Efficacy of oral amantadine among patients hospitalised with COVID-19: A randomised, double-blind, placebo-controlled, multicentre study

Background Amantadine has been proposed as a treatment for COVID-19 because it shows anti-SARS-CoV-2 activity in vitro. However, to date, no controlled study has assessed the safety and efficacy of amantadine in COVID-19. Research question Whether amantadine is effective and safe among patients with different COVID-19 severity classifications. Study design and Methods: This was multi-centre, randomised, placebo-controlled study.Patients with oxygen saturation ≤94% and no need for high-flow oxygen or ventilatory support were randomly allocated to receive oral amantadine or placebo (1:1) for 10 days in addition to standard care. The primary endpoint was time to recovery assessed over 28 days since randomisation, defined as discharge from hospital or no need for supplemental oxygen. Results The study was terminated early due to a lack of efficacy after an interim analysis. Final data from 95 patients who received amantadine (mean age, 60.2 years;65% male;66% with comorbidities) and 91 patients who received placebo (mean age, 55.8 years;60% male;68% with comorbidities) were obtained. The median (95% CI) time to recovery was 10 days both in the amantadine (9–11) and placebo arms (8–11;subhazard ratio = 0.94 [95%CI 0.7–1.3]). The percentage of deaths and percentage of patients who required intensive care at 14 and 28 days did not significantly differ between the amantadine and placebo groups. Interpretation Adding amantadine to standard care in patients hospitalised with COVID-19 did not increase the likelihood of recovery. Clinical trial registration ClinicalTrials.gov;No.: NCT04952519;www.clinicaltrials.gov.

Efficacy of oral amantadine among patients hospitalised with COVID-19: A randomised, double-blind, placebo-controlled, multicentre study.

BACKGROUND: Amantadine has been proposed as a treatment for COVID-19 because it shows anti-SARS-CoV-2 activity in vitro. However, to date, no controlled study has assessed the safety and efficacy of amantadine in COVID-19. RESEARCH QUESTION: Whether amantadine is effective and safe among patients with different COVID-19 severity classifications. STUDY DESIGN: and Methods: This was multi-centre, randomised, placebo-controlled study.Patients with oxygen saturation ≤94% and no need for high-flow oxygen or ventilatory support were randomly allocated to receive oral amantadine or placebo (1:1) for 10 days in addition to standard care. The primary endpoint was time to recovery assessed over 28 days since randomisation, defined as discharge from hospital or no need for supplemental oxygen. RESULTS: The study was terminated early due to a lack of efficacy after an interim analysis. Final data from 95 patients who received amantadine (mean age, 60.2 years; 65% male; 66% with comorbidities) and 91 patients who received placebo (mean age, 55.8 years; 60% male; 68% with comorbidities) were obtained. The median (95% CI) time to recovery was 10 days both in the amantadine (9-11) and placebo arms (8-11; subhazard ratio = 0.94 [95%CI 0.7-1.3]). The percentage of deaths and percentage of patients who required intensive care at 14 and 28 days did not significantly differ between the amantadine and placebo groups. INTERPRETATION: Adding amantadine to standard care in patients hospitalised with COVID-19 did not increase the likelihood of recovery. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT04952519; www. CLINICALTRIALS: gov.

Spirometry during the SARS-CoV-2 pandemic. Guidelines and practical advice from the expert panel of Respiratory Physiopathology Assembly of Polish Respiratory Society.

At the end of 2019, in Wuhan, the Hubei Province's capital city in China, the first cases of COVID-19 disease caused by the novel coronavirus, SARS-CoV-2, were described. The rapid spread of the infection through the world resulted in the World Health Organization announcing the COVID-19 a global pandemic in March 2020. The main routes of transmission of the novel coronavirus SARS-CoV-2, according to current evidence, are via droplets inhalation, direct contact with contaminated surfaces, and transmission via the mucous membranes of the mouth, nose, and eyes, and probably through airborne particles from the respiratory tract, generated during coughing and sneezing of infected individuals. During the pulmonary function testing (PFTs), which require strenuous breathing maneuvers and generate high-intensity airflow, aerosols, and micro-aerosols are formed from respiratory secretions and may contain viral and bacterial particles. Therefore, such forced respiratory maneuvers pose a significant risk of spreading the infection to patients and laboratory staff. According to current knowledge, the source of infection may also be an asymptomatic and a pre-symptomatic individual. Coronavirus SARS-CoV-2 has been increasingly prevalent in the community, and this increases a potential risk to all patients tested lung function and staff working there. As the patients' and staff's safety is of unprecedented importance, the additional precautions when performing pulmonary function tests are necessary and unquestionable. In consequence, the greater availability of consumables and personal protective equipment is indispensable. The reorganization of daily practice will prolong test time, reduce the number of tests performed, and slow down patients' flow. The guidance provides practical advice to health care professionals on performing pulmonary function tests during the COVID-19 pandemic. It has been developed basing on currently available information and recommendations from relevant health care institutions. As the COVID-19 pandemic is a rapidly evolving situation and the new scientific data has been becoming are available, the guidance will be updated over time.

Treatment of acute respiratory failure in the course of COVID-19. Practical hints from the expert panel of the Assembly of Intensive Care and Rehabilitation of the Polish Respiratory Society.

In 2019, a pandemic began due to infection with a novel coronavirus, SARS-CoV-2. In many cases, this coronavirus leads to the development of the COVID-19 disease. Lung damage in the course of this disease often leads to acute hypoxic respiratory failure and may eventually lead to acute respiratory distress syndrome (ARDS). Respiratory failure as a result of COVID-19 can develop very quickly and a small percent of those infected will die because of it. There is currently no treatment for COVID-19, therefore the key therapeutic intervention centers around the symptomatic treatment of respiratory failure. The main therapeutic goal is to main-tain gas exchange, mainly oxygenation, at an appropriate level and prevent the intensification of changes in the lung parenchyma. Depending on the severity of hypoxemia different techniques can be used to improve oxygenation. Medical staff dealing with COVID-19 patients should be familiar with both, methods used to treat respiratory failure and the epidemiological risks arising from their use. In some patients, conventional (passive) oxygen therapy alone is sufficient. In patients with worsening respiratory failure high flow nasal oxygen therapy (HFNOT) may be effective. The continuous positive airway pressure (CPAP) and non-invasive ventilation (NIV) methods can be used to a limited extent. With further disease progression, invasive ventilation must be used and in special situations, extracorporeal membrane oxygenation (ECMO) can also be administered. The authors of this article set themselves the goal of presenting the most current knowledge about the epidemiology and patho-physiology of respiratory failure in COVID-19, as well as the methods of its treatment. Given the dynamics of the developing pandemic, this is not an easy task as new scientific data is presented almost every day. However, we believe the knowledge contained in this study will help doctors care for patients with COVID-19. The main target audience of this study is not so much pneumonologists or intensivists who have extensive experience in the application of the techniques discussed here, but rather doctors of other specializations who must master new skills in order to help patients during the time of a pandemic.