Awareness and use of tobacco products among underage individuals: findings from the altria client services underage tobacco use survey 2020-2022.

BACKGROUND: Tobacco use among underage individuals is a public health concern. Timely data about tobacco products, especially emerging products such as novel oral nicotine products (NPs), can provide critical information for the prevention of underage tobacco use. With a recent federal law raising the legal age of purchase of tobacco products from 18 to 21, it is of interest to benchmark awareness and use of tobacco products in the new underage population, young adults 18-20 years old. This study provides estimates on awareness and use of tobacco products among underage individuals 13-20 years old during May 2020 to August 2022 in the United States. METHODS: Altria Client Services Underage Tobacco Use Survey (UTUS) is a repeated cross-sectional survey conducted every quarter-year. A stratified random sampling approach was used to draw nationally representative samples of household dwelling individuals 13-20 years old. Information about the awareness and use of tobacco products was obtained via online self-administration or phone interviews after a consent/assent process. RESULTS: A sizable portion of underage individuals were aware of NPs (~ 40% among youth and ~ 50% among underage young adults), although past 30-day use was low (< 2%). The lowest levels of awareness and use were observed for heated tobacco products and snus. E-cigarettes were the most used tobacco products among underage individuals. Underage young adults (i.e., 18-20 year olds) were more likely to use tobacco products than youth (i.e., 13-17 year olds). There was no substantial change over time in the awareness and use of tobacco products during the study period despite a slight increase in past 30-day prevalence of e-cigarette use among youth between quarter 1 of 2021 and quarter 2 of 2022. CONCLUSIONS: The awareness and use of tobacco products remained relatively stable between May 2020 and August 2022. There is a notable level of awareness of novel NPs among underage individuals.

Pulmonary Findings of [18F]FDG PET/CT Images on Asymptomatic COVID-19 Patients.

During the coronavirus disease 2019 (COVID-19) pandemic, several case studies demonstrated that many asymptomatic patients with COVID-19 underwent fluorine-18 fluorodeoxyglucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT) examination for various indications. However, there is a lack of literature to characterize the pattern of [18F]FDG PET/CT imaging on asymptomatic COVID-19 patients. Therefore, a systematic review to analyze the pulmonary findings of [18F]FDG PET/CT on asymptomatic COVID-19 patients was conducted. This systematic review was performed under the guidelines of PRISMA. PubMed, Medline, and Web of Science were used to search for articles for this review. Articles with the key words: "asymptomatic", "COVID-19", "[18F]FDG PET/CT", and "nuclear medicine" were searched for from 1 January 2020 to 20 May 2021. Thirty asymptomatic patients with COVID-19 were included in the eighteen articles. These patients had a mean age of 62.25 ± 14.85 years (male: 67.71 ± 12.00; female: 56.79 ± 15.81). [18F]FDG-avid lung lesions were found in 93.33% (28/30) of total patients. The major lesion was [18F]FDG-avid multiple ground-glass opacities (GGOs) in the peripheral or subpleural region in bilateral lungs, followed by the consolidation. The intensity of [18F]FDG uptake in multiple GGOs was 5.605 ± 2.914 (range from 2 to 12) for maximal standardized uptake value (SUVmax). [18F]FDG-avid thoracic lymph nodes (LN) were observed in 40% (12/40) of the patients. They mostly appeared in both mediastinal and hilar regions with an SUVmax of 5.8 ± 2.93 (range from 2.5 to 9.6). The [18F]FDG uptake was observed in multiple GGOs, as well as in the mediastinal and hilar LNs. These are common patterns in PET/CT of asymptomatic patients with COVID-19.

Immune Response Related to Lymphadenopathy Post COVID-19 Vaccination.

