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Background: To investigate the efficacy of different doses of corticosteroids in treating severe coronavirus disease 2019 (COVID-19) pneumonia. Methods: Between May 01, 2023, and June 20, 2023, 48 patients with severe COVID-19 pneumonia were treated at the Department of Respiratory and Critical Care Medicine of Jinan Fourth People's Hospital. The observation group (21 patients) received standard care and high-dose corticosteroids, (high-dose group). The control group (27 patients) received standard care and low-dose corticosteroids (low-dose group). We collected baseline data and recorded inflammatory marker levels after 3 days of treatment, body temperature recovery time, length of stay, and 28-day all-cause mortality. The results of outpatient follow-up were recorded after 1 month. Results: There were no significant differences in 28-day mortality and length of stay. The number of days it took for body temperature to return to normal in the high-dose group was less than in the low-dose group. The high-dose group had significantly more reduced inflammatory factors (C-reactive protein (CRP), interleukin-6 (IL-6). A total of 20 discharged patients were given 8–16 mg of methylprednisolone, depending on chest computed tomography (CT) and clinical symptoms after 1 month; in all discharged patients using oral corticosteroids, CT features improved. Conclusion: High-dose corticosteroids had a significantly positive effect on the reduction of inflammatory factors and shortening body temperature recovery time. In the treatment of severe COVID-19 pneumonia, early administration of high-dose, short-course corticosteroids should be implemented. Highlights: The highlights of the paper are: 1. High-dose corticosteroid can shorten the recovery time of body temperature. 2. High-dose corticosteroid can better reduce inflammatory factors (CRP IL-6). 3. Oral hormones in discharged patients with severe COVID-19 pneumonia are beneficial. 4. Initial dosage and course of corticosteroid might be varied case by case. [ABSTRACT FROM AUTHOR]

Background: The COVID-19 pandemic has presented unique challenges for rapidly designing, initiating, and delivering therapeutic clinical trials. PRINCIPLE (Platform Randomised Trial of Treatments in the Community for Epidemic and Pandemic Illnesses) is the UK national platform investigating repurposed therapies for COVID-19 treatment of older people in the community at high risk of complications. Standard methods of patient recruitment were failing to meet the required pace and scale of enrolment. This paper describes the development and appraisal of a near real-time, data-driven, ethical approach for enhancing recruitment in community care by contacting people with a recent COVID-19 positive test result from the central NHS Test and Trace service within approximately 24-48 h of their test result.Methods: A multi-disciplinary team was formed to solve the technical, ethical, public perception, logistical and information governance issues required to provide a near-real time (approximately within 24-48 h of receiving a positive test) feed of potential trial participants from test result data to the research team. PRINCIPLE was also given unique access to the Summary Care Record (SCR) to ensure safe prescribing, and to enable the trial team to quickly and safely bring consented patients into the trial. A survey of the public was used to understand public perceptions of the use of test data for this proposed methodology.Results: Prior to establishing the data service, PRINCIPLE registered on average 87 participants per week. This increased by up to 87 additional people registered per week from the test data, contributing to an increase from 1013 recruits to PRINCIPLE at the start of October 2020 to 2802 recruits by 20 December 2020. Whilst procedural caveats were identified by the public consultation, out of 2639 people contacted by PRINCIPLE following a positive test result, no one raised a concern about being approached.Conclusions: This paper describes a novel approach to using near-real time NHS operational data to recruit community-based patients within a few days of presentation with acute illness. This approach increased recruitment and reduced time between positive test and randomisation, allowing more rapid evaluation of treatments and increased safety for participants. End-to-end public and patient involvement in the design of the approach provided evidence to inform information governance decisions.Trial Registration: PRINCIPLE is funded by UK Research and Innovation and the Department of Health and Social Care through the National Institute for Health Research. EudraCT number: 2020-001209-22 . 26/03/2020 ISRCTN registry: ISRCTN86534580 . 20/03/2020 REC number: 20/SC/058 IRAS number: 281958. [ABSTRACT FROM AUTHOR]

Background: Numerous clinical trials have been initiated to find effective treatments for COVID-19. These trials have often been initiated in regions where the pandemic has already peaked. Consequently, achieving full enrollment in a single trial might require additional COVID-19 surges in the same location over several years. This has inspired us to pool individual patient data (IPD) from ongoing, paused, prematurely-terminated, or completed randomized controlled trials (RCTs) in real-time, to find an effective treatment as quickly as possible in light of the pandemic crisis. However, pooling across trials introduces enormous uncertainties in study design (e.g., the number of RCTs and sample sizes might be unknown in advance). We sought to develop a versatile treatment efficacy assessment model that accounts for these uncertainties while allowing for continuous monitoring throughout the study using Bayesian monitoring techniques. Methods: We provide a detailed look at the challenges and solutions for model development, describing the process that used extensive simulations to enable us to finalize the analysis plan. This includes establishing prior distribution assumptions, assessing and improving model convergence under different study composition scenarios, and assessing whether we can extend the model to accommodate multi-site RCTs and evaluate heterogeneous treatment effects. In addition, we recognized that we would need to assess our model for goodness-of-fit, so we explored an approach that used posterior predictive checking. Lastly, given the urgency of the research in the context of evolving pandemic, we were committed to frequent monitoring of the data to assess efficacy, and we set Bayesian monitoring rules calibrated for type 1 error rate and power. Results: The primary outcome is an 11-point ordinal scale. We present the operating characteristics of the proposed cumulative proportional odds model for estimating treatment effectiveness. The model can estimate the treatment's effect under enormous uncertainties in study design. We investigate to what degree the proportional odds assumption has to be violated to render the model inaccurate. We demonstrate the flexibility of a Bayesian monitoring approach by performing frequent interim analyses without increasing the probability of erroneous conclusions. Conclusion: This paper describes a translatable framework using simulation to support the design of prospective IPD meta-analyses. [ABSTRACT FROM AUTHOR]

Background: A global pandemic has been declared for coronavirus disease 2019 (COVID-19), which has serious impacts on human health and healthcare systems in the affected areas, including Vietnam. None of the previous studies have a framework to provide summary statistics of the virus variants and assess the severity associated with virus proteins and host cells in COVID-19 patients in Vietnam.Method: In this paper, we comprehensively investigated SARS-CoV-2 variants and immune responses in COVID-19 patients. We provided summary statistics of target sequences of SARS-CoV-2 in Vietnam and other countries for data scientists to use in downstream analysis for therapeutic targets. For host cells, we proposed a predictive model of the severity of COVID-19 based on public datasets of hospitalization status in Vietnam, incorporating a polygenic risk score. This score uses immunogenic SNP biomarkers as indicators of COVID-19 severity.Result: We identified that the Delta variant of SARS-CoV-2 is most prevalent in southern areas of Vietnam and it is different from other areas in the world using various data sources. Our predictive models of COVID-19 severity had high accuracy (Random Forest AUC = 0.81, Elastic Net AUC = 0.7, and SVM AUC = 0.69) and showed that the use of polygenic risk scores increased the models' predictive capabilities.Conclusion: We provided a comprehensive analysis for COVID-19 severity in Vietnam. This investigation is not only helpful for COVID-19 treatment in therapeutic target studies, but also could influence further research on the disease progression and personalized clinical outcomes. [ABSTRACT FROM AUTHOR]

Background: The COVID-19 pandemic has affected the world extraordinarily. This disease has a potential to cause a significantly severe course of disease leading to respiratory complications, multiple organ failure and possibly death. In the fight against this pandemic-causing disease, medical professionals around the world are searching for pharmacological agents that could treat and prevent disease progression and mortality. To speed the search of promising treatment options, already existing pharmacological agents are repurposed for the potential treatment of COVID-19 and tested in clinical trials. The aim of this literature review is to investigate the efficacy and safety of repurposed pharmacological agents for the treatment of COVID-19 at different pathophysiologic stages of the disease. For this literature review, online-databases PubMed and Google Scholar were utilised. Keywords "COVID-19", "SARS-CoV-2", "pathogenesis", "drug targets", "pharmacological treatment", "cytokine storm", "coagulopathy" and individual drug names were used. Scientific articles, including reviews, clinical trials, and observational cohorts, were collected and analysed. Furthermore, these articles were examined for references to find more clinical trials testing for the potential treatment of COVID-19. In total, 97 references were used to conduct this research paper.Results: The most beneficial pharmacological agent for the treatment of COVID-19 are corticosteroids, especially dexamethasone, for the treatment of mechanically ventilated COVID-19 patients. Other promising agents are remdesivir for the treatment of patients with COVID-19 pneumonia requiring minimal supplemental oxygen therapy, and IL-6 receptor antagonist monoclonal antibodies in severe COVID-19. Lopinavir/ritonavir, as well as chloroquine or hydroxychloroquine with or without azithromycin demonstrate the least efficacy in the treatment of COVID-19. The clinical benefits of the treatment of a COVID-19-specific coagulopathy with increased dosing of anticoagulation need further research and confirmation of randomised controlled trials.Conclusion: The search for pharmacological treatment of COVID-19 has elicited great controversy. Whereas drugs like chloroquine, hydroxychloroquine, and lopinavir/ritonavir have not shown proven benefit, the agents remdesivir and dexamethasone are recommended for clinical use for the treatment of COVID-19. Further randomised trials for other pharmacological treatment strategies are awaited. [ABSTRACT FROM AUTHOR]

Novel coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus-2. The virus causes an exaggerated immune response, resulting in a cytokine storm and acute respiratory distress syndrome, the leading cause of COVID-19-related mortality and morbidity. So far, no therapies have succeeded in circumventing the exacerbated immune response or cytokine storm associated with COVID-19. Mesenchymal stem cells (MSCs), through their immunomodulatory and regenerative activities, mostly mediated by their paracrine effect and extracellular vesicle production, have therapeutic potential in many autoimmune, inflammatory, and degenerative diseases. In this paper, we review clinical studies on the use of MSCs for COVID-19 treatment, including the salutary effects of MSCs on the pathophysiology of COVID-19 and the immunomodulation of the cytokine storm. Ongoing clinical trial designs, cell sources, dose and administration, and populations are summarized, and the paracrine mode of benefit is discussed. We also offer suggestions for optimizing MSC-based therapies, including genetic engineering, strategies for cell surface modification, nanotechnology applications, and combination therapies. [ABSTRACT FROM AUTHOR]

Background: Oxygenation serves as a cornerstone in the treatment of COVID-19, and several methods have been extensively studied so far. Herein, we aimed to systematically review the studies discussing hyperbaric oxygen therapy (HBOT) to examine its reported efficacy and adverse events in patients with COVID-19. Methods: We systematically searched and retrieved the relevant articles using keywords on the online databases, including PubMed, Scopus, Embase, Web of Science, and Cochrane databases up to April 11th, 2021. The retrieved records underwent a two-step title/abstract and full-text screening process, and the eligible papers were identified. National Institutes of health (NIH) quality assessment tool was used for this study. This study was registered in the International Prospective Register of Systematic Reviews (PROSPERO) with ID CRD42021269821. Results: Eight articles from three countries were included. All the included studies had good and fair quality scores, with no poor studies included in this systematic review (Good: n = 5, Fair: n = 3). Studies were divided into clinical trials and case reports/series. Most of the studies used HBOT less than 1.5–2 absolute atmospheres (ATA) for 90 min sessions and thereafter sessions were decreased to 60 min. Trials demonstrated most of the patients recovered after receiving HBOT, and blood oxygen saturation increased after several sessions of HBOT. Conclusion: Overall, HBOT seems to be a safe and effective oxygenation method in patients with COVID-19. However, there is limited knowledge and evidence regarding the effects and mechanism of HBOT in COVID-19 treatment, and further evaluations require extensive well-designed studies. [ABSTRACT FROM AUTHOR]

