Real-world experience of arbidol for Omicron variant of SARS-CoV-2.

Background: At a crucial time with the rapid spread of Omicron severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus variant globally, we conducted a study to evaluate the efficacy and safety of arbidol tablets in the treatment of this variant. Methods: From Mar 26 to April 26, 2022, we conducted a prospective, open-labeled, controlled, and investigator-initiated trial involving adult patients with confirmed Omicron variant infection. Patients with asymptomatic or mild clinical status were stratified 1:2 to receive either standard-of-care (SOC) or SOC plus arbidol tablets (oral administration of 200 mg per time, three times a day for 5 days). The primary endpoint was the negative conversion rate within the first week. Results: A total of 367 patients were enrolled in the study; 246 received arbidol tablet treatment, and 121 were in the control group. The negative conversion rate of SARS-CoV-2 within the first week in patients receiving arbidol tablets was significantly higher than that of the SOC group [47.2% (116/246) vs. 35.5% (43/121); odds ratio (OR), 1.619; 95% confidence interval (CI): 1.034-2.535; P=0.035]. Compared to those in the SOC group, patients receiving arbidol tablets had a shorter negative conversion time [median 8.3 vs. 10.0 days; hazard ratio (HR), 0.645; 95% CI: 0.516-0.808; P<0.001], and a shorter duration of hospitalization (median 11.4 vs. 13.7 days; HR, 1.214; 95% CI: 0.966-1.526; P<0.001). Moreover, the addition of arbidol tablets led to better recovery of declined blood lymphocytes, CD3+, CD4+, and CD8+ cell counts. The most common adverse event (AE) was transaminase elevation in patients treated with arbidol tablets (3/246, 1.2%). No one withdrew from the study due to AEs or disease progression. Conclusions: As a whole, arbidol may represent an effective and safe treatment in asymptomatic-mild patients suffering from Omicron variant during the pandemic of coronavirus disease 2019 (COVID-19).

Efficacy and safety of Paxlovid in severe adult patients with SARS-Cov-2 infection: a multicenter randomized controlled study.

Background: Nirmatrelvir plus ritonavir (Paxlovid) reduced the risk of hospitalization or death by 89% in high-risk, ambulatory adults with COVID-19. We aimed at studying the efficacy and safety of Paxlovid in hospitalized adult patients with SARS-Cov-2 (Omicron BA.2.2 variant) infection and severe comorbidities. Methods: We conducted an open-label, multicenter, randomized controlled trial in which hospitalized adult patients with severe comorbidities were eligible and assigned in a 1:1 ratio to receive either 300 mg of nirmatrelvir plus 100 mg of ritonavir every 12 h for 5 days with standard treatment or only standard treatment. All-cause mortality on day 28, the duration of SARS-CoV-2 RNA clearance, and safety were evaluated. Findings: 264 patients (mean age, 70.35 years; 122 [46.21%] female) who met the criteria were enrolled at 5 sites in Shanghai from April 10 to May 19 in 2022. After randomization, a total of 132 patients were assigned to receive Paxlovid treatment plus standard treatment, and 132 patients were assigned to receive only standard treatment. The overall 28-day mortality was 4.92%, 8 patients died in the standard treatment group and 5 died in the Paxlovid plus standard treatment group. There was no significant difference in mortality from any cause at 28 days between the Paxlovid plus standard treatment group and the standard treatment group (absolute risk difference [ARD], 2.27; 95% CI -2.94 to 7.49, P = 0.39). There was no significant difference in the duration of SARS-CoV-2 RNA clearance among the two groups (mean days, 10 in Paxlovid plus standard treatment group and 10.50 in the standard treatment group; ARD, -0.62; 95% CI -2.29 to 1.05, P = 0.42). The incidence of adverse events that occurred during the treatment period was similar in the two groups (any adverse event, 10.61% with Paxlovid plus standard treatment vs. 7.58% with the standard, P = 0.39; serious adverse events, 4.55% vs. 3.788%, P = 0.76). Interpretation: Paxlovid showed no significant reduction in the risk of all-cause mortality on day 28 and the duration of SARS-CoV-2 RNA clearance in hospitalized adult COVID-19 patients with severe comorbidities. Funding: National Natural Science Foundation of China (grant number: 82172152, 81873944).

