israel natural immunity study notes

natural immunity superiority: https://www.medrxiv.org/content/10.1101/2021.08.24.21262415v1.full.pdf
    - compared group 1 (vaxxed) to group 2 (natural immunity, no vax) to group 3 (natural immunity + 1 vax dose)


Model 1 - previously infected vs. vaccinated individuals, with matching for time of
first event
[Matched 16,215 persons]
> 99 cases were recorded, 191 of which were in the vaccinated group and 8 in the previously
infected group. Symptoms for all analyses were recorded in the central database
within 5 days of the positive RT-PCR test for 90% of the patients, and included
chiefly fever, cough, breathing difficulties, diarrhea, loss of taste or smell, myalgia,
weakness, headache and sore throat. After adjusting for comorbidities, we found a
27.02-fold risk (95% CI, 12.7 to 57.5) for symptomatic breakthrough infection as
opposed to symptomatic reinfection (P<0.001) (Table 2b).
> Nine cases of COVID-19-related hospitalizations were recorded, 8 of which were in
the vaccinated group and 1 in the previously infected group (Table S1). No COVID-
19-related deaths were recorded in our cohorts.

Model 2 – previously infected vs. vaccinated individuals, without matching for time
of first event
[Matched 46,035 persons in each of the groups (previously infected vs.
vaccinated)]
> When comparing the vaccinated individuals to those previously infected at any time
(including during 2020), we found that throughout the follow-up period, 748 cases of
SARS-CoV-2 infection were recorded, 640 of which were in the vaccinated group
(breakthrough infections) and 108 in the previously infected group (reinfections).
After adjusting for comorbidities, a 5.96-fold increased risk (95% CI, 4.85 to 7.33)
for breakthrough infection as opposed to reinfection could be observed (P<0.001) (Table 3a)
> There was a 7.13-fold (95% CI, 5.51 to 9.21) increased risk for symptomatic breakthrough infection than
symptomatic reinfection (Table 3b). COVID-19 related hospitalizations occurred in 4
and 21 of the reinfection and breakthrough infection groups, respectively. Vaccinated
individuals had a 6.7-fold (95% CI, 1.99 to 22.56) increased to be admitted compared
to recovered individuals.

Model 3 - previously infected vs. vaccinated and previously infected individuals
[matched 14,029 persons]
>  Examining previously infected individuals to those who were
both previously infected and received a single dose of the vaccine, we found that the
latter group had a significant 0.53-fold (95% CI, 0.3 to 0.92) (Table 4a) decreased risk
for reinfection, as 20 had a positive RT-PCR test, compared to 37 in the previously
infected and unvaccinated group. Symptomatic disease was present in 16 single dose
vaccinees and in 23 of their unvaccinated counterparts. One COVID-19-related
hospitalization occurred in the unvaccinated previously infected group. No COVID-
19-related mortality was recorded.


[CONCLUSION]
> Our analysis demonstrates that SARS-CoV-2-naïve vaccinees had a 13.06-fold
increased risk for breakthrough infection with the Delta variant compared to those
previously infected, when the first event (infection or vaccination) occurred during
January and February of 2021. The increased risk was significant for a symptomatic
disease as well.
> Although the results could suggest waning natural
immunity against the Delta variant, those vaccinated are still at a 5.96-fold increased
risk for breakthrough infection and at a 7.13-fold increased risk for symptomatic
disease compared to those previously infected. SARS-CoV-2-naïve vaccinees were
also at a greater risk for COVID-19-related-hospitalization compared to those who
were previously infected.
> Individuals who were previously infected with SARS-CoV-2 seem to gain additional
protection from a subsequent single-dose vaccine regimen. Though this finding
corresponds to previous reports24,25, we could not demonstrate significance in our
cohort.
[CONCLUSION -> Speculation on mechanism of natural immunity superiority]
> The advantageous protection afforded by natural immunity that this analysis
demonstrates could be explained by the more extensive immune response to the
SARS-CoV-2 proteins than that generated by the anti-spike protein immune activation
conferred by the vaccine26,27. However, as a correlate of protection is yet to be
proven, including the role of B-Cell and T-cell immunity, this remains a
hypothesis.