CovidRxExchange – A year into the Journey

As I take this moment to recap our one year journey with CovidRxExchange, with all humility I wish to honor and pay our gratitude to our Patrons, Mentors and SPOCs, Executive and our various teams who helped evolve CovidRxExchange as an initiative to reckon with –

Patrons –

Dr. Vikas Mahatme, Ophthalmologist, Padmashree, and Rajya Sabha Member
Dr. Sunil Deshmukh, Radiologist and Former, Minister, Govt. of Maharashtra.
Wing Commander Babu, Formerly IAF
Mr. I. S. Chahal, Commissioner, Mumbai
Dr. Zodpey, VP, PHFI, Delhi,

Mentors:

We are deeply humbled and honored to have mentors like –
Prof. Emeritus Dr. Manbar Rawat, a Prof. of great respect and repute across multiple generations.
Prof. Emeritus Dr. Vilas Jahagirdhar, Formerly, Prof Microbiology and Dean
Prof. Uday Bodhankar, Formerly, IAP President, VP COMHAD, UK
Prof. Vrinda Sahasrabhojaney, Retd. Prof. Medicine.
Dr. Naveen Thacker, Director, IAP

Intent and Objective:

CovidRxExchange, a global nonprofit initiative, started in March 2020 to disseminate expertise, insight, and experience in managing Covid for the doctors, Health Care policymakers, and policy planners, and administrators. The intent is to enable doctors across borders to leverage the expertise they have honed in Covid patients’ care.

In March 2020 (exactly a year back), our initial foray was to disseminate knowledge and expertise from the US to the experts at Mumbai. We arranged our first call between Dr. Toraskar, Chief of Critical Care at Wockhardt and HOD of Cardiology at Nair Hospital, and two experts from the US, who had by then gained significant experience managing critical cases of Covid. From that experience, we realized, it is best to institutionalize the knowledge transfer and make it global. After that, we started panel discussions on the practical care of Covid in HDU and ICU.

Over a period of time, as Covid kept raging across countries, economies, globally, nationally, and regionally, we realized the needs got more specific, and we differentiated our nonprofit services to include more services under our gamut of CovidRxExchange.

Scope and Out of Scope: We are aggregators and disseminators of expertise, insight, and experience. We occasionally conduct our own research. We are a global organization.

Our Ethical Values

CovidRxExchange adheres to strict ethical guidelines. Nondiscrimination and noncommercial form the backbone of our services. We are an inclusive organization devoid of leaning towards any political ideology or any faith-based ideology. We are committed to translating academic evidence-based medicine to enable doctors, policymakers, and administrators. We are noncommercial and agnostic of vendor bais in providing our nonprofit services.

Activities and Accomplishments:

A. Our Initial Engagement – Panel Discussions and Second Consultations

After conducting several panel discussions, we were approached for several second consultations. Our next group was the second consult, and our global group of experts offered a second consult in several cases. Dr. Ajay Chaurasia (Cardiology, HOD, Nair Hospital), Dr. Nandita Divekar (UK), Dr. Rahul Sarkar (UK), Dr. Hettiarchi (UK) and Dr. Sandip Banerjee (UK),

B. Web-based Knowledge Repository (Lifecycle and Extended Lifecycle Approach)

Eventually, we created a web-based repository, a library with a Lifecycle approach to deal with Covid. Our lifecycle approach provides end-to-end case expertise of different aspects of covid from remote consult, first visit, admission (floor) to HDU, ICU, discharge, and bereavement.

As Long Haul disease became prevalent, we extended our Lifecycle Model to Extended Lifecycle Model, including Stress Management for Doctors and HCW and rehabilitation.

C. Risk Management: Extending Individual Care to Institutions, Cities, and Corporations.

Realizing that Covid was no more a patient condition, we created a 3×3 model. The 3×3 model extended the services to institutions, cities, and corporations. Thus the policy planners too came under the aegis of Covid Care. We helped the City of Coimbatore, An City (Anonymous) with significant Covid to identify and restructure their Covid, and did a post facto analysis for a metropolitan area for What best could have been done. Indore team (comprising of Dr. Nishant Khare, Dr. Sanjay Dhanuka, Dr. Anand Sanghi, and Dr. Gaurav Gupta), the UK Team (comprising of Dr. Divekar, Dr. Banerjee, Dr. Sarkar), the US Team (comprising of Dr. Lakshimi Sambathkumar, Dr. Arvind Virmani and I), and the Mumbai Team (comprising of Dr. Chaurasia, Dr. Ashok Anand, Dr. Hemant Bhandari, and Dr. Pankaj Maheshwari), worked along with the Coimbatore Commissioner, Deans, and Professors to provide a blueprint for Covid mitigation in the Corporation of Coimbatore. Dr. Rajamani and Ms. Kruthka Govindarajalu, Director, Smart City, Coimbatore, played a pivotal role.

