Early Anticoagulant Treatment Appears to Improve Survival in Severe COVID-19

Use of anticoagulation is likely to play an increasingly large role in treating severe cases of COVID-19. Find out how much better hospitalized novel coronavirus patients, including those receiving mechanical ventilation, fared after receiving full-treatment dosages of anticoagulants in a New York hospital system.

NEW YORK – Should hospitalized COVID-19 patients be routinely treated with anticoagulants to improve their chances of survival?

A new study involving 2,773 patients with laboratory-confirmed COVID-19 between March 14 and April 11, 2020 at the Mount Sinai Health System in New York City suggests that might be the case. The report was published in the Journal of the American College of Cardiology.

https://doi.org/10.1016/j.jacc.2020.05.001

Mount Sinai researchers determined that hospitalized COVID-19 patients they treated with anticoagulants had improved outcomes, even if they were receiving intensive care. No significant difference was documented between patients receiving anticoagulants and those who did not, suggesting the treatment was safe, they add.

"This research demonstrates anticoagulants taken orally, subcutaneously, or intravenously may play a major role in caring for COVID-19 patients, and these may prevent possible deadly events associated with coronavirus, including heart attack, stroke, and pulmonary embolism," explained senior corresponding author Valentin Fuster, MD, PhD, Director of Mount Sinai Heart and Physician-in-Chief of The Mount Sinai Hospital. "Using anticoagulants should be considered when patients get admitted to the ER and have tested positive for COVID-19 to possibly improve outcomes. However, each case should be evaluated an individualized basis to account for potential bleeding risk."

The patients were treated at one of five hospitals in the Mount Sinai system: The Mount Sinai Hospital, Mount Sinai West, Mount Sinai Morningside, Mount Sinai Queens, and Mount Sinai Brooklyn.

Of the COVID-19 patients analyzed, 786, 28%, received a full-treatment dose of anticoagulants, including oral, subcutaneous, or intravenous forms. The dose received was higher than what is usually given for blood clot prevention.

For study participants, the median hospitalization duration was 5 days (3-8 days), and the median time from admission to anticoagulant initiation was two days (0-5 days). Treatment lasted a median of three days.

The authors report that in-hospital mortality for patients dosed with anticoagulants was 22.5% with a median survival of 21 days, compared to 22.8% and median survival of 14 days in patients who did not receive the treatment.

Patients who received anticoagulation were more likely to require invasive mechanical ventilation (29.8% vs 8.1%, p<0.001), they add.

“Overall, we observed significantly increased baseline prothrombin time, activated partial thromboplastin time, lactate dehydrogenase, ferritin, C reactive protein, and D-dimer values among individuals who received in-hospital AC as compared to those who did not,” the researchers point out. “These differences were not observed, however, among mechanically ventilated patients.”

For the 395 patients who were ventilated and received anticoagulants, the effect was more pronounced, according to the study. Researchers report that 62.7% of intubated patients who were not treated with anticoagulants died vs. 29.1% for intubated patients treated with anticoagulants. Of the intubated patients who did not survive, those with no anticoagulants died after nine days, while those on anticoagulants died after 21 days.

Furthermore, analysis indicates that a longer duration of anticoagulant treatment was associated with a reduced risk of mortality (adjusted HR of 0.86 per day, 95% confidence interval 0.82-0.89, p<0.001), according to the article.

Based on blood work at admission, patients who received anticoagulants had higher inflammatory markers compared to patients not treated with anticoagulants. Based on that, researchers posit that patients with more severe illness might benefit from anticoagulants early on.

Researchers caution that further analysis and prospective studies are required to determine the effectiveness for widespread use of anticoagulants in hospitalized COVID-19 patients. The team will embark on a further study of 5,000 COVID-19-positive patients, where the effectiveness of three types of antithrombotic therapy--oral antithrombotic, subcutaneous heparin, and intravenous heparin—will be evaluated.

Hyperinflammatory Shock Seen in Some Children With Current, Past COVID-19

Pharmacists should be aware of the symptoms of a new COVID-19-related condition being seen in children. Children with fevers not responding to medication, variable rash, conjunctivitis, peripheral edema, and generalized extremity pain with significant gastrointestinal symptoms should be referred for immediate evaluation/treatment and novel coronavirus testing, according to public health officials. Here are more details.

LONDON – Until now, it had been assumed that children would be a demographic groups largely escaping the dangerous health effects of COVID-19.

A very small percentage of pediatric cases were reported as serious, and, in China, where the novel coronavirus outbreak began, only two deaths of children had been reported as of a May 1 report in The Lancet Respiratory Medicine. (The U.S. National Center for Health Statistics reports 10 deaths for patients under the age of 14 as of May 2.)

https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(20)30152-1/fulltext

As with many issues involving the novel coronavirus, the situation might be changing quickly. In the UK, the South Thames Retrieval Service in London, which provides pediatric intensive care support and retrieval to two million children in South East England, has reported “an unprecedented cluster” of eight children with hyperinflammatory shock. The patients presented with features similar to atypical Kawasaki disease, Kawasaki disease shock syndrome, in mid-April, and one child died.

A report in The Lancet says the center usually sees one or two children per week. In this case, all of the children were previously in good health. The article points out that six of the children were of Afro-Caribbean descent, and five of the children were boys. Four children had known family exposure to COVID-19.

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(20)31094-1.pdf

Meanwhile, the New York State Department of Health sent out an alert stating that 64 cases of a similar condition had been report statewide. Cases also had been found in Louisiana, Mississippi and California, where a six-month old presented with the illness.

http://dmna.ny.gov/covid19/docs/all/DOH_COVID19_PediatricInflammatorySyndrome_050620.pdf

https://hosppeds.aappublications.org/content/hosppeds/early/2020/04/06/hpeds.2020-0123.full.pdf

In addition, 50 cases were reported in European countries, including the British cases.

Pharmacists should be aware of the clinical presentations for the illness: unrelenting fever (38–40°C), variable rash, conjunctivitis, peripheral edema, and generalized extremity pain with significant gastrointestinal symptoms. All progressed to warm, vasoplegic shock, refractory to volume resuscitation and eventually requiring noradrenaline and milrinone for hemodynamic support.

The report from the UK advises that none of the children had no significant respiratory involvement, although seven of the children required mechanical ventilation for cardiovascular stabilization. It notes that other notable features included development of small pleural, pericardial, and ascitic effusions, suggestive of a diffuse inflammatory process.

In the UK report, all children tested negative for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but the authors write, “We suggest that this clinical picture represents a new phenomenon affecting previously asymptomatic children with SARS-CoV-2 infection manifesting as a hyperinflammatory syndrome with multiorgan involvement similar to Kawasaki disease shock syndrome. The multifaceted nature of the disease course underlines the need for multispecialty input (intensive care, cardiology, infectious diseases, immunology, and rheumatology).”

New York health officials report, on the other hand, that many of the children who have become sick with the syndrome there fell into one of two categories: they had a positive test for COVID-19 at the time their symptoms presented or they testing positive on antibody tests, raising the question of whether the response was a post-infection condition.

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