Evaluation of efficacy and safety of Qiangzhu-qinggan formula as an adjunctive therapy in adult patients with severe influenza: study protocol for a randomized parallel placebo-controlled double-blind multicenter trial.

BACKGROUND: Influenza can fall into three categories according to severity: mild influenza, severe influenza, and critical influenza. Severe influenza can result in critical illness and sometimes death particularly in patients with comorbidities, advanced age, or pregnancy. Neuraminidase inhibitors (NAIs) are the only antiviral drugs in widespread use for influenza. However, the effectiveness of NAIs against severe influenza is uncertain. New effective drugs or regimens are therefore urgently needed. Qiangzhu-qinggan (QZQG) formula has been found to be effective against influenza virus infection during long-term application in China, which lacks support of evidence-based clinical trial till now. This study is designed to assess the efficacy and safety of QZQG formula as an adjuvant therapy in adult patients with severe influenza. METHODS: This protocol is drawn up in accordance with the SPIRIT guidelines and CONSORT Extension for Chinese herbal medicine formulas. This is a randomized, placebo-controlled, double-blind, multicenter trial. Two hundred twenty-eight adults with severe influenza are randomly assigned in a 1:1 ratio to QZQG or placebo for 7 days. All participants need to receive 1 day of screening before randomization, 7 days of intervention, and 21 days of observation after randomization. The primary outcome is the proportion of clinical improvement, defined as the proportion of patients who met the criteria of 3 points or less in the seven-category ordinal scale or 2 points or less in National Early Warning Score 2 within 7 days after randomization. DISCUSSION: This is the first randomized, controlled, parallel, double-blind clinical trial to evaluate the efficacy and safety of traditional Chinese herbal formula granules as an adjuvant therapy in adult patients with severe influenza. This study aims to redefine the value of traditional Chinese herbal medicines in the treatment of virus-related respiratory infectious diseases and serves as an example of evidence-based clinical trials of other Chinese herbal medicines.

A Review of Recent Advances in Vital Signals Monitoring of Sports and Health via Flexible Wearable Sensors.

In recent years, vital signals monitoring in sports and health have been considered the research focus in the field of wearable sensing technologies. Typical signals include bioelectrical signals, biophysical signals, and biochemical signals, which have applications in the fields of athletic training, medical diagnosis and prevention, and rehabilitation. In particular, since the COVID-19 pandemic, there has been a dramatic increase in real-time interest in personal health. This has created an urgent need for flexible, wearable, portable, and real-time monitoring sensors to remotely monitor these signals in response to health management. To this end, the paper reviews recent advances in flexible wearable sensors for monitoring vital signals in sports and health. More precisely, emerging wearable devices and systems for health and exercise-related vital signals (e.g., ECG, EEG, EMG, inertia, body movements, heart rate, blood, sweat, and interstitial fluid) are reviewed first. Then, the paper creatively presents multidimensional and multimodal wearable sensors and systems. The paper also summarizes the current challenges and limitations and future directions of wearable sensors for vital typical signal detection. Through the review, the paper finds that these signals can be effectively monitored and used for health management (e.g., disease prediction) thanks to advanced manufacturing, flexible electronics, IoT, and artificial intelligence algorithms; however, wearable sensors and systems with multidimensional and multimodal are more compliant.

Dynamic landscape mapping of humoral immunity to SARS-CoV-2 identifies non-structural protein antibodies associated with the survival of critical COVID-19 patients.

A comprehensive analysis of the humoral immune response to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is essential in understanding COVID-19 pathogenesis and developing antibody-based diagnostics and therapy. In this work, we performed a longitudinal analysis of antibody responses to SARS-CoV-2 proteins in 104 serum samples from 49 critical COVID-19 patients using a peptide-based SARS-CoV-2 proteome microarray. Our data show that the binding epitopes of IgM and IgG antibodies differ across SARS-CoV-2 proteins and even within the same protein. Moreover, most IgM and IgG epitopes are located within nonstructural proteins (nsps), which are critical in inactivating the host's innate immune response and enabling SARS-CoV-2 replication, transcription, and polyprotein processing. IgM antibodies are associated with a good prognosis and target nsp3 and nsp5 proteases, whereas IgG antibodies are associated with high mortality and target structural proteins (Nucleocapsid, Spike, ORF3a). The epitopes targeted by antibodies in patients with a high mortality rate were further validated using an independent serum cohort (n = 56) and using global correlation mapping analysis with the clinical variables that are associated with COVID-19 severity. Our data provide fundamental insight into humoral immunity during SARS-CoV-2 infection. SARS-CoV-2 immunogenic epitopes identified in this work could also help direct antibody-based COVID-19 treatment and triage patients.

