6-month SARS-CoV-2 antibody persistency in a Tyrolian COVID-19 cohort

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Austria in early 2020 [ 1] receiving utmost attention in every aspect of private and public life. By 16 November 2020 more than 200,000 people were infected with SARS-CoV‑2 in Austria with more than 1700 deaths ( https://​covid19-dashboard.​ages.​at). In order to reduce spreading of the disease political decisions had to be made that severely affected the quality of life not only of Austrians but of all people worldwide and also has a substantial socioeconomic impact [ 2].

The SARS-CoV‑2 infection induces an immune response with activation of the innate and adaptive immune system leading to viral clearance and spontaneous recovery in the majority of nonfatal cases [ 3]. Virus-specific T and B cells evolve and consequently virus-specific antibodies are produced by plasma cells usually some days up to a few weeks after infection depending on the immunoglobulin (Ig) subclass [ 3]. Depending on the sample size, population, comorbidities, treatment, and type of antibody assay the vast majority of COVID-19 patients develop an antibody response [ 4– 14].

The durability of the antibody response remains to be determined although short-term follow-up studies revealed stable antibody titers post-COVID-19 infection in symptomatic as well as asymptomatic cases [ 4, 6– 10, 12– 16].

This article presents 6 months follow-up SARS-CoV‑2 antibody results in a prospective Tyrolian cohort.

In the present study we found a persistent anti-SARS-CoV‑2 antibody response over 6 months including neutralizing activity in all participants. The epidemiology in the subcohort of high school teachers as well as in household members followed known patterns with physical vicinity and time of exposure being the driving factors of transfection rates [ 18].

We feel that these data are important and reassuring for long-term immunity after COVID-19 disease. There is little doubt that there is protective immunity in convalescent cases. The immune response follows standard patterns of anti-viral protective immunity with neutralizing antibodies in the majority of infected people [ 7, 12, 15, 16, 19]. The SARS-CoV‑2 specific T‑cells and B‑cells have been demonstrated in patients recovered from COVID-19 as well as SARS-CoV‑2 specific memory cells [ 20]. In a large outbreak of COVID-19 on a fishery vessel affecting 104 out of 122 crew members the individuals with neutralizing anti-SARS-CoV‑2 antibodies remained asymptomatic and repeatedly tested negative in SARS-CoV‑2 PCR except for one person with a very weak PCR signal [ 19]. One of our antibody positive study participants remained asymptomatic and PCR negative after re-exposure through the partner, a situation with a high likelihood of infection as shown in the partnership analyses with a transfection rate of 82%. In nonhuman primates antibody-associated protective immunity could be demonstrated by SARS-CoV‑2 infection and reinfection [ 21]. The animals had no COVID-19 symptoms after re-inoculation and a boost of their antibody response.

There are a few reports of possible SARS-CoV‑2 reinfection [ 22– 24]; however, no case occurred in a similar setting to our study population, i.e. reinfection after a reasonably stable phase of convalescence and persisting antibody response. Most of the reported reinfections were most likely reactivations shortly after primary disease onset or had no antibody response after the first event, a notion supported by a recent study on a larger population concluding that reoccurrence of viral RNA after COVID-19 recovery reflects reactivation rather than true reinfection as viral clearance may take up to 3 months after primary infection [ 25].

The technical assay performance was good with sensitivities and specificities very similar to previous reports [ 26] and a slight advantage for the RBD pan-Ig assay, which seems to be more sensitive and stable over time [ 7, 8, 12]. The decline of the anti-S1 IgG response has been described earlier [ 4], it is however, unclear how to interpret this finding. Both subjects who had S1 IgG indices below cut-off point at 6 months still had neutralizing activity and a positive response against the RBD. It seems that the S1 protein harboring the receptor binding domain is the main target for virus neutralization [ 27], corroborated by the strong correlation between binding and neutralizing titers found by us and others [ 16]. We assume that epitopes are expressed differently on RBD versus full S1 protein. Also, the assay formats differ with direct coating of S1 onto the plate for the Euroimmun assay as opposed to a sandwich design provided by the Wantai test. The difference in antibody kinetics were also observed previously [ 4]. Apart from the present study, we are aware of only one other report following COVID-19 cases for 6 months showing persisting neutralizing anti-SARS-CoV‑2 antibodies in all post-COVID-19 cases after 6–7 months along with T‑cell memory [ 15].

Of course, one can only speculate about the future persistency of antibodies but the kinetics so far seems promising for a long-lasting response which depends on titers as indicated by the strong correlation between baseline and follow-up index values. Also, the curve of decline flattens. We found the difference of S1 IgG index values to be larger between T1 and T2, an effect that was restricted to males, whereas hardly any changes occurred later. Males are usually more severely affected by the disease and might therefore display a larger boost in the first weeks of their antibody response [ 28]. Several other studies found similar results pointing towards a long-lasting immune response [ 4, 15, 16].

The limitations that need to be mentioned include the relatively low number of study participants; however, this is one of the few prospective cohorts followed for 6 months. Although few studies found an early decline of antibody levels [ 29] the majority of reports are much in line with our findings. In this respect, one has to consider the many different assays that were used by various investigators and might account for discordant results. Furthermore, our results apply to a largely healthy population aged between 29 and 65 years with mild to moderate COVID-19 disease. Therefore, we cannot speak for children, an older population, immunocompromized, and people with relevant comorbidities who might behave very differently in terms of immunity and duration thereof.

In practical terms we suggest testing all convalescent cases for antibodies a few weeks after recovery and performing follow-up tests every 3–6 months depending on the titer. Any validated S1 or RBD binding assay should suffice as there is strong evidence that these assays are a surrogate for neutralization. Given the rapidly increasing number of people recovered from COVID-19, sooner rather than later the status of immunity needs to be acknowledged, which can be applied in many different contexts. Firstly, there is no need for vaccination in already immunized persons. Also, scheduling in healthcare deployment, particularly for nurses who are frequently in close contact with patients, could consider immunity and in fact any other professions where deployment plans are needed. In workplaces, where close contact between employees occur, such as distribution centers, vessels, or meat industry knowledge of immunity can be helpful [ 19, 30]. In fact, in these environments COVID-19 clusters occurred in the past resulting in many immunized people who can now stay together for work with very low risk of new clusters for the time being.