Science on SARS-CoV2 coronavirus
The first approved adenoviral vaccine for COVID-19
Moscow-based Gamaleya Research Institute of Epidemiology and Microbiology developed a SPUTNIC V vaccine to prevent COVID-19. The vaccine is composed of two different adenoviruses, both producing the coronavirus spike protein, which are administered three weeks apart. In humans, adenoviruses generally cause mild respiratory and gastrointestinal tract infections. They are well-characterized viruses and can be easily modulated to produce safe vaccines which trigger an excellent response of the immune system. It is worth noting that Sputnic V vaccine has freeze dried formulation and is transported and stored at the regular refrigerator temperature. On 11 November 2020, the Sputnik V vaccine was reported to be 91.4% effective in preventing COVID-19 in an interim efficacy analysis report of their Phase III clinical study (with more than 16,000 participants) (https://sputnikvaccine.com/about-vaccine/).
The first approved RNA vaccine for COVID-19
On November 12, 2020, Pfizer and BioNTech received authorization from the U.S. Food and Drug Administration that their RNA vaccine could be used in people over the age of 16 to prevent COVID-19. In the third phase of the clinical trial (conducted on 43,448 participants, half of whom received the vaccine and half a placebo) this RNA vaccine showed excellent results - 95% efficacy and mild side effects in the form of fever, fatigue and chills [Walsh et al. N Engl J Med 2020 Oct 14, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7583697/]. The vaccine contains messenger RNA, a molecule that instructs our cells to make a protein characteristic for the SARS-CoV-2 virus envelope, the one that is crucial for our immune system to recognize this virus. The RNA molecule has a short lifespan and after serving as a template for protein synthesis within the cell, it is rapidly degraded. This RNA cannot affect human hereditary material in any way, and it cannot cause cancer or other diseases.
A company Moderna and the U.S. National Institute of Allergy and Infectious Diseases are also developing vaccines based on the messenger RNA molecule.
SARS-CoV-2 virus is mutating- what does it mean?
Studies show that the SARS-CoV-2 virus mutates much more slowly than most RNA viruses because it contains an enzyme that can correct genome defects that occur during its replication.
By sequencing the genomes of over 185,000 samples of this virus from around the world, about 12,700 mutations and seven main genetic strains of the virus have been identified: L, S, V, G, GR, GH, and GV. Nevertheless, after a year of the evolution of this virus in human populations, the "youngest" sequences and the "ancestral" sequence differ in a maximum of 30 nucleotide and 15 amino acid mutations, respectively.
The D614G mutation that characterizes G strains is currently dominant in the world and is found in a protein that builds a "spike" that binds SARS-CoV-2 to the cell. Several studies indicate that this mutation leads to greater infectivity of the virus but has no effect on the clinical picture. Also, it has been shown that this mutation makes the virus more sensitive to antibodies and that existing vaccines will be more effective in preventing infection with viruses with this mutation.
Patient’s genetics affects the course of the COVID-19
Most people infected by the SARS-CoV-2 virus never experience signs of viral infection, whereas others develop hard or life-threatening symptoms. There are multiple distinct COVID-19 disease phenotypes with differing patterns of presenting symptoms. The great interest of geneticists is to understand how a person’s DNA can explain why some patients develop a critical illness.
Geneticists analyze the DNA of large numbers of people for millions of marker sequences, looking for associations between specific markers and symptoms of the disease. There are at least two heritable biological components associated with specific genetic variants that increase mortality in COVID-19: susceptibility to viral infection, and the tendency to develop harmful pulmonary inflammation.
In a recent study, published in the Nature (Pairo-Castineira, E. et al. Genetic mechanisms of critical illness in Covid-19. Nature 11.12. 2020), a U.K. group of scientists from The COVID-19 Host Genetics Initiative analyzed 2244 critically ill COVID-19 patients and discovered common gene variants associated with the most severe cases of the disease. Their findings reveal that critical illness in COVID-19 is related to at least two biological mechanisms: innate antiviral defenses, which are known to be important early in disease (related to variants in IFNAR2 and OAS genes), and host-driven inflammatory lung injury, which is a key mechanism of late, life-threatening SARS-CoV-2 virus infection (related to variants in DPP9, TYK2, and CCR2 genes).
Results of this study revealed robust genetic signals relating to the host antiviral defense mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be subject to targeted treatment with existing drugs, such as inhibitors of DPP9 enzyme for diabetes and baricitinib, which blocks TYK2’s product, for arthritis.
Will SARS-CoV-2 virus disappear in the summer of 2020?
According to the experience with epidemic seasonal flu, it is expected that increasing temperature will decrease the endurance of SARS- CoV-2 virus, or even destroy it this summer. In the laboratory conditions, the virus is highly stable at 4°C for 14 days, but when the incubation temperature increases to 70°C, the time for virus inactivation is reduced to 5 minutes. However, COVID-19 is already spreading in many parts of the world where it’s hot, including Australia and South America, demonstrating that high temperatures are not enough to stop the disease. Also, the two most serious coronavirus diseases that are closely related to COVID-19, the first SARS outbreak and MERS, did not vary with the seasons after they emerged.
