COVID-19: Coronavirus Disease – Research Efforts, Vaccination and Treatment

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Thanks to the advanced genomic technology available today and which was largely lacking during the time of the 2003 SARS-CoV-1 outbreak, scientists have been able to fully sequence the genome of the corona virus covid-19 in a much shorter time.

According to Kristian Andersen of the La Jolla Scripps Research Translational Institute, “Genomics has completely transformed our ability to track viruses and understand their spread. We’re gaining insights not previously possible.”

At least 115 samples of the virus have been assessed by Chinese Scientists. The results of these have been shared with international community of geneticists. The results continue to point fingers at bats as the prime suspect wildlife host which was responsible for spreading the disease to humans and this is surmised to have indeed happened sometime in December 2019.

COVID-19: Coronavirus Disease - Research Efforts, Vaccination and Treatment
COVID-19: Coronavirus Disease – Research Efforts, Vaccination and Treatment

Comparison of strains of covid-19 with related coronaviruses, (including the  human SARS-CoV, the bat SARS-like CoV, and the human MERS-CoV), shows that they are almost identical with only five nucleotide differences in the genome of ~29.8 kb nucleotides. In terms of genome sequence, the 2019-nCoV is more similar to SARS-like bat CoV than the human SARS-CoVs and the MERS-CoV.

As at January 20 2020, there have been 14 genome sequences for covid-19 that have been released by six different laboratories,  and which  have been made available to researchers through either the National Center for Biotechnology Information’s GenBank, or through the Global Initiative on Sharing All Influenza Data (GISAID).

In another research study at China’s Wuhan Institute of virology, 10 genome sequences of the 2019-nCoV were analyzed and over 80% similarity with SARS-CoV that was responsible for the SARS epidemic of 2003 was found. While a lot of similarities exist between the two in terms of genetic sequence, the 2019-nCoV is far more contagious but fortunately, less fatal going by the case mortality rates.

The SARS of 2003 was regarded as one of the deadliest global pandemics, having successfully infected 8,098 just within eight months of its emergence and resulting in the death of 774 persons, with international spread to 29 countries and a fatality rate of 9.6%. The novel coronavirus on the other hand, successfully spread to more than 20000 persons in just over one month, with a fatality rate of 1-2%, which is considerably lower.

The significantly higher spread of the novel coronavirus might be contributed to by the relatively longer incubation period which is currently estimated to be 14 days but some new research study from the National Health Commission, China hints that it could be up to 24 days. This study is yet to be peer reviewed however.

In comparison, SARS had an incubation period of only 7 days, which meant that infected persons came down with symptoms quicker, allowing appropriate control and quarantine measures to be taken earlier.

1. Classification of COVID-19: Coronavirus Disease

The new coronavirus has been assigned an official taxonomical name by the International Committee on Taxonomy of Viruses as SARS-CoV-2. Before this time, there were concerns expressed and ongoing debates on naming the new virus. The WHO to avoid stigmatization, discourages the naming of species on the basis of geographical location.        Use of animal species in naming such as with the H1N1 in 2009 popularly referred to as the “swine flu” is also not encouraged. This designation had a serious impact on the pork industry, never mind that the disease was being spread by human-human transmission rather than pigs. In the same vein, the use of people’s names such as that of the scientists who discovered or identified the disease are equally also not allowed.

The International Committee on Taxonomy of Viruses (ICTV) has designated a new name to 2019-nCoV as “severe acute respiratory syndrome coronavirus 2” (SARS-CoV-2) which was announced on 11 February 21, 2020. Also, the WHO has re-named the disease as coronavirus disease 2019 (COVID-19). There were also concerns about the initial provisional naming of the disease as 2019-nCoV by the WHO, the concerns being largely that the absence of an official name might lead to the use of prejudicial informal names like “the new coronavirus,“ , “Wuhan coronavirus”, or simply, “coronavirus”.

The classification of viruses is done based on the collection and comparison of various characters which describe the virus, which can then be used to distinguish one virus from another. These characters can consist of any properties or feature of the virus.

