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3.
BMJ ; 374: n1648, 2021 07 26.
Article in English | MEDLINE | ID: covidwho-1327634

ABSTRACT

Since its emergence in Wuhan, China, covid-19 has spread and had a profound effect on the lives and health of people around the globe. As of 4 July 2021, more than 183 million confirmed cases of covid-19 had been recorded worldwide, and 3.97 million deaths. Recent evidence has shown that a range of persistent symptoms can remain long after the acute SARS-CoV-2 infection, and this condition is now coined long covid by recognized research institutes. Studies have shown that long covid can affect the whole spectrum of people with covid-19, from those with very mild acute disease to the most severe forms. Like acute covid-19, long covid can involve multiple organs and can affect many systems including, but not limited to, the respiratory, cardiovascular, neurological, gastrointestinal, and musculoskeletal systems. The symptoms of long covid include fatigue, dyspnea, cardiac abnormalities, cognitive impairment, sleep disturbances, symptoms of post-traumatic stress disorder, muscle pain, concentration problems, and headache. This review summarizes studies of the long term effects of covid-19 in hospitalized and non-hospitalized patients and describes the persistent symptoms they endure. Risk factors for acute covid-19 and long covid and possible therapeutic options are also discussed.


Subject(s)
COVID-19/complications , COVID-19/diagnosis , COVID-19/epidemiology , COVID-19/etiology , COVID-19/therapy , Clinical Trials as Topic , Combined Modality Therapy/methods , Combined Modality Therapy/standards , Drug Repositioning , Global Burden of Disease , Humans , Incidence , Practice Guidelines as Topic , Risk Factors , Severity of Illness Index
4.
Muscle Nerve ; 64(4): 487-490, 2021 10.
Article in English | MEDLINE | ID: covidwho-1318732

ABSTRACT

INTRODUCTION/AIMS: There are currently three medications approved for spinal muscular atrophy (SMA), but the use of these medications in combination has not been well described. METHODS: This is a retrospective report of four cases of SMA treated with dual onasemnogene and risdiplam therapy at our institution. RESULTS: Following onasemnogene therapy, all four patients experienced a perceived plateau of therapeutic benefit, at which time daily risdiplam was started. Transient fatigue and weakness was seen in two patients following risdiplam initiation, but this resolved within 1 mo. One patient was hospitalized with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and post-viral pneumonia, weeks following risdiplam initiation. No other adverse effects related to onasemnogene and risdiplam combination therapy were identified and all patients experienced objective and subjective improvement. DISCUSSION: Combination therapy with onasemnogene and risdiplam in patients with SMA appears to be well-tolerated. Further large prospective trials are needed to determine whether dual therapy is more efficacious than monotherapy, and to identify rare adverse events that may occur with the use of combination therapy.


Subject(s)
Azo Compounds/administration & dosage , Biological Products/administration & dosage , Pyrimidines/administration & dosage , Recombinant Fusion Proteins/administration & dosage , Spinal Muscular Atrophies of Childhood/diagnosis , Spinal Muscular Atrophies of Childhood/therapy , Combined Modality Therapy/methods , Drug Therapy, Combination , Female , Genetic Therapy/methods , Humans , Infant , Male , Retrospective Studies , Spinal Muscular Atrophies of Childhood/physiopathology
5.
Pharmacol Res ; 158: 104896, 2020 08.
Article in English | MEDLINE | ID: covidwho-1318933

ABSTRACT

Corona virus disease (COVID-19) has now spread to all parts of the world and almost all countries are battling against it. This study aimed to assess the efficacy and safety of Integrated Traditional Chinese and Western Medicine (Hereinafter referred to as "Integrated Medicine") to COVID-19. We searched six major Chinese and English databases to identify randomized controlled trials (RCTs) and case-control studies (CCSs) of Integrated Medicine on COVID-19. Two reviewers independently screened, identified studies, and extracted data. Cochrane Risk of Bias tool and the Newcastle-Ottawa Scale were used to assess the quality of included RCTs and CCSs, respectively. Stata (version 13.0; StataCorp) was used to perform meta-analyses with the random-effects model. Risk ratio (RR) was used for dichotomous data while the weighted mean difference (WMD) was adopted for continuous variables as effect size, both of which were demonstrated in effect size and 95% confidence intervals (CI). A total of 11 studies were included. Four were RCTs and seven were CCSs. The sample size of including studies ranged from 42 to 200 (total 982). The traditional Chinese medicine included Chinese medicine compound drugs (QingFei TouXie FuZhengFang) and Chinese patent medicine (e.g. Shufeng Jiedu Capsule, Lianhua Qingwen granules). Compared with the control group, the overall response rate [RR = 1.230, 95%CI (1.113, 1.359), P = 0.000], cure rate [RR = 1.604, 95%CI (1.181, 2.177), P = 0.002], severity illness rate [RR = 0.350, 95%CI (0.154, 0.792), P = 0.012], and hospital stay [WMD = -1.991, 95%CI (-3.278, -0.703), P = 0.002] of the intervention group were better. In addition, Integrated Medicine can improve the disappearance rate of fever, cough, expectoration, fatigue, chest tightness and anorexia and reduce patients' fever, and fatigue time (P < 0.05). This review found that Integrated Medicine had better effects and did not increase adverse drug reactions for COVID-19. More high-quality RCTs are needed in the future.


