Headline Diplomat eJournal – Issue 1
The perilous lenses of COVID-19: The impact on the economy
Writes Dr. V.E.Kalodimou, Director of Flow Cytometry-Research & Regenerative Medicine Department at IASO Maternity Hospital, LinkedIn
In a meeting on January 30, 2020, the outbreak was declared by the WHO a Public Health Emergency of International Concern (PHEIC). By that time, it had spread to 18 countries with four countries reporting human to human transmission. It has been postulated that one of the underlying pathophysiologic mechanisms of disease worsening and progression of patients with COVID-19 is massive release of inflammatory mediators, including cytokines.
On February 11, 2020, the WHO Director-General, Dr Tedros Adhanom Ghebreyesus, announced that the disease caused by the new coronavirus (CoV) was COVID-19, which is the acronym of coronavirus disease 2019. This new virus seems to be very contagious and has quickly spread globally.
COVID-19 is caused by the newly discovered coronavirus SARS CoV-2, previously called 2019-nCoV. It belongs to the Coronaviridae family and is broadly distributed in humans and other mammals.
Why is spreading faster than its two ancestors? Why is lethal? Recent publications have shown that there are differences in their genome structure and immunological response to SARS-CoV-2 infection. The key markers involved in these interactions include Spike protein (S), Nucleocapsid (N), ACE-2 receptor, FURIN protease in addition to the cytokines.
The SARS epidemic appears to have started in Guangdong, China in November 2002 where the first case was reported that same month. The patient, a farmer from Shunde, Foshan, Guangdong, was treated in the First People’s Hospital of Foshan. The patient died soon after, and no definite diagnosis was made on his cause of death. Despite taking some action to control it, Chinese government officials did not inform the World Health Organization of the outbreak until February 2003. This lack of openness caused delays in efforts to control the epidemic, resulting in criticism of the People’s Republic of China from the international community. China officially apologised for early slowness in dealing with the SARS epidemic.
The World Health Organization declared severe acute respiratory syndrome contained on July 9, 2003. In the year after SARS made the occasional appearance. There were four cases spotted in China in December 2003 and January 2004. In addition, three separate laboratory accidents resulted in infections; in one case, an ill lab worker spread the virus to several other people. Measures taken in 2003 to contain the outbreak isolating SARS patients and quarantining people who had been exposed to a SARS case to prevent them from exposing others succeeded. Did we learn our lessons?
Till today 15,100,000 people have been affected around the world. Of these 620,000 people globally have died and 8,590,000 recovered. Daily new case numbers vary widely by country and are dependent on the time that the novel coronavirus first appeared and how each country responded to outbreaks.
Johns Hopkins University shows the countries that have reported coronavirus cases. Despite those dreadful statistics a handful of countries have not yet reported any cases of COVID-19:
Why is data on testing important?
- Because no country knows the total number of people infected with COVID-19. All we know is the infection status of those who have been tested.
- All those who have a lab confirmed infection are counted as confirmed cases, as a result, the counts of confirmed cases depend on how much tests a country actually does.
- Testing is our window onto the pandemic and how it is spreading.
- Without testing there is no data. Without data we have no way of understanding the pandemic, we cannot know which countries are doing well, and which are just underreporting cases and deaths. To interpret any data on confirmed cases we need to know how much testing for COVID-19 the country actually does.
- Testing for COVID-19 informs our understanding of the pandemic and the risks it poses in different populations. This knowledge is important if we are to properly assess the interventions that should be implemented, including very costly ones such as social distancing and shutdown of entire regions and industries.
What is R0 represents?
- R0 represents the average number of people infected by one infectious individual.
- If R0 is larger than 1 the number of infected people will likely increase exponentially and an epidemic could ensue.
- If R0 is less than 1 the outbreak is likely to fade out on its own.
- R0 alone cannot definitively forecast an outbreak, but is an early warning system for the possibility of an epidemic or pandemic.
- The COVID-19 pandemic has revealed the limitations of R0 as no other disease outbreak has before.
