Miniature organs help test potential coronavirus drugs; GI symptoms linked to severe COVID-19

By Nancy Lapid

(Reuters) – The following is a roundup of some of the latest scientific studies on the novel coronavirus and efforts to find treatments and vaccines for COVID-19, the illness caused by the virus.

Miniature lungs, colons help test COVID-19 treatments

Tiny organ-like structures grown in the laboratory to behave like human lungs and colons can be used to rapidly screen drugs and identify those with potential as COVID-19 treatments, researchers reported on Wednesday in Nature. Compared with traditional pre-clinical approaches, in which drugs are tested in cells from monkeys or from human cancer patients, these so-called organoids more faithfully mimic the complex cell types and structure of human tissues, according to Dr. Shuibing Chen and Dr. Robert Schwartz of Weill Cornell Medicine in New York. Their team developed organoids containing types of lung and colon cells that are known to become infected in people with COVID-19. In collaboration with teams at Columbia University and Icahn School of Medicine at Mount Sinai, they screened 1,200 FDA-approved drugs and found three that showed activity against the novel coronavirus, including the cancer drug imatinib, sold as Gleevec by Novartis. It is currently being tested in four different COVID-19 clinical trials. (https://go.nature.com/34CLDtS)

GI symptoms linked with more severe COVID-19

Gastrointestinal (GI) symptoms are associated with more severe COVID-19 and worse outcomes, two research teams reported on Monday, a reversal of earlier data that suggested the opposite was true. One team reviewed 38 earlier studies of a total of more than 8,400 patients and found those with diarrhea were 63% more likely to develop severe COVID-19. Dr. Subash Ghimire of Guthrie Robert Packer Hospital in Pennsylvania suggested that patients with diarrhea may have higher viral loads, which can potentially lead the body to fight back with more severe responses. The other team studied 921 patients and found that the roughly 22% with at least one GI symptom had higher rates of hospital and intensive-care unit admissions and greater need for mechanical breathing assistance. The more GI symptoms patients had, the more their risk for these outcomes increased, Dr. Darbaz Adnan of Rush University Medical Center in Chicago reported. He said doctors evaluating COVID-19 patients need to bear in mind that GI symptoms may signal a markedly higher risk of a worsened disease course. Both studies were presented at the American College of Gastroenterology virtual annual meeting. (https://bit.ly/37OgZQh)

UK population with COVID-19 antibodies is shrinking

A new wave of coronavirus infections has been spreading in the UK, but the proportion of the population there with antibodies to the virus has been shrinking, potentially leaving more people vulnerable, new data show. In a report posted on Tuesday on medRxiv ahead of peer review, scientists at Imperial College London say that while 6% of the population had COVID-19 antibodies around the end of June, that rate fell to just 4.4% in September. Antibodies are not the body’s only line of defense. Also important are immune cells called T cells and B cells that

Read more

Low dose of the medicine intravenous immunoglobulin decreases the effect of dangerous toxins during severe infections

immunity
Credit: Pixabay/CC0 Public Domain

During necrotizing soft tissue infections ordinary bacteria infect our body, spread rapidly and cause tissue death. Treatment with antibiotics is not sufficient and infected tissue needs to be removed through surgery. 22% of people who suffer from this disease need to amputate a limb and 18% do not survive.

A common cause of these infections is group A streptococcus. These bacteria form toxins that lead to overactivation of the body’s otherwise helpful immune cells, causing a so called “cytokine storm” which contributes to a severe course of the disease and the need of intensive care.

Recently, a study called INSTINCT was performed. In this study patients with necrotizing soft tissue infections were randomized to treatment with either intravenous immunoglobulin (IVIG) or placebo, in addition to other treatment. This study showed a trend towards better health after treatment with IVIG in the subgroup often caused by group A streptococcus, but no clear correlation during infections caused by other bacteria. However, the study used a lower dose than in previous studies: 25 g per day.