Mass vaccination against coronavirus disease 2019 (COVID-19) is a global health strategy to control the COVID-19 pandemic. With the increasing number of vaccinations, COVID-19 vaccine-associated lymphadenopathy (C19-VAL) has been frequently reported. Current findings emphasize the characteristics of C19-VAL. The mechanism of C19-VAL is complicated to explore. Accumulated reports separately show that C19-VAL incidence is associated with receiver age and gender, reactive change within lymph nodes (LN), etc. We constructed a systematic review to evaluate the associated elements of C19-VAL and provide the mechanism of C19-VAL. Articles were searched from PubMed, Web of Science and EMBASE by using the processing of PRISMA. The search terms included combinations of the COVID-19 vaccine, COVID-19 vaccination and lymphadenopathy. Finally, sixty-two articles have been included in this study. Our results show that days post-vaccination and B cell germinal center response are negatively correlated with C19-VAL incidence. The reactive change within LN is highly related to C19-VAL development. The study results suggested that strong vaccine immune response may contribute to the C19-VAL development and perhaps through the B cell germinal center response post vaccination. From the perspective of imaging interpretation, it is important to carefully distinguish reactive lymph nodes from metastatic lymph node enlargement through medical history collection or evaluation, especially in patients with underlying malignancy.

Experience of parents in delivering pediatric tuina to children with symptoms of attention deficit hyperactivity disorder during the COVID-19 pandemic: qualitative findings from focus group interviews.

BACKGROUND: Evidence suggests that pediatric tuina, a modality of traditional Chinese medicine (TCM), might have beneficial effects on the symptoms of attention deficit hyperactivity disorder (ADHD), such as overall improvements in concentration, flexibility, mood, sleep quality, and social functioning. This study was conducted to understand the facilitators and barriers in the delivery of pediatric tuina by parents to children with ADHD symptoms. METHODS: This is a focus group interview embedded in a pilot randomized controlled trial on parent-administered pediatric tuina for ADHD in preschool children. Purposive sampling was employed to invite 15 parents who attended our pediatric tuina training program to participate voluntarily in three focus group interviews. The interviews were audio-recorded and transcribed verbatim. The data were analyzed through template analysis. RESULTS: Two themes were identified: (1) facilitators of intervention implementation and (2) barriers to intervention implementation. The theme of the facilitators of intervention implementation included the subthemes of (a) perceived benefits to children and parents, (b) acceptability to children and parents, (c) professional support, and (d) parental expectations of the long-term effects of the intervention. The theme of barriers to intervention implementation included the subthemes of (a) limited benefits for children's inattention symptoms, (b) manipulation management difficulties, and (c) limitations of TCM pattern identification. CONCLUSION: Perceived beneficial effects on the children's sleep quality and appetite and parent-child relationships, as well as timely and professional support, mainly facilitated the implementation of parent-administered pediatric tuina. Slow improvements in the children's inattention symptoms and the possible inaccuracies of online diagnosis were the dominant barriers of the intervention. Parents have high expectations for the provision of long-term professional support during their practice of pediatric tuina. The intervention presented here can be feasibly used by parents.

Nanoformulations targeting immune cells for cancer therapy: mRNA therapeutics

The approved worldwide use of two messenger RNA (mRNA) vaccines (BNT162b2 and mRNA-1273) in late 2020 has proven the remarkable success of mRNA therapeutics together with lipid nanoformulation technology in protecting people against coronaviruses during COVID-19 pandemic. This unprecedented and exciting dual strategy with nanoformulations and mRNA therapeutics in play is believed to be a promising paradigm in targeted cancer immunotherapy in future. Recent advances in nanoformulation technologies play a prominent role in adapting mRNA platform in cancer treatment. In this review, we introduce the biologic principles and advancements of mRNA technology, and chemistry fundamentals of intriguing mRNA delivery nanoformulations. We discuss the latest promising nano-mRNA therapeutics for enhanced cancer immunotherapy by modulation of targeted specific subtypes of immune cells, such as dendritic cells (DCs) at peripheral lymphoid organs for initiating mRNA cancer vaccine-mediated antigen specific immunotherapy, and DCs, natural killer (NK) cells, cytotoxic T cells, or multiple immunosuppressive immune cells at tumor microenvironment (TME) for reversing immune evasion. We highlight the clinical progress of advanced nano-mRNA therapeutics in targeted cancer therapy and provide our perspectives on future directions of this transformative integrated technology toward clinical implementation.

Immunogenicity and protective efficacy of a DNA vaccine inducing optimal expression of the SARS-CoV-2 S gene in hACE2 mice.

