Search

Importance: With the widespread use of anti-SARS-CoV-2 drugs, accumulating data have revealed potential viral load rebound after treatment., Objective: To compare COVID-19 rebound after a standard 5-day course of antiviral treatment with VV116 vs nirmatrelvir-ritonavir., Design, Setting, and Participants: This is a single-center, investigator-blinded, randomized clinical trial conducted in Shanghai, China. Adult patients with mild-to-moderate COVID-19 and within 5 days of SARS-CoV-2 infection were enrolled between December 20, 2022, and January 19, 2023, and randomly allocated to receive either VV116 or nirmatrelvir-ritonavir., Interventions: Participants in the VV116 treatment group received oral 600-mg VV116 tablets every 12 hours on day 1 and 300 mg every 12 hours on days 2 through 5. Participants in the nirmatrelvir-ritonavir treatment group received oral nirmatrelvir-ritonavir tablets with 300 mg of nirmatrelvir plus 100 mg of ritonavir every 12 hours for 5 days. Participants were followed up every other day until day 28 and every week until day 60., Main Outcomes and Measures: The primary outcome was viral load rebound (VLR), defined as a half-log increase in viral RNA copies per milliliter compared with treatment completion. Secondary outcomes included a reduction in the cycle threshold value of 1.5 or more, time until VLR, and symptom rebound, defined as an increase of more than 2 points in symptom score compared with treatment completion. The primary outcome and secondary outcomes were analyzed using the full analysis set. Sensitivity analyses were conducted using the per protocol set. Adverse events were analyzed using the safety analysis set., Results: The full analysis set included 345 participants (mean [SD] age, 53.2 [16.8] years; 175 [50.7%] were men) who received VV116 (n = 165) or nirmatrelvir-ritonavir (n = 180). Viral load rebound occurred in 33 patients (20.0%) in the VV116 group and 39 patients (21.7%) in the nirmatrelvir-ritonavir group (P = .70). Symptom rebound occurred in 41 of 160 patients (25.6%) in the VV116 group and 40 of 163 patients (24.5%) in the nirmatrelvir-ritonavir group (P = .82). Viral whole-genome sequencing of 24 rebound cases revealed the same lineage at baseline and at viral load rebound in each case., Conclusions and Relevance: In this randomized clinical trial of patients with mild-to-moderate COVID-19, viral load rebound and symptom rebound were both common after a standard 5-day course of treatment with either VV116 or nirmatrelvir-ritonavir. Prolongation of treatment duration might be investigated to reduce COVID-19 rebound., Trial Registration: Chinese Clinical Trial Registry Identifier: ChiCTR2200066811.

Background: High-flow nasal cannula (HFNC) and conventional oxygen therapy (COT) are important respiratory support strategies for acute hypoxemic respiratory failure (AHRF) in coronavirus disease 2019 (COVID-19) patients. However, the results are conflicting for the risk of intubation with HFNC as compared to COT., Objectives: We systematically synthesized the outcomes of HFNC relative to COT in COVID-19 patients with AHRF and evaluated these outcomes in relevant subpopulations., Design: This study was designed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines., Data Sources and Methods: We searched PubMed, EMBASE, Web of Science, Scopus, ClinicalTrials.gov, medRxiv, BioRxiv, and the Cochrane Central Register of Controlled Trials for randomized controlled trials and observational studies that compared the efficacy of HFNC with COT in patients with COVID-19-related AHRF. Primary outcomes were intubation rate and mortality rate. Secondary outcomes were the ratio of arterial oxygen partial pressure to fractional inspired oxygen (PaO 2 /FiO 2 ), respiratory rate, hospital length of stay, intensive care unit (ICU) length of stay, and days free from invasive mechanical ventilation., Results: In total, 20 studies with 5732 patients were included. We found a decreased risk of requiring intubation in HFNC compared to COT [odds ratio (OR) = 0.61, 95% confidence interval (CI): 0.46-0.82, p  = 0.0009, I 2  = 75%]. Similarly, we found HFNC was associated with lower risk of intubation rate compared to COT in the subgroup of patients with baseline PaO 2 /FiO 2  < 200 mmHg (OR = 0.69, 95% CI: 0.55-0.86, p  = 0.0007, I 2  = 45%), and who were in ICU settings at enrollment (OR = 0.57, 95% CI: 0.38-0.85, p  = 0.005, I 2  = 80%). HFNC was associated with an improvement of PaO 2 /FiO 2 and respiratory rate compared to COT. The use of HFNC compared to COT did not reduce the mortality rate, days free from invasive mechanical ventilation, hospital length of stay, or ICU length of stay., Conclusion: Compared to COT, HFNC may decrease the need for tracheal intubation in patients with COVID-19-related AHRF, particularly among patients with baseline PaO 2 /FiO 2  < 200 mmHg and those in ICU settings., Trial Registration: This systematic review and meta-analysis protocol was prospectively registered with PROSPERO (no. CRD42022339072).

