There has been a lot of discussion about COVID-19 immunity — does an infection, mild or serious, confer immunity? If so, then for how long? Has anyone demonstrated that infections or vaccines protect individuals from future infections?
Most studies of infected patients and vaccine phase 1 and 2 trials demonstrate the presence of antibodies, neutralizing antibodies and even B and T cells. But they do not prove protection against future infections. To demonstrate that would require a person to get re-infected and studies do not intentionally re-infect human (they have done so in animals). That is what phase 3 trails are for, where a large number of participants (upwards of 30,000) are given vaccines and placebos, typically in a region with a high infection rate. The participants are monitored over a period of months to years to observe what percentage of individuals in each group gets infected naturally. It is a time-consuming and expensive process and it cannot be rushed, although preliminary conclusions can be drawn if sufficient number of infections are detected early.
UW Virology, Bloom Lab and Greninger Lab recently published this pre-print (not peer reviewed yet) report, which provides an answer to the question of immunity, based on a simple “accidental” event that took place in May.
- In May, a fishing boat with 122 passengers+crew left port in Seattle. Nearly all passengers (120 / 122) were tested both for virus and for anti-N antibodies (Abbott assay) in tests run by UW Lab Medicine, before departure, for obvious reasons.
- As fate would have it, one of the passengers was carrying the virus and on return 103 of the 120 passengers with pre-boarding serology got infected.
- Scientists at UWLabs decided to correlate pre-boarding serology results with new infections and look for clues.
- It turned out that 3 of 120 passengers had tested positive during pre-boarding for anti-N antibodies, anti-Spike & neutralizing antibodies, implying that they had a prior infection.
- Guess what? On return, none of the 3 with the neutralizing antibodies were infected, while 103 of 117 without neutralizing antibodies were infected. According to the authors, this is highly significant by Fisher's exact test (p = 0.0024).
|
Neutralizing Ab (+) |
Neutralizing Ab (-) |
Row Total |
| Infected |
0 |
103 |
103 |
| Not infected |
3 |
14 |
17 |
| Column Total |
3 |
117 |
120 |
p = 103C0 * 17C3 / 120C3 = 0.00242
- The ship returned to shore after 18 days after a crew member became sick, tested positive for SARS-CoV-2, and required hospitalization.
- In the week after return, 98 individuals tested positive.
- Testing was performed until day 50 after departure.
The authors point out the limitations of the study —
- This study shows correlation not causation. They can't be sure they are causal vs some co-occurring immune response.
- Since there were only 3 individuals in neut antibody group, there is no certainty that they were actually exposed to the virus.
Note that this was not a planned study. So, it does not have all the data and controls one might expect if one were to do a controlled experiment (which one cannot).
This does not say anything about vaccines, but it does provide a strong hint that the human immune system does react to the COVID-19 virus and provides protection, at least for a few months.
Note that there were three additional individuals who tested seropositive before departure but they did not have neutralizing activity and had lower quantitative readings in the Abbott assay. The researchers speculate that these three individuals were false positives in the initial serological screening. Alternatively, they could have been in the early stages of active infection or they could have experienced a mild or asymptomatic infection, which can be associated with transient or low-level seroconversion.
Most of the paper deals with the meticulous testing performed on the subjects.
CDC
Along these lines, the CDC recently provided this guideline that recovered patients are protected for at least 3 months.
Many media outlets misreported the press release and scientists are hopping mad about it.
Immunity Studies in Animals
These 2 per-reviewed publications show that rhesus macaques developed immune responses that protect against a second infection.
The pre-print for the first paper was posted on March 14.
Other recent studies on Immunity
- 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.
- Furthermore, the SARS-CoV-2-specific memory lymphocytes exhibited characteristics associated with potent antiviral immunity: memory T cells secreted IFN-γ and expanded upon antigen re-encounter, while memory B cells expressed receptors capable of neutralizing virus when expressed as antibodies.
- These findings demonstrate that mild COVID-19 elicits memory lymphocytes that persist and display functional hallmarks associated with antiviral protective immunity.
One more recent study concludes that “Our collective dataset shows that SARS-CoV-2 elicits robust, broad and highly functional memory T cell responses, suggesting that natural exposure or infection may prevent recurrent episodes of severe COVID-19.”
The human immune system is marvel of nature. Most immunologists will tell you that it is extremely complicated and there is much we do not understand yet.
For an excellent primer on the human immune system, check out Ed Yong’s article in the Atlantic -
Epilogue
All this is good news and frankly not unexpected for most scientists. However, this study does not constitute proof that infection provides immunity or that vaccines will be successful. For that, we will have to wait for phase 3 results for many of the front-runner vaccines (Moderna, Oxford/AstraZeneca, Pfizer/BioNTech, CanSino, Sinovac, Sinopharm and others).
Nor does it mean getting more infections is the way to achieve herd immunity. The cost to society is too high — for those who die and even for those who survive COVID-19.
Further Reading
- Neutralizing antibodies correlate with protection from SARS-CoV-2 in humans during a fishery vessel outbreak with high attack rate — www.medrxiv.org/…
- Functional SARS-CoV-2-specific immune memory persists after mild COVID-19 — www.medrxiv.org/…
- How China Controlled COVID-19 - by Peter Hessler — www.dailykos.com/...
- COVID-19 Vaccines - Where are we now? And what lies ahead? — www.dailykos.com/…
