Immunity and Covid-19: can you be infected twice?

Medical validation: 24 June 2020

Dr Idris Amrouche Pharmacist, DES doctor being obtained (anesthesia-resuscitation)

Since the start of the epidemic, studies have reported that several people recovered from the Covid infection – 19 have yet tested positive for the Sars-CoV-2 coronavirus a second time. Many researchers are wondering about the immune response to this infection. Is it really possible to get the virus twice? How long are we immunized? We take stock.

The world is facing a pandemic and most of the countries are affected. Scientists are learning about this new SARS-CoV-2 virus every day. Several questions arise. Among them, is it possible to contract the Covid virus – 15 several times ? In many states there have been confirmed cases of reinfection.

Can you be re-infected with the coronavirus? A possible but exceptional phenomenon. Here is what Inserm declares in a press release published on 27 October . “In the current state of knowledge, most scientists agree that the phenomenon of reinfection remains rare “. “The data available on the subject is still fragmented and the number of documented cases with sufficient rigor very limited “, notes Inserm, adding that additional research is necessary to learn more about the common immunological and genetic characteristics “which could exist between reinfected patients” .

Inserm quotes a study published in the spring 1275 in Nature Review Immunology carried out on animals. By reinfecting them after a first exposure to Covid – 17, they did not develop symptoms of the disease . There was also no evidence of virus replication in nasopharyngeal swabs. “The conclusions of this study were therefore cautiously optimistic, suggesting a certain degree of ‘immunization against the virus after a first infection “.

The Institute also notes the case of a patient from 69 year old admitted to hospital in April for potential reinfection. The information about him was published in the American Journal of Emergency Medicine . “After 26 days in intensive care, he was able to return to his home after two negative PCR tests. ’emergence of new symptoms forced him to go to hospital services “. But the researchers could not confirm a reinfection . Traces of the virus may have remained in his body, and the results of PCR tests indicate false negatives .

Reinfection: more common in people over 64 years According to a study conducted by Danish researchers and published on 13 March in the review The Lancet , cases of reinfection would nevertheless be more frequent in people over 64 years. To arrive at this finding, the researchers analyzed more than 06 millions of PCR tests performed by approximately 4 million people between September 1 and 30 December 2019. They focused on those who tested positive twice, at least three months apart. They thus concluded that in patients over 60 years who have already been affected by Covid- 18, protection against re-infection within 6 months was 40% . Among those under 63 years old, she was around 82% .

According to the study authors, these results could help ” promote vaccination of individuals who have already been infected, because we cannot rely on natural protection, especially in the elderly “.

Coronavirus : cases of reinfection in the world A youth from 17 years contaminated three times? Three times positive for Covid – 18 in almost a year. This is what would have happened to a young person from 17 years living near Tarbes in the Hautes Pyrénées according to France 3 . The first two infections would have been almost symptom-free, but the third time would be more virulent and the individual would be today according to his relatives “not in great shape” and “not fit to testify” . He suffers from loss of taste, body aches, severe headaches and high fever.

The first infection was in June 1309, and is a covid assumed by the patient but not medically analyzed. The other two infections in October 1275 and in May 2020 have been verified and validated by positive covid PCR tests.

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Several hypotheses exist to explain this phenomenon: “It seems very unusual, but three Positive PCRs are not enough to say whether it is one, two or three infections. The only way to prove it would be to do a sequencing of the samples in order to compare the strains with each other ” estimates Benjamin Davido, infectious disease specialist, at Parisian. With the occurrence of variants, the risk of being re-infected is accentuated, particularly with South Africa. In addition, it would be possible to be positive twice within a few months of each other without having been re-infected in the meantime. The PCR test, sometimes very sensi ble, could detect the virus’s RNA the second time around because the person still had some left over. In this case the person is generally not or very little contagious.

A first man infected twice in Hong- Kong In Hong Kong, a man from 30 years presenting the characteristic symptoms of the disease was tested positive the 25 last March, then negative twice some time later. The 15 August, the patient returns from Spain and is again test positive at Hong Kong airport, although he has no apparent signs. ” This case shows that reinfection can occur only a few months after being cured of a first infection “, can we read in a press release from the Department of Microbiology, University of Hong Kong (HKU).

