ABSTRACT
Conversation with Dr Sushmita Roy Chowdhury (SRC), Head, Pulmonary Department, Fortis Hospital, Kolkata, India
AH: Do prophylactic medications have any role in COVID?
SRC: The basic principle of prevention better than cure forms the basis of looking for prophylactic treatment in any disease. Search for prophylactic agents started early in the case of the highly infective COVID-19. HCQ (hydroxychloroquine) was the first agent that garnered a lot of interest, especially in India. Its easy availability, known safety profile, and affordability were the key reasons. The rationale for its use was derived from results of 100 Chinese patients with COVID-19 where the group that received chloroquine had reduction in exacerbation of pneumonia, delayed viral clearing, and symptoms (Colson et al., 2020). China was the first country to include chloroquine in prophylaxis. Based on this premise, hydroxychloroquine should also work in the same way with a better safety profile, lower cost, and favourable preclinical data. HCQ was adopted as a medicine for prophylaxis by the ICMR. However, due to flaws in methodology of clinical trials, incorrect dosing, improper duration, and frequency of administration, HCQ failed to 146demonstrate appreciable benefits in preventing infection and was dropped from national guidelines of India. Similarly, ivermectin, a safe antihelminthic (helminth means worms) drug used in treatment of strongyloidiasis was found by Caly et al. (2020) to have in vitro activity against SARS CoV2 followed by a pilot clinical trial by Chaccour et al. (2021) that showed a tendency to reduce viral load and early recovery from hyposmia in the group treated with a single dose of 400mcg/kg of ivermectin. Current evidence does not lend any rationale for continuing these agents for prophylaxis, and these have been removed from revised national guidelines in India.
AH: What is the main issue with remdesivir?
SRC: Remdesivir, a repurposed drug, was initially used for treatment of hepatitis C and Ebola. When the pandemic struck, remdesivir was used as an investigational drug against COVID. It was widely used until the interim report from the WHO Solidarity trial showed no mortality benefit from it in hospitalized patients. Interestingly, the ACTT-1 trial in the United States and Recovery trial in the United Kingdom reported shortened time to recovery with remdesivir previously (Beigel et al., 2020).
Our own clinical observation has been the same in both the first and second waves. This is even more evident if it is given early in the viral phase within the first 7 days. Not only do most patients have early defervescence, they also have better sense of well-being.
I feel the Solidarity trial needs to be re-evaluated with respect to how many people on remdesivir received it within the first 7 days of illness and their rates of recovery.
AH: What is the role of steroids in treatment of COVID-19?
SRC: Steroids have certainly been the cornerstone of effective and affordable treatment in the pandemic. Its easy over-the-counter availability made it the most misused drug too. The best period of its use is in the second week in patients with moderate to severe pulmonary involvement presenting with hypoxia. Those who are prescribed steroids too early, or self-medicated with it in order to relieve symptoms of fever and myalgia invariably worsened. Also, at the height of the pandemic, when hospital beds were scarce, many 147general physicians commenced steroids at home. Sometimes the patients continued it beyond the prescribed period due to the sense of well-being and its easy availability.
AH: How did you do triage and manage the COVID patients in an ICU set-up?
SRC: Intensive care treatment for COVID pneumonia is reserved for those having severe pneumonia with respiratory failure (Type I at presentation). Most of these patients have happy hypoxia (nil or minimal symptoms) or clinical distress despite severe hypoxia. The aim of oxygenation is to keep saturations above 92% with lowest amount of oxygen. Up to 10/minute requirement of oxygen with no respiratory distress is well managed with face masks and non-rebreathing masks. This is done in addition to awake proning (a posture of lying flat with face downwards) of patients. Higher oxygen requirements are enabled with HFNO (High-flow Nasal Oxygen) which not only helps in providing higher concentration of oxygen (via a nasal device), it also helps to prevent claustrophobia associated with face masks and enables the patient to eat and drink with the oxygen supply in place. It is well tolerated at higher flow rates too, but we have observed a slightly increased rate of spontaneous pneumomediastinum (air in the middle of chest between the lungs and around the heart) in the second wave in such patients. Non- invasive ventilation is helpful in patients with increased work of breathing, in moderate ARDS (Acute Respiratory Distress Syndrome), those with associated COPD (Chronic Obstructive Pulmonary Disease) and Type 2 Respiratory failure, OSA (Obstructive Sleep Apnea)with OHS, and heart failure patients. Alternating between HFNO and NIV (Non-invasive Ventilation) seems the best tolerated option in many patients. Mechanical ventilation has been a challenging modality. We found that early elective intubation outcomes are better than delayed intubation in those who remained in severe ARDS with P/F ratio below 100 and increased work of breathing despite being on NIV or those who are drowsy at presentation with severe ARDS.
Only a small subset of these patients, who fail despite a good trial of 48–72 hours of prone mechanical ventilation, are considered as candidates for ECMO (Extracorporeal Membrane Oxygenation, a 148life support machine). Successful weaning from ECMO on an average takes 18–19 days. (personal experience). Age is never a barrier to choosing modality of treatment in our set-up. However, in those with advanced comorbidities such as malignancy, ILD (Interstitial Lung Disease), and severe COPD, the decision to mechanically ventilate is taken after prior discussion and ceiling of care established at NIV in most patients.
AH: What is mucormycosis?
SRC: Mucor is an opportunistic fungus which usually infects severely debilitated, diabetic, and immunosuppressed individuals. The infection most commonly starts in the paranasal sinuses. This is likely due to poor drainage of this area. The fungus causes angioinvasion and spreads rapidly to involve the maxillary bones, orbits, brain, and sometimes via the haematogenous route can affect the lungs, kidneys, and other organs. The fatality rate is very high.
AH: Following the COVID-19 pandemic, in India the disease has become another important health emergency. The Indian Government reported that more than 11,700 people were receiving care for mucormycosis (“black fungus”) as of 25 May 2021. (Reference, Wikipedia) Why is this mucormycosis following COVID-19 India specific?
SRC: There is some complex mechanism that has led to this surge of mucormycosis. Poor host response, abundance of mucor in certain humid (Indian weather) environments, possibly poorly maintained oxygen systems transporting the fungus to nasal passages, complex siderophore opportunities provided by COVID to merrily angio invade and cause stealthy devastation are all possible. The steroids alone are not the only culprits. Strict blood sugar control and high index of suspicion in high-risk patients who complain of nasal discharge and facial numbness must call for early CT and nasal endoscopy for sampling and fungal culture.
149AH: Does the so-called “infodemic” play a role in the pandemic development?
Infodemic creates mass hysteria. Easy accessibility to unscientific and multiple sources of information created more panic about the disease than is desirable. This led to hoarding of medicines as expensive as remdesivir and tocilizumab, equipment like oxygen cylinders and concentrators, and commencing steroids inappropriately in home settings early in the disease. This made the treatment even more difficult for the trained physicians.
I always convinced my patients with available, credible information, allaying their anxiety and by being available for online consults when they were convalescing at home. Hand-holding virtually helped immensely in reassuring and ensuring compliance to home isolation rules.
