On The Line of Fire?

What went wrong with Padmashri, Padmabhushan Mr. S. P. Balasubramanyam, the legendary singer from India? He was recovering and suddenly he deteriorated and succumbed to the illness.

COVID can surprise you anytime, even in the recovery period. I got another note from social media, of a young doctor, a father of a six-month child – obviously a young family. He succumbed to complications of COVID. He was waiting to be discharged and go home.

Well, these unusual stories are gradually becoming common, and I thought of sharing it with you since doctors are seeing such scenarios very often. What is going wrong? Can we truly control it? Understanding these 10 points may possibly help prevent COVID-19. (Reading time 5 – 6 minutes; Scientific perspective).

(Note: We are planning to conduct a cross cutting expert global advisory session to clarify all relevant questions. We are planning to conduct this half day session before the start of the SECOND WAVE. Please share your questions to me in person or on this page as we are crowd sourcing questions from all).

Well, these unusual stories are gradually becoming common, and I thought of sharing it since doctors are seeing such scenarios very often (Please scroll to the bottom of the blog to see the detailed note). 

I had another gentleman who went to a Salon. He argued that he should support the local economy, a lame excuse. Well, even if he wants to support the local economy, he can donate bigger amounts and support the local economy, like many others who have supported their dependent workforce.  Time and again, I have been sharing rejoinders on awareness and precautions, and I am summarizing those below – 

1. A Constantly Mutating Virus:

The virus is constantly changing. It has a gene called RDRP (RNA-dependent RNA Polymerase) that encodes for an enzyme that makes a template for the RNA’s to produce in copies in billions. RDRP has a vulnerable to mutations and this results in the constantly changing nature of the virus. It is this enzyme that makes a (defective) template resulting in mutations. Every time, RDRP makes a template, it ends up producing an erroneous copy that results in mutant copies with every generation of the virus reproduction. 

2. Comorbidities and Unknown Risk:

Selective comorbidities and risk factors are known,however many are yet unknown. We all now know that diabetes, hypertension, smoking, cardiac problems, asthma, immune-compromised, and other respiratory illnesses predispose to COVID. However, we are seeing several youngsters without any of these comorbidities who are suffering and sometimes succumbing to COVID. 

3. Incomplete understanding of the Impact:

Also, we see that some have comorbidities and dies of COVID, whereas others with similar comorbidities survive despite having COVID. Knowing your comorbidities, science still cannot say if your disease will be asymptomatic, mild, moderate, or severe. 

4. Clean recovery or Long Haul Disease:

Despite the recovery, Science cannot predict if you will be ‘long hauler’, i.e. those have long term consequences. According to few reports, almost 10% to 1/3 recovered patients land up with Long Haul disease. The legendary singer, mentioned above, started showing signs of recovery, including light speech and physical activities. He deteriorated due to post COVID complication and eventually died of post recovery complications. 

5. Status of Vaccines:

Vaccines are in pipeline and serious efforts are being made to develop and durable vaccines but we don’t have one that we can rely upon. 

6. Repurposed drugs but No Specific Drugs:

We have supportive drugs but no specific drugs to remove the virus. We know it very well that HCQ was the mainstay at the beginning of the pandemic. Later, it fell into disrepute. Steroids were questioned and only after the ‘Recovery Trial’ substantiated the use of steroids with a randomized controlled trial, that changed the management of COVID. Tocilizumab similarly came in and had an ignominious walkout after the COVECTA trial. Just a few days back, the Japanese FDA approved Favipiravir. the later drug, with its RNA-dependent RNA polymerase activity, has anecdotal evidence of effectiveness since it’s a proofreading enzyme that renders the removal of nucleoside analog (drug molecule) and despite continue inducing mutations. Changes to the use of these guidelines may be anticipated as well. 

Different modalities of therapy for treating COVID-19.

7. Reinfections:

Several are indeed recovering but several reports of reinfections are emerging. It is a fact that several people are recovering from COVID, however, it is equally true that many lands up with severe disease, and those recovering are having long-term debility and need rehabilitation? 

8. Asymptomatic Spreader:

Are you sure, if you will just get the mild form of COVID or remain asymptomatic? Even if you remain asymptomatic, are you sure, you will not pass it on to your family members and if they get COVID, are you sure, like you, they too will be unscathed?   

9. Herd Immunity:

It is like playing with fire. Some insist that we should expose ourselves to build our innate resistance. Remember, this is not a natural virus, also, it evokes severe inflammatory and immune reactions within the body. It is structured or has been structured to keep changing. Our immune systems are built to remember, called immune memory. The changing nature of the virus renders the previously learned immune phenomenon useless. So even if we expose ourselves, our immunity will not last long. It is similar to Influenza. We see a different strain at least every year. With COVID, we see a different strain every few weeks. 