D. Tribals and Areas of Deprived Resources: Eventually, as Covid made inroads into the tribal areas/interiors and understanding that 10% of India’s population lives in Tribal Areas, we developed our Tribal Covid Model. Dr. Ashish Satav, Dr. Sahasrabhojaney, Amod, and I, spearheaded this Tribal Covid Model. Realizing that the economically deprived areas and tribals areas have shared problems, we consolidated this capability under Tribal and Areas of Deprived Resources.

E. Holistic Health: Mindfulness, Sleep, Exercise, Nutrition, and Yoga, are crucial to achieving normal health. Ms. Gomathy Periatheruvadi, an Entrepreneur and Executive from the US, is leading this capability.

F. Rehabilitation and Long Haul: This is one area where we are still striving to expand our footprint. We are exploring to develop this capability, and Dr. Mariya Jiandani has shown interest and bandwidth to expand these services.

G. Vaccines – Developing a requisite immunity is based on critical success with Vaccine deployment. Vaccines emerged as a significant area that our doctors needed an incredible amount of support. Realizing this, we organized a series of panel discussions and one on one calls to address patient concerns.

H. Variants – Mutations and their aggregation into variants created a different challenge, both in transmission, infectivity, and the second/third/fourth surge across nations. We have set up a dedicated capability and integrated this under the vaccine capability. We are exploring the implications of the variants such as B1.1.7, B1.351, P.1, B1.521, and the recent variants found in India and other countries on the transmission, infectivity, morbidity, and mortality. Dr. Mukul Acharya (UK), Dr. Anand Kawade (India), Dr. Nitin Wairagkar (US), Dr. Kedar Toraskar (Mumbai), Dr. Naveen Thacker (India), Dr. Suhasini Balasubramiam (Chennai), Dr. Anita Mathew (Mumbai), Dr. Mala Kaneria (Mumbai), and Dr. Neetu Jain (Delhi) are working under the mentorship of Prof. Dr. Rawat and Prof. Jahagirdhar.

I. Dispelling Rumors: As rumors are flying rife; we are identifying SPOC’s to evaluate, analyze, and provide a scientific evidence-based rationale to dispel rumors

J. Socialization of scientific understanding into commonly understood language is important as we consider that if our nonmedical community is aware, they can be the necessary pivot to transgressing towards success. Thus dispelling ‘Rumors and Socialization’ are emerging as recent capabilities.

K. Liaison: Covid needs an adequate translation to policy and execution. We are currently working on establishing a capability to connect with the policymakers at different Govt. Machinery levels.

L. Awareness: Specifically for the nonmedical folks based in the US, we have created an Awareness Group to share information on awareness.

M. Strategy, Risk and Program: With my background in Strategy, Governance, and Risk Management made me realize that these should include these as independent capabilities. Thus, Strategy (Wing Commander Babu and I), Governance (Founders) and Risk (Amod and I) are maturing this capability. We reinvented the industry approach on Risk Management and tweaked it to align with Covid and Medical care. Concurrently, as capabilities were sprawling, we realized a common framework should encapsulate the entire initiative. Thus, we initiated program management (with a CMMI/ISO) capability to standardize for all the capabilities. Manish Singhal has taken the onus to develop this nascent capability.

N. Legal, Compliance, Finance: While some of these capabilities are a doctor (customer) facing, many capabilities are operational and happening on the backend: operations, Legal, Compliance, and Finance capabilities. Mr. Yogesh Vyas, Mr. Amod Manjrekar, and

O. Technology: Manish Singhal, Amod Manjrekar, Pankaj Bhakta, and Shriram Devata provide that support. This is still an incipient and nascent capability where we are expecting significant development.

P. CME: These capabilities are in embryonic stages. We are exploring global sponsors and accreditation for this capability.

Q. Editorial: We are upgrading our capability to provide updates (weekly, daily, and flash). Currently, we are scaling capability to include over 2000 of our users.

R. Emerging Technology: We are building an industry consortium to address medical problems leveraging technological advances. An example can be using Artificial Intelligence and Machine Learning to address predicting the utilization of beds, or developing a model to understand the emergence of a specific variant in a specific geography and the impact of these newer (hypothetical) variants on transmission, infectivity, and overall community-based impact.

S. Ombudsman:

We strongly encourage professional interaction and courtesies. We heavily lean on Evidence-based rationale, and we respect creativity. Our ethical values are foremost essential for us, and we cherish those with the highest order. We have identified Prof. Emeritus Dr. Manbar Rawat to resolve any residual issues if not resolved by the Founder.

All along, we have ensured that only hands-on experts are providing the knowledge transfer. We are not book-based academicians. Our experts have significant hands-on experience and expertise from their specialized domain. These experts’ work contributions are pro-bono, i.e., they do not charge us, and we do not reimburse them.

Funding: As of this writing, we the Founders, have funded all the initiatives. We have not received any funding from donations, advertisements, any pharmaceuticals, or any other industry. We have avoided all and any conflict of interest.

Scaling and Continuity: We will explore submission to foundations for support. If we secure funds for CovidRxExchange, we will announce that and develop Policies, Governance, Visibility, Transparency, and Audit/Accountability.

Slack: Slack is our global portal of Collaboration and Communication. However, WhatsUp is a transitory and stop-gap arrangement to support ease of communication.

