Comparison of two antifibrotic treatments for lung fibrosis in post-COVID-19 syndrome: A randomized, prospective study.

BACKGROUND: Although pulmonary fibrosis secondary to COVID-19 infection is uncommon, it can lead to problems if not treated effectively in the early period. This study aimed to compare the effects of treatment with nintedanib and pirfenidone in patients with COVID-19-related fibrosis. METHODS: Thirty patients who presented to the post-COVID outpatient clinic between May 2021 and April 2022 with a history of COVID-19 pneumonia and exhibited persistent cough, dyspnea, exertional dyspnea, and low oxygen saturation at least 12 weeks after diagnosis were included. The patients were randomized to receive off-label treatment with nintedanib or pirfenidone and were followed up for 12 weeks. RESULTS: After 12 weeks of treatment, all pulmonary function test (PFT) parameters, 6MWT distance, and oxygen saturation were increased compared to baseline in both the pirfenidone group and nintedanib groups, while heart rate and radiological score levels were decreased (p<0.05 for all). The changes in 6MWT distance and oxygen saturation were significantly greater in the nintedanib group than in the pirfenidone group (p=0.02 and 0.005, respectively). Adverse drug effects were more frequent with nintedanib than pirfenidone, with the most common being diarrhea, nausea, and vomiting. CONCLUSION: In patients with interstitial fibrosis after COVID-19 pneumonia, both nintedanib and pirfenidone were observed to be effective in improving radiological score and PFT parameters. Nintedanib was more effective than pirfenidone in increasing exercise capacity and saturation values but caused more adverse drug effects.

The safety and efficacy of melatonin in the treatment of COVID-19: A systematic review and meta-analysis.

BACKGROUND: As an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the common signs of coronavirus disease 2019 (COVID-19) are respiratory symptoms, fever, cough, shortness of breath, and dyspnea, with multiple organ injuries in severe cases. Therefore, finding drugs to prevent and treat COVID-19 is urgently needed and expected by the public. Several studies suggested beneficial effects of melatonin for the relevant prevention and treatment. To explore the effect and safety of melatonin in the treatment and provide theoretical support and reference for seeking the most suitable drug for COVID-19, the meta-analysis was carried out accordingly. METHODS: It included randomized clinical trials of patients with COVID-19 treated with melatonin. Total effective rate was the primary outcome, while C-reactive protein (CRP), arterial oxygen saturation (SaO2), white blood cell count (WBC) were the secondary measures. Random-effect and fixed-effect models were used to evaluate the effect size of some indicators in this meta-analysis. RESULTS: Six eligible studies with 338 participants were included. One hundred seventy subjects were treated with melatonin adjuvant therapy and 168 subjects were assigned to the control group, with total excellent effective rate in subjects treated with melatonin [odds ratio = 3.05, 95 % confidence interval (CI) = 1.47, 6.31, P = .003]. Homogeneity was analyzed by fixed effect model (I2 = 0%). There was no significant difference in CRP between the melatonin group and the control group (weighted mean difference [WMD] = -0.36, 95% CI = -3.65, 2.92, P = .83). Significant difference was not existed in SaO2 between the melatonin treatment group and the control group (WMD = 1, 95% CI = -1.21, 3.22, P = .37). In terms of WBC, there was no significant difference between the 2 groups (WMD = -1.07, 95% CI = -2.44, 0.30, P = .13). CONCLUSIONS: The meta-analysis showed that melatonin had the beneficial effects for COVID-19 prevention and treatment as an adjunctive agent in combination with basic treatment for the treatment.

Low dose of morphine to relieve dyspnea in acute respiratory failure (OpiDys): protocol for a double-blind randomized controlled study.

BACKGROUND: Dyspnea is common and severe in intensive care unit (ICU) patients managed for acute respiratory failure. Dyspnea appears to be associated with impaired prognosis and neuropsychological sequels. Pain and dyspnea share many similarities and previous studies have shown the benefit of morphine on dyspnea in patients with end-stage onco-hematological disease and severe heart or respiratory disease. In these populations, morphine administration was safe. Here, we hypothesize that low-dose opioids may help to reduce dyspnea in patients admitted to the ICU for acute respiratory failure. The primary objective of the trial is to determine whether the administration of low-dose titrated opioids, compared to placebo, in patients admitted to the ICU for acute respiratory failure with severe dyspnea decreases the mean 24-h intensity of dyspnea score. METHODS: In this single-center double-blind randomized controlled trial with 2 parallel arms, we plan to include 22 patients (aged 18-75 years) on spontaneous ventilation with either non-invasive ventilation, high flow oxygen therapy or standard oxygen therapy admitted to the ICU for acute respiratory failure with severe dyspnea. They will be assigned after randomization with a 1:1 allocation ratio to receive in experimental arm administration of low-dose titrated morphine hydrochloride for 24 h consisting in an intravenous titration relayed subcutaneously according to a predefined protocol, or a placebo (0.9% NaCl) administered according to the same protocol in the control arm. The primary endpoint is the mean 24-h dyspnea score assessed by a visual analog scale of dyspnea. DISCUSSION: To our knowledge, this study is the first to evaluate the benefit of opioids on dyspnea in ICU patients admitted for acute respiratory failure. TRIAL REGISTRATION: ClinicalTrials.gov NCT04358133 . Registered on 24 April 2020.

