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From Brief19: What Happened To Covid-19 Patients Admitted To The ICU In Italy?

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April 7, 2020

A paper published in JAMA on April 6th describes the outcomes of patients with confirmed SARS-CoV-2 infection who were admitted to Intensive Care Units in Lombardy, Italy. Of the 1,591 patients admitted to the ICUs, most were men (82 percent) and the average age was 63 years old. Almost all patients—99 percent—required at least some help with breathing, including 88 percent who required a mechanical ventilation (a breathing machine). At the time of the study, 26 percent of the patients followed in this study had already died, while another 58 percent remain in the ICU.

This study is notable for several reasons. First, this study represents the largest group of ICU patient outcomes described since the start of the covid-19 pandemic. Second, the authors shared intricate details in this publication, providing important insights into the needs of covid-19 patients ICUs. Finally, the results provide further evidence that older patients with chronic disease (high blood pressure, lung disease, etc) tend to fare poorly when they become sick with covid-19. While this study may not immediately provide “practice-changing” information for emergency physicians and other hospital providers, it is a stark reminder that older patients with multiple medical problems may require higher levels of medical care.

Shared with permission from Brief19, a daily review of #covid-19 research and policy.

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\ \ May 27, 2020\ There have been reports that some patients with covid-19 develop neurologic symptoms. In April, a study appearing in JAMA found that patients with more severe cases of SARS-CoV-2 were more likely to develop neurologic signs including strokes, loss of consciousness (or changes in general levels of alertness) and injury to the muscles of the body. A new study in The New England Journal of Medicine adds to this body of knowledge.\ The researchers gathered data on 64 SARS-CoV-2 positive patients who had been admitted to an intensive care unit in France with acute respiratory distress syndrome, a life-threatening complication of many diseases including covid-19.\ Concerning findings included evidence of disease to the corticospinal tract of the central nervous system, which is responsible for voluntary muscles, in 67 percent of the patients. These patients were seen to have more brisk reflexes, muscle spasms at the ankle (known as "clonus"), and abnormal reflexes on the soles of the feet. Amongst the patients, two were found to have experienced a stroke, and of eight who were considered at high risk of seizures, one had an abnormal EEG (electroencephalogram) which demonstrated findings that, while abnormal, were not specific to a specific disease. Interpretation of these findings poses significant challenges. It remains unclear whether these neurologic findings are specific to SARS-CoV-2 (including inflammatory crises caused by cytokines, for example), or whether such findings are only being detected because the "magnifying glass" is being applied to patients in ICUs such as the one described in this study. It is known, for example, that prolonged critical illnesses that require ICU medicine are associated with changes in brain cognition and neurologic function. Some of these changes are caused by powerful medications that must be used to keep patients alive and some are caused simply by the fact that the human mind and body are not "designed" to function in an environment like an ICU.\ Shared with permission from Brief19, a daily review of #covid-19 research and policy.](https://app.figure1.com/case-detail/0eb40d0d-601f-4105-b221-35074cd9b447)