10. Convalescent Plasma and Antibodies:

Plasma from patients having recovered from COVID-19 has antibodies to SARS CoV2. Plasma, thus drawn from recovered patients helps treat and or contain COVID in infected patients. The earliest experiment was done by Edward Jenner in 1796 when he scratched the fluid from the blisters of a cow suffering from smallpox into the skin of a normal healthy man and induced protection. As we now know, Smal Pox is completely irradicated. Convalescent plasma (CP) uses the same principle, of tapping into existing antibodies for treating existing COVID-19 patients. 

However, there is a catch. CP is nonspecific, ie. it has other unrequired antibodies that may trigger untoward reactions. Also, if the virus itself is changing, those antibodies are ineffective. More so, the antibody levels drop after a certain period. Thus monoclonal antibodies become relevant. Placebo controlled randomized trials are being underway (as of this writing) that will offer solace to the treatment of COVID-19. Antibodies have to be targeting specific proteins called epitopes. In the presence of changing epitopes, it is fluid to understand the reliance on monoclonal antibodies. 

Myriad Complexity –

a) Cytokine and Bradykinin Storm: For the common men, the difference is nimble, it does, however, matter for the doctors though. Cytokine storms – processes in which the immune system overreacts to an infection. Ideally, cytokines disappear once the virus copies reach a threshold. COVID, however, puts the body into an overdrive mode and produces cytokines that ultimately result in damage to the organs. (drives the body to produce the immune system keeps producing them and the organs take the brunt from these excess cytokines). Cytokines are associated with myeloid differentiation and disease severity, concurrently the T cells are reduced as is evident from the reduced numbers of CD4+ and CD8+ T cells in patients with COVID-19. 

b) Kallikrein–kinin system: Irrespective of the pathognomic phenomenon (mechanism of the disease), COVID unleashes vast reaction from your own body to damage itself. Think, of this like a natural defense which is supposed to protect you, has turned up against you, causing a perfect storm to disrupt and incapacitate you.

Remember the fluid build up around the lungs, which is primarily caused by bradykinins. Bradykinins causes the blood vessels leaky and result in edema (swelling) around vital organs such as the lungs (short of breath), muscle (body aches), gastrointestinal tract (diarrhea), kidneys (congestion and rising serum creatinine), and a multitude other clinical features.    

c) Endothelial Nitric Oxide System: Endothelial nitric oxide synthase (eNOS) becomes a potential therapeutic target. Hypercholesterolemia, diabetes mellitus, arterial hypertension, and smoking are associated both to nitric oxide synthesis reduction or degradation increase. This nitric oxide bioavailability reduction is followed by endothelial dysfunction

A Picture is Worth 1000 Words:

A review of the work – A great deal of work has been done in the treatment and or containment of COVID-19 in the last 9 months. LitCOV provides an exclusive insight on the amount of scientific literature exclusively within the field of COVID-19. Based on the data from Milken Institute, select treatment modalities have been captured in the pie chart below (cumulative progress in the treatment of COVID).

Reflections On Human Urge to Move Freely

Our fundamental human urge to move and intermingle has been severely constrained, however, historical evidence shows that no calamities remain constant. If you recollect, no rains, volcanoes, earthquakes, or twisters (andhi) remains forever. One day it wanes and so will this virus, it is nature’s law and this virus too will follow those laws. 

Remember, humanity has a significant resilience built-in and as the history of human evolution shows, it has never been subdued nor will it ever let any event subdue its spirit and independence. However, events have always taken a huge toll and we never know if we are on the line of fire. 

Death of COVID Treating Doctor:

A 38 yrs old male doctor gen practitioner was admitted to our hosp with COVID on the 6th day of illness with 60% lung involvement, SpO2 borderline with mild dyspnoea. He became critical in the next 2 -3 days with a typical cytokine storm. We shifted him to ICU and on NIV. He was quite tachypneic, tocilizumab 2 doses were given and his NIV requirements decreased ..and eventually, after 5 days of ICU stay, he was weaned off from NIV and stable on nasal prongs 4-5 L o2. Later, he was shifted to the ward with oxygen. On the previous day of his discharge, he developed abdominal distension and severe abdominal pain, and constipation. A Ryles tube was passed and was kept NBM, X-ray abdomen showed dilated bowel loops but no air-fluid levels. GI doc advised enema, a CT abdomen was advised, radiologist suspected some bowel ischemia, so the patient was shifted to Ruby Hospital, Pune. After struggling with the consequences of ischemic bowel complications, the patient succumbed due to Sepsis and multi-organ failure.

It is now a routine, to see notes such as the one below, on social media. 

Do you want to be on the line of Fire?

