Coronavirus: low antibody levels raise questions about reinfection risk
- Scientists in Shanghai say some recovered patients show no signs of the neutralising proteins
- Early-stage findings could have implications for vaccine development and herd immunity, they say
Researchers in Shanghai hope to determine whether some recovered coronavirus patients have a higher risk of reinfection after finding surprisingly low levels of Covid-19 antibodies in a number of people discharged from hospital.
A team from Fudan University analysed blood samples from 175 patients discharged from the Shanghai Public Health Clinical Centre and found that nearly a third had unexpectedly low levels of antibodies.
In some cases, antibodies could not be detected at all.
“Whether these patients were at high risk of rebound or reinfection should be explored in further studies,” the team wrote in preliminary research released on Monday on Medrxiv.org, an online platform for preprint papers.
Although the study was preliminary and not peer-reviewed, it was the world’s first systematic examination of antibody levels in patients who had recovered from Covid-19, the disease caused by the coronavirus, the researchers said.
All of the patients had recently recovered from mild symptoms of the disease and most of those with low antibody levels were young. The researchers excluded patients who had been admitted to intensive care units because many of them already had antibodies from donated blood plasma.
Antibodies are generated by the immune system and have unique chemical structures to inhibit specific pathogens. The coronavirus antibody intercepts the spike protein on the viral envelope to prevent it from binding with human cells.
The researchers said they were surprised to find that the antibody “titer” value in about a third of the patients was less than 500, a level that might be too low to provide protection.
“About 30 per cent of patients failed to develop high titers of neutralising antibodies after Covid-19 infection. However, the disease duration of these patients compared to others was similar,” they said.
The team also found that antibody levels rose with age, with people in the 60-85 age group displaying more than three times the amount of antibodies as people in the 15-39 age group.The low amounts of antibodies could affect herd immunity, resistance to the disease among the general population to stop its spread.
“This is a clinical observation we made at the front line. What this will mean to herd immunity will require more data from other parts of the world,” Professor Huang Jinghe, the leader of the team, said on Tuesday.
Huang said 10 of the patients in the study had an antibody presence so low it could not even be detected in the laboratory.
These patients experienced typical Covid-19 symptoms including fever, chill and a cough, but might have beaten back the virus with other parts of the immune system such as T-cells or cytokines.
How they did this was still unclear.
“Vaccine developers may need to pay particular attention to these patients,” Huang said. If the real virus could not induce antibody response, the weakened version in the vaccine might not work in these patients either.
The researchers also found that the Covid-19 antibody could bind with a distantly related strain that caused an outbreak of severe acute respiratory syndrome (Sars) in 2003.
But the binding could not suppress Sars virus replication in cells, dashing hopes of developing a vaccine for two or even more coronavirus strains at once.
Many questions about the virus remain unanswered, including how the virus made the jump from animal to humans; why some people die from Covid-19 and others are asymptomatic; and why some recovered patients test positive again.
Professor Wang Chen, a senior scientific adviser to the central government, told state media on Monday that it was way too early to declare victory against the disease even in China, where the situation was under control for now.
“Who knows whether this will become something like a seasonal flu, or chronic disease like hepatitis B, or just vanish like Sars?” he was quoted in the official Science and Technology Daily.
“Up till now we still lack imagination [to tell].”
Course: South China Morning Post
Neutralizing antibody responses to SARS-CoV-2 in a COVID-19 recovered patient cohort and their implications
Background The COVID-19 pandemic caused by SARS-CoV-2 coronavirus threatens global public health. Currently, neutralizing antibodies (NAbs) versus this virus are expected to correlate with recovery and protection of this disease.
However, the characteristics of these antibodies have not been well studied in association with the clinical manifestations in patients. Methods Plasma collected from 175 COVID-19 recovered patients with mild symptoms were screened using a safe and sensitive pseudotyped-lentiviral-vector-based neutralization assay.
Spike-binding antibody in plasma were determined by ELISA using RBD, S1, and S2 proteins of SARS-CoV-2. The levels and the time course of SARS-CoV-2-specific NAbs and the spike-binding antibodies were monitored at the same time. Findings SARS-CoV-2 NAbs were unable to cross-reactive with SARS-CoV virus. SARS-CoV-2-specific NAbs were detected in patients from day 10-15 after the onset of the disease and remained thereafter.
The titers of NAb among these patients correlated with the spike-binding antibodies targeting S1, RBD, and S2 regions. The titers of NAbs were variable in different patients. Elderly and middle-age patients had significantly higher plasma NAb titers (P<0.0001) and spike-binding antibodies (P=0.0003) than young patients.
Notably, among these patients, there were ten patients whose NAb titers were under the detectable level of our assay (ID50: < 40); while in contrast, two patients, showed very high titers of NAb, with ID50 :15989 and 21567 respectively.
The NAb titers were positive correlated with plasma CRP levels but negative correlated with the lymphocyte counts of patients at the time of admission, indicating an association between humoral response and cellular immune response. Interpretation The variations of SARS-CoV-2 specific NAbs in recovered COVID-19 patients may raise the concern about the role of NAbs on disease progression.
The correlation of NAb titers with age, lymphocyte counts, and blood CRP levels suggested that the interplay between virus and host immune response in coronavirus infections should be further explored for the development of effective vaccine against SARS-CoV-2 virus. Furthermore, titration of NAb is helpful prior to the use of convalescent plasma for prevention or treatment.
Funding Ministry of Science and Technology of China, National Natural Science Foundation of China, Shanghai Municipal Health Commission, and Chinese Academy of Medical Sciences