mRNA therapeutics for disease therapy: principles, delivery, and clinical translation.

Messenger RNA (mRNA) has become a key focus in the development of therapeutic agents, showing significant potential in preventing and treating a wide range of diseases. The COVID-19 pandemic in 2020 has accelerated the development of mRNA nucleic therapeutics and attracted significant investment from global biopharmaceutical companies. These therapeutics deliver genetic information into cells without altering the host genome, making them a promising treatment option. However, their clinical applications have been limited by issues such as instability, inefficient in vivo delivery, and low translational efficiency. Recent advances in molecular design and nanotechnology have helped overcome these challenges, and several mRNA formulations have demonstrated promising results in both animal and human testing against infectious diseases and cancer. This review provides an overview of the latest research progress in structural optimization strategies and delivery systems, and discusses key considerations for their future clinical use.

Meplazumab in hospitalized adults with severe COVID-19 (DEFLECT): a multicenter, seamless phase 2/3, randomized, third-party double-blind clinical trial.

Meplazumab, a humanized CD147 antibody, has shown favourable safety and efficacy in our previous clinical studies. In DEFLECT (NCT04586153), 167 patients with severe COVID-19 were enroled and randomized to receive three dosages of meplazumab and a placebo. Meplazumab at 0.12 mg/kg, compared to the placebo group, showed clinical benefits in significantly reducing mortality by 83.6% (2.4% vs. 14.6%, p = 0.0150), increasing the proportion of patients alive and discharged without supplemental oxygen (82.9% vs. 70.7%, p = 0.0337) and increasing the proportion of patients who achieved sustained clinical improvement (41.5% vs. 31.7%). The response rate in the 0.2 mg/kg group was relatively increased by 16.0% compared with the placebo group (53.7% vs. 46.3%). Meplazumab also reduced the viral loads and multiple cytokine levels. Compare with the placebo group, the 0.3 mg/kg significantly increased the virus negative rate by 40.6% (p = 0.0363) and reduced IL-8 level (p = 0.0460); the 0.2 mg/kg increased the negative conversion rate by 36.9%, and reduced IL-4 (p = 0.0365) and IL-8 levels (p = 0.0484). In this study, the adverse events occurred at a comparable rate across the four groups, with no unexpected safety findings observed. In conclusion, meplazumab promoted COVID-19 convalescence and reduced mortality, viral load, and cytokine levels in severe COVID-19 population with good safety profile.

Clinical features of elderly patients with COVID-19 in Wuhan, China.

BACKGROUND: Elderly patients with coronavirus disease 2019 (COVID-19) who have comorbidities, frailty or profound disabilities experience poor outcomes. We analyzed the clinical characteristics of elderly patients from Wuhan who had COVID-19 during the early stages of the pandemic. AIM: To identify factors affecting the early mortality of elderly patients with COVID-19. METHODS: The records of 234 patients who were 65-years-old or more and were hospitalized in Wuhan Huoshenshan Hospital from February 4 to March 4, 2020 were reviewed. All patients had confirmed COVID-19 and the final date of follow-up was April 4, 2020. RESULTS: There were 163 cases of mild disease (69.66%), 39 cases of severe disease (16.67%) and 32 cases of critical disease (13.68%). Twenty-nine patients died within 1 mo (12.40%), all of whom had critical disease. Surviving patients and deceased patients had no significant differences in age or chronic diseases. Overall, the most common symptoms were fever (65.4%), dry cough (57.3%), fatigue (47.4%) and shortness of breath (41%). The deceased patients had higher levels of multiple disease markers (C-reactive protein, D-dimer, lactate dehydrogenase, alanine amino transferase, aspartate aminotransferase, creatinine kinase and creatinine kinase-MB) and higher incidences of lymphocytopenia and hypoproteinemia. CONCLUSION: This single-center study of elderly patients from Wuhan, China who were hospitalized with COVID-19 indicated that age and chronic diseases were not associated with mortality. Hypertension, diabetes and cardiovascular disease were the most common comorbidities and the most common symptoms were fever, dry cough, fatigue and shortness of breath. Lymphocytopenia, increased levels of D-dimer and other markers indicative of damage to the heart, kidneys or liver were associated with an increased risk of death.

