Crew members from a Seattle-based fishing boat that experienced an explosive outbreak of the novel coronavirus have serendipitously provided what could be the first direct evidence that antibodies can protect people from reinfection.
Blood samples collected before the vessel sailed in May showed that three of the 122 people aboard had robust levels of neutralizing antibodies — the type that block the virus from entering human cells — indicating they had been previously infected and recovered. All three were spared during the shipboard outbreak, which quickly spread to more than 85% of the crew.
“It’s a strong indication that the presence of neutralizing antibodies is associated with protection from the virus,” said Dr. Alex Greninger, assistant director of the UW Medicine Clinical Virology Laboratory and co-author of a report posted on the preprint server MedRxiv that has not yet been peer-reviewed. “It’s hopeful news.”
However, it’s not really surprising, Greninger added. Researchers are generally confident that prior infection will provide some level of immunity. But what constitutes a protective immune response and how long immunity lasts is still unknown and of vital importance to the race for vaccines and other treatments.
Early vaccine trials, including one in Seattle, have induced strong antibody responses in volunteers. But the only direct evidence so far that neutralizing antibodies can protect against infection have come from monkeys and other laboratory animals.
It wouldn’t be ethical to deliberately expose humans to the virus — even people who have recovered from infection. But in this case, researchers from the University of Washington and Fred Hutchinson Cancer Research Center were able to analyze results from a natural experiment that played out in the close quarters and isolation of a vessel at sea.
“While this is a small study, it offers a remarkable, real-life, human experiment,” Danny Altmann, professor of immunology at Imperial College London, wrote in a commentary on the report. “Who knew immunology research on fishing boats could be so informative?”
The report does not identify the vessel, but Greninger confirmed it is the factory trawler FV American Dynasty, which was fishing for hake off the Washington coast when the outbreak struck. A statement from American Seafoods, which owns the ship and several others, says the company has partnered with the UW on its testing program and shares the data.
“We hope that their study will be beneficial to the broader scientific community in learning more about COVID-19,” said Valentina Zackrone, chief human resources officer at American Seafoods.
Mark Slifka, an immunologist and vaccine developer at Oregon Health & Science University who was not involved in the work, described it as “very, very interesting.”
The keys were the pre-departure blood testing of nearly the entire crew, and the stunning rate of infection — which means it’s unlikely that the three crew members with neutralizing antibodies were simply not exposed to the virus during the outbreak, Slifka said.
As part of ongoing efforts to protect fishing fleets, 120 of the 122 crew members were tested both for active infection, via nasal swabs, and previous exposure, via antibody blood testing, in the two days before the ship left port.
None of the nasal swabs was positive. But 18 days into its voyage, the ship returned to shore after a crew member became sick and needed hospitalization. Monitoring over the next 50 days showed that 104 crew members had been infected.
After learning of the outbreak, Greninger and his colleagues reexamined the results from the earlier blood tests and conducted additional tests on leftover specimens. Before departing, six crew members tested positive for antibodies that bind to the capsule of the novel coronavirus, but only three of those also had neutralizing antibodies.
While none of the crew members with neutralizing antibodies reported symptoms or became infected, the other three all got the virus — suggesting their initial results might have been false positives, Greninger said.
That adds to growing concern about the accuracy of many antibody tests and their ability to indicate immunity, Slifka pointed out.
Statistical analysis suggests it’s highly unlikely to be a random coincidence that all three people with neutralizing antibodies escaped infection. But the study doesn’t offer an explanation for the 15 other crew members who also apparently never became infected. It’s possible their jobs or actions on the boat shielded them from exposure, Greninger said.
Genomic analysis of virus from 39 crew members suggests that all the strains are closely related, but it doesn’t prove they all originated from a single infection, Greninger said.
The analysis doesn’t rule out the possibility that people can catch COVID-19 more than once, Slifka said, though it strongly suggests those who develop neutralizing antibodies may be protected. But the number of cases is too small to draw sweeping conclusions, he added.
This isn’t the first insight about the novel coronavirus to come from studying ships. Analysis of the outbreak early in the pandemic on the Diamond Princess cruise ship helped establish the importance of asymptomatic people in spreading the virus. Federal researchers who examined sailors on the aircraft carrier USS Theodore Roosevelt, where nearly 1,000 people were infected, documented a robust, neutralizing antibody response in more than half of those tested.