Efficacy and safety of Paxlovid in severe adult patients with SARS-Cov-2 infection: a multicenter randomized controlled study

Background Nirmatrelvir plus ritonavir (Paxlovid) reduced the risk of hospitalization or death by 89% in high-risk, ambulatory adults with COVID-19. We aimed at studying the efficacy and safety of Paxlovid in hospitalized adult patients with SARS-Cov-2 (Omicron BA.2.2 variant) infection and severe comorbidities. Methods We conducted an open-label, multicenter, randomized controlled trial in which hospitalized adult patients with severe comorbidities were eligible and assigned in a 1:1 ratio to receive either 300 mg of nirmatrelvir plus 100 mg of ritonavir every 12 h for 5 days with standard treatment or only standard treatment. All-cause mortality on day 28, the duration of SARS-CoV-2 RNA clearance, and safety were evaluated. Findings 264 patients (mean age, 70.35 years;122 [46.21%] female) who met the criteria were enrolled at 5 sites in Shanghai from April 10 to May 19 in 2022. After randomization, a total of 132 patients were assigned to receive Paxlovid treatment plus standard treatment, and 132 patients were assigned to receive only standard treatment. The overall 28-day mortality was 4.92%, 8 patients died in the standard treatment group and 5 died in the Paxlovid plus standard treatment group. There was no significant difference in mortality from any cause at 28 days between the Paxlovid plus standard treatment group and the standard treatment group (absolute risk difference [ARD], 2.27;95% CI −2.94 to 7.49, P = 0.39). There was no significant difference in the duration of SARS-CoV-2 RNA clearance among the two groups (mean days, 10 in Paxlovid plus standard treatment group and 10.50 in the standard treatment group;ARD, −0.62;95% CI −2.29 to 1.05, P = 0.42). The incidence of adverse events that occurred during the treatment period was similar in the two groups (any adverse event, 10.61% with Paxlovid plus standard treatment vs. 7.58% with the standard, P = 0.39;serious adverse events, 4.55% vs. 3.788%, P = 0.76). Interpretation Paxlovid showed no significant reduction in the risk of all-cause mortality on day 28 and the duration of SARS–CoV-2 RNA clearance in hospitalized adult COVID-19 patients with severe comorbidities. Funding 10.13039/501100001809National Natural Science Foundation of China (grant number: 82172152, 81873944).

Internet of medical things-enabled CRISPR diagnostics for rapid detection of SARS-CoV-2 variants of concern.

Previous studies have highlighted CRISPR-based nucleic acid detection as rapid and sensitive diagnostic methods for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, we reported an optimized CRISPR-Cas12a diagnostic platform for the safe and rapid detection of SARS-CoV-2 variants of concern (VOCs). This platform, which was referred to as CALIBURN-v2, could complete the diagnosis on extracted RNA samples within 25 min in a closed-lid reaction mode and had 100-fold increase in detection sensitivity in comparison with previous platforms. Most importantly, by integrating a portable device and smartphone user interface, CALIBURN-v2 allowed for cloud server-based data collection and management, thus transforming the point-of-care testing (POCT) platform to internet of medical things (IoMT) applications. It was found that IoMT-enabled CALIBURN-v2 could achieve 95.56% (172 out of 180) sensitivity for SARS-CoV-2 wild type and 94.38% (84 out of 89) overall sensitivity for SARS-CoV-2 variants including Delta and Omicron strains. Therefore, our study provides a feasible approach for IoMT-enabled CRISPR diagnostics for the detection of SARS-CoV-2 VOCs.