Epidemiologists typically distinguish between two forms of the reproductive number R:
- the basic reproductive number R0, which describes the initial spread of an infection in a completely susceptible population,
- and the effective reproductive number, Re, which captures transmission once a virus becomes more common and as public health measures are initiated. Re is typically much lower than R0.
Bio mathematician Robert Smith of the University of Ottawa clarifies: “ can we get the Re below one? If the Re is even slightly above one, e.g. 1.1, then the outbreak could become too much for healthcare systems to handle”.
Getting good estimates for R0 is the key but R0 is notoriously tricky to nail down because it depends not only on the biological characteristics of a virus but also on understanding how often people come into contact with one another and that can differ drastically between countries, cities, or neighborhoods. As a result, we have to make assumptions about the factors that determine human movement, which can limit the precision of their models and the accuracy of the predictions they generate, therefore if we get it wrong, then the health action plan will be misplaced.
The Genetics Behind COVID-19
Researchers around the globe hoping to find clues that might explain why many people brush off COVID-19 without even knowing they have it, while others are hospitalized or even die from the disease. Getting a complete picture of which genes affect human susceptibility to the new coronavirus will take a long time and the analysis of thousands of people’s genomes. [Harvard Medical School: coronavirus genetics may explain differences COVID-19 illnesses]
As COVID-19 infects people and replicates, the individual viruses evolve acquiring genetic mutations. Different sets of mutations begin to distinguish different lineages of the virus which can be linked to different parts of the world. Tracking these mutations allows researchers to study how the virus is moving around. [Johns Hopkins University: covid19 global spread data explained].
The virus replicates by cloning its RNA creating identical copies of itself, except for any new mutations. Researchers have identified the ACE2 receptor and molecular scissors known as TMPRSS2. Three HMS researchers contributed to an international study in Nature Medicine in April detailing the activity of genes that make these proteins in cells lining the airways, blood vessels, heart, cornea, and intestine. By uncovering each of the proteins scientists provide new opportunities to find drugs that act on the proteins and make it harder for the virus to gain ground. [Personal Genome Project (PGP)]
It is unclear which genes will be important to the seriousness of a COVID-19 infection and how much of a role each will play. Researchers are trying to change that.
The Role of the World Health Organization (WHO)
The WHO timeline responses, one more lesson to learn:
|Timeline of WHO Responses to COVID-19 Pandemic|
|31 Dec 2019:
|1 January 2020:
| 2 January 2020:
|3–5 January 2020:
|9-14 January 2020:
|16-31 January 2020:
|2-15 February 2020:
|16-29 February 2020:
|3-13 March 2020:
|16-31 March 2020:
|2-30 April 2020:
|4-29 May 2020:
|2-26 June 2020:
To prevent transmission WHO recommends, (effective July 14th,2020), a comprehensive set of measures including:
- Identify suspicious cases as soon as possible, perform diagnostic tests and isolate all suspicious cases.
- Trace, identify and quarantine all close contacts of confirmed cases and check for symptoms and special care if necessary.
- Use of a cloth mask in public places, where there is transmission to the community and where other preventive measures are not possible, such as physical distance.
- Use of special contact precautions and droplets by health care workers caring for suspected and laboratory confirmed COVID-19 cases and in addition the use of special precautions when performing aerosol production procedures.
- Continuous use of medical mask by healthcare workers and patient caregivers during all daily activities, throughout the shift.
- Always practice frequent hand hygiene and physical distance from others when possible.
- Avoid crowded spaces, spaces of narrow configuration, as well as closed spaces with insufficient ventilation.
- Ensuring good environmental ventilation in all enclosed spaces and ensuring proper environmental cleaning and disinfection.
The Economy-Research Impact
Managing an epidemic requires facing the health consequences of the outbreak, as well as its social, political, security, and economic dimensions. This implies setting priorities between various interests and goals, a lot of politics.
When examining how some countries have responded to the pandemic, bio-political factors should be taken into account:
- this includes how governments are collecting and sharing data about the coronavirus,
- the selectiveness with which governments release information about the number of confirmed cases and the deaths caused by the virus suggesting that techniques such as the “bio-power” may be applying.
The UN’s Framework for the Immediate Socio-Economic Response to the COVID-19 Crisis warns: “the COVID-19 pandemic is far more than a health crisis, it is affecting societies and economies at their core”.
