A longitudinal cohort study in India has found that some people who had COVID-19 lacked meaningful immunity against the novel coronavirus to prevent reinfection months later. The study found that 20-30% of infected people had declining virus neutralising activity despite having stable seropositivity six months later.
The declining neutralising activity seen in 20-30% of infected people would mean that they might be vulnerable to reinfection. Studies are now under way to understand the presence and activity of memory T cells which can prevent the infection from progressing to severe disease.
The first serosurvey was carried out in August-September 2020 and the six-month follow-up was carried out from the end of January to February 2021.
Widespread asymptomatic infection when the daily cases peaked in the middle of September 2020 and the subsequent decline in new cases may be attributable to increased population immunity. By September 2020, a large pool of people who had recovered still had at least partial immunity. However, the reduced neutralisation activity six months later shows that the “respite may be temporary”, says a paper that has been accepted for publication in the journal eLife .
Dr. Shantanu Sengupta, from the Institute of Genomics and Integrative Biology (IGIB) and one of the corresponding authors of the study says, “The study shows that if previously infected people are exposed to high viral loads months after infection, then 20-30% of people may not have immunity against the virus as they are unable to neutralise the microbe and might get reinfected. Similar observations have been made in a study undertaken in Denmark.”
This would mean that one in five or even one in three people may get reinfected months after the first infection. Since it is not known when each individual got infected, the precise duration of protection is not known.
Serosurvey done
The serosurvey to understand the spread of the virus in the community was carried out by 136 researchers from 31 CSIR labs across the country. In all, 10,427 people from 24 cities in 17 States and two Union Territories were included in the serosurvey. Of the nearly 10,500 people included, 1,058 tested positive. Of them, 647 (75.3%) were not able to recall symptoms, probably because they were asymptomatically infected. Also, 95% of people who tested positive had significant neutralising activity in August-September, suggesting at least partial immunity at that time.
Repeat serology tests were carried out three and six months later and included 607 and 175 people, respectively. Of the 607 infected people who were followed up at three months, the nucleocapsid antibody levels were similar or higher for most. While only 17 (2∙8%) of them turned seronegative, 34 (5.6%) of them did not have neutralising activity at three months. At five-six months, of the 175 people followed up, eight (4.6%) turned out to be seronegative and neutralising activity was not present in 31 (17.7%) people. The study shows that the duration of protection against infection may not be sufficient to prevent future outbreaks, even in highly affected regions.
“We found that when 20% neutralisation cut-off was used, 17-18% people had lost neutralisation activity six months after the first serosurvey study. But if we use a stringent neutralisation cut-off, then 30% of them have lost the ability to neutralise the virus,” says Dr. Sengupta.
“Our data show that while anti-nucleocapsid antibodies provide long-lasting evidence of viral exposure or infection, about 20% of seropositive individuals lack meaningful neutralisation activity after five-six months. Using more stringent measures (more than 30% inhibition of surrogate receptor-spike protein binding), the loss of neutralisation may be even higher. We speculate that this may be related to recurrence of outbreaks in March 2021, after the peak in September 2020,” the authors write.
Peaks and then tapers
Since nearly 75% of people were unable to recall symptoms and were probably asymptomatically infected, are they more likely to show declining neutralising activity months after infection? “We did not study for such a correlation. But a large number of people showed neutralising activity below the first observed level at six months follow-up. At three months follow-up, a large number [40-50%] showed neutralising activity above the first observed level,” says Dr. Debasis Dash from IGIB and the other corresponding author of the paper.
“The IgG antibodies [that can neutralise the virus] continue to increase and peak weeks after infection and then begin to decline. This is the reason the neutralising activity is higher than the first observed level in a significant number of people at three months follow-up. Since the IgG levels tapers after some time, a significant number have the neutralising activity below the first observed level at six-month follow-up,” says Dr. Sengupta.