COVID-19 cytokine storm: The anger of inflammation; Cytokine. 2020 Sep; 133: 155151. Published online 2020 May 30. doi: 10.1016/j.cyto.2020.155151 PMCID: PMC7260598; PMID: 32544563

https://www.bio.org/policy/human-health/vaccines-biodefense/coronavirus/pipeline-tracker

https://covid-19tracker.milkeninstitute.org/#vaccines_intro

Second Surge and COVID-19 prevention

The risk of infection is the same for everyone in that environment, but the consequences of infection are different depending on age, ethnicity, and comorbidities. Are there any formulae to calculate that? Possibly, emperical estimates can be made using known facts. However, remember, humanity is still in the discovery phase of COVID. We have identofied few risks factors, eg. Comobidities. However, a complete risk stratification is not yet available. Neither do we know who will have mild, moderate or severe disease. (On Behalf of COVIDRxExchange)

Now that aerosols are established as factors disseminating COVID, it is important to realize that COVID is persistent in the air. A few days back, I had a gentleman eating food in a restaurant or the patio of the restaurant. As usual, my relationship made me ask a few questions about his understanding of the disease. He said if we can eat outside food at home, why can’t we eat outside food in the restaurant.

Let us understand and analyze the situation. COVID is not foodborne, COVID is not water-borne, COVID is an airborne infection. The air around you will determine if you are likely to get COVID. In a setting such as a restaurant, this gentleman has a high probability of acquiring COVID. Factors that need to be considered while understanding your chances of getting COVID are the estimated prevalence of infection in that space, contact time and distance, and the degree of aerosolization.

The risk of infection is the same for everyone in that environment, but the consequences of infection are different depending on age, ethnicity, and comorbidities. I often cite an example – of inside and outside risk. Presume, it is snowing and the roads are all icy and slippery. Driving under such inclement conditions is fraught with severe risk. If during such times, you have an emergency at home, you still have to venture out and take care of that. However, if I say I just want to drive and see the fun, obviously it is stupidity.

Thus risk assessment becomes an important factor. Outside risk versus your own vulnerability. That also means that despite the outside risk is high, if you have a critical/essential function that needs immediate attention, you may want to consider doing that. However, if the vulnerability is high, ie. the impact is high, it also means that you want to seriously consider the probability of getting the disease. Thus likelihood and impact are important aspects that you want to consider.

Mitigation depends upon several aspects, face shields, masks (quality is important), and the time of exposure and the (presumably) pre & post-exposure mitigation you perform.

A simple approach to estimate your exposure can be shown in the below formula –

Exposure estimation = (Prevalence of the virus in the air) X (contact time) X (Distance of separation) X (inversely related to your protection mechanisms) X (your internal vulnerability).

The most significant aspect of COVID is that, as of now, SCIENCE DOES NOT HAVE A COMPLETE UNDERSTANDING OF AN INDIVIDUAL’S INTRINSIC RISK.

This is an opinion, not an advisory and you should consult your doctor to seek any advice. The author is not responsible or liable if you use this piece without consultation and advice from your doctor.

https://www.bmj.com/content/370/bmj.m3616

Let us not play God

It is not about China. It is about the human intrigue and opportunity to produce a new organism that unleashes vast implications for us as humanity. The day we start playing nature (God) that day, we should consider as doomsday, because we now know COVID very well and we are seeing how it erupted and further fractured our fault-lines and exposed us – logically, scientifically, politically, ideologically and just the very way we are organized and evolved as humanity.

Interesting repudiation. This is exactly what I was discussing in the first quarter of this year. The introduction is very intuitive and logically engaging. The policy makers across the world are turning a blind eye towards this synthetic source of the virus. However, it shows the power of how human can go wrong in trying to second guess the nature and remix and refactor its native form.

Again, it is not about China. It is about the human intrigue and opportunity to produce a new organism that unleashes vast implications for us as humanity. The day we start playing nature (God) that day, we should consider as doomsday, because we now know COVID very well and we are seeing how it erupted and further fractured our fault-lines and exposed us – logically, scientifically, politically, ideologically and just the very way we are organized and evolved as humanity.

  1. Has SARS-CoV-2 been subjected to in vitro manipulation?

1.1 Genomic sequence analysis reveals that ZC45, or a closely related bat coronavirus, should be the backbone used for the creation of SARS-CoV-2
1.2 The receptor-binding motif of SARS-CoV-2 Spike cannot be born from nature and should have been created through genetic engineering
1.3 An unusual furin-cleavage site is present in the Spike protein of SARS-CoV-2 and is associated with the augmented virulence of the virus

  1. Delineation of a synthetic route of SARS-CoV-2
    2.1 Possible scheme in designing the laboratory-creation of the novel coronavirus
    2.2 A postulated synthetic route for the creation of SARS-CoV-2

Step 1: Engineering the RBM of the Spike for hACE2-binding (1.5 months)
Step 2: Engineering a furin-cleavage site at the S1/S2 junction (0.5 month)
Step 3: Obtain an ORF1b gene that contains the sequence of the short RdRp segment from RaBtCoV/4991 (1 month, yet can be carried out concurrently with Steps 1 and 2)
Step 4: Produce the designed viral genome using reverse genetics and recover live viruses (0.5 month)
Step 5: Optimize the virus for fitness and improve its hACE2-binding affinity in vivo (2.5-3 months)

It is noteworthy that, based on the work done on SARS-CoV, the hACE2-mice, although suitable for SARS-CoV-2 adaptation, is not a good model to reflect the virus’ transmissibility and associated clinical symptoms in humans.