Subject(s)
Betacoronavirus , Clinical Medicine/methods , Combined Modality Therapy/adverse effects , Combined Modality Therapy/methods , Coronavirus Infections/therapy , Medicine, Chinese Traditional/methods , Pneumonia, Viral/therapy , COVID-19 , Humans , Pandemics , SARS-CoV-2
6.
Lancet Respir Med ; 9(9): 957-968, 2021 09.
Article in English | MEDLINE | ID: covidwho-1275790

ABSTRACT

BACKGROUND: The major complication of COVID-19 is hypoxaemic respiratory failure from capillary leak and alveolar oedema. Experimental and early clinical data suggest that the tyrosine-kinase inhibitor imatinib reverses pulmonary capillary leak. METHODS: This randomised, double-blind, placebo-controlled, clinical trial was done at 13 academic and non-academic teaching hospitals in the Netherlands. Hospitalised patients (aged ≥18 years) with COVID-19, as confirmed by an RT-PCR test for SARS-CoV-2, requiring supplemental oxygen to maintain a peripheral oxygen saturation of greater than 94% were eligible. Patients were excluded if they had severe pre-existing pulmonary disease, had pre-existing heart failure, had undergone active treatment of a haematological or non-haematological malignancy in the previous 12 months, had cytopenia, or were receiving concomitant treatment with medication known to strongly interact with imatinib. Patients were randomly assigned (1:1) to receive either oral imatinib, given as a loading dose of 800 mg on day 0 followed by 400 mg daily on days 1-9, or placebo. Randomisation was done with a computer-based clinical data management platform with variable block sizes (containing two, four, or six patients), stratified by study site. The primary outcome was time to discontinuation of mechanical ventilation and supplemental oxygen for more than 48 consecutive hours, while being alive during a 28-day period. Secondary outcomes included safety, mortality at 28 days, and the need for invasive mechanical ventilation. All efficacy and safety analyses were done in all randomised patients who had received at least one dose of study medication (modified intention-to-treat population). This study is registered with the EU Clinical Trials Register (EudraCT 2020-001236-10). FINDINGS: Between March 31, 2020, and Jan 4, 2021, 805 patients were screened, of whom 400 were eligible and randomly assigned to the imatinib group (n=204) or the placebo group (n=196). A total of 385 (96%) patients (median age 64 years [IQR 56-73]) received at least one dose of study medication and were included in the modified intention-to-treat population. Time to discontinuation of ventilation and supplemental oxygen for more than 48 h was not significantly different between the two groups (unadjusted hazard ratio [HR] 0·95 [95% CI 0·76-1·20]). At day 28, 15 (8%) of 197 patients had died in the imatinib group compared with 27 (14%) of 188 patients in the placebo group (unadjusted HR 0·51 [0·27-0·95]). After adjusting for baseline imbalances between the two groups (sex, obesity, diabetes, and cardiovascular disease) the HR for mortality was 0·52 (95% CI 0·26-1·05). The HR for mechanical ventilation in the imatinib group compared with the placebo group was 1·07 (0·63-1·80; p=0·81). The median duration of invasive mechanical ventilation was 7 days (IQR 3-13) in the imatinib group compared with 12 days (6-20) in the placebo group (p=0·0080). 91 (46%) of 197 patients in the imatinib group and 82 (44%) of 188 patients in the placebo group had at least one grade 3 or higher adverse event. The safety evaluation revealed no imatinib-associated adverse events. INTERPRETATION: The study failed to meet its primary outcome, as imatinib did not reduce the time to discontinuation of ventilation and supplemental oxygen for more than 48 consecutive hours in patients with COVID-19 requiring supplemental oxygen. The observed effects on survival (although attenuated after adjustment for baseline imbalances) and duration of mechanical ventilation suggest that imatinib might confer clinical benefit in hospitalised patients with COVID-19, but further studies are required to validate these findings. FUNDING: Amsterdam Medical Center Foundation, Nederlandse Organisatie voor Wetenschappelijk Onderzoek/ZonMW, and the European Union Innovative Medicines Initiative 2.