Efficacy and Safety of Lianhua Qingwen for Patients with COVID-19: A Systematic Review and Meta-Analysis.

BACKGROUND: Corona virus disease 2019 (COVID-19) has spread around the world since its outbreak, and there is no ascertained effective drug up to now. Lianhua Qingwen (LHQW) has been widely used in China and overseas Chinese, which had some advantages in the treatment of COVID-19. OBJECTIVE: To evaluate the efficacy and safety of LHQW for COVID-19 by conducting a systematic review with meta-analysis. METHODS: A comprehensive literature search was conducted in 12 electronic databases from their establishment to October 30, 2021. Note Express 3.2.0 was used for screening of trials, and the data was independently extracted in duplicate by 2 researchers. The risk of bias of randomized controlled trials (RCTs) and retrospective studies were assessed by using the Cochrane collaboration tool and Newcastle Ottawa Scale, respectively, followed by data analysis using RevMan 5.3. The RCTs or retrospective studies to treat COVID-19 using LHQW were included. The intervention measures in the experimental group were LHQW alone or combined with chemical drugs (LCWC), and that in the control group were chemical drugs (CDs). Outcome measures included computed tomography (CT) recovery rate, disappearance rates of primary (fever, cough, fatigue), respiratory, gastrointestinal and other symptoms, exacerbation rate and adverse reaction. Subgroup analysis was conducted according to whether LHQW was combined with CDs and the different treatment methods in the control group. RESULTS: Nine trials with 1,152 participants with COVID-19 were included. The CT recovery rates of LHQW and LCWC were 1.36 and 1.32 times of CDs, respectively (P<0.05). Compared with CDs, LCWC remarkably increased the disappearance rates of fever, cough, fatigue, expectoration, shortness of breath, and muscle soreness (P<0.05). LHQW also obviously decreased the exacerbation rate, which was 0.45 times of CDs alone (P<0.05). There was no obvious difference between LCWC and CDs in adverse reaction (P>0.05). CONCLUSIONS: LHQW was more suitable for treating COVID-19 patients with obvious expectoration, shortness of breath and muscle soreness. LHQW had advantages in treating COVID-19 with no obvious exacerbation. (PROSPERO No. CRD42021235937).

Efficacy and Safety of ELOM-080 as Add-On Therapy in COVID-19 Patients with Acute Respiratory Insufficiency: Exploratory Data from the Prospective Placebo-Controlled COVARI Trial.

INTRODUCTION: Enhancement of mucociliary clearance (MCC) might be a potential target in treating COVID-19. The phytomedicine ELOM-080 is an MCC enhancer that is used to treat inflammatory respiratory diseases. PATIENTS/METHODS: This randomised, double-blind exploratory study (EudraCT number 2020-003779-17) evaluated 14 days' add-on therapy with ELOM-080 versus placebo in patients with COVID-19 hospitalised with acute respiratory insufficiency. RESULTS: The trial was terminated early after enrolment of 47 patients as a result of poor recruitment. Twelve patients discontinued prematurely, leaving 35 in the per-protocol set (PPS). Treatment with ELOM-080 had no significant effect on overall clinical status versus placebo (p = 0.49). However, compared with the placebo group, patients treated with ELOM-080 had less dyspnoea in the second week of hospitalisation (p = 0.0035), required less supplemental oxygen (p = 0.0229), and were more often without dyspnoea when climbing stairs at home (p < 0.0001). CONCLUSION: These exploratory data suggest the potential for ELOM-080 to improve respiratory status during and after hospitalisation in patients with COVID-19.

Clinical and laboratory factors associated with coronavirus disease 2019 (Covid-19): A systematic review and meta-analysis.