Bergsten et. al. tested blood samples from infected patients before and after treatment with IVIG, and found that treatment with IVIG leads to decreased effect of the toxins produced by the bacteria—even at the low dose of 25 g per day that was used in the INSTINCT study. Based on these results, the researchers suggest a new dosage regime of IVIG during these infections. It is still not proven that IVIG leads to better health during these devastating infections and the researchers suggest that the new dosage is tested in a controlled clinical trial of patients with necrotizing soft tissue infections caused by group A streptococcus.


IV immunoglobulin use up in interstitial lung disease


More information:
Helena Bergsten et al. Correlation Between Immunoglobulin Dose Administered and Plasma Neutralization of Streptococcal Superantigens in Patients With Necrotizing Soft Tissue Infections, Clinical Infectious Diseases (2020). DOI: 10.1093/cid/ciaa022
Provided by
Karolinska Institutet

Citation:
Low dose of the medicine intravenous immunoglobulin decreases the effect of dangerous toxins during severe infections (2020, October 28)
retrieved 28 October 2020
from https://medicalxpress.com/news/2020-10-dose-medicine-intravenous-immunoglobulin-decreases.html

This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no
part may be reproduced without the written permission. The content is provided for information purposes only.

Source Article

Read more

Kansas nursing home faces severe federal penalties after deadly coronavirus outbreak

By the time the viral firestorm had finished sweeping through the nursing home, all 63 residents were infected and at least 10 had died. Medicare moved Monday to terminate the Andbe Home from its program, cutting it off from federal dollars and imposing thousands of dollars in fines.

Government inspectors found that infected residents were separated from their healthy roommates by little more than a privacy sheet. Communal dining continued for two days. Multiple staff members failed to wear masks — even after the outbreak took hold.

In an email Tuesday to The Washington Post, the nursing home administrator disputed some of the findings outlined in the report and stood by the response to the outbreak, saying the facility had immediately quarantined infected residents and that staff wore full personal protective equipment, including goggles, masks and gloves.

“This is a terrible virus, but I am proud of how our staff has battled COVID-19 over the course of the pandemic, coming to work every day under extenuating circumstances, and caring for all of our residents,” Mapes wrote. “I am also proud of and thankful for the mutual support between Andbe Home and our community during trying times for everyone.”

The Medicare report, however, said the facility’s failures had “placed all residents in immediate jeopardy by the spread of Covid-19 to all residents.”

The virus’s rampage through the nursing home came amid a surge of infections in Kansas’s Norton County, which led the nation in per capita case increases between Oct. 12 and Oct. 19 and ranked second this week, according to a Post analysis. Before Oct. 13, the county near the Nebraska border had been spared virus-related deaths.

Now, there are clusters of cases at the nursing home, where 55 of 70 staff members tested positive for the virus, as well as at a correctional facility and a bank. City offices are closed to the public, municipal court is postponed and multiple businesses have temporarily shut their doors. The funeral home has posted a wave of obituaries for people who lived at the Andbe Home: a stained glass artist with pieces displayed around town, a onetime staffer turned resident, a skilled home cook known especially for “fried chicken with all the fixins.”

Like many parts of rural America, the county of about 5,000 had resisted masks and other measures aimed at preventing the spread of the coronavirus. The city police department was cheered in June after announcing it would not enforce a mask mandate imposed by Gov. Laura Kelly, a Democrat.

“For months, many have mistakenly shared the idea that this virus would never reach our rural and lower-population communities,” the governor said during a news conference last week. “Now, it is worse in those towns and counties than it is in our cities.”

She called the deaths at the Andbe Home “a stark reminder” of the threat posed by the virus.

Medicare inspection reports suggest resistance to masks at the nursing home, a sprawling, single-story facility that was rated as

Read more

Researchers link severe COVID-19 cases to mental decline equal to aging a decade

People that have suffered severe cases of COVID-19 may experience mental decline equal to the brain aging by a decade, according to a new study released this month.  

Researchers from the U.K. analyzed the test data of over 84,000 participants who took the Great British Intelligence Test and were suspected or confirmed to have COVID-19. 

