简介：AbstractSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced multisystem inflammatory syndrome in children (MIS-C) is a life-threatening illness that has been reported in the United States and Europe. It affects multiple organ systems and often requires patient admission to an intensive care unit. Although some features of MIS-C overlap with Kawasaki disease, MIS-C is more common among older children and adolescents, more often affects cardiovascular and gastrointestinal systems, and more frequently presents with elevated inflammatory markers. Rapid and complete clinical recovery is possible in nearly all patients following immunomodulation therapy. Thus far, MIS-C pathophysiology and long-term prognosis are not sufficiently clear; further studies are needed.

简介：AbstractSince December 2019, increasing attention has been paid to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic in Wuhan, China. SARS-CoV-2 primarily invades the respiratory tract and lungs, leading to pneumonia and other systemic disorders. The effect of SARS-CoV-2 in transplant recipients has raised significant concerns, especially because there is a large population of transplant recipients in China. Based on the current epidemic situation, this study reviewed publications on this virus and coronavirus disease 2019 (COVID-19), analyzed common features of respiratory viral pneumonias, and presented the currently reported clinical characteristics of COVID-19 in transplant recipients to improve strategies regarding the diagnosis and treatment of COVID-19 in this special population.

简介：Thesuddenoutbreakofsevereacuterespiratorysyndrome(SARS)in2002promptedtheestablishmentofaglobalscientificnetworksubsumingmostofthetraditionalrivalriesinthecompetitivefieldofvirology.WithinmonthsoftheSARSoutbreak,collaborativeworkrevealedtheidentityofthedisastrouspathogenasSARS-associatedcoronavirus(SARS-CoV).However,althoughtherapididentificationoftheagentrepresentedanimportantbreakthrough,ourunderstandingofthedeadlyvirusremainslimited.Detailedbiologicalknowledgeiscrucialforthedevelopmentofeffectivecountermeasures,diagnostictests,vaccinesandantiviraldrugsagainsttheSARS-CoV.ThisarticlereviewsthepresentstateofmolecularknowledgeaboutSARS-CoV,fromtheaspectsofcomparativegenomics,molecularbiologyofviralgenes,evolution,andepidemiology,anddescribesthediagnostictestsandtheanti-viraldrugsderivedsofarbasedontheavailablemolecularinformation.

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简介：AbstractBackground:With the ongoing worldwide coronavirus disease 2019 (COVID-19) pandemic, an increasing number of viral variants are being identified, which poses a challenge for nucleic acid-based diagnostic tests. Rapid tests, such as real-time reverse transcription-polymerase chain reaction (rRT-PCR), play an important role in monitoring COVID-19 infection and controlling its spread. However, the changes in the genotypes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants may result in decreased sensitivity of the rRT-PCR assay and it is necessary to monitor the mutations in primers and probes of SARS-CoV-2 detection over time.Methods:We developed two rRT-PCR assays to detect the RNA-dependent RNA polymerase (RdRp) and nucleocapsid (N) genes of SARS-CoV-2. We evaluated these assays together with our previously published assays targeting the ORF1ab and N genes for the detection and confirmation of SARS-CoV-2 and its variants of concern (VOCs). In addition, we also developed two rRT-PCR assays (S484K and S501Y) targeting the spike gene, which when combined with the open reading frames (ORF)1ab assay, respectively, to form duplex rRT-PCR assays, were able to detect SARS-CoV-2 VOCs (lineages B.1.351 and B.1.1.7).Results:Using a SARS-CoV-2 stock with predetermined genomic copies as a standard, the detection limit of both assays targeting RdRp and N was five copies/reaction. Furthermore, no cross-reactions with six others human CoVs (229E, OC43, NL63, HKU1, severe acute respiratory syndrome coronavirus and Middle East respiratory syndrome coronavirus) were observed using these assays. In addition, the S484K and S501Y assays were combined with the ORF1ab assay, respectively.Conclusions:Four rRT-PCR assays (RdRp, N, S484K, and S501Y) were used to detect SARS-CoV-2 variants, and these assays were shown to be effective in screening for multiple virus strains.