Importance: Despite patients with cancer being at risk of poor outcomes from COVID-19, there are few published studies for vaccine efficacy in this group, with suboptimal immunogenicity and waning vaccine efficacy described in small studies being a concern., Objective: To assess the incidence rate of severe COVID-19 disease outcomes associated with the number of vaccine doses received and the waning of protection over time., Design, Setting, and Participants: A prospective multicenter observational cohort study was carried out over 2 time periods (September 15, 2021, to December 20, 2021 [delta wave], and January 20, 2022, to November 11, 2022 [omicron wave]) predominated by SARS-CoV-2 delta and omicron variants, respectively. Overall, 73 608 patients with cancer (23 217 active treatment, 50 391 cancer survivors) and 621 475 controls matched by age, sex, race and ethnicity, and socioeconomic status were included., Exposure: Vaccine doses received, from zero to 4 doses, and time elapsed since last vaccine dose., Outcomes: Competing-risk regression analyses were employed to account for competing risks of death in patients with cancer. Main outcomes were incidence rate ratios (IRRs) of COVID-19 infection, hospitalization, and severe disease (defined as requirement for supplemental oxygen, intensive care, or death). The IRRs stratified by time from last vaccine dose served as indicators of waning of vaccine effectiveness over time., Results: The mean (SD) age of actively treated patients with cancer, cancer survivors, and controls were 62.7 (14.7), 62.9 (12.6), and 61.8 (14.7) years, respectively. Of 73 608 patients with cancer, 27 170 (36.9%) were men; 60 100 (81.6%) were Chinese, 7432 (10.1%) Malay, 4597 (6.2%) Indian, and 1479 (2.0%) were of other races and ethnicities. The IRRs for the 3-dose and 4-dose vs the 2-dose group (reference) for COVID-19 hospitalization and severe disease were significantly lower during both the delta and omicron waves in cancer and control populations. The IRRs for severe disease in the 3-dose group for active treatment, cancer survivors, and controls were 0.14, 0.13, and 0.07 during the delta wave and 0.29, 0.19, and 0.21 during omicron wave, respectively. The IRRs for severe disease in the 4-dose group during the omicron wave were even lower at 0.13, 0.10 and 0.10, respectively. No waning of vaccine effectiveness against hospitalization and severe disease was seen beyond 5 months after a third dose, nor up to 5 months (the end of this study's follow-up) after a fourth dose., Conclusion: This cohort study provides evidence of the clinical effectiveness of mRNA-based vaccines against COVID-19 in patients with cancer. Longevity of immunity in preventing severe COVID-19 outcomes in actively treated patients with cancer, cancer survivors, and matched controls was observed at least 5 months after the third or fourth dose.