Internet of medical things-enabled CRISPR diagnostics for rapid detection of SARS-CoV-2 variants of concern

Previous studies have highlighted CRISPR-based nucleic acid detection as rapid and sensitive diagnostic methods for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, we reported an optimized CRISPR-Cas12a diagnostic platform for the safe and rapid detection of SARS-CoV-2 variants of concern (VOCs). This platform, which was referred to as CALIBURN-v2, could complete the diagnosis on extracted RNA samples within 25 min in a closed-lid reaction mode and had 100-fold increase in detection sensitivity in comparison with previous platforms. Most importantly, by integrating a portable device and smartphone user interface, CALIBURN-v2 allowed for cloud server-based data collection and management, thus transforming the point-of-care testing (POCT) platform to internet of medical things (IoMT) applications. It was found that IoMT-enabled CALIBURN-v2 could achieve 95.56% (172 out of 180) sensitivity for SARS-CoV-2 wild type and 94.38% (84 out of 89) overall sensitivity for SARS-CoV-2 variants including Delta and Omicron strains. Therefore, our study provides a feasible approach for IoMT-enabled CRISPR diagnostics for the detection of SARS-CoV-2 VOCs.

A trial of arbidol hydrochloride in adults with COVID-19.

BACKGROUND: To date, there is no effective medicine to treat coronavirus disease 2019 (COVID-19), and the antiviral efficacy of arbidol in the treatment for COVID-19 remained equivocal and controversial. The purpose of this study was to evaluate the efficacy and safety of arbidol tablets in the treatment of COVID-19. METHODS: This was a prospective, open-label, controlled and multicenter investigator-initiated trial involving adult patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Patients were stratified 1:2 to either standard-of-care (SOC) or SOC plus arbidol tablets (oral administration of 200 mg per time, three times a day for 14 days). The primary endpoint was negative conversion of SARS-CoV-2 within the first week. The rates and 95% confidential intervals were calculated for each variable. RESULTS: A total of 99 patients with laboratory-confirmed SARS-CoV-2 infection were enrolled; 66 were assigned to the SOC plus arbidol tablets group, and 33 to the SOC group. The negative conversion rate of SARS-CoV-2 within the first week in patients receiving arbidol tablets was significantly higher than that of the SOC group (70.3% [45/64] vs. 42.4% [14/33]; difference of conversion rate 27.9%; 95% confidence interval [CI], 7.7%-48.1%; P  = 0.008). Compared to those in the SOC group, patients receiving arbidol tablets had a shorter duration of clinical recovery (median 7.0 days vs. 12.0 days; hazard ratio [HR]: 1.877, 95% CI: 1.151-3.060, P = 0.006), symptom of fever (median 3.0 days vs. 12.0 days; HR: 18.990, 95% CI: 5.350-67.410, P < 0.001), as well as hospitalization (median 12.5 days vs. 20.0 days; P < 0.001). Moreover, the addition of arbidol tablets to SOC led to more rapid normalization of declined blood lymphocytes (median 10.0 days vs. 14.5 days; P > 0.05). The most common adverse event in the arbidol tablets group was the elevation of transaminase (5/200, 2.5%), and no one withdrew from the study due to adverse events or disease progression. CONCLUSIONS: SOC plus arbidol tablets significantly increase the negative conversion rate of SARS-CoV-2 within the first week anas, accelerate the recovery of COVID-19 patients. During the treatment with arbidol tablets, we find no significant serious adverse events. TRIAL REGISTRATION: Chinese Clinical Trial Registry, NCT04260594, www.clinicaltrials.gov/ct2/show/NCT04260594?term=NCT04260594&draw=2&rank=1.

Research advances and clinical management of bronchiectasis: Chinese perspective.

Bronchiectasis is a debilitating chronic suppurative airway disease that confers a substantial burden globally. Despite the notable prevalence, research on bronchiectasis in mainland China remains in its infancy. Nevertheless, there has been a significant leap in the quantity and quality of research, which has contributed to the ever-improving clinical practice. A nationwide collaborative platform has been established to foster multicentre studies, which will help increase the level of evidence further. Here, we summarise the status quo of clinical management and consider the research priorities for bronchiectasis that have been published previously. We also highlight the efforts of the Chinese medical communities to outline the core tasks that need to be addressed within the next decade.