The wide spread of coronavirus disease 2019 (COVID-19) has significantly threatened public health. Human herd immunity induced by vaccination is essential to fight the epidemic. Therefore, highly immunogenic and safe vaccines are necessary to control SARS-CoV-2, whose S protein is the antigenic determinant responsible for eliciting antibodies that prevent viral entry and fusion. In this study, we developed a SARS-CoV-2 DNA vaccine expressing the S protein, named pVAX-S-OP, which was optimized according to the human-origin codon preference and using polyinosinic-polycytidylic acid as an adjuvant. pVAX-S-OP induced specific antibodies and neutralizing antibodies in BALB/c and hACE2 transgenic mice. Furthermore, we observed 1.43-fold higher antibody titers in mice receiving pVAX-S-OP plus adjuvant than in those receiving pVAX-S-OP alone. Interferon gamma production in the pVAX-S-OP-immunized group was 1.58 times (CD3+CD4+IFN-gamma+) and 2.29 times (CD3+CD8+IFN-gamma+) lower than that in the pVAX-S-OP plus adjuvant group but higher than that in the control group. The pVAX-S-OP vaccine was also observed to stimulate a Th1-type immune response. When, hACE2 transgenic mice were challenged with SARS-CoV-2, qPCR detection of N and E genes showed that the viral RNA loads in pVAX-S-OP-immunized mice lung tissues were 104 times and 106 times lower than those of the PBS control group, which shows that the vaccine could reduce the amount of live virus in the lungs of hACE2 mice. In addition, pathological sections showed less lung damage in the pVAX-S-OP-immunized group. Taken together, our results demonstrated that pVAX-S-OP has significant immunogenicity, which provides support for developing SARS-CoV-2 DNA candidate vaccines.

Research on Internet Hospital in China

If humans lose the sun, they will find it in eight minutes. If the implementation of Internet hospitals is fully improved and matched with the government's "medical community and Medical Association", the whole country will only be able to solve the problem in minutes. There are many problems in domestic hospitals, such as the shortage of medical resources in poor areas, "difficult and expensive to see a doctor, especially tired of queuing up;more disputes, more drugs, more cross infection . Since the outbreak of COVID-19 in 2020, a number of Internet based hospitals have emerged in the wake of the policies of our government and various sectors of the society. Shanghai internet management measures define "Internet hospital" as "including the Internet hospital as the second name of the entity medical institution, and the Internet hospital independently set up relying on the entity medical institution" [1]. In short, the Internet hospital is based on the entity medical institutions, and the third party organizations provide technical support, combined with advanced technology such as AI technology, 5G transmission, three-dimensional imaging, etc., to achieve the new "Internet plus medical health" development direction of online consultation, intelligent search and consultation, remote diagnosis and treatment, chronic disease management, grading system diagnosis and treatment, and drug delivery to home. Although the emergence of the epidemic has made the internet medical service in China develop rapidly from an uneven road to Kangzhuang Avenue, the number of registered real users has reached and exceeded the total number of the past four years just a few months before the outbreak. However, there are still some problems in Internet medicine, which is still an emerging industry. These problems include the quality and safety of internet medical services, the lag of laws and regulations, the weak willingness of cooperation among top three, the problem of multi-point practice policy formulation of doctors, the problem of Internet data storage, the problem of not carrying out Internet treatment activities for newly diagnosed patients, and how to promote Internet hospitals to achieve "medicine insurance " in an all-round way. In view of these common problems in China Internet medical industry, this paper puts forward the following solutions: from the perspective of market demand as the main driving force for the development of the industry, matching with the national "medical community, medical Consortium" policy, constantly improving laws and regulations, introducing blockchain information technology, and striving to create a platform that can promote the development of medical institutions, doctors and Internet public health the development environment of the Department and other parties, combined with the big data in the field of Internet medicine and the progress of 5g science and information technology, has formed a complete and standardized comprehensive medical service closed-loop and regional collaborative integration development, so as to achieve the real "digital health ".2 This paper uses the survey method and interdisciplinary research method, the research stage is mainly divided into early and late. In the early stage, through collecting the information about the reality and historical situation of the research object, we find out the problems existing in the Internet hospital, and then make a comprehensive comparison, analysis and induction according to the data. In the later stage, we use the scientific research methods, and use the relevant disciplines including computer, Internet, medical, legal, commercial, financial and so on to carry out cross research, They are highly differentiated and integrated into a unified whole.Finally, to imagine the solution to the problem is the core of this paper.

