyopathy and ischemia generally will be of greater consequence to the elderly than to the young. Besides, young children, especially those attending daycare centers, catch far more colds than other age group, and included among the responsible pathogens are 4 coronaviruses related to SARS-CoV-2. Past infections with coronaviruses are known to generate B and T cell memory, and it seems likely (though currently unproven) that this confers a degree of protective cross-immunity to SARS-CoV-2. Thus, if protective cross immunity indeed exists, but wanes over time, children are likely to have more of it than adults, particularly elderly adults.

When obesity occurs: the amount of fat increases but stored in the wrong places. The fat will be stored in the liver and in skeletal muscle which disturbs body metabolism. This disturbance is associated with a range of abnormalities, including increases in inflammatory cytokines and a reduction of a molecule called adiponectin that directly protects the lungs. Fat increases in the lung itself may disturb how the lung handles the virus as well.

And for people who already have certain health problem, it is known that most medical conditions can cause a person to be immunocompromised, which means a weakened immune system. Therefore, those people are inevitably in a higher risk to develop sever COVID-19.

It is important to learn about risk factors for severe COVID-19 illness because it can help you:

  • Take precautions as you go about your daily life and attend events.

  • Better understand how a medical condition could affect your own health if you get sick with COVID-19.

  • Anticipate medical treatment that you might need if you get sick.

  • Reduce your risk for severe COVID-19 illness by managing any conditions you have that are risk factors.

If you are at high risk of getting sever COVID-19 illness, remember the best way is to limit your interactions with other people as much as possible and take precautions to prevent getting COVID-19 when you do interact with others.

 References:

  1. U.S. Food and drug administration: https://www.fda.gov/

  2. World Health Organization: WHO https://www.who.int/

  3. Centers for Disease Control and Prevention: https://www.cdc.gov/

  4. 新型コロナウイルス感染症(COVID-19)診療の手引き・第4.1版

 

Vol.6 Immune Memory gives hope for the long-term protection of vaccines

Last Updated 25 February 2021. Cellspect Co., Ltd.

The dramatic emergence of SARS-CoV-2 into our lives and the subsequent COVID-19 pandemic have spawned the active development of nearly 200 vaccine candidates. Vaccines typically require years of research and testing before reaching the clinic, but in order to stop the pandemic, scientists are racing to develop and administer safe and effective vaccines at a record-breaking speed. According to WHO statistics, more than 159 million doses have been administered across 76 countries. And How long people can fight off reinfection to the novel coronavirus and what immune process is involved are key to predicting the dynamics of the pandemic.

Previously, some studies seem to paint a grim picture of how long COVID-19 immunity lasts, finding evidence of viral antibody counts plummeting in COVID-19 patients a mere two months after an initial infection. People have worried that these people are vulnerable to reinfection and that long-lasting vaccines could be more difficult to develop, making widespread herd immunity impossible to obtain. 

In fact, human immune memory is more than just antibodies and may be stronger than you think. The specific antibodies do not need to be present in large numbers when the body is no longer faced with a threat from the specific pathogen involved. Once the immune system's memory cells, such as T and B lymphocytes have been created, they can, usually, rapidly produce new specific antibodies, when and as needed. Furthermore, the immunological memory can also be established by natural killer cells (NK cells). NK cells can respond to haptens or viruses, which results in generation of antigen-specific memory cells. Therefore, if there is a marked decrease in the number of specific Covid-19 antibodies, that does not mean that the body is incapable of mounting a rapid defense against re-infection from the Covid-19 virus. Rather, a decrease in the antibodies concerned can be just due to a lack of need.

Encouragingly, several new studies have come up recently to support long-lasting immune memory. A study published in “Science” have revealed that most people who recover from Covid-19 have immune memory to protect against reinfection for at least eight months. This study is so far known as the largest study ever for any acute infection as all four components (circulating antibodies, memory B cells, helper T cells and killer T cells) of immune memory have been measured. In a separate study published in “Nature” concluded that the memory B cell response to SARS-CoV-2 may last up to 6 months after infection. They found that although titers of neutralizing antibody declined over time, memory B cells specific for the receptor-binding domain of SARS-CoV-2 spike protein persisted up to 6 months after infection. These memory B cells can even generate antibodies with increased neutralization potency and breadth.