Reverse Transcription Recombinase-Aided Amplification Assay With Lateral Flow Dipstick Assay for Rapid Detection of 2019 Novel Coronavirus.

Background: The emerging Coronavirus Disease-2019 (COVID-19) has challenged the public health globally. With the increasing requirement of detection for SARS-CoV-2 outside of the laboratory setting, a rapid and precise Point of Care Test (POCT) is urgently needed. Methods: Targeting the nucleocapsid (N) gene of SARS-CoV-2, specific primers, and probes for reverse transcription recombinase-aided amplification coupled with lateral flow dipstick (RT-RAA/LFD) platform were designed. For specificity evaluation, it was tested with human coronaviruses, human influenza A virus, influenza B viruses, respiratory syncytial virus, and hepatitis B virus, respectively. For sensitivity assay, it was estimated by templates of recombinant plasmid and pseudovirus of SARS-CoV-2 RNA. For clinical assessment, 100 clinical samples (13 positive and 87 negatives for SARS-CoV-2) were tested via quantitative reverse transcription PCR (RT-qPCR) and RT-RAA/LFD, respectively. Results: The limit of detection was 1 copies/µl in RT-RAA/LFD assay, which could be conducted within 30 min at 39°C, without any cross-reaction with other human coronaviruses and clinical respiratory pathogens. Compared with RT-qPCR, the established POCT assay offered 100% specificity and 100% sensitivity in the detection of clinical samples. Conclusion: This work provides a convenient POCT tool for rapid screening, diagnosis, and monitoring of suspected patients in SARS-CoV-2 endemic areas.

The seroprevalence and kinetics of IgM and IgG in the progression of COVID-19.

BACKGROUND: SARS-CoV-2 is a novel coronavirus first recognized in late December 2019 that causes coronavirus disease 19 (COVID-19). Due to the highly contagious nature of SARS-CoV-2, it has developed into a global pandemic in just a few months. Antibody testing is an effective method to supplement the diagnosis of COVID-19. However, multicentre studies are lacking to support the understanding of the seroprevalence and kinetics of SARS-CoV-2 antibodies in COVID-19 epidemic regions. METHOD: A multicentre cross-sectional study of suspected and confirmed patients from 4 epidemic cities in China and a cohort study of consecutive follow-up patients were conducted from 29/01/2020 to 12/03/2020. IgM and IgG antibodies elicited by SARS-CoV-2 were tested by a chemiluminescence assay. Clinical information, including basic demographic data, clinical classification, and time interval from onset to sampling, was collected from each centre. RESULTS: A total of 571 patients were enrolled in the cross-sectional study, including 235 COVID-19 patients and 336 suspected patients, each with 91.9%:2.1% seroprevalence of SARS-CoV-2 IgG and 92.3%:5.4% seroprevalence of SARS-CoV-2 IgM. The seroprevalence of SARS-CoV-2 IgM and IgG in COVID-19 patients was over 70% less than 7 days after symptom onset. Thirty COVID-19 patients were enrolled in the cohort study and followed up for 20 days. The peak concentrations of IgM and IgG were reached on the 10th and 20th days, respectively, after symptom onset. The seroprevalence of COVID-19 IgG and IgM increased along with the clinical classification and treatment time delay. CONCLUSION: We demonstrated the kinetics of IgM and IgG SARS-CoV-2 antibodies in COVID-19 patients and the association between clinical classification and antibodies, which will contribute to the interpretation of IgM and IgG SARS-CoV-2 antibody tests and in predicting the outcomes of patients with COVID-19.

Estimating the Impact of COVID-19 on Urology: Data from a Large Nationwide Cohort.

