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Peace be upon you and the mercy of Allah, dear attendees. This lecture is directed towards professionals in the therapeutic field and medical science students, whether in medicine, pharmacy, or nursing.
Where do we obtain documented and updated information as therapists regarding the currently prevalent disease, which is COVID-19 caused by the novel coronavirus?
Of course, there are a large number of studies constantly being released, and one might get lost among these competing studies. So, how do we refer to sources that give you the essence and summary and inform you of what has been adopted?
For example, in America, I will speak about two American organizations. This could be the nucleus and beginning of a fruitful discussion if some of the brothers have European, Chinese, or other treatment guidelines, so that we can broaden our horizons in treating this disease.
The two organizations I will speak about today are:
In fact, the CDC refers to the NIH, which has published treatment guidelines related to the treatment of COVID-19. I will focus on some points briefly and quickly.
For example, the CDC tells us that one study – and why do I focus on this information? Because many people think that the incubation period lasts only five to seven days and will not exceed that – this study says that on average, the period between exposure to the virus and the appearance of symptoms was 11.5 days. Of course, the periods vary between studies, but I wanted to say that because some might think that if they visited a friend infected with COVID-19, or entered an environment they knew was contaminated, and five days, seven days, ten days passed and nothing happened, they are safe. No, symptoms can appear after that.
So, what about before the appearance of symptoms? Can a person without symptoms transmit the infection to another person? The answer is yes, according to the CDC under the title "asymptomatic and pre-symptomatic transmission." That is, can a person without symptoms? Or a person who will have symptoms but is still in the incubation period where symptoms have not yet appeared? Can this person transmit the disease to others? The answer is yes.
During the incubation period, the person can transmit the disease to others, and some people, as we said, do not have symptoms and will not have symptoms, meaning it is not a case of incubation followed by the appearance of symptoms, but rather that symptoms never appear on them, but they are carriers of the virus. These people can transmit the disease to others. The paragraph finally confirms that people who do not show symptoms can transmit the virus to other people, and they mention many studies in the references that indicate this.
According to the CDC, there is also a classification for:
It is noteworthy here that Severe illness has been redefined so that if the person's SPO2 is less than 94%, it is considered severe. If you refer to other guidelines, and perhaps even the same guidelines in their earlier editions, we used to say if it was between 90% and 94%, we considered it moderate, and if it was less than ninety, then we considered it severe. No, here they say in the recent updates if oxygen saturation drops below 94%, the condition is considered severe. The driving reason for this is that we noticed that if the person starts to drop, the deterioration becomes rapid, and therefore they considered any case that drops below 94% a severe case.
Now, if we come to the guidelines, which are updated first of all. First of all means that some sections tell you the last update was on 3/11, other sections the last update was on 6/6, for example. Depending on whether important information has emerged that needs to be updated with this section or not. They may also sometimes delay updating some sections, and this is why it is important for us to look at when the last update was.
The beauty of these guidelines is that at the beginning, they give you a complete section that says "What's new in these guidelines?" For example, a person who reviewed the guidelines a month ago does not want to go back and read them again and search for the new information in them. No, they give you the updates or updates at the beginning. They give them to you at the beginning, they tell you what is new from the last version of the treatment guidelines? This is important.
We also have many sections here. The most important thing I will focus on is how to treat these patients infected with the virus? It talks here about Antivirals and Antiviral drugs, of course, in their broad sense. There are antivirals in the sense that they are designed to be antivirals to work on or fight viruses, and there are other antivirals used for other purposes, all of which are included under the title antiviral drugs.
We also have Immune-based therapy and I will not focus on it. These drugs are usually expensive, so I will not talk about them in detail. But you know that under this title we have Convalescent plasma because it is related to immunity. Convalescent plasma is the serum taken from a person who has recovered from COVID-19, and according to the treatment guidelines here, the effectiveness of these sera is limited in reality and not high.
Under this title, under the title of Immune-based, we also have Corticosteroids, which are important as we will see. That is, corticosteroids, glucocorticoids, which have anti-inflammatory (inflammation) efficacy.