These two studies show consistent results with an earlier study published in “Science Immunology”. Memory B cells in patients increased rapidly after the onset of Covid-19 symptoms. Initially, these memory B cells mainly expressed IgM antibodies. With the passage of time, the proportion of IgG antibodies expressed in memory B cells increased significantly. This transition reflects the normal process of B cell maturation. Although the IgM antibodies originally produced by B cells can also neutralize the virus, their neutralizing effect is not necessarily the best. In the process of maturation, B cells will adjust the affinity of neutralizing antibodies and antigens through genetic mutations, and generate IgG antibodies with higher affinity to the antigen and stronger neutralizing ability. Moreover, the level of memory B cells, especially the memory B cells that produce IgG, remained stable more than 200 days after the onset of symptoms.

Immune memory responses are responsible for protection from reinfection, these studies provide great evidences for the longevity of protection afforded by vaccines. Although these results are encouraging, nothing about this pandemic is simple. The wide spectrum of immune responses to the SARS-CoV-2 virus means that there will likely be a range of responses to a vaccine. Not everyone will receive the same level of protection from a given vaccine and some may not get any protection at all. What’s more, the immune response in older people is different from that in children, for example, so it’s hard to make a one-size-fits-all vaccine. The question of whether a vaccine will lead to effective immunity can only be answered with more clinical trials. Researchers around the world will continue to analyze samples from Covid-19 patients in the future and to track their immune responses for longer period after the onset of symptoms.

 References:

  1. World Health Organization: WHO https://www.who.int/

  2. Jennifer M. Dan et al. 06 Jan 2021. “Immunological memory to SARS-CoV-2 assessed for up to 8 months after infection” Science.

  3. Christian Gaebler et al. 06 Jan 2021. “Evolution of antibody immunity to SARS-CoV-2” Nature. 

  4. Gemma E. Hartley et al. 22 Dec 2020. “Rapid generation of durable B cell memory to SARS-CoV-2 spike and nucleocapsid proteins in COVID-19 and convalescence” Science Immunology.

 

Vol.7 The Power of Digital Technology: How Does It Help in Fighting with Covid-19?

Last Updated 4 March 2021. Cellspect Co., Ltd.

In the fight against the covid-19, the medical system is the frontline battlefield. However, as the pandemic progresses, the digital technology apparently became a new battlefield against this disease. Digital technology cannot prevent a pandemic; however, it can help prevent spread, educate, warn, and empower field personnel to understand the situation, and significantly reduce the impact. Nowadays, with the emergence of converged technologies such as mobile, cloud, big data, robotics, AI (artificial intelligence)/ML (machine learning) and wearable devices, it has become possible to test several innovative methods for epidemic response. Here, we have listed several areas that digital technology plays a vital role in:

 

・Assisting medical healthcare

Besides COVID-19 tests, now there are AI tools to analyze the computed tomography (CT) images to lower the misjudgment and reduce the burden of doctors. AI and big data also play vital roles in allocate medical resources and guide decision-making, including hospital capacity, medical supply distribution, distinguishing of patients by their medical history etc. A team from Johns Hopkins School of Public Health leveraged big data analytics to develop a COVID-19 mortality risk calculator, which help allocate early vaccines, acting as a companion to guidelines from other organizations and ensuring that the right people are vaccinated first. Scripps Research described a wearable for early COVID detection by combines passively collected physiologic data, such as heart rate, sleep patterns, and skin temperatures from wearable devices. A team from New York Univ. developed an artificial intelligence algorithm that could accurately predict which patients newly diagnosed with COVID-19 would go on to develop severe respiratory disease. AI also contributes significantly to the treatment of COVID-19. Many drug manufacturers use AI to assist drug screening. For example, a startup company called EVQLV creates algorithms capable of computationally generating, screening, and optimizing hundreds of millions of therapeutic antibodies. Their machine learning algorithms are able to rapidly screen for therapeutic antibodies with a high probability of success.

 

・Digital epidemiological surveillance

Today, thanks to digital technologies, governments can use various real-time public health data to identify risk factors for the disease and guide effective interventions. For example, the UK and Singapore implemented an online symptom reporting system that is used for surveillance but also offers advice about isolation and referrals for further healthcare services. It’s essential that such services are connected to public health surveillance data and specific actions such as isolation of cases. After a case is identified and isolated, public health authorities need to quickly trace key contacts to prevent further transmission. Especially in areas characterized by high transmission, the implementation and monitoring of such interventions are required. This is where digital contact tracing solutions come into play. They automate contact tracing at the scale and speed that just isn’t replicable without digital tools. This reduces the authorities’ reliance on human recall, which is particularly problematic in densely populated areas with highly mobile populations. Digital contact tracing apps are now widespread around the world. However, these new approaches and technologies haven’t been previously tried at this scale and often prove controversial in terms of data privacy.

