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.
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Viana R, Moyo S, Amoako DG, Tegally H, Scheepers C, Althaus CL, Anyaneji UJ, Bester PA, Boni MF, Chand M, Choga WT, Colquhoun R, Davids M, Deforche K, Doolabh D, du Plessis L, Engelbrecht S, Everatt J, Giandhari J, Giovanetti M, Hardie D, Hill V, Hsiao NY, Iranzadeh A, Ismail A, Joseph C, Joseph R, Koopile L, Kosakovsky Pond SL, Kraemer MUG, Kuate-Lere L, Laguda-Akingba O, Lesetedi-Mafoko O, Lessells RJ, Lockman S, Lucaci AG, Maharaj A, Mahlangu B, Maponga T, Mahlakwane K, Makatini Z, Marais G, Maruapula D, Masupu K, Matshaba M, Mayaphi S, Mbhele N, Mbulawa MB, Mendes A, Mlisana K, Mnguni A, Mohale T, Moir M, Moruisi K, Mosepele M, Motsatsi G, Motswaledi MS, Mphoyakgosi T, Msomi N, Mwangi PN, Naidoo Y, Ntuli N, Nyaga M, Olubayo L, Pillay S, Radibe B, Ramphal Y, Ramphal U, San JE, Scott L, Shapiro R, Singh L, Smith-Lawrence P, Stevens W, Strydom A, Subramoney K, Tebeila N, Tshiabuila D, Tsui J, van Wyk S, Weaver S, Wibmer CK, Wilkinson E, Wolter N, Zarebski AE, Zuze B, Goedhals D, Preiser W, Treurnicht F, Venter M, Williamson C, Pybus OG, Bhiman J, Glass A, Martin DP, Rambaut A, Gaseitsiwe S, von Gottberg A, de Oliveira T. Rapid epidemic expansion of the SARS-CoV-2 Omicron variant in southern Africa. Nature 2022; 603(7902): 679–686
Servellita V, Syed AM, Morris MK, Brazer N, Saldhi P, Garcia-Knight M, Sreekumar B, Khalid MM, Ciling A, Chen PY, Kumar GR, Gliwa AS, Nguyen J, Sotomayor-Gonzalez A, Zhang Y, Frias E, Prostko J, Hackett J Jr, Andino R, Wadford DA, Hanson C, Doudna J, Ott M, Chiu CY. Neutralizing immunity in vaccine breakthrough infections from the SARS-CoV-2 Omicron and Delta variants. Cell 2022; 185(9): 1539–1548.e5
Kurhade C, Zou J, Xia H, Cai H, Yang Q, Cutler M, Cooper D, Muik A, Jansen KU, Xie X, Swanson KA, Shi PY. Neutralization of Omicron BA.1, BA.2, and BA.3 SARS-CoV-2 by 3 doses of BNT162b2 vaccine. Nat Commun 2022; 13(1): 3602
Cao Y, Wang J, Jian F, Xiao T, Song W, Yisimayi A, Huang W, Li Q, Wang P, An R, Wang J, Wang Y, Niu X, Yang S, Liang H, Sun H, Li T, Yu Y, Cui Q, Liu S, Yang X, Du S, Zhang Z, Hao X, Shao F, Jin R, Wang X, Xiao J, Wang Y, Xie XS. Omicron escapes the majority of existing SARS-CoV-2 neutralizing antibodies. Nature 2022; 602(7898): 657–663
Zhang X, Zhang W, Chen S. Shanghai’s life-saving efforts against the current omicron wave of the COVID-19 pandemic. Lancet 2022; 399(10340): 2011–2012
Ling Y, Lu G, Liu F, Tan Y, Xu X, Wei D, Xu J, Wang S, Yu S, Jiang F, Zhang X, Chen S, Wang S, Fan X, Chen S. The Omicron BA.2.2.1 subvariant drove the wave of SARS-CoV-2 outbreak in Shanghai during spring 2022. Cell Discov 2022; 8(1): 97
Markov PV, Katzourakis A, Stilianakis NI. Antigenic evolution will lead to new SARS-CoV-2 variants with unpredictable severity. Nat Rev Microbiol 2022; 20(5): 251–252
Schultze JL, Aschenbrenner AC. COVID-19 and the human innate immune system. Cell 2021; 184(7): 1671–1692
Sette A, Crotty S. Adaptive immunity to SARS-CoV-2 and COVID-19. Cell 2021; 184(4): 861–880