Movers and Shakers: We will post the list of Several Movers and Shakers who make this initiative a throbbing success. Women, Budding Leaders, Technology Team and Operations team are few who make several things happen.

Our Founders (in alphabetical order of their first name):

Dr. Ajay Chaurasia, HOD Cardiology, Nair Hospital, Saifee Hospital, Mumbai Hospital, etc.
Dr. Anand Kawade, Pediatrician and Vaccine Authority, KEM Hospital, Pune and Vadu
Dr. Arvind Virmani, Molecular Scientist, Washinton DC.
Dr. Ashok Anand, Professor and Head, Gynecology and Obstetrics, GMC and JJ, Mumbai
Dr. Hemant Bhandari, Orthopedician, Mumbai Hospital, Mumbai
Dr. Pankaj Maheshwari, Chief of Urology, Fortis Hospital, Thane, Mumbai
Dr. Shashank Heda, Molecular Pathology and Technology Executive, North America

Humble Note: If inadvertently, we have missed a name, kindly bring it to our notice and we will credit them for their contribution. We request you to pardon for any of our omissions.

The case of a swollen node?

(Note: this message is drafted for the nonmedical audience) 

What’s a swollen node? Lymph Nodes are your primary line of defense leveraged by your inbuilt immune mechanism. Everyone has it (rarely are people born with a defect with the immune mechanism). 

Suffice to say, whenever you have an infection or hurt in that part of the body, the lymph nodes enlarge to contain and control the infection. 

Illustration Credits, Wiseegeek

The same happens when vaccines are given. With Moderna, the incidence of ipsilateral node enlargement is 11% to 16% with a first and second jab, and with Pfizer, it is significantly less. Johnson and Johnson, in its emergency approval document, mentioned none. 

Both Covishield and Covaxin uncommonly initiate lymph node enlargement. Such uncommon outcomes are generally in the range of 1-3%. However, with any vaccine, as more data accumulates, the figures are likely to change. 

Why does it matter? 

Two things are crucial with swollen nodes. First, they are sometimes tender and or painful, with resulting discomfort. Most enlargements are self-limiting and subside on their own. However, occasionally few persist. Of course, it goes without saying that you need to consult your doctor. 

The second and most crucial aspect is the persistence of nodes in a female patient that may need a mammogram. Sometimes these nodes are revealed not clinically but on an accidental CT or MRI. It becomes a cause of concern that needs further workup, but in most cases, nothing significant comes out after investigations. However, it is best to investigate despite knowing the pre-investigation probability. 

Illustration credits: WebMD

Learning lesson: 

  1. Beware of an enlarging lymph node on the side of the vaccine shot. 
  2. Generally, these are self-limiting and will subside eventually.   
  3. If swelling persists or keeps enlarging, it is pragmatic to get investigated.

Commonly used terms in the illustration below

Illustration Credits: Medicine Net Inc.

Shashank Heda, MD

Founder and Chief Executive

CovidRxExchange 

Email: info@covidrxexchange.org

Phone: +1 (650) 996 6745

(A global nonprofit organization for disseminating expertise and insight in the medical care of COVID patients)

Manage COVID After A Recess

While the US, EU, UK, Brazil and South Africa were smoldering with the newer variants of COVID, many in India thought COVID was done and dusted. Life was back to normalcy, hardly realizing that India was in the same stage of ignorance as it was exactly an year ago. COVID is back, and this time it will be with a vengeance. What do we do now? I have discussed the relevant principles so that you can make changes to your lifestyle in accordance with the emerging threat from the newer variants.

A few weeks back, when I talked with several Commissioners and Administrative officers from Maharashtra, Tamil Nadu, and at the Center (Delhi), the palpable feeling was that Covid is “done and dusted”. Life was back to normalcy, and all cautions were out of the window.

A few weeks back, when I talked with several Commissioners and Administrative officers from Maharashtra, Tamil Nadu, and at the Center (Delhi), the palpable feeling was that Covid is “done and dusted”. Life was back to normalcy, and all cautions were out of the window.

I cautioned that it is not yet out, and I shared a blog called a tale of two worlds (link shared below) along with a few reports on the raging pandemic in the US, EU, UK, Brazil, and South America. The ignorance was high, and most felt that they had achieved herd immunity. ICMR reports indicated 24-26% national seroprevalence; Chennai’s reports indicated 40% seroprevalence, which again meant inadequate herd immunity. However, facts are generally relegated, and sentiments take precedence. Once again, I wrote another blog on Herd Immunity (link cited below). Always remember TWO MOST principles of herd immunity –

  1. The entire population should be 60-80%
  2. The epitope (in this case, the viral protein) should be constant, not changing

It is in the nature of this virus that the structure is changing every few weeks. Another blog that was written a long time back on this nature of virus was shared with the medical community. To summarize, the covid virus has a defect with RDRP, an enzyme that helps in multiplication. It creates typos, like the one we unintentionally do while typing. However, with covid, those typos change the structure (changes to S or Spike protein is an example) that renders the immunity from previous infection less effective.

