Inhaled budesonide easing COVID-19 infections: Scientists

Studies show that treatment for asthma can help in fending off the life-threatening COVID-19 infections. The SARS-CoV-2 virus primarily infects the lungs. People who suffer from Asthma or COPD (chronic obstructive pulmonary disorder) are more susceptible to contracting the deadly pandemic as their immunity is quite low. The treatment for asthma and COPD mainly includes inhaled corticosteroids such as budesonide, dexamethasone, ciclesonide etc which are affordable, effective, easily available and completely safe.

Inhaled corticosteroids suppress the action of inflammatory cytokines and when given with bronchodilators, helps to relieve dyspnea or breathing difficulties. The use of corticosteroids for these patients during the time of the pandemic was under debate due to its immunosuppressive nature. However, the incidence of SARS-CoV-2 was quite low in the patients who suffer from asthma and COPD, suggesting that the corticosteroids could be keeping the virus at bay. 

Clinical Trials of budesonide

Sanjay Ramakrishnan and his colleagues at the University of Oxford tested out this hypothesis using Budesonide and the results were published in the journal The Lancet Respiratory Medicine. They conducted a randomised open-label phase-2 trial in a cohort of 146 people who showed mild symptoms of the SARS-CoV-2 infection. Half of the patients were given budesonide (two pumps of 400ug twice a day, total dose 1600ug) for 14 days and the other half were given the usual care of antipyretics for fever and honey for cough (control group). The primary outcome was urgent care and hospitalisation. Ten people in the usual care control group and one in the budesonide group showed the escalated signs of the infection and need for urgent care indicating a reduction of risk by 91% for Budesonide. The secondary outcome was to assess the clinical recovery which was much faster in the budesonide group (within 8 days) as compared to the usual care group (12 days). 

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In another study (interim analysis, not yet peer-reviewed) led by Ly Mee-Yu, also at the University of Oxford, enrolled 4,663 people over the age of 65 and those above the age of 50 with comorbidities who had mild symptoms of COVID-19. At random the patients were allocated into budesonide, azithromycin, doxycycline and usual care groups. Researchers found that the budesonide group had a faster recovery time by 3 days than the usual care group. Based on these studies scientists concluded that budesonide helped in recovery from COVID-19 faster as well as reduced hospitalization. 

Budesonide was approved by the National Health Services (NHS) in the UK as a treatment for COVID-19 on 12th April 2021. The Union Ministry of Health and Family Welfare, India, released guidelines in late April 2021, stating the use of budesonide and ivermectin against the infection, if the symptoms persisted more than five days. 

Mechanism of action of budesonide

Budesonide sold under the name Pulmicort is available as an inhaler, nebulisation solution, pill or nasal sprays. Apart from treating asthma and COPD, it is also given for allergic rhinitis, nasal polyps and other gastrointestinal immune disorders like Crohn’s Disease, ulcerative colitis etc. It is an anti-inflammatory agent. Budesonide binds to the glucocorticoid receptor found on the surface of bronchial cells and traverses through the cytoplasm into the nucleus. Inside the nucleus, the budesonide-receptor complex binds to the histone acetyltransferase protein preventing the expression of inflammatory genes (capable of causing bronchoconstriction) and reducing the production of pro-inflammatory cytokines like interleukins and tumour necrosis factor. Budesonide decreases the overactivity of several immune cells involved in allergic response such as eosinophils, neutrophils, mast-cells etc, preventing airway constriction and providing relief from dyspnea, wheezing and coughing. 

Fluticasone, another inhaled corticosteroid, was found to reduce the expression of the pulmonary ACE-2 receptor preventing the entry of the SARS-CoV-2 virus into bronchial cells. Another study explores how ciclesonide reduces the viral load by blocking the activity of Nsp15, (an RNA endonuclease) an essential enzyme for the replication of the SARS-CoV-2 virus. 

Further research needs to be conducted with a larger cohort to explore the therapeutic effects of budesonide on COVID-19 symptoms. Inhaled corticosteroids have been used for decades in treating breathing disorders and hence, these findings could be extremely beneficial for low and medium-income countries since the treatment is widely available at a low cost. These steroids can help in possibly reducing the number of COVID-19 cases along with the vaccination strategy, thereby alleviating the pressure on the healthcare system. 

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