Mumbai: The number of Covid-19 cases is now coming down in many parts of India. The toll has been high, even though the extent of undercounting is unclear. It's been known since the first wave in 2020 that Covid-19 creates all kinds of complications caused by the virus and the body's immune reaction. Long Covid is now a widely recognised and reported phenomenon wherein symptoms include fatigue, tiredness and breathlessness for prolonged periods of time.
There are also pronounced side-effects of treatment. One instance of this is mucormycosis, or black fungus, which is affecting people recovering from Covid-19. So much so, that the state of Rajasthan has declared it an epidemic, and Maharashtra has reportedly said it will seek doses of the antifungal drug amphotericin B from the Centre. So, what do we know about these side-effects of the kinds of treatment people are given, what are the lessons we can take away, and how could people be more aware of what they could face, potentially, because of the medicines that they are taking? To answer these questions, we reached out to Dr Rommel Tickoo, director of Internal Medicine at Max Hospital, New Delhi.
Dr Tickoo, tell us about the side-effects of medication, such as black fungus. What are the other side-effects that could be triggered because of the drugs being used for Covid-19 treatment?
Rommel Tickoo: An indiscriminate use of steroids has led to such infections. We saw mucormycosis earlier in the first wave too, but not in as many cases. [Now], there are so many cases especially in Maharashtra and Gujarat. Even in Delhi, we are seeing an increasing number of mucormycosis cases.
It is typically a very rare fungal infection. You find [this fungus] in the air, in the soil, everywhere. It only causes disease in people who are immunocompromised--cancer patients, transplant recipients--and especially if they have diabetes. Such patients are immunocompromised, and their sugar levels are very high and not well controlled. When such critical Covid patients who are diabetics are given steroids--and not in the right dose and for a prolonged duration--they are put at a very high risk of an opportunistic infection, in this case, mucormycosis.
Mucormycosis has a mortality rate of more than 50% and there are two-three types. The most common is the rhinocerebral, which affects the nose, sinuses and possibly the eyes and brain. Pulmonary mucormycosis sees an involvement of the lungs; and the cutaneous, gastrointestinal type is not so common. Rhinocerebral remains the most common.
The lessons: In case of a Covid patient who is immunocompromised and is diabetic with uncontrolled sugar levels, if they have any sort of nasal symptoms, don't pass it off as sinusitis. The index of suspicion should be very high because the fungus is very invasive and can destroy all the tissues. The symptoms could be facial pain, headache, tooth pain and jaw pain; blurring of vision, double vision, and so on. If it is in the lungs, then look out for chest pain, breathlessness, dyspnea [shortness of breath]; and the treatment is surgery. If it is on the face then you have to remove the involved tissue, which sometimes means, if it's invasive, that you have to remove the eyeballs. So, a very disfiguring surgery. On top of that, it has to be followed with the antifungal drug amphotericin b, which is expensive and has to be given for a long time.
But, as I said earlier, the reason behind these infections is indiscriminate use of steroids. Now, what are the indications for steroids in Covid patients? So, basically, steroids are life-saving. There's enough evidence [of their effectiveness] in critical Covid patients who are experiencing respiratory distress or need oxygen, BiPAP or ventilation. Steroids are not indicated for those patients of Covid who are not having respiratory distress, are not having any kind of need for oxygen.
So, the first week of Covid is the viral replication phase. That's when you have typical flu-like symptoms--fever, headache, body ache, cough, cold. That's not when you should be using steroids. But, because you have a very high fever, you keep talking to your doctors, you pressure them because somebody who had taken steroids got well. Patients pressure doctors to prescribe steroids, and patients also self-medicate with steroids without informing their doctors. And that's when your viral load will actually increase. Steroids will temporarily mask your symptoms--the fever might sort of settle, it might give you a sense of false security that you are getting better. But in three-five days, you will have very high fever, cough, respiratory involvement. We have seen a lot of patients who took steroids initially ending up with bad pneumonia.
The indication for steroids in Covid is actually in the second week when you have respiratory distress, when your need for oxygen is high, when your oxygen saturation is less than 93. And there is pneumonia, and you need oxygen, and then your inflammatory markers in the blood are high--CRP, D-dimer, procalcitonin, all these things need to be looked into and the ferritin levels checked, and at the same time your CT scan is showing moderate to severe pneumonia. All this coupled together will give an idea whether and which type of steroid to use, and whether to administer it orally or intravenously. The dose is very important, as is the duration.