We also speculate that the extensive laboratory-adaptation, which is oriented toward enhanced transmissibility and lethality, may have driven the virus too far. As a result, SARS-CoV-2 might have lost the capacity to attenuate on both transmissibility and lethality during its current adaptation in the human population.

Serial passage is a quick and intensive process, where the adaptation of the virus is accelerated. Although intended to mimic natural evolution, serial passage is much more limited in both time and scale.

The following facts about SARS-CoV-2 are well-supported:

  1. If it was a laboratory product, the most critical element in its creation, the backbone/template virus (ZC45/ZXC21), is owned by military research laboratories in China.
  2. The genome sequence of SARS-CoV-2 has likely undergone genetic engineering, through which the virus has gained the ability to target humans with enhanced virulence and infectivity.
  3. The characteristics and pathogenic effects of SARS-CoV-2 are unprecedented. The virus is highly transmissible, onset-hidden, multi-organ targeting, sequelae-unclear, lethal, and associated with various symptoms and complications.
  4. SARS-CoV-2 caused a world-wide pandemic, taking hundreds of thousands of lives and shutting down the global economy. It has a destructive power like no other.

On point 2 above, I would like to add that, it is possible the military labs never realized the virulence of the new virus since most of the experiments were done on cell lines and animal models, such as laboratory rats and monkeys.

Bleach or Alcohol Based Disinfectant

With rapidly diminishing availability of commercial cleaning supplies, simply diluted bleach, which is readily available, can effectively disinfect homes, offices, and environment to prevent sustained transmission from inanimate objects. Bleach, when used in right dilution, can serve as an alternate option for Alcohol Based Disinfectant. However, the dilutions are important so are the adverse effects from exposure.

SARS-CoV-2 suggests that COVID-19 may remain viable for hours to days, on inanimate surfaces, such as metal, glass, or plastic, for up to 9 days. With exponentially rising COVID-19 cases in the United States, commercial disinfect supplies are in high demand and will unquestionably be limited in the near future. We will have to get creative with available resources, all the while taking safety precautions to ensure our efforts improve and not worsen the ongoing situation.

While the exact viral load on inanimate surfaces is unknown during an outbreak, it is critical to disinfect frequently touched surfaces. With rapidly diminishing availability of commercial cleaning supplies, simply diluted bleach, which is readily available, can effectively disinfect homes, offices, and environment to prevent sustained transmission from inanimate objects. As with many disinfectants, minimizing long-term skin contact and ensuring good ventilation can minimize clinical toxicity.

The virus can efficiently be inactivated by 62% to 71% ethanol, 0.5% hydrogen peroxide, or 0.1% sodium hypochlorite within 1 minute. Dilutions of ∼0.1% sodium hypochlorite are clinically effective with minimal irritation or sensitization.5 One should be mindful that corrosive injury on mucous membrane/skin contact is possible with excess volumes or mishandling, so appropriate caution and moderation are necessary. This solution should ideally be used within 1 month of preparation and stored in a closed, opaque container at room temperature.

∼0.1% sodium hypochlorite can be made by a roughly 1:50 dilution of household bleach (∼5.25% to 6% sodium hypochlorite) in tap water. The proposed formulation is shown to disinfect surfaces of the novel coronavirus. The Centers for Disease Control and Prevention (CDC) also recommends an approximately 1:50 dilution to disinfect COVID-19, explicitly noting 5 tablespoons (one-third cup) bleach per gallon of water or 4 teaspoons bleach per quart of water.

https://www.sciencedirect.com/science/article/pii/S0190962220306095

Am I Culpable for Spreading Virus?

This is a classic example of invincibility and complacency – that nothing will happen to me even while the entire world is suffering from COVID.

Passengers went on a cruise while COVID was raging, presuming that COVID won’t infect their isolation on the ship (in deep water!) never realizing that asymptomatics are the core carrier rather than those who are actively infected.

Exactly this is what happens around us. Yesterday, I was talking with a friend and I realized, he was not using a mask despite the incidence being very high in their state.

That’s pathetic, I understand coronavirus is not seen and leave behind a trail of fragrance but understand, every time an asymptomatic exhales or sneezes, they blow approximately 54 million copies of the virus in the air. It is now known that these copies stay for at least 3-6 hours in the air. That air may drift in your direction and not having a mask while exposed to the potentially infectious airborne virus is culpable negligence, especially knowing that it may make you another asymptomatic carrier.