Assessing the impacts of the COVID-19 crisis on societies, economies and vulnerable groups is fundamental to inform and tailor the responses of governments and partners to recover from the crisis and ensure that no one is left behind in this effort. Without urgent socio-economic responses, global suffering will escalate, jeopardising lives, and livelihoods for years to come.
Immediate development responses in this crisis must be undertaken with an eye to the future:
|A Timeline of EU action|
|Research||Economy||Employment & Society||Travel & Transport||
EU global response
|EU health programme||A worldwide pledging effort to fund development of diagnostics and vaccines||Easing rules to encourage banks to lend to companies and households||Helping the agri-food sector||Lifting travel restrictions gradually||Support for Central African Republic|
|New requirements for medical devices postponed||An EU vaccines strategy||ECB pandemic emergency purchase programme (€1.35 trillion)||Protecting cross-border and seasonal workers||Re-open EU website: helping free movement and tourism resume||€60 million package to help countries in the Horn of Africa|
|Providing emergency support for health sectors||€100 million for vaccine development||€750 billion to stimulate economic and social recovery||Risk group classification of SARS-CoV-2||Recommendations for safe travel||Additional €55 million for Syrian refugees and local communities in Jordan and Lebanon|
|Making it easier to import medical equipment||€314 million for innovative companies||Maximum flexibility to channel EU structural funds||EU guidance for a safe return to the workplace||Putting an end to empty flights||Additional €50 million in humanitarian aid|
|Creating a common EU reserve of medical equipment||Additional €122 million for research and innovation||EIB support for the economy (€65 billion)||Keeping people in jobs and businesses alive (€100 billion)||Ensuring the continuous flow of goods and services||€3 billion in loans for neighbouring and partner countries|
|Ramping up production capacity||€117 million to research projects to tackle the Covid-19 virus||European roadmap to phase out containment measures||Taking care of the most deprived||Restricting travel to halt the spread||EU sets up a humanitarian air bridge|
|Setting up a European expert team||A data sharing platform for researchers||Immediate help for at least 100,000 small and medium-sized enterprises||Ensuring privacy and data protection for Covid-19 tracing apps||Repatriating EU citizens||€3.3 billion EU support for the Western Balkans|
|Securing the availability of personal protective equipment||€80 million to vaccine developer CureVac||EU structural funds for essential investments and resources (€37 billion)||Financial assistance through the Solidarity Fund (€800 million)||More than €36 billion to support partner countries|
|Buying medical equipment together||€48.25 million for 18 research projects involving 151 research teams||More fiscal flexibility||Avoiding network congestion||Up to €28 million to support research in sub-Saharan Africa|
|Revised state aid rules||€700 million in financial assistance to help Greece manage migration|
The crisis provides a window of opportunity to deeply change the economy and tough decisions will have to be made. We have to consider key questions that may have a profound impact on inequalities such as:
- which companies should be saved or led to bankruptcy?
- What level of protection should be granted to various groups in the population?
Finally, diplomatic interests are also the key in the response to COVID-19 and need to be taken into consideration. The WHO has been trying to foster a global response based on “solidarity, solidarity, solidarity” as reiterated over and over again by its Director-General Dr. Tedros. Viruses do not stop at borders, and only global cooperation will help to fight the pandemic, the attempt to build a global response based on solidarity has largely failed. [United Nations Report (Brief #2): socio-economic impact of COVID-19, University of Oslo: the politics behind the COVID-19 responses].
At the same time, many health professionals have a different approach, they argue for stricter social countermeasures to keep people at home, their absolute priority is saving lives free from political interference.
However, these measures may also have negative impacts on people’s health, it may lead to an increase in domestic violence, trigger mental health issues, even affect the capacity to provide care for other medical conditions. Could put people in precarious economic situations, increase inequalities, and have many other consequences that cannot be fully anticipated in scientific models. These statements focusing on limiting the spread of the virus while policy makers have to take into account the side-effects of public health measures and other interests at stake says Antoine de Bengy Puyvallée, Doctoral Research Fellow at the Centre for Development and Environment, University of Oslo.