The Effects of Heterologous Immunization with Prime-Boost COVID-19 Vaccination against SARS-CoV-2.

Coronavirus Disease 2019 (COVID-19) pandemic, which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become the global challenge. Reaching global herd immunity will help end the COVID-19 pandemic. However, vaccine shortage and vaccine hesitancy are the obstacles to achieve global herd immunity against SARS-CoV-2. The current homologous vaccine regimen is experimentally switching to heterologous vaccination at several study sites. However, the reactogenicity of heterologous ChAdOx1-S and mRNA vaccination against SARS-CoV-2 is still unclear. We have conducted a systematic review to summarize the current findings on the safety and immunogenicity of this heterologous vaccination and elucidate their implications against SARS-CoV-2. This systematic review was conducted by the guidelines of PRISMA. Articles were searched from PubMed and other sources (MedRixv and Google scholar) starting from 1 January to 5 September 2021. The search term was heterologous ChAdOx1-S and BNT162b2 or mRNA-1273 vaccination. Our review found that participants with ChAdOx1/BNT162b2, ChAdOx1-S/mRNA-1273 or BNT162b2/ChAdOx1-S did not have the serious adverse events seen with homologous vaccination. Participants with the heterologous regimen (ChAdOx1/BNT162b2, ChAdOx1-S/mRNA-1273 or BNT162b2/ChAdOx1-S), compared with those with two doses of ChAdOx1-S, have shown a more robust immune responses against SARS-CoV-2, such as higher levels of responsive antibodies or increased numbers of spike-specific T-cells. Nevertheless, these immune responses were slightly diminished in the recipients of BNT162b2/ChAdOx1-S. Also, the safety study of heterologous ChAdOx1-S/mRNA vaccination was based on small populations. Further studies to enclose diverse categories, such as race/ethnicity or geography, may be necessary. Overall, the heterologous immunization with ChAdOX1-S and the mRNA vaccine may improve the vaccine shortage related slow pace of reaching herd immunity, especially using the heterologous immunization with ChAdOx1-S/BNT162b2.

Factors affecting duration of SARS-Cov-2 viral shedding in mildly symptomatic patients isolated in a community facility.

INTRODUCTION: Mildly symptomatic cases of Covid-19 in previously-well individuals form the majority of infections and also serve as potent vectors of transmission. The factors affecting the duration of SARS-CoV-2 RNA viral shedding (DVS) in these patients remain largely unknown. OBJECTIVES: To perform a systematic analysis of the clinical, radiologic, laboratory investigations in patients with few comorbidities infected with mild Covid-19 to identify factors associated with the DVS. METHODS: In this retrospective cohort study, patients with mild or asymptomatic Covid-19 were included. Baseline characteristics including age, nationality, comorbidities, concomitant medications, and type of isolation arrangement in the facility (single or in pairs) were collected. Clinical features and radiologic/haematologic findings were also collected. Taking day 28 as the cut-off, 187 patients who had a negative swab result up to day 28 (no prolonged DVS) were compared to 126 patients with a persistently positive result on or after day 28 (prolonged DVS). RESULTS: Of 964 consecutive patients included, 851 (88.3%) patients were symptomatic. 266 patients had a documented negative RT-PCR assay with a median DVS of 25 days (range: 13 to 96 days; interquartile range (IQR): 22 to 33 days). Patients isolated in pairs were associated with prolonged DVS (OR: 2.7; 95% CI: 1.7 to 4.5; p<0.0001) compared to those isolated individually. Among vital signs, only tachycardia was associated with prolonged DVS (OR: 2.6; 95% CI: 1.0 to 7.1; p = 0.03). Amongst investigations, only a raised CRP was associated with prolonged DVS (OR: 2.7; 95% CI: 1.1 to 6.8; p = 0.02). CONCLUSIONS: In young, mildly symptomatic Covid-19 patients, prolonged DVS was associated with being isolated in pairs compared to individually. In situations where a negative RT-PCR test result is required, retesting in patients who were not isolated individually, or who had baseline tachycardia or a raised CRP, may be delayed to increase the yield of a negative result.