This pandemic is replete with examples where the asymptomatic have infected the gullible and innocent unexposed. It is the later who has taken the brunt from SARS CoV2.

Shashank Heda, MD
Dallas, Texas, US

Coronavirus: Dozens test positive for Covid-19 on Norwegian cruise ship
https://www.bbc.co.uk/news/world-europe-53636854

The ‘Good and Not So Good’ of COVID-19

While COVID-19 is taking a huge toll across the globe, humanity is displaying a polar reaction – a not so invincible risk taking attitude and a scared, vulnerability. The answer lies in between these two polar extremes. A balanced approach will help to prevent COVID at the individual and family level, which will eventually also be reflected as a social index for measuring our progress while preventing SARS CoV2 and treating COVID-19 patients.

I discussed the ‘good and not so good’ aspects associated with the prevention of COVID-19 and our own vulnerabilities. The initial battle with COVID is in our mind, where we either think we are vulnerable or invincible.

Let us visit the “Not So Good” part early. 

The spike of COVID-19 is huge across the sunbelt of the US. Several southern states are massively infected due to the COVID-19. The virus is seeing a massive resurgence in the UK, EU, and Australia. It is still in its ascendancy in India, Pakistan, Sri Lanka, and several southeast Asian countries. The Middle East is just catching the fever. Brazil and Latin America (currently in their winter) are seeing a heavy toll. 

While COVID-19 is still raging across the globe, humanity is displaying a polar reaction. On one side, we feel strong and ready to take risk, on the other side we are scared and vulnerable. Can we balance our approach and fight this virus? The answer is a definite yes. How do we do that?
The Good and Not so Good of COVID-19

Intrinsic Vulnerabilities are in our mind

You may be thinking, our body is vulnerable and weak and so we catch the infection. While, most amongst us are following precautions., precautions are not enough. We see at least two major vulnerabilities despite following precautions – 

  1. Strictly following precautions and giving up occasionally
  2. Not understanding the innate immunity and how that helps

Let us talk about the occasional vulnerability that we create and expose. 

Restless Inside Home

Several amongst you are restless inside the confines of your home. You are frustrated, bored and some are just angry enough to throw those precautions to disdain. You want to step outside, you are thinking the risk is not what it sounds like, you may be thinking you are young and have a very low probability of acquiring the viral infection. You may be thinking some socialization is ok, more is not good, so let us go for a walk, maybe pub, may have a blast with a limited circle of friends, maybe shopping, etc. etc. 

Are you Alone? 

Think like this – 

1. If the risk is low, why do we see the resurgence or ascendancy of COVID across the globe? 

2. If you are young, have no risk factors, why are young people succumbing to illness?

3. If you say, your ethnicity provides protection? Can you check the mortality data for those exposed within your ethnicity? 

You may be thinking little social interactions are good (walks, pubs, dinners, outings, little shopping, little business, etc.). It is exactly these vulnerabilities that are perpetuating the spread of viruses. 

Do you know?

For every symptomatic patient, we have anywhere from 5 to 10 asymptomatic patients. Are you sure you are interacting with someone asymptomatic (carrier) and have no virus? I have seen several cases where the person stepping out got the asymptomatic carrier, infected those innocent parents/kids/spouse/family members and the later died. Consider these scenarios

  1. I don’t think you can live with the guilt of being responsible for the death of near or dear one. 
  2. Presuming you will survive, what is the guarantee that your organs will not be compromised for a long time? 
  3. Let us presume, you die from illness, have you thought of the implications of your loss on those surviving? Please read surviving with COVID stories and make your choice. 

How do you protect yourself?

CDC has given guidelines for protecting yourself. Every Government has made the best attempts in guiding their citizen from COVID-19. Following those is the utmost while undertaking any activities for your local area. 

Activate your Internal Resilience 

First and foremost, please decrease your exposure and risk. However, boosting your immune system with Yoga, Physical Activities, Sleep, Balanced Diet (and avoid refined diet), and meditation are great ways of doing so. I also saw some interesting read on Mayo Clinics. However, several educational institutions are providing a wealth of knowledge on those. However, reaching out to your doctor at the first instance of suspicion is best. 

The Good News

In its July 7, 2020 issue, Nature Immunology carried an interesting article on why the disease burden varies differently across regions. Simultaneously, the same paper has speculated that previous infection from Common Cold Coronaviruses (CCC) exposure also provides protection, against SARS CoV2. Excerpts from the article below

‘Pre-existing T cell immunity is related to CCC exposure, it will become important to better understand the patterns of CCC exposure in space and time. It is well established that the four main CCCs are cyclical in their prevalence, following multiyear cycles, which can differ across geographical locations. This leads to the speculative hypothesis that differences in CCC geo-distribution might correlate with the burden of COVID-19 disease severity. Furthermore, highly speculative hypotheses related to pre-existing memory T cells can be proposed regarding COVID-19 and age. Children are less susceptible to COVID-19 clinical symptoms. Older people are much more susceptible to fatal COVID-19. The reasons for both are unclear’. 

