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Coronavirus: Context, Numbers and Possible Therapies

Coronavirus: Context, Numbers and Possible Therapies

To date, SARS-CoV-2 has infected nearly two million people worldwide, killing over 110 thousand of them, figures that have now reached those recorded during the 2009 H1N1 flu pandemic

It is November 2002 in the coastal province of Guangdong (China), when a man comes to the first aid with flu symptoms and dry cough. An ordinary situation in the hospital which normally resolves in a short time, without serious consequences. In this case, however, the patient does not seem to react well to the drugs, he appears immediately stunned and confused, with a cough that worsens violently compromising his respiratory capacity up to lowering the oxygen saturation to a critical level. Intubation remains the only decision that doctors can take, and a chest X-ray is immediately arranged to understand the cause of this atypical pneumopathy. From the examination, infiltrates in both lung lobes are highlighted; therefore, the transport in intensive care follows the diagnosis of an unknown origin pneumonia. Two days later, the doctor and the nurse who assisted the patient, begin to feel feverish and the next day their symptoms worsen. Laboratory tests conducted on the first patient show that the cause of this pathology is a Coronavirus, more specifically an unknown strain that shortly after will be called SARS-CoV (Severe Acute Respiratory Syndrom by CoronaVirus). This virus, responsible for an often-severe respiratory syndrome (SARS), spread in 33 countries between November 2002 and July 2003, infecting 8,000 people and recording about 800 deaths, with a mortality average rate of 10%. According to the WHO data, for the over 65s the mortality of the virus exceeded 50%, for the under 24 it was less than 1% while in the age groups 24-40 years and 45-64 years it was established respectively at 6 % and 15%. This great variability in percentages, all in all expected, can be explained both by the greater efficiency possessed by the immune system of young individuals, and by the presence of previous pathologies that often represent the main risk of clinical complications in the elderly. In any case, the numbers recorded by the SARSCoV epidemic are certainly not comparable to those we are observing in these days with the current SARS-CoV-2 pandemic. Although both viruses belong to the Coronavirus family and possess a high genetic similarity degree, epidemic waves follow different courses.

To date, SARS-CoV-2 has infected nearly two million people worldwide, killing over 110 thousand of them, figures that have now reached those recorded during the 2009 H1N1 flu pandemic, with its more than 100 thousand deaths (according to WHO between 100 to 400 thousand only in the first year).

In short, history repeats itself, as it has been repeating for centuries now. Suffice it to say that in the twentieth century there were 3 flu pandemics, including the Spanish flu of the ‘20s which, with about 30 million deaths, was one of the most devastating pandemics in history. Even though particularly aggressive viruses have sometimes appeared, the human species has always been able to defend itself by developing powerful defense mechanisms over the evolution course. When an external agent (such as the virus) manages to come into contact with human cells, the immune system responds immediately and powerfully with a nonspecific series of actions that have the purpose of suppressing the pathogen and alerting the whole immune system of the threat encountered. This innate immunity represents the first line of defense that the body possess, but not the only one. In fact, as soon as this generic response is expressed, some specialized cells leave the infection site to reach the lymph nodes where they activate the second line of defense, adaptive immunity. The latter constitutes the greater efficacy and selectivity defense possessed by the human body against pathogenic species, such as SARS-CoV-2. This immune response can count on a powerful and extremely specific molecular weapon: antibodies. These small proteins, made to measure to challenge the infectious virus, ripen within a few days and, once ready, cover the entire surface of the viral particle, neutralizing and eradicating the threat itself. Unfortunately, the antibodies, to be ready to perform their function, can take up to a couple of weeks and, before then, the body can only count on the innate response. This is where the problems begin.

If on the one hand this type of defense is immediate, on the other hand it is non-specific and therefore does not distinguish between the parasite and the host organism cells.

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In the specific case, moreover, SARSCoV-2 further aggravates the situation by excessively stimulating, especially in the elderly, the inflammatory cytokines production pattern.

