Inflammatory Tsunami

Case in point, in isolation, a 70 Y/O Male, with uncontrolled Diabetes type 2 with HBA1C of >14 presents to ER at day 17 of symptoms, 14 days after positive Nasal swab for COVID-19, barricaded at home and now his daughter called the ambulance because the patient is unresponsive. At the onset of his infection, he developed loss of taste, smell and appetite, no oral intake for days. The patient became dangerously dehydrated with 13 litter deficit of free water, Corrected serum Sodium of 181 mmol/L (Normal 135 -145), the blood sugar level of 800 mg/dl (Normal 70-100) and acute kidney failures with BUN/Creatinine 108/2.79. Noteworthy is, he was someone with a PCP and health insurance. These are those who die at home or comes in too late to salvage, thanks to isolation methodology or lack thereof we currently practice. This patient meets the significant criteria for poor outcome, Male older than 65, uncontrolled diabetes. Sending him home to isolate without some forms of close monitoring is a recipe for poor outcome.

In some regions and healthcare system, such as the one I practice in, the methodology is patient-centered. Upon being diagnosed with COVID-19, one is sent home with Homehalth nursing and Telemedicine monitoring.  Standard discharge equipment includes thermometer and pulse oximetry, the later, for monitoring one’s oxygenation, which is crucial in early detentions of those needing hospitalizations. 

In other regions of the country, the vast majority of the times, “you are on your own.” Your safeties depend on how well you know your body, family support and on your brain remaining clear as the illness progresses. Your abilities to judge if the disease is heading in the right direction lies the outcomes of your infection. Consequently, quite often by the time patients arrived at the hospital, they are beyond phase 1 of the disease, and deep into phase 2 or tragically the final stage 3 of the disease.  Phases 2 and 3 means your body has now entered into a full-blown what I would call “inflammatory Tsunami,” as we all know, there is no practical way of stopping a Tsunami.

Amazingly quiet often as the disease progress, the patient becomes delirious and confused, so now the lifesaving call is entirely left precariously to your dwindling brain capacities given the rapidly progressing illness. I am here speaking of the high-risk group. I am fully aware of the thousands that will do fine, but it is those few but the significant percentage who are clogging the health systems and who are dying unless we intervene!

From all the available data coming from Asia to Europe, North to South America, we now seem to have a definite timeline of clinical progressions of the COVID-19. This timeline appears predictable.

In average, the incubation period is day three through day 5. The first day of symptoms is of critical importance to annotate.  Day 1 of symptoms to day # six will be phase 1. Patients in the high-risk group fare poorly from the COVID-19, as reported by The New England Journal of Medicine and other publications, herald by pulmonary phase or stage 2 with breathing difficulties which start at day seven from symptom onset.  The final stages of severe to critical step are at day 10-14 and beyond from symptom onset.

Day one of the Symptoms then is crucial to jot down. Observational Data suggest hospitalization to the medical wards occurs from day 7 to 10, admission into intensive care unit occurs between day 10-14, and death occurs between day 10-17.

While we struggle to come up with Vaccines and Antiviral to target the organism, we do have useful tools in our arsenals to prevent, mitigate and treat this death-causing damages triggered by the infection. These tools are not new, and they can be helpful, granted interventions are timely, not delayed salvage therapies at stage 3 of the illness. Given the dismal outcome of the Ventilated patients in ICU, then it seems the best window of interventions are in phase 1, which are days 1 to 6 of symptoms and latest stage 2, days 7 to 10. Beyond day 10, stage 3 is salvage therapy nothing is very much useful here, very possibly not even the hyped Remdesivir nor convalescent plasma, given the virus seems nonviable beyond day 9^th of symptoms.

During the incubation period, from day one to day 5, once infected by the virus, it got what it wanted, it needs you because it cannot reproduce (replicate) by itself, the virus cannot propagate and make more of itself.  It needs your genetic pieces of machinery to making more progenitors, numerous, trillionths of new wicked viruses.  This process is fast, and it is rapid. You are now an official Virus factory. Thus the need to cover your chimneys! By the first day of symptoms, Your body is awash with the maximum amounts of virus load, and from there on its numbers start to decline rapidly as your immune response stage a fight, such that by day # 4 of symptoms half of this viruses are destroyed, and by day nine perhaps most of them are dead. Still, by this time, your life is in the thick of thick if you are one in the high-risk group.