SARS Coronavirus-2 is one of the most widespread viruses globally during the 21st century, whose severity and ability to cause severe pneumonia and death vary. We performed a comprehensive systematic review of all studies that met our standardised criteria and then extracted data on the age, symptoms, and different treatments of Covid-19 patients and the prognosis of this disease during follow-up. Cases in this study were divided according to severity and death status and meta-analysed separately using raw mean and single proportion methods. We included 171 complete studies including 62,909 confirmed cases of Covid-19, of which 148 studies were meta-analysed. Symptoms clearly emerged in an escalating manner from mild-moderate symptoms, pneumonia, severe-critical to the group of non-survivors. Hypertension (Pooled proportion (PP): 0.48 [95% Confident interval (CI): 0.35-0.61]), diabetes (PP: 0.23 [95% CI: 0.16-0.33]) and smoking (PP: 0.12 [95% CI: 0.03-0.38]) were highest regarding pre-infection comorbidities in the non-survivor group. While acute respiratory distress syndrome (PP: 0.49 [95% CI: 0.29-0.78]), (PP: 0.63 [95% CI: 0.34-0.97]) remained one of the most common complications in the severe and death group respectively. Bilateral ground-glass opacification (PP: 0.68 [95% CI: 0.59-0.75]) was the most visible radiological image. The mortality rates estimated (PP: 0.11 [95% CI: 0.06-0.19]), (PP: 0.03 [95% CI: 0.01-0.05]), and (PP: 0.01 [95% CI: 0-0.3]) in severe-critical, pneumonia and mild-moderate groups respectively. This study can serve as a high evidence guideline for different clinical presentations of Covid-19, graded from mild to severe, and for special forms like pneumonia and death groups.

Is carbonic anhydrase inhibition useful as a complementary therapy of Covid-19 infection?

The ongoing Covid-19 is a contagious disease, and it is characterised by different symptoms such as fever, cough, and shortness of breath. Rising concerns about Covid-19 have severely affected the healthcare system in all countries as the Covid-19 outbreak has developed at a rapid rate all around the globe. Intriguing, a clinically used drug, acetazolamide (a specific inhibitor of carbonic anhydrase, CA, EC 4.2.1.1), is used to treat high-altitude pulmonary oedema (HAPE), showing a high degree of clinical similarities with the pulmonary disease caused by Covid-19. In this context, this preliminary study aims to provide insights into some factors affecting the Covid-19 patients, such as hypoxaemia, hypoxia as well as the blood CA activity. We hypothesise that patients with Covid-19 problems could show a dysregulated acid-base status influenced by CA activity. These preliminary results suggest that the use of CA inhibitors as a pharmacological treatment for Covid-19 may be beneficial.

Effect of High-Dose Zinc and Ascorbic Acid Supplementation vs Usual Care on Symptom Length and Reduction Among Ambulatory Patients With SARS-CoV-2 Infection: The COVID A to Z Randomized Clinical Trial.

Importance: There is limited evidence regarding early treatment of novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection to mitigate symptom progression. Objective: To examine whether high-dose zinc and/or high-dose ascorbic acid reduce the severity or duration of symptoms compared with usual care among ambulatory patients with SARS-CoV-2 infection. Design, Setting, and Participants: This multicenter, single health system randomized clinical factorial open-label trial enrolled 214 adult patients with a diagnosis of SARS-CoV-2 infection confirmed with a polymerase chain reaction assay who received outpatient care in sites in Ohio and Florida. The trial was conducted from April 27, 2020, to October 14, 2020. Intervention: Patients were randomized in a 1:1:1:1 allocation ratio to receive either 10 days of zinc gluconate (50 mg), ascorbic acid (8000 mg), both agents, or standard of care. Outcomes: The primary end point was the number of days required to reach a 50% reduction in symptoms, including severity of fever, cough, shortness of breath, and fatigue (rated on a 4-point scale for each symptom). Secondary end points included days required to reach a total symptom severity score of 0, cumulative severity score at day 5, hospitalizations, deaths, adjunctive prescribed medications, and adverse effects of the study supplements. Results: A total of 214 patients were randomized, with a mean (SD) age of 45.2 (14.6) years and 132 (61.7%) women. The study was stopped for a low conditional power for benefit with no significant difference among the 4 groups for the primary end point. Patients who received usual care without supplementation achieved a 50% reduction in symptoms at a mean (SD) of 6.7 (4.4) days compared with 5.5 (3.7) days for the ascorbic acid group, 5.9 (4.9) days for the zinc gluconate group, and 5.5 (3.4) days for the group receiving both (overall P = .45). There was no significant difference in secondary outcomes among the treatment groups. Conclusions and Relevance: In this randomized clinical trial of ambulatory patients diagnosed with SARS-CoV-2 infection, treatment with high-dose zinc gluconate, ascorbic acid, or a combination of the 2 supplements did not significantly decrease the duration of symptoms compared with standard of care. Trial Registration: ClinicalTrials.gov Identifier: NCT04342728.

