Blur spots persist in the portrait of the virus

Never has a new virus been the subject of as much research, studies, analyzes as SARS-CoV-2 in such a short time. But if information has accumulated since the end of 2019, essential questions remain to try to understand what the planet is facing. At first, we imagined that it was only a simple coronavirus, like the others: a little pathogenic, fairly contagious, but relatively manageable. Everything exploded. From an infectious pathology, clinicians have discovered that it is transformed and becomes an immune pathology, even later a cardiac one. And the Covid-19 surprises with its mysteries, with more than 80% of people infected without any real manifestation, 20% with more or less important symptoms, of which 5% will go to intensive care. These proportions, for several weeks, have hardly changed. But what about the rest? Of its transmission? New symptoms? Healthy carriers? These questions still do not have complete answers. “It’s like an iceberg, we only see and we can only understand the emerged part”, tells us a member of the Scientific Council. Overview, as France begins its fifth week of containment.

How is the virus transmitted?

Friday, April 3, Anthony Fauci, director of the United States Institute of Infectious Diseases and member of the White House task force, relayed by President Donald Trump, sowed a global stir. Can the Covid be transmitted “When people are just talking”, as this respected scientist claims? “Everything takes on incredible proportions when Trump opens his mouth”, quipped Professor Xavier Lescure, an infectious disease specialist at Bichat Hospital. “An American study certainly mentioned transmission by too close discussion but if this were the case, we would have a basic reproduction rate (RO) of the coronavirus close to that of measles, smiles Karine Lacombe, head of the infectious diseases department at Saint-Antoine hospital. Clearly, each infected person could contaminate 10. We are far from it. For experts, the RO rate of Covid-19, without confinement, is rather between 2 and 3. ” Professor Lacombe insists: “The contamination is mainly done by the droplets, the cough, the sneezing, the hand-held contacts.” If the Director General of Public Health, Jérôme Salomon, also mentions contact with inert surfaces, this point remains under debate. Karine Lacombe: “On inert surfaces, we remain questionable.” Xavier Lescure, careful: “Inert surfaces are a real hidden trap, probably the forgotten link in contact transmission.”

Contagious from when and for how long?

This is a crucial point to break the dynamics of the epidemic. When and for how long should patients be isolated to stop the spread of the virus? In this area, knowledge is becoming more precise. In a study published recently in Nature, German researchers have shown that if there were traces of the virus in the patient’s larynx seven days after the onset of symptoms, the pathogen did not replicate. “It means the person is no longer contagious, says Professor Lacombe. There is a consensus that an infected person can be contagious one to two days before symptoms appear, and for seven to ten days after. “

There remains the question of healthy carriers, about 30% of all infected. As they do not cough or sneeze, their contagiousness is estimated to be very low. But it is not necessarily zero to believe the first results of an Inserm survey of 300 patients, launched in January after the first cases in Contamines-Montjoie, in Haute-Savoie: the postillions and nasal excretions of the asymptomatic contain viral particles capable of infecting other people.

What are the symptoms ?

The range of Covid-19 symptoms has unfortunately grown significantly since its arrival in Europe. If a dry cough, with fever and fatigue are the most common signals, others, which had not been reported by the Chinese, have confused infectious diseases. “It’s a shock, we didn’t see it coming, says Professor Gilles Pialoux, infectious disease specialist at Tenon Hospital. The coronavirus is the cause of neurological disorders. In some cases, this results in loss of taste and smell. Above all, 88% of patients in intensive care have neurological manifestations, cognitive disorders: they are disturbed, confused. ” A geriatrician from the Pompidou hospital: “If in most cases these symptoms disappear spontaneously after seven to ten days, we still do not know the degree of recovery of the elderly, sometimes already fragile.”

Another surprise, “For six weeks, we have seen acrosyndromes, pseudo-frostbite at the extremities of the limbs”, reports Professor Lescure. This is cause for concern enough for the National Union of Dermatologists and Venerologists to launch an alert on April 8 for skin manifestations linked to Covid-19 infection – acrosyndromes, sudden onset of persistent, sometimes painful redness and temporary hives lesions.

Who is at risk?

Since the publication on February 24 of a large study by the China Center for Disease Control and Prevention, the profile of severely ill patients has been clarified. Professor Pialoux: “What strikes me is that patients admitted to intensive care are often diabetic, overweight or even obese.” A finding shared by all the hospitals that receive Covid-19 patients, French and European. And this is a real surprise because the first Chinese ascents only documented “classic” risk factors, such as age and the presence of comorbidities (high blood pressure, cardiovascular problems, pulmonary insufficiency, severe diabetes, etc.)

