Even since the first outbreak of novel coronavirus 2019 in China at the end of last year, there have been concerns around whether it’s even possible to develop lasting immunity against COVID-19. After all, even though humans are beset with thousands of disease-causing viruses, only seven are known to be coronaviruses. Of these, there are good indications that two—SARS and MERS—do generate an immune response that is thought to provide an extended period of immunity. The other four coronaviruses, which are the cause behind about 15% of chest colds, don’t generate a lasting immune response and can return after a short period.
If the body can’t develop lasting immunity, then not only is it impossible to achieve “herd immunity” as people become infected, but the quest for a effective vaccine is also very problematic. That’s why papers reporting a rapid decline in antibodies after only two months, and reports of people being reinfected with COVID-19 have generated widespread concern.
However, new information from a paper published in the New England Journal of Medicine this week, is considerably more hopeful, because it appears to show that antibody levels against the SARS-CoV-2 virus can persist months. And that those most at risk may have a stronger antibody response.
Honestly, the earlier papers showing a decline in antibodies weren’t that surprising, because they focused with patients who had light or asymptomatic cases of COVID-19. These patients had low levels of antibody production to begin with, when compared with patients who had moderate or severe cases, so it’s not really shocking that a few weeks on, some had antibody levels that dropped below the detection limits of some tests. What it does suggest is that an effective vaccine would have to generate higher levels of immune response than these light infections. Fortunately, Phase 2 trial results from the major vaccines indicate that this is the case.
When it comes to reinfection … it’s hard to say anything at this point except that it seems to be very rare, because the three cases that have been presented so far in pre-print articles are all quite different in timing and outcomes.
The new data comes from Iceland, the one nation on Earth that has approached the virus with a simple plan: Test everyone, isolate those who test positive, and continue until no one tests positive. The fact that Iceland’s population is significantly less than the state of Wyoming undoubtedly makes this more possible, but it remains one of the world’s most consistent, easy to explain, and straightforward ways of dealing with the pandemic. Iceland also has the benefit of being able to say their program worked. The first cases of the disease appeared on the island nation in February. By April, it was pretty much over. 1797 people were found to be infected before April 30—only 13 new cases appeared since then.
In this case, the authors of the paper (unsurprisingly a long list of “-sons” and “-dottirs” of Reykjavik) looked at data from 2102 samples collected from 1237 persons over a period ranging up to 4 months. Why four months? Because that’s pretty much the period between when those people were infected, and when the paper was written. That’s a review of 69% of all the people infected in the nation. Hard to ask for more than that.
91% of the people tested positive on antibody tests at the start of the test—meaning that some people who tested positive with PCR testing earlier didn’t test positive on the antibody tests even at the start of the test. Part of this may reflect some limits on the sensitivity or accuracy of the test, while part may be people whose infections never generated an antibody response. This means that some of the people who were in the earlier “antibodies falling” test may have been excluded from the ranks of the Iceland test from the outset, because by the time they got the antibody test, up to two months after recovering, they had already dropped below detectable levels.
In any case, what comes after the enrollment of patients is interesting: “Antiviral antibody titers assayed by two pan-Ig assays increased during 2 months after diagnosis by qPCR and remained on a plateau for the remainder of the study.” That is, antibody levels in those patients who tested positive initially actually rose over the first two months, they then remained fairly steady over the next two months. It’s hard to find any bad news in that.
Because they had a relatively large pool of samples, the researchers were also able to split their data out over several demographic groups.
- Women had about 9% lower antibody production than men … which seems odd, considering that men seem to die at a higher rate from COVID-19. This could be a connection between the cytokine storm responsible for a large number of COVID-19 deaths and gender, though the researchers did not speculate on this. That theory (that I just made up this moment, so even “theory” is being kind) might be bolstered by the fact that people on anti-inflammatory drugs also had a significantly lower immune response, and some anti-inflammatories have proven to lower mortality rates for COVID patients in extreme conditions. Stay tuned.
- Smokers had a much lower level of antibodies. Like 58% lower. Which could, perversely, help protect them from cytokine storms. Although COVID-19’s direct infection and inflammation of the lungs is likely connected to a higher death rate among smokers. So is smoker’s overall lower health (Warning: while the results are really, I’m still just making these conclusions up).
- SARS-CoV-2 antibody levels were higher in older people, with the level steadily increasing with age. Again, this probably shows that an over response by the immune system is one of the big factors involved in deaths due to COVID-19, just as it was with the 1918 flu pandemic. But the good news here could be that older people who recover from COVID-19 are well protected against reinfection. Oh and … see warning above.
- With all that in mind, it’s not surprising that people who were hospitalized also had very high levels of antibodies. These are the folks whose systems fought like heck … and almost got them along with the virus. “With respect to clinical characteristics, antibody levels were most strongly associated with hospitalization and clinical severity, followed by clinical symptoms such as fever, maximum temperature reading, cough, and loss of appetite. Severity of these individual symptoms, with the exception of loss of energy, was associated with higher antibody levels.”
In any case, looking at antibody production over time was not the primary goal of this paper, but the steady levels of antibodies over the four month period is a relief for anyone not relishing the idea of getting a “booster” on a monthly or quarterly basis. If older people who survived COVID-19, or those who had a really tough fight but pulled through, have good protection against reinfection, that’s great.
Now we need a vaccine that gives that protection to everyone, without the risks of catching the disease.