The study, which has not yet been peer-reviewed, found that people who had recovered from severe cases of the disease exhibited “significant cognitive deficit” after controlling for other factors such as age, gender and pre-existing medical conditions. 

Some deficits were of “substantial effect size,” the researchers found, specifically among those who had been hospitalized and those who had mild cases and reported no difficulty breathing. However, among those who ended up on a ventilator, the deficits were “equivalent to the average 10-year decline in global performance between the ages of 20 to 70.” 

The cognitive decline could be the result of other health events that are thought to be associated with COVID-19 such as stoke, inflammatory syndrome and micro bleeds, according to the study.

COVID-19 is a disease that can have critical impacts on the upper respiratory system, leading patients with severe cases to require supplemental oxygen. As a result, researchers in the study have also hypothesized that hypoxia in the brain could also lead to cognitive decline. 

However, they write, “it is yet to be established whether COVID-19 infection is associated with cognitive impairment at the population level; and if so, how this differs with respiratory symptom severity and relatedly, hospitalisation status. Measuring such associations is challenging.”

In all, the scientists said that their findings “align with the view that there are chronic cognitive consequences of having COVID-19. Individuals who recovered from suspected or confirmed COVID-19 perform worse on cognitive tests in multiple domains than would be expected given their detailed age and demographic profiles.” 

The researchers said their study should be a “clarion call” for more research into the basis cognitive deficits in recovered COVID-19 patients. 

Some scientists say that the study’s results should be viewed cautiously. 

Derek Hill, a professor of medical imaging science at University College London, told Reuters that the study did not compare before and after scores of participants, and that a large number of them only self-reported having the virus without a positive test. 

“Overall (this is) an intriguing but inconclusive piece of research into the effect of COVID on the brain,” Hill told Reuters. “As researchers seek to better understand the long term impact of COVID, it will be important to further investigate the extent to which cognition is impacted in the weeks and months after the infection, and whether permanent damage to brain function results in some people.”

Source Article

Read more

Psoriasis Meds Don’t Raise Risk of Severe COVID-19: Study | Health News

By Cara Roberts Murez, HealthDay Reporter

(HealthDay)

TUESDAY, Oct. 27, 2020 (HealthDay News) — Researchers in the United Kingdom have reassuring news for people with psoriasis based on the first analysis of a global registry of COVID-19 patients who also have the skin disease.

Moderate-to-severe cases of psoriasis are treated with drugs that suppress the immune system. This analysis of the international PsoProtect registry found that more than 90% of psoriasis patients survive infection with the new coronavirus.

“We can reassure our patients that the survival for people with psoriasis is high, and the risk factors for psoriasis patients are similar to those of the general population,” said Dr. Satveer Mahil, a consultant dermatologist at St. John’s Institute of Dermatology in London, who co-leads the registry.

The registry was established to understand how psoriasis and the medications used to treat it affect severity of COVID-19, according to a news release from the U.K.’s National Institute for Health Research.

Psoriasis is a skin disease believed to be related to an immune system problem. It causes red patches and flaky plaques of skin that are covered with silvery scales.

The findings were recently published online in the Journal of Allergy and Clinical Immunology.

For the study, the researchers analyzed 374 cases from 25 countries in which psoriasis patients had COVID-19 between March and July 2020. About 71% were taking biologic medications and 18% were taking traditional immunosuppressants. About 93% fully recovered from COVID-19, 21% were hospitalized and 2% died.

Helen McAteer is chief executive of the Psoriasis Association. She said, “From the beginning of the pandemic, we understood the importance of being proactive in order to address the many concerns expressed by people who are living with psoriasis. The PsoProtect registry is vital in helping us understand more about the interactions between psoriasis, its treatments and COVID-19 infection so patients can make the most informed choices about their care and treatment at this challenging time.”

Copyright © 2020 HealthDay. All rights reserved.

Source Article

Read more

India’s capital chokes on ‘severe’ smog as farm fires soar

New Delhi was blanketed in noxious haze Friday as air pollution levels in parts of the city soared to “severe” levels, hours after US President Donald Trump described the air in the vast nation as “filthy”.