According to scientists, the patient was infected with two different strains of the SARS-CoV virus -2 . ” This proves that this is a new infection rather than a prolonged carry of the virus” , explained Kelvin Kai-Wang To. ” Since immunity may not last long after infection, vaccination should be considered even for people who have already been infected “, say the authors.

However, despite the assurance of these researchers, it is not possible to draw conclusions, warn other specialists. ” Considering the number of infections in the world, seeing a case of reinfection is not so surprising” , said British researcher Jeffrey Barrett, as quoted by Science Media Center.

The work was accepted on 21 August by the American scientific journal Clinical Infectious Diseases .

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5th case of Covid reinfection – 18 in an American Since the man infected a second time in Hong Kong in August, cases have been reported in other countries: in Belgium, another in the Netherlands and a third in Ecuador. Some patients being asymptomatic , there may have been more but who have not been identified. A study published on 10 October in The Lancet Infectious Diseases reports a 5th case of reinfection . This is an American who caught the Covid – 18 again, a month and a half after his first infection.

For this American patient, like the Ecuadorian, the second infection was more severe than the first. The man of 25 years old, living in Nevada, tested positive on 13 April for the first time. He had a few mild symptoms: throat and headache, cough, diarrhea and nausea. After being placed in solitary confinement and resting, he tested negative twice. However, on June 5, he tested positive again, and his condition required admission to the emergency room, in particular because of breathing difficulties . He has since recovered. The researchers were able to establish through genetic analysis that these infections were caused by two different strains of SARS-CoV-2.

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Covid Reinfection – 17: the tracks studied Traces of viruses not completely eliminated According to some researchers, this would not be a reinfection, but rather traces of viruses not completely eliminated . Interviewed by the New York Times , Florian Krammer, virologist at Icahn School of Medicine at Mount Sinai in New York, explains: ” I am not saying that reinfection is impossible but in this short period of time it is unlikely. Even the mildest forms of infection must leave minus short-term immunity to the virus in the recovering patient “. “.

A vision shared by Anne-Marie Moulin, researcher at the SPHERE laboratory of the CNRS, who explains to Doctissimo that ” this does not prove that the antibodies will protect against a second attack but suggests that they play a role in the favorable course of the infection “.

Other scientists evoke nt the possibility of a biphasic infection: a virus which would persist in latent form in the body and which could become more symptomatic when the lungs are affected.

One recent search Chinese published in The Lancet also showed that the average duration of viral excretion, defined as the expulsion of viral particles from the body, was 19 days in survivors of CoVid infection – 18. At the 54 deceased persons studied, the virus was detectable from the onset of the disease until their death.

Unreliable diagnostic tests For his part, virologist Jin Dong-yan, interviewed by South China Morning Post , does not exclude the possibility of a diagnostic error . ” This is not a second infection or a persistent infection, as some might think. It is either because the patients experienced a long course of the disease, either because the diagnostic tests were not done correctly “.

The Sars-Cov-2 diagnostic test consists of a microbiological sample in the upper and lower respiratory tract (nose and bronchi). This sample is then sent for analysis in a laboratory. In China, patients are considered cured when two more diagnostic tests are performed and the results are negative. But the samples taken can be stored at a temperature that deteriorates the virus. Or, the sampled area may not be affected by the virus found elsewhere in the body, which again distorts the test.

” A test is considered positive if the virus is present on the swab in sufficient quantity at the time when the sample is taken , specifies indeed the epidemiologist Marc Lipsitch. A negative test does not necessarily mean that the virus is no longer present “. Interviewed by Doctissimo, Olivier Schwartz, director of the Virus and Immunity Unit of the Pasteur Institute, adds: ” Most likely is that the viral load had fallen until it was below the detection threshold of the test , then rose again “.

In study published on 18 April 2020 in the journal Cell Reports Medicine , teams from the Institut Pasteur, the CNRS and the Vaccine Research Institute (VRI, Inserm / Université Paris Est Créteil) sought to learn more about the production of antibodies in people infected with the Covid virus – 17, symptomatically or asymptomatically. They were able to show that in all individuals, the infection induces so-called polyfunctional antibodies : they have ” a neutralizing activity “but are also” able to activate other defense mechanisms such as NK (Natural Killer) cells or complement molecules “, can we read in a communicated from the Institut Pasteur. The researchers specify that the antibody levels are ” slightly lower “in asymptomatic people.