The Next day
Where we are with vaccines and treatments for COVID-19?:
- scientists around the world are working on potential treatments and vaccines.
- several companies working on antiviral drugs, some of which are already in use against other illnesses, to treat people who already have COVID-19.
- other companies are working on vaccines that could be used as a preventive measure against the disease.
Currently now some of the earliest treatments using drugs that are already approved/tested for other conditions:
|Developed a decade ago, this drug failed in clinical trials against Ebola in 2014. But it was found to be generally safe in people. Research with MERS, a disease caused by a different coronavirus, showed that the drug blocked the virus from replicating.
The drug is being tested in many COVID-19 clinical trials around the world. This includes studies in which remdesivir is being administered alongside other drugs, such as the anti-inflammatory drug baricitinib . The drug is also being tested in children with moderate to severe COVID-19. Despite the conflicting results, the FDA issued an orderTrusted Source on May 1 for the emergency use of remdesivir.
|Arbidol||This antiviral was tested along with the drug lopinavir/ritonavir as a treatment for COVID-19. Researchers reported in mid-April that the two drugs didn’t improve the clinical outcomes for people hospitalized with mild to moderate cases of COVID-19.|
|EIDD-2801||This drug was created by scientists at a nonprofit biotech company owned by Emory University. Research in mice has shown that it can reduce replication of multiple coronaviruses, including SARS-CoV-2. Pharmaceutical company Merck and Ridgeback Biotherapeutics LP signed an agreement in May to develop this drug. It’s already being tested in a clinical trial in the United Kingdom. Unlike remdesivir, EIDD-2801 can be taken orally, which would make it available to a larger number of people.|
|Favipiravir||This drug is approved in some countries outside the United States to treat influenza.
Some reports from China suggest it may work as a treatment for COVID-19. These results, though, haven’t been published yet. Japan, where the medication is made, is sending the drug to 43 countries for clinical trial testing in people with mild or moderate COVID-19. Canadian researchers are testing to see whether the drug can help fight outbreaks in long-term care homes.
|Kaletra||This is a combination of two drugs — lopinavir and ritonavir — that work against HIV.
Clinical trials are being done to see whether it also works against SARS-CoV-2.
One small study published May 4 in the journal Med by Cell Press found that lopinavir/ritonavir didn’t improve outcomes in people with mild or moderate COVID-19 compared to those receiving standard care. Another study, published May 7 in the New England Journal of Medicine, found that the drug combination wasn’t effective for people with severe COVID-19. But another study found that people who were given lopinavir/ritonavir along with two other drugs — ribavirin and interferon beta-1b — took less time to clear the virus from their body. This study was published May 8 in The Lancet.
|Merimepodib (VX-497)||This drug developed by ViralClear Pharmaceuticals Inc. has been shown previously to have antiviral and immune-suppressing effects. It was tested against hepatitis C but had only modest effects. The company is running a phase II trial of this drug. People with advanced COVID-19 will be randomized to receive either merimepodib with remdesivir, or remdesivir plus a placebo.|
|Ibuprofen||The theory is ibuprofen’s anti-inflammatory qualities could help ease breathing difficulties associated with the illness.|
|Monoclonal antibodies||These drugs trigger the immune system to attack the virus. Like antibodies made by the body’s immune system, these laboratory-made molecules target a specific invader, such as SARS-CoV-2. The small biotech company Sorrento Therapeutics announced it has an antibody drug that has been effective in early testing in blocking SARS-CoV-2.
AbCellera has isolated 500 unique antibodies from a person who recovered from COVID-19 and is set to start testing them. Regeneron Pharmaceuticals Inc. is testing a two-antibody combination in four groups: people hospitalized with COVID-19; people with symptoms of the disease but not hospitalized; healthy people at high risk of getting sick with COVID-19; and healthy people who have had close contact with someone with COVID-19. Vir Biotechnology has isolated antibodies from people who survived SARS, another disease caused by a coronavirus. The company is working with Chinese firm WuXi Biologics to test them as a treatment for COVID-19.
|Convalescent plasma||Along the same lines, the FDA has announced a process for medical facilities to conduct trials on an experimental treatment that uses blood plasma from people who have recovered from COVID-19.
