Inside the particles, black dots are visible – cross-sections of the viral genome.

Judging by official statistics, the number of victims of the SARS-CoV-2 coronavirus in the first six months of the pandemic was no less than a year and a half of the infamous swine flu epidemic in 2009-2011, when out of 0.7-1.4 billion cases died, according to various estimates, from 150 thousand to half a million people. As for COVID-19, in September the official number of cases exceeded 33 million people, and the number of deaths – 1 million.

SARS-CoV-2 turned out to be a tough nut to crack for humanity. On the one hand, the COVID-19 pandemic from the very beginning was accompanied by an unprecedented rapid accumulation of evidence and an increase in the number of scientific publications on this problem (by the beginning of June 2020, their number exceeded 200 thousand), and WHO has registered more than one and a half hundred candidate vaccines. On the other hand, not a single really effective drug against the causative agent of the disease has yet appeared, and the mechanisms of the interaction of SARS-CoV-2 with the body and the emergence of a wide range of pathological manifestations are still being studied.

Nevertheless, over the past months, specialists not only learned a lot of useful information about the new coronavirus infection, but also looked differently at the ARVI we are used to – acute respiratory viral infections, for example, the well-known phenomenon of asymptomaticity, which had not been paid much attention to before. Now it is becoming clear that such a feature is inherent not only in the current coronavirus.

So it’s time for us to learn from our fight against the pandemic and think about how to move on. In any case, the overriding challenge for humanity is to do everything possible to minimize the impact of this disease on daily life and the economy.

“Predecessors” SARS-COV-2

Until the beginning of this century, coronaviruses served as the cause of the usual seasonal SARS, but in the 2000s. the situation began to change. SARS-CoV-1, the causative agent of atypical pneumonia, was first “identified” in November 2002 in the Chinese province of Guangdong. It originated from the bats coronavirus, and its intermediate host, apparently, was the Himalayan civet (civet). These animals, eating coffee fruits, “process” them into kopi-luwak – one of the most expensive varieties of coffee in the world; in addition, they have tasty meat, beautiful fur, and some internal organs and body parts are used in Chinese traditional medicine. Therefore, at one time, civets began to be intensively bred in China and other countries of Southeast Asia. Accidental adaptation of the virus, which came to them from bats and then to humans, led in 2003 to more than 8 thousand cases of infection and almost 800 deaths in 37 countries of the world.

The Orthocoronavirinae subfamily, to which SARS-CoV-2 belongs, is part of the extensive Coronaviridae family. It consists of 4 genera, including several subgenera. Of these, in addition to SARS-CoV-2, SARS-CoV-1, the SARS virus of 2002-2003, which causes severe acute respiratory syndrome, or SARS, and MERS-CoV, the causative agent of pulmonary pneumonia that causes Middle East respiratory syndrome. Other human coronaviruses are the causative agents of lung and moderate ARVI

MERS-CoV was first identified in Saudi Arabia in 2012. It originated from the Egyptian rosette bats coronavirus and began to infect humans after passing through an intermediate host, the one-humped camel. For eight years (from September 2012 to January 2020), this pathogen has caused more than 2.5 thousand laboratory confirmed cases of infection, of which about 800 (more than 35%!) Were fatal. Mostly people who came into contact with camels fell ill, but cases of infection from person to person are also known. An outbreak of the disease in South Korea received widespread publicity, where more than 150 people were successively infected from one patient.

From bats to humans

Coronaviruses were discovered back in the mid-1960s. Their name (from the Latin corona – ‘solar corona’) is due to the shape of the virions, which were first seen in an electron microscope by the British virologist and microscopist June Almeida. The “crown” is formed by surface proteins, spikes, which ensure the penetration of the virus into the cell by binding to transmembrane receptors – molecules of the angiotensin-converting enzyme 2 (ACE2, or ACE2).

Since the same 1960s. we gradually began to get acquainted with the usual coronaviruses that have long infect humans. Two of them are alpha-coronaviruses NL63 and 229E; two more – betacoronaviruses HKU 1 and OC 43. The latter include the SARS-CoV-1 SARS virus and the current SARS-CoV-2.