Nebulized exosomes derived from allogenic adipose tissue mesenchymal stromal cells in patients with severe COVID-19: a pilot study.

BACKGROUND: Existing clinical studies supported the potential efficacy of mesenchymal stromal cells as well as derived exosomes in the treatment of COVID-19. We aimed to explore the safety and efficiency of aerosol inhalation of the exosomes derived from human adipose-derived MSCs (haMSC-Exos) in patients with COVID-19. METHODS: The MEXCOVID trial is a phase 2a single-arm, open-labelled, interventional trial and patients were enrolled in Jinyintan Hospital, Wuhan, China. Eligible 7 patients were assigned to receive the daily dose of haMSCs-Exos (2.0 × 108 nano vesicles) for consecutively 5 days. The primary outcomes included the incidence of prespecified inhalation-associated events and serious adverse events. We also observed the demographic data, clinical characteristics, laboratory results including lymphocyte count, levels of D-dimer and IL-6 as well as chest imaging. RESULTS: Seven severe COVID-19 related pneumonia patients (4 males and 3 females) were enrolled and received nebulized haMSC-Exos. The median age was 57 year (interquartile range (IQR), 43 year to 70 year). The median time from onset of symptoms to hospital admission and administration of nebulized haMSC-Exos was 30 days (IQR, 15 days to 40 days) and 54 d (IQR, 34 d to 69 d), respectively. All COVID-19 patients tolerated the haMSC-Exos nebulization well, with no evidence of prespecified adverse events or clinical instability during the nebulization or during the immediate post-nebulization period. All patients presented a slight increase of serum lymphocyte counts (median as 1.61 × 109/L vs. 1.78 × 109/L). Different degrees of resolution of pulmonary lesions after aerosol inhalation of haMSC-Exos were observed among all patients, more obviously in 4 of 7 patients. CONCLUSIONS: Our trial shows that a consecutive 5 days inhalation dose of clinical grade haMSC-Exos up to a total amount of 2.0 × 109 nano vesicles was feasible and well tolerated in seven COVID-19 patients, with no evidence of prespecified adverse events, immediate clinical instability, or dose-relevant toxicity at any of the doses tested. This safety profile is seemingly followed by CT imaging improvement within 7 days. Further trials will have to confirm the long-term safety or efficacy in larger population. TRIAL REGISTRATION: MEXCOVID, NCT04276987.

Neutralizing activity of BBIBP-CorV vaccine-elicited sera against Beta, Delta and other SARS-CoV-2 variants of concern.

The global pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in the generation of variants that may diminish host immune responses to vaccine formulations. Here we show a registered observational clinical trial (NCT04795414), we assess the safety and immunogenicity of the inactivated SARS-CoV-2 vaccine BBIBP-CorV in a cohort of 1006 vaccine recipients. No serious adverse events are observed during the term of the study. Detectable virus-specific antibody is measured and determined to be neutralizing in 698/760 (91.84%) vaccine recipients on day 28 post second vaccine dose and in 220/581 (37.87%) vaccine recipients on day 180 post second vaccine dose, whereas vaccine-elicited sera show varying degrees of reduction in neutralization against a range of key SARS-CoV-2 variants, including variant Alpha, Beta, Gamma, Iota, and Delta. Our work show diminished neutralization potency against multiple variants in vaccine-elicited sera, which indicates the potential need for additional boost vaccinations.