In the case of coronaviruses, the peculiar crown-like appearance of their glycoprotein envelope, as well as their specific chemistry features and mode of replication are used in their classification

2. Vaccination against COVID-19 (Coronavirus Disease)

As the viral infection continues to rage, there is a seeming scramble by a lot of research Institutes and pharmaceutical companies to develop a specific therapeutic drug, as well as a vaccine for the disease. At least a dozen pharmaceutical companies are involved in this race to find a therapeutic cure and/or a preventive vaccine drug for the disease. Amongst these are:

Johnson & Johnson, GlaxoSmithKline, Gilead, Inovio  Moderna, Novavax, and others.

While some of them are trying out novel models, some others are looking towards advancing on already established strides recorded in combating other coronaviruses in the past which for various reasons, were not successful.

Vaccination against Covid-19 : Coronavirus Disease
Vaccination against Covid-19 : Coronavirus Disease

Most of these vaccines would be focused on the “spike” proteins found on the surface of the virus which it quickly makes early in an infection. The pharmaceutical companies and agencies are working avidly across the globe to achieve this. The United States Department of Health & Human Services (HHS)  announced its intention to collaborate with Sanofi Pasteur, a subsidiary of Sanofi, to work on developing a Covid-19 vaccine. Regarding this proposed vaccine, Sanofi says it will use its egg-free, recombinant DNA platform to come up with a recombinant vaccine. Rather than the conventional method of growing a virus and then proceeding to make it inactive to obtain a vaccine, Sanofi’s new vaccine technology makes use of DNA obtained from the virus to produce its surface proteins, which could then be used in stimulating the immune system to form antibodies against the virus.

This represents a much faster method of vaccine development, as well as an easier way of producing the vaccines in very large quantities.

Other pharmaceutical companies are also involved in the race like the India- based Zydus Cadila which has launched a fast-tracked research program that involves an approach in which a DNA vaccine is developed against the viral membrane protein that the virus needs to gain entry into the cell. In the host cells, the delivered plasmid DNA would then be translated into the viral protein which would trigger an immune response through the cellular and humoral components of the immune system that are involved in protection from disease as well as clearance of the virus. Another approach being used by them is the development of a live-attenuated recombinant measles virus (rMV), a vectored vaccine that would fight the novel coronavirus.

GeoVax is a US-based pharmaceutical company, and BravoVax, is a China-based pharmaceutical company. They have together, announced their plans to develop a cure for the new coronavirus disease using a form of vaccine that is based on Geovax’s MVA-VLP vaccine platform.

BravoVax would be responsible for the vaccine testing and manufacturing as well as coordination with the Chinese public health and regulatory authorities.

NanoViricides, which is a clinical-stage company, is currently working on a treatment for covid 19, via its patented nanoviricide® technology which is used to develop ligands that are able to bind to the virus and attack it at various ppoint.

Vir Biotechnology, another clinical-stage immunology company, announced on 12th of February 2020, its success in identifying two monoclonal antibodies which are able to bind to the new coronavirus. These antibodies would target the viral spike (S) protein by gaining entry through the cellular receptor angiotensin converting enzyme 2 (ACE2).

Vaxart is another company working on developing an oral recombinant vaccine which would be in the form of a tablet. This it hopes to achieve making use of its proprietary oral vaccine platform – VAAST.

Several other companies are currently working and collaborating with various other agencies including the Janssen Research & Development and HHS, iBio, CC-Pharming, etc.

3. Drugs undergoing Clinical Trials for COVID-19 (Coronavirus Disease)

As scientists scramble to find a cure for the disease, several drugs in different classes are being tested, not excluding traditional Chinese medicine which have been used to successfully treat some patients.

Several drugs already existing have entered clinical trials to test their efficacy in treating the disease. Among these are:

Drugs undergoing Clinical Trials for COVID-19
Drugs undergoing Clinical Trials for COVID-19

Chloroquine phosphate –

An existing drug used primarily in the treatment and prevention of malaria, and also sometimes in the treatment of Rheumatoid arthritis, Chloroquine phosphate may just be the “wonder drug” we’ve been waiting for. Having demonstrated fairly good efficacy and with no recorded serious adverse effects in the patients participating in the multicenter trials in China, the head of China National Center for Biotechnology Development, Zhang Xinmin says that it is listed as one of the promising drugs for treatment.

