How complicated it is to get reinfected with coronavirus

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We have all seen reports, more or less reliable, of reinfections by SARS-CoV-2. This has rightly led us to doubt how effective the immune response to coronavirus might be. Of course, these cases exist, but how important are they in the current pandemic context? Isn’t there a cherry-picking bias? Is the concern generated justified? We need a context, which is what this article published in the NEJM magazine gives us.

Although immunity cannot be reduced to the presence of antibodies, it is true that these represent a good marker of humoral response and are attributed a very relevant protective role against SARS-CoV-2. That’s why the study authors focused on them, specifically IgGs.

Some preliminary clarifications:

Antibodies of the IgG class represent a mature and enduring response (as opposed to those of the IgM class, transient and less mature).

The authors distinguish two tests: in one they use protein S (or spicule) as antigen and in the other, N (nucleocapsid), two components of the virus recognized by antibodies. It should be clarified that N is the antigen most used in antibody tests for the diagnosis of covid-19, but S represents the antigen against which the protective response is mainly produced, by bringing together the main sites of neutralization of the virus.

The study was carried out in healthcare workers from four university hospitals in Oxford (UK). A cohort of 12,541 volunteers was gathered who underwent a PCR every two weeks and an antibody test (Y and N) every two months from April 23 to November 30, 2020.

About 90% of the health workers studied (11,364) were seronegative, while approximately 10% (1,177) presented IgG against the S of SARS-CoV-2 in serological samples. 88 seroconversions were counted during the study.

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Among the seropositive, 68% (864) declared having had some symptom compatible with covid-19 prior to the study (25% in the seronegative), and 37% (466) had a previous positive CRP (0.2% in the seronegative ). Of them, 262 presented symptoms.

During the follow-up study, the presence of anti-S IgG in serum was associated with a low rate of positivity to PCR: among the seronegative, 223 (of 11,364) were positive in the PCR (100 asymptomatic), while among the seropositive so only 2 (out of 1,265) were positive (both asymptomatic).

The incidence varied during the course of the study (between April and November) according to the dynamics of the pandemic in the United Kingdom, but always with a consistently higher rate of infections in the group that did not present serum IgG.

The result was similar whether the IgG was analyzed against S and against N. The only double positive (IgG + to S and N) detected with a history of previous positive PCR and five negative PCRs in a row were positive 190 days after the first infection.

Conclusions

Having IgG against SARS-CoV-2 protects in the vast majority of cases against infection (and 100% against disease), for at least 6 months.

Protection is effective even at low levels (at the limit of detection) of antibodies.

Only one possible reinfection has been detected in this study (not confirmed by sequencing), indicating that in any case this phenomenon is rare. It is interesting to note that the second infection was asymptomatic.

Logically, the authors point out some limitations: the health population has biases (age, sex, exposure, occupation) and the duration of the study should be longer than 6 months, and extended to other population groups. Nonetheless, it is a very robust study. It is reasonable to think that vaccines will produce a protective response at least as effective as the natural infection itself.

A version of this article was originally published on the blog Emerging viruses and global change, of the Madri + d Knowledge Foundation.

This article was originally published on The Conversation. Read the original.

Miguel Ángel Jiménez Clavero, as main researcher, is responsible for the execution of research funds from the State Research Agency and the European Commission, which is received by the public institution National Institute for Agricultural and Food Research and Technology (INIA), for the who works, and who pays him a salary for it.