Modeling transmission of SARS-CoV-2 Omicron in China

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Abstract

Having adopted a dynamic zero-COVID strategy to respond to SARS-CoV-2 variants with higher transmissibility since August 2021, China is now considering whether, and for how long, this policy can remain in place. The debate has thus shifted towards the identification of mitigation strategies for minimizing disruption to the healthcare system in the case of a nationwide epidemic. To this aim, we developed an age-structured stochastic compartmental susceptible-latent-infectious-removed-susceptible model of SARS-CoV-2 transmission calibrated on the initial growth phase for the 2022 Omicron outbreak in Shanghai, to project COVID-19 burden (that is, number of cases, patients requiring hospitalization and intensive care, and deaths) under hypothetical mitigation scenarios. The model also considers age-specific vaccine coverage data, vaccine efficacy against different clinical endpoints, waning of immunity, different antiviral therapies and nonpharmaceutical interventions. We find that the level of immunity induced by the March 2022 vaccination campaign would be insufficient to prevent an Omicron wave that would result in exceeding critical care capacity with a projected intensive care unit peak demand of 15.6 times the existing capacity and causing approximately 1.55 million deaths. However, we also estimate that protecting vulnerable individuals by ensuring accessibility to vaccines and antiviral therapies, and maintaining implementation of nonpharmaceutical interventions could be sufficient to prevent overwhelming the healthcare system, suggesting that these factors should be points of emphasis in future mitigation policies.

Abstract

Estimates from a new modeling study suggest that current levels of vaccine coverage in China are insufficient to prevent overwhelming the healthcare system, and that, if left untreated, a nationwide Omicron wave could result in up to 1.55 million deaths.

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Clinical Characteristics of Coronavirus Disease 2019 in China

Wei-jie Guan, Zheng-yi Ni, Yu Hu … (2020)

Abstract Background Since December 2019, when coronavirus disease 2019 (Covid-19) emerged in Wuhan city and rapidly spread throughout China, data have been needed on the clinical characteristics of the affected patients. Methods We extracted data regarding 1099 patients with laboratory-confirmed Covid-19 from 552 hospitals in 30 provinces, autonomous regions, and municipalities in mainland China through January 29, 2020. The primary composite end point was admission to an intensive care unit (ICU), the use of mechanical ventilation, or death. Results The median age of the patients was 47 years; 41.9% of the patients were female. The primary composite end point occurred in 67 patients (6.1%), including 5.0% who were admitted to the ICU, 2.3% who underwent invasive mechanical ventilation, and 1.4% who died. Only 1.9% of the patients had a history of direct contact with wildlife. Among nonresidents of Wuhan, 72.3% had contact with residents of Wuhan, including 31.3% who had visited the city. The most common symptoms were fever (43.8% on admission and 88.7% during hospitalization) and cough (67.8%). Diarrhea was uncommon (3.8%). The median incubation period was 4 days (interquartile range, 2 to 7). On admission, ground-glass opacity was the most common radiologic finding on chest computed tomography (CT) (56.4%). No radiographic or CT abnormality was found in 157 of 877 patients (17.9%) with nonsevere disease and in 5 of 173 patients (2.9%) with severe disease. Lymphocytopenia was present in 83.2% of the patients on admission. Conclusions During the first 2 months of the current outbreak, Covid-19 spread rapidly throughout China and caused varying degrees of illness. Patients often presented without fever, and many did not have abnormal radiologic findings. (Funded by the National Health Commission of China and others.)

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Immunological memory to SARS-CoV-2 assessed for up to 8 months after infection

Jennifer M. Dan, Jose Mateus, Yu Kato … (2021)

Understanding immune memory to SARS-CoV-2 is critical for improving diagnostics and vaccines, and for assessing the likely future course of the COVID-19 pandemic. We analyzed multiple compartments of circulating immune memory to SARS-CoV-2 in 254 samples from 188 COVID-19 cases, including 43 samples at ≥ 6 months post-infection. IgG to the Spike protein was relatively stable over 6+ months. Spike-specific memory B cells were more abundant at 6 months than at 1 month post symptom onset. SARS-CoV-2-specific CD4+ T cells and CD8+ T cells declined with a half-life of 3-5 months. By studying antibody, memory B cell, CD4+ T cell, and CD8+ T cell memory to SARS-CoV-2 in an integrated manner, we observed that each component of SARS-CoV-2 immune memory exhibited distinct kinetics.