简介：AbstractBackground:The significant morbidity and mortality resulted from the infection of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) call for urgent development of effective and safe vaccines. We report the immunogenicity and safety of an inactivated SARS-CoV-2 vaccine, KCONVAC, in healthy adults.Methods:Phase 1 and phase 2 randomized, double-blind, and placebo-controlled trials of KCONVAC were conducted in healthy Chinese adults aged 18 to 59 years. The participants in the phase 1 trial were randomized to receive two doses, one each on Days 0 and 14, of either KCONVAC (5 or 10 μg/dose) or placebo. The participants in the phase 2 trial were randomized to receive either KCONVAC (at 5 or 10 μg/dose) or placebo on Days 0 and 14 (0/14 regimen) or Days 0 and 28 (0/28 regimen). In the phase 1 trial, the primary safety endpoint was the proportion of participants experiencing adverse reactions/events within 28 days following the administration of each dose. In the phase 2 trial, the primary immunogenicity endpoints were neutralization antibody seroconversion and titer and anti-receptor-binding domain immunoglobulin G seroconversion at 28 days after the second dose.Results:In the phase 1 trial, 60 participants were enrolled and received at least one dose of 5-μg vaccine (n = 24), 10-μg vaccine (n = 24), or placebo (n = 12). In the phase 2 trial, 500 participants were enrolled and received at least one dose of 5-μg vaccine (n = 100 for 0/14 or 0/28 regimens), 10-μg vaccine (n = 100 for each regimen), or placebo (n = 50 for each regimen). In the phase 1 trial, 13 (54%), 11 (46%), and seven (7/12) participants reported at least one adverse event (AE) after receiving 5-, 10-μg vaccine, or placebo, respectively. In the phase 2 trial, 16 (16%), 19 (19%), and nine (18%) 0/14-regimen participants reported at least one AE after receiving 5-, 10-μg vaccine, or placebo, respectively. Similar AE incidences were observed in the three 0/28-regimen treatment groups. No AEs with an intensity of grade 3+ were reported, expect for one vaccine-unrelated serious AE (foot fracture) reported in the phase 1 trial. KCONVAC induced significant antibody responses; 0/28 regimen showed a higher immune responses than that did 0/14 regimen after receiving two vaccine doses.Conclusions:Both doses of KCONVAC are well tolerated and able to induce robust immune responses in healthy adults. These results support testing 5-μg vaccine in the 0/28 regimen in an upcoming phase 3 efficacy trial.Trial Registration:http://www.chictr.org.cn/index.aspx (No. ChiCTR2000038804, http://www.chictr.org.cn/showproj.aspx? proj=62350; No. ChiCTR2000039462, http://www.chictr.org.cn/showproj.aspx?proj=63353).

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简介：AbstractBackground:Critical patients with the coronavirus disease 2019 (COVID-19), even those whose nucleic acid test results had turned negative and those receiving maximal medical support, have been noted to progress to irreversible fatal respiratory failure. Lung transplantation (LT) as the sole therapy for end-stage pulmonary fibrosis related to acute respiratory distress syndrome has been considered as the ultimate rescue therapy for these patients.Methods:From February 10 to March 10, 2020, three male patients were urgently assessed and listed for transplantation. After conducting a full ethical review and after obtaining assent from the family of the patients, we performed three LT procedures for COVID-19 patients with illness durations of more than one month and extremely high sequential organ failure assessment scores.Results:Two of the three recipients survived post-LT and started participating in a rehabilitation program. Pearls of the LT team collaboration and perioperative logistics were summarized and continually improved. The pathological results of the explanted lungs were concordant with the critical clinical manifestation, and provided insight towards better understanding of the disease. Government health affair systems, virology detection tools, and modern communication technology all play key roles towards the survival of the patients and their rehabilitation.Conclusions:LT can be performed in end-stage patients with respiratory failure due to COVID-19-related pulmonary fibrosis. If confirmed positive-turned-negative virology status without organ dysfunction that could contraindicate LT, LT provided the final option for these patients to avoid certain death, with proper protection of transplant surgeons and medical staffs. By ensuring instant seamless care for both patients and medical teams, the goal of reducing the mortality rate and salvaging the lives of patients with COVID-19 can be attained.

简介：AbstractAcute respiratory distress syndrome (ARDS) is one of the most common severe diseases seen in the clinical setting. With the continuous exploration of ARDS in recent decades, the understanding of ARDS has improved. ARDS is not a simple lung disease but a clinical syndrome with various etiologies and pathophysiological changes. However, in the intensive care unit, ARDS often occurs a few days after primary lung injury or after a few days of treatment for other severe extrapulmonary diseases. Under such conditions, ARDS often progresses rapidly to severe ARDS and is difficult to treat. The occurrence and development of ARDS in these circumstances are thus not related to primary lung injury; the real cause of ARDS may be the "second hit" caused by inappropriate treatment. In view of the limited effective treatments for ARDS, the strategic focus has shifted to identifying potential or high-risk ARDS patients during the early stages of the disease and implementing treatment strategies aimed at reducing ARDS and related organ failure. Future research should focus on the prevention of ARDS.