 

・Transforming ways of business and education

The COVID-19 has resulted in schools shut all across the world. Globally, over 1.2 billion children are out of the classroom. Many companies also require employees to work remotely to reduce commuting and social contact. As a result, ways of business and education has changed dramatically with the distinctive rise of e-learning and video conferencing, whereby teaching is undertaken remotely and on digital platforms. Research suggests that online learning has been shown to increase retention of information, and take less time, meaning the changes that this pandemic have caused might be here to stay. Moreover, the pandemic also accelerated the equality and timeliness of information acquisition in various countries. The Center for Systems Science and Engineering (CSSE) of Johns Hopkins University in the United States established a platform for real-time integration of global cases and became the information adopted by various countries; it was established by many Nobel Prize winners and top scientists in the world The "Global Shared Influenza Data Initiative" (GISAID) open platform also analyzes virus gene sequences uploaded by countries in real time, providing materials for cross-border research and analysis. The White House Office of Science and Technology Policy has opened up 138,000 academic papers on COVID-19. Through resource sharing and calling on scientists from all over the world to use AI analysis, it hopes to accelerate the analysis of COVID-19. Elsevier, the world’s largest academic publisher, also provides more than 31,000 journal articles for free.

 

・Various applications of robot

More and more places are using robots to replace reception staff to reduce social contact. Especially in hospitals, handling COVID-19 patients can be difficult and a safer alternative is to use robots. In India, robots were brought in Rwanda’s hospitals to reduce doctors’ contact time with patients by performing tasks including temperature screening and keeping medical records. The Poloclinico Abano chain of hospitals, in Italy, has been using UVD Robots to disinfect patients’ rooms. The robot is capable of moving autonomously in the hospital, using ultraviolet light to kill the virus. A more special example is SoftBank Robotics, Pepper, which is not only cute, but was designed specifically to interact with humans. Pepper can be used in a lot of different industries: retail, finance, hospitality, tourism or even healthcare. During the COVID-19 outbreak, 4 Peppers were lent to the university hospitals Pitié Salpêtrière in Paris to allow patients to stay in touch with their family. Pepper is mounted with a tablet which can display video calls. Be it during the call or before and after, Pepper can offer a positive and joyful experience to patients who are isolated. Moreover, drones have also been used to transport medical samples and supplies, and to deliver educational messages by air.

 

Here are only limited examples of how people can take advantage of digital technology. It’s clear that the COVID-19 pandemic would take on a very different form if not for the digital technologies available to us right now. Technological innovation affected practically every industry out there, and companies around the world are now rethinking their approaches, investing in new solutions, and preparing themselves for similar problems that might affect them in the future.

 References:

  1.  Karol Przystalski. 15 Dec 2020. “Technology Against COVID-19: IT Solutions for Fighting the Pandemic” CODETE News.

  2.  Manjunath B S. “Covid-19: 8 ways in which technology helps pandemic management” ETCIO news.

  3.  Respective company news release

 

Vol.8 Post-COVID Symptoms Will Have Profound Impact on Global Health

Last Updated 12 March 2021. Cellspect Co., Ltd.

The current COVID-19 pandemic is gradually converging due to global efforts. However, the regional director for WHO Europe mentioned at a press conference on February 25 that one in ten European patients with COVID-19 still have symptoms of discomfort 12 weeks after recovery, and many people’s symptoms will last longer. This will lead to serious social, economic and health problems. The WHO also stated that to understand the long-term consequences and recovery from COVID-19 is a clear priority for WHO.

