Innate immune defense: Corona-positive, but not contagious – how is that possible? – Knowledge

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A positive corona test still means: quarantine, caution, fear too. There are Covid 19 patients for whom the polymerase chain reaction test, or PCR test for short, still turns out positive weeks after the onset of symptoms – often even though they have long been fine. How can that be?

“In such cases, the virus only reproduces at a low level. However, since the genetic material of the viruses is greatly multiplied in a PCR test until it can be detected, the test is still positive, ”explains the virologist Ulf Dittmer, director of the Institute of Virology at the Essen University Hospital. “Since the number of newly emerging viruses is very small, those affected are still not dangerous for their environment.”

But how accurate are the current test procedures? “The tests currently in use, the PCR test and the antigen test, detect fragments of the virus RNA in swabs or lung lavage fluid, or virus proteins of SARS-CoV-2 in the antigen test. They don’t measure the number of intact and infectious viruses, ”says Hans-Dieter Volk, Director of the Institute for Medical Immunology at the Charité in Berlin.

PCR tests are the gold standard

The PCR tests are still regarded as the gold standard, precisely because they are particularly sensitive, also significantly more sensitive than the antigen tests. They replicate the genetic material in the sample over several cycles, expressed as a CT number. And they keep checking whether the virus’s gene sequence is present. The more cycles it takes until the virus is detected, i.e. the higher the CT number, the lower the viral load or virus concentration in the sample.

It sounds as if it is comparatively easy to tell whether a patient has many or few viruses on their mucous membranes. However, cycle numbers determined with different device types cannot be directly compared. The number of cycles from which a test is considered negative also varies from device to device – it is usually between 35 and 40.

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“We are also dealing with smears that are difficult to standardize,” regrets Dittmer. “Sometimes no nasopharyngeal swab is taken, but only the cheek mucous membrane in the mouth or through the mouth in the throat.” Most viruses, however, are located in the nose. However, the smear through the nose is often found uncomfortable. The PCR test can only provide an approximate value for the viral load, if at all.

Viruses there, humans there. When the two come together, there is often a problem. But not always. What matters is how …Foto: David-W- / Photocase

The duration of quarantine measures cannot therefore be reliably derived from it. In any case, an infection test with intact viruses in a cell culture would be better. But it is far too time-consuming for large-area use.

High viral load in the first 5 days of symptoms

According to a current data analysis, published in the medical journal “Lancet”, no study has found a relevant virus excretion later than nine days after the onset of symptoms, although parts of the virus were often detectable for months afterwards. A particularly large number of viruses are therefore excreted in the first five days of symptoms.

In most cases, the viral load is directly related to the severity of the disease. In Ischgl, for example, many skiers have been infected in the Corona hotspot, the “Kitzloch”. The bartender, who was suffering from cold symptoms at the time, whistled with a whistle to bring the drinks to the table. Apparently, the violent blowing, similar to singing, released small droplets laden with virus particles into the air.

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The viral load was so high here that healthy younger people are seriously ill because they have gotten a lot of viruses and their immune system was overrun by Sars-CoV-2. At least that is the interpretation of the events at the time. But it is usually not that simple after all: “There are patients who only have a small viral load but a severe Covid-19 course and vice versa,” says Hans-Dieter Volk. And about 40 percent of those infected stay healthy, even though they have a virus count similar to that of people who get sick. How is that possible?

If the course is mild, antibodies in the blood only briefly

“No less important than the level of the viral load is how the immune system fights it,” said Volk. The innate defense against viruses relies on type 1 interferon, an antiviral cytokine, among other things. “If this defense measure works well, then the immune system can quickly reduce the viral load and has the infection under control.” After the first two to three days, the patient is “fine again,” says Volk.

But there is also a catch here: “With such a mild course with only a few symptoms, antibodies are only briefly in the blood, that is, there is only a short infection-preventing immunity against Sars-CoV-2, since the acquired immune system is hardly switched on The “acquired” immune system, now usually referred to as “adaptive”, is that part of the defense system that first has to get to know an intruder and then, with a delay, produces very special defense molecules and cells.

If the innate immune defense does not work quickly enough, the virus initially multiplies strongly and infects more and more cells. Then a lot of antibodies are also produced. As the viral load increases, the acquired immune system tries to eliminate the viruses in the cells, but destroys cells in the process. The more tissue is affected by this “friendly fire”, the more dangerous the immune system’s reaction becomes for the body. There is a built-in brake to prevent excessive immune responses to prevent inflammation from becoming too strong.