Neuro-Ophthalmic Literature Review

Greater attenuation of retinal atrophy may occur after 12 months of rituximab treatment, following which time GCIPL atrophy rates are similar to those observed among natalizumab-treated patients with RRMS and HCs. I Xiaojun Zhang i Visuomotor performance as the proxy of training-related function recovery in patients with mu... Lipp I, Foster C, Stickland R, Sgarlata E, Tallantyre EC, Davidson AE, Robertson NP, Jones DK, Wise RG, Tomassini V. Predictors of training-related improvement in visuomotor performance in patients with multiple sclerosis: A behavioural and MRI study. I Michael S. Vaphiades i Modulation of retinal atrophy with rituximab in multiple sclerosis Lambe J, Risher H, Filippatou AG, Murphy OC, Sotirchos ES, Ehrhardt H, Ogbuokiri E, Pellegrini N, Toliver B, Luciano NJ, Davis S, Fioravante N, Kwakyi O, Prince JL, Calabresi PA, Fitzgerald KC, Saidha S. Modulation of Retinal Atrophy With Rituximab in Multiple Sclerosis. This study conducted by a British multidisciplinary group of researchers chose visuo-motor performance as the proxy of functional recovery of multiple sclerosis (MS) patients after undergoing a 4-weeks homebased training session, combing demographic with baseline clinical features and magnetic resonance imaging (MRI) measures to predict function recovery of MS patients. [Extracted from the article] Copyright of Neuro-Ophthalmology is the property of Taylor & Francis Ltd and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Implementation of a pooled surveillance testing program for asymptomatic SARS-CoV-2 infections in K-12 schools and universities.

BACKGROUND: The negative impact of continued school closures during the height of the COVID-19 pandemic warrants the establishment of cost-effective strategies for surveillance and screening to safely reopen and monitor for potential in-school transmission. Here, we present a novel approach to increase the availability of repetitive and routine COVID-19 testing that may ultimately reduce the overall viral burden in the community. METHODS: We implemented a testing program using the SalivaClear࣪ pooled surveillance method that included students, faculty and staff from K-12 schools (student age range 5-18 years) and universities (student age range >18 years) across the country (Mirimus Clinical Labs, Brooklyn, NY). The data analysis was performed using descriptive statistics, kappa agreement, and outlier detection analysis. FINDINGS: From August 27, 2020 until January 13, 2021, 253,406 saliva specimens were self-collected from students, faculty and staff from 93 K-12 schools and 18 universities. Pool sizes of up to 24 samples were tested over a 20-week period. Pooled testing did not significantly alter the sensitivity of the molecular assay in terms of both qualitative (100% detection rate on both pooled and individual samples) and quantitative (comparable cycle threshold (Ct) values between pooled and individual samples) measures. The detection of SARS-CoV-2 in saliva was comparable to the nasopharyngeal swab. Pooling samples substantially reduced the costs associated with PCR testing and allowed schools to rapidly assess transmission and adjust prevention protocols as necessary. In one instance, in-school transmission of the virus was determined within the main office and led to review and revision of heating, ventilating and air-conditioning systems. INTERPRETATION: By establishing low-cost, weekly testing of students and faculty, pooled saliva analysis for the presence of SARS-CoV-2 enabled schools to determine whether transmission had occurred, make data-driven decisions, and adjust safety protocols. We provide strong evidence that pooled testing may be a fundamental component to the reopening of schools by minimizing the risk of in-school transmission among students and faculty. FUNDING: Skoll Foundation generously provided funding to Mobilizing Foundation and Mirimus for these studies.

Clinical significance of olfactory dysfunction in patients of COVID-19.

