Host protection against Omicron BA.2.2 sublineages by prior vaccination in spring 2022 COVID-19 outbreak in Shanghai

doi:10.1007/s11684-022-0977-3

Front. Med.

2023, Vol. 17

Issue (3) : 562-575 https://doi.org/10.1007/s11684-022-0977-3

RESEARCH ARTICLE

Host protection against Omicron BA.2.2 sublineages by prior vaccination in spring 2022 COVID-19 outbreak in Shanghai

Ziyu Fu¹, Dongguo Liang¹, Wei Zhang^1,², Dongling Shi³, Yuhua Ma⁴, Dong Wei⁵, Junxiang Xi¹, Sizhe Yang¹, Xiaoguang Xu¹, Di Tian³, Zhaoqing Zhu³, Mingquan Guo³, Lu Jiang¹, Shuting Yu¹, Shuai Wang¹, Fangyin Jiang¹, Yun Ling³, Shengyue Wang¹, Saijuan Chen¹(

), Feng Liu¹(

), Yun Tan¹(

), Xiaohong Fan³(

)

¹. Shanghai Institute of Hematology, National Research Center for Translational Medicine, State Key Laboratory of Medical Genomics, Ruijin Hospital Affiliated to Shanghai Jiao Tong University (SJTU) School of Medicine, Shanghai 200025, China
². National Translational Science Center for Molecular Medicine & Department of Cell Biology, Fourth Military Medical University, Xi’an 710032, China
³. Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, China
⁴. Department of Nephrology, Traditional Chinese Medicine Hospital of KunShan, Suzhou 215300, China
⁵. Department of Infectious Diseases, Ruijin Hospital Affiliated to Shanghai Jiao Tong University (SJTU) School of Medicine, Shanghai 200025, China

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Abstract

The Omicron family of SARS-CoV-2 variants are currently driving the COVID-19 pandemic. Here we analyzed the clinical laboratory test results of 9911 Omicron BA.2.2 sublineages-infected symptomatic patients without earlier infection histories during a SARS-CoV-2 outbreak in Shanghai in spring 2022. Compared to an earlier patient cohort infected by SARS-CoV-2 prototype strains in 2020, BA.2.2 infection led to distinct fluctuations of pathophysiological markers in the peripheral blood. In particular, severe/critical cases of COVID-19 post BA.2.2 infection were associated with less pro-inflammatory macrophage activation and stronger interferon alpha response in the bronchoalveolar microenvironment. Importantly, the abnormal biomarkers were significantly subdued in individuals who had been immunized by 2 or 3 doses of SARS-CoV-2 prototype-inactivated vaccines, supporting the estimation of an overall 96.02% of protection rate against severe/critical disease in the 4854 cases in our BA.2.2 patient cohort with traceable vaccination records. Furthermore, even though age was a critical risk factor of the severity of COVID-19 post BA.2.2 infection, vaccination-elicited protection against severe/critical COVID-19 reached 90.15% in patients aged ≥ 60 years old. Together, our study delineates the pathophysiological features of Omicron BA.2.2 sublineages and demonstrates significant protection conferred by prior prototype-based inactivated vaccines.

Keywords SARS-CoV-2 COVID-19 host response bronchoalveolar lavage fluid (BALF)

Corresponding Author(s): Saijuan Chen,Feng Liu,Yun Tan,Xiaohong Fan

Just Accepted Date: 07 December 2022 Online First Date: 21 March 2023 Issue Date: 28 July 2023

Cite this article:

Ziyu Fu,Dongguo Liang,Wei Zhang, et al. Host protection against Omicron BA.2.2 sublineages by prior vaccination in spring 2022 COVID-19 outbreak in Shanghai[J]. Front. Med., 2023, 17(3): 562-575.

URL:

https://academic.hep.com.cn/fmd/EN/10.1007/s11684-022-0977-3
https://academic.hep.com.cn/fmd/EN/Y2023/V17/I3/562

Fig.1 BA.2.2 cohort and risk factors of severe COVID-19. (A) Numbers and fraction of COVID-19 cases in different age groups. (B) Number and fraction of severe/critical cases in different age groups. (C) Number and fraction of vaccination states in different age groups. (D) Distribution of severe cases in different age groups between vaccinated and non-vaccinated individuals. (E) Risk factor analysis. Multivariate analysis identifies that both age and vaccination were determinate for the severity of COVID-19. Hazard ratio was plotted in the right panel.