The theory is that their plasma contains antibodies that will attack this particular coronavirus. In late May, researchers reported that 19 of 25 people with COVID-19 who were treated with convalescent plasma transfusions at Houston Methodist Hospital in Texas had improved. Eleven of those patients have been released from the hospital.
|Immune modulators||In some people with COVID-19, the immune system goes into overdrive, releasing large amounts of small proteins called cytokines. Scientists think this “cytokine storm” may be the reason certain people with severe COVID-19 develop acute respiratory distress syndrome (ARDS) and need to be put on a ventilator.
Several immune suppressants are being tested in clinical trials to see whether the drugs can quell the cytokine storm and reduce the severity of ARDS. Other drugs being tested include baricitinib, a drug for rheumatoid arthritis; CM4620-IE, a drug for pancreatic cancer; and IL-6 inhibitors. The FDA has also approved a device that filters cytokinesTrusted Source out of the blood of patients with COVID-19.
|Stem cells||Stem cell treatment could potentially benefit people with ARDS. Many companies began a phase II/III clinical trials.|
|Hydroxychloroquine and chloroquine||These drugs received emergency use authorization from the FDA at the end of March.
On June 15, the FDA revoked that authorization, citing studies that indicated hydroxychloroquine didn’t significantly help people with COVID-19 and may have caused serious health risks. The United States is now left with 63 million doses of hydroxychloroquine and 2 million doses of chloroquine in its emergency stockpile.
Clinical results for the drugs have been mixed. Studies published in May in the New England Journal of Medicine and Journal of the American Medical AssociationTrusted Source showed that the drugs didn’t help people with COVID-19. In late June, British officials announced they would restart a global clinical trial on hydroxychloroquine and chloroquine.
In the search for an effective treatment, globally, the drug development is moving from early laboratory development to laboratory and animal testing to clinical trials in people. It can take a decade or more for a new compound to go from initial discovery to the marketplace.[Clinical Pharmacology & Therapeutics: Clinical trials for Covid-19: can we better use the short window of opportunity?, Pharmacoepidemiology and Drug Safety: Considerations for pharmacoepidemiological analyses in the SARS-CoV-2 pandemic]
Dr. Robert Amler, dean of the School of Health Sciences and Practice at New York Medical College and a former chief medical officer at the Centers for Disease Control and Prevention (CDC) Agency for Toxic Substances and Disease Registry (ATSDR), says both antivirals and vaccines will be valuable tools in combating COVID-19, however, that antivirals are likely to be developed and approved before a vaccine, which typically takes longer.
Can we speed up the process for vaccine development?:
- A «human challenge trial» could speed up the vaccine clinical trials according to some scientists. In this type of trial, healthy volunteers are given a potential vaccine and then intentionally infected with the virus, then, they look at how well the person was protected by the vaccine.
- Given the scope of the pandemic, some experts think this type of trial will happen eventually, nearly 30,000 peoplein more than 140 countries have signed up to take part.
But a human challenge trial raises ethical questions:
- there’s still a lot we don’t know about this virus, including who will get seriously ill or die from COVID-19,
- people can’t actually know the risks of participating, so they wouldn’t be able to give high-quality informed consent as they supposed to.
The WHO recently released ethical guidelines to navigate these concerns.
