Tag: covid treatment

Categories : COVID Respiratory DiseasesTags :

Cystic Fibrosis Drug Improves Outcomes in Severe COVID Pneumonia

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In a new clinical trial, a drug commonly used to treat cystic fibrosis, dornase alfa, improved outcomes for patients with severe COVID pneumonia. The results, published in the journal eLife, also suggest that the drug could be used to treat other respiratory infections.

The study, found that the drug reduced hyper-inflammation in COVID pneumonia patients, which occurs when the body’s immune system reacts too strongly and can lead to tissue damage and death.

The next step will be to conduct larger clinical trials, with the ultimate goal of approving dornase alfa for wider use. As well as COVID, dornase alfa has the potential to treat other respiratory infections such as those caused by influenza or bacterial pneumonia, and even other lung diseases such as pulmonary fibrosis.

Since the beginning of the COVID pandemic, the proportion of SARS-CoV-2 infections that result in death has fallen, partly due to increased immunity from prior infection or vaccination, as well as improved treatments such as the steroid dexamethasone, which helps to tackle the hyper-inflammation that was a key factor in many COVID deaths. But this treatment isn’t suitable for some patients and is not always successful in severe cases.

In this study, researchers from UCL, UCLH and the Francis Crick Institute set out to assess whether dornase alfa could be used to improve outcomes for patients admitted to hospital with severe COVID pneumonia who required oxygen.

Out of a total of 39 participants, 30 were randomised to receive twice-daily treatment with nebulised dornase alfa in addition to best available care (BAC) which included dexamethasone, with nine patients randomised to BAC only.

Patients treated with dornase alfa had a 33% reduction in systemic inflammation on top of the reduction provided by dexamethasone, as measured by C-reactive protein (CRP) levels in the blood over seven days or until they were discharged from hospital.

Dr Venizelos Papayannopoulos, senior author of the study from the Francis Crick Institute, said: “Dexamethasone has been highly successful in treating patients with severe COVID-19 pneumonia and is now standard care in the UK. But it isn’t suitable for some patients, such as those with diabetes, those that do not require oxygen, and in very severe cases it may not be enough. Dornase alfa can be used to treat a wider variety of patients and gets right to the heart of the inflammatory response. Based on these results, we think it will be a valuable tool for tackling severe COVID-19 illness.”

Patients treated with dornase alfa were also more likely to need less oxygen and be discharged sooner compared to patients who received BAC. These additional benefits could help to free up beds and resources in the UK’s busy hospitals.

The next step will be to conduct larger clinical trials to ensure dornase alfa is safe and effective for treating severe COVID pneumonia. There is also potential for the drug to be trialled for other respiratory infections and conditions, such as acute exacerbations of pulmonary fibrosis, where inflammation of already scarred lung tissue affects how well oxygen can be absorbed.

Source: University College London

Categories : COVIDTags :

Time is Running out to Develop a Paxlovid Alternative

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Researchers from Rutgers University in the U.S. believe that they are ahead in a race to find an oral COVID-19 treatment to supplement or replace the antiviral Paxlovid. Their report, published in Science, shows that an alternative medication, a viral papain-like protease inhibitor, inhibits disease progression in animals while also possessing an important advantage over Paxlovid – fewer prescription drug contraindications.

“COVID-19 remains the nation’s third leading cause of death, so there’s already a massive need for additional treatment options,” said Jun Wang, senior author of the study and associate professor at Rutgers. “That need will grow more urgent when, inevitably, COVID-19 mutates in ways that prevent Paxlovid from working.”

The Rutgers team hoped to make a drug that interfered with viral papain-like protease (PLpro), a protein that performs important functions in all known strains of COVID-19.

Creating such a drug required detailed information about PLpro’s structure, which Wang’s team got from the Arnold Lab at Rutgers’ Center for Advanced Biotechnology and Medicine (CABM).

Precise knowledge of PLpro’s structure enabled Wang’s team to design and synthesise 85 drug candidates that would bond to – and interfere with – this vital protein.