The COVID -19 pandemic impacted acute myocardial infarction (AMI) attendances, ST-elevation myocardial infarction (STEMI) treatments, and outcomes. We collated data from majority of primary percutaneous coronary intervention (PPCI)-capable public healthcare centres in Singapore to understand the initial impact COVID-19 had on essential time-critical emergency services. We present data comparisons from 'Before Disease Outbreak Response System Condition (DORSCON) Orange', 'DORSCON Orange to start of circuit breaker (CB)', and during the first month of 'CB'. We collected aggregate numbers of weekly elective PCI from four centres and AMI admissions, PPCI, and in-hospital mortality from five centres. Exact door-to-balloon (DTB) times were recorded for one centre; another two reported proportions of DTB times exceeding targets. Median weekly elective PCI cases significantly decreased from 'Before DORSCON Orange' to 'DORSCON Orange to start of CB' (34 vs 22.5, P = 0.013). Median weekly STEMI admissions and PPCI did not change significantly. In contrast, the median weekly non-STEMI (NSTEMI) admissions decreased significantly from 'Before DORSCON Orange' to 'DORSCON Orange to start of CB' (59 vs 48, P = 0.005) and were sustained during CB (39 cases). Exact DTB times reported by one centre showed no significant change in the median. Out of three centres, two reported significant increases in the proportion that exceeded DTB targets. In-hospital mortality rates remained static. In Singapore, STEMI and PPCI rates remained stable, while NSTEMI rates decreased during DORSCON Orange and CB. The severe acute respiratory syndrome (SARS) experience may have helped prepare us to maintain essential services such as PPCI during periods of acute healthcare resource strain. However, data must be monitored and increased pandemic preparedness measures must be explored to ensure that AMI care is not adversely affected by continued COVID fluctuations and future pandemics., (© The Author(s) 2023. Published by Oxford University Press on behalf of International Society for Quality in Health Care. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Coronavirus disease 2019 (COVID-19) can cause damage to multiple organ, not only to the lungs, but also to the kidneys. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can cause acute and chronic kidney disease through direct viral infection, indirect injury, and vaccination-related injury. Like lung injury, kidney injury is also an important aspect affecting the severity and prognosis of SARS-CoV-2. This article summarizes the pathogenesis, pathological manifestations, and clinical features of SARS-CoV-2 direct or indirect renal injury. Including direct injury, indirect injury, special comorbidities (receiving kidney transplantation and chronic kidney disease), and vaccine-related renal injury, and exploring the possible therapeutic effect of anti-SARS-CoV-2 therapy on renal injury. The purpose is to provide reference for understanding COVID-19-related renal injury, guiding clinical and pathological diagnosis and treatment, and evaluating prognosis., (© 2022 Wiley Periodicals LLC.)