If these speculations are proven, it can rightly be said that T Cells have a lasting memory towards previous CCC that may be reactivated during a SARS CoV2 infection and offer protection. 

https://www.nature.com/articles/s41577-020-0389-z

Shashank Heda,

Dallas, Texas

(On behalf of CovidRxExchange) 

a nonprofit initiative to help global doctors fight Covid-19

Visit – https://www.covid-19rxexchange.org/)

A dubious distinction

The US has reached a dubious distinction of being a global leader in having 4 million cases of Coronavirus. What leads to this grim scenario? Often, that outside wonder where is the vulnerability. I shared a different perspective on the factors contributing to this grim scenario. In my opinion, there are several factors that contribute to these dismal figures. Understanding the failure is as important as understanding the success, it is through failures that we get a glimpse of success as it offers us an understanding of modeling success and our collective behavior. In this article, I have made attempts to capture aspects across major democracies that offer an insight into success and failure.

The US – then 4 million coronavirus cases. The US is the global leader in Covid-19 cases, followed by Brazil, India, Russia, and South Africa. The statistics run like this –

99 days to reach 1 million
43 days to reach 2 million
28 days to reach 3 million
15 days to reach 4 million
… days to reach 5 million

https://ourworldindata.org/coronavirus-data?country=USA~BRA~IND~RUS~GBR~OWID_WRL

A global leader again (pun intended), how could a country reach such epic proportions of the disease in just 180 days. At least 143,820 people have died across the country. Where is the indiscretion? Is it that the population is vulnerable? Or are we following flawed models of prevention?

Let me cite an example – my HOA asked me to fix the turf, stating it is an essential service. Of course, I responded saying why it is not but this is a reflection of a flawed model being followed.

A confusion between essential and non-essential is the major factor. Another aspect that is scientific activism by gullible people called ‘Corona Mixer’. It is akin to a flawed model of Herd Immunity followed in the UK, Sweden, and few other countries, where COVID-19 eventually exploded.

Third, fatigue from indoor has wrongly motivated several families to stride outside. Of course, a gullible common man cannot see the 54 million viruses that were just sprayed by an unexpected asymptomatic person in the vicinity that followed that infects other innocent bystanders as it drifts along the path of air currents.

There are more factors to the proliferation of the disease. Another complex issue is Political liberalism and assertion for a cause. Subversion or a feeling of being subverted is causing people to rebel and aggregate. Incorrect policies and guidance by WHO and other policy-making bodies is another contributing aspect factor.

Policies – a bedrock for containment: Policies offer a solid fabric for control and on the converse is equally true that not having consistent machinery to execute policies is an equal deterrent. I will shy to quote an example from a major city from central India where a breakdown of communication amongst the policy executioners resulted in a flare-up of COVID across the town. Remember, if only the infected (symptomatic and asymptomatic) can strictly isolate, we can contain the virus.

Indore a success story

We have several success stories from around the globe but visit CovidRxExchange to learn about, Indore – A Success Story. You will see how a metropolitan city controlled the disease at the outset with a well-executed policy and a diligent team of doctors.

Can we change this? Possibly that’s the Midas touch that would delay and possibly deter further infection.

Shashank Heda, MD
Dallas, Texas

References:

https://ourworldindata.org/coronavirus-data?country=USA~BRA~IND~RUS~GBR~OWID_WRL

https://www.ncbi.nlm.nih.gov/research/coronavirus/publication/32691016

Stay Safe! It’s a cliche!

The tidal second wave of Coronavirus is surging across the globe. What went wrong? Was easing the lockdown a wrong decision? or was it our inadequacy to understand the virus behavior? Can we understand what went wrong? We each define the microcosm of the society and we contribute towards the spread via our Social Bubble or contain the Spread with our responsible behavior.

I have captured all the risks factors and how to fix our own behavior during this tidal surge of COVID wave.

Stay safe has become a cliche, like Good morning, bye etc.

Friends, this week has been extremely bothersome as the second wave has been not just huge, not just a tidal wave but a seismic wave, and a tsunami that may overwhelm our healthcare system. Not just in Texas alone, it is across the US mainland, the UK, the EU, China, India, Brazil, Mexico, etc. It is extremely scary.

What went wrong?

First – let us understand some principles of transmission of the virus. Second, let us understand our fallacies. Next, let us understand our social dynamics.

A) Virus Transmission –

A virus multiplies in 100,000 copies in one single day. Almost, one bout of coughing produces 54 million copies, that fly as aerosol and also settle as fomites. Being a tough virus, it survives in the air for almost 3 -5 hours, depending upon the ambient conditions. The warm and humid environment makes it hang around longer. It drifts with the air current or stays suspended without a drifting, with no wind current. The peak is 14 days, thereafter the virus gets neutralized in the patient.

