COVID-19: Triple antiviral drug combo shows promise

A 2 week course of antiviral therapy that combines the power of 3 drugs has shown promise in treating hospitalised patients with mild to moderate COVID-19 in a carefully undertaken phase 2 clinical trial.

The results of the trial published in the journal Lancet, involved 127 adults from 6 public hospitals in Hong Kong.

The drug combinatipn tested in the trial included-- interferon beta-1b which was developed to treat multiple sclerosis (MS), lopinavir-ritonavir which is normally used to treat HIV and ribavirin, an oral hepatitis C virus durg.

The findings of the phase 2 trial provided evidence that early treatment with triple therapy alongside standard care is safe and shortens duration of viral shedding ( when the virus is detectable and potentially transmissible) compared to lopinavir-ritonavir alone-- average 7 days vs 12 days--- in patients with mild to moderate COVID-19.

People in the triple combination group spent 5.5 days less in hospital on average compared to those in the control group who received the lopinavir-ritonavir treatment alone.

Our trial demonstrates that early treatment of mild to moderate COVID-19 with a triple combination of antiviral drugs may rapidly suppress the amount of virus in a patient's body, relieve symptoms, and reduce the risk to health-care workers by reducing the duration and quantity ofviral shedding, said the lead researcher.

Furthermore, the treatment combination appeared safe and well tolerated by patients, he said.

Previous research found that a combination of oral lopinavir-ritonavir and ribavirin significantly reduced respiratory failure and death in patients hospitalised with severe acute respiratory syndrome (SARS) during the 2003 outbreak.

Interferon beta-1b has been shown to reduce viral load and improve lung problems in animal studies of Middle East respiratory syndrome (MERS) coronavirus infection.

The new study involving COVID-19 patients enrolled 127 adults admitted to one of 6 public hospitals with laboratory-confirmed SARS-Cov-2 ( the virus responsible for CVID-19) infection between February 10 and March 20 this year.

Participants were randomly assigned to 1 days of either the triple combination of oral lopinavir-ritonavir ( 400mg/100mg and ribavirin (400mg) every 12 hours, plus up to 3 doses of injectable interferon beta-1b ( 8 million international units) on alternate days for patients admitted to hospital less than 7 days from sympotm onset  ( 86 patients; combination group); or lopinavir-ritonavir alone every 12 hours ( 41 patients; control group).

In the trial, all patients received standard care including ventilation support, dialysis support, antibiotics and corticosteroids.

Treatment with the triple drug combination effectively suppressed viral load ( with no detectable virus) in the nasopharynheal swab within an average 7 days of starting treatment, which was signifcantly shorter than the average 12 days in the control group, treated with lopinavir-ritonavir alone.

Secondary outcomes supported the findings, indicating that clinical improvement was significantly better in the triple combination group-- with the triple therapy halving the time to complete alleviation of symptoms ( average 4 days vs 8 days) and resulting in significantly shorter average hospital stay ( 9 days vs 14.5 days).

These findings suggest that interferon beta 1-b may be a key component of the combination treatment and is worth further investigation for the treatment  of COVID-19, said study's co-author.

Interferons are naturally occurring proteins, produced in response to viral infection , and the hope is that interferon beta 1-b will boost the body's ability to fight SARS-Cov-2. Future phase 3 trials will soon confirm or refute the usefulness of this candidate drug as a backbone treatment for COVID-19.

There was no difference in adverse events between the treatment groups, and none of the side effects in the combination group were severe.

No patients died during the study.

However,  the researchers stressed the need for larger phase 3 trials to examine the effectiveness of this triple combination in critically ill patients.

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Arthritis drug Tocilizumab joins list of drugs that may help fight COVID-19

Since the beginning of the COVID-19 pandemic, scientists are trying desperately to find a cure for the disease. But despite many false hopes, they have not been able to zero in on any potential cure. Trials of possible cures have started in different parts of the world. But it may still be a long time before we see a vaccine in the market for the general public. Besides trying to find a new drug, scientists are also trying to figure out if any existing drug can be used to fight the pandemic. Examples include the malaria drug hydroxychloroquine and the tuberculosis vaccine. The latest drug to join the list is the rheumatoid arthritis medication Tocilizumab.