“The PLpro crystal structures showed an unexpected arrangement of how the drug candidate molecules bind to its protein target, leading to innovative design ideas implemented by professor Wang’s medicinal chemistry team,” said Eddy Arnold, who is a professor at CABM.

Laboratory testing established that the most effective of those drug candidates, a compound dubbed Jun12682, inhibited several strains of the SARS-CoV-2 virus, including strains that resist treatment with Paxlovid.

Oral treatment with Jun12682 on SARS-CoV-2-infected mice was shown to reduce viral lung loads and lesions while improving survival rates.

“Our treatment was about as effective in mice as Paxlovid was in its initial animal tests,” said Wang, who added the experimental drug appears to have at least one major advantage over the older drug.

“Paxlovid interferes with many prescription medications, and most people who face the highest risk of severe COVID-19 take other prescription medicines, so it’s a real problem,” Wang said.

“We tested our candidate Jun12682 against major drug-metabolising enzymes and saw no evidence that it would interfere with other medications.”

Source: Rutgers University

Categories : COVIDTags :

Paxlovid does not Reduce Risk of Long COVID, Study Finds

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A recent has study found that Paxlovid (Nirmatrelvir-ritonavir) did not reduce the risk of developing long COVID for vaccinated, non-hospitalised individuals during their first COVID infection. The study also revealed a higher proportion of individuals with acute symptoms rebound and test-positivity than previously reported.

The study, by a team of researchers from UC San Francisco, is published in the Journal of Medical Virology.

Paxlovid treatment for acute COVID has been shown to be effective for high-risk unvaccinated individuals. But the effect of the treatment on long COVID risk, including whether it protects vaccinated people from getting long COVID, has been less clear.

The research team selected a group of vaccinated people from the UCSF Covid-19 Citizen Science study who had reported their first positive test for COVID-19 between March and August of 2022 and who were not hospitalised.

Some of these participants reported taking oral Paxlovid treatment during the acute phase of their COVID infection, while others did not.

In December of 2022, they were invited to answer a follow-up survey with questions about long COVID, COVID rebound symptoms and how long they continued to test positive.

Researchers found the two groups were similar. About 16% of those treated with Paxlovid had long COVID symptoms compared to 14% of those who were not treated with the medication.

Commonly reported symptoms included fatigue, shortness of breath, confusion, headache, and altered taste and smell.

Those who took Paxlovid and then went on to develop long COVID reported as many long COVID symptoms as those who were not treated with Paxlovid.

A small percentage of people developed severe long COVID, and those who had received Paxlovid were just as likely to have severe Long COVID symptoms as those who did not.

Among individuals who experienced symptomatic improvement during Paxlovid treatment, 21% reported rebound symptoms.

And among those with rebound symptoms, 10.8% reported one or more Long COVID symptom compared to 8.3% without rebound symptoms.

For participants who repeated antigen testing after testing negative and completing treatment, 25.7% reported rebound test positivity.

In total, 26.1% reported rebound symptoms or test positivity.

“We found a higher proportion with clinical rebound than previously reported but did not identify an effect of post-treatment rebound on long COVID symptoms,” said study first author Matthew Durstenfeld, MD, MAS, a cardiologist and UCSF assistant professor of Medicine.

“Our finding that Paxlovid treatment during acute infection is not associated with lower odds of long COVID surprised us, but it is consistent with two other rigorously conducted studies finding no difference in post-COVID conditions between 4 and 6 months after infection.”

The authors note that the study may have been impacted by limitations arising from its observational nature with researchers relying on patient self-reporting of treatment and Long COVID symptoms.

Source: University of California San Francisco Medical Center

Categories : COVIDTags : 1 Comment

WHO Updates COVID Treatment Guidelines

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A panel of international experts representing the World Health Organization’s (WHO) Guideline Development Group has updated its guidance on treatments for patients with COVID.