Prevalence and correlates of chronic fatigue syndrome and post-traumatic stress disorder after the outbreak of the COVID-19.

As the SARS-COV-2 becomes a global pandemic, many researchers have a concern about the long COVID-19 complications. Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a persistent, debilitating, and unexplained fatigue disorder. We investigated psychological morbidities such as CFS and post-traumatic stress disorder (PTSD) among survivors of COVID-19 over 6 months. All COVID-19 survivors from the university-affiliated hospital of Tehran, Iran, were assessed 6 months after infection onset by a previously validated questionnaire based on the Fukuda guidelines for CFS/EM and DSM-5 Checklist for PTSD (The Post-traumatic Stress Disorder Checklist for DSM-5 or PCL-5) to determine the presence of stress disorder and chronic fatigue problems. A total of 120 patients were enrolled. The prevalence rate of fatigue symptoms was 17.5%. Twelve (10%) screened positive for chronic idiopathic fatigue (CIF), 6 (5%) for CFS-like with insufficient fatigue syndrome (CFSWIFS), and 3 (2.5%) for CFS. The mean total scores in PCL-5 were 9.27 ± 10.76 (range:0-44), and the prevalence rate of PTSD was 5.8%. There was no significant association after adjusting between CFS and PTSD, gender, comorbidities, and chloroquine phosphate administration. The obtained data revealed the prevalence of CFS among patients with COVID-19, which is almost similar to CFS prevalence in the general population. Moreover, PTSD in patients with COVID-19 is not associated with the increased risk of CFS. Our study suggested that medical institutions should pay attention to the psychological consequences of the COVID-19 outbreak.

Opsoclonus-myoclonus syndrome, a post-infectious neurologic complication of COVID-19: case series and review of literature.

Opsoclonus-myoclonus-ataxia syndrome is a heterogeneous constellation of symptoms ranging from full combination of these three neurological findings to varying degrees of isolated individual sign. Since the emergence of coronavirus disease 2019 (COVID-19), neurological symptoms, syndromes, and complications associated with this multi-organ viral infection have been reported and the various aspects of neurological involvement are increasingly uncovered. As a neuro-inflammatory disorder, one would expect to observe opsoclonus-myoclonus syndrome after a prevalent viral infection in a pandemic scale, as it has been the case for many other neuro-inflammatory syndromes. We report seven cases of opsoclonus-myoclonus syndrome presumably parainfectious in nature and discuss their phenomenology, their possible pathophysiological relationship to COVID-19, and diagnostic and treatment strategy in each case. Finally, we review the relevant data in the literature regarding the opsoclonus-myoclonus syndrome and possible similar cases associated with COVID-19 and its diagnostic importance for clinicians in various fields of medicine encountering COVID-19 patients and its complications.

Meningoencephalitis associated with COVID-19: a systematic review.

With the growing number of COVID-19 cases in recent times. significant set of patients with extra pulmonary symptoms has been reported worldwide. Here we venture out to summarize the clinical profile, investigations, and radiological findings among patients with SARS-CoV-2-associated meningoencephalitis in the form of a systemic review. This review was carried out based on the existing PRISMA (Preferred Report for Systematic Review and Meta analyses) consensus statement. The data for this review was collected from four databases: Pubmed/Medline, NIH Litcovid, Embase, and Cochrane library and Preprint servers up till 30 June 2020. Search strategy comprised of a range of keywords from relevant medical subject headings which includes "SARS-COV-2," "COVID-19," and "meningoencephalitis." All peer reviewed, case-control, case report, pre print articles satisfying our inclusion criteria were involved in the study. Quantitative data was expressed in mean ± SD, while the qualitative date in percentages. Paired t test was used for analysing the data based on differences between mean and respective values with a p < 0.05 considered to be statistically significant. A total of 61 cases were included from 25 studies after screening from databases and preprint servers, out of which 54 of them had completed investigation profile and were included in the final analysis. Clinical, laboratory findings, neuroimaging abnormalities, and EEG findings were analyzed in detail. This present review summarizes the available evidences related to the occurrence of meningoencephalitis in COVID-19.