SARS-CoV-2 nucleocapsid protein triggers hyperinflammation via protein-protein interaction-mediated intracellular Cl- accumulation in respiratory epithelium.

SARS-CoV-2, the culprit pathogen of COVID-19, elicits prominent immune responses and cytokine storms. Intracellular Cl- is a crucial regulator of host defense, whereas the role of Cl- signaling pathway in modulating pulmonary inflammation associated with SARS-CoV-2 infection remains unclear. By using human respiratory epithelial cell lines, primary cultured human airway epithelial cells, and murine models of viral structural protein stimulation and SARS-CoV-2 direct challenge, we demonstrated that SARS-CoV-2 nucleocapsid (N) protein could interact with Smad3, which downregulated cystic fibrosis transmembrane conductance regulator (CFTR) expression via microRNA-145. The intracellular Cl- concentration ([Cl-]i) was raised, resulting in phosphorylation of serum glucocorticoid regulated kinase 1 (SGK1) and robust inflammatory responses. Inhibition or knockout of SGK1 abrogated the N protein-elicited airway inflammation. Moreover, N protein promoted a sustained elevation of [Cl-]i by depleting intracellular cAMP via upregulation of phosphodiesterase 4 (PDE4). Rolipram, a selective PDE4 inhibitor, countered airway inflammation by reducing [Cl-]i. Our findings suggested that Cl- acted as the crucial pathological second messenger mediating the inflammatory responses after SARS-CoV-2 infection. Targeting the Cl- signaling pathway might be a novel therapeutic strategy for COVID-19.

A Sustainability Improvement Strategy of Interconnected Data Centers Based on Dispatching Potential of Electric Vehicle Charging Stations

With the rapid development of information technology, the electricity consumption of Internet Data Centers (IDCs) increases drastically, resulting in considerable carbon emissions that need to be reduced urgently. In addition to the introduction of Renewable Energy Sources (RES), the joint use of the spatial migration capacity of IDC workload and the temporal flexibility of the demand of Electric Vehicle Charging Stations (EVCSs) provides an important means to change the carbon footprint of the IDC. In this paper, a sustainability improvement strategy for the IDC carbon emission reduction was developed by coordinating the spatial-temporal dispatch flexibilities of the IDC workload and the EVCS demand. Based on the Minkowski sum algorithm, a generalized flexible load model of the EVCSs, considering traffic flow and Road Impedance (RI) was formulated. The case studies show that the proposed method can effectively increase the renewable energy consumption, reduce the overall carbon emissions of multi-IDCs, reduce the energy cost of the DCO, and utilize the EV dispatching potential. Discussions are also provided on the relationship between workload processing time delay and the renewable energy consumption rate.

The roles of inactivated vaccines in older patients with infection of Delta variant in Nanjing, China.

BACKGROUND: The coronavirus disease 2019 (COVID-19) is spreading around the world. The COVID-19 vaccines may improve concerns about the pandemic. However, the roles of inactivated vaccines in older patients (aged ≥60 years) with infection of Delta variant were less studied. METHODS: We classified the older patients with infection of Delta variant into three groups based on the vaccination status: no vaccination (group A, n = 113), one dose of vaccination (group B, n = 46), and two doses of vaccination (group C, n = 22). Two inactivated COVID-19 vaccines (BBIBP-CorV or CoronaVac) were evaluated in this study. The demographic data, laboratory parameters, and clinical severity were recorded. RESULTS: A total of 181 older patients with infection of Delta variant were enrolled. 111 (61.3%) patients had one or more co-morbidities. The days of "turn negative" and hospital stay in Group C were lower than those in the other groups (P < 0.05). The incidences of multiple organ dysfunction syndrome (MODS), septic shock, acute respiratory distress syndrome (ARDS), acute kidney injury, and cardiac injury in Group A were higher than those in the other groups (P < 0.05). The MV-free days and ICU-free days during 28 days in Group A were also lower than those in the other groups (P < 0.05). In patients with co-morbidities, vaccinated cases had lower incidences of MODS (P = 0.015), septic shock (P = 0.015), and ARDS (P = 0.008). CONCLUSIONS: The inactivated COVID-19 vaccines were effective in improving the clinical severity of older patients with infection of Delta variant.

