What immunity after infection with SARS-CoV-2?

The message from epidemiologists, widely relayed by the media to professionals, politicians and the general population, is that to stop the spread of the COVID-19 epidemic, due to the high transmissibility of Sars-Cov -2 (R0 between 2 and 3), it is necessary that 60 to 70% of the population is immunized.

However, in the absence of a vaccine, the only way to be immunized is to have been infected with Sars-CoV-2, either by having expressed COVID-19 disease (ranging from pauci-symptomatic forms to the most severe) or without clinical sign (asymptomatic subjects). It should be noted that the clinical manifestations of COVID-19 are very variable and most often have no clinical particularities, with the exception of:

  1. severe pneumonitis occurring in the second week of the disease for which the CT images are characteristic
  2. brutal, annoying anosmia and / or ageusia, without nasopharyngitis
  3. skin lesions such as acrosyndrome

As a result, many people who have had fever and / or ENT and respiratory and respiratory signs during a pandemic period, without having been tested, often wrongly consider that they have been infected with Sars-Cov-2. Today, the only subjects who should be considered immune are those who have had a positive PCR test or typical CT scan and have recovered, or those who have shown clinical signs on direct, family or prolonged contact with a child. person tested positive.

The availability of reliable and sufficient serological tests is a turning point in the epidemic. Infected people activate virus-specific T and B cells and produce antibodies. After contamination, Sars-Cov-2 multiplies in the nasopharynx and at this early stage its RNA is detectable by specific PCR in high quantities.

When the immune response appears (translated by the rise of antibodies) the quantity of virus decreases gradually to become most often undetectable after a few days. A positive serological result indicates exposure to the SARS-Cov-2 virus. It is not yet known whether the antibodies detected play a role in protection and doubts have been expressed about the quality of protection: some studies report some cases of re-excretion of viral RNA, even the presence of some clinical symptoms, without description of serious form.

However, since the majority of COVID-19 patients recover from this infection, the presence of antibodies allows a presumption of protection for the vast majority of patients. In addition, another essential question is that of the duration of this protection: months, years (like usual coronaviruses) or whole life (for Sars-CoV-1, 17 years after exposure, cured patients still have neutralizing antibodies).

The use of reliable serologies will thus allow:

  1. Carry out seroprevalence studies to better describe the “pyramid” of infections caused by Sars-CoV-2, and, secondly, to assess the epidemic risk in a given region, and therefore the risks deconfinement and, in particular the intensity of subsequent waves.
  2. To more easily mobilize doctors and nurses whose serology will be positive (despite sometimes negative PCRs), and therefore with probable immunity, who will no longer risk being contaminated during treatment.
  3. In the general population, to lift the containment measures, to relax the hygiene measures and to be able to return to work with minimal risk in the presence of a positive serology.

COVID-19 Serology

In the course of an immunizing infection, patients produce antibodies against the antigens (often proteins) specific to the pathogen. The first to appear (less than a week) are the IgMs which persist for a few weeks or months, then the IgGs which appear very few days later but which will persist for years. For Sars-CoV-2, certain viral proteins are common with other coronaviruses and with Sars-CoV-1.

 The challenge is to avoid false positives from cross-reactions with other coronaviruses. Determining the best performing target antigens and expressing the protein in the right structure are often the most difficult steps in developing the tests. Two proteins are used: the surface protein (spike) allowing the virus to bind to cellular receptors (ACE) and the nucleocapsid which is the most abundant viral protein, probably easier to detect.

Two types of test are in development: classical serological tests (ELISA) carried out in the laboratory from serum and rapid diagnostic tests using a few drops of whole blood (Immunochromatography), often less sensitive than ELISA, similar to those used for pregnancy tests or other RDTs, performed directly by caregivers or even by the patients themselves and whose result is obtained in less than 20 minutes.

Although some of these tests seem to have excellent performance (sensitivity and specificity> 95%), none of the test candidates has been fully validated to date, but the urgency in the epidemic context has led regulatory authorities many countries to relax the usual assessment criteria.

In France, as in Europe, any reagent with the CE-IVD marking can be marketed. However, authorization to use will only be issued in France for reagents (TDR and ELISA), the performance of which will have been assessed and deemed sufficient by the CNR for respiratory viruses. The results of these assessments will be gradually available from mid-April.