Hydroxychloroquine in patients with mainly mild to moderate coronavirus disease 2019: open label, randomised controlled trial

Objective: To assess the efficacy and safety of hydroxychloroquine plus standard of care compared with standard of care alone in adults with coronavirus disease 2019 (covid-19). Design: Multicentre, open label, randomised controlled trial. Setting 16 government designated covid-19 treatment centres in China, 11 to 29 February 2020. Participants: 150 patients admitted to hospital with laboratory confirmed covid-19 were included in the intention to treat analysis (75 patients assigned to hydroxychloroquine plus standard of care, 75 to standard of care alone). Interventions Hydroxychloroquine administrated at a loading dose of 1200 mg daily for three days followed by a maintenance dose of 800 mg daily (total treatment duration: two or three weeks for patients with mild to moderate or severe disease, respectively). Main outcome measure: Negative conversion of severe acute respiratory syndrome coronavirus 2 by 28 days, analysed according to the intention to treat principle. Adverse events were analysed in the safety population in which hydroxychloroquine recipients were participants who received at least one dose of hydroxychloroquine and hydroxychloroquine non-recipients were those managed with standard of care alone.

Distinct immune signatures discriminate between asymptomatic and presymptomatic SARS-CoV-2pos subjects.

Increasing numbers of SARS-CoV-2-positive (SARS-CoV-2pos) subjects are detected at silent SARS-CoV-2 infection stage (SSIS). Yet, SSIS represents a poorly examined time-window wherein unknown immunity patterns may contribute to the fate determination towards persistently asymptomatic or overt disease. Here, we retrieved blood samples from 19 asymptomatic and 12 presymptomatic SARS-CoV-2pos subjects, 47 age/gender-matched patients with mild or moderate COVID-19 and 27 normal subjects, and interrogated them with combined assays of 44-plex CyTOF, RNA-seq and Olink. Notably, both asymptomatic and presymptomatic subjects exhibited numerous readily detectable immunological alterations, while certain parameters including more severely decreased frequencies of CD107alow classical monocytes, intermediate monocytes, non-classical monocytes and CD62Lhi CD8+ Tnaïve cells, reduced plasma STC1 level but an increased frequency of CD4+ NKT cells combined to distinguish the latter. Intercorrelation analyses revealed a particular presymptomatic immunotype mainly manifesting as monocytic overactivation and differentiation blockage, a likely lymphocyte exhaustion and immunosuppression, yielding mechanistic insights into SSIS fate determination, which could potentially improve SARS-CoV-2 management.

Inactivated SARS-CoV-2 vaccine does not influence the profile of prothrombotic antibody nor increase the risk of thrombosis in a prospective Chinese cohort.

The presence of antiphospholipid antibodies was shown to be associated with thrombosis in coronavirus disease 2019 (COVID-19) patients. Recently, according to reports from several studies, the vaccine-induced immune thrombotic thrombocytopenia is mediated by anti-platelet factor 4 (PF4)-polyanion complex in adenovirus-vectored COVID-19 vaccine recipients. It is impendent to explore whether inactivated COVID-19 vaccine widely used in China influences prothrombotic autoantibody production and induces thrombosis. In this prospective study, we recruited 406 healthcare workers who received two doses, 21 days apart, of inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine (BBIBP-CorV, Sinopharm). Paired blood samples taken before vaccination and four weeks after the second vaccination were used in detecting prothrombotic autoantibodies, including anticardiolipin (aCL), anti-ß2 glycoprotein I (aß2GP1), anti-phosphatidylserine/prothrombin (aPS/PT), and anti-PF4-heparin. The seroconversion rate of SARS-CoV-2 specific antibodies was 95.81% (389/406) four weeks after vaccination. None of the subjects had spontaneous thrombosis or thrombocytopenia over a minimum follow-up period of eight weeks. There was no significant difference in the presence of all ten autoantibodies between samples collected before and after vaccination: for aCL, IgG (7 vs. 8, P = 0.76), IgM (41 vs. 44, P = 0.73), IgA (4 vs. 4, P = 1.00); anti-ß2GP1, IgG (7 vs. 6, P = 0.78), IgM (6 vs. 5, P = 0.76), IgA (3 vs. 5, P = 0.72); aPS/PT IgG (0 vs. 0, P = 1.00), IgM (6 vs. 5, P = 0.76); aPF4-heparin (2 vs. 7, P = 0.18), and antinuclear antibody (ANA) (18 vs. 21, P = 0.62). Notably, seven cases presented with anti-PF4-heparin antibodies (range: 1.18-1.79 U/mL) after vaccination, and none of them exhibited any sign of thrombotic disorder. In conclusion, inactivated SARS-CoV-2 vaccine does not influence the profile of antiphospholipid antibody and anti-PF4-heparin antibody nor increase the risk of thrombosis.