The impact of the coronavirus disease 2019 (COVID-19) pandemic on urology worldwide has been the subject of frequent speculation, but population-level estimates on changes in urology care are sparsely reported. Here, we use newly released data from a large USA-based cohort to provide further insight into the impact of the pandemic on our field. For a final cohort of 900,900 patient encounters in 418 hospitals, we describe an approximately 20% decrease in urology-specific emergency room (ER) visits (19.4%, 95% confidence interval [CI] 17.4-21.5%), admissions to a urology service (19.3%, 95% CI 13.7-24.9%), and ambulatory urology surgeries (22.9%, 95% CI 13.2-32.6%) during March 2020 relative to baseline. On linear regression, region was the sole predictor of decrease in volume, reflecting the heterogeneous spread of the SARS-CoV-2 virus within the USA. Selected higher-acuity ER presentations, such as obstructing kidney stones and "acute scrotum", appeared to be preserved relative to lower-acuity presentations, such as nonobstructing stones, hematuria, and urinary retention. These data create context for changes observed by individual urology practices and shed light on triage patterns during natural disasters. PATIENT SUMMARY: The coronavirus disease 2019 (COVID-19) pandemic decreased the amount of urology care provided in the USA by approximately 20% during March 2020. Patients with complaints potentially requiring imaging tests or surgery seemed to come to the emergency room at nearly normal levels.

SARS-CoV-2 Proteome Microarray for Mapping COVID-19 Antibody Interactions at Amino Acid Resolution.

Comprehensive profiling of humoral antibody response to severe acute respiratory syndrome (SARS) coronavirus-2 (CoV-2) proteins is essential in understanding the host immunity and in developing diagnostic tests and vaccines. To address this concern, we developed a SARS-CoV-2 proteome peptide microarray to analyze antibody interactions at the amino acid resolution. With the array, we demonstrate the feasibility of employing SARS-CoV-1 antibodies to detect the SARS-CoV-2 nucleocapsid phosphoprotein. The first landscape of B-cell epitopes for SARS-CoV-2 IgM and IgG antibodies in the serum of 10 coronavirus disease of 2019 (COVID-19) patients with early infection is also constructed. With array data and structural analysis, a peptide epitope for neutralizing antibodies within the SARS-CoV-2 spike receptor-binding domain's interaction interface with the angiotensin-converting enzyme 2 receptor was predicted. All the results demonstrate the utility of our microarray as a platform to determine the changes of antibody responses in COVID-19 patients and animal models as well as to identify potential targets for diagnosis and treatment.

Antiphospholipid Antibodies in Critically Ill Patients With COVID-19.

OBJECTIVE: Coagulopathy is one of the characteristics observed in critically ill patients with coronavirus disease 2019 (COVID-19). Antiphospholipid antibodies (aPLs) contribute to coagulopathy, though their role in COVID-19 remains unclear. This study was undertaken to determine the prevalence and characteristics of aPLs in patients with COVID-19. METHODS: Sera collected from 66 COVID-19 patients who were critically ill and 13 COVID-19 patients who were not critically ill were tested by chemiluminescence immunoassay for anticardiolipin antibodies (aCLs), anti-ß2 -glycoprotein I (anti-ß2 GPI) (IgG, IgM, and IgA), and IgG anti-ß2 GPI-domain 1 (anti-ß2 GPI-D1) and IgM and IgG anti-phosphatidylserine/prothrombin (anti-PS/PT) antibodies were detected in the serum by enzyme-linked immunosorbent assay. RESULTS: Of the 66 COVID-19 patients in critical condition, aPLs were detected in 31 (47% ). Antiphospholipid antibodies were not present among COVID-19 patients who were not in critical condition. The IgA anti-ß2 GPI antibody was the most commonly observed aPL in patients with COVID-19 and was present in 28.8% (19 of 66) of the critically ill patients, followed by IgA aCLs (17 of 66, or 25.8%) and IgG anti-ß2 GPI (12 of 66, or 18.2%). For multiple aPLs, IgA anti-ß2 GPI + IgA aCLs was the most common antibody profile observed (15 of 66, or 22.7%), followed by IgA anti-ß2 GPI + IgA aCL + IgG anti-ß2 GPI (10 of 66, or 15.2%). Antiphospholipid antibodies emerge ~35-39 days after disease onset. A dynamic analysis of aPLs revealed 4 patterns based on the persistence or transient appearance of the aPLs. Patients with multiple aPLs had a significantly higher incidence of cerebral infarction compared to patients who were negative for aPLs (P = 0.023). CONCLUSION: Antiphospholipid antibodies were common in critically ill patients with COVID-19. Repeated testing demonstrating medium to high titers of aPLs and the number of aPL types a patient is positive for may help in identifying patients who are at risk of developing cerebral infarction. Antiphospholipid antibodies may be transient and disappear within a few weeks, but in genetically predisposed patients, COVID-19 may trigger the development of an autoimmune condition similar to the antiphospholipid syndrome (APS), referred to as "COVID-19-induced APS-like syndrome." Long-term follow-up of COVID-19 patients who are positive for aPLs would be of great importance in understanding the pathogenesis of this novel coronavirus.