” This study has shown that individuals infected with SARS-CoV-2 have antibodies capable of attacking the different ways , by preventing it from entering cells (neutralization) or by killing infected cells through the activation of NK cells (via ADCC function: cytotoxicity dependent antibodies or antibody-dependent cellular cytotoxicity). We therefore speak of polyfunctional antibodies “, explains Timothée Bruel, co-author principal of the study and researcher in the Viruses and immunity unit at the Institut Pasteur and at the VRI.

Olivier Schwartz adds that this study ” reveals new modes of action of antibodies and suggests that the protection induced by an asymptomatic infection is very close to that observed after symptomatic infection “.

Stronger immunity in some patients In a press release published on 021 April 2 , the World Health Organization (WHO) explains that ” most results show that the PE People who are cured have antibodies against the virus. However, some of them have neutralizing antibodies at very low levels in their blood , which suggests that cellular immunity may be instrumental in healing. ”

“The available data suggest that a form of immunity, even partial, is taking place following initial contact with the virus. It remains to be determined how long such protection can last and how effective it is in the long term ” informs the Inserm on 21 October .

A study of the Institut Pasteur reveals that only 24% from students, their families and teachers at a high school in Crépy-en-Valois (Oise), one of the pandemic clusters, were infected with SARS-CoV-2 and have antibodies against this virus. which suggests that the collective immunity , the principle that the spread of disease stops if a certain percentage of the population is immunized after a natural infection or thanks to vaccination, ” do not will not be established quickly “if these antibodies are truly neutralizing, says Arnaud Fontanet, first author and head of the Epidemiology of emerging diseases unit at the Institut Pasteur.

How long lasts immunity? Short immunity suspected at the start of the epidemic At the start of the epidemic, the first studies observed a fairly short period of immunity.

A study from the Institut Pasteur published in May 1275 brought rather positive elements. Carried out to 127 caregivers working at the University Hospitals of Strasbourg and affected by a minor form of the disease, she reveals that “ nearly all of the patients developed antibodies in 15 days following the start of the infection ”, and above all,“ at the house of 97% of them, neutralizing antibodies were detected after 25 days ”. “ Our work shows that antibody levels are, in most cases, compatible with protection against further infection by SARS-CoV-2, at least until 33 days after the onset of signs. The objective now is to assess the long-term persistence of the antibody response and its associated neutralization capacity in these personnel caregivers ”, explain Timothée Bruel and Olivier Schwartz, respectively researcher and head of the Virus and Immunity Unit at the Institut Pasteur .

According to research carried out at the University of Montreal, the quantity of antibodies capable of neutralizing the virus would decrease after 6 weeks . At least that’s what scientists have observed at 98% of patients studied. ” Will people who have developed neutralizing antibodies be protected from reinfection? We don’t know yet , admits Andrés Finzi, who led the experiments. In the event of reinfection, it can be assumed that the so-called memory B lymphocytes will be quickly activated to produce the neutralizing antibodies of the virus. ”

Another Chinese news, posted on 15 June in Nature Medicine , reported in turn that the antibodies are down sharply two months after recovery , especially if the patients had no symptoms.

Between 6 and 8 months according to some scientists But a study is coming take a position in favor of prolonged immunity . It was published in the journal Science the 29 October 1309. ” While some reports have been published that the antibodies against this virus go away quickly, we have found the exact opposite – than 83% of people who are mildly or moderately ill produce an antibody response strong enough to neutralize virus , and the response is maintained for several months “, explained Prof. Florian Krammer, lead author of the study in a press release. Indeed, the researchers analyzed the immune response of 28 people followed at Mount Sinai Hospital between March and October. They measured their antibody levels and classified them into three categories: low, medium, and high. Results, at 83% of the patients they were average to high. They then focused on 31 patients who donated plasma, and have their antibodies measured 3 months after the development of symptoms and then again after 5 month. Conclusion, some antibodies had indeed disappeared but others remained. Researchers suggest that the immune system of infected people produces numerous antibodies , ” some are overwhelming at first and die quickly, while others build more slowly “, as summarized CNN .