For the past two weeks, research work has confirmed clinical observations. A study published in late March in the Journal of the American Medical Association by Italian researchers, involving 955 deceased patients, established that 35% were diabetic. “We thought that only severe diabetics were concerned. Not at all, small diabetics are too. We have even discovered diabetes during hospitalization ”, points to Professor Lescure.

1er April, a new Chinese study published in The Lancet confirmed the role of the body mass index: out of 383 coronavirus patients admitted to a hospital in Shenzhen, 42% were overweight or obese. Researchers conclude: overweight people have an 86% chance of developing a severe form of Covid-19. Those who suffer from obesity have “Showed a 2 to 42 times higher probability of developing severe pneumonia” than other patients. The danger is real even for young patients: “Obesity is often the only risk factor for patients under 50 years of age in intensive care in Bichat”, says Professor Lescure. What confirms Professor Lila Bouadma, resuscitator at Bichat Hospital : “We have patients, young people, who were in perfect health, with only one weight problem.” A phenomenon that has not yet been elucidated. “Maybe it’s due to the fat cells that let the virus pass more easily”, wonders Karine Lacombe. It is also possible that being overweight amplifies the inflammatory reactions induced by the presence of the coronavirus in the body.

Another characteristic of heavily affected patients, which was already reported in the first Chinese study, caught infectious disease specialists short: gender inequality. “The coronavirus infects men and women in the same proportions but 80% of our intensive care patients are men”, notes Professor Lescure. This difference in resistance between the two sexes is not elucidated. Assumptions flourish. Researchers are particularly interested in the role of an enzyme (ACE2 installed on the X chromosome), essential in the production of estrogen, known for its anti-inflammatory influence.

How is the infection going?

The pattern is often repeated identically. In one in five cases, Covid-19 infection requires hospitalization for respiratory distress. A majority of these severely affected patients then have severe pneumonia with bilateral involvement, according to the WHO. Respiratory support is not always enough to overcome the infection. About seven days after the first symptoms appear, some patients suddenly get worse, with an inflammatory over-reaction of the immune system, known as the “cytokine storm”. However, this runaway can be fatal: instead of defending the body against inflammation, cytokines destroy not only infected cells but also healthy tissue in the lungs, heart or kidneys. Assessment: 20% of severe forms of Covid-19 have heart damage linked to the immune reaction. Professor Lacombe: “Compared to the first few weeks, the change is spectacular. We are facing an immunological disease much more than viral as we might have thought. It’s new. ” Professor Pialoux completes: “Like the first Chinese death on French soil, 10% of intensive care patients die not from the coronavirus directly but from pulmonary complications and sometimes pulmonary embolism. Such vascular complications have never been seen with influenza or SARS. “

Professor Lescure summarizes: “Clinical observation has allowed us to identify three sides of the disease. The first is infectious, viral. But in a certain number of serious patients, the inflammatory aspect becomes preponderant after the runaway of the immune system. The last side is vascular: the disease causes microvascular damage, thrombosis, which is supposed to be linked to inflammation, without being certain. “

When are you immunized and for how long?

This is a key point, and of particular interest to the High Scientific Council, currently mobilized on possible scenarios of deconfinement. In this area, he must do with good news, very bad news and a lot of uncertainty.

The good news first. According to a study by German researchers on the replication of the virus in the upper respiratory tract published in Nature 1er April, patients begin to produce antibodies seven to fourteen days after the first symptoms appear, and their viral load slowly decreases. “We think these antibodies are neutralizing, and therefore protect against re-infection, says Professor Lescure. It is a clinical hypothesis, not scientific certainty. But apart from a few cases reported in China at the start of the epidemic, which may have been only false positives, no one has seen any cases of reinfection. “

Next is the big tile. According to the modellers of the High Council, the French are not more than 10 to 15% to have been in contact with the virus until now, including in areas with high incidence such as the Grand-Est or the Ile-de -France. And this projection is undoubtedly still optimistic: the test campaign launched in the cluster of Oise concluded with a collective immunity of hardly more than 7%… In any case, we are very far from the rate of 60% of protected persons, floor threshold to claim this “group immunity” which would ward off the risk of a second wave of Covid-19. “In terms of public health, this is very problematic, confirms Xavier Lescure. A brutal lifting of containment would inevitably revive the epidemic. “. But too late, the problem could get worse. Because if a healed individual is immune, it is not known for how long …

Eric Favereau


Nathalie Raulin


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