The coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), continues to spread worldwide. Since the virus first emerged in late-2019, over 95.55 million cases and more than 2 million deaths have been reported.
Many countries have commenced targeted vaccination efforts to control the spread of the virus and immunize vulnerable groups. However, vaccine rollout may still lag behind ongoing infections, as fast-spreading new variants threaten many countries. Finding an effective therapy to help patients fight the infection remains crucial.
Passive immunotherapy treatment, wherein SARS-CoV-2-neutralizing antibodies (nAbs) from the plasma of recovered patients are administered to acutely sick patients, is a promising method for COVID-19 treatment in severe cases.
A team of researchers at the University of Washington, Fred Hutchinson Cancer Research Center, and the National Institute of Health, USA, recently studied the neutralizing antibodies from patients recovering from COVID-19 to investigate which clinical factors predict good passive immunotherapy donors.
In the study, published in the Journal of Clinical Investigation, the research team measured SARS-CoV-2-nAb titers in the plasma of 250 people with SARS-CoV-2 infection.
In the USA, convalescent plasma therapy for COVID-19 patients was approved under emergency use authorization by the Food and Drug Administration (FDA) on August 23, 2020. This mode of therapy uses antibody-containing blood from recovered individuals to help promote passive immunity in severely ill patients still battling the infection.
Blood donated by people who have recovered from COVID-19 is processed to remove blood cells, leaving behind the plasma and neutralizing antibodies against SARS-CoV-2.
The plasma given to severely ill patients will help boost the body’s immune system. In a recent phase II clinical trial in Argentina, scientists found that convalescent plasma with high levels of neutralizing antibodies, particularly when given early in the infection, had a marked beneficial health impact.
Yet, not all SARS-CoV-2-infected people produce a strong neutralizing antibody response. Hence, convalescent plasma from donors should be screened for SARS-CoV-2-neutralizing antibody activity to make sure the recovered patients are suitable donors.
In the current study, the researchers tested the serum of 250 potential convalescent plasma donors with confirmed SARS-CoV-2 infection for the presence of SARS-CoV-2 spike protein S1 domain, nucleoprotein (NP), and for neutralizing antibodies.
The team found that among the participants, 97 percent were seropositive on one or more assays. About 60 percent of the donors had nAb titers. The correlates of higher nAb titer included old age, male, and severity of the illness. Also, patients with more severe COVID-19 symptoms, like the difficulty of breathing and fever, had higher levels of neutralizing antibodies against SARS-CoV-2.
Moreover, a longer period between the infection and antibody screening had decreased nAb titers. The study results showed that severe COVID-19 illness produces higher levels of antibodies than less severe illness. This also means that the neutralizing antibodies in the blood of recovered patients wane over time.
COVID-19 seems to be one of a group of infections where the sicker one is, and presumably the more virus and therefore the more antigen that is around, the higher the levels of antibody,” Dr. David Koelle of the Koelle Laboratory, University of Washington, said in a statement.
He explained that the potential cause of this discrepancy is that the immune system in people who had a severe illness, was not effective in stopping it. There is a probable temporal race between the proliferation of the virus and host adaptive immunity.
The researchers concluded that nAb titers correlated with disease severity, sex, and age. Also, they suggested that commercially available SARS-CoV-2 immunoglobulin G (IgG) results can become an alternative for nAb testing.
Functional nAb levels were found to decline and a small proportion of persons recovered from COVID-19 lack adaptive immune responses,” they added.
- Boonyaratanakornkit, J., Morishima, C., Selke, S., Zamora, D., et al. (2021). Clinical, laboratory, and temporal predictors of neutralizing antibodies to SARS-CoV-2 among COVID-19 convalescent plasma donor candidates. Journal of Clinical Investigation. DOI: https://www.jci.org/articles/view/144930, https://pubmed.ncbi.nlm.nih.gov/33320842/