Recurrent SARS-CoV-2 RNA positivity and prolonged viral shedding in a patient with COVID-19: a case report.

BACKGROUND: The ongoing coronavirus disease 2019 (COVID-19) global pandemic caused by the SARS-CoV-2 virus remains a major threat to public health. At present, it is recommended that patients with known or suspected COVID-19 undergo quarantine or medical observation for 14 days. However, recurrent SARS-CoV-2 RNA positivity and prolonged viral shedding have been documented in convalescent COVID-19 patients, complicating efforts to control viral spread and ensure patient recovery. CASE PRESENTATION: We report the case of a patient who experienced two recurrent episodes of SARS-CoV-2 RNA and IgM positivity and viral shedding over 60 days during hospitalization. CONCLUSIONS: This case report demonstrates that relapses of SARS-CoV-2 RNA and IgM positivity may occur even after COVID-19 symptoms have resolved, possibly as a consequence of prolonged viral shedding rather than re-infection.

A cohort autopsy study defines COVID-19 systemic pathogenesis.

Severe COVID-19 disease caused by SARS-CoV-2 is frequently accompanied by dysfunction of the lungs and extrapulmonary organs. However, the organotropism of SARS-CoV-2 and the port of virus entry for systemic dissemination remain largely unknown. We profiled 26 COVID-19 autopsy cases from four cohorts in Wuhan, China, and determined the systemic distribution of SARS-CoV-2. SARS-CoV-2 was detected in the lungs and multiple extrapulmonary organs of critically ill COVID-19 patients up to 67 days after symptom onset. Based on organotropism and pathological features of the patients, COVID-19 was divided into viral intrapulmonary and systemic subtypes. In patients with systemic viral distribution, SARS-CoV-2 was detected in monocytes, macrophages, and vascular endothelia at blood-air barrier, blood-testis barrier, and filtration barrier. Critically ill patients with long disease duration showed decreased pulmonary cell proliferation, reduced viral RNA, and marked fibrosis in the lungs. Permanent SARS-CoV-2 presence and tissue injuries in the lungs and extrapulmonary organs suggest direct viral invasion as a mechanism of pathogenicity in critically ill patients. SARS-CoV-2 may hijack monocytes, macrophages, and vascular endothelia at physiological barriers as the ports of entry for systemic dissemination. Our study thus delineates systemic pathological features of SARS-CoV-2 infection, which sheds light on the development of novel COVID-19 treatment.

Hope Levels and Resilience in Patients with Severe Novel Coronavirus Pneumonia: The Current Situation and a Correlation Analysis.

OBJECTIVE: The study aims to analyze the correlation between hope levels and resilience in patients with severe novel coronavirus pneumonia (COVID-19). METHODS: Fifty-six patients with severe COVID-19 were investigated, with the use of a general information questionnaire, the Herth Hope Index, and the Connor-Davidson resilience scale. RESULTS: There was a significant difference in patients' hope levels with respect to marital status and educational background (P < 0.05), and there was a significant difference in resilience scores depending on gender and family economic situation (P < 0.05). In the present study, the hope levels and resilience in the patients were moderate, with an average score of (34.93 ± 5.45) and (69.36 ± 15.52), respectively. There was a significant positive correlation between the hope level and the resilience score in these patients (P < 0.05). CONCLUSION: In patients with severe COVID-19, the higher the hope level, the higher the resilience score.

Examination of Community Sentiment Dynamics due to COVID-19 Pandemic: A Case Study from a State in Australia.