BACKGROUND: Currently, as the coronavirus disease (COVID-19) has become a pandemic, rapidly obtaining accurate information of patient symptoms and their progression is crucial and vital. Although the early studies in China have illustrated that the representative symptoms of COVID-19 include (dry) cough, fever, headache, fatigue, gastrointestinal discomfort, dyspnea, and muscle pain, there is increasing evidence to suggest that olfactory and taste disorder are related to the COVID-19 pandemic. Therefore, we conduct this study to review the present literature about the correlation between anosmia or dysgeusia and COVID-19. METHODS: A comprehensive literature search in 2020 of the electronic journal databases, mainly PubMed or Web of Science, was performed using the keywords COVID-19 or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with hyposmia, anosmia, dysgeusia, olfactory disorder, or olfactory dysfunction. The country, study period, case number, inpatient or outpatient medical visit, evaluation method (subjective complaints of dysfunction or objective evaluation), and occurrence rate of olfactory or gustatory function were reviewed. RESULTS: Many studies reported that the recoverable olfactory or gustatory dysfunction may play an important role as the early clinical symptom of COVID-19. It is associated with better prognosis, although further investigation and validation should be carried out. CONCLUSION: Studies have shown that smell and taste disturbances may represent an early symptom of COVID-19 and healthcare professionals must be very vigilant when managing patients with these symptoms. In the pandemic era, this implies testing for COVID-19 by healthcare workers with full personal protective equipment.

Profiles of Peripheral Immune Cells of Uncomplicated COVID-19 Cases with Distinct Viral RNA Shedding Periods.

The heterogeneity of immune response to COVID-19 has been reported to correlate with disease severity and prognosis. While so, how the immune response progress along the period of viral RNA-shedding (VRS), which determines the infectiousness of disease, is yet to be elucidated. We aim to exhaustively evaluate the peripheral immune cells to expose the interplay of the immune system in uncomplicated COVID-19 cases with different VRS periods and dynamic changes of the immune cell profile in the prolonged cases. We prospectively recruited four uncomplicated COVID-19 patients and four healthy controls (HCs) and evaluated the immune cell profile throughout the disease course. Peripheral blood mononuclear cells (PBMCs) were collected and submitted to a multi-panel flowcytometric assay. CD19+-B cells were upregulated, while CD4, CD8, and NK cells were downregulated in prolonged VRS patients. Additionally, the pro-inflammatory-Th1 population showed downregulation, followed by improvement along the disease course, while the immunoregulatory cells showed upregulation with subsequent decline. COVID-19 patients with longer VRS expressed an immune profile comparable to those with severe disease, although they remained clinically stable. Further studies of immune signature in a larger cohort are warranted.

Chloroquine and Hydroxychloroquine: Efficacy in the Treatment of the COVID-19.

Chloroquine (CQ) and its derivative, hydroxychloroquine (HCQ), have attracted wide attention for treating coronavirus disease 2019 (COVID-19). However, conflicting outcomes have been found in COVID-19 clinical trials after treatment with CQ or HCQ. To date, it remains uncertain whether CQ and HCQ are beneficial antiviral drugs for combating COVID-19. We performed a systematic review to depict the efficacy of CQ or HCQ for the treatment of COVID-19. The guidelines of PRISMA were used to conduct this systematic review. We searched through articles from PubMed, Web of Science and other sources that were published from 1 January 2020 to 31 October 2020. The search terms included combinations of human COVID-19, CQ, and HCQ. Eleven qualitative articles comprising of four clinical trials and seven observation studies were utilized in our systematic review. The analysis shows that CQ and HCQ do not have efficacy in treatment of patients with severe COVID-19. In addition, CQ and HCQ have caused life-threatening adverse reactions which included cardiac arrest, electrocardiogram modification, and QTc prolongation, particularly during the treatment of patients with severe COVID-19. Our systematic review suggested that CQ and HCQ are not beneficial antiviral drugs for curing patients with severe COVID-19. The treatment effect of CQ and HCQ is not only null but also causes serious side effects, which may cause potential cardiotoxicity in severe COVID-19 patients.

Single-cell transcriptomes of peripheral blood cells indicate and elucidate severity of COVID-19.