Danger of the “cycotine storm”

But apparently this brake doesn’t always work. Then immune cells, even if the actual pathogen is no longer a major threat, constantly release large amounts of inflammatory messengers, so-called cytokines, which in turn activate other immune cells. There is an excessive, self-reinforcing inflammatory reaction, a “cytokine storm”.

A high viral load usually correlates with a severe course. But there are other factors as well.Photo: Jens Büttner / dpa

“This is why these patients are now being treated at this advanced stage of the disease with drugs such as dexamethasone, which suppress the immune system,” says Dittmer. It is speculated whether, in addition to the cytokines, pro-inflammatory proteins could also play an additional driving role.

But what “load” a pathogen ultimately means also depends on other factors. Respiratory viruses such as Sars-CoV-2 spread better in cold winter than in warmer seasons. There are several reasons for this, including the fact that they simply cope better in dry, wintry air. And: “The performance of the interferon defense is temperature-dependent,” says the Essen virologist. If you inhale cold air, the temperature in the nasopharynx drops to 32 to 33 degrees Celsius, which reduces the efficiency of the interferon defense system. Then a smaller dose of virus is enough for an infection.

Simple remedies for high viral loads

Therefore, it is advisable to wrap a scarf around the nose and mouth area on cold days outdoors. Warm heating air, on the other hand, dries out the nasopharynx and mucous membranes, which is also bad for the interferon defense. The conclusion: drink a lot and use a nasal ointment. “With these simple measures, anyone can achieve an increase in the virus dose necessary for an infection,” says Dittmer.

The other strategy is and will be to keep the virus dose as low as possible, says Volk. For the Berlin immunologist, one thing is clear: you should protect yourself and others by consistently wearing a mask. Dittmer also sees it this way: “We need the masks because in everyday life it is not always possible to keep a minimum distance of 1.50 meters.”

If everyone were to wear FFP-2 masks, the virus would have a much worse chance of spreading.Photo: Hauke-Christian Dittrich / dpa

The layers of fibers that make up the masks capture large and small virus-laden droplets. Tightly woven cotton in fabric masks, however, performs significantly worse than non-woven synthetic material with crisscrossed, electrostatically charged fibers of different thicknesses, such as in FFP2 and FFP3 masks (FFP stands for Filtering Face Piece).

FFP2 masks can filter out about 90 percent of the virus-laden droplets from the air we breathe. FFP3 masks even filter 95 percent. “If everyone were to wear these masks, the number of infections would look very different,” said Volk. However, this only applies to masks without a valve, because they let out breath unfiltered.

But can mutations mean that a lower viral load is sufficient after all, or that the immune system can react worse? Viruses mutate, that’s completely normal. The flu virus, for example, does this much faster than Sars-CoV-2. “Every time the virus replicates in a cell, small copying errors can occur that may change the virus properties, but they can also be completely irrelevant,” says physicist Richard Neher from the Biozentrum of the University of Basel.

Permanent mutations

A mutation is not at all worrying per se. “It is pure scare-mongering when mutations are constantly labeled as dangerous.” The D614G mutation in the gene for the spike protein of Sars-CoV-2, which has now dominated the world, has significantly increased the infectivity of the virus in cell cultures and animal experiments. However, it has at least not changed its pathogenicity, i.e. the disease-causing effect, as researchers recently reported in Science.

The mutation makes it easier for the viruses to penetrate cells and use them to multiply. They spread faster, especially in the nasal mucous membrane – but this could also mean that the infected person excretes more viruses. “It cannot be predicted whether this will always be the case with future mutations,” says Neher. The four mutations in the spike protein found in minks in Denmark also make the virus less pathogenic.

“But one of the mutations, the Y543F, affects a region of all places where an important, highly active antibody normally docks,” says Dittmer. “This mutation could therefore reduce the effectiveness of a vaccine if it spreads among people.” The mink themselves produce incredibly large amounts of virus and could “easily infect” people, says Dittmer.

Another concern is that vaccinations will also encourage mutations. In fact, they increase the pressure on the virus to change. “If people become immune to Sars-CoV-2 through a vaccination, then the virus has to change the exact target location of the vaccination in order to survive,” says the Essen-based virologist Dittmer. “That is why it is so important that a vaccine has multiple targets.”



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