Researchers from UC San Diego Health have started a Phase III clinical trial to see if this medication has any therapeutic value for COVID-19 patients who develop or at high risk of developing serious lung damage from SARS-CoV-2 infections. Doctors commonly use this drug to treat rheumatoid arthritis and other inflammatory disorders. This endeavor is part of a global effort to find a cure for the ongoing pandemic at the earliest.Also Read - Scientists identify mobile phones as 'Trojan horses' for COVID-19

About the trial

This randomized, double-blind, placebo-controlled interventional trial will enroll around 330 participants at nearly 70 sites across the world. In UC San Diego, researchers will recruit around 20 participants who are 18 years or older. All participants are in hospital with COVID-19 pneumonia and have evidence of impaired gas exchange. They will receive one intravenous infusion of either tocilizumab or the placebo, with a possible second infusion if clinical symptoms worsen or show improvement. At the end of it, researchers are hopeful of being able to answer questions on whether tocilizumab can improve the health and clinical status of treated COVID-19 patients or if it can reduce the mortality rate due to COVID-19 pneumonia.  

About the drug

Tocilizumab is an immunosuppressive drug, which doctors use in the treatment of rheumatoid arthritis and systemic juvenile idiopathic arthritis. It is basically a monoclonal antibody-based therapy, which blocks cellular receptors for interleukin-6 (IL-6), a protein or cytokine that is known to trigger inflammation.

How it may help COVID-19 patients

The immune system of some COVID-19 patients seem to go haywire. There is an overexpression of IL-6 and this generates a ‘cytokine storm’. This can cause severe and fatal damage to the lungs and other organs of the body. Scientists have known for a long time that cytokine storms can lead to many serious inflammatory diseases including respiratory ailments caused by coronaviruses, influenza, multiple sclerosis and also pancreatitis.

Now, to control the COVID-19 outbreak in Wuhan, China, doctors there had used this drug to treat a few patients with serious lung damage. They were surprised to see promising results. Because of this, the Chinese National Health Commission now includes tocilizumab in its guidelines for treating COVID-19-related pneumonia and other lung issues.

What experts say

Many voices from the scientific community warn that this must not be seen as a cure for COVID-19. It is important to reiterate again and again right now that there are no approved therapies for COVID-19. Doctors treat the patient only for the symptoms that he or she may exhibit. Moreover, COVID-19 affects patients in many different ways and inflammation of lungs is just one of the symptoms. Tocilizumab can suppress this inflammatory response and it may reduce the need for more extreme medical interventions like mechanical ventilation and greater risk of chronic injury and death, say UC San Diego researchers.

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New immune cell with 'Jekyll and Hyde properties' identified

Scientists at Trinity College Dublin have identified a rare, new cell in the immune system with "Jekyll and Hyde properties". These cells play a key protective role in immunity to infection but - if unregulated - also mediate tissue damage in autoimmune disorders.

The findings should help us design more effective vaccines to prevent infections such as MRSA, and may also assist help us develop of new therapies for autoimmune diseases, such as multiple sclerosis or rheumatoid arthritis.

The immune system functions to control infection, utilizing various immune cells, such as T cells to respond to and control invading microbes. However, if these immune cells are not highly regulated, they can attack and damage body tissues, leading to the development of autoimmune diseases.

Molecules called T cell receptors (TCRs) allow T cells to recognize components of infectious agents with exquisite specificity. The TCRs enable T cells to respond to and eventually eliminate the infectious agent.

Professor Kingston Mills said:   Until now scientists thought that there were two discrete populations of T cells, expressing either 'αβ' or 'γδ' TCRs. The αβs are the most common T cells in the body. They play a key role in remembering prior infection or immunization and thereby help protect us against re-infection and mediate vaccine-induced protective immunity. The γδs are more prevalent at mucosal surfaces, such as the lung or gut, and provide an immediate first line of defense against pathogens that invade through these routes."