\ \ May 12, 2020\ A new study published in JAMA assessed 1,438 hospitalized patients with covid-19 who received hydroxychloroquine and azithromycin (HCQ+AZ), hydroxychloroquine (HCQ) alone, azithromycin (AZ) alone, or neither drug. These 1,438 patients represent 88.2 percent of all covid-19 patients admitted across 25 hospitals in the New York metropolitan region between March 15 and 28, 2020 with a final follow-up date of April 24, 2020. The authors compared in-hospital mortality, cardiac arrest, and abnormal ECG findings (irregular heartbeat or elongation of the "QT interval," which indicates whether the heart is resetting normally after every beat). During the study period, 20.3 percent of all admitted patients died. The probability of dying from covid-19 after receiving HCQ+AZT was 25.7 percent; after receiving HCQ alone, 19.9 percent; after receiving AZ alone, 10 percent, and after receiving neither drug, 12.7 percent. After statistical correction for patient differences among the groups, there were no significant differences in mortality among any of the groups. Many side effects were reported in this study. Patients receiving HCQ+AZ were more likely to suffer from cardiac arrest compared with those in the other groups. However, some caveats are worth noting. This study was an observational study and not a randomized clinical trial, so which patients received various treatments were non-random events. The patients who received HCQ+AZ were notably sicker than the other groups and, therefore, more likely to die regardless of the intervention. Of note, 13 percent of HCQ+AZ patients were mechanically ventilated in less than a day compared to 5 percent of patients who did not receive any drug.\ Meanwhile, in the face of increasingly negative evidence regarding HCQ, some optimists have advanced the theory that HCQ fare better if zinc were included in protocols. While we are aware of no evidence to support this claim, a study preprint published in the journal medRxiv looked at this question. Hospitalized covid-19 patients in New York City who received HCQ+AZ plus zinc were compared with those who received HCQ+AZ alone. The researchers observed no difference in the number of days patients spent in the hospital, in intensive care units or on mechanical ventilators.\ While the paper states that patients who received zinc had half the odds of dying or transitioning to hospice when patients in the ICU were excluded, the methods of the paper are incomplete as currently published; the methods for how the data were pulled from electronic medical records are not adequately described.)\ There has been a steady stream recently of negative studies on HCQ. However, the largest ones have been observational studies, not true trials. An important randomized clinical trial performed in Europe that included patients receiving HCQ is expected to be published this week.\ Shared with permission from Brief19, a daily review of #covid-19 research and policy.](https://app.figure1.com/case-detail/60091b21-13e0-44c5-aa0a-4fdb83409499)

\ \ May 29, 2020\ Editor's note: Yesterday a group of concerned scientists issued an open letter with concerns regarding a recent study of hydroxychloroquine published last week in The Lancet, and covered here in Brief19. The letter, signed by 120 researchers all over the world, alleges that the study has irregularities that may suggest research misconduct. Problems identified include more patients from certain hospitals than are known to have been treated at such facilities and dosing problems. If the paper were to be retracted, it could be seen as a major setback for those seeking to stop hydroxychloroquine proponents from advancing the use of a medication not proven to benefit patients with covid-19. It was in part based upon this study (which described poorer outcomes amongst patients who received hydroxychloroquine). While the study was "observational," and thus cannot be used to imply a cause-and-effect, the fact that there were 96,032 patients included in the analysis impressed many observers. Regardless of the outcome of any investigation that may stem from this open letter, to date, no high-quality study has demonstrated that hydroxychloroquine helps patients with SARS-CoV-2.\ Shared with permission from Brief19, a daily review of #covid-19 research and policy.](https://app.figure1.com/case-detail/6e9e8e3b-ddf5-4769-943e-84f369a93ad4)

\ \ April 10, 2020\ A new report from the CDC describes pediatric outcomes of covid-19 in the United States. Most previous data on this topic came primarily from China and Spain. At the time of this report (through 2 April 2020), two percent of 149,760 laboratory-confirmed U.S. SARS-CoV-2 cases were diagnosed in children. The majority of pediatric cases were detected in New York City and New York State (55 percent).\ While fever and cough are common in children with covid-19, these symptoms are not as common as they were in adults with covid-19. Children with covid-19 were found to be more likely to have sore throat, headache, and muscle aches, than shortness of breath which was more common in adults. Consistent with data from China and Spain, children with covid-19 generally do not become severely ill. Although the data was limited, the CDC estimates that only 5.7 to 20 percent of cases required hospitalization, though this figure may be an overestimate due to reporting bias. Less than 2 percent of children with covid-19 required intensive care units. To-date, three children have died with covid-19, though the CDC states that investigations are ongoing to determine whether the SARS-CoV-2 virus was the culprit.\ Shared with permission from Brief19, a daily review of #covid-19 research and policy.](https://app.figure1.com/case-detail/7f13f9fe-22d5-4ad0-9de0-8a2093997632)

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