Tag: covid treatment

Categories : COVIDTags :

Anti-Spike Antibodies Key for Surviving Severe COVID

On By ModernMedia
SARS-CoV-2 viruses (yellow) infecting a human cell. Credit: NIH

In a study of patients with COVID being treated in intensive care units, people mounting only a low antibody response against the SARS-CoV-2 virus had a greater risk of dying. 

Previous studies by the researchers had indicated that levels of SARS-CoV2 viral RNA and antigens in the blood was related to COVID severity.

The study, which is published in the Journal of Internal Medicine, recruited 92 patients severely ill with COVID who were admitted to the ICU. The researchers found that patients with strong antibody responses against the virus had low levels of viral RNA in their blood, especially anti-S (Spike protein) antibodies. Those with poor antibody responses had high viral RNA levels and disseminated viral proteins in the blood, 2.5 times higher than those with strong antibody responses. 

Previous studies have shown that critical COVID patients develop higher titers of SARS-CoV-2 antibodies than those with milder disease, suggesting that antibody response alone is insufficient to avoid severe disease. The findings nonetheless support that critical COVID patients would need to mount a robust anti-S antibody response to survive.

The results could help establish the optimal antibody levels needed for an individual to overcome COVID when critically ill. The study also provided evidence of the importance of antibodies against the Spike protein of SARS-CoV-2 to block the virus’ replication, which are the antibodies induced by vaccination.  

“Our findings support that treatment with exogenous antibodies in COVID should be personalised, reserving this therapy for those patients with absent or low endogenous antibodies levels,” said co–senior author Jesús F. Bermejo-Martin, MD, PhD, of the Instituto de Investigación Biomédica de Salamanca (IBSAL) & CIBERES, in Spain.

Source: Wiley

Categories : COVIDTags :

New Drug Molnupiravir Halves COVID Hospitalisation Risk

On By ModernMedia
Source: Fusion Medical Animation on Unsplash

Merck today announced that their investigational oral antiviral drug molnupiravir significantly reduced the risk of hospitalisation or death in a Phase III trial in at risk patients with mild-to-moderate COVID. 

Interim analysis showed that molnupiravir reduced the risk of hospitalisation or death by approximately 50%; 7.3% of patients randomised to receive molnupiravir were either hospitalised or died through Day 29 following randomisation, compared with 14.1% of placebo-treated patients. Through Day 29, no deaths were reported in patients who received molnupiravir, as compared to 8 deaths in patients who received placebo. Study recruitment is being stopped early due to these positive results, and the company plans to submit an application for Emergency Use Authorisation (EUA) to the U.S. FDA as soon as possible.

Molnupiravir is an oral form of a potent ribonucleoside analog that inhibits the replication of SARS-CoV-2. Molnupiravir has been shown to be active in several preclinical models of SARS-CoV-2, including for prophylaxis, treatment, and prevention of transmission. 

All 775 patients had laboratory-confirmed mild-to-moderate COVID, with symptom onset within 5 days of study randomization and were required to have at least one risk factor associated with poor disease outcome at study entry. Across all key subgroups, molnupiravir reduced the risk of hospitalisation and/or death; efficacy was unaffected by timing of symptom onset or underlying risk factor. Additionally, based on the participants with available viral sequencing data (approximately 40% of participants), molnupiravir demonstrated consistent efficacy across viral variants Gamma, Delta, and Mu.

The incidence of any adverse event was comparable in the molnupiravir and placebo groups, as was incidence of drug-related adverse events, and the drug was well tolerated.

In addition, molnupiravir is being evaluated for post-exposure prophylaxis in MOVe-AHEAD, a global, multicenter, randomised, double-blind, placebo-controlled Phase III study, which is evaluating the efficacy and safety of molnupiravir in preventing the spread of COVID within households. 

Source: Merck

Categories : COVID HospitalsTags :

ECG Readings Can Predict Worsening and Mortality in COVID and Influenza

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Photo by Towfiqu barbhuiya from Pexels

Specific and dynamic changes on electrocardiograms (ECGs) of hospitalised COVID patients with COVID or influenza can help predict a timeframe for worsening health and death, according to a new Mount Sinai study.