The outbreak of the novel Coronavirus Disease 2019 (COVID-19) has caused unprecedented impacts to people's daily life around the world. Various measures and policies such as lockdown and social-distancing are implemented by governments to combat the disease during the pandemic period. These measures and policies as well as virus itself may cause different mental health issues to people such as depression, anxiety, sadness, etc. In this paper, we exploit the massive text data posted by Twitter users to analyse the sentiment dynamics of people living in the state of New South Wales (NSW) in Australia during the pandemic period. Different from the existing work that mostly focuses on the country-level and static sentiment analysis, we analyse the sentiment dynamics at the fine-grained local government areas (LGAs). Based on the analysis of around 94 million tweets that posted by around 183 thousand users located at different LGAs in NSW in 5 months, we found that people in NSW showed an overall positive sentimental polarity and the COVID-19 pandemic decreased the overall positive sentimental polarity during the pandemic period. The fine-grained analysis of sentiment in LGAs found that despite the dominant positive sentiment most of days during the study period, some LGAs experienced significant sentiment changes from positive to negative. This study also analysed the sentimental dynamics delivered by the hot topics in Twitter such as government policies (e.g. the Australia's JobKeeper program, lockdown, social-distancing) as well as the focused social events (e.g. the Ruby Princess Cruise). The results showed that the policies and events did affect people's overall sentiment, and they affected people's overall sentiment differently at different stages.

Effects of progressive muscle relaxation training on negative emotions and sleep quality in COVID-19 patients: A clinical observational study.

This study investigates the effect of progressive muscle relaxation training on negative mood and sleep quality in Coronavirus Pneumonia (COVID-19) patients.COVID-19 is an emerging infectious disease, and there is still uncertainty about when the outbreak will be contained and the effectiveness of treatments. Considering that this disease is highly contagious, patients need to be treated in isolation. This may lead to psychological symptoms such as anxiety and depression, and even sleep problems.This study is a clinical observation study.Participants included 79 COVID-19 patients admitted to a designated hospital for COVID-19 patients in Wuhan from February to March, 2020. Patients were selected and assigned to the control group and the observation group according to their wishes, with 40 and 39 cases in each group, respectively. The control group received routine treatment and nursing, and the observation group received progressive muscle relaxation training, in addition to the routine treatment and nursing. We compared scores of the Pittsburgh Sleep Quality Index Scale (PSQI), the Generalized Anxiety Disorder (GAD-7), and the Patient Health Questionnaire (PHQ-9) before and after the intervention.There was no significant difference in PSQI, GAD-7, and PHQ-9 scores between the control group and the observation group before the intervention (P > .05). After the intervention, the difference in scores of PSQI, GAD-7, and PHQ-9 in the 2 groups were statistically significant (P < .05).Progressive muscle relaxation training can significantly reduce anxiety and depression and improve sleep quality in COVID-19 patients during isolation treatment.Progressive muscle relaxation training was shown to improve the treatment effect of patients and is worthy of clinical promotion.

Chemoprophylaxis, diagnosis, treatments, and discharge management of COVID-19: An evidence-based clinical practice guideline (updated version)

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of a rapidly spreading illness, coronavirus disease 2019 (COVID-19), affecting more than seventeen million people around the world. Diagnosis and treatment guidelines for clinicians caring for patients are needed. In the early stage, we have issued "A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version)";now there are many direct evidences emerged and may change some of previous recommendations and it is ripe for develop an evidence-based guideline. We formed a working group of clinical experts and methodologists. The steering group members proposed 29 questions that are relevant to the management of COVID-19 covering the following areas: chemoprophylaxis, diagnosis, treatments, and discharge management. We searched the literature for direct evidence on the management of COVID-19, and assessed its certainty generated recommendations using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. Recommendations were either strong or weak, or in the form of ungraded consensus-based statement. Finally, we issued 34 statements. Among them, 6 were strong recommendations for, 14 were weak recommendations for, 3 were weak recommendations against and 11 were ungraded consensus-based statement. They covered topics of chemoprophylaxis [including agents and Traditional Chinese Medicine (TCM) agents], diagnosis [including clinical manifestations, reverse transcription-polymerase chain reaction (RT-PCR), respiratory tract specimens, IgM and IgG antibody tests, chest computed tomography, chest X-ray, and CT features of asymptomatic infections], treatments [including lopinavir-ritonavir, umifenovir, favipiravir, interferon, remdesivir, combination of antiviral drugs, hydroxychloroquine/chloroquine, interleukin-6 inhibitors, interleukin-1 inhibitors, glucocorticoid, Qingfei Paidu decoction, Lianhua Qingwen granules/capsules, convalescent plasma, lung transplantation, invasive or noninvasive ventilation, and extracorporeal membrane oxygenation (ECMO)], and discharge management (including discharge criteria and management plan in patients whose RT-PCR retesting shows SARS-CoV-2 positive after discharge). We also created two figures of these recommendations for the implementation purpose. We hope these recommendations can help support healthcare workers caring for COVID-19 patients. © 2020 People's Military Medical Press. All rights reserved.

