Immune imprinting and protection against recurrent reinfection with SARS-CoV-2

To the editor:

More than 2 years after the 2019 coronavirus illness (Covid-19) pandemic, the world’s inhabitants carries heterogeneous immune histories ensuing from totally different exposures to an infection, viral variants, and vaccinations.1 Evidence on the ranges of binding and neutralizing antibodies and B-cell and T-cell immunity suggests {that a} historical past of extreme acute respiratory syndrome coronavirus 2 (SARS-CoV-2) an infection could negatively affect subsequent protecting immunity.1 In specific, the immune response to B.1.1.529 (omicron) subvariants could also be impaired by differential immune imprinting in people beforehand contaminated with the unique virus or the B.1.1.7 (alpha) variant.1

We investigated the epidemiological proof of immune imprinting in people with a particular immune historical past related with pure an infection. We evaluated the incidence of recurrence in a nationwide cohort of people with documented omicron BA.1 or BA.2 reinfection after a primary an infection with non-omicron SARS-CoV-2 (the “dual-primed” cohort) in Qatar. Compared with the incidence of reinfection in a nationwide cohort of people with documented major an infection with BA.1 or BA.2 omicrons (“omicron-primed” cohort).two This evaluation was carried out as a matched retrospective cohort examine (Section S1 within the Supplementary Appendix , which is obtainable with the complete textual content of this letter at NEJM.org).

Data on SARS-CoV-2 laboratory testing, medical an infection, vaccination, and demographic traits had been obtained from Qatar’s nationwide SARS-CoV-2 database. Individuals within the two cohorts had been precisely matched in a 1:3 ratio for intercourse, 10 years of age, ethnicity, variety of coexisting circumstances, and calendar week of omicron subvariant an infection. The follow-up interval started 90 days after documentation of Omicron subvariant an infection. Vaccinated people had been excluded. Associations had been assessed utilizing Cox proportional-hazards regression fashions. Hazard ratios had been adjusted for confounding elements.

Figure S1 within the Supplementary Appendix exhibits the inhabitants choice course of, and Table S1 exhibits the baseline traits of the entire and matched cohorts. Matched cohorts included 7,873 people within the doubling cohort and 22,349 people within the omicron cohort. The examine inhabitants was consultant of the unvaccinated inhabitants of Qatar by way of demographic traits and historical past of SARS-CoV-2 an infection (desk S2).

Incidence of SARS-CoV-2 Reinfection in Double-Primed and Omicron-Primed Cohorts.

The dual-primed cohort included people with documented reinfection with B.1.1.529 (omicron) subvariant BA.1 or BA.2 after a primary an infection with coronavirus 2 (SARS-CoV-2) and the omicron-primed cohort included omicron BA.1 or BA. Individuals with documented major an infection with subtype 2 had been included. Insects in panel A present the identical information on an expanded y-axis. The major evaluation included totally matched cohorts; in an extra evaluation (Panel B), the dual-prime cohort included solely people whose major an infection was both the unique virus or the B.1.1.7 (alpha) variant. Hazard ratios had been adjusted for confounding elements. This examine was carried out in Qatar from December 19, 2021 to August 15, 2022. Follow-up started 90 days after documentation of reinfection. The median period of follow-up in every cohort was 125 days (interquartile vary, 114 to 132).

During follow-up, there have been 63 reinfections within the dual-primed cohort and 343 within the micron-primed cohort; not one of the infections progressed to extreme, vital, or deadly Covid-19 (Figure S1). After 135 days of follow-up, the cumulative incidence of reinfection was 1.1% (95% confidence interval). [CI]0.8 to 1.4) within the double-primed cohort and 2.1% (95% CI, 1.8 to 2.3) within the omicron-primed cohort (Figure 1A). Comparing the totally matched double-primed cohort with the omicron-primed cohort, the adjusted hazard ratio for reinfection was 0.52 (95% CI, 0.40 to 0.68). In an evaluation that included the subgroup of people within the dual-prime cohort with major an infection with both the unique virus or the alpha variant, in contrast with the omicron cohort, the adjusted hazard ratio for an infection was 0.59 (95% CI, to 0.40). 0.85) (Figure 1B).