Published in the American Journal of Cardiology, the study shows that shrinking waveforms on these tests can be used to help better identify high-risk patients and provide them more aggressive monitoring and treatment.  

“Our study shows diminished waveforms on ECGs over the course of COVID illness can be an important tool for health care workers caring for these patients, allowing them to catch rapid clinical changes over their hospital stay and intervene more quickly. […] ECGs may be helpful for hospitals to use when caring for these patients before their condition gets dramatically worse,” said senior author Joshua Lampert, MD, Cardiac Electrophysiology fellow at The Mount Sinai Hospital. “This is particularly useful in overwhelmed systems, as there is no wait for blood work to return and this test can be performed by the majority of health care personnel. Additionally, the ECG can be done at the time of other bedside patient care, eliminating the potential exposure of another health care worker to COVID.”

Researchers did a retrospective analysis of ECGs on 140 hospitalised COVID patients across the Mount Sinai Health System in New York City, and compared them with 281 ECGs from patients with laboratory-confirmed influenza A or B admitted to The Mount Sinai Hospital.  
For each patient, the researchers compared three ECG time points: a baseline scan done within a year prior to COVID or influenza hospitalisation, a scan taken at hospital admission, and follow-up ECGs performed during hospitalisation.

They manually measured QRS waveform height on all electrocardiograms – changes in this electrical activity can indicate failing ventricles. The researchers analysed follow-up ECGs after hospital admission and analysed changes in the waveforms according to a set of criteria they designed  called LoQRS amplitude (LoQRS) to identify a reduced signal. LoQRS was defined by QRS amplitude of less than 5mm measured from the arms and legs or less than 10mm when measured on the chest wall as well as a relative reduction in waveform height in either location by at least 50%.

Fifty-two COVID patients in the study did not survive, and 74% of those had LoQRS. Their ECG QRS waveforms reduced approximately 5.3 days into their hospital admission and they died approximately two days after the first abnormal ECG was observed.

Out of the 281 influenza patients studied, LoQRS was identified in 11 percent of them. Seventeen influenza patients died, and 39% had LoQRS present. Influenza patients met LoQRS criteria a median of 55 days into their hospital admission, and the median time to death was six days from when LoQRS was identified. Overall, these results show influenza patients followed a less virulent course of illness when compared to COVID patients.

“When it comes to caring for COVID patients, our findings suggest it may be beneficial not only for health care providers to check an EKG when the patient first arrives at the hospital, but also follow-up ECGs during their hospital stay to assess for LoQRS, particularly if the patient has not made profound clinical progress. If LoQRS is present, the team may want to consider escalating medical therapy or transferring the patient to a highly monitored setting such as an intensive care unit (ICU) in anticipation of declining health,” added Dr Lampert.

Source: The Mount Sinai Hospital / Mount Sinai School of Medicine

Categories : COVIDTags :

New Antiviral Drug for COVID to Be Trialled in SA

On By ModernMedia
Source: CDC

Codivir, a new antiviral drug with promising effects against COVID, will be trialled in South Africa.

Following on from the phase I study’s successful completion, Code Pharma, a Dutch pharmaceutical company developing Codiviir, is starting phase II double-blind controlled study in Spain, Brazil, South Africa and Israel.

Codivir is a short synthetic 16 amino-acid peptide, originally derived from HIV peptides. Code Pharma discovered the peptide’s direct antiviral effect against SARS-CoV-2 after in vitro studies at the British virology research laboratory, Virology Research Services in London.

Codivir was tested in a phase I trial in São Paulo, Brazil, where researchers found that Codivir had a high safety profile while significantly suppressing viral replication in most of the fully assessed patients. All treated patients recovered quickly and no side effects often associated with COVID infections were seen. The results also indicated that Codivir might have a similar beneficial effect on other RNA viruses such as influenza.

Lead researchers from the Department of Medicine at Hadassah Medical Center, Dr Yotam Kolben and Dr Asa Kesler said the antiviral drug had potential for improving the current therapies for COVID.

