Immunology’s Dirty Secret – Adjuvants
April 15, 2018
Covid-19 — Navigating the Uncharted
März 30, 2020

New Corona Virus: COVID-19

About Corona

Animal coronaviruses were first described in 1930. The first report of human coronavirus was in 1965 by David Arthur John Tyrrell and his team. (1) He isolated a virus from the nasal washings of a male child. The child had typical symptoms of a common cold. Common colds account for a third of all acute respiratory infection in the Western World. The virus was termed B814 after the number of the nasal washing. Due to the characteristic morphology of these agents, Tyrrell proposed the term “Coronavirus” in 1968 which was broadly accepted. Tyrrell (1925–2005) was a British virologist and the final director of the Medical Research Council's Common Cold Unit.


Virus classification

Coronaviruses are pathogenic for animals and humans. The coronaviruses typically cause respiratory symptoms mainly of the upper respiratory tract, in some cases also of the lower respiratory tract. The family Coronaviridae comprises 4 genera of which alpha coronavirus and beta coronavirus are pathogenic for humans and animals. Gamma coronavirus and delta coronavirus are specific for animals. Among the seven corona strains circulating in the human population are three strains that are potentially severe:

1. Middle East respiratory syndrome-related coronavirus (MERS-CoV), known as novel coronavirus 2012 and HCoV-EMC: 2 main outbreaks, 2012 and 2015

2. Severe acute respiratory syndrome coronavirus (SARS-CoV): Outbreak 2003

and since December 2019:

3. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), known as newCOVID-19 or novel coronavirus 2019. On February 11th 2020 the WHO definitively named the new coronavirus 2019 SARS-Cov-2 and the disease caused by this virus was named ‘Coronavirus Disease 2019’ (COVID-19).

In 2017 the impact of co-infection of influenza A virus on the severity of Middle East Respiratory Syndrome Coronavirus was reported. (2) Currently SARS-CoV-2 is co-circulating with Influenza A(H1N1). Bothe viruses provoke similar symptoms. On this ground every suspected patient should be tested for both viruses. A flu vaccine does exist.


Virus Biology

Coronaviruses are enveloped single stranded (ss) RNA Virus, 80 to 120 nm in size. The genome comprises about 31,000 nucleotides. Coronaviruses encode three conserved membrane-associated proteins that are incorporated in virions: spike (S), envelope (E), membrane (M), and nucleoprotein (N). These four proteins occur in the order S–E–M–N in every known coronavirus lineage. (3) The other 10 proteins are non-structural proteins.


COVID-19: Symptoms

COVID-19 typically causes flu-like symptoms as fever, cough, sore throat and fatigue, shortness of breath. COVID-19 may present with mild, moderate, or severe illness; the latter includes severe pneumonia, ARDS (Acute Respiratory Distress Syndrome), sepsis and septic shock:

Risk of death increases the older you are. Patients with underlying health conditions affecting the immune system are also at risk. Relatively few cases are seen among young people. But all these facts match with influenza infection, too. (4, 5)

COVID-19: Tenacity

The virus is stable for several hours to days in aerosols and on surfaces. Scientists from the NIH/ USA and Princeton University/ USA found that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was detectable in aerosols for up to three hours, up to four hours on copper, up to 24 hours on cardboard and up to two to three days on plastic and stainless steel. The results provide key information about the stability of SARS-CoV-2, which causes COVID-19 disease, and suggests that people may acquire the virus through the air and after touching contaminated objects. (6,7)

Global Vaccine Projects

At least 35 global big and small pharmaceutical companies and lots of academic institutes are engaged in vaccine development against SARS-CoV-2. (Last update 03/25/2020)
According to the WHO (8) various types of vaccine approaches are in progress:

Some well-known RNA-companies (mainly dedicated to cancer vaccines) are also engaged in vaccine development against SARS-CoV-2. For example CureVac/ Tubingen/ Germany, BioNTech/ Mainz/ Germany and Moderna Inc./ Cambridge/ U.S.A.

CureVac: founded in 2000, not any registered RNA vaccines on the market

BioNTech: founded in 2008, not any registered RNA vaccines on the market

Moderna: founded in 2010, not any registered RNA vaccines on the market

The same is for all other RNA vaccine companies! It should be underlined that worldwide no RNA vaccine is on the market so far. It seems that RNA vaccines are a complete flop.

Globally, there are some 160 companies and 65 academic teams currently involved in RNA-based therapies and vaccines. (9) After this very long time of unsuccessful, and very expensive commercial minus development of RNA vaccines, this approach is to be critically reviewed.


Clinical Trials

Last update 03/25/2020 (10):

• Safety and Immunity Evaluation of A Covid-19 Coronavirus Artificial Antigen Presenting Cell Vaccine
• Phase I/II Multicenter Trial of Lentiviral Minigene Vaccine (LV-SMENP) of Covid-19 Coronavirus
• Phase I Clinical Trial to Evaluate Recombinant Novel Coronavirus Vaccine (Adenovirus Type 5 Vector)
• Phase I Study of the Safety and Immunogenicity of 2019-nCoV Vaccine (mRNA-1273)





Sources

1. Cultivation of viruses from a high proportion of patients with colds. Tyrrell DA, Bynoe ML., Lancet 1966: 1: 76–77
2. The impact of co-infection of influenza A virus on the severity of Middle East Respiratory Syndrome Coronavirus. Sarah H. Alfaraj et al., Journal of Infection May 2017 Volume 74, Issue 5, Pages 521–523
3. Chapter One - Supramolecular Architecture of the Coronavirus Particle. B.W. Neuman and M.J. Buchmeier, Advances in Virus Research Volume 96, 2016,1-27
4. Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus–Infected Pneumonia in Wuhan, China. Dawei Wang et al., https://jamanetwork.com/journals/jama/fullarticle/2761044?guestAccessKey=f61bd430-07d8-4b86-a749-bec05bfffb65
5. https://www.worldometers.info/coronavirus/coronavirus-symptoms/
6. Aerosol and surface stability of HCoV-19 (SARS-CoV-2) compared to SARS-CoV-1. N van Doremalen, et al., The New England Journal of Medicine. DOI: 10.1056/NEJMc2004973 (2020).
7. https://www.nih.gov/news-events/news-releases/new-coronavirus-stable-hours-surfaces
8. DRAFT landscape of COVID-19 candidate vaccines – 20 March 2020. https://www.who.int/blueprint/priority-diseases/key-action/novel- coronavirus-landscape-ncov.pdf?ua=1
9. Latest development on RNA-based drugs and vaccines. Lundstrom K., Future Sci OA. 2018 Jun; 4(5): FSO300.
10. https://clinicaltrials.gov/ct2/results?term=covid+19+vaccine


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