Risk factors for secondary hemophagocytic lymphohistiocytosis in severe coronavirus disease 2019 adult patients.

BACKGROUND: Secondary hemophagocytic lymphohistiocytosis (sHLH) is a life-threatening hyperinflammatory event and a fatal complication of viral infections. Whether sHLH may also be observed in patients with a cytokine storm induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is still uncertain. We aimed to determine the incidence of sHLH in severe COVID-19 patients and evaluate the underlying risk factors. METHOD: Four hundred fifteen severe COVID-19 adult patients were retrospectively assessed for hemophagocytosis score (HScore). A subset of 7 patients were unable to be conclusively scored due to insufficient patient data. RESULTS: In 408 patients, 41 (10.04%) had an HScore ≥169 and were characterized as "suspected sHLH positive". Compared with patients below a HScore threshold of 98, the suspected sHLH positive group had higher D-dimer, total bilirubin, alanine aminotransferase, aspartate aminotransferase, blood urea nitrogen, serum creatinine, triglycerides, ferritin, interleukin-6, C-reactive protein, procalcitonin, lactate dehydrogenase, creatine kinase isoenzyme, troponin, Sequential Organ Failure Assessment (SOFA) score, while leukocyte, hemoglobin, platelets, lymphocyte, fibrinogen, pre-albumin, albumin levels were significantly lower (all P < 0.05). Multivariable logistic regression revealed that high ferritin (>1922.58 ng/mL), low platelets (<101 × 109/L) and high triglycerides (>2.28 mmol/L) were independent risk factors for suspected sHLH in COVID-19 patients. Importantly, COVID-19 patients that were suspected sHLH positive had significantly more multi-organ failure. Additionally, a high HScore (>98) was an independent predictor for mortality in COVID-19. CONCLUSIONS: HScore should be measured as a prognostic biomarker in COVID-19 patients. In particular, it is important that HScore is assessed in patients with high ferritin, triglycerides and low platelets to improve the detection of suspected sHLH.

Psychological Impact During the First Outbreak of COVID-19 on Frontline Health Care Workers in Shanghai.

Background: The COVID-19 pandemic is a significant health threat. Health care worker (HCWs) are at a significant risk of infection which may cause high levels of psychological distress. The aim of this study was to investigate the psychological impact of the COVID-19 on HCWs and factors which were associated with these stresses during the first outbreak in Shanghai. Methods: Between February 9 and 21, 2020, a total of 3,114 frontline HCWs from 26 hospitals in Shanghai completed an online survey. The questionnaire included questions on their sociodemographic characteristics, 15 stress-related questions, and General Health Questionnaire-12 (GHQ-12). Exploratory factor analysis was applied to the 15 stress-related questions which produced four distinct factors for evaluation. Multiple linear regression models were performed to explore the association of personal characteristics with each score of the four factors. Binary logistic analysis was used to explain the association of personal characteristics and these four factors with the GHQ-12. Results: There were 2,691 valid surveys received. The prevalence of emotional distress (defined as GHQ-12 ≥ 12) was noted in 47.7% (95%CI:45.7-49.6%) HCWs. Females (OR = 1.43, 95%CI:1.09-1.86) were more likely to have a psychological distress than males. However, HCWs who work in secondary hospitals (OR = 0.71, 95% CI:0.58-0.87) or had a no contact history (OR = 0.45, 95%CI: 0.35-0.58) were less likely to suffer psychological distress. HCWs who were nurses, married, and had a known contact history were highly likely to have anxiety. HCWs working at tertiary hospitals felt an elevated anxiety regarding the infection, a lack of knowledge, and less protected compared to those who worked at secondary hospitals. Conclusions: Our study shows that the frontline HCWs had a significant psychosocial distress during the COVID-19 outbreak in Shanghai. HCWs felt a lack of knowledge and had feelings of being not protected. It is necessary for hospitals and governments to provide additional trainings and psychological counseling to support the first-line HCWs.