Symptomatic patients are not the only bug spreaders, for every symptomatic patient, we have 10 asymptomatic patients who are spreading the virus. However, for asymptomatic patients, the virus cycle continues for almost 28 days. Unfortunately for us and fortunately for the virus, it is colorless and invisible and since it is invisible, we feel pseudo confidence that we are invincible.

B) Our fallacies –

We presume the virus is not there. That and given our boredom of staying inside makes us extremely prone to catching the infection. We are frustrated staying secluded, within the confines of our four walls. But you are not alone, almost over two billion people on this planet earth are secluded and claustrophobic within the confines of their home. We all know social distancing but I see several families taking a stroll without masks, not knowing that they may be inhaling the virus.

Somewhere, we presume, it is a disease of the elderly. I have seen several case reports of a death within the young and healthy. I have seen case reports of kids suffering immensely from COVID. I have seen elderly parents escaping death. This all points towards one thing – that Science has not yet definitely identified risk factors for mortality and morbidity. Thus the virus behavior remains elusive and erratic. You may get the bug, harbor it and unknowingly, you become a super spreader. I see school kids interacting with each other. How can we ensure that those they are playing with have no disease (asymptomatic carrier)?

Social Bubble – Exactly, this small social network connects us with other tiny bubbles, and this is becoming the route of spread. New Zealand is the first country to realize this and they broke the vicious cycle and almost eradicated the virus. They will, however, get reinjected, once they start air travel though.

Work Bubble – We think, we are acutely dependent on running our family for a livelihood, not realizing that those who are working can become asymptomatic carriers and transmit to vulnerable parents staying with us. Are we so careless? (@Dr. Shashank Heda, for COVIDRxExchange.Org). If we have to essentially step outside for a living, let us live under a different roof, not with those family members who are vulnerable.

What Do We Do?

  1. Strict Social Distancing is not enough, we will be inhaling the bug via several routes.
  2. You all need to suspend all strolls, shopping, and other errands. Let us minimize exposure as much as we can. Can we buy online?
  3. Fomite transmission is deprecated. That means fomites do not pose as much risk as was considered previously. Please visit CDC for the guidance.

Summary: If you have let your guards down, a “new high probability” risk factor that will determine your chance of getting the infection. You can make your choices.

COVID & Spanish Flu – Comparison and Contrast

102 Not out – Approximately 102 years back, the world was ravaged by Spanish Flu (a misnomer) and today, we are reeling under COVID-19. Both pandemics caused significant pandemonium, and share a common pattern. While it is understandable to see an intermittent new ‘human – microbe’ interaction, going awry, the current pandemic has exposed our fault lines and our preparedness after 102 years. It is not about microbes and our immunity, it is a testimony of our (un)evolved human journey or rather stagnation of evolution in the last 102 years.

102 Not Out, provides a succinct comparison and contrast between the Spanish Flu and COVID-19 and a poignant story of our collective failure.

Background

1918-19 – That period must be the one coinciding with your grandparents or great parent’s birth. So, memories are only through archival records. The global toll was almost 50-100 million, whereas the US lost some 685000 people (a very high percentage for the population at that time). India had 5% mortality with over 12 million succumbing to Spanish Flu.

Spanish Flu – What is that?

Is it truly Spanish flu? It started in France and England. However, they both were at war and wanted to keep this covered. However, Spain being neutral, and news being public, it was reported transparently. It is a misnomer to call it Spanish flu. That is derisive, as Spain was neutral during WW I. It was World War I and soldiers were living in overcrowded barracks. It started in Etaples, France in 1916. It will similarly be wrong to construe that it was an element of French warfare because a similar disease was also observed in 1917 at Aldershot, England. Then too, it was commonly thought to have jumped the animal-human borders as pigs and poultry were a mainstay at these hospitals.

It never occurred to them that they would take the Influenza bug along with them while traveling back home. A disease that once was restricted to specific geography quickly became ubiquitous and spread out indiscriminately. As John Barry said, in New York Times, “None alone provides great protection, but the hope was that if most people followed most of the advice most of the time, the interventions could significantly reduce the spread of the disease, or “flatten the curve,” a phrase now all too familiar. This may sound simple, but it is not. As with a diet, people know what to eat but often stray; here straying can kill”.

3D_Influenza_transparent_key_pieslice_med

(Picture Credit – CDC illustration on influenza virus. Influenza A viruses are classified by subtypes based on the properties of their hemagglutinin (H) and neuraminidase (N) surface proteins. There are 18 different HA subtypes and 11 different NA subtypes. Subtypes are named by combining the H and N numbers – e.g., A(H1N1), A(H3N2). Click on the image to enlarge the picture).