Zhang X, Tan Y, Ling Y, Lu G, Liu F, Yi Z, Jia X, Wu M, Shi B, Xu S, Chen J, Wang W, Chen B, Jiang L, Yu S, Lu J, Wang J, Xu M, Yuan Z, Zhang Q, Zhang X, Zhao G, Wang S, Chen S, Lu H. Viral and host factors related to the clinical outcome of COVID-19. Nature 2020; 583(7816): 437–440
Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, Xiang J, Wang Y, Song B, Gu X, Guan L, Wei Y, Li H, Wu X, Xu J, Tu S, Zhang Y, Chen H, Cao B. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet 2020; 395(10229): 1054–1062
Bálint G, Vörös-Horváth B, Széchenyi A. Omicron: increased transmissibility and decreased pathogenicity. Signal Transduct Target Ther 2022; 7(1): 151
Ai J, Wang X, He X, Zhao X, Zhang Y, Jiang Y, Li M, Cui Y, Chen Y, Qiao R, Li L, Yang L, Li Y, Hu Z, Zhang W, Wang P. Antibody evasion of SARS-CoV-2 Omicron BA.1, BA.1.1, BA.2, and BA.3 sub-lineages. Cell Host Microbe 2022; 30(8): 1077–1083.e4
Cao Y, Yisimayi A, Jian F, Song W, Xiao T, Wang L, Du S, Wang J, Li Q, Chen X, Yu Y, Wang P, Zhang Z, Liu P, An R, Hao X, Wang Y, Wang J, Feng R, Sun H, Zhao L, Zhang W, Zhao D, Zheng J, Yu L, Li C, Zhang N, Wang R, Niu X, Yang S, Song X, Chai Y, Hu Y, Shi Y, Zheng L, Li Z, Gu Q, Shao F, Huang W, Jin R, Shen Z, Wang Y, Wang X, Xiao J, Xie XS. BA.2.12.1, BA.4 and BA.5 escape antibodies elicited by Omicron infection. Nature 2022; 608(7923): 593–602
Dejnirattisai W, Huo J, Zhou D, Zahradník J, Supasa P, Liu C, Duyvesteyn HME, Ginn HM, Mentzer AJ, Tuekprakhon A, Nutalai R, Wang B, Dijokaite A, Khan S, Avinoam O, Bahar M, Skelly D, Adele S, Johnson SA, Amini A, Ritter TG, Mason C, Dold C, Pan D, Assadi S, Bellass A, Omo-Dare N, Koeckerling D, Flaxman A, Jenkin D, Aley PK, Voysey M, Costa Clemens SA, Naveca FG, Nascimento V, Nascimento F, Fernandes da Costa C, Resende PC, Pauvolid-Correa A, Siqueira MM, Baillie V, Serafin N, Kwatra G, Da Silva K, Madhi SA, Nunes MC, Malik T, Openshaw PJM, Baillie JK, Semple MG, Townsend AR, Huang KA, Tan TK, Carroll MW, Klenerman P, Barnes E, Dunachie SJ, Constantinides B, Webster H, Crook D, Pollard AJ, Lambe T; OPTIC Consortium; ISARIC4C Consortium, Paterson NG, Williams MA, Hall DR, Fry EE, Mongkolsapaya J, Ren J, Schreiber G, Stuart DI, Screaton GR. SARS-CoV-2 Omicron-B.1.1.529 leads to widespread escape from neutralizing antibody responses. Cell 2022; 185(3): 467–484.e15
Iketani S, Liu L, Guo Y, Liu L, Chan JF, Huang Y, Wang M, Luo Y, Yu J, Chu H, Chik KK, Yuen TT, Yin MT, Sobieszczyk ME, Huang Y, Yuen KY, Wang HH, Sheng Z, Ho DD. Antibody evasion properties of SARS-CoV-2 Omicron sublineages. Nature 2022; 604(7906): 553–556
Barouch DH. Covid-19 vaccines—immunity, variants, boosters. N Engl J Med 2022; 387(11): 1011–1020
Tan Y, Zhang W, Zhu Z, Qiao N, Ling Y, Guo M, Yin T, Fang H, Xu X, Lu G, Zhang P, Yang S, Fu Z, Liang D, Xie Y, Zhang R, Jiang L, Yu S, Lu J, Jiang F, Chen J, Xiao C, Wang S, Chen S, Bian XW, Lu H, Liu F, Chen S. Integrating longitudinal clinical laboratory tests with targeted proteomic and transcriptomic analyses reveal the landscape of host responses in COVID-19. Cell Discov 2021; 7(1): 42
