ELISA tests at Icahn School of Medicine contradict earlier studies which found that antibodies developed to combat the SARS-CoV-2 coronavirus are short-lived
Medical laboratories at the forefront of the COVID-19 pandemic will be intrigued to learn that antibodies produced by the body to combat the coronavirus infection may actually provide long-term immunity, contrary to previous studies that found otherwise.
A recent study from the Icahn School of Medicine at Mount Sinai found that the protection may be more robust than previously believed. This may surprise many clinical laboratory scientists and clinical pathologists. Since the outbreak of the pandemic, multiple studies have been published with conflicting findings about the strength of the immune response to SARS-CoV-2 and the length of immunity provided after an infection.
In a Mount Sinai news release, however, Florian Krammer, PhD, microbiologist and Professor of Vaccinology in the Department of Microbiology at the Icahn School of Medicine at Mount Sinai, and a senior author of the paper, said, “While some reports have come out saying antibodies to this virus go away quickly, we have found just the opposite—that more than 90% of people who were mildly or moderately ill produce an antibody response strong enough to neutralize the virus, and the response is maintained for many months.”
The researchers published the findings of their study—which was based on an internally-developed antibody test—in Science.
The study concludes, “Although this cannot provide conclusive evidence that these antibody responses protect from reinfection, we believe it is very likely that they will decrease the odds ratio of reinfection and may attenuate disease in the case of breakthrough infection. We believe it is imperative to swiftly perform studies to investigate and establish a correlate of protection from infection with SARS-CoV-2.”
Details of the Icahn School of Medicine Study
The study arose from an effort by Mount Sinai to identify potential donors for a convalescent plasma therapy program. Beginning in late March, the health system used an enzyme-linked immunosorbent assay (ELISA) to screen thousands of individuals for presence of antibodies to the spike protein in the SARS-CoV-2 virus. The virus uses the spike protein to bind to a receptor in host cells, the researchers noted, making it “the main, and potentially only target for neutralizing antibodies.”
Screened patients either had confirmed cases of COVID-19, as determined by a polymerase chain reaction (PCR) test, or suspected cases, “defined as being told by a physician that symptoms may be related to SARS-CoV-2 or exposure to someone with confirmed SARS-CoV-2 infection,” the researchers wrote. The Mount Sinai health system also offered the test to employees.
Samples from each person were diluted in five discrete titers (concentrations) ranging from 1:80 to 1:2880, and each was tested for detectable presence of the antibodies. This allowed the researchers to categorize the samples as low, moderate, or high:
- Low titers: 1:80 or 1:160
- Moderate titers: 1:320
- High titers: 1:960 or >1:2880
Between the start of the program and early October, the health system screened 72,401 people, of whom 30,082 tested positive for at least the lowest levels of antibodies. Among those who tested positive, a large majority fell into the moderate or high categories:
- 1:80: 690 (2.29%)
- 1:160: 1453 (4.83%)
- 1:320: 6765 (22.49%)
- 1:960: 9564 (31.79%)
- 1:2880: 11610 (38.60%)
The researchers also wanted to see whether the antibodies offered actual protection against the virus. So, they selected 120 samples and ran a quantitative microneutralization assay. In the lowest of the three categories, 50% of the samples showed neutralizing activity. That rose to 90% in the moderate category and 100% in the high category.
Finally, to determine how long protection might last, the researchers recalled 121 plasma donors for additional tests at two different points during the study. The researchers reported a slight drop in antibody levels about three months after onset of symptoms, and then a larger drop after five months. But antibodies were still present in most samples.
“It is still unclear if infection with SARS-CoV-2 in humans protects from reinfection and for how long,” the researchers wrote. “We know from work with common human coronaviruses that neutralizing antibodies are induced, and these antibodies can last for years and provide protection from reinfection or attenuate disease, even if individuals get reinfected.”
Previous ‘Conflicting’ Research
As previously noted, other studies raised doubts about the longevity of the antibodies produced by the body’s immune system. For example, the Mount Sinai researchers cited a study from China published in Nature Medicine that looked at the immune responses of 37 symptomatic patients and an equal number of asymptomatic individuals with laboratory-confirmed cases of the COVID-19 disease. In the latter group, 40% had no detectable levels of IgG antibodies after eight weeks.
The study also found a decrease in neutralizing antibodies in 30 of the asymptomatic individuals (81.1%) and 23 of the symptomatic individuals (62.2%) over the same period.
However, the Mount Sinai researchers pointed out that the antibody test in the Chinese study targeted a different protein. “The same paper also reported relatively stable (slightly declining) neutralizing antibody titers, which shows much higher concordance with our present findings,” they wrote. “Thus, the stability of the antibody response over time may also depend on the target antigen.”
A different study from England saw a 26% decline in antibodies over three months, CNN reported. That study, conducted by Imperial College London and Ipsos MORI, a market research firm, was based on responses from more than 365,000 randomly selected people who had self-administered a lateral flow antibody test.
But the seemingly conflicting studies from New York and the UK may not be contradictory, CNN reported. “People’s bodies produce an army of immune compounds in response to an infection and some are overwhelming at first, dying off quickly, while others build up more slowly. Measurements that show a waning antibody response in the first months after infection might be measuring this first wave—but there’s a second team building its forces in the background.”
In the same CNN report, Ania Wajnberg, MD, Director of Clinical Antibody Testing at Mount Sinai Hospital and co-author of the Icahn Mount Sinai study, said, “The serum antibody titer we measured in individuals initially were likely produced by plasmablasts—cells that act as first responders to an invading virus and come together to produce initial bouts of antibodies whose strength soon wanes.”
She added, “The sustained antibody levels that we subsequently observed are likely produced by long-lived plasma cells in the bone marrow. This is similar to what we see in other viruses and likely means they are here to stay. We will continue to follow this group over time to see if these levels remain stable as we suspect and hope they will.”
Does this mean that most people who get infected with the COVID-19 coronavirus will retain an immunity to the disease? Maybe. In the Icahn Mount Sanai study, Florian Kramer wrote, “More than 90% of people who were mildly or moderately ill produce an antibody response strong enough to neutralize the virus, and the response is maintained for many months.”
Thus, clinical laboratories engaged in serological testing may be asked to perform follow-up antibody tests to see if we do indeed create long-term immunity to COVID-19. Further, pathologists and medical laboratory scientists will want to follow future studies published in peer-reviewed journals to see if the findings of the Mount Sinai study are replicated at other sites.