Competing Interests: None

Background: Awake prone positioning has been broadly utilised for non-intubated patients with COVID-19-related acute hypoxaemic respiratory failure, but the results from published randomised controlled trials (RCTs) in the past year are contradictory. We aimed to systematically synthesise the outcomes associated with awake prone positioning, and evaluate these outcomes in relevant subpopulations., Methods: In this systematic review and meta-analysis, two independent groups of researchers searched MEDLINE, Embase, PubMed, Web of Science, Scopus, MedRxiv, BioRxiv, and ClinicalTrials.gov for RCTs and observational studies (with a control group) of awake prone positioning in patients with COVID-19-related acute hypoxaemic respiratory failure published in English from Jan 1, 2020, to Nov 8, 2021. We excluded trials that included patients intubated before or at enrolment, paediatric patients (ie, younger than 18 years), or trials that did not include the supine position in the control group. The same two independent groups screened studies, extracted the summary data from published reports, and assessed the risk of bias. We used a random-effects meta-analysis to pool individual studies. We used the Grading of Recommendations Assessment, Development, and Evaluation approach to assess the certainty and quality of the evidence. The primary outcome was the reported cumulative intubation risk across RCTs, and effect estimates were calculated as risk ratios (RR;95% CI). The analysis was primarily conducted on RCTs, and observational studies were used for sensitivity analyses. No serious adverse events associated with awake prone positioning were reported. The study protocol was prospectively registered with PROSPERO, CRD42021271285., Findings: A total of 1243 studies were identified, we assessed 138 full-text articles and received the aggregated results of three unpublished RCTs; therefore, after exclusions, 29 studies were included in the study. Ten were RCTs (1985 patients) and 19 were observational studies (2669 patients). In ten RCTs, awake prone positioning compared with the supine position significantly reduced the need for intubation in the overall population (RR 0·84 [95% CI 0·72-0·97]). A reduced need for intubation was shown among patients who received advanced respiratory support (ie, high-flow nasal cannula or non-invasive ventilation) at enrolment (RR 0·83 [0·71-0·97]) and in intensive care unit (ICU) settings (RR 0·83 [0·71-0·97]) but not in patients receiving conventional oxygen therapy (RR 0·87 [0·45-1·69]) or in non-ICU settings (RR 0·88 [0·44-1·76]). No obvious risk of bias and publication bias was found among the included RCTs for the primary outcome., Interpretation: In patients with COVID-19-related acute hypoxaemic respiratory failure, awake prone positioning reduced the need for intubation, particularly among those requiring advanced respiratory support and those in ICU settings. Awake prone positioning should be used in patients who have acute hypoxaemic respiratory failure due to COVID-19 and require advanced respiratory support or are treated in the ICU., Funding: OpenAI, Rice Foundation, National Institute for Health Research, and Oxford Biomedical Research Centre., Competing Interests: Declaration of interests SE discloses consultancy fees from Aerogen, research support from Aerogen and Fisher & Paykel Healthcare, and travel reimbursements from Aerogen and Fisher & Paykel Healthcare. JL discloses research funding from Fisher & Paykel Healthcare, Aerogen, and Rice Foundation, and speaker fees from American Association for Respiratory Care, Aerogen, Heyer, and Fisher & Paykel Healthcare. IP discloses a research grant and speaker fees from Fisher & Paykel Healthcare. YP discloses research support from Fisher & Paykel Healthcare. OR discloses a research grant from Hamilton Medical and speaker fees from Hamilton Medical, Ambu, Fisher & Paykel and Aerogen, and non-financial research support from Timpel and Masimo. DV discloses research funding from Teleflex Medical and Rice Foundation, and speaker fees from Theravance Biopharma. MT discloses consulting fees from Fisher & Paykel Healthcare. JRM discloses research support from Fisher & Paykel Healthcare, and speaker fees from Fisher & Paykel Healthcare, Gilead, Dextro and Linet. JGL discloses consulting fees from Baxter Healthcare and GlaxoSmithKline. KM is the primary investigator for the industry funded trial NCT03808922. MF is a consultant for a start-up company (ProofDx) developing a CRISPR based diagnostic test for COVID-19. All other authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The SARS-CoV-2 pandemic is rapidly evolving and remains a major health challenge worldwide. With an increase in pregnant women with COVID-19 infection, we recognized an urgent need to set up a multidisciplinary taskforce to provide safe and holistic care for this group of women. In this review of practice in a tertiary hospital in Singapore, we discuss the key considerations in setting up an isolation maternity unit and our strategies for peripartum and postpartum care. Through teleconsultation, we involve these women and their families in the discussion of timing and mode of birth, disposition of babies after birth and safety of breastfeeding to enable them to make informed decisions and individualize their care., (© 2022. The Author(s).)

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., (© 2022. The Author(s).)

Background: Coronavirus disease 2019 (COVID-19) has spread globally, and many patients with severe cases have received oxygen therapy through a high-flow nasal cannula (HFNC)., Objectives: We assessed the efficacy of HFNC for treating patients with COVID-19 and risk factors for HFNC failure., Methods: We searched PubMed, Embase, and the Cochrane Central Register of randomized controlled trials (RCTs) and observational studies of HFNC in patients with COVID-19 published in English from January 1st, 2020 to August 15th, 2021. The primary aim was to assess intubation, mortality, and failure rates in COVID-19 patients supported by HFNC. Secondary aims were to compare HFNC success and failure groups and to describe the risk factors for HFNC failure., Results: A total of 25 studies fulfilled selection criteria and included 2851 patients. The intubation, mortality, and failure rates were 0.44 (95% confidence interval (CI): 0.38-0.51, I 2  = 84%), 0.23 (95% CI: 0.19-0.29, I 2  = 88%), and 0.47 (95% CI: 0.42-0.51, I 2  = 56%), respectively. Compared to the success group, age, body mass index (BMI), Sequential Organ Failure Assessment (SOFA) score, Acute Physiology and Chronic Health Evaluation (APACHE) II score, D-dimer, lactate, heart rate, and respiratory rate were higher and PaO 2 , PaO 2 /FiO 2 , ROX index (the ratio of SpO 2 /FiO 2 to respiratory rate), ROX index after the initiation of HFNC, and duration of HFNC were lower in the failure group (all Ps < 0.05). There were also more smokers and more comorbidities in the failure group (all Ps < 0.05). Pooled odds ratios (ORs) revealed that older age (OR: 1.04, 95% CI: 1.01-1.07, P = 0.02, I 2  = 88%), a higher white blood cell (WBC) count (OR: 1.06, 95% CI: 1.01-1.12, P = 0.02, I 2  = 0%), a higher heart rate (OR: 1.42, 95% CI: 1.15-1.76, P < 0.01, I 2  = 0%), and a lower ROX index(OR: 0.61, 95% CI: 0.39-0.95, P = 0.03, I 2  = 93%) after the initiation of HFNC were all significant risk factors for HFNC failure., Conclusions: HFNC is an effective way of providing respiratory support in the treatment of COVID-19 patients. Older age, a higher WBC count, a higher heart rate, and a lower ROX index after the initiation of HFNC are associated with an increased risk of HFNC failure.

