Immune Imprinting and Coverage in opposition to Repeat Reinfection with SARS-CoV-2


To the Editor:

Greater than 2 years into the coronavirus illness 2019 (Covid-19) pandemic, the worldwide inhabitants carries heterogeneous immune histories derived from quite a lot of exposures to an infection, viral variants, and vaccination.1 Proof on the degree of binding and neutralizing antibodies and B-cell and T-cell immunity suggests {that a} historical past of an infection with serious acute breathing syndrome coronavirus 2 (SARS-CoV-2) may have a adverse impact on next protecting immunity.1 Particularly, the immune reaction to B.1.1.529 (omicron) subvariants may well be compromised by means of differential immune imprinting in individuals who’ve had a prior an infection with the unique virus or the B.1.1.7 (alpha) variant.1

We investigated the epidemiologic proof for immune imprinting in individuals with explicit immune histories associated with herbal an infection. We evaluated the prevalence of repeat reinfection within the nationwide cohort of individuals in Qatar who had had a documented omicron BA.1 or BA.2 reinfection after a number one an infection with non-omicron SARS-CoV-2 (the “double-primed” cohort) as when compared with the prevalence of reinfection within the nationwide cohort of individuals who had had a documented number one an infection with omicron BA.1 or BA.2 (the “omicron-primed” cohort).2 This research was once carried out as a matched retrospective cohort find out about (Segment S1 within the Supplementary Appendix, to be had with the overall textual content of this letter at NEJM.org).

Information on SARS-CoV-2 laboratory checking out, medical an infection, vaccination, and demographic traits have been extracted from the Qatar nationwide SARS-CoV-2 databases. Individuals in each cohorts have been precisely matched in a 1:3 ratio consistent with intercourse, 10-year age team, nationality, selection of coexisting prerequisites, and calendar week of the omicron subvariant an infection. The follow-up length began at 90 days after documentation of the omicron subvariant an infection. Vaccinated individuals have been excluded. Associations have been estimated with the usage of Cox proportional-hazards regression fashions. Danger ratios have been adjusted for the standards used for matching.

Determine S1 within the Supplementary Appendix displays the inhabitants variety procedure, and Desk S1 displays the baseline traits of the overall and paired cohorts. The matched cohorts incorporated 7873 individuals within the double-primed cohort and 22,349 individuals within the omicron-primed cohort. The find out about inhabitants was once consultant of the unvaccinated inhabitants of Qatar with admire to demographic traits and histories of SARS-CoV-2 an infection (Desk S2).

Prevalence of SARS-CoV-2 Reinfection within the Double-Primed and Omicron-Primed Cohorts.

The double-primed cohort incorporated individuals with a documented reinfection with B.1.1.529 (omicron) subvariant BA.1 or BA.2 after a number one an infection with pre-omicron serious acute breathing syndrome coronavirus 2 (SARS-CoV-2), and the omicron-primed cohort incorporated individuals with a documented number one an infection with an omicron BA.1 or BA.2 subvariant. The inset in Panel A displays the similar knowledge on an expanded y axis. The principle research incorporated the overall matched cohorts; in an extra research (Panel B), the double-primed cohort incorporated simplest individuals whose number one an infection were with the unique virus or the B.1.1.7 (alpha) variant. Danger ratios have been adjusted for the standards used for matching. This find out about was once performed in Qatar between December 19, 2021, and August 15, 2022. Practice-up began 90 days after documentation of reinfection. The median period of follow-up was once 125 days (interquartile vary, 114 to 132) in each and every cohort.

All through follow-up, 63 reinfections befell within the double-primed cohort and 343 befell within the omicron-primed cohort; not one of the infections advanced to serious, vital, or deadly Covid-19 (Fig. S1). At 135 days after the beginning of follow-up, the cumulative prevalence of reinfection was once 1.1% (95% self belief period [CI], 0.8 to one.4) within the double-primed cohort and a pair of.1% (95% CI, 1.8 to two.3) within the omicron-primed cohort (Determine 1A). Within the comparability of the overall matched double-primed cohort with the omicron-primed cohort, the adjusted danger ratio for reinfection was once 0.52 (95% CI, 0.40 to 0.68). In an research involving the subgroup of individuals within the double-primed cohort whose number one an infection was once with the unique virus or the alpha variant as when compared with the omicron-primed cohort, the adjusted danger ratio for an infection was once 0.59 (95% CI, 0.40 to 0.85) (Determine 1B).