Multiple potential targets of opioids in the treatment of acute respiratory distress syndrome from COVID-19.

COVID-19 can present with a variety of clinical features, ranging from asymptomatic or mild respiratory symptoms to fulminant acute respiratory distress syndrome (ARDS) depending on the host's immune responses and the extent of the associated pathologies. This implies that several measures need to be taken to limit severely impairing symptoms caused by viral-induced pathology in vital organs. Opioids are most exploited for their analgesic effects but their usage in the palliation of dyspnoea, immunomodulation and lysosomotropism may represent potential usages of opioids in COVID-19. Here, we describe the mechanisms involved in each of these potential usages, highlighting the benefits of using opioids in the treatment of ARDS from SARS-CoV-2 infection.

An audit of end-of-life symptom control in patients with corona virus disease 2019 (COVID-19) dying in a hospital in the United Kingdom.

BACKGROUND: The literature contains limited information on the problems faced by dying patients with COVID-19 and the effectiveness of interventions to manage these. AIM: The aim of this audit was to assess the utility of our end-of-life care plan, and specifically the effectiveness of our standardised end-of-life care treatment algorithms, in dying patients with COVID-19. DESIGN: The audit primarily involved data extraction from the end-of-life care plan, which includes four hourly nursing (ward nurses) assessments of specific problems: patients with problems were managed according to standardised treatment algorithms, and the intervention was deemed to be effective if the problem was not present at subsequent assessments. SETTING/PARTICIPANTS: This audit was undertaken at a general hospital in England, covered the 8 weeks from 16 March to 11 May 2020 and included all inpatients with COVID-19 who had an end-of-life care plan (and died). RESULTS: Sixty-one patients met the audit criteria: the commonest problem was shortness of breath (57.5%), which was generally controlled with conservative doses of morphine (10-20 mg/24 h via a syringe pump). Cough and audible respiratory secretions were relatively uncommon. The second most common problem was agitation/delirium (55.5%), which was generally controlled with standard pharmacological interventions. The cumulative number of patients with shortness of breath, agitation and audible respiratory secretions increased over the last 72 h of life, but most patients were symptom controlled at the point of death. CONCLUSION: Patients dying of COVID-19 experience similar end-of-life problems to other groups of patients. Moreover, they generally respond to standard interventions for these end-of-life problems.

End-of-life care in COVID-19: An audit of pharmacological management in hospital inpatients.

BACKGROUND: Hospital clinicians have had to rapidly develop expertise in managing the clinical manifestations of COVID-19 including symptoms common at the end of life, such as breathlessness and agitation. There is limited evidence exploring whether end-of-life symptom control in this group requires new or adapted guidance. AIM: To review whether prescribing for symptom control in patients dying with COVID-19 adhered to existing local guidance or whether there was deviation which may represent a need for revised guidance or specialist support in particular patient groups. DESIGN/SETTING: A retrospective review of the electronic patient record of 61 hospital inpatients referred to the specialist palliative care team with swab-confirmed COVID-19 who subsequently died over a 1-month period. Intubated patients were excluded. RESULTS: In all, 83% (40/48) of patients were prescribed opioids at a starting dose consistent with existing local guidelines. In seven of eight patients where higher doses were prescribed, this was on specialist palliative care team advice. Mean total opioid dose required in the last 24 h of life was 14 mg morphine subcutaneous equivalent, and mean total midazolam dose was 9.5 mg. For three patients in whom non-invasive ventilation was in place higher doses were used. CONCLUSION: Prescription of end-of-life symptom control drugs for COVID-19 fell within the existing guidance when supported by specialist palliative care advice. While some patients may require increased doses, routine prescription of higher starting opioid and benzodiazepine doses beyond existing local guidance was not observed.

Treatment of SARS-CoV-2 with high dose oral zinc salts: A report on four patients.

Coronavirus 2019 (COVID-19) is a pandemic with substantial mortality and no accepted therapy. We report here on four consecutive outpatients with clinical characteristics (CDC case definition) of and/or laboratory-confirmed COVID-19 who were treated with high dose zinc salt oral lozenges. All four patients experienced significant improvement in objective and symptomatic disease measures after one day of high dose therapy suggesting that zinc therapy was playing a role in clinical recovery. A mechanism for zinc's effects is proposed based on previously published studies on SARS- CoV-1, and randomized controlled trials assessing zinc shortening of common cold duration. The limited sample size and study design preclude a definitive statement about the effectiveness of zinc as a treatment for COVID-19 but suggest the variables to be addressed to confirm these initial findings in future trials.