Knowledge, attitudes, and practices related to Coronavirus disease 2019 during the outbreak among workers in China: A large cross-sectional study.

Coronavirus disease 2019 (COVID-19) has recently emerged as a global threat. Understanding workers' knowledge, attitudes, and practices (KAP) regarding this new infectious disease is crucial to preventing and controlling it. This study aimed to assess KAP regarding COVID-19 during the outbreak among workers in China. The present study was part of a cross-sectional online survey study conducted based on a large labor-intensive factory, which has 180,000 workers from various Chinese provinces, from 2 February 2020 to 7 February 2020. KAP related to COVID-19 were measured by 32 items, each item was measured with an agree/disagree/unclear format, and only correct responses were given 1 point. KAP regarding COVID-19 were measured with 20 items, 6 items and 6 items, respectively. A total of 123,768 valid responses (68.8%) were included in the analysis. Generally, the levels of knowledge (mean: 16.3 out of 20 points), attitudes (mean: 4.5 out of 6 points), and practices (mean: 5.8 out of 6 points) related to COVID-19 were high. Only 36,373 respondents (29.4%) disagreed that gargling with salt water is effective in protecting against COVID-19. Moreover, older respondents had decreased levels of knowledge and practices related to COVID-19 (both P values for the trend <0.001), while better-educated respondents had increased levels of knowledge and practices related to COVID-19 (both P values for the trend <0.001). These results suggest that Chinese workers are highly aware of COVID-19, but health authorities still need to provide correct information on COVID-19 prevention and strengthen health interventions, particularly for older and less-educated workers.

Prevalence of anxiety and depression symptoms, and association with epidemic-related factors during the epidemic period of COVID-19 among 123,768 workers in China: A large cross-sectional study.

BACKGROUND: COVID-19 has gained intense attention globally. However, little is known about the COVID-19-ralated mental health status among workers. METHODS: The cross-sectional online survey with 123,768 workers was conducted from February 2, 2020 to February 7, 2020 on a mega-size labor-intensive factory in Shenzhen, China. Oral consent was obtained prior to the questionnaire survey. The information collected in the survey included demographic characteristics, psychological symptoms, COVID-19-related information, and demands for psychological education and interventions. Symptoms of anxiety and depression were measured by the Zung's Self-Rating Anxiety Scale and Self-Rating Depression Scale. Logistic regression models were performed to determine the association between related factors and mental health status. RESULTS: The prevalence of anxiety and depression symptoms was 3.4% and 22.8%, respectively. The dominant epidemic-related factors were having confirmed cases in the community (odds ratio [OR], 2.75, 95% CI, 2.37-3.19) and having confirmed friends (OR, 2.44; 95% CI, 1.69-3.52) for the increased risk of anxiety and depression symptoms, respectively. Nevertheless, major traditional risk factors such as general or poor health status and always drinking alcohol were still the dominant factors associated with the increased risk of anxiety and depression symptoms. Overall, 67.3% and 26.8% workers reported desire for psychological education and interventions, respectively. LIMITATIONS: All assessments were self-reported, resulting in a risk of method bias. CONCLUSIONS: Our findings show a relatively low prevalence of anxiety symptoms, a relatively high prevalence of depression symptoms, and urgent demand for psychological education and interventions among workers during the COVID-19 outbreak.