The new recommendations published by The BMJ are part of a living guideline, developed by the WHO with the methodological support of MAGIC Evidence Ecosystem Foundation, to provide up to date, trustworthy guidance on the management of COVID and help doctors make better decisions with their patients.

The guidance incorporates the latest clinical trial evidence for existing and new COVID therapies and takes account of evidence relating to safety, prognosis, resources, access, and equity issues, as well as patient values and preferences. 

The updates include:

  • Distinct risk categories to help doctors more accurately assess whether an individual is at high, moderate, or low risk of hospital admission and tailor treatment accordingly.
  • A new treatment benefit threshold of 1.5% (down from 6%) reduction in the risk of hospital admission. This reflects the lower baseline risk for most patients with non-severe COVID as well as more safety evidence and wider availability of therapies.
  • A recommendation to use the antiviral drug nirmatrelvir-ritonavir in patients with non-severe COVID at high and moderate risk of hospital admission.
  • A recommendation against use of the antiviral drugs remdesivir and molnupiravir for patients with non-severe COVID at moderate and low risk of hospital admission (treatment is suggested for patients at high risk of admission).
  • A recommendation against use of a new antiviral (VV116) for patients with COVID except in clinical trials, regardless of illness severity.
  • A strong recommendation against the use of ivermectin for patients with non-severe COVID(advice against use of ivermectin in patients with severe or critical COVID, except in clinical trials, still exists).

The experts say the new recommendations reflect changes in the virulence and transmissibility of circulating SARS-CoV-2 variants and sub-variants, along with changes in immunity related to global vaccinations, which have led to lower baseline risks of severe illness and death for most patients with non-severe COVID.

They acknowledge that there are still uncertainties around COVID therapeutics and emerging evidence and say these recommendations need to be used in light of these uncertainties.

An interactive decision support tool is available to accompany this guidance.

Source: The BMJ

Categories : COVIDTags :

Omega-3 Fatty Acids Could Help Elderly COVID Patients

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Intravenous treatment with omega-3 fatty acids in elderly hospitalised patients in intensive care due to COVID seems to help the immune system’s ability to cope with the virus, according to a study published in the journal Clinical and Translational Medicine. These findings could lead to a complementary, cost-effective treatment for COVID.

In COVID patients, the immune system and the body’s activation of white blood cells are over-activated. It can lead to a so-called systemic inflammatory storm, which worsens the disease state and can cause complications such as sepsis and heart failure.

Researchers at Karolinska Institutet, among others, have now shown that omega-3 fatty acids can stimulate active healing of inflammation, without inhibiting the immune response. By accelerating the healing of the inflammation without compromising the body’s immune system, it could be possible to counteract the most serious complications of COVID, researchers believe.

Stimulated inflammation-healing molecules

The treatment effect was found by mapping inflammatory biomarkers and immunological reactions.

“First, we showed that fatty acid metabolism to inflammation-healing molecules was stimulated in those patients treated with omega-3 fatty acids. By isolating immune cells before, during, and after treatment, we were able to show that immune function improved,” said corresponding author Magnus Bäck, senior consultant in cardiology and professor at Karolinska Institutet.

Planning further studies

Researchers are now planning for larger clinical studies, which will be needed to show whether the course of the disease in severe COVID is improved through treatment with omega-3 fatty acids.

“It is important that even our weakest and frailest patients have the opportunity to participate in studies when the enemy, in this case, COVID, is on the attack and that they can fight the disease with the help of the medicine,” said Dorota Religa, senior consultant and professor in geriatrics at Karolinska Institutet.

“Stimulating the healing of inflammation with omega-3 fatty acids has the potential to lead to a new, cost-effective low-risk treatment for COVID-19, as a complement to existing treatment,” said Prof Magnus Bäck.

