Authors: Albert Bosch, Amelia Nieto, Ana María Doménech Gómez, Carlos Briones, Covadonga Alonso Martí, Inmaculada Casas Flecha, Javier Buesa Gómez, Jesús Navas Castillo, José Antonio López Guerrero, Josep Quer Sivila, Juan E. Echevarría Mayo, Vicente Pallas Benet .
For Peter Medawar, winner of the 1960 Nobel Prize in Medicine, viruses were a set of “bad news wrapped in protein.” Although it does not respond to any scientific criteria, this definition perfectly reflects the perception we have of the SARS-CoV-2 coronavirus pandemic in these days of confinement.
The “bad news” in a virus can be written in two slightly different “alphabets”, depending on whether its genome is DNA or RNA. Coronaviruses (family Coronaviridae) constitute one of the groups of viruses with the longest known RNA genome. The information it contains can be used to synthesize at least 16 proteins.
The most essential are those that allow you to make copies of your own genome, those that protect your RNA, and those that allow you to enter the cell it is about to infect. The latter is a protein that contains sugars in its skeleton and that projects like spicules (protein S, for spike in English) from the envelope to the outside. Under the electron microscope they create an image that resembles a corona, hence the name of the virus.
The copy fidelity of viral RNA molecules is always much lower than that of DNA, so RNA viruses tend to accumulate more mutations and adapt to new hosts more easily than those with a DNA genome. Within viruses with an RNA genome, coronaviruses are an exception: they have a copy correction system that makes them show less variability.
The sequencing of more than 11,000 SARS-CoV-2 genomes has shown that it has a mutation rate 1,000 times slower than that of influenza or HIV. On the other hand, viruses with a DNA genome are generally more difficult to eliminate because some of them can cause latent infections or even integrate into the host genome (the latter also occurs with RNA viruses of the retrovirus family).
Sus parientes: SARS-CoV y MERS-CoV
Human coronaviruses have been known for many years and most of them are related to colds or mild respiratory conditions. In 2002, the first lethal to humans, SARS-CoV (name that comes from “severe acute respiratory syndrome”), appeared in China, infecting around 8,000 people causing the death of 800, which represents a rate mortality rate of 10%. It disappeared in the spring of 2004 and has caused no further problems since then.
The second, MERS-CoV (named after the “Middle East respiratory syndrome”), appeared in Saudi Arabia in 2012 and caused roughly the same number of deaths, although it only infected 2,400 people. Its mortality rate was 30%, very high, but far from that observed for the Ebola virus (50%) and the rabies virus (95%).
Among the thousands of known viruses, only a small proportion are human pathogens. Cells do not have a gate available for entry for most of these microorganisms.
But these tiny infectious agents have evolved through high rates of mutation and recombination to use some host protein as a route of entry into the cell, where they can multiply and perpetuate themselves: that is what every replicative entity aspires to, and viruses cannot do it. by themselves outside the cells they infect.
Coronaviruses use the S proteins that these spicules form on their exterior to bind to a cellular enzymatic protein called ACE2. This enzyme is located on the surface of the cells of the mucosa, lungs, arteries, heart, kidney and intestines, and has the function of regulating blood pressure, but the virus uses it as a gateway to the cellular context.
Once inside its host, the virus roams freely because it carries its own replicase that will allow it to make multiple copies of its genome (up to 100,000 copies in each cell) and because the alphabet of information it carries in its RNA is the same one we humans use.
Cellular ribosomes are unable to identify this RNA as foreign. It acts like a Trojan horse using cellular machinery and translates that information into virus proteins. This causes a drop in the essential functions of the cell.
An unknown animal origin
SARS-CoV-2 is of animal origin, although an identical or very similar coronavirus has not been found in any species. Some species of bats and the Malayan pangolin, used as food and in traditional Chinese medicine, are quite similar virus reservoirs, but bats were hibernating in China in December 2019, when the first human cases were detected.
Further research is needed to identify the animal species involved in the origin of the COVID-19 pandemic. The markets for live animals, wild and domestic, in China are very frequent and are part of the traditional food chain of the country.
After this pandemic, the Chinese government should regularize or ban them. In fact, the next virus pandemic may already be beginning to unfold in those same environments.
How to detect COVID-19
The diagnosis of the COVID-19 disease, caused by this coronavirus, is carried out by detecting the RNA or antigens (proteins) of the SARS-CoV-2 virus, or the antibodies developed by the patient after being infected.
In the first case, the samples used are respiratory secretions that may contain the virus (nasopharyngeal exudate, nasal exudate, tracheo-bronchial aspirate, sputum), and in them the presence of viral RNA is identified (by means of its extraction and amplification by Quantitative PCR) or of certain antigens (using different types of biosensor systems).
On the other hand, the antibodies of the infected patient are analyzed in blood, plasma or serum. The detection of antibodies against SARS-CoV-2 allows knowing which patients are infected (after a “window period” of between 5 and 7 days from exposure to the virus, which is what the body uses to generate the immune response) and also who have overcome the infection even without suffering symptoms.