Thus previous infections or vaccines are likely not to provide the anticipated immunity. Besides, this virus’s immunity lasts for 3-6 months, as against the smallpox vaccine, which lasts life long.

So, what do we do next?

  1. Should we stop all our social activities?
  2. Should we stop interacting with our professional friends, coworkers, staff, and others?
  3. Should we quarantine and put ourselves in lockdown?

None of these are practical and pragmatic. Before I tell you what is appropriate, let me share what is inappropriate. Yesterday, I talked with a prominent businessman from Nagpur. He said he uses the alcohol-based hand cleaning solution, cloth-based face masks, and takes a shower after returning home, and puts the laundry clothes.

All except face masks are not required. This is an airborne virus, not a virus spreading through fomites (bugs on your clothes or body via touch).

What is airborne and aerosol? When an infected person sneezes, he/she blows almost over 50 million copies of the virus in one bout of coughing/sneezing. These are invisible and disperse in the air around you. An aerosol is similar to airborne, except that you can see those droplets.

Either way, noninfected people end up inhaling those viruses and ultimately increase their risk of getting infected. There are several factors involved between the sneeze/cough bout and infection by normal people. Closed space versus open space influences the outcome. Similarly, centralized air conditioning circulates the virus via the duct system, thus exposing people in other contiguous areas.

Using n95 or similar masks is THUS CRITICAL. I generally add another layer of the surgical mask when i presume exposures are likely to increase.

Social distancing helps, but it is not a panacea. Just imagine, I am not on the same floor as the infected person but connected via centralized air ducts. Will it help? No. I am logically in the same environment though I am in a different place physically. That also means you have to focus on the principles and not just the practices. Understand the principles and act accordingly.

Lockdown or Quarantine?
The most considerable toll this pandemic has taken is from lockdown. Even during the first lockdown implemented in March/April 2020, I was firmly against global lockdown. The answer is never global lockdown; it is always micro lockdown.

What is Micro Lockdown?
Only lockdown that part of the city or segment where the incidence is likely to be high. However, even micro lockdowns are easier said than done. It is difficult to identify a community of infected (but asymptomatic) people and quarantine them against a traveler arriving outside (by flight, vehicle, or train). Remember, once lockdowns are implemented, they ideally last 3-5 weeks, unlikely to be gone in one week. However, it is best to contain and segregated those suspicious of carrying the virus, be it communities, individuals, or activities.

Curtail all Social Activities
Certain activities are unavoidable, critical business, social activities (marriages, deaths, illnesses, and adverse events). However, remodeling our way of interaction is always possible. Certain principles are absolute and non-compromising (wearing a good quality mask); yet, remodeling can be done for the day’s activity, the place, the interaction, etc.

Let us understand those and tailor our activities.

Dr. Shashank Heda, MD
Founder and Chief Executive
CovidRXExchange
(A US global non-profit initiative for disseminating medical expertise and insight; working for Covid since March 2020)

Links to the blogs below –

If only we proactively spread the message within our network, engage in an active dialog, resolve the misgivings around the vaccine, start Fastrack the process to curtail the virus. Our ability to bounce back, as a nation and as a community, depends upon how we counter the virus. https://mymilieu.org/2021/02/01/evangelizing-vaccination/

The variants with the infectivity, implications on testing, therapy, and vaccines. https://mymilieu.org/2020/12/26/emergent-variants-and-infectivity/

That provides a simple explanation of how vaccination will halt the spread of the virus. https://mymilieu.org/2021/01/28/a-triple-whammy-variant-vaccination-and-complacency/,

It is an ultimate hope that the vaccine provides herd immunity or the virus comes to a state of symbiosis with humanity. Luck is never the best strategy, but it had to happen. We wish to stumble across a variant that is as good as Common Cold, leaves minimal health impacts, and possibly with minimal mutations to stabilize. In the search for this haplotype, I shared this perspective https://mymilieu.org/2021/01/10/in-search-of-a-haplotype/

COVID- A tale of two worlds

A Triple Whammy – Variant, Vaccination, and Complacency

Evangelizing Vaccination

COVID- A tale of two worlds

Breaking the transmission cycle by interrupting these traversals of the virus is critical. Travel restrictions, strict screening and surveillance, and mass vaccination and precautions are all CRITICAL to the successful CONTROL of COVID. Let’s keep our fingers crossed and follow all the right protection.

COVID- A tale of two worlds

(Words – 678; reading time 3-4 minutes, Why should you read? The pandemic is not over and out, do not drop the guards)

While the western world is dealing with one of its worst phases of Covid – 19, the so-called Covid-2, several nations, including India, are almost calling the game is over. Let’s revisit and understand the pandemic’s delicate dynamics and the evolving mutant variants of the virus.

As of late January 2021, hospitals in London and its suburbs were out of any beds for admitting the patients infected with Covid. The modeling predicted one of the worst shutdowns in the history of the great kingdom. Boris Johnson, a nationalist and a populist by inkling (a Trump category leader) too, caved into the worst pandemic. My doctor colleagues from Kent are working almost continuous long hour shifts (18 hours at a stretch). Elsewhere in the UK, the scenario was no different.