High Dose Intravenous Vitamin C for Preventing The Disease Aggravation of Moderate COVID-19 Pneumonia. A Retrospective Propensity Matched Before-After Study.

Background: Coronavirus disease 2019 (COVID-19) pandemic is continuing to impact multiple countries worldwide and effective treatment options are still being developed. In this study, we investigate the potential of high-dose intravenous vitamin C (HDIVC) in the prevention of moderate COVID-19 disease aggravation. Methods: In this retrospective before-after case-matched clinical study, we compare the outcome and clinical courses of patients with moderate COVID-19 patients who were treated with an HDIVC protocol (intravenous injection of vitamin C, 100 mg/kg/day, 1 g/h, for 7 days from admission) during a one-month period (between March 18 and april 18, 2020, HDIVC group) with a control group treated without the HDIVC protocol during the preceding two months (January 18 to March 18, 2020). Patients in the two groups were matched in a 1:1 ratio according to age and gender. Results: The HDIVC and control groups each comprised 55 patients. For the primary outcomes, there was a significant difference in the number of patients that evolved from moderate to severe type between the two groups (HDIVC: 4/55 vs. control: 12/55, relative risk [RR] = 0.28 [0.08, 0.93], P = 0.03). Compared to the control group, there was a shorter duration of systemic inflammatory response syndrome (SIRS) (P = 0.0004) during the first week and lower SIRS occurrence (2/21 vs 10/22, P = 0.0086) on Day 7 (6-7 days after admission). In addition, HDIVC group had lower C-reactive protein levels (P = 0.005) and higher number of CD4+ T cells from Day 0 (on admission) to Day 7 (P = 0.04)." The levels of coagulation indicators, including activated partial thromboplastin time and D-dimer were also improved in the HDIVC compared to the control group on Day 7. Conclusion: HDIVC may be beneficial in limiting disease aggravation in the early stage of COVID-19 pneumonia, which may be related to its improvements on the inflammatory response, immune function and coagulation function. Further randomized controlled trials are required to augment these findings.

Management of hospitalised adults with coronavirus disease 2019 (COVID-19): a European Respiratory Society living guideline.

INTRODUCTION: Hospitalised patients with coronavirus disease 2019 (COVID-19) as a result of SARS-CoV-2 infection have a high mortality rate and frequently require noninvasive respiratory support or invasive ventilation. Optimising and standardising management through evidence-based guidelines may improve quality of care and therefore patient outcomes. METHODS: A task force from the European Respiratory Society and endorsed by the Chinese Thoracic Society identified priority interventions (pharmacological and non-pharmacological) for the initial version of this "living guideline" using the PICO (population, intervention, comparator, outcome) format. The GRADE approach was used for assessing the quality of evidence and strength of recommendations. Systematic literature reviews were performed, and data pooled by meta-analysis where possible. Evidence tables were presented and evidence to decision frameworks were used to formulate recommendations. RESULTS: Based on the available evidence at the time of guideline development (20 February, 2021), the panel makes a strong recommendation in favour of the use of systemic corticosteroids in patients requiring supplementary oxygen or ventilatory support, and for the use of anticoagulation in hospitalised patients. The panel makes a conditional recommendation for interleukin (IL)-6 receptor antagonist monoclonal antibody treatment and high-flow nasal oxygen or continuous positive airway pressure in patients with hypoxaemic respiratory failure. The panel make strong recommendations against the use of hydroxychloroquine and lopinavir-ritonavir. Conditional recommendations are made against the use of azithromycin, hydroxychloroquine combined with azithromycin, colchicine, and remdesivir, in the latter case specifically in patients requiring invasive mechanical ventilation. No recommendation was made for remdesivir in patients requiring supplemental oxygen. Further recommendations for research are made. CONCLUSION: The evidence base for management of COVID-19 now supports strong recommendations in favour and against specific interventions. These guidelines will be regularly updated as further evidence becomes available.