We also have a special section for Adjunctive therapy (supportive treatments), under which fall Antithrombotic therapy whether it is antiplatelet (antiplatelet) or anticoagulant (anticoagulant). And we have Vitamin C, Vitamin D, Zinc supplementation. I wonder what is the latest we have reached under these titles? There may be things that are strange to you, because they are contrary to the common practice among some patients, perhaps those who act based on the general culture spread around Vitamin C, D, Zinc, etc.
Then, for example, a person taking ACE inhibitor (blood pressure medications that caused a lot of controversy at the beginning of the disease at the beginning of the epidemic). Does he continue taking the ACE inhibitor or not? A person taking Statins, a person taking Non-steroidal anti-inflammatories such as ibuprofen and diclofenac, etc. Does he continue taking them or not? We also have a section dedicated to Special populations such as pregnant women, children, and others.
Alright, let's start, esteemed guests, with "Therapeutic Management of Patients with COVID-19". This section summarizes a lot. Its last update was about a month and a half ago on the ninth of October 2020. Notice that it divides disease severity into:
So, the conclusion tells us what to do with each category according to the severity:
In the first category, people who are not in the hospital or are in the hospital but do not need oxygen, the "Panel" (the body overseeing the writing of these guidelines) "recommends against the use of Dexamethasone". That is, they advise against using dexamethasone. Of course, in the guidelines themselves, they do not only talk about dexamethasone. If dexamethasone is not available, we have prednisone, for example, prednisolone, hydrocortisone. So, corticosteroids in general.
Therefore, the recommendation for people outside the hospital is not to take corticosteroids to treat COVID-19. Of course, those who take corticosteroids, the philosophy is not to eliminate the virus but to deal with the body's reaction to the virus. So, the committee advises against taking dexamethasone and steroids in general. Of course, if a person is taking steroids for another indication, for example, a person with asthma who is already taking one of the steroids, it is within the recommendations that they continue to take it. There is no problem in taking it. But if we take it for the sake of COVID-19 in outpatient cases, the committee advises otherwise. Of course, here they say there is no recommendation to give a specific antiviral.
In cases that require oxygen, for example, nasal cannula with a moderate concentration of oxygen: "Remdesivir 200 mg IV for one day followed by Remdesivir 100 mg IV once daily for four days until hospital discharge". So, this is the recommendation regarding Remdesivir.
Of course, you notice, brothers, here in parentheses we have letters like A1, B1, C3, with Roman numerals. What do these numbers mean? Those who work in the field of treatments know that here it refers to the level of confidence in the recommendation. If the code is A1, it means we strongly recommend it. A is a strong recommendation, B is a moderate recommendation, C is a weak recommendation. As for the numbers 1, 2, 3, they refer to the strength of the evidence. 1 means a randomized controlled clinical trial, which is the highest level of clinical studies. 2 could be non-randomized or, for example, a cohort study. 3 means expert opinion. It is just the opinion of the expert in the field. Of course, it is not a matter of whim and randomness, but it is often based on practice and observation. For example, we will see shortly that many doctors recommend prone positioning (lying on the stomach), saying that we have clearly seen the effect of that on blood oxygen saturation. So, since no clinical studies have been conducted, we consider it an expert recommendation, and this recommendation, as I said, is often based on the observation they have witnessed.
So, for those who need oxygen in the hospital but not high flow rate, it is recommended to use Remdesivir, and this is a strong recommendation (A1). Adding dexamethasone is weaker (B2). The level of the recommendation is weaker. Giving dexamethasone as an alternative to Remdesivir is also weaker in terms of the level of the recommendation (C3). The confidence in the recommendation is weaker, and the evidence for it is weaker.
If the patient is in the hospital and needs, meaning what we will know in this case, the recommendation is stronger to give dexamethasone with Remdesivir. And you notice here that the doses and duration are the same in all categories. If we start giving dexamethasone, whether the condition is moderate or severe or more severe, in all these cases, they say we will give the same concentration and for the same duration of dexamethasone. The level of the recommendation here is high (A1) or dexamethasone with Remdesivir. You notice here that adding Remdesivir, we are not as confident in it as we are in dexamethasone alone (C3). When they say C3, it means we are not at the same level of confidence or even the strength of the studies. The more established is giving dexamethasone alone. Adding Remdesivir is a matter that has less evidence.