We have discovered a new cell type that expresses both αβ and γδ TCRs. This rare population of chimeric or hybrid αβ-γδ T cells has properties of both αβ and γδ T cells. Importantly, they are normally highly activated and poised to act as first responders to control bacterial infection. However, given this high level of activation, they are effectively 'Jekyll and Hyde cells' because in certain contexts they can also precipitate autoimmune responses."

Using a model of Staphylococcus aureus infection, Professor Mills and his team found that these cells are rapidly mobilized during infection and play a key role in quickly eliminating the microbes from the body.

The induction of these hybrid αβ-γδ T cells may thus represent a novel approach in the design of more effective vaccines against Staph aureus and other infectious diseases, while advancing our ability to control their response may yield additional therapeutic options.

Professor Mills added:   In a model of autoimmune disease, we found that the hybrid T cells can also trigger the inflammatory cascade that mediates tissue damage in autoimmunity. Therefore, approaches for inhibiting these highly activated immune cells in susceptible individuals may open up new approaches for the treatment of autoimmune diseases such as psoriasis and multiple sclerosis."

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Causes and treatment for internal vibrations

Internal vibrations, also known as internal tremors, can affect people with Parkinson's disease, multiple sclerosis, or essential tremor. Internal tremors are not harmful, but they be can be worrying and may interfere with a person's daily life.

 

Internal tremors are shaking sensations felt inside the body. They occur without visible movement, which external tremors produce.

A person may experience internal tremors in the trunk, arms, legs, or internal organs.

In this article, we look at the causes and treatment of internal tremors.

Causes

Internal tremors can occur in the trunk or the limbs.

People with Parkinson's disease (PD), multiple sclerosis (MS), or essential tremor (ET) may experience internal and external tremors.

The causes of internal tremors are not well understood, and current research is limited. However, doctors tend to believe that these tremors stem from the same neurological causes of external tremors.
A study published in 2017 found a link between tremors and social anxiety. Some researchers have also suggested that internal tremors may produce physical movement too slight to detect.

Authors of a 2016 study have suggested that internal tremors are early, unusual symptoms of movement disorders, such as PD. Other researchers have proposed that anyone can experience internal tremors, but they are more pronounced in people with PD, MS, and ET.
Below, find more information about PD, MS, and ET, the three most common causes of internal tremors.

Parkinson's disease

PD is a neurological disease that results from the loss of dopamine-producing brain cells. It usually occurs in people over 60 years old.
People with PD may experience some of the following symptoms:

• slowness of movement
• external tremors, including visible trembling in the hands, limbs, face, and jaw
• internal tremors
• stiffness of the arms, legs, and trunk
• poor coordination and balance

These symptoms may progress quickly or slowly, and they can make daily activities difficult. Tremors are not always the most evident symptom of PD, though many people with the condition have tremors.
Initially, a person may only experience a tremor in one limb. As the condition progresses, the tremor can spread to both sides of the body. Strong emotions and stress can make tremors worse.

Treatments for PD

There is no cure for PD. It is a chronic condition that progresses over time. However, there are several treatment options.
A doctor may prescribe a combination of levodopa and carbidopa to replenish the brain's dopamine supply. This can help to treat advanced PD.
Other drug-related options include bromocriptine, pramipexole, and ropinirole.
A doctor may recommend surgery for people who do not respond to medication. The primary type is called deep brain stimulation (DBS).
During the procedure, a surgeon implants electrodes in a person's brain. These stimulate targeted areas to alleviate some symptoms of PD. DBS can also reduce the need for certain drugs, and this may especially benefit people experiencing unpleasant side effects.

Multiple sclerosis (MS)

Damage to the nerves characterizes multiple sclerosis.

MS is a chronic condition that affects the central nervous system (CNS).
Many experts believe that in a person with MS, the immune system attacks and damages the body's nerves.
This can affect many parts of the body, and it can have a significant impact on a person's quality of life.
Symptoms of MS usually develop between the ages of 20 and 40. They can include:

• blurred or double vision
• color blindness
• blindness in one eye
• muscle weakness
• poor coordination and balance
• a sensation of numbness or pins and needles
• pain
• speech difficulties
• internal and external tremors
• dizziness

Around half of the people with MS also experience difficulty with:

• memory
• attention
• concentration
• judgment

A person may also experience tremor.

