SPECIAL REPORT #21

COVID-19: What have we learned.

The current pandemic Covid-19 is clearly getting under control in many areas in the world, Asia, Europe, some states in the United States. But the infection continues to spike in Brazil, Mexico, French Guyana as well as in Arizona, Texas and Florida. Last week Dr. Anthony Fauci, head of the American National Institute of Allergy and Infectious Diseases stated that “the US is still knee deep in the first wave of the coronavirus pandemic and must confront the serious situation immediately” when the US reported more than 60,500 new cases, the largest single-day spike seen in any country, since the pandemic started.

According to the latest report of July 13, 2020, the first COVID-19 wave has infected more than 13 million people worldwide, with a death toll of 571.697 people and with still 4.882.059 active cases.

An increasing and worrisome trend indicates that a second Covid-19 wave is on its way. Areas around Melbourne in Australia, in South Africa, in Spain, in France, in Serbia have spotted a notable increase in new cases and have decided to seriously consider halting their reopening process and declare selective lockdowns in order to best control the spread of the infection. Many people wrongly thought that the SARS-CoV-19 virus would not spread over summertime and have unconsciously decided to lower their attention and compliance of the advocated physical distancing and sanitation measures. As a consequence, in an increasing part of the world the disease resumes slowly but steadily.

What if a second wave of Covid-19 strikes in the fall and what have we learned?

In terms of awareness it would not come as a surprise this time. Political leaders, physicians and care givers, as well as the general population have already been confronted with the first wave, its death toll and seen how easy protective measures such as physical distancing, hand washing and wearing of masks are efficient and can rapidly be implemented. In several countries the mandatory mask-wearing in closed area is going to be required by law although there is still an ongoing debate of its beneficial effect. Political leaders are now confronted with the economic impact of week-long country lockdowns and are not prepared to resume them by any means. Selective lockdowns of clearly identified clusters will now become the norm. One of the most crucial decision to be taken is school reopening in the fall which would be strongly jeopardized if a second wave of Covid-19 was to appear.

Testing and diagnosis are generally available. Rapid, easy to use and repeated testing of individuals and of groups of individuals has become far easier and can be performed everywhere with no need to require a laboratory. Saliva is a major vector in the spread of Covid-19 virus and molecular saliva based screening test have been clinically validated and confirmed a highly satisfactory performance in terms of specificity and sensitivity. The test can be completed in less than one hour. Massive testing will be required because most infected subjects will remain asymptomatic and severe cases usually appear one to two weeks after a person is first infected.

Scientists have learned a lot about the virus that causes Covid-19. It is a beta-coronavirus named SARS-Cov-2 with strong analogies with SARS and MERS. When SARS was successfully contained almost all efforts to better understand how coronaviruses specifically work out were stopped and no selective SARS inhibitor is currently available. The good news is that one knows that SARS-Cov-2 needs polymerases to copy their genomes and proteases to cut larger proteins into smaller fragments required for it to reproduce.  Previous studies of proteases have allowed the elucidation of the selective structure right down to the atom-to-atom potential contacts of the active sites.

In terms of clinical signs and features, the spectrum has been increased and improved. Clinical abnormalities now go far beyond symptoms such as fewer, cough and respiratory distress. More than 50% of asymptomatic infected subjects who underwent chest computed tomography (CT) had typical ground-glass opacities in their lungs and 20% had atypical imaging abnormalities. The most striking new symptoms which were not originally reported in China were the loss of smell (anosmia) and the loss of taste (ageusia). Several health authorities have now added anosmia and ageusia to the list of symptoms that should warn people to self-isolate for seven days. In elderly patients, it is not rare to see infected Covid-19 patients develop micro-emboli in their lower limbs and in more severe cases they develop pulmonary embolism which has a poor diagnosis. The so-called “inflammatory cytokine storm” is still being investigated and also constitutes an area of therapeutic strategy of interest.

In terms of treatment of Covid-19 our arsenal has widened although not to full satisfaction. As of today, Gilead’s remdesivir is the only approved drug for the treatment of SARS-Cov-2 virus infection. Although still controversial, the use of hydroxychloroquine is common in many places in particular in less developed countries. For patients at risk (age, diabetes, hypertension) several hospitals are recommending the use of anticoagulants to the usual protocols. In a controlled study performed in the United Kingdom, the use of dexamethasone reduced the death rate of those needing breathing assistance by 35% and those needing oxygen support by 20%. The treatment of the “cytokine storm” can be hampered by the use of Roche’s Actemra or tocilizumab, an interleukin-6 selective antibody and by SOBI’s Kineret, or anakinra, a selective interleukin-1 antibody. A cocktail of antibodies known as REGN-COV2 from Regeneron, comparing the two-drug combination against placebo including almost 4,000 patients, will be initiated this summer

Our internal records indicate that 180 Covid-19 vaccines are being investigated with as many as 10 in advanced clinical settings. Recently Moderna and Novavax have received as much as $2 billion from the US government as part of its coronavirus vaccine program named “Warp Speed Operation”. The issues to be solved with these vaccines is three fold: will the new vaccine induce sufficient immunity to protect subjects for more than a few weeks, will the companies be able to produce billion of doses required to immunize at least 50% of the worldwide population and who will make the hard decision who should get treated. “If we just let drugs and vaccines go to the highest bidder, instead of to the people and places where they are the most needed, we will have a longer more unjust, deadlier pandemic” said Bill Gates during a Covid-10 conference. Pfizer CEO Albert Bourla announced that his company will start producing the vaccine it develops with German partner BioNTech before receiving approval from any health authority. Pfizer is set to launch a large-scale clinical trial which will involve 30,000 people at 150 locations and plans to price the vaccine to make a profit but believes government should distribute the first doses to the most vulnerable at no cost. Like other companies Pfizer is planning to have hundred million doses for this year end and approximately 1.1 -1.3 billion doses in 2021.

In case of a second Covid-19 wave in October-November, the world population would clearly not have access to efficient anti-viral treatments and to sufficient doses of vaccines. They would therefore have to rely on their political leaders to decide who will be eligible to be immunized.

We wish all our readers a nice and healthy summer break.

La Baule, July 13, 2020.

This document has been prepared by btobioinnovation and is provided to you for information purposes only.  The information contained in this document has been obtained from sources that btobioinnovation believes are reliable but btobioinnovation does not warrant that it is accurate or complete. The views presented in this document are those of btobioinnovation’s editor at the time of writing and are subject to change.  btobioinnovation has no obligation to update its opinions or the information in this document.