“The pre-clinical data and the results of the clinical trial support the safety of Codivir administration in humans and suggest its significant anti-COVID effect,” the researchers said.

Professor Shlomo Maayan, director of the Infectious Disease division at the Barzilai Medical Center, said Codivir had a very good safety profile and an impressive antiviral effect, both in the lab and in the phase I clinical trials.

“We eagerly await the results of the double-blind studies using Codivir. It may be a breakthrough in the field of antiviral therapy for COVID patients,” said Prof Maayan.

Source: Biospace

Categories : COVIDTags :

A KZN Doctor’s Observations and Treatments of COVID

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SARS-CoV-2 viruses (yellow) infecting a human cell. Credit: NIH

Dr Shankara Chetty, a general practitioner with a natural science background in genetics, advanced biology, microbiology and biochemistry, has been critically reviewing information that has arisen from observations of the COVID pandemic from around the world. Knowledge gained from a broad natural science background convinced him that there was a missing element in these reports. This is a summary of an article published in Issue 5 of Modern Medicine in 2020.

“A wealth of knowledge of hospital presentations, pathology and investigations has been generated, but there has been a distinct lack of information regarding initial presentation, progression and pathogenesis,” said Dr Chetty.

Type 1 hypersensitivity reaction
When COVID arrived in South Africa, Dr Chetty isolated himself so as to limit interactions with family and the public and erected a tented field clinic in his practice parking so as to be able to examine and follow up on every COVID patient without risk to his other patients. According to him he had a theoretical understanding of the possible pathogenesis but needed to verify his suspicions.

“From the examination, treatment and follow up of over 200 symptomatic COVID patients, it is my opinion that COVID illness has two aetiologies. It is initially a respiratory viral infection with typical symptoms, progression and outcomes over the initial 7 days. On around day 7, a Type 1 hypersensitivity reaction is triggered in those that are sensitive, leading to the sequelae typically seen on admission.

“This reaction causes the release of chemical mediators in the ling, resulting in inflammation, oedema, and in time, massive cell damage. The resultant cellular disruption is what triggers the ‘cytokine storm’ in an attempt to repair damaged cells and remove debris. This release of cytokine produces the variety of pathologies that are seen,” said Dr Chetty.

Rapid response to treatment
His treatment protocol included the use of hydrochloroquine, azithromycin and doxyclcline to combat the viral component and antihistamines, leukotriene receptor antagonists and steroids, amongst others, for the Type 1 hypersensitivity reaction. This protocol produced consistent outcomes, no sequelae, and rapid recovery of all patients. In all, they had no deaths, no hospitalisations and recover of all patients, regardless of age, within 14 days.

“Outcomes of identifying and treating a Type 1 hypersensitivity reaction were most telling in the more severe dyspnoiec patients, with saturations below 85% on presentation that had improvement to over 95% in 24 hours, with outpatient management on room air, negating the need for oxygen or hospitalisation,” said Dr Chetty.

According to Dr Chetty, the rapid response to these medications used to treat Type 1 hypersensitivity reactions confirmed its existence. This could have some serious implications for the future management of the COVID pandemic. Monitoring for a hypersensitivity reaction and prompt treatment would decrease morbidity and mortality significantly.

Source: Modern Medicine

Categories : COVID HospitalsTags :

Prone Positioning Reduces Need for Mechanical Ventilation

On By ModernMedia
Source: Martha Dominguez de Gouveia on Unsplash

A ‘meta-trial’ of 1100 hospitalised COVID patients requiring high-flow nasal cannula oxygen therapy suggests that prone positioning soon after admission can significantly reduce the need for mechanical ventilation.

While acute respiratory distress syndrome patients have been placed prone for years by critical care specialists, this study provides clinical evidence needed to support the use of prone positioning for patients with COVID requiring high-flow nasal cannula oxygen therapy.

The findings, published today in the Lancet Respiratory Medicine, were conducted on severely ill COVID patients between April 2020 and January 2021.

