Coronavirus Outbreak On A Fishing Vessel — What It Does And Doesn’t Tell Us About Covid-19 Immunity
Three persons on a boat of 122, among whom the virus spread widely, returned from a voyage virus-free
The presence of neutralising antibodies, on account of prior infection, appears to have protected them
What this tells us about coronavirus immunity – and what it doesn’t
Can you catch the coronavirus infection twice?
That’s a simple question on the surface. But underneath it is a complex set of moving parts, almost all of them under one kind of scientific investigation or another and evoking a wide range of expert predictions.
As seroprevalence surveys in Indian cities point to widespread coronavirus infections, one of the key aspects challenging researchers is whether infected people could recover and get re-infected upon exposure to the virus.
Finding the answer to this question is important for scientists and policymakers to chart a course forward in the battle against Covid-19.
In May this year, a fishing vessel with 122 crew members on board departed from Seattle, Washington.
The crew was tested before leaving, both by molecular and serological means, as a routine procedure.
While the reverse transcription-polymerase chain reaction (RT-PCR) test through nasopharyngeal swabbing would indicate the presence of the virus in the body, the testing of blood serum using an assay would tell if antibodies to SARS-CoV-2 were present in any of the crew members.
The screening occurred two days prior to departure.
The RT-PCR tests threw a negative result for the 120 crew members for whom the data was available, and the serological surveillance identified six individuals with antibodies, indicating a prior or ongoing infection in these persons.
They set sail on day three.
During the 16-day voyage, the virus took hold of most of the crew on the boat. After all, a fishing vessel is a confined space facilitating a high degree of contact between the people on board.
One of the crew members fell ill to the extent that he required hospitalisation.
In the meanwhile, on learning about the virus outbreak on the boat, researchers went back to the remaining serum samples from before and tested them further. They wanted to know if the antibodies detected in six crew members were of the “neutralising” kind.
Neutralising antibodies are important in mounting a defence against viral invaders. They bind to the virus in such a way so as to prevent infection.
After testing, it turned out that three of the six crew members with antibodies had neutralising antibodies against SARS-CoV-2.
After the boat’s return, crew members were tested again in the two ways. This time, the RT-PCR test data was available for all 122 crew members (as opposed to 120 pre-departure) and the antibody test yielded data for 114.
Data from within three weeks of return showed that 101 crew members of the 121 tested positive for the presence of virus in the body (a series of tests were conducted for a half-dozen weeks). Most of these individuals also registered a rise in serological response.
An attack rate of over 85 per cent was, eventually, registered for the outbreak on the vessel.
The key takeaway, which is being called a breakthrough, was that the three individuals who carried neutralising antibodies on to the boat tested negative for Covid-19 on return. They appear to have gone unscathed in the middle of a virus outbreak.
In contrast, 103 of the 117 individuals who were seronegative (no antibodies to SARS-CoV-2) before departure turned positive on tests post-arrival.
“This difference is statistically significant, indicating that pre-existing neutralizing antibodies are significantly associated with protection against SARS-CoV-2 infection,” the researchers write in the preprint.
The three individuals who had antibodies but not of the neutralising kind, tested Covid-19 positive after their return.
The researchers speculate that they had either registered false positives in initial screening – raising a doubt over the high specificity of the Abbott Architect assay – or were in the early stages of infection.
But the persons with neutralising antibodies came back virus-free, as per RT-PCR.
“If the claims are indeed what they are made to be, it says that if neutralising antibodies are available (presumably triggered by an earlier infection) in sufficient amounts (titre) at the time of a second infection, then there is protection from reinfection,” says Dr Aurnab Ghose, an associate professor at the Indian Institute of Science Education and Research, Pune, and a principal investigator behind the Pune seroprevalence survey.
The Seattle fishing boat study is, therefore, said to offer the first direct evidence that possessing neutralising antibodies against SARS-CoV-2 will protect an individual from re-infection.
“The basic principles outlined in this study are not new, so while it does not add anything new in that sense, it is good to see data that confirms expectations,” says Dr Ghose.