Brazil has just surpassed India as the second-worst country after the US to be affected by the virus. Europe, with its defining economies, is jettisoned with the virus. France, Germany, Spain, Italy, and all the Scandinavian countries are on the highest alert, with restricted and severely clamped down inbound and internal traffic, almost reducing the countries to secluded pockets.

Here in the US, of course, statistics are grim, the economy has bounced back a little, but guards are not down, like in India and its peninsula. A quick view of the hospital bed availability for most regions, states, and cities are still red, not to mention LA and its suburbs, which is chronically deprived of beds for almost a few months.

Let us unfold the mysterious virus.

While the simmering stories in the western world are true, it is equally true and a reality that life in India (and the peninsular countries) has bounced back to normalcy.

What can be the reason?
Yes, its is an existential dilemma, that has created a completely divided world with distinct response and behavior to the virus.

Continuous mutation and evolution of the virus
While we know all the mutations such as B 1.1.7, D614G, N501, and its variants, and several subspecies of the evolving new generation-of the virus, what is least understood is that avowed variant that is circulating in those countries where life has bounced back to normalcy. Let’s call this hypothetical mystic variant “Benign Covid-21” (I just coined this word, so no Google search will yield any additional documents). This haplotype, if widely circulating in these populations, maybe an answer to the nature mitigation of the virus. Ultimately, as my friend and a noted prominent vaccine expert Dr. Anand Kawade said, the virus has to live amicably with its hosts. It, too, has to find a symbiotic relationship to survive. This metaphysical aspect cannot be discounted though it needs scientific validation.

Should we drop our guards?
It is too early to say if those in India (and countries with a similar pattern of Benign Covid -21, should drop their guards. One thing is clear, global lockdowns (and lock-jams) are definitely not an answer. At the outset of the pandemic, i had called out the hypothesis if the degree of separation concept, retrospectively, in hindsight, it seems obvious to lean and review that model. Summarily, the degree of separation talks about the interaction amongst the population and not the distance that influences the outcome of the disease dynamics during the covid pandemic. Thus, putting entire cities, regions, and states in mass lockdown is not a pragmatic idea.

Breaking the transmission cycle by interrupting these traversals of the virus is critical. Travel restrictions, strict screening and surveillance, and mass vaccination and precautions are all CRITICAL to the successful CONTROL of COVID. Let’s keep our fingers crossed and follow all the right protection.

Shashank Heda, MD
Dallas, Texas
Founder and Chief Executive,
COVIDRxExchange, a global nonprofit initiative for disseminating the expertise and insight for doctors in the care of COVID)

To Visit our repository of over 1000 best practice documents, please visit – http://www.covidrxexchange.org

To join our global community of over a thousand doctors, please use the below link, https://join.slack.com/t/covidrxexchange/shared_invite/zt-le49a2h0-QUsrvUe_5xsdBwgWvEQxrQ

Evangelizing Vaccination

If only we proactively spread the message within our network, engage in an active dialog, resolve the misgivings around the vaccine, start Fastrack the process to curtail the virus. Our ability to bounce back, as a nation and as a community, depends upon how we counter the virus.

The UK is now reeling under one of the most severe public health crisis, not seen since the start of the current pandemic. Despite adequate care, few variants are loose in the community with a propensity for increased transmission, ability to evade the RT PCR tests, cause severe disease and a potential for decreased vaccine efficacy. The later is still under review, while the available data is indicating that the efficacy is probably not compromised.

On Dec 26, 2020, I shared a link associating the variants with the infectivity, implications on testing, therapy, and vaccines. https://mymilieu.org/2020/12/26/emergent-variants-and-infectivity/ Now, these variants are gradually becoming pervasive. In the UK, the lockdown has become commonplace. LA is Southern California, is no exception.

Credit: New York Times, https://www.nytimes.com/interactive/2021/health/coronavirus-mutations-B117-variant.html

As the mutant variants in fast-moving across communities, they will strengthen by our resistance to vaccinate. I shared another link, https://mymilieu.org/2021/01/28/a-triple-whammy-variant-vaccination-and-complacency/, that provides a simple explanation on how vaccination will halt the spread of the virus. The medical community and other healthcare workers have to put all their might to counter the anti-science (believes) and the rumors generated from conspiracy theories to increase adoption of the virus. However, the responsibility falls on all the elites, not just those from medicine and allied faculty, to spread vaccination.

If only we proactively spread the message within our network, engage in an active dialog, resolve the misgivings around the vaccine, start Fastrack the process to curtail the virus. Our ability to bounce back, as a nation and as a community, depends upon how we counter the virus.

In Search of a Haplotype

The new variant of the virus has already spread out to over 45 countries. While scientists are understanding the impact of the mutant variants, what should we do as individuals and societies to counter the potential threat from the virus?

In this article, I have provided an insight on personal and administrative/social preparation that needs attention.

(Word Count 942, reading time 4 -5 minutes).