Subject(s)
COVID-19/therapy , Imatinib Mesylate/administration & dosage , Protein Kinase Inhibitors/administration & dosage , Respiration, Artificial/statistics & numerical data , Respiratory Insufficiency/therapy , Aged , COVID-19/complications , COVID-19/diagnosis , COVID-19/virology , Capillary Permeability/drug effects , Combined Modality Therapy/adverse effects , Combined Modality Therapy/methods , Double-Blind Method , Female , Humans , Imatinib Mesylate/adverse effects , Male , Middle Aged , Netherlands , Oxygen/administration & dosage , Placebos/administration & dosage , Placebos/adverse effects , Protein Kinase Inhibitors/adverse effects , Respiratory Insufficiency/diagnosis , Respiratory Insufficiency/virology , SARS-CoV-2/isolation & purification , Severity of Illness Index , Time Factors , Treatment Outcome
7.
Medicine (Baltimore) ; 100(21): e26059, 2021 May 28.
Article in English | MEDLINE | ID: covidwho-1242122

ABSTRACT

BACKGROUND: : Coronavirus disease 2019 (COVID-19) is an emerging and rapidly evolving disease, with no recommended effective anti-coronavirus treatments. Traditional Chinese Medicine (TCM) has been widely used to treat COVID-19 in China, and the most used one is Lianhuaqingwen (LH). This study aimed to assess the efficacy and safety of LH combined with usual treatment vs usual treatment alone in treating mild or moderate COVID-19 by a meta-analysis of randomized controlled trials (RCTs). METHODS AND ANALYSIS: : We systematically searched the Medline (OVID), Embase, the Cochrane Library, and 4 Chinese databases from inception to July 2020 to include the RCTs that evaluated the efficacy and safety of LH in combination with usual treatment vs usual treatment for mild or moderate COVID-19. A meta-analysis was performed to calculate the risk ratio (RR) and 95% confidence interval (CI) for binary outcomes and mean difference (MD) for continuous outcomes. RESULTS: : A total of 5 RCTs with 824 individuals with mild or moderate COVID 19 were included. Compared with the usual treatment alone, LH in combination with usual treatment significantly improved the overall clinical efficacy (RR = 2.39, 95% CI 1.61-3.55), increased the rate of recovery of chest computed tomographic manifestations (RR = 1.80, 95% CI 1.08-3.01), reduced the rate of conversion to severe cases (RR = 0.47, 95% CI 0.29-0.74), shorten the duration of fever (MD = -1.00, 95% CI -1.17 to -0.84). Moreover, LH in combination with usual treatment did not increase the occurrence of the adverse event compared to usual treatment alone. CONCLUSION: : Our meta-analysis of RCTs indicated that LH in combination with usual treatment may improve the clinical efficacy in patients with mild or moderate COVID-19 without increasing adverse events. However, given the limitations and poor quality of included trials in this study, further large-sample RCTs or high-quality real-world studies are needed to confirm our conclusions.


Subject(s)
Antiviral Agents/administration & dosage , COVID-19/therapy , Drugs, Chinese Herbal/administration & dosage , Oxygen/administration & dosage , Antiviral Agents/adverse effects , COVID-19/diagnosis , COVID-19/virology , China , Combined Modality Therapy/adverse effects , Combined Modality Therapy/methods , Drugs, Chinese Herbal/adverse effects , Humans , Lung/diagnostic imaging , Nutritional Support , Oxygen/adverse effects , Randomized Controlled Trials as Topic , SARS-CoV-2/isolation & purification , Severity of Illness Index , Tomography, X-Ray Computed , Treatment Outcome
8.
Am Soc Clin Oncol Educ Book ; 41: 1-11, 2021 Mar.
Article in English | MEDLINE | ID: covidwho-1218295

ABSTRACT

In the care of patients with operable breast cancer, there has been a shift toward increasing use of neoadjuvant therapy. There are benefits to neoadjuvant therapy, such as monitoring for response, as well as an increased rate of breast conservation and reduction of potential morbidity associated with breast surgery, including axillary management. Among patients with highly proliferative tumors, such as HER2-positive or triple-negative breast cancer, those with residual disease are at higher risk of recurrence, which informs the recommended systemic therapy in the adjuvant setting. For instance, in patients with residual disease after neoadjuvant chemotherapy and HER2-targeted therapy, there is a role for adjuvant trastuzumab emtansine for those with residual disease at the time of surgery. The same holds true regarding the role of adjuvant capecitabine in patients with residual disease after neoadjuvant chemotherapy. With the added complexities of treating patients in the era of the COVID-19 outbreak, additional considerations are critical, including initiation of surgery within an appropriate time from completion of neoadjuvant therapy. National consensus guidelines on time to surgery must be developed to improve measurement and comparison across systems. In addition, there is emerging radiation treatment management research addressing a number of factors, including hypofractionation, role of proton beam therapy, safe omission of radiotherapy, and preoperative radiotherapy with or without drug combination. In this article, the multidisciplinary approach of treating patients with operable breast cancer is highlighted, with updates and future considerations described.