So, this is the most important paragraph indeed. As I said, the beautiful thing about the guidelines is that they are updated, but honestly, it is disappointing that you notice the options are very limited. The talk here is about dexamethasone and Remdesivir.
Okay, what about anticoagulants and antiplatelets? I mean anticoagulants like Clexane, Heparin. Antiplatelets like Plavix and Aspirin. What about Vitamin C and Vitamin D? You will see that for most of these things, the answer is "there is not enough evidence," "studies are conflicting," "the topic is still under study," and similar phrases.
Of course, dear audience, within the guidelines, you will find the justification for each of these recommendations. For example, for patients who have not been hospitalized or have been hospitalized but do not need oxygen, why does the committee recommend against giving Dexamethasone and corticosteroids in general? They say that there was a study conducted in the United Kingdom that found no benefit in giving Dexamethasone to these patients. So, in almost every section, there is a rationale for recommending against or for something specific, meaning the justification or reasoning behind this recommendation that they issue.
By the way, even the World Health Organization regarding Dexamethasone says here that it strongly recommends the use of corticosteroids for people who have a severe or critical condition, while for others, cases that are not severe or critical, the World Health Organization recommends against the use of Dexamethasone or corticosteroids in general for treatment.
Also, in the NIH guidelines, you will find, dear audience, information about each drug from the recommended or widely studied drugs. For example, Remdesivir selected clinical data, they talk about selected studies regarding this drug that indicated whether it is effective or not effective or effective in certain cases. And in each of these sections, they write when it was last updated. They give you the name of the study, the population or target group in it, what the results are, what the limitations are (the flaws or shortcomings in the study), and finally what the conclusion or interpretation (the interpretation of these results) is. I mean, in summary, this study says the drug is good and not good and good for certain groups and not good for other groups, and so on.
Okay, now for example, under the topic of Antivirals, we have Chloroquine and Hydroxychloroquine with or without Azithromycin. You know that initially, several guidelines recommended the use of Hydroxychloroquine, then later there was a lot of controversy about the drug being given alone or not given or possibly given with Azithromycin or both given with Zinc. There is a lot of talk about this drug.
As of now, the NIH recommendations are as follows: no Chloroquine and no Hydroxychloroquine (meaning neither alone nor with Azithromycin) for people outside the hospital, and by the way, these people are usually in the early stages of the disease, meaning we will see shortly that this drug may be more beneficial if given early in the disease, unless it is part of a clinical study. So, the door is still open to trying Hydroxychloroquine for certain conditions or with Azithromycin, but that should be within a clinical study, within a clinical study, not as a general routine recommendation for every patient with COVID-19.
Here, they also provide the rationale (the justification) why they issued these recommendations. By the way, for example, notice here the last update date is 19/10/2020. After this date, a beautiful study came out titled "COVID-19." In this study, what did they do? What distinguished it from some previous studies? Giving Hydroxychloroquine in the early stages of the disease, that's one. Number two, what is called "stratification," where you divide the patients, you do not treat them all as one group, you categorize them based on certain conditions, based on certain risks present. This is what they did and came out with recommendations or a result that "low dose Hydroxychloroquine with Zinc and Azithromycin was an effective therapeutic approach against COVID-19" that these drugs were effective if given together against COVID-19 and that they "significantly reduced hospitalization" reduced hospital admission, meaning the group that was given this trio had a lower percentage of hospital admissions, and there was also a lower number of deaths.
Now again, here something called "stratification" happened, and this is an important point that in some studies, treating all infected people the same way may result in a conclusion that the drug is not beneficial, but if you divide the population or this group of people into groups and give the drug to certain groups, then see the result or give it to these groups but perform statistical analysis to see if certain groups benefit more than others, this is what they did here. I mean, they gave this trio only to those who met certain conditions and came out with the result that this trio is beneficial for those who meet these conditions.
Okay, now what about Adjunctive Therapies, supportive drugs? So far, you have noticed from the world of Antivirals, the guidelines from NIH only talk about Remdesivir, and also only talk about Dexamethasone for certain cases, and they consider everything else supportive drugs, is there evidence for them or not? This is what we will see now.
