Covid-19: Proportion of antibodies targeting crucial viral protein can impact severity of infection, says study

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Covid-19 antibodies target a different part of the novel coronavirus in severe cases of the infection as compared to mild cases of Covid-19 according to a new study by researchers at Stanford Medicine.

The research aimed to identify new links between the course of the disease and a patient’s immune response. It was published in Science Immunology.

Findings

As part of the study, researchers studied 254 people with asymptomatic, mild or severe Covid-19. These patients had been identified either through routine testing or occupational health screening at Stanford Health Care or had come to a Stanford Health Care clinic with symptoms of the infection, according to an official release by Standford Medicine.

Scott Boyd, MD, PhD, associate professor of pathology who is a senior author of the study said, “We assessed multiple time points and sample types, and also analyzed levels of viral RNA in patient nasopharyngeal swabs and blood samples.”

According to the study, the number antibodies in severe Covid-19 infection targeting the spike protein used by the virus to enter human cells is less as compared to the number of antibodies targeting proteins of the virus’s inner shell.

SARS-CoV-2, the virus that causes Covid-19 binds to human cells through spike protein which is a structure on its surface. The spike protein binds to a receptor on human cells called ACE2. The virus can then enter and infect human cells after binding. Once inside the cell, the virus sheds its outer coat to reveal an inner shell encasing its genetic material and adopts the cell’s protein-making machinery to generate more viral particles, which are then released to infect other cells.

Antibodies that target the spike protein on the virus can prevent infection rather than those that target other parts of the virus. Potential vaccine candidates generate an immune response using portions of the spike protein.

“Although previous studies have assessed the overall antibody response to infection, we compared the viral proteins targeted by these antibodies,” Boyd said.

“We found that the severity of the illness correlates with the ratio of antibodies recognizing domains of the spike protein compared with other nonprotective viral targets. Those people with mild illness tended to have a higher proportion of anti-spike antibodies, and those who died from their disease had more antibodies that recognized other parts of the virus.”

Other findings

Researchers also found that there was a significant difference in terms of a sustainable immune response in mild and severe cases of Covid-19 in individual patients. According to the research, antibodies also wane significantly within several months of infection in mild cases of the disease.

“Antibody responses are not likely to be the sole determinant of someone’s outcome,” Boyd said. “Among people with severe disease, some die and some recover. Some of these patients mount a vigorous immune response, and others have a more moderate response. So, there are a lot of other things going on. There are also other branches of the immune system involved. It’s important to note that our results identify correlations but don’t prove causation.”

Researchers found that people with asymptomatic and mild Covid-19 infection had lower levels of antibodies overall than in patients with severe infection.

The levels of IgM and IgA antibodies decreased steadily in patients after recovery to low or undetectable levels over a period of about one to four months after infection.

“This is quite consistent with what has been seen with other coronaviruses that regularly circulate in our communities to cause the common cold,” Boyd said.

“It’s not uncommon for someone to get re-infected within a year or sometimes sooner. It remains to be seen whether the immune response to SARS-CoV-2 vaccination is stronger, or persists longer than that caused by natural infection. It’s quite possible it could be better. But there are a lot of questions that still need to be answered,” Boyd added.



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