Subject(s)
Breast Neoplasms/diagnosis , Breast Neoplasms/therapy , Biomarkers, Tumor , Breast Neoplasms/etiology , Clinical Decision-Making , Combined Modality Therapy/adverse effects , Combined Modality Therapy/methods , Comorbidity , Disease Management , Disease Susceptibility , Female , Humans , Outcome Assessment, Health Care , Perioperative Care , Time-to-Treatment
9.
J Pharm Pharm Sci ; 24: 210-219, 2021.
Article in English | MEDLINE | ID: covidwho-1212102

ABSTRACT

PURPOSE: The purpose of this study was to compare how treatment with convalescent plasma (CP) monotherapy, remdesivir (RDV) monotherapy, and combination therapy (CP + RDV) in patients with COVID-19 affected clinical outcomes. METHODS: Patients with COVID-19 infection who were admitted to the hospital received CP, RDV, or combination of both. Mortality, discharge disposition, hospital length of stay (LOS), intensive care unit (ICU) LOS, and total ventilation days were compared between each treatment group and stratified by ABO blood group. An exploratory analysis identified risk factors for mortality. Adverse effects were also evaluated. RESULTS: RDV monotherapy showed an increased chance of survival compared to combination therapy or CP monotherapy (p = 0.052). There were 15, 3, and 6 deaths in the CP, RDV, and combination therapy groups, respectively. The combination therapy group had the longest median ICU LOS (8, IQR 4.5-15.5, p = 0.220) and hospital LOS (11, IQR 7-15.5, p = 0.175). Age (p = 0.036), initial SOFA score (p = 0.013), and intubation (p = 0.005) were statistically significant predictors of mortality. Patients with type O blood had decreased ventilation days, ICU LOS, and total LOS. Thirteen treatment-related adverse events occurred. CONCLUSION: No significant differences in clinical outcomes were observed between patients treated with RDV, CP, or combination therapy. Elderly patients, those with a high initial SOFA score, and those who require intubation are at increased risk of mortality associated with COVID-19. Blood type did not affect clinical outcomes.


Subject(s)
Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , Antiviral Agents/administration & dosage , COVID-19/therapy , Hospitals, Community/trends , Adenosine Monophosphate/administration & dosage , Adult , Aged , Alanine/administration & dosage , COVID-19/diagnosis , COVID-19/epidemiology , COVID-19/mortality , California/epidemiology , Combined Modality Therapy/methods , Female , Humans , Immunization, Passive/mortality , Length of Stay/trends , Male , Middle Aged , Retrospective Studies , Treatment Outcome
10.
Nat Commun ; 12(1): 2349, 2021 04 15.
Article in English | MEDLINE | ID: covidwho-1189222

ABSTRACT

Substantial COVID-19 research investment has been allocated to randomized clinical trials (RCTs) on hydroxychloroquine/chloroquine, which currently face recruitment challenges or early discontinuation. We aim to estimate the effects of hydroxychloroquine and chloroquine on survival in COVID-19 from all currently available RCT evidence, published and unpublished. We present a rapid meta-analysis of ongoing, completed, or discontinued RCTs on hydroxychloroquine or chloroquine treatment for any COVID-19 patients (protocol: https://osf.io/QESV4/ ). We systematically identified unpublished RCTs (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, Cochrane COVID-registry up to June 11, 2020), and published RCTs (PubMed, medRxiv and bioRxiv up to October 16, 2020). All-cause mortality has been extracted (publications/preprints) or requested from investigators and combined in random-effects meta-analyses, calculating odds ratios (ORs) with 95% confidence intervals (CIs), separately for hydroxychloroquine and chloroquine. Prespecified subgroup analyses include patient setting, diagnostic confirmation, control type, and publication status. Sixty-three trials were potentially eligible. We included 14 unpublished trials (1308 patients) and 14 publications/preprints (9011 patients). Results for hydroxychloroquine are dominated by RECOVERY and WHO SOLIDARITY, two highly pragmatic trials, which employed relatively high doses and included 4716 and 1853 patients, respectively (67% of the total sample size). The combined OR on all-cause mortality for hydroxychloroquine is 1.11 (95% CI: 1.02, 1.20; I² = 0%; 26 trials; 10,012 patients) and for chloroquine 1.77 (95%CI: 0.15, 21.13, I² = 0%; 4 trials; 307 patients). We identified no subgroup effects. We found that treatment with hydroxychloroquine is associated with increased mortality in COVID-19 patients, and there is no benefit of chloroquine. Findings have unclear generalizability to outpatients, children, pregnant women, and people with comorbidities.


Subject(s)
COVID-19/drug therapy , COVID-19/mortality , Chloroquine/adverse effects , Hydroxychloroquine/adverse effects , Pregnancy Complications, Infectious/mortality , Adult , COVID-19/complications , COVID-19/virology , Child , Chloroquine/administration & dosage , Combined Modality Therapy/adverse effects , Combined Modality Therapy/methods , Comorbidity , Female , Humans , Hydroxychloroquine/administration & dosage , International Cooperation , Odds Ratio , Patient Participation/statistics & numerical data , Pregnancy , Pregnancy Complications, Infectious/drug therapy , Pregnancy Complications, Infectious/virology , Randomized Controlled Trials as Topic/statistics & numerical data , SARS-CoV-2
11.
Parkinsonism Relat Disord ; 85: 109-113, 2021 04.
Article in English | MEDLINE | ID: covidwho-1179945