Fig.2 Clinical laboratory features associated with COVID-19 severity in the BA.2.2 cohort. (A) Multi-variant tests of various clinical parameters in association with severe COVID. (B–F) Longitudinal analysis of a subset of routine blood test, anemia, coagulation, kidney damage, and liver function related features from 1 to 30 days post hospitalization (dph) in severe/critical, younger mild/moderate (< 60 years old), and elder mid/moderate (≥ 60 years old) COVID-19 infected by BA.2.2. Results are plotted by time. (B) Analysis of lymphocyte counts and high-sensitivity C-reactive protein (HS-CRP) on 1–30 dph. (C) Analysis of markers related to liver function/damage. Levels of albumin and pre-albumin are shown. (D) Analysis of markers related to kidney injury. Levels of blood urea nitrogen and creatinine are shown. (E) Analysis of anemia related features. Levels of hematocrit and hemoglobin are shown. (F) Analysis of coagulation related features. Results of D-dimers are shown.

Fig.3 Vaccination suppressed lymphocytopenia, anemia, coagulation disorder, and kidney injury in severe/critical COVID-19. (A–G) Longitudinal analysis of a subset of routine blood test (lymphocyte counts and HS-CRP), anemia (hemoglobin and hematocrit), liver function (albumin and pre-albumin), kidney injury (blood urea nitrogen), and coagulation (D-dimer) related features from 1 to 30 days post hospitalization (dph) in vaccinated and unvaccinated COVID-19 infected by BA.2.2. Severe/critical, mild/moderate of ≥ 60 years old, and mild/moderate of < 60 years old COVID-19 cases were enrolled for analysis. Samples were divided into two groups, including the vaccinated and the unvaccinated. Results are plotted by time; results from 1–5, 6–10, 11–15, and 16–30 dph are shown. n, the number of samples used for analysis. A patient might have several tests on bio-analytes at multiple time points due to clinical requirement. Wilcox-test: ****P < 0.0001, ***P < 0.001, **P < 0.05, *P < 0.01. ns, not significant.

Fig.4 Comparison of clinical laboratory features of patient cohorts with BA.2.2 and the prototype strain infection. (A) Age distribution in BA.2.2 and prototype infected severe/critical COVID-19. ^at-test, ^bFisher exact test. (B–F) Longitudinal analysis of a subset of routine blood test, cytokines, coagulation, liver injury, and kidney injury related features from 1 to 30 days post hospitalization (dph) in prototype and BA.2.2 infected severe/critical COVID-19. Prototype and BA.2.2-infected unvaccinated severe/critical COVID-19 cases were enrolled for analysis. Samples were divided into two groups, including the prototype and the unvaccinated BA.2.2 ones. Results are plotted by time, i.e., on 1–5, 6–10, 11–15, and 16–30 dph. Data of neutrophil counts and lymphocyte counts (B), hematocrit and hemoglobin (C), D-dimers and prothrombin time/international normalized ratio (PT/INR) (D), albumin and pre-albumin (E), blood urea nitrogen and creatinine (F) are shown. (G) Heatmap showing relative cytokine levels in prototype and BA.2.2-infected unvaccinated severe/critical COVID-19 cases. n, the number of samples used for analysis. A patient might have several tests on bio-analytes at multiple time points due to clinical requirement. Wilcox-test: ****P < 0.0001, ***P < 0.001, **P < 0.01, *P < 0.05. ns, not significant.

Fig.5 Elevated virus burden and altered host responses in BALF of BA.2.2 infected patients. (A) Principal component analysis (PCA) of prototype and unvaccinated SARS-CoV-2-infected BALF samples in severe/critical COVID-19 samples. RNA-seq was conducted in the BALF samples of 5 prototype and 19 BA.2.2 infected severe/critical COVID-19 cases. (B) Gene ontology analysis of genes differentially expressed in BALF samples between BA.2.2 and prototype infected COVID-19. FDR values were shown by color. Enriched gene numbers were shown by circle size. (C) Heatmap showing representative differential expressed genes. (D) Cell distribution in the BALF of prototype and BA.2.2-infected severe/critical COVID-19. Relative ratio of 16 cell types were calculated by the CIBERSORT tools using bulk RNA-seq of BALF samples.

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