By now, we all know the virus is mutating, and mutating every few weeks. For those who are not aware of what a mutation is, it is a change in the genetic program embedded within the virus. However, only a few mutations have possible implications on the infectivity, ability to induce severity, response to the drug, and the response to vaccines. All of these are critical for individuals, families, and society in general. Of course, everything is intertwined and ultimately has an impact on the socioeconomic structure. We have seen the devastation of several families. When the virus went on the rampage, we saw how the economies faltered and GDP’s collapse.

Variants and their implications

We all know that the UK, EU, and the US are badly reeling under the virus. Hospital beds and ICU bed availability in many regions are critically stretched, and so are the human resources like HCW. London Mayor Sadik has already implemented a lockdown with punitive citations for overriding the lockdown. Rightly so, despite our freedom mongering and yearning for personal freedom, we ultimately land up with the hospitals.

At least three variants are known with possible implications on the infectivity, severity of the disease, resistance to drugs, and efficacy of the vaccines. N501, B1.1.1.7, D614G and A222 are mainly prevalent in the UK, South Africa, and the EU. All these variants are known to be more contagious than the wild type, that is universally prevalent. Also, a collaborative study between Duke University, Los Alamos National Laboratory and Sheffield University has revealed that D614G variant is associated with higher viral loads in the upper respiratory tract. As of now, we are not yet sure if there is a variant that exists in LA and other parts of the US that are reeling under the virus. At least 45 countries have so far reported the presence of these new variants as of Jan 10, 2021. The National Laboratories from individual countries are searching for the virus’s existence within their societies and implications if any.

Japanese National Institute of Infectious Disease has similarly identified a new strain after the Japanese Government realized passengers’ arrival with the variant viruses. Naturally, the imposition of a ban on incoming flights from infected countries is the first knee jerk response. Many countries have reimposed the ban on travel from those countries with the presence of this virus. While the respective Governments are working to identify the new virus variants, individuals and the administration should gear up to deal with the increased threat level.

Credits: News Medical Lifesciences, Dr. Liji Thomas, MD. D614G mutation now the dominant variant in the global COVID-19 pandemic
  1. Individually, we all should follow the precautions stringently. Masks, social distancing, and containment strategies such as quarantine are basic. However, never presume that asymptomatic individuals are non-infectious. Research has proven without a doubt that asymptomatics are the ones who are spreading the virus. It goes beyond saying that kids harbor more viruses and remain asymptomatic. Kindergarten and schools can be the potential source of spread. While many schools have opted to go into virtual schooling, it is challenging for the daycare centers to do so. It is best to huddle into your bubble and only interact when it is essential or critical, understanding that those interactions should follow the strictest precautions mentioned above.

Vaccines
Vaccines are derived based on a certain genotype of the virus. If the virus changes its structure, the vaccines may have a potential dent in its efficacy. Second, vaccines, even if they are efficacious, may protect only the ones who are vaccinated. Vaccinated individuals may still harbor the virus. Thus, protection has to continue despite vaccines.

  1. City and Corporation Planning – Many cities, especially in South East Asia, are basking and boasting their success with COVID-19. COVID-19, as well all know, can strike back anytime. Complacency is not alone a defunct but also a counterproductive strategy. Europe and other countries undergoing a severe COVID-19 pandemic spike have realized how the spike overstretches the HCW. Doctors are overburdened, and so are the supporting staff.

Realistic modeling of the unfolding second spike is critical. R Naught, which was widely used at the pandemic initiation, has been revealed to have several flaws. It only threw our economy into shambles and society into unrequired chaos. Newer modeling that is closer to realism is the need of the time.

Second, the infrastructure that was propped up during the pandemic’s initial phase helped but was not necessarily sufficient. We need to identify a more long term viable solution to our healthcare services to deal with the virus. Using the same knee jerk response is unlikely to provide an adequate safeguard. Mere lockdowns are too insufficient and, at best knee jerk; we need more than a rational response, now that we know the pandemic better from our recent experience.

  1. Society – Herd Immunity
    Sweden, the UK, and the US are great examples that serve as potent examples that herd immunity is not enough. It does not offer protection without collateral. The collateral is the death and devastation of an individual with a permanent compromise with residual sequelae on health. Those who survived COVID-19 are physically either compromised in functioning or occasionally rendered dependent on supplemental oxygen.

The only and ultimate panacea would be a natural selection of a haplotype (a genotype) that would be less infective, cause inconsequential disease, and still respond to drugs and vaccines. The emergence of such strains is a natural selection process. The virus will possibly realize that if it has to cohabitate like several other bugs, in a symbiotic relationship with human beings.

Shashank Heda, MD.
Dallas, Texas
(For COVIDRxExchange, a global nonprofit initiative for disseminating insight and expertise in the care of COVID)

https://www.lanl.gov/discover/news-release-archive/2020/July/0702-newer-variant-covid-dominates-infections.php

https://www.news-medical.net/news/20200925/D614G-mutation-now-the-dominant-variant-in-the-global-COVID-19-pandemic.aspx

Rubber Meets the Road.

Let’s start where I want to end this topic, and I know you won’t like me saying this. The pandemic is likely to swagger around more than anticipated. If we anticipated it to end sooner, if not early 2021, it bores disappointment. It’s just not the delay in rolling out the vaccine. Let’s see the multitude of issues why the pandemic is likely to last longer.

