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Actual Mortality Rate of COVID-19-Affected Adults Is Less Than What Was Previously Reported

AHA Publisher — Wed, 10 Jun 2020 07:00:18 +0000

Wolters Kluwer Health via News-Medical Net – An online first study published in Critical Care Medicine indicates the actual mortality rate of adults with critical illness from COVID-19 is less than what was previously reported. Compared to earlier reports of a 50 percent mortality rate, the study finds that the mortality rate of critically ill patients who required mechanical ventilation was only 35.7 percent. About 60 percent of patients observed in the study survived to hospital discharge. The study observed patients 18 years and older from six COVID-19 designated intensive care units in three hospitals in Atlanta, Ga. from March to April 2020. The authors note that several considerations may have influenced the outcomes of the study including that all critically ill patients with COVID-19 in the hospital network were admitted to pre-existing ICUs that had adequate staffing ratios and equipment. An accompanying online first editorial examines the role of mainstream and social media in creating the narrative that intubation and mechanical ventilation were “the cause of suboptimal outcomes” for critically ill COVID-19 patients, without accounting for hospital staffing and equipment shortages. To read the original article click here.

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Wuhan Study Shows Lying Face Down Improves Breathing in Severe COVID-19

AHA Publisher — Wed, 25 Mar 2020 07:00:51 +0000

American Thoracic Society via EurekAlert – In a new study of patients with severe COVID-19 (SARS-CoV-2) hospitalized on ventilators, researchers found that lying face down was better for the lungs. March 24, 2020– The research letter was published online in the American Thoracic Society’s American Journal of Respiratory and Critical Care Medicine. In “Lung Recruitability in SARS–CoV-2 Associated Acute Respiratory Distress Syndrome: A Single-Center, Observational Study,” Haibo Qiu, MD, Chun Pan, MD, and co-authors report on a retrospective study of the treatment of 12 patients in Wuhan Jinyintan Hospital, China, with severe COVID-19 infection-related acute respiratory distress syndrome (ARDS) who were assisted by mechanical ventilation. Drs. Qiu and Pan were in charge of the treatment of these patients, who were transferred from other treatment centers to Jinyintan Hospital. A majority of patients admitted to the ICU with confirmed COVID-19 developed ARDS. The observational study took place during a six-day period the week of Feb. 18, 2020. “This study is the first description of the behavior of the lungs in patients with severe COVID-19 requiring mechanical ventilation and receiving positive pressure,” said Dr. Qiu, professor, Department of Critical Care Medicine, Zhangda Hospital, School of Medicine, Southeast University, Nanjing, China. “It indicates that some patients do not respond well to high positive pressure and respond better to prone positioning in bed (facing downward).” The clinicians in Wuhan used an index, the Recruitment-to-Inflation ratio, that measures the response of lungs to pressure (lung recruitability). Members of the research team, Lu Chen, PhD, and Laurent Brochard, PhD, HDR, from the University of Toronto, developed this index prior to this study. The researchers assessed the effect of body positioning. Prone positioning was performed for 24-hour periods in which patients had persistently low levels of blood oxygenation. Oxygen flow, lung volume and airway pressure were measured by devices on patients’ ventilators. Other measurements were taken, including the aeration of their airway passages and calculations were done to measure recruitability. Seven patients received at least one session of prone positioning. Three patients received both prone positioning and ECMO (life support, replacing the function of heart and lungs). Three patients died. Patients who did not receive prone positioning had poor lung recruitability, while alternating supine (face upward) and prone positioning was associated with increased lung recruitability. “It is only a small number of patients, but our study shows that many patients did not re-open their lungs under high positive pressure and may be exposed to more harm than benefit in trying to increase the pressure,” said Chun Pan, MD, also a professor with Zhongda Hospital, School of Medicine, Southeast University. “By contrast, the lung improves when the patient is in the prone position. Considering this can be done, it is important for the management of patients with severe COVID-19 requiring mechanical ventilation.” The team consisted of scientists and clinicians affiliated with four Chinese and two Canadian hospitals, medical schools and universities. To read the original article click here.

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Huge WHO Trial of COVID-19 Therapies Begins