Features of family clusters of COVID-19 patients: A retrospective study.

BACKGROUND: To investigate and compare the clinical and imaging features among family members infected with COVID-19. METHODS: We retrospectively collected a total of 34 COVID-19 cases (15 male, 19 female, aged 48 ± 16 years, ranging from 10 to 81 years) from 13 families from January 17, 2020 through February 15, 2020. Patients were divided into two groups: Group 1 - part of the family members (first-generation) who had exposure history and others (second-generation) infected through them, and Group 2 - patients from the same family having identical exposure history. We collected clinical symptoms, laboratory findings, and high-resolution computed tomography (HRCT) features for each patient. Comparison tests were performed between the first- and second-generation patients in Group 1. RESULTS: In total there were 21 patients in Group 1 and 20 patients in Group 2. For Group 1, first-generation patients had significantly higher white blood cell count (6.5 × 109/L (interquartile range (IQR): 4.9-9.2 × 109/L) vs 4.5 × 109/L (IQR: 3.7-5.3 × 109/L); P = 0.0265), higher neutrophil count (4.9 × 109/L (IQR: 3.6-7.3 × 109/L) vs 2.9 × 109/L (IQR: 2.1-3.3 × 109/L); P = 0.0111), and higher severity scores on HRCT (3.9 ± 2.4 vs 2.0 ± 1.3, P = 0.0362) than the second-generation patients. Associated underlying diseases (odds ratio, 8.0, 95% confidence interval: 3.4-18.7, P = 0.0013) were significantly correlated with radiologic severity scores in second-generation patients. CONCLUSION: Analysis of the family cluster cases suggests that COVID-19 had no age or sex predominance. Secondarily infected patients in a family tended to develop milder illness, but this was not true for those with existing comorbidities.

Ocular manifestation, comorbidities, and detection of severe acute respiratory syndrome-coronavirus 2 from conjunctiva in coronavirus disease 2019: A systematic review and meta-analysis.

The coronavirus disease 2019 (COVID 19) pandemic has presented major challenges to ophthalmologists. Reports have shown that ocular manifestations can be the first presenting symptoms of COVID 19 infection and conjunctiva may be a portal of entry for the severe acute respiratory syndrome (SARS) associated coronavirus 2 (SARS CoV 2). The purpose of this article is to provide general guidance for ophthalmologists to understand the prevalence of ocular presentation in COVID 19 patients and to reduce the risk of transmission during practice. Relevant studies published in the period of November 1, 2019, and July 15, 2020, regarding ocular manifestations of COVID 19 and detection of SARS CoV 2 in the eye were included in this systematic review and meta analysis. The pooled prevalence of the ocular manifestations has been estimated at 7% (95% confidence interval [CI]: 0.03-0.10) among COVID 19 patients. The pooled detection rate of SARS CoV 2 from conjunctiva was low (1%, 95% CI: 0.00-0.03). Conjunctival symptoms were the most common ocular manifestations in COVID 19, but the positive detection rate of the SARS CoV 2 virus by reverse transcription-polymerase chain reaction of conjunctival tears or secretions remained low. No study has shown a definite transmission of COVID 19 through ocular mucosa or secretions. In summary, ocular manifestations in COVID 19 patients commonly comprise ocular surface symptoms. Although a low prevalence of ocular symptoms was encountered among patients infected by SARS CoV 2, it is imperative for all ophthalmologists to understand the full spectrum of COVID 19 symptoms or signs including those of the eyes as well as to adopt appropriate protective measures during clinical practice.

