Seroconversion occurs in up to 99% of people following infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the pathogen that is responsible for the ongoing coronavirus disease 2019 (COVID-19) pandemic. The question, however, is how long these antibodies persist and how far they protect against reinfection. A new study released on the medRxiv* preprint server offers hope that recovered patients are largely immune to reinfection for at least eight months.
The absence of testing in the early stages of the pandemic, as well as the high incidence of asymptomatic infection, led to estimated seropositivity rates of less than 10%. Reinfection, meanwhile, has been reported in a rarity of cases and has mostly resulted in mild symptoms, indicating a high degree of protective immunity following recovery from COVID-19.
The current study takes advantage of the two waves of COVID-19 that occurred in Switzerland, the first peaking in March and the second in November, 2020. The city of Geneva had a high incidence of confirmed SARS-CoV-2 infections, at about 8,600/100,000 people.
The researchers looked at the risk of reinfections in a situation with high community transmission. The two groups they compared either had or did not have detectable antibodies to SARS-CoV-2. The aim was to estimate the infection rate in either group.
The study matched each individual in the seropositive group to two seronegative controls. The sociodemographic characteristics of each group were comparable. So were the body mass index, and type and number of comorbidities in each group.
The follow-up continued for 36 and 25 weeks in the seropositive and seronegative groups, respectively. The testing rate was slightly higher among the seronegatives, at 1.52 per person vs. 1.39 in the seropositives.
However, the positive test fraction was lower in the seropositive group, at 2.4% vs. 11% in the seronegative group.
What were the results?
Only seven of 448 seropositive individuals had a positive polymerase chain reaction test for the virus. Five were likely to be reinfections, the other two probably not.
Conversely, 16% of seronegative individuals were positive, which indicates an incidence of 5 per 1,000 person-weeks. Over the entire follow-up period, the chances of being infected were 94% less for seropositive individuals compared to the other group.
What are the implications?
The study provides strong evidence that the presence of antibodies to SARS-CoV-2 is associated with strong protection against reinfection, as indicated by a positive test, at eight or more months following the first positive test.
Earlier reports have also shown that among over 1,200 seropositive healthcare workers in the UK, only two infections were detected after six months of follow-up. Both were asymptomatic. This yields an incidence rate ratio of 0.12.
The sample in the above study was composed of healthy participants of working age, and the period of the study was one of low incidence, with only 1 positive test per 10,000 days at risk. In contrast, the current study was carried out over a period with six-fold higher incidence.
A Qatar study, including over 1,30,000 confirmed infections, showed that reinfection was detected in only 0.05% of them. In this case, reinfection was determined on the basis of a positive PCR test at 45 or more days from the first positive swab.
This was, however, a study in a country that had only one wave of COVID-19, and where young workers were chiefly affected during the early phase, which was characterized by the rapid, extensive spread. Here, the infections dropped steeply following August 2020.
Strengths of this study
The current study covers a more representative sample, including many elderly individuals. Moreover, the follow-up period extended into the second wave, several months after seroconversion, with a high incidence of infection.
Thus, this supports the hypothesis that SARS-CoV-2 infection is followed by robust and durable antibody-mediated protection against reinfection. The degree of protection matches, at least, the preliminary results reported following vaccination with lipid nanoparticle-mRNA-based vaccines, at 90%.
Some degree of underestimation of actual reinfection is inevitable, perhaps, given that reinfections are milder in clinical presentation, and also because seropositive patients are aware that they have already had and recovered from the infection.
This is likely to be low, because testing was extensively carried out in the second wave, more so than in the first, with the ratio of undetected cases to detected ones falling from about 12 to 3, respectively. Secondly, both seropositive and seronegative subjects had similar testing rates, but a drastically lower positive test rate in the former.
Documented SARS-CoV-2 reinfections were exceedingly rare, with an incidence of 0.3 infections for every 1000 persons-week, and none were severe.”
The risk of reinfection is apparently reduced ten-fold by seroconversion after SARS-CoV-2 infection, as recorded at eight or more months after initial infection. These findings will help shape vaccination policies to provide maximum coverage while allowing appropriate relaxations of non-pharmaceutical interventions as soon as possible.
The extent of protection against variants of concern such as the UK variant cannot be estimated from this study, since these were present in very low numbers at that time. Further research may explore the correlation, if any, between antibody titers and the risk of reinfection, and the percentage of persistent seropositivity with prolonged monitoring.
medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.