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Oral Nirmatrelvir for High-Risk, Nonhospitalized Adults with Covid-19

Jennifer Hammond, Heidi Leister-Tebbe, Annie Gardner … (2022)

Background Nirmatrelvir is an orally administered severe acute respiratory syndrome coronavirus 2 main protease (M pro ) inhibitor with potent pan–human-coronavirus activity in vitro. Methods We conducted a phase 2–3 double-blind, randomized, controlled trial in which symptomatic, unvaccinated, nonhospitalized adults at high risk for progression to severe coronavirus disease 2019 (Covid-19) were assigned in a 1:1 ratio to receive either 300 mg of nirmatrelvir plus 100 mg of ritonavir (a pharmacokinetic enhancer) or placebo every 12 hours for 5 days. Covid-19–related hospitalization or death from any cause through day 28, viral load, and safety were evaluated. Results A total of 2246 patients underwent randomization; 1120 patients received nirmatrelvir plus ritonavir (nirmatrelvir group) and 1126 received placebo (placebo group). In the planned interim analysis of patients treated within 3 days after symptom onset (modified intention-to treat population, comprising 774 of the 1361 patients in the full analysis population), the incidence of Covid-19–related hospitalization or death by day 28 was lower in the nirmatrelvir group than in the placebo group by 6.32 percentage points (95% confidence interval [CI], −9.04 to −3.59; P<0.001; relative risk reduction, 89.1%); the incidence was 0.77% (3 of 389 patients) in the nirmatrelvir group, with 0 deaths, as compared with 7.01% (27 of 385 patients) in the placebo group, with 7 deaths. Efficacy was maintained in the final analysis involving the 1379 patients in the modified intention-to-treat population, with a difference of −5.81 percentage points (95% CI, −7.78 to −3.84; P<0.001; relative risk reduction, 88.9%). All 13 deaths occurred in the placebo group. The viral load was lower with nirmaltrelvir plus ritonavir than with placebo at day 5 of treatment, with an adjusted mean difference of −0.868 log 10 copies per milliliter when treatment was initiated within 3 days after the onset of symptoms. The incidence of adverse events that emerged during the treatment period was similar in the two groups (any adverse event, 22.6% with nirmatrelvir plus ritonavir vs. 23.9% with placebo; serious adverse events, 1.6% vs. 6.6%; and adverse events leading to discontinuation of the drugs or placebo, 2.1% vs. 4.2%). Dysgeusia (5.6% vs. 0.3%) and diarrhea (3.1% vs. 1.6%) occurred more frequently with nirmatrelvir plus ritonavir than with placebo. Conclusions Treatment of symptomatic Covid-19 with nirmatrelvir plus ritonavir resulted in a risk of progression to severe Covid-19 that was 89% lower than the risk with placebo, without evident safety concerns. (Supported by Pfizer; ClinicalTrials.gov number, NCT04960202 .)

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Author and article information

Contributors

Hongjie Yu:

ORCID: http://orcid.org/0000-0002-6335-5648

yhj@fudan.edu.cn

Journal

Journal ID (nlm-ta): Nat Med

Journal ID (iso-abbrev): Nat Med

Title: Nature Medicine

Publisher: Nature Publishing Group US (New York )

ISSN (Print): 1078-8956

ISSN (Electronic): 1546-170X

Publication date (Electronic): 10 May 2022

Publication date PMC-release: 10 May 2022

Publication date (Print): 2022

Volume: 28

Issue: 7

Pages: 1468-1475

Affiliations

[1 ]GRID grid.8547.e, ISNI 0000 0001 0125 2443, School of Public Health, , Fudan University, Key Laboratory of Public Health Safety, Ministry of Education, ; Shanghai, China

[2 ]GRID grid.8547.e, ISNI 0000 0001 0125 2443, Shanghai Institute of Infectious Disease and Biosecurity, , Fudan University, ; Shanghai, China

[3 ]GRID grid.453035.4, ISNI 0000 0004 0533 8254, Division of International Epidemiology and Population Studies, Fogarty International Center, National Institutes of Health, ; Bethesda, MD USA

[4 ]GRID grid.411377.7, ISNI 0000 0001 0790 959X, Laboratory for Computational Epidemiology and Public Health, Department of Epidemiology and Biostatistics, , Indiana University School of Public Health, ; Bloomington, IN USA

Author information

Jun Cai http://orcid.org/0000-0001-9495-1226

Juan Yang http://orcid.org/0000-0001-5028-2227

Hengcong Liu http://orcid.org/0000-0003-2591-2201

Hongjie Yu http://orcid.org/0000-0002-6335-5648

Article

Publisher ID: 1855

DOI: 10.1038/s41591-022-01855-7

PMC ID: 9307473

PubMed ID: 35537471

SO-VID: 698e9227-8cf5-4b1b-a49f-a6687548763b

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Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

History

Date received : 22 March 2022

Date accepted : 3 May 2022

Funding

Funded by: FundRef https://doi.org/10.13039/501100010903, National Science Foundation of China | Key Programme;

Award ID: 82130093

Award Recipient : Hongjie Yu

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ScienceOpen disciplines: Medicine

Keywords: viral infection,epidemiology

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ScienceOpen disciplines: Medicine

Keywords: viral infection, epidemiology

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Modeling transmission of SARS-CoV-2 Omicron in China

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Novel Coronavirus Disease COVID-19

Most cited references 39

Clinical Characteristics of Coronavirus Disease 2019 in China

Immunological memory to SARS-CoV-2 assessed for up to 8 months after infection

Oral Nirmatrelvir for High-Risk, Nonhospitalized Adults with Covid-19

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Cited by 122

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