Background: High-flow nasal cannula (HFNC) and noninvasive ventilation (NIV) are important treatment approaches for acute hypoxemic respiratory failure (AHRF) in coronavirus disease 2019 (COVID-19) patients. However, the differential impact of HFNC versus NIV on clinical outcomes of COVID-19 is uncertain., Objectives: We assessed the effects of HFNC versus NIV (interface or mode) on clinical outcomes of COVID-19., Methods: We searched PubMed, EMBASE, Web of Science, Scopus, MedRxiv, and BioRxiv for randomized controlled trials (RCTs) and observational studies (with a control group) of HFNC and NIV in patients with COVID-19-related AHRF published in English before February 2022. The primary outcome of interest was the mortality rate, and the secondary outcomes were intubation rate, PaO 2 /FiO 2 , intensive care unit (ICU) length of stay (LOS), hospital LOS, and days free from invasive mechanical ventilation [ventilator-free day (VFD)]., Results: In all, 23 studies fulfilled the selection criteria, and 5354 patients were included. The mortality rate was higher in the NIV group than the HFNC group [odds ratio (OR) = 0.66, 95% confidence interval (CI): 0.51-0.84, p  = 0.0008, I 2  = 60%]; however, in this subgroup, no significant difference in mortality was observed in the NIV-helmet group (OR = 1.21, 95% CI: 0.63-2.32, p  = 0.57, I 2  = 0%) or NIV-continuous positive airway pressure (CPAP) group (OR = 0.77, 95% CI: 0.51-1.17, p  = 0.23, I 2  = 65%) relative to the HFNC group. There were no differences in intubation rate, PaO 2 /FiO 2 , ICU LOS, hospital LOS, or days free from invasive mechanical ventilation (VFD) between the HFNC and NIV groups., Conclusion: Although mortality was lower with HFNC than NIV, there was no difference in mortality between HFNC and NIV on a subgroup of helmet or CPAP group. Future large sample RCTs are necessary to prove our findings., Registration: This systematic review and meta-analysis protocol was prospectively registered with PROSPERO (no. CRD42022321997).

Purpose: The COVID-19 pandemic has led to the cancellation or deferment of many elective cancer surgeries. We performed a systematic review on the oncological effects of delayed surgery for patients with localised or metastatic renal cell carcinoma (RCC) in the targeted therapy (TT) era., Method: The protocol of this review is registered on PROSPERO(CRD42020190882). A comprehensive literature search was performed on Medline, Embase and Cochrane CENTRAL using MeSH terms and keywords for randomised controlled trials and observational studies on the topic. Risks of biases were assessed using the Cochrane RoB tool and the Newcastle-Ottawa Scale. For localised RCC, immediate surgery [including partial nephrectomy (PN) and radical nephrectomy (RN)] and delayed surgery [including active surveillance (AS) and delayed intervention (DI)] were compared. For metastatic RCC, upfront versus deferred cytoreductive nephrectomy (CN) were compared., Results: Eleven studies were included for quantitative analysis. Delayed surgery was significantly associated with worse cancer-specific survival (HR 1.67, 95% CI 1.23-2.27, p < 0.01) in T1a RCC, but no significant difference was noted for overall survival. For localised ≥ T1b RCC, there were insufficient data for meta-analysis and the results from the individual reports were contradictory. For metastatic RCC, upfront TT followed by deferred CN was associated with better overall survival when compared to upfront CN followed by deferred TT (HR 0.61, 95% CI 0.43-0.86, p < 0.001)., Conclusion: Noting potential selection bias, there is insufficient evidence to support the notion that delayed surgery is safe in localised RCC. For metastatic RCC, upfront TT followed by deferred CN should be considered., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: The COVID-19 pandemic has affected the world for more than a year, with multiple waves of infections resulting in morbidity, mortality and disruption to the economy and society. Response measures employed to control it have generally been effective but are unlikely to be sustainable over the long term., Methods: We examined the evidence for a vaccine-driven COVID-19 exit strategy including academic papers, governmental reports and epidemiological data, and discuss the shift from the current pandemic footing to an endemic approach similar to influenza and other respiratory infectious diseases., Results: A desired endemic state is characterised by a baseline prevalence of infections with a generally mild disease profile that can be sustainably managed by the healthcare system, together with the resumption of near normalcy in human activities. Such an endemic state is attainable for COVID-19 given the promising data around vaccine efficacy, although uncertainty remains around vaccine immunity escape in emergent variants of concern. Maintenance of non-pharmaceutical interventions remains crucial until high vaccination coverage is attained to avoid runaway outbreaks. It may also be worthwhile to de-escalate measures in phases, before standing down most measures for an endemic state. If a variant that substantially evades immunity emerges, it will need to be managed akin to a new disease threat, with pandemic preparedness and response plans., Conclusion: An endemic state for COVID-19, characterised by sustainable disease control measures, is likely attainable through vaccination.

