Hello, and welcome to my channel Medicine with Dr. Moran. I'm a consultant in internal medicine.
How does previous Covid infection otherwise known as natural immunity fair with Omicron?
This strain has a number of mutations which allows it to have a degree of immune evasion
and it's a somewhat different virus to the original strain.
Now we know from previous extensive studies that natural immunity is at least as good
and some studies actually show that it's better than vaccinated immunity but that was based on
the Alpha and the Delta waves. This was one of the major mistakes of course made in the pandemic
that of ignoring those people who through no fault of their own got infected and developed natural
immunity. It was scientifically dishonest or said another way against evidence-based
medicine to actually ignore natural immunity. I presented many months ago in this video
which was based on a meta-analysis of natural immunity studies. There's a link to this video in
the description below if you're interested. I also made a community post last week on my channel when
one of those studies in the meta-analysis which was not previously peer-reviewed actually was
published in the New England Journal of Medicine one of our eminent medical journals. Today I want
to talk about a peer-reviewed study also published in the New England Journal of Medicine and it was
published this week. Now here is the study and as always there's a link below in the description if
you want to read it for yourself. The study was done in Qatar in the middle east. Now they use
data from December 23, 2021 all the way through February 21, 2022 which was during the omicron
wave to look at protection conferred by previous infection from variants other than omicron
and wanted to compare it with vaccination with either two or three doses of Pfizer or Moderna
as well as hybrid immunity, which means previous infection and then vaccination.
They looked at how effective the protection was against symptomatic omicron infection as well
as protection against severe disease. In Qatar they only use the Pfizer and Moderna vaccines.
They also have an extensive national medical database. The study I'm going to talk about
is an observational study it's a test negative case control design where they compared previous
infection or vaccination or hybrid immunity to control subjects with no infection or vaccination
and they try to match the cases and controls according to age, sex, nationality, and calendar
week of the PCR test, but not other things such as comorbidities which are health problems which
is one of the limitations of the study and notwithstanding the observational nature of
this study and despite some of the limitations of the observational study it does give us an idea
of how interventions did work in the Qatari population. Now the Qatari population is a little
younger than most countries which would be another limitation. Now on to the results and I'm going
to show all of their slides. This slide shows in figure a the effectiveness of the Pfizer vaccine
against any symptomatic omicron infection with previous infection in blue, two-dose vaccination
with no infection in light green, and three dose vaccination with no infection in dark green
and they compared that with time since previous infection or previous vaccination.
People in the blue group were people who had previously been infected with a variant
other than omicron and as you can see the effectiveness stayed relatively constant
even out well past 12 months the confidence intervals even out past 12 months actually
overlapped the initial numbers at 4 to 6 months. Now if you compare this with the group that had
the two-dose vaccination with Pfizer with no previous infection the vaccine efficacy dropped
off from 40 initially down to 13 and then down to minus -3.4% after more than six months. Remember
that this is protection against getting an infection not protection against severe disease.
Lastly if you look at the third group who received three doses of Pfizer but had never been
infected the effectiveness of the third dose did transiently increase the effectiveness to 58
within a month but this fell significantly to 44 beyond one month. Now it's important to note that
most people got their third vaccination within 45 days and so there's very little long-term data in
this group beyond three months and this group may very well have declining vaccine efficacy
going beyond that period of time just like the people in the 2 dose vaccine group did. This
figure obviously demonstrates the power of natural immunity and clearly shows like many previous
studies that it's better than two doses of vaccine and at least as good as a recent third booster.
Now looking at figure B this shows the same results for the Moderna vaccine.
As you can see the same kind of effectiveness is seen in the natural immunity group in blue,
the declining effectiveness of the two dose Moderna in light green,
and the higher numbers for the third dose. The next slide I want to show you
in figure A you can see the effectiveness of Moderna against symptomatic BA1 infection which
is a subvariant of Omicron and you can see that previous infection at 45.1 is better than two
doses of vaccine minus 2.7 and similar to two doses of vaccine and previous infection of 44.3
as well as three doses of vaccine at 56.5. In fact the confidence intervals actually overlap to show
that previous infection alone is not statistically significantly different to three doses of vaccine
and previous infection even though the average number is 45.1 is a little different than 77.2. I
should note that many of the people with previous infection had been infected more than six months
previously and in fact even more than 12 months previously as mentioned before the group with the
three doses and previous infection had their third dose within 45 days that was the vast majority.
Now figure B shows the effectiveness of Moderna against severe BA1 infection and you can see that
due to small numbers of people who had severe disease the confidence intervals or the bars
in the figure are very wide but the numbers are actually very similar. It's nice to see that not
only previous infection but two doses of vaccine have high protection against severe disease.
Now figure C and D show them the results from Moderna against BA2 and similar findings are noted
to BA1 as I just mentioned. This slide shows the same data for Pfizer against BA1 and BA2
and again they're quite wide confidence intervals due to the small numbers of people in figure B
and figure D but none of the groups are statistically different from each other.
In figure C there is better effectiveness with three doses of the vaccine and previous infection
compared to just previous infection alone but as I've mentioned before the higher effectiveness
is likely due to the recent third dose and this may very well wane with time.
The last slide I want to show shows effectiveness against any symptomatic Omicron infection for the
Pfizer vaccine in A and Moderna in C and once again previous infection is equivalent to two
doses of vaccine and previous infection and three doses of vaccine with no infection. It shows that
three doses of vaccine with previous infection gives numbers that are statistically higher which
is 76.3 for Pfizer and 79.4 for Moderna than someone with only a previous infection at 50.8
and 52.2. Again the study authors mentioned that most people received their third dose
less than 45 days earlier which likely explains the relatively high effectiveness in this group.
I would speculate though if you wait the people with three doses of vaccine and previous infection
would likely have declining effectiveness as antibodies start to wane and they may
come down into that 50 to 60 range. This is an important point as timing is everything.
We know antibodies wane after these booster injections we've seen that in study after study
what we really want to know is whether a third dose or a fourth dose of a vaccine affords any
long-term not short-term but long-term durability against severe disease
and if it does in what patient populations but we don't have any data on this at this time.
It would make sense that in people at high risk for severe disease a booster vaccine
dose would afford protection for a short period of time while the antibody levels are increased.
In figure B and figure D there are again wide confidence intervals but it's reassuring to
see that protection against severe disease is well maintained in all of the groups.
Now the conclusions from this observational study as stated by the authors are that there are no
discernible differences in protection against symptomatic BA1 and BA2 Omicron infections
in people with previous infection, three doses of vaccination, and even hybrid immunity. There was
no difference between Pfizer and Moderna vaccines in the study. They indicate that hybrid immunity
resulting from previous infection then booster vaccination conferred the strongest protection
but as I've mentioned several times the booster vaccination in most people was actually recent
within 45 days and it's possible that that benefit is very short-lived and not sustained.
In addition all five forms of immunity that I've discussed in the study were associated with strong
and durable protection against Covid-19 related hospitalization and death which
is the most important metric by far. So if you're wondering how well natural immunity with previous
variants stack up against Omicron this study is our best evidence from Qatar and really
the only good study that I've seen so far in regards to this. Thank you for joining
me today on Medicine with Dr. Moran. I'm Dr. Keith Moran and remember get healthy and stay healthy,
Meow!