ABSTRACT

INTRODUCTION: During the first peak phase of the COVID-19 pandemic, the German Ministry of Health recommended that elective treatments should be postponed to increase hospital capacities. This has also compromised the capacity for application of specialized Parkinson's disease (PD) therapies to an unknown extent. METHODS: We conducted a nationwide cross-sectional study using administrative database of all hospitalized patients with main diagnosis of PD receiving multimodal complex treatment (PD-MCT), initial setup of levodopa/carbidopa intestinal gel (LCIG) or continuous subcutaneous apomorphine infusion (CSAI) in Germany. We compared case numbers and clinical characteristics of the pandemic (March 16th - May 15th, 2020) and post-lockdown (July 16th - September 15th, 2020) period with the pre-pandemic (January 16th - March 15th, 2020) and historical control period (March 16th - May 15th, 2019). RESULTS: We identified a strong decline for PD-MCT(-62.8%) and for the application of drug pump-based therapies (-69.4%) during the first peak phase of the pandemic as compared to the pre-pandemic period while specialized PD treatment procedures increased again in the post-lockdown phase. Advanced disease was a marker for PD-MCT patients during the pandemic period. CONCLUSION: Besides the marked decline in specialized PD treatments during the first peak phase of the COVID-19 pandemic, we found recuperative effects for these procedures in the post-lockdown period without reaching pre-pandemic levels. Strengthening treatment capacities for PD patients, even in the event of a persistent pandemic, is urgently needed in order to maintain the quality of care.


Subject(s)
Antiparkinson Agents/administration & dosage , COVID-19/epidemiology , Infusion Pumps/trends , Parkinson Disease/epidemiology , Parkinson Disease/therapy , Aged , Aged, 80 and over , COVID-19/prevention & control , Combined Modality Therapy/methods , Combined Modality Therapy/trends , Cross-Sectional Studies , Female , Germany/epidemiology , Humans , Male , Middle Aged
12.
Med Sci Monit ; 27: e930278, 2021 Apr 09.
Article in English | MEDLINE | ID: covidwho-1148370

ABSTRACT

The high infectivity and severity of SARS-CoV-2 infection (COVID-19), and our limited understanding of the biology of the novel coronavirus, as well as the lack of an effective treatment for COVID-19, have created a global pandemic. Those most likely to become seriously ill with COVID-19 are adults, especially the elderly and those who are already weak or sick. At present, a specific drug for treatment of COVID-19 has not been developed. This, combined with the typical coexistence of a variety of chronic diseases in elderly patients, makes treatment challenging at present. In addition, for elderly patients, COVID-19 isolation measures during the epidemic can easily lead to psychological problems. Thus, how to manage elderly patients has become a focus of social attention in the current circumstances. This article reviews the effects of COVID-19 and makes management suggestions for elderly patients during this epidemic period. In addition to the elderly, critically ill people are also highly susceptible to this novel coronavirus. For elderly COVID-19 patients, antiviral therapy, immune regulation, and even auxiliary respiratory therapy can be given after a comprehensive evaluation of the disease. With the approval and use of COVID-19 vaccines, it is reasonable to expect that we can conquer SARS-CoV-2.


Subject(s)
Antiviral Agents/therapeutic use , COVID-19/therapy , Chronic Disease/epidemiology , Respiratory Therapy/methods , Age Factors , Aged , Aging/immunology , COVID-19/diagnosis , COVID-19/epidemiology , COVID-19/immunology , COVID-19 Vaccines/administration & dosage , Combined Modality Therapy/methods , Comorbidity , Critical Illness/epidemiology , Disease Susceptibility , Humans , Risk Factors , SARS-CoV-2/drug effects , SARS-CoV-2/immunology , SARS-CoV-2/isolation & purification , Severity of Illness Index
13.
Rev Med Virol ; 31(6): e2225, 2021 11.
Article in English | MEDLINE | ID: covidwho-1095682

ABSTRACT

Convalescent plasma therapy (CPT) has been investigated as a treatment for COVID-19. This review evaluates CPT in COVID-19 and other viral respiratory diseases, including severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS) and influenza. PubMed and Google scholar databases were used to collect eligible publications until 8 December 2020. Meta-analysis used Mantel-Haenszel risk ratio (RR) with 95% confidence interval (CI) and pooled analysis for individual patient data with inverse variance weighted average. The study is registered at PROSPERO with the number of CRD4200270579. Forty-four studies with 36,716 participants were included in the pooled analysis and 20 studies in the meta-analysis. Meta-analysis showed reduction of mortality (RR 0.57, 95% CI [0.43, 0.76], z = 3.86 [p < 0.001], I2  = 44% [p = 0.03]) and higher number of discharged patients (RR 2.53, 95% CI [1.72, 3.72], z = 4.70 [p < 0.001], I2  = 3% [p = 0.39]) in patients receiving CPT compared to standard care alone. A possible mechanism of action is prompt reduction in viral titre. Serious transfusion-related adverse events were reported to be less than 1% of cases, suggesting the overall safety of CPT; nevertheless, the number of patients participating in the studies was still limited. It is also important to notice that in all the studies, the majority of patients were also given other medications, such as antivirals, antibiotics and corticosteroid; furthermore, randomized controlled studies involving more patients and in combination with other treatment modalities are urgently needed.