Post-COVID symptoms, or known as “long COVID”, is the condition characterized by long-term sequelae—persisting after the typical convalescence period—of COVID-19. It is currently unknown why most people recover fully within two to three weeks and others experience symptoms for weeks or months longer. Anyone infected with SARS-CoV-2 can suffer from long COVID even after the infection is considered to have ended, including young, healthy people, and patients who showed only minor symptoms. An early analysis by the United Kingdom's National Institute for Health Research suggests that ongoing long COVID symptoms may be due to four syndromes:

1. Permanent damage to the lungs and heart

2. Post-intensive care syndrome (PICS)

3. Post-viral fatigue, also known as Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)

4. Continuing COVID-19 symptoms.

In other words, from the physical damage due to virus infection to the medical treatment may result in long COVID. The most commonly reported persistent symptoms include:

․Fatigue, headache, low fever

․Shortness of breath, cough, chest pain

․Arthralgia, muscle pain and weakness

․Depression, cognitive impairment

Moreover, there are some more serious complications appear to be less common but have been reported, including:

․Cardiovascular: myocardial inflammation, ventricular dysfunction

․Respiratory: pulmonary function abnormalities

․Renal: acute kidney injury

․Dermatologic: rash, alopecia

․Neurological: olfactory and gustatory dysfunction, sleep dysregulation, altered cognition, memory impairment

․Psychiatric: anxiety, changes in mood

 

The US National Institutes of Health have published interim guidelines for the medical management of COVID-19, including a section on persistent symptoms or illnesses after recovery from acute COVID-19. As long-term studies will be crucial in elucidating longer-term sequelae, these guidelines will be updated as new information emerges. WHO also calls on all nations for continuous investigation into the full spectrum of COVID-19 to establish a more complete understanding of the natural history of SARS-CoV-2 infection and COVID-19 related illnesses, which can inform care strategies as well as the public health response to this virus.

So far, there is no effective treatment for the long COVID in the world. The only way is to alleviate each symptom. Many countries have paid a heavy price for not paying attention to the COVID-19 pandemic. It now appears that even if the pandemic will pass someday, there are still many challenges awaiting. At present there have been "COVID-19 Survivor Support Group" that provide support for recovering people's health tracking, sequelae consultation, and medical assistance in the US. Currently, there is no such group in Japan and inevitably, more medical and public support for the recovered is needed in the future.

 References:

  1. World Health Organization: WHO https://www.who.int/

  2. CDC “Coronavirus Disease 2019 (COVID-19) Treatment Guidelines”: https://www.covid19treatmentguidelines.nih.gov/

  3. Taquet M et al. November 2020. "Bidirectional associations between COVID-19 and psychiatric disorder: retrospective cohort studies of 62 354 COVID-19 cases in the USA". The Lancet. Psychiatry.

 

Vol.9 Post-COVID Symptoms Will Have Profound Impact on Global Health

2021年3月19日 最終更新 セルスペクト(株)科学調査班編集

COVID-19 vaccination will help protect you from getting COVID-19. You may have some side effects, which are normal signs that your body is building protection. These side effects may affect your ability to do daily activities, but they should go away in a few days.

 

According to the results of the third phase of clinical trials, no matter AZ, Pfizer BNT, and Moderna vaccines will have some related side effects. Generally, as to the incidence of side effects:

    ・the young is higher than that of the elderly

    ・ for adenovirus vector vaccine (for example, AZ vaccine), the first dose is higher than the second dose

    ・for mRNA vaccine (for example, BNT vaccine), the second dose is higher than the first dose

 

Here are side effects incidence rate reported from the third clinical trial results of 3 major vaccine developers:

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With most COVID-19 vaccines, you will need 2 shots in order for them to work. Get the second shot even if you have side effects after the first shot, unless a vaccination provider or your doctor tells you not to get a second shot. It takes time for your body to build protection after any vaccination. COVID-19 vaccines that require 2 shots may not protect you until a week or two after your second shot. In most cases, discomfort from fever or pain is normal. Contact your doctor or healthcare provider if the following happens:

 

    ・redness or tenderness where you got the shot increases after 24 hours

    ・side effects are worrying you or do not seem to be going away after a few days

 

As for the allergic reaction after vaccination that everyone is concerned about, the following is a summary based on “Vaccines and Related Biological Products Advisory Committee Meeting”, the newly announced data published by the US CDC meeting on February 26

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The US has not yet administered the AZ vaccine, and the UK has not yet administered the MODERNA vaccine.

A total of 1,099 deaths cases were investigated, and the results of the investigation have nothing to do with the vaccination. In order to deal with the extremely low incidence of severe allergic reactions after vaccination, it is currently recommended to rest and observe for 30 minutes in the same place after vaccination.

