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The body’s protective antibodies against the novel coronavirus target a different part of the virus in severe cases of COVID-19 than they do in mild forms of the disease, and wane significantly within several months of infection, a new study says. According to the scientists, including those from Stanford University in the US, the findings shed new light on the links between the course of the disease and a patient’s immune response.

The research, published in the journal Science Immunology, found that people with severe COVID-19 have lower levels of antibodies targeting the spike protein used by the virus to enter human cells than those targeting proteins of the inner shell of the SARS-CoV-2 virus.

“This is one of the most comprehensive studies to date of the antibody immune response to SARS-CoV-2 in people across the entire spectrum of disease severity, from asymptomatic to fatal,” said Scott Boyd, co-author of the study from Stanford University.  “We assessed multiple time points and sample types, and also analyzed levels of viral RNA in patient nasopharyngeal swabs and blood samples. It’s one of the first big-picture looks at this illness,” Boyd said.

In the study, the scientists studied 254 people with asymptomatic, mild, or severe COVID-19 who were identified either through routine testing or occupational health screening at Stanford Health Care or who came to a Stanford Health Care clinic with symptoms of COVID-19.  According to the scientists, 25 of the people with symptoms were treated as outpatients, 42 were hospitalized outside the intensive care unit and 37 were treated in the intensive care unit.

The study noted that 25 people in the study died of the disease. From the analysis of patient samples, the scientists said antibodies that recognize and bind to the spike protein prevent the virus from infecting the cells.  However, they said the antibodies which recognize other viral components are unlikely to prevent viral spread.  The researchers assessed the levels of three types of antibodies — IgG, IgM, and IgA — in the patients.

They estimated the proportions of antibodies that targeted the viral spike protein or the virus’ inner shell as the disease progressed and patients either recovered or grew sicker. “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,” Boyd said.  “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,” he added.

While the study identified trends among a group of patients, the scientists said there is still substantial variability in the immune response mounted by individual patients, particularly those with severe disease. They believe antibody responses are not likely to be the sole determinant of someone’s outcome.  “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,” Boyd said.

“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,” he added. The scientists also found that people with asymptomatic and mild illness had lower levels of antibodies overall than did those with severe disease.

Levels of IgM and IgA decreased steadily in patients post-recovery to low or undetectable levels over a period of about one to four months after symptom onset, and IgG levels dropped significantly. “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.