Background and Aims: The application of prone positioning with acute hypoxemic respiratory failure (AHRF) or acute respiratory distress syndrome (ARDS) in non-intubation patients is increasing gradually, applying prone positioning for more high-flow nasal oxygen therapy (HFNC) and non-invasive ventilation (NIV) patients. This meta-analysis evaluates the efficacy and tolerance of prone positioning combined with non-invasive respiratory support in patients with AHRF or ARDS., Methods: We searched randomized controlled trials (RCTs) (prospective or retrospective cohort studies, RCTs and case series) published in PubMed , EMBASE and the Cochrane Central Register of Controlled Trials from 1 January 2000 to 1 July 2020. We included studies that compared prone and supine positioning with non-invasive respiratory support in awake patients with AHRF or ARDS. The meta-analyses used random effects models. The methodological quality of the RCTs was evaluated using the Newcastle-Ottawa quality assessment scale., Results: A total of 16 studies fulfilled selection criteria and included 243 patients. The aggregated intubation rate and mortality rate were 33% [95% confidence interval (CI): 0.26-0.42, I 2  = 25%], 4% (95% CI: 0.01-0.07, I 2  = 0%), respectively, and the intolerance rate was 7% (95% CI: 0.01-0.12, I 2  = 5%). Prone positioning increased PaO 2 /FiO 2 [mean difference (MD) = 47.89, 95% CI: 28.12-67.66; p  < 0.00001, I 2  = 67%] and SpO 2 (MD = 4.58, 95% CI: 1.35-7.80, p  = 0.005, I 2 were significantly improved in COVID-19 patients and non-COVID-19 patients.p  = 0.005, I 2  = 85%). Subgroup analyses demonstrated that the intubation rate of shorter duration prone (⩽5 h/day) and longer duration prone (>5 h/day) were 34% and 21%, respectively; and the mortality rate of shorter duration prone (⩽5 h/day) and longer duration prone (>5 h/day) were 6% and 0%, respectively. PaO 2 /FiO 2 and SpO 2 were significantly improved in COVID-19 patients and non-COVID-19 patients., Conclusion: Prone positioning could improve the oxygenation and reduce respiratory rate in both COVID-19 patients and non-COVID-19 patients with non-intubated AHRF or ARDS. The reviews of this paper are available via the supplemental material section.