Background: Currently, there is an urgent need for efficient tools to assess the diagnosis of COVID-19 patients. In this paper, we present feasible solutions for detecting and labeling infected tissues on CT lung images of such patients. Two structurally-different deep learning techniques, SegNet and U-NET, are investigated for semantically segmenting infected tissue regions in CT lung images. Methods: We propose to use two known deep learning networks, SegNet and U-NET, for image tissue classification. SegNet is characterized as a scene segmentation network and U-NET as a medical segmentation tool. Both networks were exploited as binary segmentors to discriminate between infected and healthy lung tissue, also as multi-class segmentors to learn the infection type on the lung. Each network is trained using seventy-two data images, validated on ten images, and tested against the left eighteen images. Several statistical scores are calculated for the results and tabulated accordingly. Results: The results show the superior ability of SegNet in classifying infected/non-infected tissues compared to the other methods (with 0.95 mean accuracy), while the U-NET shows better results as a multi-class segmentor (with 0.91 mean accuracy). Conclusion: Semantically segmenting CT scan images of COVID-19 patients is a crucial goal because it would not only assist in disease diagnosis, also help in quantifying the severity of the illness, and hence, prioritize the population treatment accordingly. We propose computer-based techniques that prove to be reliable as detectors for infected tissue in lung CT scans. The availability of such a method in today's pandemic would help automate, prioritize, fasten, and broaden the treatment of COVID-19 patients globally. [ABSTRACT FROM AUTHOR]

Background: The coronavirus disease 2019 (COVID-19) has become a serious public health issue. In COVID-19 patients, the elevated levels of inflammatory cytokines lead to the manifestation of COVID-19 symptoms, such as lung tissue edema, lung diffusion dysfunction, acute respiratory distress syndrome (ARDS), secondary infection, and ultimately mortality. Mesenchymal stem cells (MSCs) exhibit anti-inflammatory and immunomodulatory properties, thus providing a potential treatment option for COVID-19. The number of clinical trials of MSCs for COVID-19 has been rising. However, the treatment protocols and therapeutic effects of MSCs for COVID-19 patients are inconsistent. This meta-analysis was performed to systematically determine the safety and efficacy of MSC infusion in COVID-19 patients. Methods: We conducted a comprehensive literature search from PubMed/Medline, Web of Science, EMBASE, and Cochrane Library up to 22 November 2023 to screen for eligible randomized controlled trials. Inclusion and exclusion criteria for searched literature were formulated according to the PICOS principle, followed by the use of literature quality assessment tools to assess the risk of bias. Finally, outcome measurements including therapeutic efficacy, clinical symptoms, and adverse events of each study were extracted for statistical analysis. Results: A total of 14 randomized controlled trials were collected. The results of enrolled studies demonstrated that patients with COVID-19 pneumonia who received MSC inoculation showed a decreased mortality compared with counterparts who received conventional treatment (RR: 0.76; 95% CI [0.60, 0.96]; p = 0.02). Reciprocally, MSC inoculation improved the clinical symptoms in patients (RR: 1.28; 95% CI [1.06, 1.55]; p = 0.009). In terms of immune biomarkers, MSC treatment inhibited inflammation responses in COVID-19 patients, as was indicated by the decreased levels of CRP and IL-6. Importantly, our results showed that no significant differences in the incidence of adverse reactions or serious adverse events were monitored in patients after MSC inoculation. Conclusion: This meta-analysis demonstrated that MSC inoculation is effective and safe in the treatment of patients with COVID-19 pneumonia. Without increasing the incidence of adverse events or serious adverse events, MSC treatment decreased patient mortality and inflammatory levels and improved the clinical symptoms in COVID-19 patients. However, large-cohort randomized controlled trials with expanded numbers of patients are required to further confirm our results. [ABSTRACT FROM AUTHOR]

Objectives: 1. To assess the efficacy of Mesenchymal Stromal Cells (MSC) versus a control arm as described in the primary endpoint. 2. To evaluate the effects of MSC on the secondary efficacy endpoints. 3. To evaluate the safety and tolerability profiles of MSC. 4. To study soluble and cellular biomarkers that might be involved in the course of the disease and the response to the investigational product.Trial Design: A double-blind, randomized, controlled, trial to evaluate the efficacy and safety of MSC intravenous administration in patients with COVID-induced Acute Respiratory Distress Syndrome (ARDS) compared to a control arm.Participants: The trial is being conducted at a third level hospital, Hospital Universitario Puerta de Hierro, in Majadahonda, Madrid (Spain). Inclusion criteria 1. Informed consent prior to performing study procedures (witnessed oral consent with written consent by representatives will be accepted to avoid paper handling). Written consent by patient or representatives will be obtained whenever possible. 2. Adult patients ≥18 years of age at the time of enrolment. 3. Laboratory-confirmed SARS-CoV-2 infection as determined by Polymerase Chain Reaction (PCR), in oropharyngeal swabs or any other relevant specimen obtained during the course of the disease. Alternative tests (e.g., rapid antigen tests) are also acceptable as laboratory confirmation if their specificity has been accepted by the Sponsor. 4. Moderate to severe ARDS (PaO2/FiO2 ratio equal or less than 200 mmHg) for less than 96 hours at the time of randomization. 5. Patients requiring invasive ventilation are eligible within 72 hours from intubation. 6. Eligible for ICU admission, according to the clinical team. Exclusion criteria 1. Imminent and unavoidable progression to death within 24 hours, irrespective of the provision of treatments (in the opinion of the clinical team). 2. "Do Not Attempt Resuscitation" order in place. 3. Any end-stage organ disease or condition, which in the investigator's opinion, makes the patient an unsuitable candidate for treatment. 4. History of a moderate/severe lung disorder requiring home-based oxygen therapy. 5. Patient requiring Extracorporeal Membrane Oxygenation (ECMO), haemodialysis or hemofiltration at the time of treatment administration. 6. Current diagnosis of pulmonary embolism. 7. Active neoplasm, except carcinoma in situ or basalioma. 8. Known allergy to the products involved in the allogeneic MSC production process. 9. Current pregnancy or lactation (women with childbearing potential should have a negative pregnancy test result at the time of study enrolment). 10. Current participation in a clinical trial with an experimental treatment for COVID-19 (the use of any off-label medicine according to local treatment protocols is not an exclusion criteria). 11. Any circumstances that in the investigator's opinion compromises the patient's ability to participate in the clinical trial. INTERVENTION AND COMPARATOR: - Experimental treatment arm: Allogeneic MSC (approximately 1 x 106 cells/kg). - Control arm: placebo solution (same composition as the experimental treatment, without the MSC). One single intravenous dose of the assigned treatment will be administered on Day 0 of the study. All trial participants will receive standard of care (SOC). In the context of the current worldwide pandemic, SOC can include medicines that are being used in clinical practice (e.g. lopinavir/ritonavir; hydroxy/chloroquine, tocilizumab, etc.), as well as those authorised for COVID (e.g., remdesivir).Main Outcomes: Primary endpoint: Change in the PaO2/FiO2 ratio from baseline to day 7 of treatment administration, or to the last available PaO2/FiO2 ratio if death occurs before day 7. Secondary endpoints: - All-cause mortality on days 7, 14, and 28 after treatment. - PaO2/FiO2 ratio at baseline and days 2, 4, 7, 14 and 28 after treatment. - Oxygen saturation (by standardized measurement) at baseline, daily until day 14, and on day 28 after treatment. - Time to PaO2/FiO2 ratio greater than 200 mmHg. - Subjects' clinical status on the WHO 7-point ordinal scale at baseline, daily until day 14, and on day 28 after treatment. - Time to an improvement of one category from admission on the WHO 7-point ordinal scale. - Percentage of patients that worsen at least one category on the WHO 7-point ordinal scale. - Percentage of patients that improve at least one category (maintained 48h) on the WHO 7-point ordinal scale. - Sequential Organ Failure Assessment (SOFA) scale at baseline and days 2, 4, 7, 14 and 28 after treatment. - Duration of hospitalization (days). - Duration of ICU stay (days). - Oxygen therapy-free days in the first 28 days after treatment. - Duration of supplemental oxygen. - Incidence of and duration of non-invasive and invasive mechanical ventilation in the first 28 days after treatment. - Mechanical ventilation-free days in the first 28 days after treatment. - Ventilation parameters. - Incidence of new onset pulmonary fibrosis at 3 and 12 months after treatment, based on CT scan and pulmonary function tests. - Survival at 3 and 12 months. - Cumulative incidence of Serious Adverse events (SAEs) and Grade 3 and 4 Adverse Events (AEs). - Cumulative incidence of Adverse Drug Reactions (ADR) in the experimental treatment arm. - Cumulative incidence of AEs of special interest. - Levels of analytical markers (C-Reactive Protein, lymphocyte and neutrophil counts, lymphocyte subpopulations, LDH, ferritin, D-dimer, coagulation tests and cytokines...) at baseline and days 2, 4, 7, 14 and 28 after treatment. - Other soluble and cellular biomarkers that might be involved in the course of the disease and the response to MSC.Randomisation: The assignment to treatment will be carried out randomly and blinded, with a 1:1 allocation. Randomization will be done through a centralized system embedded in the electronic Case Report Form (CRF).Blinding (masking): To ensure blinding, treatments will be prepared for administration at the Cell Production Unit and the administration of the treatment will be masked, not allowing the identification of the Investigational Medicinal Product (IMP).Numbers To Be Randomised (sample Size): A total of 20 participants are planned to be randomized, 10 to each treatment group.Trial Status: Protocol version: 1.2, dated October 14th, 2020 Start of recruitment: 01/10/2020 End of recruitment (estimated): December 2020.Trial Registration: EudraCT Number: 2020-002193-27 , registered on July 14th, 2020. NCT number: NCT04615429 , registered on November 4th, 2020.Full Protocol: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. [ABSTRACT FROM AUTHOR]

