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Anti-SARS-CoV-2 Antibodies Do Not Decline Within Four Months, New Study Finds

NEW YORK — Antibodies against SARS-CoV-2 did not decline among Icelandic patients in the four months following diagnosis, according to a new study from DeCode Genetics researchers.

Two recent studies had suggested that antibodies against SARS-CoV-2 might dwindle as patients recover from the disease, a finding that suggested immunity to the virus could be brief.

By examining thousands of people in Iceland — including those who recovered from infections, those who were quarantined following viral exposure, and those with unknown exposure to SARS-CoV-2 — DeCode's Kari Stefansson and his colleagues assessed the prevalence of anti-SARS-CoV-2 antibodies in the country and, for a subset of participants, examined changes in antibody levels in the months following infection. The first COVID-19 case in Iceland was confirmed in late February 2020 and the epidemic was largely under control by the end of April. 

As they reported Tuesday in the New England Journal of Medicine, the researchers found more than 90 percent of the people diagnosed with COVID-19 by qPCR testing were seropositive. In addition, patients' antibody titers increased in the two months following diagnosis, then stabilized for the next two months of the study.

"We are pleased to be able to put to rest the concern that the titer of the antiviral antibodies may decline within weeks of infection," senior author Stefansson, CEO of DeCode, which is a subsidiary of Amgen, said in a statement.

The researchers measured antibody levels using six established assays but relied in particular on two pan-immunoglobulin (pan-Ig) assays to determine seroprevalence. Because of the low infection rate in Iceland, a sample had to be positive by both pan-Ig assays for it to be deemed seropositive.

When the researchers tested samples from 1,263 individuals who had tested positive by qPCR, they found that 90 percent of these individuals also tested positive for SARS-CoV-2 antibodies 25 days after their diagnosis. Individuals who had been hospitalized were more likely to have seroconverted and tended to seroconvert faster following their diagnosis than those who were not hospitalized. 

For 487 recovered individuals, the researchers had more than one sample that was obtained at least 30 days apart. In general, they found that antibody levels measured with pan-Ig assays increased during the first two months following qPCR diagnosis, then plateaued for the next two months of the study.

This, Galit Alter from the Ragon Institute of MGH, MIT, and Harvard and Robert Seder from the Vaccine Research Center at the National Institutes of Health noted in a related editorial appearing in NEJM, contrasts with recent reports that suggested a decline in antibody levels over time from diagnosis. 

They noted that the contradictory results could be due to when the samples were collected. Following infections, there are two waves of antibodies: the first is dominated by short-lived plasma cells and the second by long-lived plasma cells. Alter and Seder wrote that sampling during the first wave might reveal a strong response that wanes, whereas sampling later or over time might capture a different pattern of immunity.

"[T]his study provides hope that host immunity to this unpredictable and highly contagious virus may not be fleeting and may be similar to that elicited by most other viral infections," they added.

Stefansson and his colleagues also found that antibody levels were higher among people who had been more severely ill as well as among older individuals.

In addition to measuring antibody levels among individuals who tested positive by qPCR for COVID-19, the researchers also tested samples from people who tested negative by qPCR or who were not tested at all. Through this, they estimated that 0.9 percent of Icelanders had been infected with SARS-CoV-2.

Because of this low seroprevalence, the researchers cautioned that "the Icelandic population is vulnerable to a second wave of infection."