Over the past decade, Chinese and American scientists have studied in detail the genomes of dozens of horseshoe bat viruses, including coronaviruses, so they were able to quickly identify a new pathogen. By January 10, 2020, specialists from the Chinese Center for Disease Control and Prevention (Beijing) have decoded the genomes of 9 SARS-CoV-2 isolates obtained from patients. It turned out that the new virus is genetically different from both the SARS-CoV-1 SARS virus (about 79% similarity) and from MERS-CoV (about 50% similarity). The differences are quite serious.

Isolate SARS-CoV-2 (spherical viral particles, blue) from the first case in the United States. Inside the particles, black dots are visible – cross-sections of the viral genome. Transmission Electron Microscopy. Photo: Centers for Disease Control

However, SARS-CoV-2 is not a snuff box devil at all. All of its characterized isolates turned out to be genetically close (with a similarity of more than 88%) to two previously known bat coronaviruses discovered in 2018 in East China. And the binding sites argumentative synthesis essay outline of this virus with human cells were similar to those of the SARS virus. A little later, the RatG13 strain was identified in bats, which is even closer to the new pathogen, with a similarity of more than 96%.

The first eight complete genomes of SARS-CoV-2 were found to be more than 99.98% identical to each other, indicating its recent appearance in the human population. At the same time, it has not yet been established whether bats were directly an “incubator” for him. A lot of hypotheses have been put forward about the origin of this virus, the most realistic is the one according to which the virus became pathogenic for humans, “passing” through the organism of an intermediate host, most likely, pangolin – a distant “relative” of armadillos.

As for the controversy over the artificial origin of SARS-CoV-2, in favor of this theory, “couch” virologists point to a hybrid described in an article in the journal Nature in 2015, which talks about an experiment that mimics the natural evolution of coronaviruses. The main object of this study is one of the bats coronaviruses, in the genome of which a slightly modified gene encoding the spike protein of the SARS-CoV-1 virus has been inserted. The main modification consisted in the fact that scientists inserted into its genome a region responsible for binding to the human ACE2 receptor.

Bats are carriers of many viruses potentially dangerous to humans, while they themselves do not get sick or die from viral infections. The photo shows a bat in a zoo in Beijing (PRC). Photo: Silly Rabbit, Trix are for Kids

This recombinant virus was constructed at the University of North Carolina (USA) and tested at the Wuhan Institute of Virology (PRC). The features of such a chimera were tested on a cell culture, and it turned out that it is potentially dangerous to humans. By the way, such experiments with the English name Gain-of-Function have been banned twice over the past ten years and twice allowed by the world scientific community.

However, this hybrid virus is significantly different from the pandemic SARS-CoV-2 – the genetic similarity is no more than 87%. According to another “conspiracy” scenario, another bat virus, RatG13, could be accidentally released from the center in Wuhan, the similarity to which in SARS-CoV-2 is much higher.

Conspiracy research is a fascinating and very contagious activity, but it will not help in the fight against a pathogen, in contrast to a competent scientific investigation of the origin and spread of a new infectious agent.

For example, when tested for sensitivity to SARS-CoV-2 of various animals living in contact with humans, it turned out that it reproduces very poorly in the organisms of dogs, pigs, chickens and ducks, but well in ferrets and cats and can be transmitted between by respiratory tract, and from infected animals to humans. This happened on mink farms in Denmark and some other countries, and minks could only become infected with the virus from humans. Therefore, it is necessary to further study wild and domestic animals as possible reservoirs of coronavirus infections.

On the way to man

Viruses cause more than 70% of all infectious diseases in humans and domestic animals. If it were not for industrial antiviral vaccines, then human life would be much shorter, and it would be very difficult for humanity to provide itself with animal food.

Decades ago, it was shown that all the so-called new or emerging infections are the fruit of the adaptive evolution of animal pathogens through the “leaps” from wild animals to domesticated, and then to humans. As evidenced by molecular genetic studies of viral genomes of humans and animals, this statement is also true in relation to the long-known viruses of measles, mumps, rubella, hepatitis C, HIV. Therefore, for strategic purposes in order to prevent human diseases, it is necessary not only to vaccinate animals against the most dangerous diseases, but also to conduct monitoring studies in order to identify the entire gamut of pathogens of wild animals, with the subsequent development of measures to prevent new infections in humans.

It is equally important in the industrial breeding of domestic animals to protect them from pathogens of wild relatives. At the same time, it is necessary to breed farm animals only in closed conditions, and “wild” markets for the sale of live animals should be prohibited. In modern poultry farms, air enters the birds through filters, workers completely change clothes, and feed is disinfected. The same palm civets in China are now also bred only in closed nurseries so that no bat gets there.