Vaccine Nationalism is an integrated world is unlikely to protect a nationality unless the borders are strictly closed. Well, any isolationism and walls are unlikely to stop the Humboldt of global integration. If the rich or the have (those with technology), are planning to cover their nationals, the virus is likely to linger longer in those deprived.

What are the consequences?

Most of us are aware of the new mutations in the virus that imposed an immediate lockdown in the UK. This mutant variant is secondary to the virus gaining survival by mutating and escaping. Such mutants are like to hamper our interventions right from screening to vaccination.

Is it a global vaccine rollout?

Of course nor, the vaccine rollout has started in the EU, UK, US, Brazil, Mexico, Canada, Japan, China, and a select few countries. However, several countries are lagging behind either because they have no funds or no technology or logistics to deploy a complex vaccine delivery program. Add to that the regular protagonist of the ‘conspiracy theory’ school, and you compound the problem to a level of practical reality.

Surprise – Many doctors are evading vaccine

I was surprised to see practicing doctors avoiding vaccines. This is not an isolated but a pervasive phenomenon. There are still lingering doubts about the virus getting integrated into the human genome, which is unlikely to happen. Another misconception is heavy metal contamination of the vaccine. You and I are more exposed to the unknown quantity of heavy metals in our produce from Mexico or the disposable material we are exposed to. First, I may disagree if such contaminations are possible with the vaccines, and even if those were, it is unlikely that you get a significant dose to perturb your system. Another misconception that is going around – that the vaccine is made in cow or pig. I just piety these folks who work on churning the rumors mills devoid of research, reasoning, and rationale.

The cold chain and logistics

It is a formidable challenge to manage the cold chain in a diverse world like ours, even if we presume that vaccination will be adopted uniformly. Having worked as a molecular oncology fellow, I know that especially the RNA vaccines from Moderna and Pfizer need a distinct cold chain, and any disruption is likely to compromise the efficacy of the vaccine significantly. Now consider the vast and remote corners where the vaccines have to be carried out if we were to target complete eradication of the virus.

These are not easily surmountable challenges and devoid of a strategy and execution plan that is customized to individual locales (countries, regions, etc.), it is unlikely to achieve the desired goal of covering 60%-80% population. If the virus lingers, it will mutate and likely stay with humanity for longer than the expected period of time. It will evade our detection gold standard, such as RT PCR. It may create resistance to drugs such as Remdesevir, or worst, become more aggressive and, last, render our vaccines useless. That’s why we vaccinate ourselves annually for flu.

Let us hope for the best.

Hope is not the best strategy; instead, hope is the worst strategy. A thorough understanding of the global target population dynamics vis a vis the vaccination program is required. Strategies alone cannot help; execution of the plan will be the harbinger to success. Until then…

I wish you all a very safe 2021!

Shashank Heda,

Dallas, Texas

The Culpable Trend Continues

Of course, we saw during Covid how China suppressed the Covid investigation, manipulated the data and cleared the crime scene.

Recently, I saw news that China is targeting a GDP of 8 and above fir 2021. It is no news that China is under severe debt, industry is recuperating to gradual recovery, (and of course it will be, because its global customers are still reeling under recession), and it has quadrupled its expenses during a time depleted revenue flow and persistent pressure of aggressive spending on aggressive militarization.

Credits: John H Tuckers, The Riverfront Times

Now comes the real news

It has suspended the regulating agency which rates the progress. And why not? It has to, if it needs to pain all hunky dory, like the old style communist propaganda.

Eventually, we know, with one stroke of Perestroika, the entire communist castle came crumbling down. It’s just a matter of time, such artificial models have no sustenance, they glitter like a nighttime bugs, and lose the flare with the arrival of twilight.

Shashank Heda
Dallas, Texas

Chinese regulator suspends rating agency over Yongcheng default
https://asia.nikkei.com/Business/Markets/China-debt-crunch/Chinese-regulator-suspends-rating-agency-over-Yongcheng-default

Emergent Variants and Infectivity

SARS CoV2 is continuously mutating. However, at least three mutations are known to have an impact on various aspects of the pandemic. N501V1.0, B.1.1.7, and D614G each have an impact on the pandemic. These mutations may impact the diagnostic testing, severity, infectivity, efficacy of the vaccine, modulating the effect of medicines (such as Remdesivir) and finally, recalibrating the policies. Thus, the most appropriate action immediately after understanding the new variant is to evaluate the potential impact on public health. (898 words, reading time 4-5 minutes).

SARS CoV2 is continuously mutating. However, at least three mutations are known to have an impact on various aspects of the pandemic. N501V1.0, B.1.1.7, and D614G each have an impact on the pandemic. These mutations mat impact the diagnostic testing, severity, infectivity, efficacy of the vaccine, modulating the effect of medicines (such as Remdesivir) and finally, recalibrating the policies. Thus, the most appropriate action immediately after understanding the new variant is to evaluate the potential impact on public health.