Remdesivir –

Another experimental drug belonging to the Gilead biotechnology company, United States which is undergoing trials. Remdesivir is an antiviral drug, a nucleotide analogue which has reportedly shown some efficacy in the treatment of the disease, and also some success in animal coronavirus disease.

However due to a lack of eligible patients, the drug trials which are taking place in over ten Wuhan medical institutions is not progressing as fast as expected.

Favilavir –

One of the experimental drugs showing promise, Favilavir is a drug belonging to the Zhejiang Hisun Pharmaceutical company and originally approved for marketing for influenza treatment. Contrary to initial misleading news of its approval for COVID-19 treatment, it has rather, received approval from China’s National Medical Products Administration to be used as a test drug in covid-19 patients, having shown efficacy with little side effects in a 70-patient trial conducted in Shenzhen, Guangdong province.

Anti-HIV drugs –

Lopinavir and Ritonavir: Clinical trials have already commenced with a drug combination of Lopinavir and Ritonavir (marketed as Kaletra by the Illinois-based pharma, AbbVie), in the fight against Covid-19. The Chinese scientists who are working on the project are targeting the virus vital enzyme – protease which it needs to split up protein into smaller protein molecules during its replication. A combination treatment with the anti-HIV combo and an influenza drug oseltamivir in large doses has been shown to vastly improve the health conditions of patients who had severe cases of Covid-19.

Studies are equally ongoing with the use of Traditional Chinese medicine. According to China’s well known Respiratory Specialist Dr Zhong Nanshan, a herbal drug referred to as “Pneumonia No. 1” had been able to treat Covid-19 patients in the Guangdong Province of South China.

According to Professor Yang Zifeng of the Guangzhou Institute of Respiratory Health, in vitro experiments conducted on the 54 existing traditional Chinese medicines available have shown 5 of them to be effective in inhibiting the infection.

As at 15th of February 2020, the Chinese Clinical trials registry has about 15 trials listed to be conducted using traditional Chinese medicine, a notable one amongst them being shuanghuanglian, a traditional herbal drug which is primarily composed of the dried fruit lianqiao extract (Forsythiae fructus), that has reportedly been effective in treating several infections over several hundreds of years.

Scientists are also looking into stem cells as a possible cure. China’s registry has two stem cell trials listed in it as at 15th of February 2020, with one of them proposing to infuse the patients with stem cells gotten from menstrual blood. The WHO’s database of clinical trial shows 10 total studies of stem cells research for COVID-19.

Plasma therapy –

The use of convalescent plasma derived from patients who have recovered from a disease has been done in the past. Convalescent human sera (plasma without clotting factors) was employed in the fight against measles and Yellow fever in the 1930s, and during the great 1918 influenza pandemic. This was also employed for some patients during the last Ebola outbreak. It is an effective means of boosting immunity as it provides the recipient with concentrated, antibody – rich plasma, a form of passive vaccination.

In like manner, Shanghai Doctors employing the use of plasma infusions derived from convalescent COVID-19 patients. This approach has gotten a big nod from the WHO, referring to it as “Very valid”.

The trick however, lies in the timing which is crucial to ensure that the infusion is given at a point in the infection when the patient would get the maximum benefit from the treatment. This also does not work in all cases.

Presently however, there is no drug yet approved as a cure for coronavirus and it’d take about a year before a vaccine is developed and approved for the disease.

The WHO is making efforts to bring some order to this scramble for a cure as several stakeholders dabble into the fray. They are coming up with a plan that would involve a more flexible clinical trial protocol that would be suitable for the research scientists, while maintaining necessary standards for the patients’ benefits.

There are presently over 80 clinical drug trials either ongoing or pending in China, including both new pharmaceutical drugs, as well as very old drugs.

With this high number of trials (which is likely to further increase) taking place or intending to take place simultaneously, and with the little time available, the WHO has its work cut out in providing recommendations and guidance on which ones to proceed with and which ones to be laid off.

Ultimately, the hope is that the scramble for a cure for COVID-19 would not be like that of the 2003 SARS epidemic which saw many scientific research efforts abandoned after the outbreak.