This leads to intense inflammation of the involved tissues which, in the case of Covid-19, are the pulmonary alveoli. When the tissue is inflamed edema is formed which, pouring into the alveoli themselves, compromises the patient’s respiratory capacity up to the point that mechanical respiration is necessary. When edema is excessive, despite the help of respirators, the alveolar gas exchange surface is compromised to levels that are no longer compatible with life. In these cases, unfortunately, nothing can be done.

During an epidemic, human losses are inevitable and always dramatic, however we are part of the terrestrial ecosystem and towards us, as well as towards all other life forms, nature is brutal. However, unlike other living species, we have medicine. A great tool that in this case can provide help on at least two fronts: vaccines and antiviral therapies. However, the medicine is not perfect and takes time to provide effective treatments.

Vaccines are perhaps the most awaited solution since they are able to stimulate the adaptive response and therefore provide definitive immunity, but they have a weak point: they take a long time to be developed and produced on a global scale. For this reason, biotech industries need to simultaneously launch several test versions of the vaccine in order to increase the chances of obtaining an effective version, within a reasonable time. As reported by a Science article, from March 16 the Moderna biotech industry is already testing an experimental version (based on mRNA) on 45 volunteers; at the same time, China’s CanSino Biologics, with the participation of the Chinese military’s Institute of Biotechnology, has launched a small clinical trial to evaluate the safety and ability of its vaccine to trigger an adequate immune response. Pietro Di Lorenzo (CEO of the Italian biotech Advent-Irbm), in collaboration with the Jenner Institute of the Oxford University, has instead announced that by the end of April he will launch a trial on 550 healthy volunteers and that, if phase I is successfully passed, he plans to make the vaccine usable for healthcare professionals and security forces as early as September. Meanwhile, other companies are testing their versions, each with its own technology (from mRNA to the protein subunit, via non-replicating vectors), thus offering an extremely broad spectrum of options. Both Moderna and Johnson & Johnson have said that if everything goes according to plans, they will be able to launch trials with around 5,000 individuals by the end of autumn and, in the following two months, to determine if the vaccine works. For drugs, however, the situation is simpler. If the development of a new specific antiviral for SARS-CoV-2 presents the same problems as vaccines, at the same time in the hope to find one, among the drugs already spread on the market, which shows a good efficacy against this Coronavirus. In fact, hearing the news, it would seem so.

A couple of weeks ago, the Italian virologist Roberto Burioni has announced that a study, conducted at San Raffaele Hospital in Milan, showed promising results.

The in vitro efficacy, against viral replication of SARS-CoV-2, of a drug used in the 1950s for the treatment of malaria, Plaquenil, was assessed and demonstrated. A work from 2005 had already shown its in vitro ability to inhibit the replication of the SARS virus, cousin of the current Coronavirus, and it is thanks to this study that the molecule was taken into consideration and tested in the laboratory. This does not mean that the drug is really effective in infected patients, but it is certainly a significant step that leaves room for some optimism.

It is hoped that subsequent clinical tests will give concrete results but, if this does not happen, there are still other promising molecules being tested: the monoclonal antibody Tocilizumab (used in the treatment of rheumatoid arthritis); the anti-viral Remdesivir which has shown the ability, similar to Plaquenil, to inhibit the replication of SARS-CoV-2 in vitro; the antiparasitic Ivermectin, already in use to combat scabies but which has also proven effective against some viruses such as HIV, Dengue, West Nile etc. Finally, even if it does not fall into the “drugs” category, the plasma treatment, deriving from donors previously cured of the infection (and therefore rich in neutralizing antibodies), has shown the ability to mitigate clinical symptoms in just three days. In short, an interesting range of therapeutic options that give hope and, quoting the words of the Italian virologist: “I would not be surprised if good news arrived in the coming weeks”

Bibliography:

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