 References:

  1. World Health Organization: WHO https://www.who.int/

  2. CDC “Coronavirus Disease 2019 (COVID-19) Treatment Guidelines”: https://www.covid19treatmentguidelines.nih.gov/

  3. UK Medicines and Healthcare Products Regulatory Agency: https://www.gov.uk/government/organisations/medicines-and-healthcare-products-regulatory-agency

 

Vol.10 J&J COVID-19 vaccine added: what does efficacy actually mean for vaccines?

Last Updated 26 March 2021. Cellspect Co., Ltd.

On 11 March, Johnson & Johnson (J&J) COVID-19 Vaccine, also known as Ad26.COV2.S or JNJ-78436735, granted conditional marketing authorization by European Commission and earlier on 24 Feb, the US FDA had also endorsed J&J vaccine for emergency use, making it become the third to enter US vaccine market following the mRNA vaccines from Pfizer/BioNTech and Moderna.

 

The J&J vaccine added the gene for the coronavirus spike protein to a modified adenovirus to induce an immune response. But unlike the Pfizer and Moderna vaccines, which use single-stranded RNA, the J&J vaccine uses double-stranded DNA. In the Phase 3 trial that enrolled almost 44,000 people across the US, Latin America, and South Africa, the efficacy of J&J’s vaccine was 100% at preventing hospitalizations and deaths, 66% in preventing moderate to severe COVID-19, and 85% at preventing severe disease.

 

Importantly, J&J’s vaccine was protective against the B.1.351 variant first observed in South Africa. Additionally, J&J’s vaccine offers significant logistical advantages since it is stable at -20°C for 2 years and at 2°C to 8°C for at least 3 months, and it requires just a single shot.

 

Many people are asking what "efficacy" actually mean for vaccines? Efficacy is a crucial concept in vaccine trials, but it’s also a tricky one. If a vaccine has an efficacy of, say, 95 percent, that doesn’t mean that 5 percent of people who receive that vaccine will get Covid-19. Statisticially, efficacy is a measurement of how much a vaccine "lowers the risk of getting Covid-19". For example, J&J observed how many people who received a vaccine nevertheless got Covid-19. Then they compared that to how many people contracted Covid-19 after receiving a placebo. The difference in infection risk can be calculated as a percentage where zero percent means that vaccinated people are at as much risk as people who got the placebo and a hundred percent means that the risk was entirely eliminated by the vaccine.

 

Take the J&J vaccine in the United States as an example, the efficacy is 72% because approximately 63 of 5000 people in the control group became ill, compared with 18 in the vaccinated group. Therefore, the reduced risk is calculated as (63-18) /63=71.4%.

 

In the case of Pfizer vaccine, the efficacy is 95%, which means that in the similar condition, only 3 people in the vaccine group will get the disease. The reduced risk is calculated as (63-3) divided by 63=95%.

 

Efficacy also depends on the details of the trial, such as where it took place. J&J ran trials at three sites: in the United States, Latin America and South Africa. In the United States trial site, J&J determined that the efficacy is 72 percent while In South Africa, the efficacy was 64 percent. One reason for the overall efficacy was lower than that in the United States alone is that the South Africa trial took place after a new variant had swept across that country. Called B.1.351, the variant has mutations that enable it to evade some of the antibodies produced by vaccination. The variant didn’t make the vaccine useless, however.

 

For a number of reasons, it’s very difficult to make a precise comparison between these vaccines. One vaccine may have a higher efficacy than another, but their statistical confidence intervals may overlap. That effectively makes their results indistinguishable. Making matters more complicated, the vaccines were tested on different groups of people at different stages in the pandemic. In addition, their efficacy was measured in different ways. J&J’s efficacy was measured 28 days after a single dose, for example, while Moderna’s was measured 14 days after a second dose.

 

A clinical trial is just the start of the research on any vaccine. Once it goes into widespread use, researchers follow its performance. Instead of efficacy, these scientists now measure effectiveness: how much the vaccine reduces the risk of a disease out in the real world, in millions of people rather than thousands. In the months to come, researchers will keep an eye on this data to see if they become less effective — either because the immunity from the vaccine wanes or because a new variant arises. In either case, new vaccines will be created, and manufacturers will provide new measures of their efficacy.

 References:

  1. U.S. Food and Drug Administration: FDA https://www.fda.gov/ 

  2. Johnson & Johnson: https://www.jnj.com/ 

  3. Carl Zimmer and Keith Collins. 3 Mar 2021, “What Do Vaccine Efficacy Numbers Actually Mean?” The New York Times.

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