Since the early weeks of the COVID-19 outbreak in Hubei province, China, there have been reports of patients who were released after testing negative for the virus, only to test positive again at a later date. There are a lot of possible reasons for this, including testing error and lack of sufficient sensitivity in a test. But in some small studies, the number of people who were negative then positive again was as high as 15%, which seems like a lot to miss even for a sloppy, badly-pressed testing system.
These numbers have definitely raised concerns over whether it is possible to be reinfected by 2019 novel coronavirus, and whether having the disease and recovering really confers lasting immunity. On the other hand, there has been every reason to expect that immunity is a given, based on the example of many similar viruses. However, a new study in Shanghai may have the answer: Having COVID-19 provides lasting, strong immunity … for most people. But there may actually be a group that’s vulnerable to reinfection, and that group may not be what anyone was expecting.
After multiple attempts to figure out just how many people have few or no symptoms from an infection of novel coronavirus, the consensus remains that this fraction represents about one-half of those carrying COVID-19. Identifying just why some people have a very mild case has been much more difficult to determine, but these patients seem as likely to be 60 years old as 30. It’s among this group of asymptomatic to very mild cases that a study reported in the South China Morning Post found some puzzling results.
The study, which was not random and has not been subject to peer review, looked at blood samples taken from 175 patients who had at some point tested positive for COVID-19, but who had never developed critical symptoms. Of this group, one-third had very low levels of antibodies. Some were so low that the blood test did not detect them.
While this number—one-third of a group that represents about one-half of those who catch COVID-19—comes very close to the 15% number some earlier studies had indicated as people who subsequently tested positive a second time, this doesn’t definitely mean that the group with the very low antibody count is subject to being reinfected. The chance of errors in testing at some point in the process remains, and many of those who tested negative then positive may have experienced a rebound of the same infection rather than a genuine reinfection from another source.
But while the distribution of those catching COVID-19 may be more or less even across age brackets, the distribution of these “low antibodies” cases was not. Most of those who had low antibodies were young. In fact, the study showed the level of antibodies increased with age. Patients over 60 had three times the amount of antibodies as those under 40, even though both groups had mild cases of COVID-19.
If accurate, these results have a number of considerations:
- A portion of low-symptom COVID-19 patients may be subject to reinfection or rebound. It’s completely unclear whether a second round of infection is more or less mild than the first round, or whether this second round would increase the number of antibodies present.
- This weak response to the virus may also have implications for teams working on vaccines for COVID-19. If the fragments of the virus chosen for vaccine mimic this result, some portion of those vaccinated might not develop sufficient antibodies to proof them against infection. This may lead to suggestions for increased dosages or multiple-shot vaccines.
- A portion of those now considered “safe” because they’ve had the disease and recovered may be subject to reinfection, representing a danger to both themselves and acting as a vector to others.
- Vaccines may actually work better for the older population most at risk from the COVID-19 infection.
All of this is very early, unconfirmed research and 175 patients is still a very small group to characterize the tens of thousands who have already recovered from COVID-19 or the millions who will follow. Nothing about this study suggests that it was done in any randomized way, and the lack of peer review on the published paper means that there could be serious issues in methodology, even aside from some obvious issues with how the test group was defined.
One very interesting point: The researchers in Shanghai excluded any patients who had more serious cases of COVID-19 from the study exactly because use of plasma or antibodies from recovered patients has become common in treatment of critical cases there. So in anyone who had a more serious cases of COVID-19, they would have a mix of their own antibodies and those given to them as treatment. That this treatment has become so common in the country where the pandemic began may suggest that they’ve seen good results with these treatments. But, just as with the antibody study covered here, those results don’t seem to be well-documented.