Objective: To compare the similarities and differences between patients with Coronavirus Disease 2019 (COVID-19) and those with other community-acquired pneumonia (CAP) admitted to the intensive care unit (ICU), utilizing propensity score matching (PSM), regarding hospitalization expenses, treatment options, and prognostic outcomes, aiming to inform the diagnosis and treatment of COVID-19. Methods: Patients admitted to the ICU of the Third People's Hospital of Datong City, diagnosed with COVID-19 from December 2022 to February 2023, constituted the observation group, while those with other CAP admitted from January to November 2022 formed the control group. Basic information, clinical data at admission, and time from symptom onset to admission were matched using PSM. Results: A total of 70 patients were included in the COVID-19 group and 119 in the CAP group. The patients were matched by the propensity matching method, and 37 patients were included in each of the last two groups. After matching, COVID-19 had a higher failure rate than CAP, but the difference was not statistically significant (73% vs. 51%, p = 0.055). The utilization rate of antiviral drugs (40% vs. 11%, p = 0.003), γ-globulin (19% vs. 0%, p = 0.011) and prone position ventilation (PPV) (27% vs. 0%, p < 0.001) in patients with COVID-19 were higher than those in the CAP, and the differences were statistically significant. The total hospitalization cost of COVID-19 patients was lower than that of CAP patients, and the difference was statistically significant (27889.5 vs. 50175.9, p = 0.007). The hospital stay for COVID-19 patients was shorter than for CAP patients, but the difference was not statistically significant (10.9 vs. 16.6, p = 0.071). Conclusion: Our findings suggest that limited medical resources influenced patient outcomes during the COVID-19 pandemic. Addressing substantial demands for ICU capacity and medications during this period could have potentially reduced the mortality rate among COVID-19 patients. [ABSTRACT FROM AUTHOR]

Background: Monoclonal antibody therapy for Covid-19 springs up all over the world and get some efficiency. This research aims to explore the treating effect of BRII-196(Ambavirumab) plus BRII-198(Lomisivir) on Covid-19. Methods: In this retrospective cohort research, patients received standard care or plus BRII-196 /BRII-198 monoclonal antibodies. General comparison of clinical indexes and prognosis between Antibody Group and Control Group was made. Further, according to the antibody using time and patients' condition, subgroups included Early antibody group, Late antibody group, Mild Antibody Group, Mild Control Group, Severe Antibody Group and Severe Control Group. Results: Length of stay(LOS) and interval of Covid-19 nucleic acid from positive to negative of Antibody Group were 12.0(IQR 9.0–15.0) and 14.0(IQR 10.0–16.0) days, less than those(13.0 (IQR 11.0–18.0) and 15.0 (IQR 12.8–17.0) days) of Control Group(p = 0.004, p = 0.004). LOS(median 10days) of Early Antibody Group was the shortest, significantly shorter than that of Control Group (median 13days)(p < 0.001). Interval(median 12days) of Covid-19 nucleic acid from positive to negative of Early Antibody Group also was significantly shorter than that of Control Group(median 15days) and Late Antibody Group(median 14days)(p = 0.001, p = 0.042). LOS(median 12days) and interval(median 13days) of Covid-19 nucleic acid from positive to negative of Mild Antibody Group was shorter than that of Mild Control Group(median 13days; median 14.5days)(p = 0.018, p = 0.033). Conclusion: The neutralizing antibody therapy, BRII-196 plus BRII-198 could shorten LOS and interval of Covid-19 nucleic acid from positive to negative. However, it didn't show efficacy for improving clinical outcomes among severe or critical cases. [ABSTRACT FROM AUTHOR]

Background: COVID-19 pneumonia causes hyperinflammatory response that culminates in acute respiratory syndrome (ARDS) related to increased multiorgan dysfunction and mortality risk. Antiviral-neutralizing immunoglobulins production reflect the host humoral status and illness severity, and thus, immunoglobulin (Ig) circulating levels could be evidence of COVID-19 prognosis. Methods: The relationship among circulating immunoglobulins (IgA, IgG, IgM) and COVID-19 pneumonia was evaluated using clinical information and blood samples in a COVID-19 cohort composed by 320 individuals recruited during the acute phase and followed up to 4 to 8 weeks (n = 252) from the Spanish first to fourth waves. Results: COVID-19 pneumonia development depended on baseline Ig concentrations. Circulating IgA levels together with clinical features at acute phase was highly associated with COVID-19 pneumonia development. IgM was positively correlated with obesity (ρb = 0.156, P = 0.020), dyslipemia (ρb = 0.140, P = 0.029), COPD (ρb = 0.133, P = 0.037), cancer (ρb = 0.173, P = 0.007) and hypertension (ρb = 0.148, P = 0.020). Ig concentrations at recovery phase were related to COVID-19 treatments. Conclusions: Our results provide valuable information on the dynamics of immunoglobulins upon SARS-CoV-2 infection or other similar viruses. [ABSTRACT FROM AUTHOR]

Background: Following the outbreak of the COVID-19 pandemic, several clinical trials have evaluated postexposure prophylaxis (PEP) among close contacts of an index individual with a confirmed SARS-CoV-2 infection. Because index individuals do not directly inform the efficacy of prevention interventions, they are seldom enrolled in COVID-19 PEP studies. However, adjusting for prognostic covariates such as an index individual's COVID-19 illness and risk behaviors can increase precision in PEP efficacy estimates, so approaches to accurately collecting this information about the index individual are needed. This analysis aimed to assess whether surveying household contacts captures the same information as surveying the index individual directly. Methods: REGN 2069/CoVPN 3502, a randomized controlled trial of COVID-19 PEP, enrolled household contacts of SARS-CoV-2 index individuals. CoVPN 3502-01 retrospectively enrolled and surveyed the index individuals. We compared responses to seven similar questions about the index individuals' transmission cofactors that were asked in both studies. We estimated the percent concordance between index individuals and their household contacts on each question, with 50% concordance considered equivalent to random chance. Results: Concordance between index individuals and contacts was high on the most objective questions, approximately 97% (95% CI: 90–99%) for index individual age group and 96% (88–98%) for hospitalization. Concordance was moderate for symptoms, approximately 85% (75–91%). Concordance on questions related to the index individual's behavior was only slightly better or no better than random: approximately 62% (51–72%) for whether they received COVID-19 treatment, 68% (57–77%) for sharing a bedroom, 70% (59–79%) for sharing a common room, and 49% (39–60%) for mask wearing at home. However, while contacts were surveyed within 96 h of the index individual testing positive for SARS-CoV-2, the median time to enrollment in CoVPN 3502-01 was 240 days, which may have caused recall bias in our results. Conclusions: Our results suggest a need to survey index individuals directly in order to accurately capture their transmission cofactors, rather than relying on their household contacts to report on their behavior. The lag in enrolling participants into CoVPN 3502-01 also highlights the importance of timely enrollment to minimize recall bias. [ABSTRACT FROM AUTHOR]

Objective: The coronavirus disease 2019 (COVID-19) pandemic has resulted in millions of confirmed cases and deaths globally. The purpose of this study was to investigate the therapeutic effect of airway clearance technology combined with prone ventilation on patients infected with COVID-19. Methods: 38 patients with COVID-19 (severe) who were treated in the intensive rehabilitation group of Shengli Oilfield Central Hospital. They were randomly divided into a control group and an observation group. The control group received prone position ventilation intervention, and the observation group received airway clearance technology combined with prone position ventilation intervention. The changes of oxygen and index, procalcitonin (PCT), interleukin-6 (IL-6) and chest X-ray image indexes were compared between the two groups. Result: There was no significant difference in age, gender and other general data between the control group and the observation group. The results showed that oxygen index, PCT, IL-6 and chest X-ray image index in the observation group were better than that indexes in the control group. Conclusion: Airway clearance technology combined with prone ventilation intervention in patients with COVID-19 can improve the total effective rate and oxygenation index, improve the inflammatory indicators and respiratory function of patients. And it may be widely promoted and used in the treatment of patients with COVID-19 (severe). [ABSTRACT FROM AUTHOR]

Background: The COVID-19 pandemic has adversely affected access to essential healthcare services. This study aimed to explore healthcare providers' perceptions and experiences of the response to the COVID-19 pandemic in three referral maternal and neonatal hospitals in Guinea. Methods: We conducted a longitudinal qualitative study between June and December 2020 in two maternities and one neonatology referral ward in Conakry and Mamou. Participants were purposively recruited to capture diversity of professional cadres, seniority, and gender. Four rounds of in-depth interviews (46 in-depth interviews with 18 respondents) were conducted in each study site, using a semi-structured interview guide that was iteratively adapted. We used both deductive and inductive approaches and an iterative process for content analysis. Results: We identified four themes and related sub-themes presented according to whether they were common or specific to the study sites, namely: 1) coping strategies & care reorganization, which include reducing staffing levels, maintaining essential healthcare services, suspension of staff daily meetings, insertion of a new information system for providers, and co-management with COVID-19 treatment center for caesarean section cases among women who tested positive for COVID-19; 2) healthcare providers' behavior adaptations during the response, including infection prevention and control measures on the wards and how COVID-19-related information influenced providers' daily work; 3) difficulties encountered by providers, in particular unavailability of personal protective equipment (PPE), lack of financial motivation, and difficulties reducing crowding in the wards; 4) providers perceptions of healthcare service use, for instance their fear during COVID-19 response and perceived increase in severity of complications received and COVID-19 cases among providers and parents of newborns. Conclusion: This study provides insights needed to be considered to improve the preparedness and response of healthcare facilities and care providers to future health emergencies in similar contexts. [ABSTRACT FROM AUTHOR]

Background: In April 2020, in response to the COVID-19 public health emergency, South Eastern Sydney Local Health District (SESLHD) Drug and Alcohol services modified their delivery of opioid dependency treatment (ODT) to reduce spread of COVID-19 and maintain continuity of care by increasing use of takeaway doses (TADs), transferring clients to local community pharmacies for dosing and encouraging the use of long-acting depot buprenorphine (LADB) which enabled once a month dosing. Methods: This study was a retrospective longitudinal case–control study conducted from August 1st, to November 30th, 2021. Eligible clients were those admitted for treatment with SESLHD ODT Services prior to August 1st,2021 and who remained in treatment beyond November 30th, 2021. COVID-19 diagnoses were determined by a COVID-19 PCR and extracted from the electronic Medical Records (eMR) Discern Reporting Portal. Demographic, clinical and dosing related data were collected from eMR and the Australian Immunisation Register (AIR). Results: Clients attending SESLHD ODT services had significantly greater odds of acquiring COVID-19 than the NSW adult population at large (OR: 13.63, 95%CI: 9.64,18.88). Additionally, amongst SESLHD ODT clients, being of Aboriginal and Torres Strait Islander origin was associated with greater odds of acquiring COVID-19 (OR = 2.18, CI: 1.05,4.53); whilst being employed (OR = 0.06, CI:0.01,0.46), receiving doses at pharmacy (OR = 0.43, CI: 0.21,0.89), and being vaccinated (OR = 0.12, CI: 0.06,0.26) were associated with lower odds. Every additional day of attendance required for dosing was associated with a 5% increase in odds of acquiring COVID-19 (OR = 1.05, CI: 1.02,1.08). Conclusions: Clients attending SESLHD ODT services are significantly more likely to acquire COVID-19 than the NSW population at large. Promoting vaccination uptake, transferring clients to pharmacy, and reducing the frequency of dosing (by use of takeaway doses or long-acting depot buprenorphine) are all potential methods to reduce this risk. [ABSTRACT FROM AUTHOR]