“Breathing in the prone position helps the lungs work more efficiently,” explained the study’s lead author Dr. Jie Li, associate professor and respiratory therapist at Rush University Medical Center. “When people with severe oxygenation issues are laying on their stomachs, it results in better matching of the blood flow and ventilation in the lungs which improves blood oxygen levels.”

Prof Li noted that several interventions are available to improve oxygenation in critically ill patients, but that there was little outcomes-focused clinical evidence to show that prone positioning prior to mechanical ventilation is beneficial.

Adult patients with COVID needing respiratory support from a high-flow nasal cannula agreed to participate in this clinical trial, and were randomly assigned to the supine or prone positioning groups. They were asked to stay in that position for as long as they could tolerate. Both positioning groups received high-flow oxygen therapy and standard medical management.

Patients were continually monitored to determine if mechanical ventilation was needed. This study’s data showed that patients in the prone positioning group were significantly less likely to require mechanical ventilation (33% in the awake prone positioning group vs 40% in the supine group).

Another study lead author, Stephan Ehrmann, MD, PhD, said that “for the clinical implications of our study, awake prone positioning is a safe intervention that reduces the risk of treatment failure in acute severe hypoxemic respiratory failure due to COVID-19. Our findings support the routine implementation of awake prone positioning in critically ill patients with COVID19 requiring high flow nasal cannula oxygen therapy. It appears important that clinicians improve patient comfort during prone positioning, so the patient can stay in the position for at least 8 hours a day.”

Reducing the need for mechanical ventilation cuts down on resources needed. “Ventilators can indeed save the lives of people who are no longer able to breathe on their own. That said, we now have strategies to keep patients off the ventilator, saving those devices for the sickest patients who truly need them.” Prof Li added.

Source: Medical Xpress

Categories : COVIDTags :

Molnupiravir Works by Inducing Mutations in SARS-CoV-2

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Researchers have shown that the antiviral drug molnupiravir, currently in clinical trials as a COVID treatment, works by inducing mutations in SARS-CoV-2 which prevent the coronavirus from replicating further.

Since the onset of the corona pandemic, researchers have been developing various vaccines and drugs to varying degrees of success. Previous studies have shown why the antiviral drug remdesivir, the first one approved against COVID, has a rather weak effect on the virus. “Remdesivir does interfere with the [viral] polymerase while doing its work, but only after some delay. And the drug does not fully stop the enzyme,” said Max Planck Director Patrick Cramer. 

Molnupiravir was originally developed to treat influenza and in preliminary clinical trials, the compound is promising against SARS-CoV-2. “Knowing that a new drug is working is important and good. However, it is equally important to understand how molnupiravir works at the molecular level in order to gain insights for further antiviral development,” explained Cramer. “According to our results, Molnupiravir acts in two phases.”

Induced RNA mutations halt replication
Molnupiravir, an orally available drug, becomes activated through metabolisation in the body. When it enters the cell, it is converted into RNA-like building blocks. In the first phase, viral RNA polymerase incorporates the building blocks into the virus’ own RNA. However, unlike remdesivir, which merely slows the viral RNA polymerase, molnupiravir does not interfere with its copying functions. Instead, in the second phase, the RNA-like building blocks connect with the building blocks of the viral genetic material. “When the viral RNA then gets replicated to produce new viruses, it contains numerous errors, so-called mutations. As a result, the pathogen can no longer reproduce,” explained Florian Kabinger, a doctoral student in Cramer’s department.
Molnupiravir also appears to do this for other viruses “The compound could potentially be used to treat a whole spectrum of viral diseases,” said Höbartner, a professor of chemistry at the University of Würzburg. “Molnupiravir has a lot of potential.” 
Currently, molnupiravir is in phase III studies, where it is being tested on a large number of patients and is being evaluated for safety. The US government has already secured 1.7 million doses, at a cost of US$1 billion. However, working out at a cost of nearly US$600 per dose, it will not be cheap.

The researchers published their findings in Nature Structural & Molecular Biology.