Source: Karolinska Institutet

Categories : COVIDTags :

Trial Suggests Early Metformin is Effective in COVID Treatment

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In a study published in the New England Journal of Medicine, researchers have found that metformin, a commonly prescribed diabetes medication, lowers the odds of emergency department visits, hospitalisations, or death due to COVID by over 40%; and over 50% if prescribed early in onset of symptoms. The study also found no positive effect from treatment with either ivermectin or low-dose fluvoxamine.

“Our trial suggests that metformin may reduce the likelihood of needing to go to the emergency room or be hospitalised for COVID,” said Carolyn Bramante, MD, principal investigator of the study.

The primary outcome was in fact low oxygen on a home oxygen monitor, which none of the medications in the trial prevented.

The COVID-OUT trial studied whether metformin, low-doses of the antidepressant fluvoxamine, the controversial antiparasitic ivermectin, or their combinations could serve as possible treatments to prevent ER visits or hospitalisation, as well as Long COVID.

Patients were randomised to receive one of the three drugs individually: placebo, or a combination of metformin and fluvoxamine or metformin and ivermectin. Although the study was placebo-controlled with exact-matching placebo pills, Dr Bramante said that 83% of volunteers received medications supported by existing data because of the six-arm design. Each participant received 2 types of pills to keep their treatment assignment masked, for 3 to 14 days of treatment. Each volunteer tracked their symptoms, and after 14 days, they completed a survey.

The 1323 participants in the trial were limited to adults with a body mass index greater than or equal to 25 kg/m2, which qualifies as overweight. To qualify for the study, volunteers enrolled within three days after receiving a positive COVID test. It was among the first randomised clinical trials for COVID to include pregnant women.

The study included those who were vaccinated and those who were not. This is the first published trial where the majority of participants were vaccinated. 

“Although we know COVID vaccines are highly effective, we know that some new strains of the virus may evade immunity and vaccines may not be available worldwide. So we felt we should study safe, available and inexpensive outpatient treatment options as soon as possible,” said Dr Bramante. “Understanding whether outpatient treatments could ensure more people survive the illness if they contract it and have fewer long-term symptoms is an important piece of the pandemic response.”

The clinical trial launched in January 2021 after researchers noticed that outpatient metformin use appeared to decrease the likelihood of mortality from, or being hospitalised for COVID. Their research was published in the Journal of Medical Virology and in The Lancet Healthy Longevity. Test-tube studies also found that metformin inhibited the -CoV-2 in lab settings. These findings, along with additional prospective studies supporting the use of higher-dose fluvoxamine and ivermectin, provided the evidence to include all three medications as well as combination arms.

Source: University of Minnesota

Categories : COVIDTags :

Few Patients get ‘Rebound COVID’ after Paxlovid Treatment

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Mayo Clinic researchers studied the outcomes of 483 high-risk patients  treated for COVID with a five-day oral regimen of Paxlovid, a combination of nirmatrelvir and ritonavir. Only a handful developed COVID rebound symptoms, something which the researchers say needs further investigation. Their findings appear in the journal Clinical Infectious Diseases.

All of the patients benefited from Paxlovid and recovered, including the patients who developed rebound symptoms, which were generally mild.

“We found that rebound phenomenon was uncommon in this group of patients,” says senior author Aditya Shah, MBBS, an infectious diseases physician and researcher at Mayo Clinic. “The four individuals who experienced rebound [symptoms] represent only 0.8% of the group, and all of them recovered quickly without additional COVID-directed therapy.”

Most of the patients had been vaccinated, and many had received booster vaccinations. The median age was 63. While these patients were high-risk for COVID, none was immunocompromised. Only two patients were admitted to the hospital, and it was for reasons other than COVID.

The study focussed on four patients with rebound symptoms:

  • A 75-year-old man with coronary artery disease who had increased cough and muscle aches 19 days after treatment.
  • A 40-year-old woman with obesity, hypertension and kidney disease who developed fatigue and sore throat six days after treatment.
  • A 69-year-old man with hypertension and obesity who exhibited nasal discharge and cough 10 days following therapy.
  • A 70-year-old man with a history of prostate cancer, obesity, hypertension and high cholesterol, who developed significant sinus congestion 10 days after treatment.