Background: Convalescent plasma (CP) and hyperimmune plasma (HP) are passive immunotherapies consisting in the infusion of plasma from recovered people into infected patients. Following pre-existing evidence in many other viral diseases, such as SARS, MERS and Ebola, CP and HP have also been proposed for the treatment of COVID-19. Nevertheless, due to the lack of large, well-designed, clinical trials, no clear-cut guidelines exist about what subtype of patient CP and HP should be administered to.Case Presentation: We have reported the cases of 3 patients, all immunosuppressed and affected by non-severe, prolonged COVID-19. They were treated with HP, whose neutralizing titer was higher than 1/80. The first patient was a 55-year-old male, who had undergone lung transplant. He was under therapy with Tacrolimus and developed non-neutralizing antibodies against SARS-CoV2. The second patient was a 77-year-old female, affected by follicular lymphoma. She had tested positive for SARS-CoV2 after 6 months. The third was a 60-year-old patient, affected by chronic leukemia. He did not develop antibodies after 2-month disease. All 3 patients received HP and had tested negative for SARS-CoV2 within 2 weeks.Conclusion: Despite encouraging initial data, no strong evidence exist in support of CP and HP to treat COVID-19. In our experience, although limited due to the reduced number of patients, we found a good safety and efficacy of HP in 3 immuno-deficient subjects. Further data are needed in order to assess whether this subtype of patients may particularly benefit from passive immunization. [ABSTRACT FROM AUTHOR]

Background: Preprints are increasingly used to disseminate research results, providing multiple sources of information for the same study. We assessed the consistency in effect estimates between preprint and subsequent journal article of COVID-19 randomized controlled trials. Methods: The study utilized data from the COVID-NMA living systematic review of pharmacological treatments for COVID-19 (covid-nma.com) up to July 20, 2022. We identified randomized controlled trials (RCTs) evaluating pharmacological treatments vs. standard of care/placebo for patients with COVID-19 that were originally posted as preprints and subsequently published as journal articles. Trials that did not report the same analysis in both documents were excluded. Data were extracted independently by pairs of researchers with consensus to resolve disagreements. Effect estimates extracted from the first preprint were compared to effect estimates from the journal article. Results: The search identified 135 RCTs originally posted as a preprint and subsequently published as a journal article. We excluded 26 RCTs that did not meet the eligibility criteria, of which 13 RCTs reported an interim analysis in the preprint and a final analysis in the journal article. Overall, 109 preprint–article RCTs were included in the analysis. The median (interquartile range) delay between preprint and journal article was 121 (73–187) days, the median sample size was 150 (71–464) participants, 76% of RCTs had been prospectively registered, 60% received industry or mixed funding, 72% were multicentric trials. The overall risk of bias was rated as 'some concern' for 80% of RCTs. We found that 81 preprint–article pairs of RCTs were consistent for all outcomes reported. There were nine RCTs with at least one outcome with a discrepancy in the number of participants with outcome events or the number of participants analyzed, which yielded a minor change in the estimate of the effect. Furthermore, six RCTs had at least one outcome missing in the journal article and 14 RCTs had at least one outcome added in the journal article compared to the preprint. There was a change in the direction of effect in one RCT. No changes in statistical significance or conclusions were found. Conclusions: Effect estimates were generally consistent between COVID-19 preprints and subsequent journal articles. The main results and interpretation did not change in any trial. Nevertheless, some outcomes were added and deleted in some journal articles. [ABSTRACT FROM AUTHOR]

Background: During the COVID-19 pandemic, some populations, including immunocompromised patients, could not tolerate COVID-19 vaccination or had low responses. Evusheld is a combined neutralizing monoclonal antibody containing tixagevimab and cilgavimab. The World Health Organization (WHO) has approved this combination as pre-exposure prophylaxis (PrEP) and treatment for immunocompromised patients. With the new variant, the (WHO) recommended an increase in dose from 300 to 600 mg with a booster dose after 6 months. The target of this review was to compare the efficacy of the two doses, 300 mg and 600 mg of tixagevimab/cilgavimab (Evusheld) as prophylaxis for higher-risk individuals to reveal if there is a significant difference in efficacy between those two doses of the drug. Methods: In this study, electronic databases (PubMed, Web of Science core collection, Scopus, and Cochran) were investigated for articles up to 31/12/2022 in English using a well-established search strategy. We included studies conducted in immunocompromised patients (aged ≥ 12 years) (WHO) received Evusheld as prophylaxis or treatment for COVID-19. After excluding studies inconsistent with the selection criteria, 24 were involved, 22 of which were included in the meta-analysis. We analyzed the data by using RevMan 5.4 program software. Results: In the double-arm subgroup analysis, Evusheld 600 mg, administered as prophylaxis, showed no significant difference in the COVID-19 infection rate, mortality rate, or needed hospitalization rate compared with the dose of 300 mg (p = 0.13, p = 0.29, and p = 0.25, respectively). In the single-arm subgroup analysis, Evusheld 600 mg, administered as prophylaxis, showed a significant decrease in the COVID-19 infection rate and the hospitalization rate compared with the dose of 300 mg (p = 0.0001, p = 0.007, respectively). As a treatment, Evusheld showed a significant decrease in the mortality rate over the placebo group (p = 0.01) in COVID-19 patients. Conclusion: This result indicated that Evusheld was an effective prophylactic and therapeutic drug for COVID-19 infection, especially for immunocompromised patients, but there was no considerable variation between the high and low doses. Further prospective and randomized controlled trials (RCTs) with increased population sizes are necessary to show the valuable benefit of the high dose of Evusheld in COVID-19 prevention and treatment and to compare the difference between the two doses within adverse events. [ABSTRACT FROM AUTHOR]

Background: The objective of this study was to identify potential biomarkers for predicting response to MSC therapy by pre-MSC treatment plasma proteomic profile in severe COVID-19 in order to optimize treatment choice. Methods: A total of 58 patients selected from our previous RCT cohort were enrolled in this study. MSC responders (n = 35) were defined as whose resolution of lung consolidation ≥ 51.99% (the median value for resolution of lung consolidation) from pre-MSC to 28 days post-MSC treatment, while non-responders (n = 23) were defined as whose resolution of lung consolidation < 51.99%. Plasma before MSC treatment was detected using data-independent acquisition (DIA) proteomics. Multivariate logistic regression analysis was used to identify pre-MSC treatment plasma proteomic biomarkers that might distinguish between responders and non-responders to MSC therapy. Results: In total, 1101 proteins were identified in plasma. Compared with the non-responders, the responders had three upregulated proteins (CSPG2, CTRB1, and OSCAR) and 10 downregulated proteins (ANXA1, AGRG6, CAPG, DDX55, KV133, LEG10, OXSR1, PICAL, PTGDS, and S100A8) in plasma before MSC treatment. Using logistic regression model, lower levels of DDX55, AGRG6, PICAL, and ANXA1 and higher levels of CTRB1 pre-MSC treatment were predictors of responders to MSC therapy, with AUC of the ROC at 0.910 (95% CI 0.818–1.000) in the training set. In the validation set, AUC of the ROC was 0.767 (95% CI 0.459–1.000). Conclusions: The responsiveness to MSC therapy appears to depend on baseline level of DDX55, AGRG6, PICAL, CTRB1, and ANXA1. Clinicians should take these factors into consideration when making decision to initiate MSC therapy in patients with severe COVID-19. [ABSTRACT FROM AUTHOR]

Importance: Acellular human amniotic fluid (hAF) is an antimicrobial and anti-inflammatory fluid that has been used to treat various pro-inflammatory conditions. In a feasibility study, we have previously demonstrated that hAF could be safely administered to severely ill patients with coronavirus disease-19 (COVID-19). The impact of acellular hAF on markers of systemic inflammation and clinical outcomes during COVID-19 infection remain unknown. Objective: To determine the safety and efficacy of acellular, sterile processed intravenously administered hAF on markers of systemic inflammation during COVID-19. Design, settings and participants: This single-center Phase I/II randomized, placebo controlled clinical trial enrolled adult (age ≥ 18 years) patients hospitalized for respiratory symptoms of COVID-19, including hypoxemia, tachypnea or dyspnea. The study was powered for outcomes with an anticipated enrollment of 60 patients. From 09/28/2020 to 02/04/2022 we enrolled and randomized 47 (of an anticipated 60) patients hospitalized due to COVID-19. One patient withdrew consent after randomization but prior to treatment. Safety outcomes to 30 days were collected through hospital discharge and were complete by the end of screening on 6/30/2022. Interventions: Intravenous administration of 10 cc sterile processed acellular hAF once daily for up to 5 days vs placebo. Main outcome and measures: Blood biomarkers of inflammation, including C-Reactive protein (CRP), lactate dehydrogenase, D-dimer, and interleukin-6 (IL-6), as well as safety outcomes. Results: Patients who were randomized to hAF (n = 23) were no more likely to have improvements in CRP from baseline to Day 6 than patients who were randomized to placebo (n = 24) hAF: -5.9 [IQR -8.2, -0.6] vs placebo: -5.9 [-9.4, -2.05]; p = 0.6077). There were no significant differences in safety outcomes or adverse events. Secondary measures of inflammation including lactate dehydrogenase, D-dimer and IL-6 were not statistically different from baseline to day 6. Conclusions and relevance: In this randomized clinical trial involving hospitalized patients with COVID-19, the intravenous administration of 10 cc of hAF daily for 5 days did not result in statistically significant differences in either safety or markers of systemic inflammation compared to placebo, though we did not achieve our enrollment target of 60 patients. Trial registration: This trial was registered at ClinicalTrials.gov as #NCT04497389 on 04/08/2020. [ABSTRACT FROM AUTHOR]

Background: Opioid use disorder (OUD) has been associated with adverse health outcomes, and its potential impact on COVID-19 outcomes is of significant concern. This study aimed to assess the susceptibility and clinical outcomes of hospitalized COVID-19 patients with OUD using a propensity score-matched design. Methods: A historical cohort study was conducted in Alborz province, Iran, during the early months of the COVID-19 pandemic. Patients aged 18 years and above with confirmed COVID-19 were included in the study. OUD was defined as a compulsive urge to use opioids or opioid-derivative drugs. Non-opioid abusers with COVID-19 were selected as the control group. Data on demographics, clinical characteristics, laboratory factors, comorbidities, and vital signs were collected. Propensity score matching (PSM) was used to balance the groups and assess the impact of OUD on ICU admission, mortality, the need for intubation, and the severity of pulmonary involvement on CT scans. Results: A total of 442 patients were included in the study, with 351 discharged and 34 deceased. The PSM analysis showed that OUD was not significantly associated with ICU admission (OR: 1.87, 95% CI: 0.22–2.91, p = 0.631). However, opium users had an increased risk of mortality (OR: 2.38, 95% CI: 1.30–4.35, p = 0.005) and a higher likelihood of requiring intubation (OR: 3.57, 95% CI: 1.38–9.39, p = 0.009) compared to non-opioid abusers. The severity of pulmonary involvement on CT scans did not show a significant association with OUD. Conclusion: OUD among hospitalized COVID-19 patients was associated with an increased risk of mortality and the need for intubation. These findings highlight the importance of addressing OUD as a potential risk factor in the management and treatment of COVID-19 patients. Further research is warranted to explore the underlying mechanisms and develop appropriate interventions to mitigate the impact of OUD on COVID-19 outcomes. [ABSTRACT FROM AUTHOR]