In 2019, a novel coronavirus (SARS-CoV-2) was found to cause a highly contagious disease characterized by pneumonia. The disease (COVID-19) quickly spread around the globe, escalating to a global pandemic. In this review, we discuss the virological, immunological, and imaging approaches harnessed for COVID-19 diagnosis and research. COVID-19 shares many clinical characteristics with other respiratory illnesses.Accurate and early detection of the infection is pivotal to controlling the outbreak, as this enables case identification, isolation, and contact tracing. We summarize the available literature on current laboratory and point-of-care diagnostics, highlight their strengths and limitations, and describe the emerging diagnostic approaches on the horizon.We also discuss the various research techniques that are being used to evaluate host immunity in laboratory-confirmed patients. Additionally, pathological imaging of tissue samples from affected patients has a critical role in guiding investigations on this disease. Conventional techniques, such as immunohistochemistry and immunofluorescence, have been frequently used to characterize the immune microenvironment in COVID-19. We also outline the emerging imaging techniques, such as the RNAscope, which might also aid in our understanding of the significance of COVID-19-specific biomarkers, such as the angiotensin-converting enzyme 2 (ACE2) cellular receptor.Overall, great progress has been made in COVID-19 research in a short period. Extensive, global collation of our current knowledge of SARS-CoV-2 will provide insights into novel treatment modalities, such as monoclonal antibodies, and support the development of a SARS-CoV-2 vaccine.

Autoregressive models in time series are useful in various areas. In this article, we propose a skew-t autoregressive model. We estimate its parameters using the expectation-maximization (EM) method and develop the influence methodology based on local perturbations for its validation. We obtain the normal curvatures for four perturbation strategies to identify influential observations, and then to assess their performance through Monte Carlo simulations. An example of financial data analysis is presented to study daily log-returns for Brent crude futures and investigate possible impact by the COVID-19 pandemic. [ABSTRACT FROM AUTHOR]

Digital rectal examination (DRE) is routinely performed as part of a urology clinical assessment in patients with a clinical suspicion of prostate cancer. An abnormal DRE or a raised prostate specific antigen (PSA) level are part of the criteria for primary care referral to secondary care due to a suspicion of prostate cancer. The current Coronavirus-19 (COVID-19) pandemic has resulted in the rapid adoption of virtual consultations in the form of telephone or video consultations making clinical examination difficult. In the case of prostate cancer diagnostic pathways, often clinicians now rely on PSA measurements and MRI, where radiological services are available, without the requirement for a DRE. We discuss the limited role DRE has in the modern prostate cancer diagnostic pathway due to the widespread adoption of MRI particularly in the COVID-19 era. [ABSTRACT FROM AUTHOR]

Simple Summary: We reviewed the evidence available for postponing or delaying cancer surgery for localised prostate cancer. Watchful waiting is an acceptable option in low-risk patients. Evidence is uncertain in postponing surgery, but conservative estimates suggest delays of over 5 months, 4 months, and 30 days for low-, intermediate-, and high-risk patients, respectively, can lead to worse survival outcomes. Neoadjuvant therapy can shrink the tumours prior to surgery and can be a useful adjunct in delaying surgery for, at the most, 3 months. External factors, such as the coronavirus disease 2019 (COVID-19), can lead to cancellations and backlogs of cancer surgeries. The effects of these delays are unclear. This study summarised the evidence surrounding expectant management, delay radical prostatectomy (RP), and neoadjuvant hormone therapy (NHT) compared to immediate RP. MEDLINE and EMBASE was searched for randomised controlled trials (RCTs) and non-randomised controlled studies pertaining to the review question. Risks of biases (RoB) were evaluated using the RoB 2.0 tool and the Newcastle–Ottawa Scale. A total of 57 studies were included. Meta-analysis of four RCTs found overall survival and cancer-specific survival were significantly worsened amongst intermediate-risk patients undergoing active monitoring, observation, or watchful waiting but not in low- and high-risk patients. Evidence from 33 observational studies comparing delayed RP and immediate RP is contradictory. However, conservative estimates of delays over 5 months, 4 months, and 30 days for low-risk, intermediate-risk, and high-risk patients, respectively, have been associated with significantly worse pathological and oncological outcomes in individual studies. In 11 RCTs, a 3-month course of NHT has been shown to improve pathological outcomes in most patients, but its effect on oncological outcomes is apparently limited. [ABSTRACT FROM AUTHOR]