How to stop an epidemic

The most important characteristic of any pathogen is its transmissibility (infectivity), described by the basic reproductive number (R0), equal to the average number of people that one sick person can infect. The usual influenza virus has R0 – a little more than one, in its highly epidemic strains – up to 1.4, and in the new coronavirus – presumably from three to five. This indicator is gradually being refined, and the spread is due to the fact that it is defined slightly differently in different countries.

Germany turned out to be one of the most successful countries in overcoming the epidemic situation. In May 2020, German researchers evaluated the R0 decline curve depending on the implementation of various anti-epidemic measures. It turned out that neither the isolation of patients, nor social distancing without the use of masks, nor the closure of schools brought significant results. The maximum effect was obtained from the prohibition of mass events, the introduction of a harsh, with fines, mask regime and the closure of organizations where there is intensive communication. As a result of these measures, the reproductive number dropped below one, and the epidemic began to subside.

The early introduction of anti-epidemic measures and widespread testing in Germany helped to quickly reduce the effective reproduction rate of the virus and prevent many deaths. By: (National Geographic, May 1, 2020)

A similar situation was observed in Austria, Norway, Italy and other European countries. There, too, the closure of schools turned out to be ineffective (schoolchildren actively communicate outside of educational institutions), and the main contribution to stopping the epidemic was made by wearing masks, refusing mass actions, social distancing and isolation of patients. At the same time, in Sweden, where such measures were not introduced immediately and not in full, the mortality rate, primarily among the elderly, turned out to be one of the highest in Europe. And in Iran, Iraq, Saudi Arabia, after the weakening of quarantine measures, a second wave of morbidity began.

Patients with COVID-19 in a clinic in Barcelona (Spain). Photo: Francisco Avia Hospital Clinic de Barcelona

The most striking example of the effectiveness of anti-epidemic measures was given by the United States. We are talking about the actions of the administrations of the two largest American cities: San Francisco and New York. The San Francisco government (California Governor and City Mayor) announced on March 16 that the state was imposing tough quarantine measures, including self-isolation, wearing masks and a near-complete cessation of business activity. In New York, the same was done only six days later. As a result, about 20,000 people died in this largest city in the United States within two months, while San Francisco, the second densest and thirteenth most populous, had only 35 deaths. This clearly shows how large-scale the consequences of even a small delay in the adoption of antiviral preventive measures can be.

In New York City, 77% of the deceased patients diagnosed with coronavirus also had diabetes, lung disease, cardiovascular diseases, including hypertension and asthma, and only 1.5% of the deaths were relatively healthy. For reference: about 66% of people in the United States are overweight or highly obese, which increases the risk of death from coronavirus infection. In addition, about half of the adult population in New York City has high blood pressure.

Photo: Nik Anderson

Covid or not?

Coronavirus belongs to RNA-containing viruses and, in addition to ribonucleic acid itself, also contains lipids and virus-specific proteins. It can be diagnosed in different ways. Firstly, by the presence of components of the virus itself in samples from the patient’s nasopharynx: RNA (reverse transcription PCR, RT-PCR) and viral antigen – surface S-protein (enzyme-linked immunosorbent assay).

On the viral particles of SARS-CoV-2, spike S-proteins are clearly visible, from which the virus got its name. Transmission Electron Microscopy. Image: NIAID

Another way is to assess the components of the body’s immunity, for example, the production of specific antibodies. To do this, simultaneously with the onset of symptoms, the content of “primary” IgM antibodies is measured in the patient’s blood samples. Past disease can be identified by the presence of “secondary” antibodies of the IgG class. These tests are also performed using the enzyme immunoassay.

As of August 20, 2020, 157 different test systems were registered in Russia: 126 detect antibodies to coronavirus, 31 – viral RNA. But why, with such an impressive number, are we talking about the unreliability of diagnostics?

Firstly, in the case of using test systems for viral RNA, it is very important to correctly take material from the nasopharynx, which, moreover, must be quickly placed in a special liquid for the isolation and preservation of viral RNA, which requires special samplers. Secondly, today there are many laboratories where tests are conducted, but not all stages of the testing procedure are performed correctly at all stages.