Background: The results of clinical trials should be completely and rapidly reported during public health emergencies such as COVID-19. This study aimed to examine when, and where, the results of COVID-19 clinical trials were disseminated throughout the first 18 months of the pandemic. Methods: Clinical trials for COVID-19 treatment or prevention were identified from the WHO ICTRP database. All interventional trials with a registered completion date ≤ 30 June 2021 were included. Trial results, published as preprints, journal articles, or registry results, were located using automated and manual techniques across PubMed, Google Scholar, Google, EuropePMC, CORD-19, the Cochrane COVID-19 Study Register, and clinical trial registries. Our main analysis reports the rate of dissemination overall and per route, and the time from registered completion to results using Kaplan–Meier methods, with additional subgroup and sensitivity analyses reported. Results: Overall, 1643 trials with completion dates ranging from 46 to 561 days prior to the start of results searches were included. The cumulative probability of reporting was 12.5% at 3 months from completion, 21.6% at 6 months, and 32.8% at 12 months. Trial results were most commonly disseminated in journals (n = 278 trials, 69.2%); preprints were available for 194 trials (48.3%), 86 (44.3%) of which converted to a full journal article. Trials completed earlier in the pandemic were reported more rapidly than those later in the pandemic, and those involving ivermectin were more rapidly reported than other common interventions. Results were robust to various sensitivity analyses except when considering only trials in a "completed" status on the registry, which substantially increased reporting rates. Poor trial registry data on completion status and dates limits the precision of estimates. Conclusions: COVID-19 trials saw marginal increases in reporting rates compared to standard practice; most registered trials failed to meet even the 12-month non-pandemic standard. Preprints were common, complementing journal publication; however, registries were underutilized for rapid reporting. Maintaining registry data enables accurate representation of clinical research; failing to do so undermines these registries' use for public accountability and analysis. Addressing rapid reporting and registry data quality must be emphasized at global, national, and institutional levels. [ABSTRACT FROM AUTHOR]

Background: Rapid diagnostic testing may support improved treatment of COVID patients. Understanding COVID testing and care pathways is important for assessing the impact and cost-effectiveness of testing in the real world, yet there is limited information on these pathways in low-and-middle income countries (LMICs). We therefore undertook an expert consultation to better understand testing policies and practices, clinical screening, the profile of patients seeking testing or care, linkage to care after testing, treatment, lessons learnt and expected changes in 2023. Methods: We organized a qualitative consultation with ten experts from seven LMICs (India, Indonesia, Malawi, Nigeria, Peru, South Africa, and Zimbabwe) identified through purposive sampling. We conducted structured interviews during six regional consultations, and undertook a thematic analysis of responses. Results: Participants reported that, after initial efforts to scale-up testing, the policy priority given to COVID testing has declined. Comorbidities putting patients at heightened risk (e.g., diabetes) mainly relied on self-identification. The decision to test following clinical screening was highly context-/location-specific, often dictated by local epidemiology and test availability. When rapid diagnostic tests were available, public sector healthcare providers tended to rely on them for diagnosis (alongside PCR for Asian/Latin American participants), while private sector providers predominantly used polymerase chain reaction (PCR) tests. Positive test results were generally taken at 'face value' by clinicians, although negative tests with a high index of suspicion may be confirmed with PCR. However, even with a positive result, patients were not always linked to care in a timely manner because of reluctance to receiving care or delays in returning to care centres upon clinical deterioration. Countries often lacked multiple components of the range of therapeutics advised in WHO guidelines: notably so for oral antivirals designed for high-risk mild patients. Severely ill patients mostly received corticosteroids and, in higher-resourced settings, tocilizumab. Conclusions: Testing does not always prompt enhanced care, due to reluctance on the part of patients and limited therapeutic availability within clinical settings. Any analysis of the impact or cost-effectiveness of testing policies post pandemic needs to either consider investment in optimal treatment pathways or constrain estimates of benefits based on actual practice. [ABSTRACT FROM AUTHOR]

Background: Adherence to antiretroviral therapy and COVID-19 preventive behaviours among people living with HIV during the pandemic has received little attention in the literature. To address this gap in knowledge, the present study assessed the associations between viral load, adherence to antiretroviral therapy and the use of COVID-19 prevention strategies during the first wave of the COVID-19 pandemic. This was a secondary analysis of data generated through an online survey recruiting participants from 152 countries. Complete data from 680 respondents living with HIV were extracted for this analysis. Results: The findings suggest that detectable viral load was associated with lower odds of wearing facemasks (AOR: 0.44; 95% CI:0.28–0.69; p < 0.01) and washing hands as often as recommended (AOR: 0.64; 95% CI: 0.42–0.97; p = 0.03). Also, adherence to the use of antiretroviral drugs was associated with lower odds of working remotely (AOR: 0.60; 95% CI: 0.38–0.94; p = 0.02). We found a complex relationship between HIV positive status biological parameters and adherence to COVID-19 preventive measures that may be partly explained by risk-taking behaviours. Further studies are needed to understand the reasons for the study findings. [ABSTRACT FROM AUTHOR]

Background: The COVID-19 pandemic spurred publication of a rapid proliferation of studies on potential therapeutic agents. While important for the advancement of clinical care, pressure to collect, analyze, and report data in an expedited manner could potentially increase the rate of important errors, some of which would be captured in published errata. We hypothesized that COVID-19 therapeutic studies published in the early years of the pandemic would be associated with a high rate of published errata and that, within these errata, there would be a high prevalence of serious errors. Methods: We performed a review of published errata associated with empirical studies of COVID-19 treatments. Errata were identified via a MEDLINE and Embase search spanning January 2020 through September 2022. Errors located within each published erratum were characterized by location within publication, error type, and error seriousness. Results: Of 47 studies on COVID-19 treatments with published errata, 18 met inclusion criteria. Median time from publication of the original article to publication of the associated erratum was 76 days (range, 12–511 days). A majority of errata addressed issues with author attribution or conflict of interest disclosures (39.5%) or numerical results (25.6%). Only one erratum contained a serious error: a typographical error which could have misled readers into believing that the treatment in question had serious adverse effects when in fact it did not. Conclusions: Despite accelerated publication times, we found among studies of COVID-19 treatments the majority of errata (17/18) reported minor errors that did not lead to misinterpretation of the study results. Retractions, an indicator of scientific misdirection even more concerning than errata, were beyond the scope of this review. [ABSTRACT FROM AUTHOR]

Background: Transplant recipients are at high risk of coronavirus disease 2019, and a timely supply of antivirals should be prioritized for those patients. Complicated drug‒drug interactions limit the use of Paxlovid (nirmatrelvir/ritonavir) coadministered with tacrolimus. Here, we report a patient with a kidney transplant who received Paxlovid and reduced-dose tacrolimus at the same time and suffered a severe tacrolimus toxicity. Case presentation: We present a 56-year-old man of Han ethnicity with a kidney transplant who suffered from coronavirus disease 2019 twice. For the first infection, the immunosuppressants were substituted by dexamethasone when the patient used Paxlovid, and everything went well. For the second time, tacrolimus at a reduced dose concomitant with Paxlovid caused severe diarrhea, inducing combined diabetic ketoacidosis and a hyperglycemic hyperosmolar state. Conclusion: This case challenges the dose-adjustment strategy of managing drug‒drug interactions. We suggest that tacrolimus should be stopped when Paxlovid is applied and that corticosteroids could be a good substitution. [ABSTRACT FROM AUTHOR]

Background: The coronavirus disease 2019 (Covid-19) pandemic is a global public health problem. The Covid-19 pandemic has had a substantial impact on the economy of developing countries, including Ethiopia.This study aimed to determine the hospitalisation costs of Covid-19 and the factors associated with the high cost of hospitalisation in South Central Ethiopia. Methods: A retrospective cost analysis of Covid-19 patients hospitalised between July 2020 and July 2021 at Bokoji Hospital Covid-19 Treatment Centre was conducted using both the micro-costing and top-down approaches from the health system perspective. This analysis used cost data obtained from administrative reports, the financial reports of the treatment centre, procurement invoices and the Covid-19 standard treatment guidelines. The Student's t-test, Mann-Whitney U test or Kruskal-Wallis test was employed to test the difference between sociodemographic and clinical factors when appropriate.To identify the determinants of cost drivers in the study population, a generalised linear model with gamma distribution and log link with a stepwise algorithm were used. Results: A total of 692 Covid-19 patients were included in the costing analysis. In this study, the mean cost of Covid-19–infected patients with no symptoms was US$1,073.86, with mild symptoms US$1,100.74, with moderate symptoms US$1,394.74 and in severe–critically ill condition US$1,708.05.The overall mean cost was US$1,382.50(95% CI: 1,360.60–1,404.40) per treated episode.The highest mean cost was observed for personnel, accounting for 64.0% of the overall cost. Older age, pre-existing diseases, advanced disease severity at admission, admission to the intensive care unit, prolonged stay on treatment and intranasal oxygen support were strongly associated with higher costs. Conclusions: This study found that the clinical management of Covid-19 patients incurred significant expenses to the health system. Factors such as older age, disease severity, presence of comorbidities, use of inhalation oxygen therapy and prolonged hospital stay were associated with higher hospitalisation costs.Therefore, the government should give priority to the elderly and those with comorbidities in the provision of vaccination to reduce the financial burden on health facilities and health systems in terms of resource utilisation. [ABSTRACT FROM AUTHOR]

Background: Critically ill patients commonly receive proton pump inhibitors (PPIs) to prevent gastrointestinal (GI) bleeding from stress-induced ulceration. Despite widespread use in the intensive care unit (ICU), observational data suggest that PPIs may be associated with adverse outcomes in patients with COVID-19 infection. This preplanned study is nested within a large randomized trial evaluating pantoprazole versus placebo in invasively ventilated patients. The 3 objectives are as follows: (1) to describe the characteristics of patients with COVID-19 in terms of demographics, biomarkers, venous thromboembolism, tracheostomy incidence and timing, and other clinical outcomes; (2) to evaluate the impact of COVID-19 infection on clinically important GI bleeding, 90-day mortality, and other outcomes compared to a propensity-matched non-infected cohort; and (3) to explore whether pantoprazole has a differential treatment effect on clinically important GI bleeding, 90-day mortality, and other outcomes in patients with and without COVID-19 infection. Methods: The ongoing trial Re-EValuating the Inhibition of Stress Erosions (REVISE) compares pantoprazole 40 mg IV to placebo on the primary efficacy outcome of clinically important GI bleeding and the primary safety outcome of 90-day mortality. The protocol described in this report is for a substudy focused on patients with COVID-19 infection that was not in the original pre-pandemic trial protocol. We developed a one-page case report form to characterize these patients including data related to biomarkers, venous thromboembolism, COVID-19 therapies, tracheostomy incidence and timing, duration of mechanical ventilation, and ICU and hospital stay. Our analysis will describe the trajectory of patients with COVID-19 infection, a propensity-matched analysis of infected and non-infected patients, and an extended subgroup analysis comparing the effect of PPI among patients with and without COVID-19 infection. Discussion: Prophylactic acid suppression in invasively ventilated critically ill patients with COVID-19 infection has unknown consequences. The results of these investigations will inform practice, guidelines, and future research. Trial registration: REVISE Trial [NCT03374800 December 15, 2017], COVID-19 Cohort Study [NCT05715567 February 8, 2023]. [ABSTRACT FROM AUTHOR]