The Recovery Trial in the UK showed that if given to patients who are in respiratory distress, steroids really benefit and reduce mortalities; but when given to people who don't have respiratory distress, steroids can increase mortality. So, it was recommended that steroids should be given for 5-10 days and at a low dose. But we are seeing much more than that being used for a longer duration.
So, black fungus is already in the environment, in hospitals or intensive care units, but only infects some people and not others?
RT: It's there in the air, soil but it infects only those people who are immunocompromised. As I said, diabetics who have very high sugar levels are at the biggest risk for developing mucormycosis. Covid itself decreases your immunity and then if you are already immunocompromised--say, if you are a diabetic with chronic kidney disease or chronic liver disease, or are a transplant recipient, or if you've been on steroids for some auto-immune disorder--you are at high risk. If you are a cancer patient, then whether you are diabetic or not, you receive steroids. Steroids increase your sugar levels, and high sugar is a basic risk for developing mucormycosis.
Mucormycosis only causes disease when it receives this sort of "fertile soil", when an immunocompromised person with high sugar levels takes steroids, and perhaps next-generation antibiotics for prevention of secondary infection, and also immuno-suppressant drugs like tocilizumab and itolizumab. All that increases their risk of opportunistic infections.
So, if you stick to the right indication for giving steroids in the right dose, for the right duration, then it's not a major risk--and especially, if you handle their sugar levels.
So in your experience, those patients who have not been given steroids may not develop black fungus? Does that correspond with your experience from last year as well?
RT: No, they can still develop it, but that's very, very rare.
You're saying that we did know from last year that patients could develop black fungus because of steroids? Because of over-prescription or over-consumption of steroids?
RT: We knew that but I don't think we had such a huge number of patients who needed steroids in the first wave. In the present second wave, a lot of patients have had lung involvement, early lung involvement. Lots of patients have needed oxygen, which basically means their lungs were involved, so steroid use has also increased. Some patients are actually not responding to the conventional dose of steroids, so at times you can't even blame the doctors for using high doses, because otherwise you lose your patient. But the flip side is that the sugars go for a toss. You have to maintain a balance--you have to watch the sugar levels and guard against opportunistic infection.
What are the other side-effects? Every drug or treatment may not be fatal but could be damaging in the near or long term. What else could we have missed or are seeing right now for which we need to be more alert?
RT: Other than this, there are the side-effects of Covid itself, which can cause cardiac complications, myocardial infarction [heart attack], arrhythmia [irregular heartbeat], myocarditis [inflammation of the heart muscle] or stroke, which is basically brain involvement. Or for that matter, deep vein thrombosis [blood clotting inside a blood vessel], embolism [blockage due to any kind of material inside a blood vessel] in the lungs or any system for that matter--liver, kidney gets affected. These are the side-effects of COVID by itself.
If we talk about treatment leading to complications, then it is mostly related to steroid use and if it is not mucor [which causes mucormycosis], which is rare, then it has to be secondary bacterial infections that are very common in immunocompromised or even otherwise very sick patients who are on steroids. So, pneumonia, secondary bacterial pneumonia over and above the viral pneumonia which they have, and urosepsis, urinary tract infections (UTIs) spilling into the blood causing multi-organ dysfunction are the secondary bacterial infections. Because apart from steroids, we also give tocilizumab and other drugs that reduce immunity, a fertile ground gets created for invasive fungal and bacterial infections.
Assuming black fungus was one key side-effect of medical intervention or over-intervention, what would be the numbers two and three, from your experience?
RT: I actually haven't seen too many secondary infections, fortunately. Very rarely. I have treated thousands of patients who were under home isolation. The majority did not actually develop any fulminant [severe or sudden] bacterial infection. Some of them did develop UTIs because they were on steroids or were diabetics, but most of them never landed up in hospital. So, secondary infections we haven't seen and this is what many doctors have shared with me. It is almost always complications related to Covid or high sugars and then these mucor kind of things. Though bacterial infections are common, UTIs are the second most common infection that we see in Covid patients, especially the ones who are on steroids.