Prior to this study, direct evidence was limited to laboratory animals.
However, several questions arise from the study that demands further investigation.
Dr Gobardhan Das, a professor at the Jawaharlal Nehru University’s Center for Molecular Medicine, asks, “How long do these antibodies last? Many reports are coming out that indicate antibody responses in natural infection do not last long.”
Dr Ghose makes a similar point – “Studies from Wuhan and the UK (United Kingdom) indicate that antibody levels may wane in a couple of months. Does this mean antibody-based immunity is only short term?”
The half life of antibodies varies significantly depending on the type of antibody, genetic make-up, and aspects related to the presence of plasma and memory B cells.
Public discourse has revolved largely around antibodies, but the arsenal of immune memory B and T cells are critical to lasting immunity.
Evidence has emerged of T-cell-based immunity against SARS-CoV-2. The presence of T cells – possibly arising from infection to similar viruses in the past – is also being suggested as an explanation for why some people fend off the virus with relative ease while others fall severely ill.
Dr Das reminds, however, that “it is highly likely that if there is an antibody response, there is a T cell response too.”
“Without the help of T cells, affinity maturation of antibodies and class switching does not occur.” The process referred to here is one where T cells activate B cells to induce a proliferation of antibodies with greater affinity to the foreign substance that has entered the body.
A separate University of Washington study recently observed that the body’s defences, which include antibodies, T cells, and B cells, put up a fight against coronavirus for three months.
“We found that recovered individuals developed SARS-CoV-2-specific IgG antibody and neutralizing plasma, as well as virus-specific memory B and T cells that not only persisted, but in some cases increased numerically over three months following symptom onset,” the researchers in a preprint.
Ultimately, knowledge of the immune response to coronavirus can help shape our understanding of, and enable action on, how to slow the virus spread down to a trickle and safely evacuate from the Covid-19 pandemic.
The immunity can come about in two ways – one induced by the virus, the other by a vaccine.
Virus-induced immunity is when people get infected, recover, and then keep the infection out, protecting others around them in the process.
Vaccine-induced immunity is when enough people get inoculated in order to develop collective resistance against the virus and, consequently, its spread.
For both these cases, the outcome of the study on this Seattle fishing vessel is key, as also the questions that have come up around them. It is especially important for vaccine development.
“If a vaccine triggers long-lasting neutralising antibodies, that would, of course, be great. Along with T-cell responses, this is a parameter all vaccine developers are testing,” says Dr Ghose.
According to Dr Das, “One has to design a vaccine in a way that these antibodies last long and generate B cell memory responses.”
Dr Das and team are involved in developing a vaccine that induces an antibody response against the receptor-binding domain of the spike protein.
The good news with the Seattle trawler study is that the amount of antibodies found in the protected crew members is similar to the levels that would come with a vaccine.
Besides the broad questions around coronavirus immunity, the study has aspects that are searching for clarity.
For instance, how did the virus spread on the boat?
Professor Das suspects it may have been the individuals with the antibodies. “Preboard RT-PCR testing indicated none of the crew members as having RT-PCR positivity. I suspect that these three individuals who had sero positivity may have been the carriers.”
The protected individuals tested negative on RT-PCR before departure with nasopharyngeal swabbing, but the virus could have been present elsewhere, points out Dr Das. “The virus can survive in the intestine for a long time.”
In addition, for how significant the result of the study is, the size of the cohort in question – three – is extremely small.
Dr Ghose explains: “One reason for the slight hesitation about the claim is, this is not a controlled study and, in principle, purely by chance, the three individuals with neutralising activity (and about 14 others, I think) may have missed being infected.
“Perhaps they did not come in contact with enough viral particles. The chances of this in a heavily infected, contained environment is probably low, but it is still non-zero.”
Essentially, we may have gained a key insight into coronavirus immunity and a hope for ejecting from the pandemic with the Seattle fishing boat study, yet some key questions are unanswered. Hopefully, we’ll know soon.
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