Restrictions on human activities remarkably reduced emissions of air pollutants in China during the COVID-19 lockdown periods. However, distinct responses of O3 concentrations were observed across China. In the Beijing–Tianjin–Hebei (BTH) and Yangtze River Delta (YRD) regions, O3 concentrations were enhanced by 90.21 and 71.79% from pre-lockdown to lockdown periods in 2020, significantly greater than the equivalent concentrations for the same periods over 2015–2019 (69.99 and 43.62%, p < 0.001). In contrast, a decline was detected (−1.1%) in the Pearl River Delta (PRD) region. To better understand the underlying causes for these inconsistent responses across China, we adopted the least absolute shrinkage and selection operator (Lasso) and ordinary linear squares (OLS) methods in this study. Statistical analysis indicated that a sharp decline in nitrogen dioxide (NO2) was the major driver of enhanced O3 in the BTH region as it is a NOx-saturated region. In the YRD region, season-shift induced changes in the temperature/shortwave radiative flux, while lockdown induced declines in NO2, attributable to the rise in O3. In the PRD region, the slight drop in O3 is attributed to the decreased intensity of radiation. The distinct regimes of the O3 response to the COVID-19 lockdown in China offer important insights into different O3 control strategies across China. [ABSTRACT FROM AUTHOR]

• An semi-supervised learning method is proposed to improve diagnostic efficiency of covid-19 CT images. • Based on MixMatch, new data enhancement methods and training methods are introduced to reduce the risk of model over fitting. • Data enhancement method with MixMatch is introduced to reduce model over fitting. • CNN with attention mechanism is constructed to learn features from images more effectively. COVID-19 has spread rapidly all over the world and has infected more than 200 countries and regions. Early screening of suspected infected patients is essential for preventing and combating COVID-19. Computed Tomography (CT) is a fast and efficient tool which can quickly provide chest scan results. To reduce the burden on doctors of reading CTs, in this article, a high precision diagnosis algorithm of COVID-19 from chest CTs is designed for intelligent diagnosis. A semi-supervised learning approach is developed to solve the problem when only small amount of labelled data is available. While following the MixMatch rules to conduct sophisticated data augmentation, we introduce a model training technique to reduce the risk of model over-fitting. At the same time, a new data enhancement method is proposed to modify the regularization term in MixMatch. To further enhance the generalization of the model, a convolutional neural network based on an attention mechanism is then developed that enables to extract multi-scale features on CT scans. The proposed algorithm is evaluated on an independent CT dataset of the chest from COVID-19 and achieves the area under the receiver operating characteristic curve (AUC) value of 0.932, accuracy of 90.1%, sensitivity of 91.4%, specificity of 88.9%, and F1-score of 89.9%. The results show that the proposed algorithm can accurately diagnose whether a chest CT belongs to a positive or negative indication of COVID-19, and can help doctors to diagnose rapidly in the early stages of a COVID-19 outbreak. [ABSTRACT FROM AUTHOR]

• We estimated the time to the most recent common ancestor (TMRCA) and evolutionary rate of SARS-CoV-2 to be 12 November 2019 (95% BCI: 11 October 2019 and 09 December 2019) and 9.90 × 10-4 substitutions per site per year (95% BCI: 6.29 × 10-4–1.35 × 10-3), respectively. • Our results emphasize the importance of using phylogenetic and phylodynamic analyses to provide insights into the roles of various interventions to limit the spread of SARS-CoV-2 in China and beyond. • Understanding epidemic dynamics of SARS-CoV-2 in real time is increasingly important for guiding prevention efforts. To investigate the evolutionary and epidemiological dynamics of the current COVID-19 outbreak, a total of 112 genomes of SARS-CoV-2 strains sampled from China and 12 other countries with sampling dates between 24 December 2019 and 9 February 2020 were analyzed. We performed phylogenetic, split network, likelihood-mapping, model comparison, and phylodynamic analyses of the genomes. Based on Bayesian time-scaled phylogenetic analysis with the best-fitting combination models, we estimated the time to the most recent common ancestor (TMRCA) and evolutionary rate of SARS-CoV-2 to be 12 November 2019 (95 % BCI: 11 October 2019 and 09 December 2019) and 9.90 × 10−4 substitutions per site per year (95 % BCI: 6.29 × 10−4–1.35 × 10−3), respectively. Notably, the very low R e estimates of SARS-CoV-2 during the recent sampling period may be the result of the successful control of the pandemic in China due to extreme societal lockdown efforts. Our results emphasize the importance of using phylodynamic analyses to provide insights into the roles of various interventions to limit the spread of SARS-CoV-2 in China and beyond. [ABSTRACT FROM AUTHOR]