AHA Publisher — Tue, 24 Mar 2020 07:00:21 +0000

Dr. Liji Thomas, MD via News-Medical Net – As the world reels from the devastating impact and the looming threat of the novel coronavirus COVID-19, researchers around the globe are racing to find a cure that will reduce symptom severity and reverse the course of the disease, freeing up more hospital space and making it possible to treat more of the severely affected cases. A large trial In tune with this, the World Health Organization (WHO) has commenced a large trial of four treatments that hold the most significant promise of controlling the coronavirus. This is a trial without precedent, with researchers from multiple locations working in unison to collate as much data on the efficacy of these treatments, even while the pandemic is raging. The study is designed with the greatest simplicity, to include thousands of patients in dozens of countries. It is an intentional plan to enable the most overwhelmed hospitals to take part in the trial to collect the most results possible within the shortest time frame. Recycling Drugs The shortest route to developing effective treatments for the virus is to look at existing drugs, either those that are already approved for other diseases, as well as those that are not yet approved but have been shown to help relieve the disease in animal models of the two previous coronavirus epidemics, namely, severe acute respiratory syndrome (SARS) and Middle East Respiratory Syndrome (MERS). The hope is to find that one or more of these drugs will slow down or kill the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This would play a significant role in saving many critically ill patients, but would also protect thousands upon thousands of healthcare professionals and other associated workers who put their lives at risk each moment they are in their workplace. Also, effective treatments could also push down the time spent by patients in intensive care, making more beds available for those who need it. The Trial The participants in the trial, called SOLIDARITY, will be any patient who is confirmed to have COVID-19 and fulfills the eligibility criteria as decided by the treating physician. After informed consent procedures are completed, the patient’s details are then entered into a website set up specifically for the trial by the WHO. The physician lists the hospital’s available drugs from the four being studied in the trial, and the website randomizes the patient to either one of these drugs or the local standard care being offered for the infection. This completes the enrolment procedure for the trial. The only remaining details, according to one of WHO’s medical officers, Ana Maria Henao-Restrepo, are the day the patient is hospitalized, the date of discharge, leaving or death, the duration of hospitalization, and the need for oxygen or ventilation during the patient’s stay. Design of the trial The design of the trial is not double-blinded, in that the patients know if they are receiving one of the trialed drugs, and may, therefore, show benefit due to the placebo effect. On the other hand, in this particular situation, the WHO is less concerned about conforming to the highest scientific standards and less about optimizing the efficiency of the process to get results as fast as possible. The trial itself was conceived less than a couple of weeks ago, and the agency is hustling to get the required documents and data management facilities up and running within one more week – which is ‘record time,’ according to Henao-Restrepo. The Advantages The simplicity of the trial design has won the approval of many researchers, who feel that more details about the course of the disease aren’t relevant at this stage of knowledge. Virologist Christian Drosten from Berlin says, for instance, “We don’t really know enough about this disease to be sure what it means when the viral load decreases in the throat.” Meanwhile, others are following WHO’s cue. France, for example, is starting an add-on trial in Europe called Discovery, including 3,200 patients from 7 or more countries, testing the same drugs except for chloroquine. Others could also do the same while modifying the requirements to suit their own research goals as well. For instance, they could add on virology tests, do blood chemistry, or imaging of the lungs. Yet, Henao-Restrepo points out, these are not ‘core requirements’ at this stage, though they might well be of great value in the future. The Candidates The drugs to be tested were shortlisted based on: The chances of success The safest drugs The drugs most likely to be available in sufficient numbers to treat a large number of people if found effective These include: Remdesivir This drug inhibits an important viral enzyme called the RNA-dependent RNA polymerase, which is required for viral replication inside the host cell. First developed to fight viruses such as Ebola, it failed to prove effective when tested in the 2019 Ebola epidemic in the Democratic Republic of the Congo. However, laboratory studies in test tubes and animals show it might be effective in fighting coronaviruses, and anecdotal evidence supports this possibility, with at least two patients who were in a critical state being reported to have turned the corner when given the drug. The drawback is that it has to be given intravenously, it is expensive, and is required in only 15% of patients. Chloroquine and Hydroxychloroquine These antimalarials are included chiefly because of the need to decide whether they are useful or not, based on the interest shown in their use in many countries. They reduce the acidity level within endosomes, which are intracellular compartments that receive material from outside the cell. These can be hijacked by viruses to achieve the same aim, namely, to enter the cell. However, the virus that causes COVID-19 enters via a spike receptor on the cell surface rather than endosomes. While cell culture studies indicate some antiviral activity, high doses are required, carrying the potential for toxicity. Animal studies have not shown benefit either. However, over 20 Chinese studies reporting evidence of benefit with chloroquine in COVID-19 patients have been published – all without supporting data. This makes it difficult to evaluate the claims of efficacy. According to the WHO, “WHO is engaging with Chinese colleagues at the mission in Geneva and have received assurances of improved collaboration; however, no data has been shared regarding the chloroquine studies.” A French study was similarly confusing. Moreover, the diversion of these drugs to treat COVID-19 could lead to a deficit for people who use it for well-established indications like malaria or rheumatoid arthritis. The toxicity of hydroxychloroquine, in particular, is disturbing, because it can, though rarely, cause cardiac injury – a concern when people with heart disease are already at risk for severe COVID-19 symptoms. The guideline issued by the U.S. Society of Critical Care Medicine states that “there is insufficient evidence to issue a recommendation on the use of chloroquine or hydroxychloroquine in critically ill adults with COVID-19.” Ritonavir/lopinavir This antiviral combination was first approved for the treatment of HIV and consists of a pair of protease inhibitors. However, it also works with other proteases, including coronaviruses, such as in animal models of the MERS, as well as in human SARS and MERS patients. The results in the latter were not encouraging, and neither was the first human trial studying the effect of this combination in COVID-19. Ritonavir/lopinavir with Interferon-Beta The trial will also look at how the two protease inhibitors act together with the inflammation-regulating interferon-beta, now being tested for the first time in human patients with MERS in Saudi Arabia in a randomized controlled design. The use of interferon-beta in severe COVID-19 could well backfire, feel some experts. Drugs tested in the trial The drugs tested in the trial may soon change based on interim results of lack of efficacy, or evidence of harmful effects. The aim, according to Henao-Restrapo, is simple: “It will be important to get answers quickly, to try to find out what works This article has been modified. To read the original article click here.

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