Within the first 70 days of follow-up, when infections have been ruled by means of the BA.2 subvariant,2,3 the adjusted danger ratio for an infection was once 0.92 (95% CI, 0.51 to one.65). Alternatively, the cumulative prevalence curves diverged when the BA.4 and BA.5 subvariants have been presented and therefore ruled4 (adjusted danger ratio, 0.46; 95% CI, 0.34 to 0.62) (Determine 1A).

Obstacles of the find out about are mentioned in Segment S1. One possible limitation was once the adaptation within the frequencies of checking out between the 2 cohorts, however a sensitivity research with adjustment for those variations confirmed effects very similar to the ones in the principle research.

Omicron an infection induces robust coverage in opposition to a next omicron an infection.2,4 Within the provide cohort find out about, an extra, previous an infection with non-omicron SARS-CoV-2 was once discovered to beef up this coverage in opposition to a next omicron an infection. The sooner pre-omicron an infection can have broadened the immune reaction in opposition to a long term reinfection problem.

Hiam Chemaitelly, Ph.D.
Weill Cornell Medication–Qatar, Doha, Qatar
[email protected]

Houssein H. Ayoub, Ph.D.
Qatar College, Doha, Qatar

Patrick Tang, M.D., Ph.D.
Mohammad R. Hasan, Ph.D.
Sidra Medication, Doha, Qatar

Peter Coyle, M.D.
Hamad Scientific Company, Doha, Qatar

Hadi M. Yassine, Ph.D.
Hebah A. Al-Khatib, Ph.D.
Maria Okay. Smatti, M.Sc.
Qatar College, Doha, Qatar

Zaina Al-Kanaani, Ph.D.
Einas Al-Kuwari, M.D.
Andrew Jeremijenko, M.D.
Anvar H. Kaleeckal, M.Sc.
Ali N. Latif, M.D.
Riyazuddin M. Shaik, M.Sc.
Hamad Scientific Company, Doha, Qatar

Hanan F. Abdul-Rahim, Ph.D.
Gheyath Okay. Nasrallah, Ph.D.
Qatar College, Doha, Qatar

Mohamed G. Al-Kuwari, M.D.
Number one Well being Care Company, Doha, Qatar

Adeel A. Butt, M.B., B.S.
Hamad Scientific Company, Doha, Qatar

Hamad E. Al-Romaihi, M.D.
Mohamed H. Al-Thani, M.D.
Ministry of Public Well being, Doha, Qatar

Abdullatif Al-Khal, M.D.
Hamad Scientific Company, Doha, Qatar

Roberto Bertollini, M.D., M.P.H.
Ministry of Public Well being, Doha, Qatar

Laith J. Abu-Raddad, Ph.D.
Weill Cornell Medication–Qatar, Doha, Qatar
[email protected]

Supported by means of the Biomedical Analysis Program and the Biostatistics, Epidemiology, and Biomathematics Analysis Core at Weill Cornell Medication–Qatar; the Qatar Ministry of Public Well being; Hamad Scientific Company; and Sidra Medication. The Qatar Genome Program and Qatar College Biomedical Analysis Middle supported viral genome sequencing.

Disclosure paperwork supplied by means of the authors are to be had with the overall textual content of this letter at NEJM.org.

This letter was once revealed on October 12, 2022, at NEJM.org.

  1. 1. Reynolds CJ, Pade C, Gibbons JM, et al. Immune boosting by means of B.1.1.529 (omicron) is dependent upon earlier SARS-CoV-2 publicity. Science 2022;377(6603):eabq1841eabq1841.

  2. 2. Chemaitelly H, Ayoub HH, Coyle P, et al. Coverage of omicron sub-lineage an infection in opposition to reinfection with any other omicron sub-lineage. Nat Commun 2022;13:46754675.

  3. 3. Altarawneh HN, Chemaitelly H, Ayoub HH, et al. Results of earlier an infection and vaccination on symptomatic omicron infections. N Engl J Med 2022;387:2134.

  4. 4. Altarawneh HN, Chemaitelly H, Ayoub HH, et al. Protecting impact of earlier SARS-CoV-2 an infection in opposition to omicron BA.4 and BA.5 subvariants. N Engl J Med 2022;387:16201622.


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