The blood and immune system of coronavirus disease 2019 (COVID-19) infected patients are dysfunctional, and numerous studies have been conducted to resolve their characteristics and pathogenic mechanisms. Nevertheless, the variations of immune responses along with disease severity have not been comprehensively documented. Here, we profiled the single-cell transcriptomes of 96,313 peripheral blood mononuclear cells (PBMCs) derived from 12 COVID-19 patients (including four moderate, four severe and four critical cases) and three healthy donors. We showed that proliferative CD8 effector T cells with declined immune functions and cytotoxicity accumulated in the critical stage. By contrast, the quantity of natural killer (NK) cells was significantly reduced, while they exhibited enhanced immune activities. Notably, a gradually attenuated responseto COVID-19 along with disease severity was observed in monocytes, in terms of cellular composition, transcriptional discrepancy and transcription factor regulatory network. Furthermore, we identified immune cell-type dependent cytokine signatures distinguishing the severity of COVID-19 patients. In addition, cell interactions between CD8 effector T/NK cells and monocytes mediated by inflammatory cytokines were enhanced in moderate and severe stages, but weakened in critical cases. Collectively, our work uncovers the cellular and molecular players underlying the disordered and heterogeneous immune responses associated with COVID-19 severity, which could provide valuable insights for the treatment of critical COVID-19 patients.

Ruxolitinib in treatment of severe coronavirus disease 2019 (COVID-19): A multicenter, single-blind, randomized controlled trial.

BACKGROUND: Accumulating evidence proposed Janus-associated kinase (JAK) inhibitors as therapeutic targets warranting rapid investigation. OBJECTIVE: This study evaluated the efficacy and safety of ruxolitinib, a JAK1/2 inhibitor, for coronavirus disease 2019. METHODS: We conducted a prospective, multicenter, single-blind, randomized controlled phase II trial involving patients with severe coronavirus disease 2019. RESULTS: Forty-three patients were randomly assigned (1:1) to receive ruxolitinib plus standard-of-care treatment (22 patients) or placebo based on standard-of-care treatment (21 patients). After exclusion of 2 patients (1 ineligible, 1 consent withdrawn) from the ruxolitinib group, 20 patients in the intervention group and 21 patients in the control group were included in the study. Treatment with ruxolitinib plus standard-of-care was not associated with significantly accelerated clinical improvement in severe patients with coronavirus disease 2019, although ruxolitinib recipients had a numerically faster clinical improvement. Eighteen (90%) patients from the ruxolitinib group showed computed tomography improvement at day 14 compared with 13 (61.9%) patients from the control group (P = .0495). Three patients in the control group died of respiratory failure, with 14.3% overall mortality at day 28; no patients died in the ruxolitinib group. Ruxolitinib was well tolerated with low toxicities and no new safety signals. Levels of 7 cytokines were significantly decreased in the ruxolitinib group in comparison to the control group. CONCLUSIONS: Although no statistical difference was observed, ruxolitinib recipients had a numerically faster clinical improvement. Significant chest computed tomography improvement, a faster recovery from lymphopenia, and favorable side-effect profile in the ruxolitinib group were encouraging and informative to future trials to test efficacy of ruxolitinib in a larger population.

Atypical presentation of SARS-CoV-2 infection: A case report.

BACKGROUND: The first case of pneumonia subsequently attributed to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) occurred in Wuhan, Hubei Province on December 8, 2019. The symptoms included fever, coughing, and breathing difficulties. A few patients with this infection may only have atypical symptoms, which could lead to a misdiagnosis and subsequently further facilitate the spread of the virus. CASE SUMMARY: A 74-year-old female patient complained of severe diarrhea. She did not have fever, coughing, or breathing difficulties. A physical examination revealed no obvious positive signs. The patient had been hypertensive for more than 10 years. Her blood pressure was well controlled. On January 9, 2020, the patient's son visited a colleague who was later confirmed positive for SARS-CoV-2 and his first close contact with our patient was on January 17. The patient was first diagnosed with gastrointestinal dysfunction. However, considering her indirect contact with a SARS-CoV-2-infected individual, we suggested that an atypical pneumonia virus infection should be ruled out. A computed tomography scan was performed on January 26, and showed ground-glass nodules scattered along the two lungs, suggestive of viral pneumonia. Given the clinical characteristics, epidemiological history, and examination, the patient was diagnosed with coronavirus disease-2019 (COVID-19). CONCLUSION: Our patient had atypical symptoms of COVID-19. Careful acquisition of an epidemiological history is necessary to make a correct diagnosis and strategize a treatment plan.