For example, regarding antithrombotic therapy, which includes, as mentioned, antiplatelet and anticoagulant drugs, meaning the world of aspirin and clopidogrel (Plavix) or, for example, heparin, enoxaparin, and others.
The last update of the recommendations was on 12/5/2020, and the first recommendation states that for people who have not been hospitalized, there is currently no information supporting the measurement of D-dimer or coagulation factors, signs of coagulation such as D-dimer. That is, there is no justification for recommending that patients measure these things to know if they are high or low, etc.
Of course, as an introduction to the topic, why do we care about thrombosis and antithrombotic therapy? You may know that it is an essential part of the pathophysiology of this disease that the disease causes damage to endothelial cells and causes thrombogenesis (clot formation). These clots can cause problems in the lungs, can cause a stroke, can cause a heart attack. Some people died of myocardial infarction (heart attack), some of them by stroke. And these clots, by the way, can also be venous and can be arterial, they can be in the veins or in the arteries. Therefore, the logic says that since this disease causes clots, then why not give prevention? Give antiplatelets or anticoagulants. This is what the theoretical side says from a theoretical point of view, but from a practical point of view, from the point of view of studies, it does not say that. But it says that for people who have not been hospitalized, the level of recommendation is high, the evidence is weak (A3). This is what it means. And by the way, I talked a bit about the hierarchy of evidence in an episode titled "Corona and the Proliferation of Claims" if you search on YouTube "Corona and the Proliferation of Claims" you will find an episode that classifies the levels of evidence in the world of treatments.
So the committee recommends not to give these drugs because we should not start these drugs for people who are outside the hospital unless there is another indication. Suppose a person has deep vein thrombosis (deep vein clot) and takes it for this reason, yes for this reason continue the treatment. But do not give these drugs for COVID-19. Do not start these drugs to prevent COVID-19 clots.
As for the rest, people who have been hospitalized say that there are recommendations for people who are hospitalized. It is known that if a person is immobile and bedridden, if he was admitted to the hospital and will remain bedridden or with little movement for long periods of course he will be given anticoagulants regardless of the subject of COVID. That is, this person will be given the drug just because he is bedridden. Therefore, they say here we will treat these hospitalized patients as we treat others who are admitted to the hospital regardless of whether they are COVID-19 patients.
Now, regarding antiplatelets, antiplatelet drugs, and aspirin at the top. Again, I say some doctors may be tempted to give aspirin because logically, since many cases occur in which arterial clots occur, why not give aspirin to prevent these clots from occurring? As we saw, the NIH recommends that we do not do that. However, there is a relatively recent study about a month ago titled "Aspirin use is associated with decreased mechanical ventilation, ICU admission, and in-hospital mortality in hospitalized COVID-19 patients". That is, giving aspirin was accompanied by or resulted in a reduction in the need for mechanical ventilation and admission to intensive care units, as well as a reduction in in-hospital deaths. But who is this about? About patients in the hospital. Patients in the hospital. Will this study be recognized by the NIH and included in its recommendations? Only God knows, we will see that in the coming days.
You may say, well, it's clear, if a study is indeed respectable and published in a global journal, why not rely on it? The NIH may impose certain limitations on this study, that there is a certain deficiency in this study that prevents it from taking its results, or this result may be opposed by other studies. Therefore, until further notice, the NIH does not recommend giving aspirin to prevent arterial thrombosis from arterial clots.
Also, in the NIH, there is a recommendation related to prone positioning, and it seems that there is a lack of awareness of its importance. In fact, I did not just read the recent recommendations before talking to you in this lecture, but I also spoke with a number of doctors, brothers, inside and outside, especially in America. And I asked them about their experimental experience. All the doctors I contacted confirmed that they saw good results for prone positioning. Prone positioning means the prone position. The patient lies on his stomach. If he is on the hospital bed, he sleeps on his stomach. If he is not comfortable, pillows can be placed under his chin, under his knee, under his stomach, for example. But he lies on his stomach, which reduces the accumulation of fluids in the lungs. And they all said that we saw the effect of this on oxygen saturation. They saw that, it affected the oxygen saturation of the blood. There are other different positions that may be, for example, on the right side with the left hand raised, the left side with the right hand raised. The important thing is that the patient reduces sleeping flat on his back during this period.