SARS-CoV-2 is particularly contagious.
An overestimated fatality rate
Coronaviruses are transmitted by aerosols, where they can remain viable for up to three hours, and are stable on various surfaces: they resist four hours on copper (coins), a whole day on cardboard and two to three days on plastic or steel stainless. The infection coefficient R₀ (average number of people contacted by each infected person) is around 2.5 (similar to the flu, but much less than smallpox or measles, which present R₀ of 6 and 15 on average) as recently published in The Lancet magazine, and therefore its progression is necessarily exponential.
The other important numerical aspect for the progression of the pandemic is its fatality rate. To determine it reliably requires a very extensive sampling. Current calculations based on the available data give a fatality rate of around 7% on average (although they vary widely in different age groups: from 0.7% for those under 30 years of age to 20% for those under 30 years of age). over 80) in Italy and Spain.
This average rate is certainly overstated. As the mathematician Andrejs Dunkels said, “it is easy to lie with statistics” although he went on to add that “it is difficult to tell the truth without them.” For an accurate calculation, it would be necessary to know the real number of infected, that is, to carry out the analyzes on the entire cohort (group that is part of a clinical trial, in this case the entire population), which is practically unfeasible.
But if we have that cohort confined to a cruise ship, for example, this is the perfect experiment. This is what happened on the Diamond Princess, which after a first positive tests were carried out on the 3 711 passengers, including the crew, and in some cases twice. During the next 4 weeks, 711 positives were detected, 18% of which were asymptomatic.
One million infected?
In an article published by researchers at the London Center for Mathematical Modeling for Infectious Diseases, published in the journal Eurosurveillance, a fatality rate of 1.1% was estimated on this cruise, much lower than the 3.8% estimated by the Organization World Health Organization (WHO) at the global level. If the data of this study are correct and extrapolated, it could be estimated that in Spain the number of infected would exceed one million people today and this would increase our chances of acquiring a herd immunity that protects us for the future.
Coronaviruses have a lipid membrane that gives the particle relatively low stability, especially when compared to the naked particle of the common cold virus. That makes it relatively easy to remove them from your hands using soapy solutions. Therefore, protection seems simple: social distance (following the successful hashtag #YoMeQuedoEnCasa) and correct hand hygiene.
According to a recent study by Imperial College London, if the confinement measures had not been taken, the number of deaths could have reached 40 million people worldwide. But lasting preventive measures require the development of effective vaccines. Spain has a long tradition of internationally recognized virology research, essentially concentrated, but not only, in Madrid and Barcelona.
Our colleagues from the National Center for Biotechnology of the CSIC, Drs. Luis Enjuanes and Mariano Esteban, are actively working to develop vaccines against SARS-CoV-2 with two methods based on different principles. Enjuanes’ team intends to attenuate the virus by eliminating the virulence genes of SARS-CoV-2, keeping the genes responsible for immune defense.
For its part, Mariano Esteban’s group uses viral vectors to express the virus’s protein S on the surface of the smallpox vaccine virus, which opens the cell door, waiting for it to trigger the immune response. Other strategies of public laboratories and companies in several countries focus their efforts on the use of fragments of viral RNA, DNA or proteins to generate this protective response in the body.
But in the current situation, obviously, more than preventive methods, curative ones are urgently needed, based on antiviral compounds that can treat the infection. In infected patients, among other antivirals, (hydroxy) chloroquine, which would prevent the entry route of the virus, Remdesivir, which would act on the viral replicase, and the Ritonavir / Lopinavir combination, which would inhibit the protease used by the virus, are being tested. to express your information.
Other drugs that are being administered to patients have the purpose of controlling or modulating the exaggerated response of the immune defense against the virus itself, including interferons, corticosteroids, monoclonal antibodies such as Tocilizumab against the interleukin receptor IL-6, Eculizumab inhibitor of complement activation, etc.
Let’s be optimistic, but patient
There are several ongoing clinical trials worldwide (some of them with the active participation of hospitals in our country), but for the moment the results are not conclusive and the success stories refer to small-scale trials, without statistical validity.
We have to be optimistic, but patient. In these circumstances it is an investigation under great pressure and based almost exclusively on the concept of trial and error with pharmacologically approved and sometimes previously used compounds against other viruses.
In the current phase of fear socialization, which is understandable, it is important to be well informed and not contribute to transmitting, at speeds faster than the virus itself, totally or partially false information. The latter do even more damage, because they introduce erroneous, manipulated and biased data in an apparently well-argued context.
This pandemic should help us so that world governments (especially Spanish) realize the urgent need to invest in the generation of knowledge , and that investment in Science, Education and Health must be the basis on which it is built a just, egalitarian and prosperous society.
Let’s not forget that, according to a study by researchers from the Boston School of Public Health recently published in the journal Science , even in the case of the apparent elimination of the pandemic in the coming months, estimates for post-pandemic periods foresee occasional outbreaks until 2024. We have no choice but to be prepared.
The pharmacist Mª Dolores García and the doctor Juan García Costa have also collaborated on this article.
This article was originally published on The Conversation. Read the original.
