In this era of natural catastrophe, darkening the horizon of human progression and threatening the very existence of humanity, there appears to be glimpses of optimism in our quest for the prevention against and treatment options adjunct to averting the illness brought on by this unprecedented agent of calamity unique to this century.
It is well indubitable by now that the infective agent, a coronavirus, known as SARS-CoV-2, causes an illness, Covid-19, and is particularly malicious to older people with co-morbidities of pre-existing heart and lung disease, or diabetes.
These people are at the greatest risk of developing the most severe form of the illness often adjudicating in fatality. To begin with and until only recently, there has been no prospect of an early vaccination or drugs to prevent or effectively treat the disease, necessitating urgent need for development of novel vaccines and new treatments, particularly in the battle against the most severe and potentially fatal form of the illness.
Only a few weeks ago, Dhaka Tribune published my article on the “drug study” of medical treatment of Covid-19 by the researchers from the University of Oxford. Their study had revealed the beneficiary effect of Dexamethasone, a synthetic corticosteroid on Covid-19 infective illness.
Glimpses of hope
On July 20, another research study has been conducted by the researchers from University of Southampton, UK on the effect of treatment of Covid-19 by the drug Interferon-beta (INF-beta), and successfully demonstrated significant positive results from its clinical trial on inhaled formulation of the drug, in hospitalized Covid-19 patients.
The study, a prospective, randomized, double blinded placebo-controlled trial in hospitalized Covid-19 patients, recruited 101 patients from nine specialist hospital sites in the UK between March 30 to May 27, with evenly matched study groups in terms of average age, comorbidities, and average duration of Covid-19 symptoms prior to enrolment.
The odds of developing severe disease requiring ventilation or resulting in death during the treatment period were significantly reduced by 79% for patients receiving INF-beta compared to patients who received placebo. Patients who received INF-beta were more than twice as likely to recover (defined as no limitation of activities or no clinical or virological evidence of infection) over the course of the treatment period compared to those receiving placebo. The symptom of breathlessness was markedly reduced in patients receiving INF-beta. There was no death in the INF-beta group in contrast to the deaths of three patients (6%) in the placebo group.
INF-beta is a drug already used in the treatment of multiple sclerosis (MS) manufactured by Synairgen PLC, a British drug discovery and drug development company, based at Southampton. Interferon beta (IFN-beta) is a naturally occurring protein, which is produced in the human body and is predestined to inform and initiate the body’s initial anti-viral responses.
Once the coronavirus gains access to our organ systems, mainly the respiratory system through our nostril, mouth, and eyes, the endogenous INF-beta’s response, preordained to warn body’s immune mechanism of the impending viral attack, culminates in an organized all-out immune offensive against the entering virus mitigating any potential threat of harm.
However, there is evidence that the coronavirus has cleverly evolved mechanisms, which suppresses body’s IFN-beta production, relinquishing to the ability of the virus to evade our intrinsic immune system.
This suppression of the INF-beta production in the lung by the coronavirus may explain the increased susceptibility of the infected to developing pneumonia and other form of severe respiratory conditions, such as the Acute Respiratory Distress Syndrome (ARDS), ramifications being worse in the higher risk groups.
The administration of exogenous IFN-beta (drug), before or during viral infection of the lung cells, either prevents or greatly diminishes cell damage and viral replication, when delivered directly to the lungs through aerosol spray or nebulization.
The Southampton researchers believe that interferon-beta has huge potential as an inhaled drug to be able to restore the lung’s immune response, enhancing protection, accelerating recovery and countering the impact of SARS-CoV-2 virus.
The inhaled treatment of high local concentrations of INF-beta overcomes the virus’s mutating ability to evade our initial immune response, restores the lung’s ability to neutralize the virus, or any mutation of the virus, or any co-infection with another respiratory virus such as influenza, as could be encountered in the winter months, if there is a resurgence of Covid-19.
The Southampton study is a Phase II trial designed to test the efficacy of Interferon-beta before the drug is approved or able to be marketed. The study protocol was approved by the UK regulators, and the drug is in the process of regulatory approval prior to the marketing on a commercial basis.
So, these two drugs are confirmed to be effective in reducing severity of Covid-19 illness and preventing consequent death -- INF-beta and Dexamethasone. We are aware that Dexamethasone is widely available, cheap, relatively safe, and not uncommonly prescribed in certain inflammatory conditions like rheumatoid arthritis, asthma, eczema, etc because of its property of reducing inflammation by mimicking anti-inflammatory hormones produced by our body.
Dexamethasone, the drug, acts in combating the illness produced by the specific type of coronavirus through dampening down our body’s immune system. Coronavirus infection triggers inflammation as the body tries to fight it off.
The risks at hand
However, it appears that in some cases, coronavirus is capable of pushing our immune system, possibly one person in every six infected, into an overdrive. The subsequent immune reaction is exceptionally heightened, culminating in the body’s own immune mechanism, instead of committing to protect us against the virus, attacks our body’s own cells and tissues, accentuating the cytokine storm to a destructive stature, leading to multi-system failure and death.
Dexamethasone in small doses may calm this heightened inflammatory response while avoiding any major complications, which may be associated with the use of high doses of the drug. However, the Oxford University-led UK study shows that the application of dexamethasone is only suitable for people who are already in hospitals and receiving oxygen or mechanical ventilation, the severely unwell, and that the drug does not work on people with milder symptoms.
The Dexamethasone study, part of the Recovery UK Covid therapy trial, has been robustly scrutinized, is one of the largest of its kind in the world on Covid-19 treatment and Dexamethasone is the first of all tried medications for Covid-19 to conclusively demonstrate statistical significance in reducing fatality in a particular group of Covid-19 patients; hospitalized on respiratory support with oxygen and/or ventilation. Dexamethasone is a synthetic steroid produced in 1957 and has been in medical use since.
The study, a randomized controlled study, recruited a total of 6,425 patients from 175 hospitals across the UK, 2,104 patients were randomized to receive Dexamethasone in a low dose, administered once daily, either orally if appropriate or by intravenous injection, for 10 consecutive days, and their outcomes were compared with a group of 4,321 similar patients used as control, who received all the supportive treatment but no specific medication directly related to coronavirus.
The study found that in the control group (no Dexamethasone), the 28-day mortality (death within 28 days of hospitalization) was 41% in more severely affected patients requiring ventilation, and adding Dexamethasone cut the risk of death from 41% to 28%.
The death rate in the control group, who required oxygen therapy but was not severely ill enough to warrant ventilatory support was 25%, and Dexamethasone treatment in these patients sliced the risk of death from 25% to 20%. The study’s conclusion was that Dexamethasone successfully reduced the death rate by a third in those hospitalized Covid-19 severely ill patients requiring oxygen and/or ventilation.
There is also continued and substantial progress in our hunt for the development of vaccines effective against coronavirus pandemic, and I intend to write on that development in my next article. In the meantime, my message to my fellow Bangladeshis would be: “If we wish to celebrate Eid and other religious festivities, if we desire to return to our mosques, temples, churches, and pagodas, if we are serious about going back to full employment, and if our commitment is to return to living a normal life, we need to maintain safe social distance, wash hands with soap and water frequently, avoid large gatherings, and wear masks in public.”
Raqibul Mohammad Anwar is Specialist Surgeon and Global Health Policy and Planning Expert, and Retired Colonel, Royal Army Medical Corps, UK Armed Forces.