Background: Since the beginning of the COVID-19 pandemic, therapeutic options for treating COVID-19 have been investigated at different stages of clinical manifestations. Considering the particular impact of COVID-19 in the Americas, this document aims to present recommendations for the pharmacological treatment of COVID-19 specific to this population. Methods: Fifteen experts, members of the Brazilian Society of Infectious Diseases (SBI) and the Pan-American Association of Infectious Diseases (API) make up the panel responsible for developing this guideline. Questions were formulated regarding prophylaxis and treatment of COVID-19 in outpatient and inpatient settings. The outcomes considered in decision-making were mortality, hospitalisation, need for mechanical ventilation, symptomatic COVID-19 episodes, and adverse events. In addition, a systematic review of randomised controlled trials was conducted. The quality of evidence assessment and guideline development process followed the GRADE system. Results: Nine technologies were evaluated, and ten recommendations were made, including the use of tixagevimab + cilgavimab in the prophylaxis of COVID-19, tixagevimab + cilgavimab, molnupiravir, nirmatrelvir + ritonavir, and remdesivir in the treatment of outpatients, and remdesivir, baricitinib, and tocilizumab in the treatment of hospitalised patients with severe COVID-19. The use of hydroxychloroquine or chloroquine and ivermectin was discouraged. Conclusion: This guideline provides recommendations for treating patients in the Americas following the principles of evidence-based medicine. The recommendations present a set of drugs that have proven effective in the prophylaxis and treatment of COVID-19, emphasising the strong recommendation for the use of nirmatrelvir/ritonavir in outpatients as the lack of benefit from the use of hydroxychloroquine and ivermectin. [ABSTRACT FROM AUTHOR]

The outbreak of coronavirus disease 2019 (COVID-19) posed an unprecedented challenge on public health systems. Despite the measures put in place to contain it, COVID-19 is likely to continue experiencing sporadic outbreaks for some time, and individuals will remain susceptible to recurrent infections. Chimeric antigen receptor (CAR)-T recipients are characterized by durable B-cell aplasia, hypogammaglobulinemia and loss of T-cell diversity, which lead to an increased proportion of severe/critical cases and a high mortality rate after COVID-19 infection. Thus, treatment decisions have become much more complex and require greater caution when considering CAR T-cell immunotherapy. Hence, we reviewed the current understanding of COVID-19 and reported clinical experience in the management of COVID-19 and CAR-T therapy. After a panel discussion, we proposed a rational procedure pertaining to CAR-T recipients with the aim of maximizing the benefit of CAR-T therapy in the post COVID-19 pandemic era. [ABSTRACT FROM AUTHOR]

Importance: COVID-19 has adversely affected global healthcare infrastructure since 2019. Currently, there are no large-scale published reports on the efficacy of combination therapy of dexamethasone, remdesivir, and tocilizumab on COVID-19 patients. Objectives: Is the combination therapy of dexamethasone, remdesivir, and tocilizumab superior to other treatments on hospitalized COVID-19 patients? Design: This is a retrospective, comparative effectiveness study. Setting: Single-center study Participants/interventions: We analyzed different inpatient COVID-19 treatment options available in the United States and their impact on hospital length of stay (LOS) and mortality. Hospitalized COVID-19 were categorized as "mild," "moderate" and "severe'' based on the highest level of oxygen required; room air, nasal cannula, or high flow/PAP/intubation, respectively. Patients were treated in accordance with the availability of medications and the latest treatment guidelines. Main outcomes: The endpoints of the study are hospital discharges and death during hospitalization. Results: 1233 COVID-19 patients were admitted from 2020 to 2021. No treatment combinations showed a statistically significant decrease in hospital LOS in mild COVID-19 patients (p = 0.186). In moderate patients, the combination of remdesivir and dexamethasone slightly decreased LOS by 1 day (p = 0.007). In severe patients, the three-drug combination of remdesivir, dexamethasone, and tocilizumab decreased LOS by 8 days (p = 0.0034) when compared to nonviable treatments, such as hydroxychloroquine and convalescent plasma transfusion. However, it did not show any statistically significant benefit when compared to two-drug regimens (dexamethasone plus remdesivir) in severe COVID-19 (p = 0.116). No treatment arm appeared to show a statistically significant decrease in mortality for severe COVID-19 patients. Conclusions: Our findings suggest that three-drug combination may decrease LOS in severe COVID-19 patients when compared to two-drug therapy. However, the trend was not supported by statistical analysis. Remdesivir may not be clinically beneficial for mild hospitalized COVID-19 patients; considering its cost, one could reserve it for moderate and severe patients. Triple drug therapies, while potentially reducing LOS for severe patients, do not affect overall mortality. Additional patient data may increase statistical power and solidify these findings. Key points: Question: Is the three-drug combination therapy of dexamethasone, remdesivir, and tocilizumab effective in decreasing the length of stay for patients with severe COVID-19 disease?. Findings: The three-drug combination of remdesivir, dexamethasone, and tocilizumab decreased LOS by 8 days (p=0.0034) compared to nonviable treatments like hydroxychloroquine and convalescent plasma transfusion. However, it did not show any statistically significant benefit when compared to two-drug regimens (dexamethasone plus remdesivir) in severe COVID-19 (p=0.116). No treatment arm appeared to show a statistically significant decrease in mortality for severe COVID-19 patients. Meaning: Triple drug therapies that include tocilizumab may potentially reduce LOS for severe patients but we did not find statistically significant data to support this statement [ABSTRACT FROM AUTHOR]

The ongoing coronavirus disease 2019 (COVID-19) pandemic constitutes a serious public health concern worldwide. Currently, more than 6 million deaths have occurred despite drastic containment measures, and this number is still increasing. Currently, no standard therapies for COVID-19 are available, which necessitates identifying effective preventive and therapeutic agents against COVID-19. However, developing new drugs and vaccines is a time-consuming process, and therefore, repurposing the existing drugs or redeveloping related targets seems to be the best strategy to develop effective therapeutics against COVID-19. Autophagy, a multistep lysosomal degradation pathway contributing to nutrient recycling and metabolic adaptation, is involved in the initiation and progression of numerous diseases as a part of an immune response. The key role of autophagy in antiviral immunity has been extensively studied. Moreover, autophagy can directly eliminate intracellular microorganisms by selective autophagy, that is, "xenophagy." However, viruses have acquired diverse strategies to exploit autophagy for their infection and replication. This review aims to trigger the interest in the field of autophagy as an antiviral target for viral pathogens (with an emphasis on COVID-19). We base this hypothesis on summarizing the classification and structure of coronaviruses as well as the process of SARS-CoV-2 infection and replication; providing the common understanding of autophagy; reviewing interactions between the mechanisms of viral entry/replication and the autophagy pathways; and discussing the current state of clinical trials of autophagy-modifying drugs in the treatment of SARS-CoV-2 infection. We anticipate that this review will contribute to the rapid development of therapeutics and vaccines against COVID-19. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID-19) is caused by a new member of the Coronaviridae family known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). There are structural and non-structural proteins (NSPs) in the genome of this virus. S, M, H, and E proteins are structural proteins, and NSPs include accessory and replicase proteins. The structural and NSP components of SARS-CoV-2 play an important role in its infectivity, and some of them may be important in the pathogenesis of chronic diseases, including cancer, coagulation disorders, neurodegenerative disorders, and cardiovascular diseases. The SARS-CoV-2 proteins interact with targets such as angiotensin-converting enzyme 2 (ACE2) receptor. In addition, SARS-CoV-2 can stimulate pathological intracellular signaling pathways by triggering transcription factor hypoxia-inducible factor-1 (HIF-1), neuropilin-1 (NRP-1), CD147, and Eph receptors, which play important roles in the progression of neurodegenerative diseases like Alzheimer's disease, epilepsy, and multiple sclerosis, and multiple cancers such as glioblastoma, lung malignancies, and leukemias. Several compounds such as polyphenols, doxazosin, baricitinib, and ruxolitinib could inhibit these interactions. It has been demonstrated that the SARS-CoV-2 spike protein has a stronger affinity for human ACE2 than the spike protein of SARS-CoV, leading the current study to hypothesize that the newly produced variant Omicron receptor-binding domain (RBD) binds to human ACE2 more strongly than the primary strain. SARS and Middle East respiratory syndrome (MERS) viruses against structural and NSPs have become resistant to previous vaccines. Therefore, the review of recent studies and the performance of current vaccines and their effects on COVID-19 and related diseases has become a vital need to deal with the current conditions. This review examines the potential role of these SARS-CoV-2 proteins in the initiation of chronic diseases, and it is anticipated that these proteins could serve as components of an effective vaccine or treatment for COVID-19 and related diseases. 5GsYi7yKA3Znyv5bMow8Zr Video Abstract [ABSTRACT FROM AUTHOR]

The coronavirus disease 2019 (COVID-19) pandemic has impacted human lifestyles around the world, causing huge distress in terms of public health systems, emergency response capacity and economic development. The causative agent of COVID-19, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is associated with respiratory involvement, cardiovascular-related diseases, and ultimately causes multiple organ failure and death in severely affected individuals. Thus, effective prevention or early treatment of COVID-19 is critical. An effective vaccine offers a way out of the pandemic for governments, the scientific community and people worldwide, but we still lack effective drug therapies, including treatments for the prevention and treatment of COVID-19. This had led to a high global demand for many complementary and alternative medicines (CAMs). Moreover, many healthcare providers are now requesting information about CAMs that prevent, relieve, or treat the symptoms of COVID-19 and even alleviate vaccine-related side effects. Experts and scholars must therefore become familiar with the use of CAMs in COVID-19, current research directions and effectiveness of CAMs for COVID-19. This narrative review updates the current status and research worldwide on the use of CAMs for COVID-19. The review provides reliable evidence on theoretical viewpoints and therapeutic efficacies of CAM combinations, and evidence in support of the therapeutic strategy of Taiwan Chingguan Erhau (NRICM102) against moderate-to-severe novel coronavirus infectious disease in Taiwan. [ABSTRACT FROM AUTHOR]

Millions of people have been affected ever since the emergence of the corona virus disease of 2019 (COVID-19) outbreak, leading to an urgent need for antiviral drug and vaccine development. Current experimentation on traditional two-dimensional culture (2D) fails to accurately mimic the in vivo microenvironment for the disease, while in vivo animal model testing does not faithfully replicate human COVID-19 infection. Human-based three-dimensional (3D) cell culture models such as spheroids, organoids, and organ-on-a-chip present a promising solution to these challenges. In this report, we review the recent 3D in vitro lung models used in COVID-19 infection and drug screening studies and highlight the most common types of natural and synthetic polymers used to generate 3D lung models. [ABSTRACT FROM AUTHOR]