Serum Protein Profiling Reveals a Landscape of Inflammation and Immune Signaling in Early-stage COVID-19 Infection.

Coronavirus disease 2019 (COVID-19) is a highly contagious infection and threating the human lives in the world. The elevation of cytokines in blood is crucial to induce cytokine storm and immunosuppression in the transition of severity in COVID-19 patients. However, the comprehensive changes of serum proteins in COVID-19 patients throughout the SARS-CoV-2 infection is unknown. In this work, we developed a high-density antibody microarray and performed an in-depth proteomics analysis of serum samples collected from early COVID-19 (n = 15) and influenza (n = 13) patients. We identified a large set of differentially expressed proteins (n = 132) that participate in a landscape of inflammation and immune signaling related to the SARS-CoV-2 infection. Furthermore, the significant correlations of neutrophil and lymphocyte with the CCL2 and CXCL10 mediated cytokine signaling pathways was identified. These information are valuable for the understanding of COVID-19 pathogenesis, identification of biomarkers and development of the optimal anti-inflammation therapy.

Lessons learned from early compassionate use of convalescent plasma on critically ill patients with Covid-19.

BACKGROUND: The management of critically ill patients with coronavirus disease 2019 (COVID-19), caused by a new human virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is challenging. Recently, there have been several reports with inconsistent results after treatment with convalescent plasma (CP) on critically ill patients with COVID-19, which was produced with a neutralizing antibody titer and tested in a P3 or P4 laboratory. However, due to the limitation of the conditions on mass production of plasma, most producers hardly had the capability to isolate the neutralizing antibody. Here, we report the clinical courses of three critically ill patients with COVID-19 receiving CP treatments by total immunoglobulin G (IgG) titer collection. METHODS: Three patients with COVID-19 in this study were laboratory confirmed to be positive for SARS-CoV-2, with radiographic and clinical features of pneumonia. CP was collected by total IgG titer of 160 (range, 200-225 mL), and patients were transfused between 20 and 30 days after disease onset at the critical illness stage as a trial in addition to standard care. The clinical courses of these patients, including laboratory results and pulmonary functional and image studies after receiving convalescent plasma infusions, were reviewed. RESULTS: No therapeutic effect of CP was observed in any of the patients; instead, all three patients deteriorated and required extracorporeal membrane oxygenation treatment. A potential cytokine storm 4 hours after infusion of CP in Patient 2 was observed. No more patients were put on the trial of CP transfusion. CONCLUSIONS: We recommend extreme caution in using CP in critically ill patients more than 2 weeks after the onset of COVID-19 pneumonia.

Prevalence of anxiety and depression symptom, and the demands for psychological knowledge and interventions in college students during COVID-19 epidemic: A large cross-sectional study.

BACKGROUND: Although studies have suggested experiencing the epidemic of severe infectious diseases increased the prevalence of mental health problems, the association between COVID-19 epidemic and risk of anxiety and depression symptom in college students in China was unclear. METHODS: A large cross-sectional online survey with 44,447 college students was conducted in Guangzhou, China. The Zung's Self-rating Anxiety Scale (SAS) and the Center for Epidemiologic Studies Depression Scale (CES-D Scale) were used to define the anxiety and depression symptom, respectively. Multivariable logistic regression models were used to analyze the association between COVID-19 epidemic and risk of anxiety and depression symptom. RESULTS: The prevalence of anxiety and depression symptom was 7.7% (95% confidence interval [CI]: 7.5%, 8.0%) and 12.2% (95%CI: 11.9%, 12.5%), respectively. Compared with students who reported have not infected or suspected cases in family members and relatives, students who reported having confirmed (OR=4.06; 95%CI: 1.62, 10.19; P = 0.003), and suspected (OR=2.11; 95%CI: 1.11, 4.00; P = 0.023) cases in family members and relatives had higher risk of depression symptom. Additionally, the proportions of students with anxiety and depression symptom reported more demand of psychological knowledge and interventions than those without (P<0.001). LIMITATIONS: All the data in this study was collected through online questionnaire, and we did not evaluate the reliability and validity. CONCLUSIONS: The prevalence of anxiety and depression symptom was relatively low in college students, but the COVID-19 epidemic-related factors might be associated with higher depression symptom risk.