Treatment of MS

There is currently no cure for MS, and its severity varies from person to person.
Disease-modifying therapies (DMTs)
In the past, doctors considered MS untreatable, but new drugs and treatment options are changing the outlook.
Current guidelines from the American Academy of Neurology (AAN) advise doctors to start prescribing a type of medication known as disease-modifying therapy (DMT) as soon as possible after a diagnosis.
With early use, these drugs appear to reduce the numbers of flares that a person experiences in relapsing-remitting MS (RRMS), and they may slow the progression of the disease.
Examples include:

• injectable interferon beta-1a and 1-b, such as Avonex and Extavia
• injectable glatiramer acetate, for example, Copaxone and Glatopa
• oral medications, such as siponimod (Mayzent) and fingolimod (Gilenya)
• infusions, including alemtuzumab (Lemtrada) and ocrelizumab (Ocrevus)

Mitoxantrone is an older DMT that can have severe adverse effects. A doctor will only prescribe it if a person has severe symptoms and if the possible benefits outweigh the risks for the individual.
Anyone who has been using mitoxantrone for some time should ask their doctor about newer drugs that may be safer and more effective.
Flares and symptoms
A person will take a DMT regularly, whether they are experiencing a relapse or not.
When flares occur, a doctor may prescribe:

• steroid injections to reduce inflammation and help manage severe symptoms
• specific medications to help with specific symptoms, such as weakness and muscle spasms

A doctor may prescribe muscle relaxers or tranquilizers for people with sustained muscle stiffness and spasticity.
Treatment for tremor
Drugs to help relieve tremor include:

• isoniazid, for example, Laniazid or Nydrazid
• clonazepam, for instance, Klonopin, Rivotril or Syn-Clonazepam

Non-drug therapies
Exercise, occupational therapy, and physical therapy can also help. A doctor can advise on an exercise plan to suit an individual's needs.
They may also advise on assistive devices that may help, such as a walking cane.
The symptoms and progress of MS vary widely between individuals. Each person will make a treatment plan with their doctor to suit their needs.

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Essential tremor

ET is the most common type of abnormal tremor.
The condition is sometimes associated with mild degeneration of some of the cerebellum. This is the part of the brain that receives information needed to regulate the quality of a person's movements.
The cerebellum receives this information from other parts of the brain, the spinal cord, and the body's sensory systems.
People with ET may experience unintentional, rhythmic movements, most commonly a hand tremor. The tremor may also affect the head, tongue, limbs, trunk, and the ability to speak.
Symptoms can develop at any age, but they usually become noticeable in people over the age of 40. Triggers of ET can include:

• stress and anxiety
• heightened emotions
• fever
• feeling physically tired
• low blood sugar

The tremor usually appears on both sides of the body, but it is often more noticeable in the dominant hand.

Treatment of ET

While there is no cure for ET, medications can help to reduce symptoms. These can include beta-blockers or anti-convulsants.
Some people with ET find physical, occupational therapy, and DBS helpful. Treatment plans often involve reducing triggers, such as caffeine and other stimulants.

Treatment

A doctor will prescribe treatment for internal tremors according to the cause.

There are currently no diagnostic tests for internal tremors. However, anyone experiencing a tingling sensation, shaking, muscle weakness, or poor coordination should speak with a doctor.
For people with internal tremors, doctors may recommend treatments similar to those for other movement or neurological disorders.
However, the severity of internal tremors can vary from person to person, and some may find that no treatment is necessary.
When PD, MS, or ET is responsible for internal tremors, doctors will aim to treat the underlying condition.
Treatments for internal tremors can include:

• reducing anxiety and stress
• avoiding dietary stimulants, such as caffeine
• avoiding intense exercise and heat

For some people, doctors may recommend DBS or medications similar to those for PD, MS, and ET.

Outlook
While internal tremors are not harmful, they can be disconcerting and may interfere with daily activities.
PD, MS, and ET are the most common causes of internal tremors. For many people, treatments for tremors will be similar to treatments for these neurological conditions.
Avoiding known triggers, such as stress or stimulants, can also help.

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