Background: This study attempts to estimate the cost-effectiveness of the antiviral remdesivir, as recommended in the 2021 COVID treatment guidelines for the United Arab Emirates, compared to standard of care (SOC), but also favipiravir (FAVI), which was also recommended for the treatment of hospitalized COVID patients. Methods: A cost-effectiveness model was built using published efficacy data for RDV, FAVI and SOC as well as local epidemiology data. The outcomes measured included hospital bed days averted, mortality, costs and cost per outcome over one year. One-way, probabilistic and scenario analyses were undertaken to reflect uncertainty in the estimates. Results: When modelled over one year, the results indicated that treatment of adults in need of supplemental oxygen with RDV + SOC could result in 11,338 fewer general ward bed days, 7,003 fewer ICU days and 5,451 fewer ICU + MIV bed days compared to SOC alone and similar results when compared with FAVI + SOC. The model results also showed that there were 374 fewer deaths associated with the use of RDV + SOC compared to SOC alone. The model also estimates substantial potential cost-savings associated with RDV + SOC treatment compared with SOC alone (USD 3,454 per patient). The results of the one-way sensitivity analysis showed that the model was sensitive to estimates of length of stay and the cost of hospitalization. Despite this, the model predicted cost-savings in all scenarios versus all comparators. Conclusions: The model estimated that using RDV + SOC could result in substantial reductions in HCRU and cost savings regardless of the comparator. However, it should be noted that reliable clinical information on FAVI was limited therefore it is challenging to interpret these results. All the potential benefits modelled here for RDV + SOC can have implications not only for the health of the UAE population but for improving hospital capacity to deal with other conditions. [ABSTRACT FROM AUTHOR]

Objective: To examine changes in use patterns, cost of healthcare services before and after the outbreak of the COVID-19 pandemic, and their impacts on expenditures for patients receiving treatment for depression, anxiety, eating disorders, and substance use. Methods: This cross-sectional study employed statistical tests to analyze claims in MarketScan® Commercial Database in March 2020-February 2021 and quarterly from March 2020 to August 2021, compared to respective pre-pandemic periods. The analysis is based on medical episodes created by the Merative™ Medical Episode Grouper (MEG). MEG is a methodology that groups medical and prescription drug claims to create clinically relevant episodes of care. Results: Comparing year-over-year changes, proportion of patients receiving anxiety treatment among all individuals obtaining healthcare services grew 13.7% in the first year of the pandemic (3/2020–2/2021) versus 10.0% in the year before the pandemic (3/2019–2/2020). This, along with a higher growth in price per episode (5.5% versus 4.3%) resulted in a greater increase in per claimant expenditure ($0.61 versus $0.41 per month). In the same periods, proportion of patients receiving treatment for depression grew 3.7% versus 6.9%, but per claimant expenditure grew by same amount due to an increase in price per episode (4.8%). Proportion of patients receiving treatment for anorexia started to increase 21.1% or more in the fall of 2020. Patient proportion of alcohol use in age group 18–34 decreased 17.9% during the pandemic but price per episode increased 26.3%. Patient proportion of opioid use increased 11.5% in March–May 2020 but decreased or had no significant changes in subsequent periods. Conclusions: We investigated the changes in use patterns and expenditures of mental health patients before and after the outbreak of the COVID-19 pandemic using claims data in MarketScan®. We found that the changes and their financial impacts vary across mental health conditions, age groups, and periods of the pandemic. Some changes are unexpected from previously reported prevalence increases among the general population and could underlie unmet treatment needs. Therefore, mental health providers should anticipate the use pattern changes in services with similar COVID-19 pandemic disruptions and payers should anticipate cost increases due, in part, to increased price and/or service use. [ABSTRACT FROM AUTHOR]

Public health experts are looking into the current coronavirus outbreak to see if there are any ways to prevent potentially fatal symptoms. Low-Dose Radiotherapy (LD-RT) induces anti-inflammatory cytokine responses that act as a counterweight to pro-inflammatory cytokines, potentially providing therapeutic benefits for COVID-19-related diseases associated with significant morbidity and mortality. This study will look into positive immuno-radiological reactions to see if they are feasible, practicable, and effective in lowering the critical inflammatory condition of the crucial stage COVID-19. This study aims to investigate the use of low-dose lung radiation in bacterial and viral pneumonia, as well as to provide a treatment plan for COVID-19-associated pneumonia. This article discusses the evidence for and against LD-RT theories in COVID-19 patients. The use of LD-RT at various stages of COVID-19 appears to be beneficial, with fewer side effects than other currently being studied treatments. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic has the potential to cause high morbidity and mortality in crisis-affected populations. Delivering COVID-19 treatment services in crisis settings will likely entail complex trade-offs between offering services of clinical benefit and minimising risks of nosocomial infection, while allocating resources appropriately and safeguarding other essential services. This paper outlines considerations for humanitarian actors planning COVID-19 treatment services where vaccination is not yet widely available. We suggest key decision-making considerations: allocation of resources to COVID-19 treatment services and the design of clinical services should be based on community preferences, likely opportunity costs, and a clearly articulated package of care across different health system levels. Moreover, appropriate service planning requires information on the expected COVID-19 burden and the resilience of the health system. We explore COVID-19 treatment service options at the patient level (diagnosis, management, location and level of treatment) and measures to reduce nosocomial transmission (cohorting patients, protecting healthcare workers). Lastly, we propose key indicators for monitoring COVID-19 health services. [ABSTRACT FROM AUTHOR]

Background: The efficacy of early treatment with convalescent plasma in patients with COVID-19 is debated. Nothing is known about the potential effect of other plasma components other than anti-SARS-CoV-2 antibodies.Methods: To determine whether convalescent or standard plasma would improve outcomes for adults in early phase of Covid19 respiratory impairment we designed this randomized, three-arms, clinical trial (PLACO COVID) blinded on interventional arms that was conducted from June 2020 to August 2021. It was a multicentric trial at 19 Italian hospitals. We enrolled 180 hospitalized adult patients with COVID-19 pneumonia within 5 days from the onset of respiratory distress. Patients were randomly assigned in a 1:1:1 ratio to standard of care (n = 60) or standard of care + three units of standard plasma (n = 60) or standard of care + three units of high-titre convalescent plasma (n = 60) administered on days 1, 3, 5 after randomization. Primary outcome was 30-days mortality. Secondary outcomes were: incidence of mechanical ventilation or death at day 30, 6-month mortality, proportion of days with mechanical ventilation on total length of hospital stay, IgG anti-SARS-CoV-2 seroconversion, viral clearance from plasma and respiratory tract samples, and variations in Sequential Organ Failure Assessment score. The trial was analysed according to the intention-to-treat principle.Results: 180 patients (133/180 [73.9%] males, mean age 66.6 years [IQR 57-73]) were enrolled a median of 8 days from onset of symptoms. At enrollment, 88.9% of patients showed moderate/severe respiratory failure. 30-days mortality was 20% in Control arm, 23% in Convalescent (risk ratio [RR] 1.13; 95% confidence interval [CI], 0.61-2.13, P = 0.694) and 25% in Standard plasma (RR 1.23; 95%CI, 0.63-2.37, P = 0.544). Time to viral clearance from respiratory tract was 21 days for Convalescent, 28 for Standard plasma and 23 in Control arm but differences were not statistically significant. No differences for other secondary endpoints were seen in the three arms. Serious adverse events were reported in 1.7%, 3.3% and 5% of patients in Control, Standard and Convalescent plasma arms respectively.Conclusions: Neither high-titer Convalescent nor Standard plasma improve outcomes of COVID-19 patients with acute respiratory failure. Trial Registration Clinicaltrials.gov Identifier: NCT04428021. First posted: 11/06/2020. [ABSTRACT FROM AUTHOR]

Background: Concerns have grown that post-acute sequelae of COVID-19 may affect significant numbers of survivors. However, the analyses used to guide policy-making for Australia's national and state re-opening plans have not incorporated non-acute illness in their modelling. We, therefore, develop a model by which to estimate the potential acute and post-acute COVID-19 burden using disability-adjusted life years (DALYs) associated with the re-opening of Australian borders and the easing of other public health measures, with particular attention to longer-term, post-acute consequences and the potential impact of permanent functional impairment following COVID-19. Methods: A model was developed based on the European Burden of Disease Network protocol guideline and consensus model to estimate the burden of COVID-19 using DALYs. Data inputs were based on publicly available sources. COVID-19 infection and different scenarios were drawn from the Doherty Institute's modelling report to estimate the likely DALY losses under the Australian national re-opening plan. Long COVID prevalence, post-intensive care syndrome (PICS) and potential permanent functional impairment incidences were drawn from the literature. DALYs were calculated for the following health states: the symptomatic phase, Long COVID, PICS and potential permanent functional impairment (e.g., diabetes, Parkinson's disease, dementia, anxiety disorders, ischemic stroke). Uncertainty and sensitivity analysis were performed to examine the robustness of the results. Results: Mortality was responsible for 72-74% of the total base case COVID-19 burden. Long COVID and post-intensive care syndrome accounted for at least 19 and 3% of the total base case DALYs respectively. When included in the analysis, potential permanent impairment could contribute to 51-55% of total DALYs lost. Conclusions: The impact of Long COVID and potential long-term post-COVID disabilities could contribute substantially to the COVID-19 burden in Australia's post-vaccination setting. As vaccination coverage increases, the share of COVID-19 burden driven by longer-term morbidity rises relative to mortality. As Australia re-opens, better estimates of the COVID-19 burden can assist with decision-making on pandemic control measures and planning for the healthcare needs of COVID-19 survivors. Our estimates highlight the importance of valuing the morbidity of post-COVID-19 sequelae, above and beyond simple mortality and case statistics. [ABSTRACT FROM AUTHOR]

Background: In the context of the COVID-19 pandemic, randomized controlled trials (RCTs) are essential to support clinical decision-making. We aimed (1) to assess and compare the reporting characteristics of RCTs between preprints and peer-reviewed publications and (2) to assess whether reporting improves after the peer review process for all preprints subsequently published in peer-reviewed journals.Methods: We searched the Cochrane COVID-19 Study Register and L·OVE COVID-19 platform to identify all reports of RCTs assessing pharmacological treatments of COVID-19, up to May 2021. We extracted indicators of transparency (e.g., trial registration, data sharing intentions) and assessed the completeness of reporting (i.e., some important CONSORT items, conflict of interest, ethical approval) using a standardized data extraction form. We also identified paired reports published in preprint and peer-reviewed publications.Results: We identified 251 trial reports: 121 (48%) were first published in peer-reviewed journals, and 130 (52%) were first published as preprints. Transparency was poor. About half of trials were prospectively registered (n = 140, 56%); 38% (n = 95) made their full protocols available, and 29% (n = 72) provided access to their statistical analysis plan report. A data sharing statement was reported in 68% (n = 170) of the reports of which 91% stated their willingness to share. Completeness of reporting was low: only 32% (n = 81) of trials completely defined the pre-specified primary outcome measures; 57% (n = 143) reported the process of allocation concealment. Overall, 51% (n = 127) adequately reported the results for the primary outcomes while only 14% (n = 36) of trials adequately described harms. Primary outcome(s) reported in trial registries and published reports were inconsistent in 49% (n = 104) of trials; of them, only 15% (n = 16) disclosed outcome switching in the report. There were no major differences between preprints and peer-reviewed publications. Of the 130 RCTs published as preprints, 78 were subsequently published in a peer-reviewed journal. There was no major improvement after the journal peer review process for most items.Conclusions: Transparency, completeness, and consistency of reporting of COVID-19 clinical trials were insufficient both in preprints and peer-reviewed publications. A comparison of paired reports published in preprint and peer-reviewed publication did not indicate major improvement. [ABSTRACT FROM AUTHOR]