Why did some rebound?

Researchers think one explanation could be that a replication of SARS-CoV-2 could have triggered a secondary immune response, which showed up as mild COVID symptoms. This question could be answered by prospective studies could answer the question. They also note that all four patients with rebound symptoms had many serious health problems known as comorbidities — a factor shown to complicate recoveries. And all four patients had been vaccinated more than 90 days before becoming infected with COVI.

Source: Mayo Clinic

Categories : COVIDTags :

End of the Road for Ivermectin as COVID Treatment in South Africa

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Stop sign

South Africa’s medicines regulator has officially terminated the special dispensation to use Ivermectin as a treatment for COVID, stating that “there is currently no credible evidence to support a therapeutic role for Ivermectin” in the treatment of the disease.

On Monday 30 May, the South African Health Products Regulatory Authority (SAHPRA) officially withdrew its authorisation [PDF], bringing to end something of a saga which saw vocal proponents pitched against the scientific and regulatory establishment.

The antiparasitic Ivermectin gained considerable notoriety as the COVID pandemic went on, based on preliminary studies that seemed to demonstrate its effectiveness. Pressure born out of desperation for some kind of treatment led to SAHPRA – amidst its own apparent misgivings – granting compassionate use authorisation under strict guidelines in January 2021. Use was allowed under Section 21 guidelines without having to wait for Section 21 authorisation, which was misinterpreted as full authorisation by some media sources.

The social media furore and misinformation surrounding Ivermectin led to dangerous instances of COVID self-treatment, with hospitalisations and even deaths reported.

In its terribly botched response to COVID, Brazil adopted Ivermectin on a mass scale, and essentially became a living laboratory for its effectiveness. Despite even administering Ivermectin as prophylaxis, Brazil’s health system was overwhelmed with COVID patients during the surge caused by the Gamma variant.

Studies turned up scant evidence in favour of Ivermectin’s effectiveness, with serious flaws and even outright data fabrication were picked up in a number of studies that seemed to show a significant benefit – even flying right through the peer review process only to be picked up at a later stage. This lead to a major meta-analysis by Hill et al. showing a effectiveness instead being retracted, which SAHPRA noted in its decision.

Finally, the I-TECH and the Together randomised clinical trials of 2021 showed no effect. Like hydroxychloroquine before it, Ivermectin prescribing was found to be driven by political interests. Thus, Ivermectin quietly disappeared from the media as viable antivirals such as Paxlovid came into the market.

The termination comes after a distinct decline in demand for Ivermectin use in South Africa, with no new applications for importation of unregistered Ivermectin products place since August 2021. SAHPRA also noted a marked decline in the number of health facilities applying for permission to hold bulk stock after August 2021.

Furthermore, no individual named patient applications have been approved since December 2021. Finally, there was little in the way of reporting of outcomes achieved by the treating healthcare providers.

Categories : Allergies COVIDTags :

Montelukast Can Block Harmful SARS-CoV-2 Protein and Protect Immune Cells

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Targeting Nsp1 with montelukast helps prevent shutdown of host protein synthesis Credit: Mohammad Afsar

Montelukast can bind to and block a crucial protein produced by SARS-CoV-2, reducing viral replication in human immune cells, according to a new study by researchers at the Indian Institute of Science (IISc).

Montelukast has been around for more than 20 years and is usually prescribed to reduce inflammation caused by conditions like asthma, hay fever and hives.

In the study, published in eLife, the researchers showed that the drug binds strongly to the C-terminal, which is one end of a SARS-CoV-2 protein called Nsp1, which is one of the first viral proteins unleashed inside human cells. NSp1 can bind to ribosomes inside immune cells, shutting down production of vital proteins that the immune system needs, thereby weakening it. Nsp1 could therefore be a target to reduce the virus’s damage.