Corticosteroid treatment in severe COVID-19 patients with acute respiratory distress syndrome.

BACKGROUNDCorticosteroids are widely used in patients with COVID 19, although their benefit-to-risk ratio remains controversial.METHODSPatients with severe COVID-19-related acute respiratory distress syndrome (ARDS) were included from December 29, 2019 to March 16, 2020 in 5 tertiary Chinese hospitals. Cox proportional hazards and competing risks analyses were conducted to analyze the impact of corticosteroids on mortality and SARS-CoV-2 RNA clearance, respectively. We performed a propensity score (PS) matching analysis to control confounding factors.RESULTSOf 774 eligible patients, 409 patients received corticosteroids, with a median time from hospitalization to starting corticosteroids of 1.0 day (IQR 0.0-3.0 days) . As compared with usual care, treatment with corticosteroids was associated with increased rate of myocardial (15.6% vs. 10.4%, P = 0.041) and liver injury (18.3% vs. 9.9%, P = 0.001), of shock (22.0% vs. 12.6%, P < 0.001), of need for mechanical ventilation (38.1% vs. 19.5%, P < 0.001), and increased rate of 28-day all-cause mortality (44.3% vs. 31.0%, P < 0.001). After PS matching, corticosteroid therapy was associated with 28-day mortality (adjusted HR 1.46, 95% CI 1.01-2.13, P = 0.045). High dose (>200 mg) and early initiation (≤3 days from hospitalization) of corticosteroid therapy were associated with a higher 28-day mortality rate. Corticosteroid use was also associated with a delay in SARS-CoV-2 coronavirus RNA clearance in the competing risk analysis (subhazard ratio 1.59, 95% CI 1.17-2.15, P = 0.003).CONCLUSIONAdministration of corticosteroids in severe COVID-19-related ARDS is associated with increased 28-day mortality and delayed SARS-CoV-2 coronavirus RNA clearance after adjustment for time-varying confounders.FUNDINGNone.

Development of a Broadly Applicable Cas12a-Linked Beam Unlocking Reaction for Sensitive and Specific Detection of Respiratory Pathogens Including SARS-CoV-2.

The outbreak of novel coronavirus SARS-CoV-2 has caused a worldwide threat to public health. COVID-19 patients with SARS-CoV-2 infection can develop clinical symptoms that are often confused with the infections of other respiratory pathogens. Sensitive and specific detection of SARS-CoV-2 with the ability to discriminate from other viruses is urgently needed for COVID-19 diagnosis. Herein, we streamlined a highly efficient CRISPR-Cas12a-based nucleic acid detection platform, termed Cas12a-linked beam unlocking reaction (CALIBURN). We show that CALIBURN could detect SARS-CoV-2 and other coronaviruses and influenza viruses with little cross-reactivity. Importantly, CALIBURN allowed accurate diagnosis of clinical samples with extremely low viral loads, which is a major obstacle for the clinical applications of existing CRISPR diagnostic platforms. When tested on the specimens from SARS-CoV-2-positive and negative donors, CALIBURN exhibited 73.0% positive and 19.0% presumptive positive rates and 100% specificity. Moreover, unlike existing CRISPR detection methods that were mainly restricted to respiratory specimens, CALIBURN displayed consistent performance across both respiratory and nonrespiratory specimens, suggesting its broad specimen compatibility. Finally, using a mouse model of SARS-CoV-2 infection, we demonstrated that CALIBURN allowed detection of coexisting pathogens without cross-reactivity from a single tissue specimen. Our results suggest that CALIBURN can serve as a versatile platform for the diagnosis of COVID-19 and other respiratory infectious diseases.