Source: Max Planck Institute

Categories : COVIDTags :

High-dose Heparin Reduces Worsening in Moderate COVID

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Source: Fusion Medical Animation on Unsplash

Giving moderately ill hospitalised COVID patients a full-dose of heparin reduced the risk for organ support, and shortened hospital stays, a large clinical trial has found.

However, the use of this treatment strategy for critically ill COVID patients did not result in the same outcomes. 

“These results make for a compelling example of how important it is to stratify patients with different disease severity in clinical trials. What might help one subgroup of patients might be of no benefit, or even harmful, in another,” said NHLBI Director Gary H. Gibbons, M.D.

Researchers have observed that in some people who died from COVID, blood clots had formed throughout their bodies, even in their smallest blood vessels. Antithrombotics, which include blood thinners or anticoagulants, help prevent clot formation in certain diseases. It was not known which antithrombotic drug, what dose, and at what point during the course of COVID, antithrombotics might be effective. To answer these urgent questions, three international partners came together and harmonised their trial protocols to study the effects of using a full, or therapeutic dose, of heparin versus a low, or prophylactic dose, of heparin in moderately and critically ill patients hospitalised with COVID.

Moderately ill patients were defined as being hospitalised for COVID without needing organ support, and critically ill patients as hospitalised for COVID and needing intensive care level of support, including respiratory and/or cardiovascular organ support.

In April 2020, hospitalised COVID patients received either a low or full dose of heparin for up to 14 days after enrollment. By December 2020, interim results suggested that in critically ill patients, full-dose anticoagulation did not reduce the need for organ support and may even be harmful. However, one month later, results suggested full heparin doses likely benefited moderately ill patients.
“The formal conclusions from these studies suggest that initiating therapeutic anticoagulation is beneficial for moderately ill patients and once patients develop severe COVID-19, it may be too late for anticoagulation with heparin to alter the consequences of this disease,” said Judith Hochman, M.D., senior associate dean for Clinical Sciences at New York University, a corresponding author. “The medication evaluated in these trials is familiar to doctors around the world and is widely accessible, making the findings highly applicable to moderately ill COVID-19 patients.”

Fnal trial data analysis included 1098 critically ill and 2219 moderately ill patients. Among moderately ill patients, researchers found that the likelihood of full-dose heparin to reduce the need for organ support compared to those who received low-dose heparin was 99%. Major bleeding was rare. For critically ill patients, full-dose heparin also decreased the number of major thrombotic events, but it did not reduce the need for organ support or shorten hospital stay.

“More work needs to be done to continue to improve outcomes in patients with COVID-19,” said Matthew D. Neal, M.D., the Roberta G. Simmons Associate Professor of Surgery at the University of Pittsburgh, co-senior author. “Given what we know about the type of blood clots in patients with COVID-19, testing anti-platelet agents is a particularly exciting approach.”

Source: NIH

Categories : COVID Ethics and LawTags :

Large Ivermectin Study Retracted Due to Data Problems Ethical Concerns

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Photo by Markus Winkler on Unsplash

MedPage Today reports that a large ivermectin study has been retracted over concerns of plagiarism and serious problems with their raw data.

Michele Avissar-Whiting, PhD, editor-in-chief of the preprint server Research Square, wrote in a July 14 statement that the study was retracted “because we were presented with evidence of both plagiarism and anomalies in the dataset associated with the study, neither of which could reasonably be addressed by the author issuing a revised version of the paper.”

Dr Avissar-Whiting noted that the concerns were first raised by Jack Lawrence, a British medical student, according to The Guardian.

“Based on what Jack found, we have reason to believe the preprint’s conclusions are compromised, so the withdrawal was done to stop its propagation as sound science,” she said. “This is the strategy employed by a number of preprint servers, per best practice guidance.”

The 400-patient Egyptian trial, from Ahmed Elgazzar, MD, of Benha University, and colleagues, had been included in two recent meta-analyses (Bryant et al. and Hill et al.) which drew significant attention for their positive results — especially the much-anticipated Hill review. Two ivermectin proponent groups, the Front Line COVID-19 Critical Care Alliance (FLCCC) and the British Ivermectin Recommendation Development Group (BIRD), released a statement saying that removing the Algazzar data from the two studies did not change their overall positive result.