Langmead B, Salzberg SL. Fast gapped-read alignment with Bowtie 2. Nat Methods 2012; 9(4): 357–359
Dobin A, Davis CA, Schlesinger F, Drenkow J, Zaleski C, Jha S, Batut P, Chaisson M, Gingeras TR. STAR: ultrafast universal RNA-seq aligner. Bioinformatics 2013; 29(1): 15–21
Anders S, Pyl PT, Huber W. HTSeq—a Python framework to work with high-throughput sequencing data. Bioinformatics 2015; 31(2): 166–169
Love MI, Huber W, Anders S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol 2014; 15(12): 550
Steen CB, Liu CL, Alizadeh AA, Newman AM. Profiling cell type abundance and expression in bulk tissues with CIBERSORTx. Methods Mol Biol 2020; 2117: 135–157
Ling Y, Lu G, Liu F, Tan Y, Xu X, Wei D, Xu J, Wang S, Yu S, Jiang F, Zhang X, Chen S, Wang S, Fan X, Chen S. The Omicron BA.2.2.1 subvariant drove the wave of SARS-CoV-2 outbreak in Shanghai during spring 2022. Cell Discov 2022; 8(1): 97
Tan Y, Liu F, Xu X, Ling Y, Huang W, Zhu Z, Guo M, Lin Y, Fu Z, Liang D, Zhang T, Fan J, Xu M, Lu H, Chen S. Durability of neutralizing antibodies and T-cell response post SARS-CoV-2 infection. Front Med 2020; 14(6): 746–751
Zhong J, Liu S, Cui T, Li J, Zhu F, Zhong N, Huang W, Zhao Z, Wang Z. Heterologous booster with inhaled adenovirus vector COVID-19 vaccine generated more neutralizing antibodies against different SARS-CoV-2 variants. Emerg Microbes Infect 2022; 11(1): 2689–2697
Zhang Y, Zeng G, Pan H, Li C, Hu Y, Chu K, Han W, Chen Z, Tang R, Yin W, Chen X, Hu Y, Liu X, Jiang C, Li J, Yang M, Song Y, Wang X, Gao Q, Zhu F. Safety, tolerability, and immunogenicity of an inactivated SARS-CoV-2 vaccine in healthy adults aged 18–59 years: a randomised, double-blind, placebo-controlled, phase 1/2 clinical trial. Lancet Infect Dis 2021; 21(2): 181–192
Feikin DR, Higdon MM, Abu-Raddad LJ, Andrews N, Araos R, Goldberg Y, Groome MJ, Huppert A, O’Brien KL, Smith PG, Wilder-Smith A, Zeger S, Deloria Knoll M, Patel MK. Duration of effectiveness of vaccines against SARS-CoV-2 infection and COVID-19 disease: results of a systematic review and meta-regression. Lancet 2022; 399(10328): 924–944
Fiolet T, Kherabi Y, MacDonald CJ, Ghosn J, Peiffer-Smadja N. Comparing COVID-19 vaccines for their characteristics, efficacy and effectiveness against SARS-CoV-2 and variants of concern: a narrative review. Clin Microbiol Infect 2022; 28(2): 202–221
WHO. COVID-19 Weekly Epidemiological Update (Edition 115). 2022
de Prost N, Audureau E, Heming N, Gault E, Pham T, Chaghouri A, de Montmollin N, Voiriot G, Morand-Joubert L, Joseph A, Chaix ML, Préau S, Favory R, Guigon A, Luyt CE, Burrel S, Mayaux J, Marot S, Roux D, Descamps D, Meireles S, Pène F, Rozenberg F, Contou D, Henry A, Gaudry S, Brichler S, Timsit JF, Kimmoun A, Hartard C, Jandeaux LM, Fafi-Kremer S, Gabarre P, Emery M, Garcia-Sanchez C, Jochmans S, Pitsch A, Annane D, Azoulay E, Mekontso Dessap A, Rodriguez C, Pawlotsky JM, Fourati S. Clinical phenotypes and outcomes associated with SARS-CoV-2 variant Omicron in critically ill French patients with COVID-19. Nat Commun 2022; 13(1): 6025
Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y, Qiu Y, Wang J, Liu Y, Wei Y, Xia J, Yu T, Zhang X, Zhang L. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet 2020; 395(10223): 507–513
Antonelli M, Pujol JC, Spector TD, Ourselin S, Steves CJ. Risk of long COVID associated with delta versus omicron variants of SARS-CoV-2. Lancet 2022; 399(10343): 2263–2264
Vora SM, Lieberman J, Wu H. Inflammasome activation at the crux of severe COVID-19. Nat Rev Immunol 2021; 21(11): 694–703
Kerget B, Kerget F, Aksakal A, Aşkın S, Sağlam L, Akgün M. Evaluation of alpha defensin, IL-1 receptor antagonist, and IL-18 levels in COVID-19 patients with macrophage activation syndrome and acute respiratory distress syndrome. J Med Virol 2021; 93(4): 2090–2098
Hanna RN, Shaked I, Hubbeling HG, Punt JA, Wu R, Herrley E, Zaugg C, Pei H, Geissmann F, Ley K, Hedrick CC. NR4A1 (Nur77) deletion polarizes macrophages toward an inflammatory phenotype and increases atherosclerosis. Circ Res 2012; 110(3): 416–427
Dai L, Gao GF. Viral targets for vaccines against COVID-19. Nat Rev Immunol 2021; 21(2): 73–82
Ministry-of-Health-Singapore. COVID-19 Statistics. 2022
China-Government-Network. The latest news on epidemic prevention and control of SARS-CoV-2 on April 28. 2022
Live-Shanghai. Build a strong immune “firewall”! Increase the vaccination rate of the elderly and other groups, and complete the booster immunization as soon as possible. 2022
Acknowledgements
We thank the support from the National Natural Science Foundation of China (Nos. 82100158 and 81861148030), the Natural Science Foundation of Shanghai (Nos. 21ZR1480900 and 21YF1427900), Shanghai Clinical Research Center for Hematologic Disease (No. 19MC1910700), Shanghai Major Project for Clinical Medicine (No. 2017ZZ01002), Shanghai Shenkang Hospital Development Center (No. SHDC2020CR5002), Innovative Research Team of High-level Local Universities in Shanghai, and Shanghai Collaborative Innovation Program on Regenerative Medicine and Stem Cell Research (No. 2019CXJQ01). We thank the support from the ASTRA computing platform in the National Research Center for Translational Medicine (Shanghai) and the Pi computing platform in the Center for High-Performance Computing at Shanghai Jiao Tong University.
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Ziyu Fu, Dongguo Liang, Wei Zhang, Dongling Shi, Yuhua Ma, Dong Wei, Junxiang Xi, Sizhe Yang, Xiaoguang Xu, Di Tian, Zhaoqing Zhu, Mingquan Guo, Lu Jiang, Shuting Yu, Shuai Wang, Fangyin Jiang, Yun Ling, Shengyue Wang, Saijuan Chen, Feng Liu, Yun Tan, and Xiaohong Fan declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000(5). Informed consent was obtained from all patients for being included in the study.
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Fu, Z., Liang, D., Zhang, W. et al. Host protection against Omicron BA.2.2 sublineages by prior vaccination in spring 2022 COVID-19 outbreak in Shanghai. Front. Med. 17, 562–575 (2023). https://doi.org/10.1007/s11684-022-0977-3
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DOI: https://doi.org/10.1007/s11684-022-0977-3