“The mutation rate in this protein, especially the C-terminal region, is very low compared to the rest of the viral proteins,” explained IISc’s Assistant Professor Tanweer Hussain, senior author of the study. Since Nsp1 is unlikely to change in future variants, targeting it with drugs is a viable strategy, he added.

The researchers screened more than 1600 FDA-approved drugs with computational modelling to find the ones that bound strongly to Nsp1, coming up with a shortlist of drugs including montelukast and saquinavir, an anti-HIV drug. “The molecular dynamic simulations generate a lot of data, in the range of terabytes, and help to figure out the stability of the drug-bound protein molecule. To analyse these and identify which drugs may work inside the cell was a challenge,” said Mohammad Afsar, first author of the study.

The researchers then cultured human cells which produced Nsp1, treated them with montelukast and saquinavir separately, and found that only montelukast was able to rescue the inhibition of protein synthesis by Nsp1.

“There are two aspects [to consider]: one is affinity and the other is stability,” explained Afsar. This means that the drug needs to not only bind to the viral protein strongly, but also stay bound for a sufficiently long time to prevent the protein from affecting the host cell, he adds. “The anti-HIV drug (saquinavir) showed good affinity, but not good stability.” Montelukast, on the other hand, was found to bind strongly and stably to Nsp1, allowing the host cells to resume normal protein synthesis.

The researchers then tested the effect of the drug on live viruses and found that the drug was able to reduce viral numbers in infected cells in the culture.

“Clinicians have tried using the drug … and there are reports that said that montelukast reduced hospitalisation in COVID patients,” said A/Prof Hussain, adding that the exact mechanisms behind it still need to be fully understood. His team plans to work with chemists to see if they can modify the structure of the drug to increase its potency, and also plan to continue the hunt for more drugs.

Source: Indian Institute of Science

Categories : COVIDTags :

WHO Panel Recommends Paxlovid for at-Risk Mild COVID

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Pfizer’s oral antiviral Paxlovid (nirmatrelvir/ritonavir) is strongly recommended for patients with non-severe COVID with greater hospitalisation risk, such as unvaccinated, older, or immunosuppressed patients, according to a WHO Guideline Development Group writing in The BMJ. 

The experts explained that Pfizer’s Paxlovid, a comnbination of nirmatrelvir and ritonavir tablets, is likely a better choice for these patients because it may prevent more hospitalisations than the alternatives, is safer than molnupiravir, and is easier to administer than intravenous options such as remdesivir and antibody treatments. 

Use in low-risk patients is not recommended due to trivial benefits. It is also not recommended for patients with severe or critical COVID, as there are currently no trial data on nirmatrelvir/ritonavir for this group.

Their recommendation is based on new data from two randomised controlled trials with 3100 patients.

In these trials, moderate certainty evidence showed that nirmatrelvir/ritonavir reduced hospital admission (84 fewer admissions per 1000 patients), low certainty evidence suggested no important difference in mortality, and high certainty evidence suggested little or no risk of adverse effects leading to drug discontinuation.

Additionally, WHO also makes a conditional (weak) recommendation to use the antiviral drug remdesivir for patients with non-severe COVID at highest risk of hospitalisation.

This is based on new data from five randomised controlled trials involving 2700 patients and replaces a previous recommendation against treatment with remdesivir in all patients with covid-19 regardless of disease severity.

Antiviral drugs should be administered as early as possible, but this may be challenging in low- and middle-income countries, the panel noted, and also that access to these drugs is tied to COVID tests.

The emergence of resistance is also an uncertain risk, they add.

This guidance adds to previous conditional recommendations for the use of molnupiravir for high-risk patients with non-severe COVID and for the use of sotrovimab or casirivimab-imdevimab (monoclonal antibody treatments) in selected patients; and against the use of convalescent plasma, ivermectin and hydroxychloroquine in patients with COVID regardless of disease severity. For patients with severe COVID, WHO strongly recommends corticosteroids, with the addition of IL-6 receptor blockers or baricitinib.

Source: EurekAlert!