Engineering Extracellular Vesicles Enriched with Palmitoylated ACE2 as COVID-19 Therapy (Adv. Mater. 49/2021)

COVID-19 Therapy In their work reported in article number 2103471, Long Zhang, Fangfang Zhou, and co-workers fuse the S-palmitoylation-dependent plasma membrane (PM) targeting sequence with angiotensin converting enzyme 2 (ACE2) and engineer extracellular vesicles (EVs) on their surface enriched with palmitoylated ACE2 (PM-ACE2-EVs). The PM-ACE2-EVs can bind to the SARS-CoV-2 S-RBD with high affinity and block its interaction with cell-surface ACE2, thereby preventing SARS-CoV-2 from entering the host cell. This study provides a novel EV-based candidate for prophylactic and therapeutic treatment against COVID-19.

Characteristics of Lymphocyte Subsets and Cytokine Profiles of Patients with Coronavirus Disease 2019 (preprint)

Background: To explore the changes in lymphocyte subsets and cytokine profiles in patients with coronavirus disease 2019 (COVID-19) and their relationship with disease severity. Methods: This study included 228 patients with COVID-19 who were treated at Chongqing University Three Gorges Hospital from January 1, 2020 to February 20, 2020. The characteristics of lymphocyte subsets and cytokine profiles of severe and mild COVID-19 patients were compared. Of the 228 patients enrolled, 48 were severe patients and 180 were mild patients. Results: Lymphocyte counts, absolute number of total T lymphocytes, CD4+T cells, CD8+T cells, and total B lymphocytes were significantly lower in severe patients (0.8×109/L, 424.5×106/L, 266×106/L, 145.5×106/L, 109.5×106/L, respectively) than in mild patients (1.2×109/L, 721×106/L, 439.5×106/L, 281.5×106/L, 135×106/L, respectively). A multivariate logistic regression analysis showed that age, C-reactive protein (CRP) and the neutrophil-to-lymphocyte ratio (NLR) were independent risk factors for developing into severe condition. The lymphocyte subsets decreased and cytokine profiles increased more significantly in severe patients than in mild patients. Conclusions: CRP, NLR, and age may serve as powerful factors for early identification of severe patients.

Transmission Dynamics of Coronavirus Disease 2019 (COVID-19) in the World: The Roles of Intervention and Seasonality (preprint)

The coronavirus disease 2019 (COVID-19) is spreading rapidly all over the world. The transmission dynamics of the COVID-19 pandemic is still unclear, but developing strategies for mitigating the severity of the pandemic is yet a top priority for global public health. In this study, we developed a novel compartmental model, SEIR-CV(susceptible-exposed-infectious-removed with control variables), which not only considers the key characteristics of asymptomatic infection and the effects of seasonal variations, but also incorporates different control measures for multiple transmission routes, so as to accurately predict and effectively control the spread of COVID-19. Based on SEIR-CV, we predicted the COVID-19 epidemic situation in China out of Hubei province and proposed corresponding control strategies. The results showed that the prediction results are highly consistent with the outbreak surveillance data, which proved that the proposed control strategies have achieved sound consequent in the actual epidemic control. Subsequently, we have conducted a rolling prediction for the United States, Brazil, India, five European countries (the United Kingdom, Italy, Spain, Germany, and France), southern hemisphere, northern hemisphere, and the world out of China. The results indicate that control measures and seasonal variations have a great impact on the progress of the COVID-19 pandemic. Our prediction results show that the COVID-19 pandemic is developing more rapidly due to the impact of the cold season in the southern hemisphere countries such as Brazil. While the development of the pandemic should have gradually weakened in the northern hemisphere countries with the arrival of the warm season, instead of still developing rapidly due to the relative loose control measures such as the United States and India. Furthermore, the prediction results illustrate that if keeping the current control measures in the main COVID-19 epidemic countries, the pandemic will not be contained and the situation may eventually turn to group immunization, which would lead to the extremely severe disaster of about 5 billion infections and 300 million deaths globally. However, if China's super stringent control measures were implemented from 15 July, 15 August or 15 September 2020, the total infections would be contained about 15 million, 32 million or 370 million respectively, which indicates that the stringent and timely control measures is critical, and the best window period is before September for eventually overcoming COVID-19.