Σάββατο 16 Μαΐου 2020

COVID RISK SCORE-DRUGS AND VACCINES

Researchers in China have developed and validated a COVID-19 risk score that may help predict at the time of admission a patient's risk of progressing to severe disease.
The score has been translated into an online risk calculator that is freely available (here: http://118.126.104.170/).
Dr. Jianxing He of Guangzhou Medical University and colleagues collaborated with the National Health Commission of China to establish a cohort of COVID-19 patients from 575 hospitals in 31 provincial regions from November 2019-January 2020.
The data were used to develop a risk score that predicts whether a hospitalized COVID-19 patient will develop critical illness - e.g., sepsis, respiratory failure, acute respiratory distress syndrome, heart failure, and septic shock.
Data from four other comparable cohorts were used to validate the score
As reported in JAMA Internal Medicine, the development cohort included 1,590 patients and the validation cohort, 710. For both groups, the mean age was 48 and about 55% were men. On admission, 1.3% had severe disease and the rest, mild; 25% had at least one coexisting condition - e.g., hypertension (16.9%), diabetes (8.2%), or cardiovascular disease (3.7%)
Ten variables from among 72 were independent predictive factors and were included in the score: chest radiographic abnormality (OR, 3.39); age (OR, 1.03); hemoptysis (OR, 4.53); dyspnea (OR, 1.88); unconsciousness (OR, 4.71); number of comorbidities (OR, 1.60); cancer history (OR, 4.07); neutrophil-to-lymphocyte ratio (OR, 1.06); lactate dehydrogenase (OR, 1.002); and direct bilirubin (OR, 1.15).
The mean area under the curve was 0.88 in both cohorts.
Dr. He did not respond to a request for a comment, but three U.S. experts commented in emails to Reuters Health.
Dr. Frederick Bucker of the Division of Allergy and Infectious Diseases at the University of Washington School of Medicine in Seattle, said, "Overall, the risk calculator could be a helpful tool for clinicians The variables are easily obtainable, so running the calculator shouldn't be difficult. Being able to risks-stratify patients could help triage patients in the ER or clinic for admission to the hospital versus discharge to home, and help decide if patients should be admitted or transferred to the ICU."
The calculator may also be useful in decision making about therapy, he noted. "This will need to be studied more, but it will be very helpful to have a tool to help us decide who might benefit from treatment with immune plasma or drugs in limited supply, such as remdesivir. It (also) will help in our conversations with patients and their families to help set expectations about the chances of recovery."
"An important caveat is that the work was done in a Chinese population, thus the accuracy may not be as good in different populations," he added. "It will be helpful to see it put to use - and studied - in U.S. clinics and hospitals to see if it continues to be an accurate predictor of outcomes. Also, some of the variables (i.e., hemoptysis and unconsciousness) are quite uncommon (1-2% of all their patients) so they rarely factor into the overall score."
Dr. Luis Marcos, fellowship program director in the division of infectious diseases at Stony Brook Medicine in New York, commented, "A caveat is that this score only took a single-time point of laboratory results or symptoms. In practice, what I have seen in hundreds of patients...is that they can get very sick anywhere from mild to critical in 1-2 days and this score does not take that into account."
"Future research on this preliminary score has to be more dynamic and reach patients who will require ICU after 24-48 hours in the emergency department, comparing more than one time point analysis (laboratory, symptoms)," he said.
"Another limitation is the small-moderate sample size," he noted. "The population was mostly middle-age healthy people; few had more than one disease and only 16% had hypertension. This score...may not apply in other populations, such as those seen in tertiary large academic centers - i.e., advanced age, obese, diabetic, hypertensive, kidney disease, immunosuppressed, transplant, etc."
Dr. Miriam Smith, chief of infectious disease at Long Island Jewish Forest Hills in Queens, New York, said "The scoring system may have utility in identifying patients who would benefit from hospitalization in an institution where resources are available to provide aggressive care. Clinicians would have to judge if the risk calculator captures high-risk patients who may otherwise not have been identified."