In an email to MedPage Today, lead author Andrew Hill, PhD, of the University of Liverpool in England, said  that his team will be “re-running our analysis with the Elgazzar trial removed.”

Dr Hill added that the analysis would also be updated with a recent 500-patient randomised controlled trial from Argentina, which found no effect for ivermectin in terms of preventing hospitalisation in patients with COVID. The study also fiend that patients receiving ivermectin required invasive ventilation sooner than those on placebo.

“In our published paper, we emphasised the preliminary nature of our results and the need to continue more definitive studies,” Hill wrote in his email.

The Elgazzar study’s main findings have already been cited by other publications: Hospitalised patients with COVID who were treated with ivermectin were 90% less likely to die than those who didn’t receive the drug. 

Lawrence had taken on an assignment for medical school which had prompted a deeper look at the paper, coming across plagiarism with entire paragraphs copied from other sources.

Additionally, the raw data, which can be purchased online, contradicted the study in several instances. Gideon Meyerowitz-Katz, an epidemiologist from the University of Wollongong in Australia, highlighted some of those discrepancies in a Medium post.

“For example, the study reports getting ethical approval and beginning on the 8th of June, 2020, but in the data file uploaded by the authors onto the website of the preprint fully 1/3 of the people who died from COVID were already dead when the researchers started to recruit their patients,” Meyerowitz-Katz wrote.

“Moreover, about 25% of the entire group of patients who were recruited for this supposedly prospective randomised trial appear to have been hospitalised before the study even started, which is either a mind-boggling breach of ethics or a very bad sign of potential fraud,” he continued.
Other phase III randomised clinical trials continue to investigate ivermectin for COVID such as the PRINCIPLE trial which seeks 1500 participants for its ivermectin arm.

Source: MedPage Today

Categories : COVID Diet and NutritionTags :

Could Nutritional Supplements Play a Role in Fighting COVID?

On By ModernMedia
Photo by Diana Polekhina on Unsplash
Photo by Diana Polekhina on Unsplash

Researchers suggest that nutritional supplements such as Vitamin C do play a role in reinforcing the immune system against SARS-CoV-2.

An article in Advances in Experimental Medicine and Biology lays out the scientific rationale and possible benefits — as well as possible drawbacks — of several dietary supplements currently in clinical trials related to COVID-19 treatment. The article was written by Johns Hopkins Medicine gastroenterologist Gerard Mullin, MD, and colleagues.

Dr Mullin, associate professor of medicine at the Johns Hopkins University School of Medicine, and his colleagues shine a light on melatonin, vitamin C, vitamin D, zinc and several plant-based compounds, such as green tea and curcumin. For instance, the authors explained that vitamin C (ascorbic acid), “contributes to immune defense by supporting cell functions of both the innate and adaptive immune systems.”

The authors discuss in the journal article the mechanism of action of each of the supplements works, how each could benefit a patient with COVID.

Zinc is well tolerated, and well known for its antioxidant, anti-inflammatory, immunomodulatory, and antiviral activities, the latter possibly mediated by its ability to inhibit RNA virus replication, thereby protecting cells from viral infection, oxidative damage, and dysfunction. It has been shown “to inhibit coronavirus RNA replication.” They also noted that, when administered at symptom onset, zinc “can reduce the duration of symptoms from illness attributed to more innocuous coronavirus infections, such as the common cold.”

Finally, Dr Mullin and colleagues gave short summaries of the clinical trials underway to test each supplement’s effectiveness in fighting COVID.

Regarding Vitamin D, which has received a lot of attention with regard to COVID outcomes, Dr Mullin said that, “to date, there are abundant data associating low vitamin D status to higher vulnerability to COVID-19 and poor clinical outcomes.”

The authors however struck a note of caution in that “any benefit of dietary supplements against COVID-19 depends on results of randomised controlled trials” and peer-reviewed literature.

Source: John Hopkins Medicine