What are the NIH recommendations? It says it recommends trying the prone position, that the patient lies on his stomach if he is awake, we try that to improve blood oxygenation. You notice the recommendation is not A1, it is B2.
We often hear about the use of vitamin C as a prevention and treatment for COVID-19. What are the NIH recommendations? It starts by talking about its role as an antioxidant and its benefits, etc. But for COVID-19 patients specifically, is there sufficient evidence? The recommendations say (C3) and by the way the same recommendations below until (C3). So whether the patient is severe and critical or not severe, moderate, simple, in all cases they tell you that there is no sufficient evidence that vitamin C is recommended in these cases. There is no sufficient evidence.
Peace be upon you. What about Vitamin D? The recommendation states that there is no prevention or treatment as we do not have sufficient evidence to recommend for or against it. Therefore, I will be honest, the topic is a bit disappointing from this perspective. The recommendations do not cure everything. However, I will say here, esteemed audience, why do some doctors not strictly adhere to this recommendation? They might try Vitamin D in certain cases. Initially, many situations start with expert opinion, trying it on a patient and getting certain results. Then, perhaps a case report is published, followed by a case series, and then maybe a cohort study. We then progress to a randomized clinical trial.
In this case, for example, some doctors might relate Vitamin D to a study, even if it is loosely connected to the topic. Note that the study I will discuss is old, about three and a half years. However, it is relevant to the topic. This study is published in a well-known global journal, BMJ, which has an impact factor of over thirty. It is a prestigious and very well-known journal. It has been cited, meaning referenced or opposed, 875 times. 875 times of citation or opposition. The main point is that it is a strong and well-known study titled "Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data." The use of Vitamin D to prevent infections in the respiratory system. It is known that systematic review and meta-analysis have a high level in the hierarchy of evidence.
Therefore, some doctors might say that for them, they will connect things and measure and say that in COVID-19, there is a type of infection, and based on this old study, yes, they will give Vitamin D because it is generally safe. Of course, unless there is an excess in the dose. Incidentally, the conclusion of this study stated that patients with severe Vitamin D deficiency were the most benefited in terms of preventing respiratory infections.
Therefore, esteemed audience, honestly, for example, here in Jordan and in many countries around the world, it is known that men and women, especially women, have a deficiency in Vitamin D. Therefore, if someone consults me, I would tell them if you can test for Vitamin D, do so. If you have a deficiency, we tell you that in normal days, compensate for this deficiency by taking the appropriate dose of Vitamin D. And now, if you are infected with COVID-19 or have been in contact with someone who is infected, I advise and strongly advise that you compensate for this deficiency by taking Vitamin D. If you are not going to test, we assume that you will test. Therefore, I do not prescribe this for everyone, but I say that this is relatively a safe dose. For example, a person infected with COVID-19 in its early stages or has symptoms that make us highly suspect COVID-19 and has not taken a full course of Vitamin D recently, it may be appropriate to prescribe a total quantity that does not exceed one hundred thousand international units, even if no test was conducted as long as they have not taken quantities of Vitamin D recently.
By the way, there is also a relatively recent study from a few months ago titled "Does vitamin D deficiency increase the severity of COVID-19?" Does Vitamin D deficiency increase the severity of COVID-19? Here, they talk about how Vitamin D deficiency increases inflammatory cytokines, which work, even though this has become controversial as to whether the cytokine storm significantly contributes to COVID-19. However, what appears until the last notice is that yes, then Vitamin D deficiency increases these cytokines that work and thus harm the patient, and also increases clotting. It is a very logical and reasonable thing that a person who has a Vitamin D deficiency is more likely and more likely, if infected with COVID-19 or suspects they are infected, to start taking Vitamin D. For example, 10,000 international units for ten days or two weeks, and if it is two weeks, they can take 10,000 international units for five days, rest for two days, then another five days, and rest for two days.