The European Medicines Agency’s (EMA) is interacting with developers of potential COVID-19 treatments and vaccines to enable promising medicines to reach patients as soon as possible:
|Next steps for treatments|
|No company has offered a timeline for when its drug might be used more widely to treat COVID-19. This isn’t an easy thing to estimate. After laboratory and animal testing, drugs have to pass through several clinical trial stages before they can be approved for widespread use in people. It’s also difficult to speed things up, because scientists have to enroll enough people in each stage to have useful results. They also have to wait long enough to see whether there are harmful side effects of the drug. However, drugs can sometimes be given to people outside a clinical trial through the FDA’s “compassionate useTrusted Source” program. For this to happen, people must have an “immediately life-threatening condition or serious disease or condition.” The FDA has granted emergency use authorizations for many diagnostic tests. Companies and universities around the world also continue to develop new ones.|
|A vaccine is designed to protect people before they’re exposed to a virus, in this case, the new coronavirus SARS-CoV-2. A vaccine basically trains the immune system to recognize and attack the virus when it encounters it. There are more than 100 projects around the world centered on the development of a COVID-19 vaccine. As of May 11, eight candidate vaccines were being tested in clinical trials in people. An official at the National Institutes of Health said in mid-May that large-scale testing could begin in July, with a vaccine potentially available by January.|
|Moderna||In March, the company began testing its messenger RNA (mRNA) vaccine in a phase I clinical trial in Seattle, Washington. In mid-May, the company announced the vaccine had produced antibodies in all 45 trial participants in this initial clinical phase. The study included 45 healthy volunteers, ages 18 to 55, which are getting two shots 28 days apart. The company has developed other mRNA vaccines before. Those earlier studies showed that their platform is safe, which allowed the company to skip certain animal testing for this specific vaccine. In early May, the company received permission from the FDA to start a phase II study of its vaccine. The company expects to begin a phase III clinical trial in July. The FDA also agreed to fast-track regulatory review of this vaccine if it succeeds in a phase III clinical trial.|
|Inovio||When COVID-19 appeared in December, the company had already been working on a DNA vaccine for MERS. This allowed the company to quickly develop a potential COVID-19 vaccine. Company officials announced at the end of April that it had enrolled 40 healthy volunteers in its phase I clinical trial. It’s preparing to start a phase II/III clinical trial this summer.|
|University of Oxford in England||A clinical trial with more than 500 participants began in late April. Oxford officials said the potential vaccine has an 80 percent chance for success and could be available as early as September. The vaccine uses a modified virus to trigger the immune system. The university has partnered with pharmaceutical company AstraZeneca. The company reported in mid-May the vaccine was effective against COVID-19 after it was given to six rhesus macaque monkeys. The company expects to begin a late-stage clinical trial by the middle of this year. Officials said in mid-May that if the clinical trial is successful, they could deliver 30 million doses by September.|
|University of Queensland in Australia||Researchers are developing a vaccine by growing viral proteins in cell cultures. They began preclinical testing stages in early April. The phase I trial in people will begin in early July|
|Pharmaceutical companies||Johnson & Johnson and Sanofi are both working on a vaccine of their own. Johnson & Johnson announced it will begin early stage human clinical trials in July. Pfizer has also teamed up with German biotech company BioNTech to develop a vaccine. In early July, Pfizer announced that the vaccine produced an immune response in people during an early stage clinical trial. They added: ‘the vaccine did cause side effects such as fever at higher doses’.|
It is also making use of real-world data to monitor the safety and effectiveness of medicines used in patients with COVID-19 .
Meanwhile, clinical trials are underway trying to prove whether existing vaccines for tuberculosis might also used against COVID-19. Shibo Jiang, a virologist at Fudan University in China, noted in the journal NatureTrusted Source: «A rush into potentially risky vaccines and therapies will betray that trust and discourage work to develop better assessments».Top of Form
Many lessons need to be learned globally from this pandemic in order to avoid new ones in the future. We need more education of the public as we need policy makers and scientists. But we need more experts to be involved in the decision process in order to avoid catastrophic pandemics in the future.
 “WHO targets SARS ‘super spreaders'”. CNN. 6 April 2003. Archived from the original on 7 March 2006. Retrieved 5 July 2006.
 European Parliament: coronavirus a timeline of EU action.
 European Medicines Agency response to IQWIG on transparency of COVID-19 related activities (PDF/114.93 KB) First published: 29/05/2020, EMA/280976/2020, Max Roser, Hannah Ritchie, Esteban Ortiz-Ospina and Joe Hasell (2020) – “Coronavirus Pandemic (COVID-19)”. Published online at OurWorldInData.org. , A Proposed Protocol of Derived Mesenchymal Stem Cells for the Treatment of COVID-19 Patients. Cell & Gene Therapy insights 2020; 6(6), 807-811, Kalodimou et all.
 [AABB’s Coronavirus Resources, FDA Coronavirus Disease 2019 (COVID-19)].
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