By the first day of symptoms, either the direct effect of the infection or the beginning of the inflammatory response, your body reacting against and to the virus results in some of the typical symptoms comparative to the influenzas, Malaria, dengue perhaps even to allergies.  These symptoms include a scratchy throat, congested nose, headache, muscle aches, fevers, loss of taste, loss of appetite, diarrhea and nausea.  You may have most of the symptoms or just 1 of them. 

if you are someone who suffers from chronic sinuses, you explain your headaches away as sinus pain. If you suffer from migraine headaches, it is straightforward to convince yourself as having a migraine attack.  If you live in a place where there are Dengue fevers, it is natural to tell yourself; you are having Dengue fever. Again if you live in an area where there is Malaria, it is easy to say you have the sickness.  It is of utmost importance; this worldwide crisis, COVID-19 must precede all of this other common diagnosis when you have any of the above symptoms.  It is of critical importance that, if experiencing any of these symptoms, one must not assume h/she is dealing with other illnesses such as Malaria. Doing so will delay time as the clock is ticking. Do not diagnose yourself, you must seek help from your physician, or your health authorities, let them decipher whether you are dealing with COVID-19 or you are dealing with a common illness. It took them decades of schooling and continual educations to be able to give diagnoses, a read in google search will not cut it, don’t short change yourself. You will not seek medical treatment from me if I were to get my medical education on Google search; why will you practice such medicine on yourself?

Additionally, keep a logbook and Mark in your calendar the very first day of symptoms.  If you have any headache, cough, loss of taste or smell, nausea/vomiting or diarrhea, write it down.  Pay attention to your body language.  Day one of symptom is where the marathon begins, because, as from the first day of symptoms, the clock is on.  If you are one of the high risked people who are going to do poorly, you will start breaking down by day seven, and at that point, you must seek help quickly.

This inflammatory response leads to damaging of the lining of your blood vessels. The body tries to repair these damages by forming clots, and there are widespread clots in the presence of overwhelming inflammations.

 In the second phase, your blood vessels, the microvascular bed are overwhelmed by inflammations and damages sets in but dangerously by blood clots. Once this happens in the lungs, it starts to fail, and you develop shortness of breath, in the kidneys, you develop kidney failures. In the Livers, your liver enzymes begin to rise. In the heart, Chest pain and the brain, confusions to strokes set in. You develop extreme weakness, and at this point, it is critically important you get to the hospital promptly and without delays.

By day seven to ten, the inflammatory damages and blood clot formations are significant enough to require you head to the hospital and get treated. Those who continue to sit at home through stage 3, which is day ten and beyond, at this point, the damages are complete, and any management is salvage therapy. The Tsunami is entirely on the course, and it is challenging if not impossible, stopping a Tsunami. Why get to this stage in the first place? Is there an effective way of avoiding this stage? That is the million-dollar question. My answer to this question is yes, and it goes contrary to the current model of going home and returns when dying!

This finding is of significant importance to any future use of antiviral beyond day 9.  It begs to answer the question if the virus cannot be cultured after day nine, then why is it that patients are becoming the sickest at day ten and beyond, requiring ICU admissions and death occurring after day 10 of symptoms?  By day ten, that means your body has been with the virus for 15 days.  It is merely telling us then after two weeks; the virus no longer is the problems, but what it caused to happen is the killer.

If the virus cannot be cultured, then the virus is dead, or the virus does not have enough living quantity to be grown in the laboratory.  The extreme inflammatory, mechanical and immune response has fried and annihilated the virus but likewise triggered and inflicted fatal collateral injuries which now your doctors have to try to salvage you, if in stage 3. Thus the need to understand these three phases and seeking help promptly not sitting at home until you can’t, by then it is simply too late for even the best health centers to save you from your immune systems and clots are gone rough and wild.

