C o r r e s p o n d e n c e Detection of Covid-19 in Children in Early January 2020 in Wuhan, China To the Editor: A small number of cases of coronavirus disease 2019 (Covid-19) have been described in children, 1,2 and our understanding of the spectrum of illness is limited. 3 We conducted a retrospective analysis involving hospitalized children in Wuhan, China. From January 7 to January 15, 2020, a total of 366 hospitalized children (≤16 years of age) were enrolled in a retrospective study of respiratory infections at three branches of Tongji Hospital, which are located 14 km to 34 km from one another in central Wuhan (Fig. S1 in the Supplementary Appendix, available with the full text of this letter at NEJM.org). The study was approved by the ethics committee of Tongji Hospital. Among the 366 children, the most frequently detected pathogens were influenza A virus (in 23 patients [6.3%]) and influenza B virus (in 20 [5.5%]). SARS-CoV-2, the virus that causes Covid-19, was detected in 6 patients (1.6%). In

Recently emerged SARS-CoV-2 variants may pose a threat to immunity. A systematic landscape of neutralizing antibodies against emerging variants is needed. We systematically searched for studies that evaluated neutralizing antibodies titers induced by previous infection or vaccination against SARS-CoV-2 variants and collected individual data. We identified 106 studies meeting the eligibility criteria. Lineage B.1.351 (Beta), P.1 (Gamma) and B.1.617.2 (Delta) significantly escaped natural-infection-mediated neutralization, with an average of 4.1-fold (95% CI: 3.6-4.7), 1.8-fold (1.4-2.4), and 3.2-fold (2.4-4.1) reduction in live virus neutralization assay, while neutralizing titers against B.1.1.7 decreased slightly (1.4-fold, 95%CI: 1.2-1.6). Serum from vaccinees also led to significant reductions in neutralization of B.1.351 across different platforms, with an average of 7.1-fold (5.5-9.0) for non-replicating vector platform, 4.1-fold (3.7-4.4) for mRNA platform, and 2.5-fold (1.7-2.9) for protein subunit platform. Neutralizing antibodies levels induced by mRNA vaccines against SARS-CoV-2 variants were similar, or higher, than that derived from naturally-infected individuals.

BackgroundRegulatory T cells (Tregs) and B cells (Bregs) play an important role in the development of lung cancer. The present study aimed to investigate the phenotype of circulating Tregs and Bregs in patients with lung cancer and explore potential mechanism by which lung cancer cells act on the development of both.MethodsPatients with lung cancer (n = 268) and healthy donors (n = 65) were enrolled in the study. Frequencies of Tregs and Bregs were measured by flow cytometry with antibodies against CD4, CD25, CD127, CD45RA, CD19, CD24, CD27 and IL-10 before and after co-cultures. qRT-PCR was performed to evaluate the mRNA levels of RANTES, MIP-1α, TGF-β, IFN-γ and IL-4.ResultsWe found a lower frequency of Tregs and a higher frequency of Bregs in patients with lung cancer compared to healthy donors. Co-culture of lung cancer cells with peripheral blood mononuclear cells could polarize the lymphocyte phenotype in the similar pattern. Lipopolysaccharide (LPS)-stimulated lung cancer cells significantly modulated regulatory cell number and function in an in vitro model.ConclusionWe provide initial evidence that frequencies of peripheral Tregs decreased or Bregs increased in patients with lung cancer, which may be modulated directly by lung cancer cells. It seems cancer cells per se plays a crucial role in the development of tumor immunity.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-014-0304-0) contains supplementary material, which is available to authorized users.

Objective To assess the case fatality risk (CFR) of COVID-19 in mainland China, stratified by region and clinical category, and estimate key time-to-event intervals. Methods We collected individual information and aggregated data on COVID-19 cases from publicly available official sources from December 29, 2019 to April 17, 2020. We accounted for right-censoring to estimate the CFR and explored the risk factors for mortality. We fitted Weibull, gamma, and lognormal distributions to time-to-event data using maximum-likelihood estimation. Results We analyzed 82,719 laboratory-confirmed cases reported in mainland China, including 4,632 deaths, and 77,029 discharges. The estimated CFR was 5.65% (95%CI: 5.50%-5.81%) nationally, with highest estimate in Wuhan (7.71%), and lowest in provinces outside Hubei (0.86%). The fatality risk among critical patients was 3.6 times that of all patients, and 0.8-10.3 fold higher than that of mild-to-severe patients. Older age (OR 1.14 per year; 95%CI: 1.11-1.16), and being male (OR 1.83; 95%CI: 1.10-3.04) were risk factors for mortality. The time from symptom onset to first healthcare consultation, time from symptom onset to laboratory confirmation, and time from symptom onset to hospitalization were consistently longer for deceased patients than for those who recovered. Conclusions Our CFR estimates based on laboratory-confirmed cases ascertained in mainland China suggest that COVID-19 is more severe than the 2009 H1N1 influenza pandemic in hospitalized patients, particularly in Wuhan. Our study provides a comprehensive picture of the severity of the first wave of the pandemic in China. Our estimates can help inform models and the global response to COVID-19.

Acute lung injury (ALI) is a severe clinical condition responsible for high mortality and the development of multiple organ dysfunctions, because of the lack of specific and effective therapies for ALI. Increasing evidence from pre-clinical studies supports preventive and therapeutic effects of mesenchymal stem cells (MSCs, also called mesenchymal stromal cells) in ALI/ARDS (acute respiratory distress syndrome). Therapeutic effects of MSCs were noticed in various delivery approaches (systemic, local, or other locations), multiple origins (bone marrow or other tissues), or different schedules of administrations (before or after the challenges). MSCs could reduce the over-production of inflammatory mediators, leucocyte infiltration, tissue injury and pulmonary failure, and produce a number of benefit factors through interaction with other cells in the process of lung tissue repair. Thus, it is necessary to establish guidelines, standard operating procedures and evaluation criteria for translating MSC-based therapies into clinical application for patients with ALI.