Smoke from agricultural burning, vehicle fumes and industrial emissions — combined with cooler temperatures and slow-moving winds that trap pollutants over the city — turns air in the Indian capital into a toxic soup every winter.

The air quality index at Delhi’s 36 pollution monitoring sites — which monitors tiny PM2.5 and PM10 particles that get into the bloodstream and vital organs — was between 282 and 446, pushing levels into the “severe” category, the Central Pollution Control Board said.

The “good” category is between 0-50, the government’s environmental watchdog added.

A “significant increase in stubble fire count” to 1,213 in Haryana and Punjab states was the highest of this season and made up 17 percent of Delhi’s PM2.5 levels, the state-run System of Air Quality Weather Forecasting and Research added Friday.

“Further deterioration of (air quality) is expected for the two days,” SAFAR said.

This season’s burning started earlier because of advanced sowing and harvesting by farmers amid fears of labour shortages during the coronavirus pandemic, officials said.

The worsening conditions came as Trump complained that action on climate change was unfair to the US.

“Look at China, how filthy it is. Look at Russia, look at India — it’s filthy. The air is filthy,” Trump said at his presidential debate with Democratic rival Joe Biden.

Scientists warned this year’s pollution season would make Delhi’s 20 million residents more vulnerable to the coronavirus.

“Air pollution increases the risk of noncommunicable diseases — the same underlying conditions that make people more likely to experience severe illness or death from Covid-19,” epidemiologist Sumi Mehta from global non-profit Vital Strategies told AFP.

Healthcare systems, stretched by the pandemic, could be further stressed by more hospitalisations from pollution-related illnesses, researchers added.

“There are serious worries that during winter when higher air pollution levels in any case worsens respiratory illness and increases hospitalisation, the vulnerability to Covid-19 may be further enhanced,” Anumita Roy Chowdhury of the Delhi-based Centre for Science and Environment told AFP.

The chief medical officer of Gurugram city near New Delhi, Virender Yadav, told The Times of India Thursday some recovering Covid-19 patients were experiencing a reoccurence of respiratory conditions triggered by the heightened air pollution.

grk-ja/je

Source Article

Read more

Convalescent plasma did not reduce Covid-19 deaths or keep patients from severe illness in new study

The study, conducted in India and published in the medical journal the BMJ on Thursday, suggests that “as a potential treatment for patients with moderate Covid-19, convalescent plasma showed limited effectiveness.”

Convalescent plasma is the antibody-rich serum taken from the blood of people who recovered from Covid-19. The idea is that the plasma can help the immune response of patients still fighting the disease.

In August, the US Food and Drug Administration authorized the emergency use of convalescent plasma as a treatment option for hospitalized Covid-19 patients. However, data were still being collected in randomized controlled trials — the gold standard — to study the safety and effectiveness of the treatment. Last month, a National Institutes of Health panel said there’s no evidence backing the use of convalescent plasma to treat coronavirus patients and that doctors should not treat it as a standard of care until more study has been done.

Randomized controlled trials of convalescent plasma to treat Covid-19 patients are still underway in the United States.

The new study, called the PLACID trial, included data on 464 adults with moderate Covid-19 in 39 hospitals across India. Among them, 235 patients were randomly selected to receive convalescent plasma along with standard care for treatment and 229 patients received only standard care.

The new study showed that a higher proportion of patients who received convalescent plasma saw improvements in their symptoms of fatigue and shortness of breath compared with those given standard care, but there was no difference between patients when it came to resolving fever and cough.

The proportion of patients who needed invasive ventilation did not differ among the two groups, and overall, the researchers found that 34 patients who received convalescent plasma, or 15%, had died — compared with 31 who were given standard care, or 14%.

Dozens of hospitals poised to defy FDA's directive on Covid plasma

The study had some limitations, including that it was an “open label design” so the physicians treating the patients knew who was given convalescent plasma and who wasn’t. Additionally, more research is needed to determine whether similar findings would emerge among a larger group of patients in other parts of the world.