4. How can you reduce your Risk of Infection for COVID-19 ?

As there is no specific treatment available yet for COVID-19, with the management being mostly aimed at alleviating the symptoms, surely there must be a way one can protect themselves from the disease, or at least greatly reduce their chances of contracting it. Let’s see.

Herbal Remedies for COVID-19 : Do they work ? How effective are they?

Throughout history, herbal, dietary, complementary, and natural therapies have been used widely in the prevention and treatment of viral infections. The mechanism of action is not fully understood but it is believed that these herbal remedies may strengthen the immune system against infections. As China and indeed other affected countries battle to contain the disease, in the absence of any specific treatments for COVID-19, many have turned to less conventional remedies which offer any sort of hope.

Traditional Chinese medicine (TCM) has been widely used in the management of several conditions in china. The latest to join the fray is in the treatment of COVID-19 pneumonia. The treatment involves a combination of Traditional Chinese Medicine (TCM) and western drugs at Wuhan hospitals. Two coronavirus patients in Wuhan were reported to have been discharged after receiving holistic medicine. TCM has proven to be effective in stopping patients from developing symptoms when they are in the early stages of illness. For mild and moderate cases, traditional Chinese medicine has been found to have significant effects.  It was noted that COVID 19 patients who received traditional Chinese medicine along with western medicine, recorded significant improvements.

Seeing the noted favourable effects of TCM, their government called for an enhanced cooperation between western medicine and TCM. The government called for local authorities to promote the use of TCM, as herbal remedy offers hope as a COVID-19 treatment.

Some Chinese scientists laid a claim that a liquid made with honeysuckle and flowering plants could help fight the coronavirus infection. However, it is advised not to use traditional medicine without professional consultation.

The turn to alternative traditional remedies is not restricted to China. On the 29th of January 2020, the Indian government’s Ministry of AYUSH, that promotes the use of alternative medicine in the country, issued a health advisory, advocating for the use of homeopathy and traditional remedies (Arsenicum album 30C and sesame oil, Unani medicines), in the management of COVID 19.

The use of herbal medicine has also cast doubts in some minds. Even though AYUSH was relying on a background of experience in alternative medicine practice as it claimed, the media as well as the scientific community felt that this approach was counterproductive to the overall efforts being made towards finding a cure for the disease, with some persons outrightly condemning it due to a lack of supporting evidence of its efficacy.

Supplements to Boost Immunity

With the quite understandable scare caused by the deadly corona virus in China, many of the residents have turned towards supplements that make claims to boost immunity, with many sellers of such supplements claiming to have run out of supply as a result of high demand. But do they really have the effects that are claimed?

According to Michael Starnbach, a professor of microbiology at Harvard Medical School, products that claim to boost immunity don’t offer much benefit. It is not sure whether they help in fighting the disease or not. An average healthy individual produces much more white blood cells than it makes use of, with the extra cells eliminating themselves through the process of self-induced cell death (apoptosis). With the complex interplay of the immune response and function, it’s not easy to decipher for certain exactly what cells are to be boosted, or to what extent. If indeed there is a boost to the immune system, it could trigger some form of autoimmunity among other problems.

These supplements are usually vitamins or probiotics. It is known that vitamins can help boost immunity, but they’re mostly more beneficial if you are unhealthy. Vitamin formulations may not do much to help you stay healthy if you are healthy already. For the elderly (>65 years), they may benefit more from these supplements as micronutrient deficiency is quite common in them, probably due to their tendency to eat less and also have a reduced dietary variety.

Probiotics may also have a role in boosting immunity as bacteria and organisms living in the gut may play a role in health. Not only do they have an overall health boosting effect, they have also been shown to be quite effective in the prevention and management of acute respiratory tract infections as several studies have shown. A recent study by a Canadian group of researchers suggest that their use in prevention respiratory tract infections, as well as reducing the duration of illness may help save millions of dollars.

Vitamin D, zinc, elderberry, probiotics, oil of oregano, chlorella, mushroom extracts, garlic, astragalus, ginseng, multivitamin, vitamin C, south African geranium are some of the immune boosters used. Maitake mushrooms, burdock, shitake & maitake Mushrooms, umeboshi plums, Ume-Sho-kuzu, Shio-Kombu, tekka are some herbal immune boosters.