We are in the middle of May, after a big surge in the second wave in April. Is it possible that there may be other secondary effects of these medications that may come later? What can you tell us from your experience of the first wave?
RT: Well, if it's something like mucormycosis or secondary bacterial infections, then it has to be in the coming few weeks, two to four weeks, it can't be beyond that. But if you were to look at long-term complications as you were speaking about earlier, Long Covid symptoms, then it can be those. Fatigue is the commonest of symptoms, followed by cough, chest pain, palpitations, dyspnea, anxiety, insomnia, change in the taste in the month, depressive tendencies and tiredness after minimal exertion, mental or physical. And fever also, low-grade fever goes on and on for quite some time in certain patients; they keep investigating it but nothing comes out and eventually, on its own it goes away. So, those are the Long COVID symptoms.
Many people have taken medicines that are not necessarily the best medicines as per what physicians from other parts of the world are saying. And also, as you said, patients have pressured doctors to give them something. What is your advice to patients, going ahead?
RT: There's no one-size-fits-all prescription. What I would like to tell people is that in the first one week, there is actually nothing that really helps. Because there is no treatment, there is no specific treatment for Covid as for now, and whatever we use is based on anecdotal evidence or minimal scientific evidence. Now, even if we use doxycycline or azithromycin, which are antibiotics, or for that matter ivermectin, an antiviral, there is hardly any evidence [they will work].
Take ivermectin. One recent study in the US showed that yes, it does reduce the progression from mild to moderate, but that's one study. There are many other studies which have shown that it doesn't really have much of a benefit. But there are 40 trials going on so we really don't know. But as of now, there is not much evidence but we keep using it because there is nothing [else] we can use. Azithromycin, doxycycline being used extensively has no role actually, if you ask me. But sometimes we do use it because there is nothing else to use, because you feel there might be a secondary infection or there is too much of sputum or whatever indication of secondary infection, so you use it.
So actually you're left with nothing but paracetamol and supplements--zinc, vitamin C. Paracetamol is the only thing you can use in the first week and now, there's a role of inhaled budesonide which is an inhaled steroid, because now the studies again done in Oxford have shown that it does prevent progression from mild to moderate to severe disease. So, if you use it early on in the disease when you have upper respiratory symptoms, for 10-14 days, it does wonders. It does prevent [worsening of the patient's condition]. So, that is something which we can use--inhaled steroids--because they don't have systemic side-effects. But again, [it must be taken] in three-four days when the fever is again going up and things are not settling, under medical supervision and not on your own. Don't self-medicate. That is the message which needs to go across, especially when it comes to steroids. I am also talking about antibiotics for that matter. Don't even take those, don't take any drugs without medical supervision.
Steroids might have minimal side-effects if used for 5-10 days, which is the recommendation. It might increase your sugar. But [when used] beyond 10-14 days, there are a whole lot of side-effects apart from the fact that in the first week if you use it, it can give you pulmonary pneumonia, secondary infection. Other side-effects of steroids are basically weight gain, psychological effects such as anxiety and panic attacks, long-term glaucoma, cataract. There are so many things which steroids do so try not to over-do it. Do it only under medical supervision and when there's an indication and then it has to be given in the right dose at the right time. And don't do it just because someone else in the family, some friend or some colleague of yours was given the steroid. Don't follow blindly the prescription that has been sent to you on WhatsApp, saying that 'This worked wonders for me, your doctor doesn't know what he's doing, please do this'. A lot of patients actually don't listen to us but they listen to their friends and family.
What should patients do once discharged?
RT: Post discharge from the hospital, Covid patients have to be very careful for the next two-four weeks. They have to keep monitoring their sugars or the non-diabetic patients who were on steroids might not know their sugars might have gone up. A lot of patients that I have seen in the last couple of weeks, who were non-diabetics, are now having high sugars. Even the blood pressure fluctuates with steroids--the BP goes up. And with Covid, we have seen a lot of fluctuations in blood pressure. It usually goes up and you have tachycardia [heart rate higher than 100 beats per minute], you have a high heart rate and all these issues keep bothering you once you go back home. Keep doing your tests whenever required, maybe every week to two weeks as has been advised by the physician. And then, be in touch with your doctor.
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