Simon Clarke, an associate professor in cellular microbiology at the University of Reading in the United Kingdom, called the new study “a blow” to the use of convalescent plasma as a Covid-19 treatment.

“While this is a blow to the use of plasma therapy for Covid-19, it should not be abandoned, there may be ways to refine it as a treatment and deliver solid, demonstrable benefits,” Clarke said in a written statement distributed by the UK-based Science Media Centre.
Researchers hope this old-fashioned treatment will work for coronavirus

“Use of someone’s blood plasma that contains antibodies against a virus or bacteria to treat an infection in someone else, is not a new technology and although usually safe, is not entirely without risk,” said Clarke, who was not involved in the new study.

“The PLACID trial was able to show a small effect on the rate at which patients were able rid themselves of the virus, but this

Read more

AB Science announces positive top-line Phase 3 results for oral masitinib in severe asthma

Paris, October 20, 2020, 9.15pm

AB Science announces positive top-line Phase 3 results
 for oral masitinib in severe asthma

This is the second Phase 3 study to demonstrate efficacy for masitinib in severe asthma

AB Science SA (Euronext – FR0010557264 – AB) today announced that the Phase 3 study (AB14001) evaluating oral masitinib in severe asthma uncontrolled by high-dose inhaled corticosteroids (ICS) and with eosinophil level >150 cells/μL met its primary endpoint.

The pre-specified primary analysis was rate of severe asthma exacerbations, with masitinib demonstrating a statistically significant 29% reduction in severe exacerbations relative to placebo (p=0.022). The frequency of severe asthma exacerbations was 0.43 in the masitinib arm, versus 0.62 in the placebo arm. Duration of exposure was well-balanced between the treatment-arms (16 months in the masitinib arm and 17 months in the placebo arm). Sensitivity analysis based on the rate of moderate and severe asthma exacerbations was consistent with the primary analysis and detected a statistically significant 31% reduction in exacerbations (p=0.005) between masitinib and placebo. The frequency of moderate and severe asthma exacerbations was 0.55 in the masitinib arm, versus 0.80 in the placebo arm.

This is the second time that masitinib has demonstrated efficacy in reducing severe asthma exacerbations in patients with severe asthma. The treatment effect observed in study AB14001 is comparable with the effect previously reported for study AB07015. In that first phase 3 study, which evaluated masitinib in severe asthma uncontrolled by oral corticosteroids (OCS), masitinib significantly (p=0.010) reduced the rate of severe asthma exacerbations by 35% as compared with placebo. The frequency of severe asthma exacerbations in study AB07015 was 0.34 in the masitinib arm, versus 0.45 in the placebo arm. Duration of exposure was also well-balanced between the treatment arms (13 months in both treatment arms).
Safety was consistent with the known tolerability profile for masitinib.

Detailed results will be presented at an upcoming medical meeting.

The study AB14001 enrolled patients with blood eosinophil level >150 cells/μL, which differs from the population usually addressed by biological treatments, targeting patients with high eosinophils (>300 cells/μL or above) defined as Th2-high eosinophilic asthma.

Masitinib is a first in class drug in severe asthma, distinct from biological treatments targeting type-2 high eosinophilic phenotypes of asthma. Masitinib has a dual mechanism of action, targeting mast cells and PDGFR signaling that are both involved in airway remodeling associated with severe asthma. It has also been shown that increased mast cell activity is associated with both eosinophilic (Th2-high) and non-eosinophilic (Th2-low) asthma phenotypes. Furthermore, masitinib is orally administered, whereas biologics are sub-cutaneous, which is an advantage because oral administration is less of a burden for patients and facilitates compliance for long-term use.

There is still a need for effective therapy of patients with severe asthma. Biologics are established in first line treatment in severe asthma patients with blood eosinophil levels of ≥300 cells/µL. However, these therapies have limited efficacy in reducing severe asthma exacerbations for severe asthmatics with blood eosinophil levels of <300 cells/µL. In

Read more