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简介：AbstractBackground:The ongoing transmission of the Middle East respiratory syndrome coronavirus (MERS-CoV) in the Middle East and its expansion to other regions are raising concerns of a potential pandemic. An in-depth analysis about both population and molecular epidemiology of this pathogen is needed.Methods:MERS cases reported globally as of June 2020 were collected mainly from World Health Organization official reports, supplemented by other reliable sources. Determinants for case fatality and spatial diffusion of MERS were assessed with Logistic regressions and Cox proportional hazard models, respectively. Phylogenetic and phylogeographic analyses were performed to examine the evolution and migration history of MERS-CoV.Results:A total of 2562 confirmed MERS cases with 150 case clusters were reported with a case fatality rate of 32.7% (95% CI: 30.9-34.6%). Saudi Arabia accounted for 83.6% of the cases. Age of ≥ 65 years old, underlying conditions and ≥ 5 days delay in diagnosis were independent risk factors for death. However, a history of animal contact was associated with a higher risk (adjusted OR = 2.97, 95% CI: 1.10-7.98) among female cases < 65 years but with a lower risk (adjusted OR = 0.31, 95% CI: 0.18-0.51) among male cases ≥ 65 years old. Diffusion of the disease was fastest from its origin in Saudi Arabia to the east, and was primarily driven by the transportation network. The most recent subclade C5.1 (since 2013) was associated with non-synonymous mutations and a higher mortality rate. Phylogeographic analyses pointed to Riyadh of Saudi Arabia and Abu Dhabi of the United Arab Emirates as the hubs for both local and international spread of MERS-CoV.Conclusions:MERS-CoV remains primarily locally transmitted in the Middle East, with opportunistic exportation to other continents and a potential of causing transmission clusters of human cases. Animal contact is associated with a higher risk of death, but the association differs by age and sex. Transportation network is the leading driver for the spatial diffusion of the disease. These findings how this pathogen spread are helpful for targeting public health surveillance and interventions to control endemics and to prevent a potential pandemic.

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简介：AbstractSwine acute diarrhea syndrome coronavirus (SADS-CoV) is a recently discovered coronavirus that causes severe and acute diarrhea and rapid weight loss in piglets. SADS-CoV was reported to be capable of infecting cell lines derived from diverse species, including bats, mice, hamsters, rats, chickens, pigs, nonhuman primates, and humans, implying its high risk of cross-species infection. However, its receptor is still unknown. In this study, the receptor-binding domain of the SADS-CoV spike (S) protein was purified and then subjected to affinity purification (AP)-coupled mass spectrometry (MS)-based proteomic analysis to identify the interactors of the SADS-CoV S protein. Forty-three host proteins were identified, and a Gene Ontology analysis indicated that these interactors can be grouped into categories such as "cell-cell adhesion" , "translation" "viral transcription" , suggesting that these processes may participate in the SADS-CoV life cycles. RNA interference-based screening of these interactors indicated that PPIB and vimentin can affect SADS-CoV replication. Our study provides an overarching view into the host interactome of the SADS-CoV S protein and highlights potential targets for the development of therapeutics against SADS-CoV.

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简介：客观：与严重煽动性的反应症候群(先生)在创伤的病人调查甲状腺荷尔蒙的引申。方法：有严重先生的五十个创伤的病人被注册并且根据他们是否介绍了multiorgandysfunction症候群(MODS)把组划分了成二。甲状腺荷尔蒙大小被拿，包括totaltriiodothyronine(TT3)，全部的甲状腺素(TT4)，免费triiodothyronine(FT3)，免费甲状腺素(FT4)和甲状腺刺激荷尔蒙(TSH)。尖锐生理学和长期的健康评估Ⅱ(APACHEⅡ)20根据临床的数据被计算。恢复或恶化的结果被记录，以及从到时间甲状腺荷尔蒙的先生的发作的时间的长度被测量。结果：Euthyroid病了的症候群(S字)在45cases.TT3水平被介绍否定地与APACHEH分数被相关(r=-0.330,P<0。05)，并且TT3/TT4value否定地与先生的持续时间被相关(r=-0.316,P<0.05)。没有MODS，在MODS病人的TT3，TT4和FT3levels是比那些显著地低的(P<0.05)。没有MODS，给低TT4或FT4的MODS病人比那些经常铺平更多(P<0.05)。与在正常TSH组的病人相比，有有的减少的TSH的病人降低T3，T4，恢复率和更高的APACHEⅡ分数，MODS发生，但是二个组之间没有差别(P>0.05).Conclusions：有严重先生的损伤病人有高可能性得到S字，它更经常并且严重地发生在MODS病人。它在甲状腺轴上显示出先生的影响。Withthe坚持和先生的恶化，有甲状腺荷尔蒙的进步减小。

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