We probably should question any study designs for hydroxychloroquine plus Zinc or Remdesivir, in hospitalized patients, which occurs days seven and beyond but particularly for ICU patients, which arises primarily days ten and beyond. Should the virus be minutely present or nonviable, then Antivirals like Remdesivir possibly missed the window of entry into the course of the viral illness, more so ICU, in which the virus could not be cultured.

 At the sickest stages, the available data seems to suggest that our patients are being taken down by body loads of inflammatory and microvascular clot burdens rather than the direct viral effect since it is no longer culturable beyond day # 9 from symptom onset. This being true, then purported anti-replication medication such as hydroxychloroquine and Zinc, Remdesivir and any upcoming regimen directed against the virus missed its window of entry at stage 1 but late in 2 of the illness but surely, phase 3, i.e. day ten and beyond.

At stages 2 to 3, that is severe to critical stages, our focuses should no longer be the virus whose life has given ghost to the staged inflammations by the host cells. What is left is now to navigate through myriads of collateral damages of the nuclear weapons just released by the immune systems, the inflammatory Tsunami!

The available scientific data suggests anti-replications medications are to interject when replications are active or 1^st day of symptoms to latest day 7th. Best at day 1 of incubation period, but this is not practical as the patients have no symptoms to pick them up at such an early stage.

We have a model, in influenza A and B, and the use of oseltamivir, this must be given within 48 hours, before viral release.  If we are targeting to block replication or diminishing replications/release, then the right timing to give antiviral is at days 1 to 6 of symptoms, not ICU.

On the other hands, it is not practical to target the experimental drugs early on to everyone given the thousands of those infected. Still, the overwhelming nature of the Pandemic should not make us design studies against our prior well-established data.

Given, on average, patients start to arrive at the ER on day Seven, and this is happening because of inflammatory Tsunami, we need an objective analysis of the internal battle taking place with the virus. It means at day 5 and 6; among the high-risk groups, we should run basic laboratories to include CBC, CMP, inflammatory markers, particularly d-dimer and CRP.  Once the inflammatory markers are out of control or the patient is starting to show an end-organ injury such as elevation of liver function tests and rising creatinine, then, the patient needs potent anti-inflammatory regiments in attempt to blocking the Tsunami from taking off and antithrombotic interventions. It calls for dexamethasone and therapeutic anticoagulation after risk assessments.  By starting steroid at day 5 and 6 of symptoms (10, 11 days since infections), it is maybe quite possible to block the inflammatory Tsunami; we may avoid hospitalizations all together, more important if we are to have a second wave or in surge situation of the Pandemic. This approach could be achievable and cheaper than the overran hospital scenarios observed in Italy and New York! It may be, this is the stage we should seek to intervene, which may seem overwhelming given the sheer numbers of COVID cases but probably cheaper than the weeks spend in the ICU on vents. This method calls for sharpening the triage by the very highest clinical risks group. It also calls for increased outpatient care not just isolation and self-monitoring such that we catch patients who are deteriorating early on at or before entering phase 2 of the infection.

Additionally, It seems to me then, anyone requiring treatment because their inflammatory markers are out of control and having symptoms requiring admissions, the cornerstone treatment protocol must rest on what thus far, have shown results in literature and practices; anti-inflammatory medications such as tocilizumab, anakinra or best yet, a well known drug to us, a high dose dexamethasone to bend the inflammatory curve and full-dose anticoagulation to arrest further micro-vascular bed thrombosis. However, Acting early on may prevent hospitalizations altogether.

The right, real and timely cure could be in the outpatient world with PCP and home health nursing/Telemedicine; this is where the focus may need to shift as the numbers are overtaking us. Timely and early on Oral dexamethasone, Xarelto and the likes could be the answer, and these are safe well established and known outpatient regimen.

Once admitted, there is no reason to give anticoagulation in a graded fashion as practiced in most centers; how did we coin such? While the virus is new to us, these medications are not. Post day Nine and in the ward or ICU, At this stages, the virus is an afterthought, and we must save our patient from the inflammatory and micro-vascular thrombotic damages left behind by the COVID Tsunami!