The malaria treatment repeatedly championed by U.S. President Donald Trump as a "game changer" in the fight against the novel coronavirus has again failed to show a benefit in patients hospitalized with COVID-19, according to a study released on Thursday.
While the study published in The New England Journal of Medicine had certain limitations, doctors reported that the use of hydroxychloroquine lessened neither the need for mechanical ventilation nor the risk of death.
"We didn't see any association between getting this medicine and the chance of dying or being intubated," lead researcher Dr. Neil Schluger told Reuters in a telephone interview. "The patients who got the drug didn't seem to do any better."
Among patients given hydroxychloroquine, 32.3% ended up needing a ventilator or dying, compared with 14.9% of patients who were not given the drug.
But doctors were more likely to give hydroxychloroquine to sicker patients, so researchers at New York-Presbyterian Hospital and Columbia University Irving Medical Center adjusted the rates to account for that. They concluded that the drug may not have hurt patients, but it clearly did not help.
Decades old hydroxychloroquine, which is also used to treat lupus and rheumatoid arthritis, also showed no benefit when combined with the antibiotic azithromycin, Schluger's team reported. Azithromycin alone also showed no benefit.
Last month, doctors at the U.S. Department of Veterans Affairs reported that hydroxychloroquine did not help COVID-19 patients and might pose a higher risk of death.
That analysis of medical records showed a death rate of 28% when the drug was given in addition to standard treatments, compared to 11% with standard care alone.
In the latest study, 811 patients got hydroxychloroquine and 565 did not.
Because they were not randomly assigned to receive hydroxychloroquine or a placebo, "the study should not be taken to rule out either benefit or harm" for the drug, researchers said. Randomized trials, the gold standard for tests of new therapies, should continue, they added.
But for now, "the guidance in our hospital has changed so we don't recommend giving hydroxychloroquine to hospitalized patients," said Dr. Schluger, chief of the division of pulmonary, allergy and critical care medicine at Irving.
Smaller studies, including one done in China, had suggested hydroxychloroquine might be useful, "but these were tiny studies and not of good quality. People seized on them because patients were dying," he said.
There are currently no approved treatments for COVID-19, although Gilead Sciences Inc's experimental antiviral drug remdesivir last week receive emergency use authorization from U.S. regulators.

Manufacturers will begin producing COVID-19 vaccine doses in anticipation of approval so that if a product gets the okay for usage, distribution can begin quickly, according to Anthony S. Fauci, MD, director of the National Institute of Allergy and Infectious Diseases.
"We will be producing vaccine at risk, which means we'll be [investing] considerable resources in developing doses even before we know any given candidate or candidates work," he testified during a May 12, 2020, hearing of the Senate Health, Education, Labor, and Pensions Committee.
During the hearing, Dr. Fauci did not elaborate on how the production at risk would be undertaken, what criteria would be in place for selecting which candidates would be in the pipeline, or how much would be spent on the advanced production of these vaccines.
And while Dr. Fauci, a member of the White House coronavirus task force, remained optimistic that one or more vaccine candidates would ultimately be viable, he cautioned that there remain many unknowns that could slow the development of a vaccine for COVID-19.
"I must warn that there's also the possibility of negative consequences that certain vaccines can actually enhance the negative effect of the infection," he said. "The big unknown is efficacy. Will it be present or absent and how durable will it be?"
It's unlikely that either a vaccine or an effective treatment will be available in the next 3 months, Dr. Fauci told the committee.
Sen. Lamar Alexander (R-Tenn.), the committee chairman, asked Dr. Fauci what he would say to college, primary, and secondary school administrators about how the availability of treatments and vaccines could influence the ability to reopen campuses to students. Dr. Fauci replied that the idea of having treatments or a vaccine available to facilitate the reentry of students in the fall term would be "a bit of a bridge too far."
The emphasis in the coming months should be on testing, contact tracing, and isolation of those infected with the virus, Dr. Fauci said.

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