About 30% of patients with mild symptoms failed to develop high amounts of neutralising antibodies even after recovering from COVID-19 disease. If natural infection with novel coronavirus does not elicit strong immune response, how much will vaccines be able to achieve.
Analysis of blood samples from 175 patients with mild COVID-19 disease who were discharged from the Shanghai Public Health Clinical Centre as on February 26 revealed that about 30% of patients had unexpectedly low levels of antibodies against novel coronavirus (SARS-CoV-2). Ten patients had low levels of neutralising antibodies that they could be detected, while two patients showed very high levels.
The study threw up another surprise — the plasma of elderly and middle-age patients had significantly higher amount of neutralising antibodies and spike-binding antibodies than young patients. The median age of the patients was 50 years and the median length of hospital stay was 16 days and median disease duration was 21 days.
The study was posted on medRxiv preprint server on April 6. Preprints are yet to be peer-reviewed and published in scientific journals.
Though about 30% of patients failed to develop high amounts of neutralising antibodies even after recovering from COVID-19 disease, the disease duration was not longer than older patients. Likewise, older patients who had more neutralising antibodies did not recover faster. So immaterial of the amount of neutralising antibodies found, both young and old patients took the same time to recover.
How effective will vaccines be
The amount of neutralising antibodies generated in response to vaccination determines the efficacy of the vaccine in protecting against the virus. In this case, if infection with actual virus has not resulted in eliciting strong antibody response and hence elevated neutralising antibodies, it is not clear if vaccine which have killed or weakened viruses would be able to produce high amounts of antibodies.
But the researchers were not able to detect viral DNA in the blood samples collected and information about viral load was not available for all the patients. So it is not known if young patients had lower viral load thus resulting in lower amounts of neutralising antibodies. “This study is preliminary,” the authors caution.
The team led by Dr. Jinghe Huang was able to detect coronavirus-specific neutralising antibodies 10-15 days after onset of the disease, and the levels remained stable thereafter.
All the 175 patients included in the study had only mild symptoms. The researchers excluded patients who had been admitted to intensive care units because many of them already had antibodies from donated blood plasma.
Convalescent plasma therapy
The efficacy of passive antibody therapy, otherwise called as convalescent plasma therapy, relies on the concentration of neutralising antibodies in the plasma or antibodies. The low levels of neutralising antibodies in younger patients who have recovered from the disease strongly suggest that convalescent plasma should be titrated before being used for therapy.
The authors wonder if the low levels of neutralising antibodies in about 30% of patients would put them at risk of infection rebound or reinfection, and suggest that further studies are undertaken to understand this.
The higher amounts of neutralising antibodies found in older patients may be due to “strong immune response” in aged people, the study suggests. But whether the elevated neutralising antibodies found in older people protect them from progression to severe and critical conditions is not known. But world over, it has become clear that older COVID-19 patients are at higher risk of adverse disease outcomes. Studies carried out earlier using the SARS virus infection in aged macaques resulted in elevated immune responses, resulting in severe pathology than younger adult macaques.
The researchers also found antibodies generated in response to novel coronavirus (SARS-CoV-2) could bind with 2003 SARS strains. However, the binding was not able to stop the SARS virus from replicating. This raises the possibility of developing a vaccine that might be effective against both novel coronavirus as well the 2003 SARS virus.