Subject(s)
COVID-19/therapy , Coronavirus Infections/therapy , Influenza, Human/therapy , Severe Acute Respiratory Syndrome/therapy , Adrenal Cortex Hormones/therapeutic use , Anti-Bacterial Agents/therapeutic use , Antiviral Agents/therapeutic use , COVID-19/immunology , COVID-19/mortality , COVID-19/virology , Combined Modality Therapy/methods , Coronavirus Infections/immunology , Coronavirus Infections/mortality , Coronavirus Infections/virology , Humans , Immunization, Passive , Influenza A Virus, H1N1 Subtype/genetics , Influenza A Virus, H1N1 Subtype/immunology , Influenza, Human/immunology , Influenza, Human/mortality , Influenza, Human/virology , Middle East Respiratory Syndrome Coronavirus/drug effects , Middle East Respiratory Syndrome Coronavirus/immunology , Middle East Respiratory Syndrome Coronavirus/pathogenicity , RNA, Viral/antagonists & inhibitors , RNA, Viral/genetics , RNA, Viral/immunology , SARS Virus/drug effects , SARS Virus/immunology , SARS Virus/pathogenicity , SARS-CoV-2/drug effects , SARS-CoV-2/immunology , SARS-CoV-2/pathogenicity , Severe Acute Respiratory Syndrome/immunology , Severe Acute Respiratory Syndrome/mortality , Severe Acute Respiratory Syndrome/virology , Survival Analysis , Treatment Outcome
14.
Trials ; 22(1): 9, 2021 Jan 06.
Article in English | MEDLINE | ID: covidwho-1011237

ABSTRACT

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.


Subject(s)
Antiviral Agents/administration & dosage , COVID-19/therapy , Mesenchymal Stem Cell Transplantation/methods , Respiratory Distress Syndrome/therapy , Administration, Intravenous , Adult , Biomarkers/blood , COVID-19/complications , COVID-19/diagnosis , COVID-19/virology , Clinical Trials, Phase II as Topic , Combined Modality Therapy/adverse effects , Combined Modality Therapy/methods , Double-Blind Method , Female , Humans , Male , Mesenchymal Stem Cell Transplantation/adverse effects , Randomized Controlled Trials as Topic , Respiration, Artificial , Respiratory Distress Syndrome/blood , Respiratory Distress Syndrome/diagnosis , Respiratory Distress Syndrome/virology , SARS-CoV-2/isolation & purification , SARS-CoV-2/pathogenicity , Severity of Illness Index , Spain , Standard of Care , Transplantation, Homologous/adverse effects , Transplantation, Homologous/methods
15.
Trials ; 21(1): 981, 2020 Nov 27.
Article in English | MEDLINE | ID: covidwho-947944

ABSTRACT

BACKGROUND: The COVID-19 pandemic has imposed an enormous burden on health care systems around the world. In the past, the administration of convalescent plasma of patients having recovered from SARS and severe influenza to patients actively having the disease showed promising effects on mortality and appeared safe. Whether or not this also holds true for the novel SARS-CoV-2 virus is currently unknown. METHODS: DAWn-Plasma is a multicentre nation-wide, randomized, open-label, phase II proof-of-concept clinical trial, evaluating the clinical efficacy and safety of the addition of convalescent plasma to the standard of care in patients hospitalized with COVID-19 in Belgium. Patients hospitalized with a confirmed diagnosis of COVID-19 are eligible when they are symptomatic (i.e. clinical or radiological signs) and have been diagnosed with COVID-19 in the 72 h before study inclusion through a PCR (nasal/nasopharyngeal swab or bronchoalveolar lavage) or a chest-CT scan showing features compatible with COVID-19 in the absence of an alternative diagnosis. Patients are randomized in a 2:1 ratio to either standard of care and convalescent plasma (active treatment group) or standard of care only. The active treatment group receives 2 units of 200 to 250 mL of convalescent plasma within 12 h after randomization, with a second administration of 2 units 24 to 36 h after ending the first administration. The trial aims to include 483 patients and will recruit from 25 centres across Belgium. The primary endpoint is the proportion of patients that require mechanical ventilation or have died at day 15. The main secondary endpoints are clinical status on day 15 and day 30 after randomization, as defined by the WHO Progression 10-point ordinal scale, and safety of the administration of convalescent plasma. DISCUSSION: This trial will either provide support or discourage the use of convalescent plasma as an early intervention for the treatment of hospitalized patients with COVID-19 infection. TRIAL REGISTRATION: ClinicalTrials.gov NCT04429854 . Registered on 12 June 2020 - Retrospectively registered.