Background: Despite the fast establishment of new therapeutic agents in the management of COVID-19 and large-scale vaccination campaigns since the beginning of the SARS-CoV-2 pandemic in early 2020, severe disease courses still represent a threat, especially to patients with risk factors. This indicates the need for alternative strategies to prevent respiratory complications like acute respiratory distress syndrome (ARDS) associated with COVID-19. Aviptadil, a synthetic form of human vasoactive intestinal peptide, might be beneficial for COVID-19 patients at high risk of developing ARDS because of its ability to influence the regulation of exaggerated pro-inflammatory proteins and orchestrate the lung homeostasis. Aviptadil has recently been shown to considerably improve the prognosis of ARDS in COVID-19 when applied intravenously. An inhaled application of aviptadil has the advantages of achieving a higher concentration in the lung tissue, fast onset of activity, avoiding the hepatic first-pass metabolism, and the reduction of adverse effects. The overall objective of this project is to assess the efficacy and safety of inhaled aviptadil in patients hospitalized for COVID-19 at high risk of developing ARDS.Methods: This multicenter, placebo-controlled, double-blinded, randomized trial with 132 adult patients hospitalized for COVID-19 and at high risk for ARDS (adapted early acute lung injury score ≥ 2 points) is conducted in five public hospitals in Europe. Key exclusion criteria are mechanical ventilation at baseline, need for intensive care at baseline, and severe hemodynamic instability. Patients are randomly allocated to either inhale 67 μg aviptadil or normal saline (three times a day for 10 days), in addition to standard care, stratified by center. The primary endpoint is time from hospitalization to clinical improvement, defined as either hospital discharge, or improvement of at least two levels on the nine-level scale for clinical status suggested by the World Health Organization.Discussion: Treatment strategies for COVID-19 are still limited. In the context of upcoming new variants of SARS-CoV-2 and possible inefficacy of the available vaccines and antibody therapies, the investigation of alternative therapy options plays a crucial role in decreasing associated mortality and improving prognosis. Due to its unique immunomodulating properties also targeting the SARS-CoV-2 pathways, inhaled aviptadil may have the potential to prevent ARDS in COVID-19.Trial Registration: ClinicalTrials.gov, NCT04536350 . Registered 02 September 2020. [ABSTRACT FROM AUTHOR]

Background: Patients with chronic lymphocytic leukemia (CLL) may be more susceptible to COVID-19 related poor outcomes, including thrombosis and death, due to the advanced age, the presence of comorbidities, and the disease and treatment-related immune deficiency. The aim of this study was to assess the risk of thrombosis and bleeding in patients with CLL affected by severe COVID-19. Methods: This is a retrospective multicenter study conducted by ERIC, the European Research Initiative on CLL, including patients from 79 centers across 22 countries. Data collection was conducted between April and May 2021. The COVID-19 diagnosis was confirmed by the real-time polymerase chain reaction (RT-PCR) assay for SARS-CoV-2 on nasal or pharyngeal swabs. Severe cases of COVID-19 were defined by hospitalization and the need of oxygen or admission into ICU. Development and type of thrombotic events, presence and severity of bleeding complications were reported during treatment for COVID-19. Bleeding events were classified using ISTH definition. STROBE recommendations were used in order to enhance reporting. Results: A total of 793 patients from 79 centers were included in the study with 593 being hospitalized (74.8%). Among these, 511 were defined as having severe COVID: 162 were admitted to the ICU while 349 received oxygen supplementation outside the ICU. Most patients (90.5%) were receiving thromboprophylaxis. During COVID-19 treatment, 11.1% developed a thromboembolic event, while 5.0% experienced bleeding. Thrombosis developed in 21.6% of patients who were not receiving thromboprophylaxis, in contrast to 10.6% of patients who were on thromboprophylaxis. Bleeding episodes were more frequent in patients receiving intermediate/therapeutic versus prophylactic doses of low-molecular-weight heparin (LWMH) (8.1% vs. 3.8%, respectively) and in elderly. In multivariate analysis, peak D-dimer level and C-reactive protein to albumin ratio were poor prognostic factors for thrombosis occurrence (OR = 1.022, 95%CI 1.007‒1.038 and OR = 1.025, 95%CI 1.001‒1.051, respectively), while thromboprophylaxis use was protective (OR = 0.199, 95%CI 0.061‒0.645). Age and LMWH intermediate/therapeutic dose administration were prognostic factors in multivariate model for bleeding (OR = 1.062, 95%CI 1.017–1.109 and OR = 2.438, 95%CI 1.023–5.813, respectively). Conclusions: Patients with CLL affected by severe COVID-19 are at a high risk of thrombosis if thromboprophylaxis is not used, but also at increased risk of bleeding under the LMWH intermediate/therapeutic dose administration. [ABSTRACT FROM AUTHOR]

Background: The Randomised Evaluation of COVID-19 Therapy (RECOVERY) trial is aimed at addressing the urgent need to find effective treatments for patients hospitalised with suspected or confirmed COVID-19. The trial has had many successes, including discovering that dexamethasone is effective at reducing COVID-19 mortality, the first treatment to reach this milestone in a randomised controlled trial. Despite this, it continues to use standard or 'fixed' randomisation to allocate patients to treatments. We assessed the impact of implementing response adaptive randomisation within RECOVERY using an array of performance measures, to learn if it could be beneficial going forward. This design feature has recently been implemented within the REMAP-CAP platform trial.Methods: Trial data was simulated to closely match the data for patients allocated to standard care, dexamethasone, hydroxychloroquine, or lopinavir-ritonavir in the RECOVERY trial from March-June 2020, representing four out of five arms tested throughout this period. Trials were simulated in both a two-arm trial setting using standard care and dexamethasone, and a four-arm trial setting utilising all above treatments. Two forms of fixed randomisation and two forms of response-adaptive randomisation were tested. In the two-arm setting, response-adaptive randomisation was implemented across both trial arms, whereas in the four-arm setting it was implemented in the three non-standard care arms only. In the two-arm trial, randomisation strategies were performed at the whole trial level as well as within three pre-specified patient subgroups defined by patients' respiratory support level.Results: All response-adaptive randomisation strategies led to more patients being given dexamethasone and a lower mortality rate in the trial. Subgroup specific response-adaptive randomisation reduced mortality rates even further. In the two-arm trial, response-adaptive randomisation reduced statistical power compared to FR, with subgroup level adaptive randomisation exhibiting the largest power reduction. In the four-arm trial, response-adaptive randomisation increased statistical power in the dexamethasone arm but reduced statistical power in the lopinavir arm. Response-adaptive randomisation did not induce any meaningful bias in treatment effect estimates nor did it cause any inflation in the type 1 error rate.Conclusions: Using response-adaptive randomisation within RECOVERY could have increased the number of patients receiving the optimal COVID-19 treatment during the trial, while reducing the number of patients needed to attain the same study power as the original study. This would likely have reduced patient deaths during the trial and lead to dexamethasone being declared effective sooner. Deciding how to balance the needs of patients within a trial and future patients who have yet to fall ill is an important ethical question for the trials community to address. Response-adaptive randomisation deserves to be considered as a design feature in future trials of COVID-19 and other diseases. [ABSTRACT FROM AUTHOR]

Background: The SARS-CoV-2 pandemic has become a challenge for the entire healthcare system. Treatment for COVID-19 includes casual and symptomatic management in the acute phase of the disease and focuses on the treating early complications of the disease. Long-term health consequences of the infection have not yet been fully identified. A special group of patients with comorbidities, including neoplastic disease for whom the interpretation and management of symptoms is a major challenge. Case presentation: In this case report, we present a 73-year-old woman with recently diagnosed gastric adenocarcinoma in whom we diagnosed orthostatic hypotonia in the aftermath of SARS-CoV-2 infection. We administered thiethylperazine maleate 6.5 mg daily. Additionally, we advised the patient to slowly lift from the recumbent position, raise the headboard, take meals in small portions, and increase fluid intake. These pharmacological and nonpharmacological measures resulted in sustained relief of dizziness and nausea. Conclusions: The occurrence of orthostatic hypotonia seems a possible late sequela of SARS-CoV-2 infection, and simple measures appeared sufficient to achieve sustained symptom control. [ABSTRACT FROM AUTHOR]

Background: SARS-CoV-2 is the highly transmissible etiologic agent of coronavirus disease 2019 (COVID-19) and has become a global scientific and public health challenge since December 2019. Several new variants of SARS-CoV-2 have emerged globally raising concern about prevention and treatment of COVID-19. Early detection and in-depth analysis of the emerging variants allowing pre-emptive alert and mitigation efforts are thus of paramount importance. Results: Here we present ClusTRace, a novel bioinformatic pipeline for a fast and scalable analysis of sequence clusters or clades in large viral phylogenies. ClusTRace offers several high-level functionalities including lineage assignment, outlier filtering, aligning, phylogenetic tree reconstruction, cluster extraction, variant calling, visualization and reporting. ClusTRace was developed as an aid for COVID-19 transmission chain tracing in Finland with the main emphasis on fast screening of phylogenies for markers of super-spreading events and other features of concern, such as high rates of cluster growth and/or accumulation of novel mutations. Conclusions: ClusTRace provides an effective interface that can significantly cut down learning and operating costs related to complex bioinformatic analysis of large viral sequence sets and phylogenies. All code is freely available from https://bitbucket.org/plyusnin/clustrace/ [ABSTRACT FROM AUTHOR]

Background: Quantitative computed tomography (QCT) analysis may serve as a tool for assessing the severity of coronavirus disease 2019 (COVID-19) and for monitoring its progress. The present study aimed to assess the association between steroid therapy and quantitative CT parameters in a longitudinal cohort with COVID-19.Methods: Between February 7 and February 17, 2020, 72 patients with severe COVID-19 were retrospectively enrolled. All 300 chest CT scans from these patients were collected and classified into five stages according to the interval between hospital admission and follow-up CT scans: Stage 1 (at admission); Stage 2 (3-7 days); Stage 3 (8-14 days); Stage 4 (15-21 days); and Stage 5 (22-31 days). QCT was performed using a threshold-based quantitative analysis to segment the lung according to different Hounsfield unit (HU) intervals. The primary outcomes were changes in percentage of compromised lung volume (%CL, - 500 to 100 HU) at different stages. Multivariate Generalized Estimating Equations were performed after adjusting for potential confounders.Results: Of 72 patients, 31 patients (43.1%) received steroid therapy. Steroid therapy was associated with a decrease in %CL (- 3.27% [95% CI, - 5.86 to - 0.68, P = 0.01]) after adjusting for duration and baseline %CL. Associations between steroid therapy and changes in %CL varied between different stages or baseline %CL (all interactions, P < 0.01). Steroid therapy was associated with decrease in %CL after stage 3 (all P < 0.05), but not at stage 2. Similarly, steroid therapy was associated with a more significant decrease in %CL in the high CL group (P < 0.05), but not in the low CL group.Conclusions: Steroid administration was independently associated with a decrease in %CL, with interaction by duration or disease severity in a longitudinal cohort. The quantitative CT parameters, particularly compromised lung volume, may provide a useful tool to monitor COVID-19 progression during the treatment process. Trial registration Clinicaltrials.gov, NCT04953247. Registered July 7, 2021, https://clinicaltrials.gov/ct2/show/NCT04953247. [ABSTRACT FROM AUTHOR]