Chemoprophylaxis, diagnosis, treatments, and discharge management of COVID-19: An evidence-based clinical practice guideline (updated version).

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of a rapidly spreading illness, coronavirus disease 2019 (COVID-19), affecting more than seventeen million people around the world. Diagnosis and treatment guidelines for clinicians caring for patients are needed. In the early stage, we have issued "A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version)"; now there are many direct evidences emerged and may change some of previous recommendations and it is ripe for develop an evidence-based guideline. We formed a working group of clinical experts and methodologists. The steering group members proposed 29 questions that are relevant to the management of COVID-19 covering the following areas: chemoprophylaxis, diagnosis, treatments, and discharge management. We searched the literature for direct evidence on the management of COVID-19, and assessed its certainty generated recommendations using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. Recommendations were either strong or weak, or in the form of ungraded consensus-based statement. Finally, we issued 34 statements. Among them, 6 were strong recommendations for, 14 were weak recommendations for, 3 were weak recommendations against and 11 were ungraded consensus-based statement. They covered topics of chemoprophylaxis (including agents and Traditional Chinese Medicine (TCM) agents), diagnosis (including clinical manifestations, reverse transcription-polymerase chain reaction (RT-PCR), respiratory tract specimens, IgM and IgG antibody tests, chest computed tomography, chest x-ray, and CT features of asymptomatic infections), treatments (including lopinavir-ritonavir, umifenovir, favipiravir, interferon, remdesivir, combination of antiviral drugs, hydroxychloroquine/chloroquine, interleukin-6 inhibitors, interleukin-1 inhibitors, glucocorticoid, qingfei paidu decoction, lianhua qingwen granules/capsules, convalescent plasma, lung transplantation, invasive or noninvasive ventilation, and extracorporeal membrane oxygenation (ECMO)), and discharge management (including discharge criteria and management plan in patients whose RT-PCR retesting shows SARS-CoV-2 positive after discharge). We also created two figures of these recommendations for the implementation purpose. We hope these recommendations can help support healthcare workers caring for COVID-19 patients.

Proposed measures to be taken by ophthalmologists during the coronavirus disease 2019 pandemic: Experience from Chang Gung Memorial Hospital, Linkou, Taiwan.

PURPOSE: Although Taiwan was one of the first countries to develop coronavirus disease 2019 (COVID-19), with effective antiepidemic measures, Taiwan has effectively controlled the spread of the disease. The purpose of this article is to provide useful safety strategies for ophthalmologists in daily practice during the COVID-19 pandemic. MATERIALS AND METHODS: Infection control strategies in the hospital and Department of Ophthalmology, Chang Gung Memorial Hospital, Linkou, are discussed. RESULTS: Ophthalmologists are at high risk of contracting COVID-19 infection, as they have close contact with patients during ocular examinations, and are also facing high patient volume in outpatient clinics as well as emergency consultations. Furthermore, ocular symptoms, such as conjunctivitis, may be the presenting signs of COVID-19 infection. We provide our strategies, which include hospital's gate control with triage station, patient volume control, proper personal protective equipment, and consultation with telemedicine technology, to decrease the risk of cross-infection between medical staffs and patients. CONCLUSION: To achieve the goal of preventing viral spread and maximizing patient and medical staffs' safety, besides providing proper protective equipment, it is also crucial for staffs and patients to strictly follow antiepidemic measures. We hope that our experience can help ophthalmologists and health-care workers to have a safer working environment when facing COVID-19 pandemic.

[Discussion on the effect pathways of preventing and treating coronavirus disease 2019 by acupuncture and moxibustion from the regulation of immune inflammatory response].