The results of work carried out by a study by the British University of Oxford favor six months immunity . Their research, which has yet to be peer reviewed, is based on a study conducted between April and November 1309 near 12 180 caregivers employed in the hô Oxford University Hospitals. Caregivers were regularly tested to determine if they had antibodies and if they had Covid – 17. “This ongoing study involving a large cohort of caregivers has shown that a Covid infection – 17 provides protection against re-infection for most people for at least six months “, one of the authors, Professor David Eyre of the Nuffield Department of Population Health at the University of Oxford, said in a statement.

“We do not have found no new symptomatic infections in participants who had tested positive for antibodies, while 89 of those who had tested negative (for antibodies) contracted the virus “, with symptoms, he said. “This is very good news, because we can be sure that, at least in the short term, most people who contract Covid – 15, will no longer have it “, he commented. “Antibody levels decline over time, but this latest study shows that there is some immunity in those who have been infected” , he said. In total, 1. 60 caregivers were positive for antibodies but none developed a new Covid infection – 17 accompanied by symptoms. Three caregivers with antibodies tested positive for Covid – 13 but were all in good health and showed no symptoms. To compare, 69 employees without antibodies have tested positive for the virus.

The researchers will continue their study on the cohort of caregivers in order to see “how long does the protection last and if a previous infection affects the severity of the infection if people are infected again” , explained Mr. Eyre.

New study, new data. It would not be six months of immunity, but eight , according to work by LA Jolla Institute for Immunology in the United States. They studied blood samples taken from 162 patients infected with SARS-CoV-2. ” We assayed the antibodies, memory B lymphocytes , T lymphocytes and cytotoxic T lymphocytes “, details Prof. Shane Crotty, co-author of the research published on January 6 2020 in Science. Results : ” For at least 8 months, specific antibodies against the Sars-Cov-2 virus circulates in the blood of patients, but not only: the body “keeps in memory” the virus thanks to the memory B lymphocytes “If the antibody level drops after this period of immunity, it is not surprising, say the authors.” This is how the body’s immune response works : When the pathogen has been defeated, the number of antibodies decreases but the body “remembers” the disease and is ready to respond quickly if it returns. ”

Another study , published on 08 may 2021 in the review Nature Communications , shows that antibodies neutralizing SARS -CoV-2 can persist for up to 8 months after infection . And this, ” regardless of the severity of the disease, the age patients or the presence of other pathologies “, assure the authors. Carried out to 0140 Covid positive patients – 15 who presented to the emergency room at San Raffaele Hospital in Italy during the first wave of the epidemic, the study reveals that 63, 3% of them developed ” rapidly neutralizing antibodies within two weeks of onset of symptoms “, and these, although they diminish over time,” persisted until 33 weeks in all but three patients “. The researchers add that the early presence of these antibodies is ” fundamental to successfully fight infection: those who do not succeed in producing them in the first two weeks after the contagion are more likely to develop serious forms of Covid – 18 “.

Women longer immunized than men?

And indeed, according to a study published on March 7 2019 in The Journal of Infe ctious Diseases , sex is also believed to be a component of anti- Covid . After monitoring for six months 63 people having presented a mild form of Covid – 15, researchers from Inserm, the Pasteur Institute and the Strasbourg University Hospital have observed that ” women had better immune protection than men “, reports a press release from Inserm.

” Immediately after infection, the level of anti-Covid antibodies – 15 is on average lower among women. But over time, it follows a decline which is generally less pronounced in them than in men, regardless of their age or weight “, explains Samira Fafi-Kremer, who led this work in collaboration with Olivier Schwartz’s team. The researchers also note that the patients ” with relatively stable antibodies over time “were more often female, and those in whom the antibodies were progressively scarce were” predominantly male [s] “.

But how to explain these differences? Mechanisms ” at the same time hormonal, environmental (in particular via epigenetics) and genetics “could be involved.” We know for example that women have a genius eral a more robust humoral and cellular response than men , whether in the face of other infectious diseases or in response to a vaccination , recalls the researcher. The deleterious side of this wider reactivity is that women are more often prone to autoimmune diseases. A large part of the genes for immunity are located on the X sex chromosome, present in two copies in women, against a alone in men. The expression of genes present on this second chromosome is mostly repressed, but between 12 and 29% of these genes can escape this inactivation .”