During the 70-day follow-up interval, when the infections had been first dominated by the BA.2 subvariant,2.3 The adjusted hazard ratio was 0.92 (95% CI, 0.51 to 1.65). However, cumulative incidence curves differed when subvariants BA.4 and BA.5 had been included and turned dominant later.4 (adjusted hazard ratio, 0.46; 95% CI, 0.34 to 0.62) (Figure 1A).

Limitations of the examine are mentioned in Section S1. One potential limitation was the distinction in testing frequency between the 2 cohorts, however a sensitivity evaluation adjusting for these variations confirmed comparable outcomes to these in the primary evaluation.

Omicron an infection induces sturdy protection against subsequent omicron an infection.2.4 In the present cohort examine, extra, earlier an infection with SARS-CoV-2 enhanced protection against subsequent omicron an infection. A earlier pre-omicron an infection could amplify the immune response against future reinfection.

Hiam Chemaitelli, Ph.D.
Weill Cornell Medicine – Qatar, Doha, Qatar
[email protected]

Hussain H. Ayyub, candidate of philosophy.
Qatar University, Doha, Qatar

Patrick Tang, Ph.D.
Mohammad R Hasan, Ph.D.
Sidr Medicine, Doha, Qatar

Peter Coyle, MD
Hamad Medical Corporation, Doha, Qatar

Hadi M. Yassine, Ph.D.
Hebach A. Al-Khatib, candidate of philosophy.
Maria Okay. Smatty, M.D.
Qatar University, Doha, Qatar

Zaina Al-Kanaani, Ph.D.
Einas Al-Kuwari, MD
Andrew Jeremienko, MD
Anwar Kh. Kaleekkal, Master.
Ali N. Latif, physician of medical sciences
Riyazuddin M. Shaik, M.Sc.
Hamad Medical Corporation, Doha, Qatar

Hanan F. Abdul-Rahim, candidate of philological sciences.
Geyat Okay. Nasrallah, Ph.D.
Qatar University, Doha, Qatar

Mohamed G. Al-Kuwari, MD
Primary Health Care Corporation, Doha, Qatar

Adeel A. Butt, MB, BS
Hamad Medical Corporation, Doha, Qatar

Hamad E. Al-Romaihi, MD
Mohamed H. Al-Thani, MD
Ministry of Public Health, Doha, Qatar

Abdullatif Al-Khal, Doctor of Medicine
Hamad Medical Corporation, Doha, Qatar

Roberto Bertolini, MD, MPH
Ministry of Public Health, Doha, Qatar

Light J. Abu-Raddad, Candidate of Philosophical Sciences.
Weill Cornell Medicine – Qatar, Doha, Qatar
[email protected]

supported by Biomedical Research Program and Biostatistics, Epidemiology, and Biomathematics Research Core Weill Cornell Medicine – Qatar; the Qatar Ministry of Health; Hamad Medical Corporation; and Cider Medicine. The Qatar Genome Program and Qatar University Biomedical Research Center supported the sequencing of the viral genome.

Disclosure varieties supplied by the authors can be found at NEJM.org, alongside with the complete textual content of this letter.

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

  1. 1. Reynolds CJ, Pad C, Gibbons JM, and many others. Immune enhancement to B.1.1.529 (omicron) is determined by earlier publicity to SARS-CoV-2. science 2022;377(6603):eabq1841eabq1841.

  2. two. Chemical H, Ayoub HH, Coyle P, and many others. Protection of omicron sub-line an infection from re-infection with one other omicron sub-line. Nat Common 202213:46754675.

  3. 3. Altaravneh H.N, Chemical H, Ayoub HH, and many others. Effect of earlier an infection and vaccination on symptomatic micron infections. N Engl J Med 2022;387:2134.

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