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Volume 28, Number 5—May 2022
Research Letter

Cross-Variant Neutralizing Serum Activity after SARS-CoV-2 Breakthrough Infections

Pinkus Tober-Lau1, Henning Gruell1, Kanika Vanshylla1, Willi M. Koch, David Hillus, Philipp Schommers, Isabelle Suárez, Norbert Suttorp, Leif Erik Sander2, Florian Klein2, and Florian Kurth2Comments to Author 
Author affiliations: Charité–Universitätsmedizin Berlin, Berlin, Germany (P. Tober-Lau, W.M. Koch, D. Hillus, N. Suttorp, L.E. Sander, F. Kurth); University of Cologne, Cologne, Germany (H. Gruell, K. Vanshylla, P. Schommers, I. Suárez, F. Klein); German Center for Infection Research, Bonn-Cologne, Germany (F. Klein); Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany (F. Kurth); University Medical Centre Hamburg-Eppendorf, 20359, Hamburg (F. Kurth)

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Figure

SARS-CoV-2 serum neutralizing titers across variants after postvaccination breakthrough infection. A) Schematic of the study cohort of 2×VI patients and age-matched reference cohorts (1). B) Serum neutralizing activity against Wu01 and SARS-CoV-2 variants in 2×V persons (triangles) and 2×V/I persons (circles). Horizontal lines indicate geometric mean ID50s; error bars, 95% CIs. Groups were compared by using the Mann-Whitney test. p values are shown at top. C) Correlation of serum neutralizing activity against SARS-CoV-2 Wu01 (blue) or Omicron (red) and interval between second vaccination and non-Omicron breakthrough infection (Spearman ρ and p values). Breakthrough infections within 3 months (90 days) from vaccination are indicated by light shaded symbols. Solid lines indicate linear regression, and dashed lines indicate 95% CIs. Correlation was determined by Spearman ρ. D) Serum neutralizing activity against SARS-CoV-2 Wu01 (blue) and Omicron (red) in 2×V or 3×V persons (triangles) compared with 2×V/I non-Omicron (circles) or Omicron (triangles) persons after 2 and 3 doses of mRNA vaccine. Only persons with vaccine-to-infection intervals >3 months are shown. Groups were compared by using the Kruskal-Wallis test with the Dunn multiple testing correction. Horizontal lines indicate geometric mean ID50s; error bars, 95% CIs. p values are shown at top. Black dotted lines in panels B, C, and D indicate the lower limit of quantification (ID50 = 10); ID50s <10 were imputed to half the lower limit of quantification (ID50 = 5). ID50, 50% inhibitory serum dilution; O, Omicron; pNT, pseudovirus neutralization test; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; V/I, vaccination with subsequent breakthrough infection; Wu01, ancestral (wild-type) SARS-CoV-2 strain; 2xV/I non-Omicron, vaccinated persons with non-Omicron breakthrough infection that occurred 1–8 months after vaccination (circles); 2xV/I Omicron, vaccinated persons with Omicron breakthrough infection that occurred 4–7 months after vaccination (squares); 2xV, vaccinated persons after 2 doses of mRNA vaccine; 3xV, vaccinated persons after 3 doses of mRNA vaccine (triangles).

Figure. SARS-CoV-2 serum neutralizing titers across variants after postvaccination breakthrough infection. A) Schematic of the study cohort of 2×VI patients and age-matched reference cohorts (1). B) Serum neutralizing activity against Wu01 and SARS-CoV-2 variants in 2×V persons (triangles) and 2×V/I persons (circles). Horizontal lines indicate geometric mean ID50s; error bars, 95% CIs. Groups were compared by using the Mann-Whitney test. p values are shown at top. C) Correlation of serum neutralizing activity against SARS-CoV-2 Wu01 (blue) or Omicron (red) and interval between second vaccination and non-Omicron breakthrough infection (Spearman ρ and p values). Breakthrough infections within 3 months (90 days) from vaccination are indicated by light shaded symbols. Solid lines indicate linear regression, and dashed lines indicate 95% CIs. Correlation was determined by Spearman ρ. D) Serum neutralizing activity against SARS-CoV-2 Wu01 (blue) and Omicron (red) in 2×V or 3×V persons (triangles) compared with 2×V/I non-Omicron (circles) or Omicron (triangles) persons after 2 and 3 doses of mRNA vaccine. Only persons with vaccine-to-infection intervals >3 months are shown. Groups were compared by using the Kruskal-Wallis test with the Dunn multiple testing correction. Horizontal lines indicate geometric mean ID50s; error bars, 95% CIs. p values are shown at top. Black dotted lines in panels B, C, and D indicate the lower limit of quantification (ID50 = 10); ID50s <10 were imputed to half the lower limit of quantification (ID50 = 5). ID50, 50% inhibitory serum dilution; O, Omicron; pNT, pseudovirus neutralization test; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; V/I, vaccination with subsequent breakthrough infection; Wu01, ancestral (wild-type) SARS-CoV-2 strain; 2xV/I non-Omicron, vaccinated persons with non-Omicron breakthrough infection that occurred 1–8 months after vaccination (circles); 2xV/I Omicron, vaccinated persons with Omicron breakthrough infection that occurred 4–7 months after vaccination (squares); 2xV, vaccinated persons after 2 doses of mRNA vaccine; 3xV, vaccinated persons after 3 doses of mRNA vaccine (triangles).

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References
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1These authors contributed equally to this article.

2These authors co-led this study.

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Page updated: April 19, 2022
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