Caution must be applied with the intake of vitamin E supplements. There is little clinical research showing that vitamin E supplements benefit health and they may in fact be harmful in some situations. In a large clinical trial, it was found that the people who consumed 400 our of Vitamin E had a higher risk of heart problems as compared to their counterparts who didn’t. Immune supplements may have side effects, especially if taken alongside other medicines. Supplements may also not be suitable for individuals with certain health conditions. Also, the effects of many of these supplements especially regarding safety hasn’t been ascertained in pregnant women, children, and other groups.

As it stands, one’s best bet towards protection from the disease is following the recommended guidelines by relevant health bodies and in addition, making healthy lifestyle choices.

Strengthening Your Immunity

As the popular saying goes, “Prevention is better than cure”.

It is generally more cost effective to prevent an illness than to treat same. It also saves the individual the physical and mental stress of illness. One of the major ways to protect oneself in infectious disease epidemics such as the covid-19 asides following the recommended guidelines for prevention and control as have been discussed above is boosting your own immunity. People who have strong immune systems are far less likely to come down with infections even with exposure to the causative agent. The body on its own already has mechanisms put in place to fight any foreign agents, ranging from physical barriers, to humoral, and to cellular immune mechanisms.

How then can one improve their immunity? For viral infections like the COVID19, cell-mediated immunity involving the recognition and/or elimination of a virus and the cells infected with it is important in the protection against them. Viral infections also stimulate antibody production by the B lymphocyte cells which is the humoral component of the immune response.  A stronger immunity will prevent a viral infection in the first place, and equally mean a less severe and shorter course of infection. Certain factors play a role in boosting the immunity levels:

Getting adequate sleep helps to strengthen the immune system. It enhances the binding of antigen-presenting cells with CD4+ cells, stimulates the production of interleukins, increases the effectiveness of CD8+ cells, and increases the production of antibodies. Sleep-deprived persons are at a higher risk of viral infections due to a weaker immune system.

The growth hormone also has a role to play in immunity. It is released during the first phase of sleep and induces the production of Interleukin-12.

Lifestyle greatly affects the immune system of a person in relation to exercise, diet, age, stress, etc. This is more or less the first line of defense, as it enhances not just your immune system, but all parts of your body.

Good nutrition is necessary to maintain an optimal immune system. It is a critical determinant of the immune response. Cell-mediated immunity which is vital in fighting viral infections is impaired in protein-energy malnutrition states. It is also associated with an impairment in the function of phagocytes, the complement system, and the formation of antibodies. Deficiency in single micro nutrients can also influence the immune system negatively. It is therefore important to consume a diet rich in fresh, whole foods with abundant organic vegetables, and fruits. As much as possible, avoid refined sugar, fried foods, and processed foods.

Reduce stress. There has been increasing evidence to support a link between stress and development of some health conditions, including infectious diseases. This is especially true when the stress is chronic, resulting in more enduring changes in the body. The chronic stressed state is associated with a suppression of immunity due to the high level of circulating stress hormones, and this is even more so for the elderly. One of the infections which a person who is stressed is likely to get is the common cold, according to a classic study conducted in 1991 at the Carnegie Mellon University, United States.

Regular exercising especially outdoors is good for the immune system. According to the US National Library of Medicine, exercise may help to decrease the chances of coming down with a cold or a flu, and even other illnesses.

Don’t smoke. Smoking has a negative impact on almost all parts of the body. It makes the immune system weak, in particular the function of the T- helper cells involved in cell-mediated immunity, and increases the susceptibility to infections like the influenza and pneumonia.

Immune boosters can also be used when necessary such as in established immune deficiencies.

Caution should be applied in the use of antibiotics as they can weaken the immune system and microbial resistance may develop due to abuse. Staying hydrated can also help to strengthen immune system function.

Generally, improving your immunity goes a long way in offering you protection from the virus. Even if you do get infected, it’s still your best bet towards recovery as call available evidence and epidemiological statistics show that those who are much more susceptible to the virus and are also more likely to have a more severe infection are the elderly age group and people with reduced immunity. These same groups of persons have also recorded the highest case mortality.

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