The effect of acupuncture-moxibustion on respiratory system and systemic immune inflammatory response were reviewed to explore the possible role of neuroimmunomodulation in the control of inflammatory response and the effect mechanism of cholinergic anti-inflammatory pathway on coronavirus disease 2019 (COVID-19). Acupuncture-moxibustion could produce the local and systemic anti-inflammatory effect on COVID-19 through the activation of cholinergic anti-inflammatory pathway. Compared with humoral anti-inflammatory pathway, the neuronal anti-inflammatory pathway has earlier initiation, rapider action, and more localization, which play a more important role in the initial stage of inflammatory response. This may be an important basis for acupuncture-moxibustion intervention in the early stage of COVID-19. In addition to cholinergic anti-inflammatory pathway, acupuncture-moxibustion may also play an anti-inflammatory role in activating sympathetic nerve, hypothalamic-pituitary-adrenal axis and other neural anti-inflammatory pathways. How acupuncture-moxibustion play its role in stimulating the vagus nerve and sympathetic nerve in different periods of inflammatory response, and whether the effect is based on the selection of acupoints and the methods of stimulation, will be the research direction of the transformation from basic research to clinical research for acupuncture-moxibustion.

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.

Updating the diagnostic criteria of COVID-19 "suspected case" and "confirmed case" is necessary.

On 6 February 2020, our team had published a rapid advice guideline for diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infection, and this guideline provided our experience and make well reference for fighting against this pandemic worldwide. However, the coronavirus disease 2019 (COVID-19) is a new disease, our awareness and knowledge are gradually increasing based on the ongoing research findings and clinical practice experience; hence, the strategies of diagnosis and treatment are also continually updated. In this letter, we answered one comment on our guideline and provided the newest diagnostic criteria of "suspected case" and "confirmed case" according to the latest Diagnosis and Treatment Guidelines for COVID-19 (seventh version) that issued by the National Health Committee of the People's Republic of China.

Meplazumab treats COVID-19 pneumonia: an open-labelled, concurrent controlled add-on clinical trial (preprint)

Background: SARS-CoV-2 is a novel human coronavirus, there is no specific antiviral drugs. It has been proved that host-cell-expressed CD147 could bind spike protein of SARS-CoV-2 and involve in host cell invasion. Antibody against CD147 could block the infection of SARS-CoV-2. We aimed to assess the efficacy and safety of meplazumab, a humanized anti-CD147 antibody, as add-on therapy in patients with COVID-19 pneumonia. Methods: All patients received recommended strategy from Diagnosis and Treatment for 2019 Novel Coronavirus Diseases released by National Health Commission of China. Eligible patients were add-on administered 10 mg meplazumab intravenously at days 1, 2, and 5. Patients hospitalized in the same period were observed as concurrent control. The endpoints include virological clearance rate, case severity, chest radiographic, and laboratory test. This trial was approved by the Ethics Committee of Institution at the Tangdu hospital, and registered with ClinicalTrials.gov, NCT 04275245. Findings:17 patients were enrolled and assigned to meplazumab group between Feb 3, 2020 and Feb 10, 2020. 11 hospitalized patients served as concurrent control. Baseline characteristics were generally balanced across two groups. Compared to control group, meplazumab treatment significantly improved the discharged (p=0.006) and case severity (p=0.021) in critical and severe patients. The time to virus negative in meplazumab group was reduced than that in control group (median 3, 95%CI[1.5-4.5] vs. 13, [6.5-19.5]; p=0.014, HR=0.37, 95%CI[0.155-0.833]). The percentages of patients recovered to the normal lymphocyte count and CRP concentration were also increased remarkably and rapidly in meplazumab group. No adverse effect was found in meplazumab-treated patients. Interpretation:Meplazumab efficiently improved the recovery of patients with SARS-CoV-2 pneumonia with a favorable safety profile. Our results support to carry out a large-scale investigation of meplazumab as a treatment for COVID-19 pneumonia. Funding:National Science and Technology Major Project.