Loss of smell or taste as symptoms of COVID-19
Loss of smell or taste as symptoms of COVID-19 were reported in studies from North Korea, Germany, China, Italy, Great Britain and USA. These symptoms are frequently reported by mildly symptomatic patients with SARS-CoV-2 infection and often are the first apparent symptom. Although a number of physicians agree that a consideration should be given to testing and self-isolation of patients with sudden loss of taste or smell during the COVID-19 pandemic, WHO did not include these symptoms in the list of initial signs of COVID-19.
SARS-CoV-2 genomic sequencing
Genetic basis of SARS-CoV-2 virus, causing COVID-19, is a 30 000 bp RNA molecule. The first sequenced genome of SARS-CoV-2 virus, isolated in Wuhan, China, was reported 12.01. 2020. Four thousands of genomes, isolated in 36 countries across 6 continents, have been sequenced ever since. NextStrain (https://nextstrain.org/ncov) is a database which collects information on SARS-CoV-2 genomic sequences. Based on genetic relationships between sampled viruses, a phylogenetic tree was made. This phylogeny shows an initial emergence in Wuhan, in Nov-Dec 2019 followed by sustained human-to-human transmission leading to pandemia. It also enables the reconstruction of geographic spread of SARS-CoV-2 virus.
What can we learn from genomic mutations of SARS-CoV-2 virus?
The SARS-CoV-2 virus that causes COVID-19 is constantly mutating. There are more than 100 nonsynonymous mutations that have been identified in the outbreak, but there is no evidence that any of them has any significance in a functional context of transmission rates or association with severity of the disease. It appears the seasonal flu mutates roughly four to eight times as fast as SARS-CoV-2. The significantly slower mutation rate of SARS-CoV-2 gives us hope for the potential development of effective herd immunity and long-lasting vaccines against the virus.
A new type of vaccine to combat SARS-CoV-2
The race for a vaccine against the novel coronavirus, or SARS-CoV-2, is on, with 54 different vaccines under development, two of which are already being tested in humans. Among the different candidates is a new type of vaccine, a messenger RNA (mRNA) vaccine that contains information for the viral protein synthesis. Human cells produce these proteins that are incapable of assembling in an active virus but stimulate both innate and acquired immune responses more efficiently than traditional, inactivated virus-based vaccines. Using messenger RNA instead of whole virus simplifies production and upscaling.
COVID-19 and masks
Regarding the effectiveness of the respiratory masks for the coronavirus, it is important to know that the coronavirus is only 120 to 160 nanometers in size. Special mask, so called the N95 respirator, blocks 95% of 300-nanometer particles. They are commonly used in healthcare settings. Wearing a regular surgical mask reduces the odds of infecting family members or others. Mathematical models simulate that if 50% of the population wears masks, the share of the population infected by the virus is cut in half. Once 80% of the population wears a mask, it theoretically stops an outbreak. The 2008 study notes that any type of general mask use decreases infection risk on a population level.
Coronaviruses (CoV), similar to all other viruses, are able to multiply only within the living cells of a host. They are very small and numerous (800 million viruses cascade onto every square meter of the planet). Coronavirus particles consist of an envelope and genetic material. In humans, genetic material which carries complete information needed to build and maintain functioning an organism, is a DNA molecule, made up of 3 billion “letters” (nucleotides). Genetic material of coronavirus is RNA molecule, made up of 30 thousand “letters”. Coronaviruses are named for the crown-like spikes on their surface, seen under an electron microscope.
The coronavirus epidemics
Diseases caused by coronaviruses are zoonotic diseases, meaning that coronaviruses that infect animals can evolve and become a new human coronaviruses. That is the consequence of the incidental change (mutation) in the viral genetic material. There are seven coronaviruses that can infect people. Only three of them cause severe form of disease: SARS -CoV (Severe Acute Respiratory Syndrome - Coronavirus) (2002, China); MERS-CoV (Middle East respiratory syndrome- Coronavirus) (2012, Saudi Arabia); SARS-CoV- 2 virus causing COVID-19 ( Corona virus diseases 2019) (2019, China).
Differences between coronavirus epidemics
SARS -CoV virus caused an epidemic in China in 2002. Bats were a source of infection in humans. There were 8000 confirmed cases of infection and more than 750 associated deaths in 37 countries. No new cases of SARS were diagnosed from 2004.
MERS-CoV virus caused an epidemic in Saudi Arabia in 2012. Dromedary camels were a source of infection in humans. Up to now there are 2500 confirmed cases of infection and 800 associated deaths in 27 countries. 80% cases are registered in Saudi Arabia.
SARS-CoV-2 virus caused COVID-19 epidemic in China in 2019. It reached the pandemic status. Bats and pangolins were a source of infection in humans. Up to now there are more than 300 000 confirmed cases of infection and 14 000 associated deaths in 190 countries.
Why does the coronavirus spread so easily between people?
Why does SARS-CoV-2 virus (COVID-19) virus infect human cells so easily? What type of mutation (a change in genetic material) has contributed to the potential of the new virus to spread much more readily? To infect a cell, the new coronavirus uses a ‘spike’ protein that binds to the cell membrane. It binds to a receptor on human cells, angiotensin-converting enzyme 2 (ACE2), ten times more tightly than SARS virus. Then the virus is activated by enzyme furin. The spike protein of the new coronavirus differs from those of close coronavirus relatives. Furin is found in the lungs, liver and small intestines, which means that the virus attacks multiple organs.