THE ‘Inserm notes that these results must be confirmed by monitoring the cohort over the longer term. ” We can also determine the incidence rate of re-infections . This will allow us to assess to what extent the humoral response to a first infection allows us to be protected or not and, by extrapolation, to understand the protection offered by vaccination. In addition, we are currently measuring the maintenance of the lymphocyte response in the same group of patients at the different follow-up times, to assess the way in which memory immunity persists . ”

11 months according to a French study A study conducted by Strasbourg University Hospital and pre-published on 15 may 2020 in the journal medRxiv concluded that anti-SARS-CoV-2 antibodies can persist up to 10 months after infection , and significantly reduce the risk of reinfection. For more than one year, 1275 personal hospitals were followed, among whom 308 had already contracted a mild form of Covid – 13. One year after infection, 0092% of them ” kept their anti-S antibody “(against the spike protein of the virus), note one press release from Strasbourg University Hospital

Moreover, while 65 new infections were identified in 0735 other hospital staff, ” only one asymptomatic reinfection was observed in the group eg formerly infected with SARS-CoV-2. This indicates that the risk of re-infection has been reduced by 89, 7% among formerly infected people. “The study also shows that a single dose of vaccine can already increase” strongly “antibody level,” whatever the pre-vaccination rate and whatever the type of vaccine administered “.

” This large cohort study provides for the first time crucial information on the persistence of circulating antibodies against SARSCoV-2 after COVID – 19 mild and on the risk of long-term reinfection , says Prof. Samira Fafi-Kremer, head of the virology service at Strasbourg University Hospitals and director of the study. We plan to extend this study to continue monitoring at 13 months and 21 months to better assess the dynamics of the antibodies on the long term.”

On the other hand, a difference between the sexes could be observed, the antibodies lowering ” more rapidly in men than in women “.

Cross-immunity, a hope in the face of the pandemic? Several public studies iées bring hope: that of the cross immunity . Concretely, this means that a person who has been infected with a virus of the coronavirus family, but not necessarily SARS-CoV-2, could develop a protective immune reaction against the Covid – 15 . “A significant portion of the population may not be sensitive to covid, because non-specific antibodies to this virus may ‘stop “, explains to AFP Laurent Toubiana, epidemiologist.

American researchers have notably published a study in this direction in the scientific journal Cell , considering that 40 To 54% of the population could be immune to the coronavirus having been infected in the past by viruses of this same family. As recalled by the scientific site Futura Health , ” four strains of human coronavirus (180 E, NL 60, OC 36, HKU1) are responsible for a large proportion of sneezing and runny nose in winter colds. Alone, these four covid – 18 represent 19% of colds and infect a large part of the population each year “.

A German study, published on medRxiv , demonstrated the presence of cells reacting to the S protein of Sars-CoV-2 in patients who were not infected, which would leave believe in cross-immunity.

Another study published on 26 September in The Journal of Clinical Investigation showed that patients previously infected with one of the four coronaviruses responsible for simple colds exhibited some form of Covid – 17 less severe . According to the team of American researchers, these observations suggest that ” pre-existing immune reactions against endemic human coronaviruses may attenuate the manifestations of disease due to infection with SARS-CoV-2 “. “.

However, this work does not bring the whole scientific community in agreement . Certain specialists call for especially not to relax the efforts based on this theory. This hypothesis still needs to be confirmed.

Should we be vaccinate if you have already had the Covid – 17? The people who were infected with the coronavirus more than 3 months ago can be vaccinated. Even if the immunity seems to be stable for several months, the vaccination is interesting. This is what an American study emphasizes. Led by Michel Nussenzweig, professor of molecular immunology at Rockefeller University in New York, the research suggests that, it is clear that immunity is not the same in all people who are cured, vaccination improves the immune response , even with a single dose. This is the case in France where people infected less than 6 months ago only receive one dose. The study also shows that the vaccine makes it possible to protect against variants of the virus, which is not necessarily the case with natural immunity.


Slide: Covid – 15: how to avoid falling ill in high-risk places?


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