It almost engulfed an entire then connected globe. However, the definition of connectedness, which was ignored then and which is ignored now too, is common to both the Spanish Flu and COVID-19. An estimated 500 million people worldwide were affected. It was a rudimentary period in the evolution of medicine and of course, there were no vaccines or medicines to treat the patients. The findings were, as usual, generally, healthy young adults succumbed to the illness, contrary to most diseases that took the life of the young and old. Today, we call this onslaught of infection against those with a mature immune system as Cytokine Storm. Then, we only knew it killed the young. Then too, people used hand washing, isolation, masks, avoiding public places, and quarantining those ill/suspected ill. It ravaged the economy and disrupted public life, basic civic services like garbage clean up, and postal delivery government services etc. were compromised. There was no one to cremate dead bodies; garbage was flying astray across the streets, no one to light neither lamp posts nor sufficient people to deliver the mail. City offices started digging mass graves, closed schools, public places including theaters. The truth was not transparent, trust in authorities deprecated. Then too, there was a lurking fear that ““civilization could easily disappear from the face of the earth.” Reopening then was marked by a rebound in cases.

Rebound after Reopening

Spanish Flu Rebound

In its intense and acute form, the malady lasted for almost 15 months, from the spring of 1918 to the summer of 1919. It is said that this pandemic Flu almost killed 50-100 million people. Today, we call that Influenza A or H1N1 flu. H1N1 kept lingering, again due to mutations, for 38 years until it was controlled with specific therapies.

Antigenic Shift versus Antigenic Drift

Influenza A and B, each has 8 genes and a variation keeps happening to make a combination each year. As investigations reveal, the 1918 pandemic started with an H1N1 strain, that kept mutating. At this moment, it is wise to understand the meaning of H and N, H stands for those proteins which are required to latch on the cell (inside) and release themselves (N proteins) when mature to infect other cells. This protein structure keeps changing slightly, called antigenic drift. Sometimes, the virus mutates significantly with major changes in the structure of the H and N proteins, called an Antigenic shift.

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Fast Forward 2019-20 – Comparison and Contrast

It is commonly accepted believe that SARS CoV2 jumped the animal-human barrier. It too spread out from densely populated places. Like COVID-19, it took the world by surprise. No one anticipated that the global burden of death would be over 250, 000 in just 4 months. Then, there was no medicine and here again, we have no specific remedy. The mechanism of death was the same, cytokine storm prevailed then and it is reigning now. It took away the young healthy adults then, however, it is incapacitating for those young adults now, though the mortality is very high in the elderly. Then too, we used masks, isolation, and barrier protection, which we see as the mainstay of stopping the virus within the communities. We call it social distancing, back then, they called it crowding control.

What have we learned?

We see a commonality in the pattern. The biological behavior of the bugs is not changeable. The human response was almost the same. We respond exactly the same way how we responded then. We distanced from each other, we realized, it was spreading through our breath and mouth, so we used masks in 1918 and again, we are using masks. Is there anything wrong with this?

Quotable quotes from Christopher Nichols, Associate Professor of History at Oregon State University –

“The questions they asked then are the questions being asked now,”

“And while it’s very rare that history provides a simple straightforward lesson for the present, this is one of those instances. The Spanish flu tells us that social distancing works. And it works best if we act early, act fast and stick together — and base our decisions not on social or economic concerns, but on science and data and facts.”

References:

 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1997248/
https://www.nytimes.com/2020/03/17/opinion/coronavirus-1918-spanish-flu.html
https://www.webmd.com/lung/news/20200420/four-lessons-from-the-1918-spanish-flu-pandemic#4
https://www.cdc.gov/flu/about/viruses/types.htm
https://www.cdc.gov/flu/about/viruses/change.htm

 

https://interactives.nejm.org/iv/playlist/index.html?media_id=siCcYW3U&pcs=sidebar

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1997248/https://www.nytimes.com/2020/03/17/opinion/coronavirus-1918-spanish-flu.htmlhttps://www.webmd.com/lung/news/20200420/four-lessons-from-the-1918-spanish-flu-pandemic#4https://www.cdc.gov/flu/about/viruses/types.htm

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1997248/https://www.nytimes.com/2020/03/17/opinion/coronavirus-1918-spanish-flu.htmlhttps://www.webmd.com/lung/news/20200420/four-lessons-from-the-1918-spanish-flu-pandemic#4https://www.cdc.gov/flu/about/viruses/types.htm

Stopping the Pandemonium from Pandemic

To me, this situation is like a war that is imposed on a country. You don’t want to lose lives whereas, you still have to fight a war. It’s a dilemma, difficult to discern. None of this was anticipated in advance, or rather, most Govt’s. were not aware of these.

Even doctors make a decision based on benefits versus cost. Most planners struggle with this dilemma and much of their decision-making nodes are based on this.

Losing life is not the option but when you factor in those folks who have run out of money and be in their shoes, we realize the hurt and the pathos of daily living. Politicians and Policy makers alike face this challenge. If they ignore, it will end up with rioting, anarchy and add further to the pandemonium created by this pandemic.