Subject(s)
Antibodies, Viral/immunology , COVID-19/therapy , SARS-CoV-2/genetics , Adult , Antibodies, Viral/blood , Belgium/epidemiology , COVID-19/diagnosis , COVID-19/epidemiology , COVID-19/virology , Combined Modality Therapy/methods , Female , Global Burden of Disease , Hospitalization/trends , Humans , Immunization, Passive/methods , Male , Mortality , Respiration, Artificial/statistics & numerical data , SARS-CoV-2/immunology , Safety , Standard of Care/statistics & numerical data , Treatment Outcome
16.
Aging (Albany NY) ; 12(22): 22405-22412, 2020 11 20.
Article in English | MEDLINE | ID: covidwho-940612

ABSTRACT

Severe pneumonia caused by COVID-19 has resulted in many deaths worldwide. Here, we analyzed the clinical characteristics of the first 17 reported cases of death due to COVID-19 pneumonia in Wuhan, China. Demographics, initial symptoms, complications, chest computerized tomography (CT) images, treatments, and prognoses were collected and analyzed from the National Health Committee of China data. The first 17 reported deaths from COVID-19 were predominately in older men; 82.35% of patients were older than 65 years, and 76.47% were males. The most common initial symptoms were fever or fatigue (14 cases, 82.35%), respiratory symptoms, such as cough (12 cases, 70.59%), and neurological symptoms, such as headache (3 cases, 17.65%). The most common finding of chest CT was viral pneumonia (5 cases, 29.41%). Anti-infectives (11 cases, 64.71%) and mechanical ventilation (9 cases, 52.94%) were commonly used for treatment. Most of the patients (16 cases, 94.12%) died of acute respiratory distress syndrome (ARDS). Our findings show that advanced age and male gender are effective predictors of COVID-19 mortality, and suggest that early interventions to reduce the incidence of ARDS may improve prognosis of COVID-19 pneumonia patients.


Subject(s)
COVID-19/mortality , Respiratory Distress Syndrome/mortality , SARS-CoV-2/pathogenicity , Aged , Aged, 80 and over , Anti-Infective Agents/therapeutic use , COVID-19/complications , COVID-19/therapy , COVID-19/virology , China/epidemiology , Combined Modality Therapy/methods , Female , Hospital Mortality , Humans , Lung/diagnostic imaging , Male , Middle Aged , Pandemics , Respiration, Artificial/statistics & numerical data , Respiratory Distress Syndrome/diagnosis , Respiratory Distress Syndrome/therapy , Respiratory Distress Syndrome/virology , SARS-CoV-2/isolation & purification , Tomography, X-Ray Computed
17.
Med Hypotheses ; 145: 110353, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-894130

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic, which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has killed more than one million people as of October 1, 2020. Consequently, a search is on for a treatment that can bring the pandemic to an end. However, treatments (vaccine, antiviral, plasma) that are directed at specific viral proteins (RNA polymerase, spike proteins) may not work well against all strains of the virus. Therefore, it is hypothesized that a therapy based on multiple treatments is needed for COVID-19 patients and to bring the pandemic to an end. Here, it is proposed that a combination of cool air therapy (CAT) and purified air technology (PAT) in an oxygen species cool air respirator (OSCAR) could be used to reduce viral (SARS-CoV-2) load and severity of illness in COVID-19 patients through the individual dose-response relationship. In addition, the proposed therapy (CAT + PAT in OSCAR), which works by a more general physical and chemical mechanism, should work well with other treatments (vaccine, antiviral, plasma) that target specific viral proteins (RNA polymerase, spike proteins) to provide a safe and effective multiple therapy approach for ending the COVID-19 pandemic caused by SARS-CoV-2.


Subject(s)
Air , COVID-19/therapy , Combined Modality Therapy/methods , Oxygen/therapeutic use , Antiviral Agents/therapeutic use , Cold Temperature , Humans , Models, Theoretical , Pandemics , Treatment Outcome
18.
BMJ Case Rep ; 13(10)2020 Oct 07.
Article in English | MEDLINE | ID: covidwho-841363

ABSTRACT

In March 2020, a 74-year-old man affected by end-stage renal disease and on peritoneal dialysis was referred to an emergency room in Modena, Northern Italy, due to fever and respiratory symptoms. After ruling out COVID-19 infection, a diagnosis of chronic obstructive pulmonary disease exacerbation was confirmed and he was thus transferred to the nephrology division. Physical examination and blood tests revealed a positive fluid balance and insufficient correction of the uraemic syndrome, although peritoneal dialysis prescription was maximised. After discussion with the patient and his family, the staff decided to start hybrid dialysis, consisting of once-weekly in-hospital haemodialysis and home peritoneal dialysis for the remaining days. He was discharged at the end of the antibiotic course, after an internal jugular vein central venous catheter placement and the first haemodialysis session. This strategy allowed improvement of depuration parameters and avoidance of frequent access to the hospital, which is crucial in limiting exposure to SARS-CoV-2 in an endemic setting.