Now, esteemed audience, what about zinc? In Jordan, for example, zinc has run out in pharmacies. Many people are taking zinc to prevent COVID-19, and some take it as treatment if they suspect they have COVID-19 or if it is confirmed that they have COVID-19. Here, honestly, there is precision in the topic and caution. There is important information that we must stop at. Initially, we do not have sufficient information regarding what? Treatment. If you are infected with COVID-19, we do not have information from the NIH to tell you to take or not take zinc. As for prevention, it is recommended not to take zinc, and the evidence is weak (C3). However, note here that it is recommended not to take zinc.
Why, esteemed audience? Note now that it says here that a person should not take zinc regarding men 11 milligrams daily, non-pregnant women 8 milligrams daily. This quantity is usually obtained from their food. So, what is the problem if I take extra zinc? What is the problem if I take 25 milligrams of zinc as some say or 50 milligrams as some recommend we use these doses? It tells you here that taking zinc for long periods may lead to a deficiency of copper in the body. This may lead to possible problems in the blood, although these problems can be reversed, while it may lead to possible irreversible damage to the nerves.
Therefore, note now, brothers, if a person is infected with COVID-19, they will take zinc for a week, two weeks, three weeks. This period is not sufficient to cause the side effect we discussed. However, people who assume that someone said as long as there is COVID-19 in the country, I will continue to take zinc. We tell them no, let there be a clinical study that regulates the quantity and duration. As for you continuing to take zinc in high doses of 25 and 50 and extending that for months, that may indeed be harmful. Therefore, if you are sick with COVID or symptoms appear that make you suspect you have COVID, it is okay to take zinc for ten days or two weeks, do not worry about side effects. However, taking it for months for prevention is not advisable.
So, what about NSAIDs? For example, today one of the sisters sent me a message asking for my opinion on something. One of the brothers posted saying, "People, be very careful with many Voltaren injections. Voltaren is diclofenac, which is one of the NSAIDs. These injections may be fatal. Share this with your relatives and loved ones." There has been a lot of hype about this topic. In reality, there is no evidence that these medications, whether Voltaren or others in this group, harm COVID-19 patients more than the general public. It is known that these medications can cause stomach ulcers and kidney problems in the general public, and there are certain groups more susceptible to these side effects. Otherwise, these medications are very commonly used and sometimes indispensable, and they are safer than some alternative medications.
The recommendation here from the NIH says: "Persons with COVID-19 who are taking non-steroidal anti-inflammatories for a comorbid condition" — people who are taking these medications for a condition they have, such as rheumatoid arthritis, should continue their treatment and not stop it. The NIH also recommends that there is no difference between COVID-19 patients and others regarding the use of these medications and acetaminophen (i.e., paracetamol or Tylenol). Someone might say, "I have COVID-19, so I will only take paracetamol and not these medications." The answer is no. If, for example, a doctor advises you to alternate because you have a high fever, sometimes you take paracetamol and sometimes you take an NSAID, the recommendations for you are the same as for someone who does not have COVID-19.
It is mentioned here that in mid-March 2020, some reports suggested that these medications might be harmful and explained a certain mechanism in COVID-19. However, the FDA (U.S. Food and Drug Administration) later stated that there is no evidence that these medications actually harm COVID-19 patients specifically. Therefore, they advised patients to take NSAIDs as their doctor had previously recommended before COVID-19, with the same doses and in the same way.
Of course, there are many other rules in the NIH recommendations, but I wanted to focus on some of them. Dear audience, it is important to refer to relatively reliable sources that provide a summary in an updated manner so that you do not get lost in the enormous amount of studies that are published daily. In fact, we now have hundreds of studies, if not more. There is a lot of information, and one might feel lost and confused, especially since the results are sometimes contradictory.
The panel responsible for these recommendations usually has good methods for appraising or evaluating the results of studies, comparing them, and assessing that a particular study has certain limitations or flaws that make us not take its results seriously, while another study is stronger, and so on. Once again, I hope this video starts a discussion where some brothers bring other guidelines with recommendations that may contradict what we have mentioned, and we try to update our information firsthand. May Allah bless us with the ability to benefit people, and may Allah bless you. Peace be upon you.