Subject(s)
Coronavirus Infections , Kidney Failure, Chronic , Pandemics , Peritoneal Dialysis/methods , Pneumonia, Viral , Pulmonary Disease, Chronic Obstructive , Renal Dialysis/methods , Aged , Anti-Bacterial Agents/administration & dosage , Betacoronavirus , COVID-19 , Combined Modality Therapy/methods , Combined Modality Therapy/trends , Coronavirus Infections/diagnosis , Coronavirus Infections/epidemiology , Coronavirus Infections/prevention & control , Diagnosis, Differential , Hemodialysis Units, Hospital , Humans , Infection Control/methods , Kidney Failure, Chronic/diagnosis , Kidney Failure, Chronic/physiopathology , Kidney Failure, Chronic/therapy , Male , Organizational Innovation , Pandemics/prevention & control , Pneumonia, Viral/diagnosis , Pneumonia, Viral/epidemiology , Pneumonia, Viral/prevention & control , Pulmonary Disease, Chronic Obstructive/diagnosis , Pulmonary Disease, Chronic Obstructive/drug therapy , Pulmonary Disease, Chronic Obstructive/physiopathology , SARS-CoV-2 , Symptom Flare Up
19.
J Cardiovasc Med (Hagerstown) ; 21(10): 765-771, 2020 10.
Article in English | MEDLINE | ID: covidwho-745112

ABSTRACT

AIMS: The aim of this study was to evaluate the clinical course of COVID-19 in patients who had recently undergone a cardiac procedure and were inpatients in a cardiac rehabilitation department. METHODS: All patients hospitalized from 1 February to 15 March 2020 were included in the study (n = 35; 16 men; mean age 78 years). The overall population was divided into two groups: group 1 included 10 patients who presented with a clinical picture of COVID-19 infection and were isolated, and group 2 included 25 patients who were COVID-19-negative. In group 1, nine patients were on chronic oral anticoagulant therapy and one patient was on acetylsalicylic acid (ASA) and clopidogrel. A chest computed tomography scan revealed interstitial pneumonia in all 10 patients. RESULTS: During hospitalization, COVID-19 patients received azithromycin and hydroxychloroquine in addition to their ongoing therapy. Only the patient on ASA with clopidogrel therapy was transferred to the ICU for mechanical ventilation because of worsening respiratory failure, and subsequently died from cardiorespiratory arrest. All other patients on chronic anticoagulant therapy recovered and were discharged. CONCLUSION: Our study suggests that COVID-19 patients on chronic anticoagulant therapy may have a more favorable and less complicated clinical course. Further prospective studies are warranted to confirm this preliminary observation.


Subject(s)
Anticoagulants/therapeutic use , Azithromycin/administration & dosage , Cardiac Surgical Procedures , Coronavirus Infections , Hydroxychloroquine/administration & dosage , Pandemics , Platelet Aggregation Inhibitors/therapeutic use , Pneumonia, Viral , Postoperative Complications , Aged , Anti-Infective Agents/administration & dosage , COVID-19 , Cardiac Surgical Procedures/adverse effects , Cardiac Surgical Procedures/methods , Combined Modality Therapy/methods , Coronavirus Infections/blood , Coronavirus Infections/diagnosis , Coronavirus Infections/mortality , Coronavirus Infections/physiopathology , Female , Humans , Male , Outcome and Process Assessment, Health Care , Pneumonia, Viral/blood , Pneumonia, Viral/diagnosis , Pneumonia, Viral/etiology , Pneumonia, Viral/mortality , Pneumonia, Viral/physiopathology , Postoperative Complications/blood , Postoperative Complications/prevention & control , Postoperative Complications/virology , Tomography, X-Ray Computed/methods
20.
Medicine (Baltimore) ; 99(35): e21927, 2020 Aug 28.
Article in English | MEDLINE | ID: covidwho-740206

ABSTRACT

BACKGROUND: The number of patients infected with novel coronavirus disease (COVID-19) has exceeded 10 million in 2020, and a large proportion of them are asymptomatic. At present, there is still no effective treatment for this disease. Traditional Chinese medicine (TCM) shows a good therapeutic effect on COVID-19, especially for asymptomatic patients. According to the search results, we found that although there are many studies on COVID-19, there are no studies targeting asymptomatic infections. Therefore, we design a network meta-analysis (NMA) to evaluate the therapeutic effect of TCM on asymptomatic COVID-19. METHODS: We will search Chinese and English databases to collect all randomized controlled trials (RCTs) of TCM combined with conventional western medicine or using only TCM to treat asymptomatic COVID-19 from December 2019 to July 2020. Then, two investigators will independently filter the articles, extract data, and evaluate the risk of bias. We will conduct a Bayesian NMA to evaluate the effects of different therapies. All data will be processed by Stata 16.0 and WinBUGS. RESULTS: This study will evaluate the effectiveness of various treatments for asymptomatic COVID-19. The outcome indicators include the time when the nucleic acid turned negative, the proportion of patients with disease progression, changes in laboratory indicators, and the side effects of drugs. CONCLUSION: This analysis will further improve the treatment of asymptomatic COVID-19. INPLASY REGISTRATION NUMBER: INPLASY202070022.


Subject(s)
Combined Modality Therapy/methods , Coronavirus Infections/therapy , Medicine, Chinese Traditional/methods , Pneumonia, Viral/therapy , Asymptomatic Infections/therapy , Bayes Theorem , Betacoronavirus/drug effects , Betacoronavirus/isolation & purification , COVID-19 , Coronavirus Infections/drug therapy , Humans , Network Meta-Analysis , Pandemics , Research Design , SARS-CoV-2 , Treatment Outcome
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