(Credits: https://www.nature.com/articles/s41467-020-19818-2)

Recently, at least two aggressive variants have been identified, one in the UK N501V1.0 and the other, B1.1.7 in South Africa. Multiple spike protein mutations define these variants. Apart from the nine mutations or 20 mutations on either of the variants. deletion 69-70, deletion 144, N501Y, A570D, D614G, P681H, T716I, S982A, D1118H. It has multiple spike protein mutations (deletion 144, A570D, deletion 69-70, N501Y, D614G, D1118H, P681H, T716I, and S982A).

D614G is increasing in frequency at an alarming rate”. It had rapidly become the dominant SARS-CoV-2 lineage in Europe. It had then taken hold in the United States, Canada, and Australia. D614G represented a “more transmissible form of SARS-CoV-2 (https://www.nature.com/articles/d41586-020-02544-6).

What are the implications for diagnosis, the severity of the disease, policies, infectivity, and efficacy of the vaccine?

  1. Diagnosis: Ideally, at least two epitopes are considered while designing an RT PCR test for SARS CoV2. One of the proteins is on Spike protein. If the mutation affects the exact domain as the epitope, there is a strong possibility of redesigning the primers for RT PCR. Labs should revisit their primer design if those are based on the S-gene.

Does that invalidate the Antigen based or Antibody-based test? Possibly the first one may need to be revisited closely. However, the antibody test may still be valid and relevant.

  1. Severity: Severity of the disease is depends upon intrinsic factors, whereas infectivity is based upon extrinsic factors, predominant amongst those are the avidity and affinity of the virus for the receptor ACE2, and priming of these receptors via TMPRSS also plays a significant role.

However, noteworthy amongst the intrinsic factors are the IFN genes. A down-regulation, Loss of heterozygosity, methylation, or other factors that reduce the expression is one of the major putative factors in the progression of severity.

  1. Policies and Complacency: Just today, I read the news that there are no new cases in Mumbai. Absolutely, hats off. Great achievement, but let’s not forget the empire strikes back. Right now, Mumbai and places like Mumbai have dismantled their Covid hospitals. We need to be prepared earlier or possibly better if the virus strikes back. These mutations come at a (mis) opportune time of vacations, Christmas and New year when the society wants to revile and enjoy with their near and dear ones.

Some communities are basking that Covid has disappeared from their communities. Often, mutations within the virus are likely to be highly deleterious, preventing the invasion of the virus into the host resulting in the purging of the population. Policymakers need to understand that selective mutation in the virus might have conferred a disadvantage to the virus, rendering the virus into oblivion. However, aggressive variants like the one from the Uk or South Africa, may rekindle the reinfection within the community. I will caution; kindly watch out; it’s not over. The enemy strikes best when we let our guards down, a perfect situation for a storm.

  1. Infectivity: R-actor will be affected since the new variant is more infective if not aggressive in severity. The new variant is estimated to increase the reproductive number (R) by 0.4 or greater, along with an estimated increase in the transmissibility by 70%. Those R factor reporters will be back into play. However, remember, the R-factor has less reliability. It’s not a game of statistics. The complexity is compounded by several factors. R factor experts should reinvent themselves.
(Credits: https://www.cell.com/trends/immunology/fulltext/S1471-4906(20)30260-X).
  1. Effect on the Vaccines: it is too early to say if these variants are likely to affect the efficacy of the vaccine. If the mRNA vaccines are designed on the epitopes with putative mutants, it is likely to affect the vaccine’s efficacy. However, it is too early to say that.
  2. Effect on Medications: The D614G variant has a mutation that affects the action of the drug Remdesivir. The new mutants from the UK or South Africa may or may not have any impact on the known mechanism of the existing drugs.

In a nutshell:

SARS CoV2 is known to mutate at least once in two weeks, primarily because of three distinct mechanisms – a. the RDRP enzyme’s intrinsic vulnerability during replication resulting in proof-reading errors, b. host RNA-editing systems, which is considered as a defense mechanism, and c. existence of multiple lineages simultaneously in the same patient (https://www.nature.com/articles/s41467-020-19818-2).

Another possible mechanism for the emergence of a variant is the persistent and prolonged infection, thus offering the virus an opportunity to evade the immune mechanism, called an immune escape. (https://www.ecdc.europa.eu/sites/default/files/documents/SARS-CoV-2-variant-multiple-spike-protein-mutations-United-Kingdom.pdf).

We have to revisit our primer design, severity, policies, and operational procedures, while the studies will unravel the impact on vaccine efficacy. R factor experts should consider renegade, relent, and renovate their R factor formulae and models to guide the policymakers and community.

Shashank Heda, MD
Dallas, Texas

https://www.cell.com/cell-reports-medicine/fulltext/S2666-3791(20)30213-5

https://www.cell.com/immunity/fulltext/S1074-7613(20)30537-9

https://www.cell.com/trends/genetics/fulltext/S0168-9525(20)30334-6

https://www.cell.com/chem/fulltext/S2451-9294(20)30195-9

https://www.cell.com/trends/microbiology/fulltext/S0966-842X(20)30324-3

Kraken, Kaliya and Conspiracies

This is a derivative work, an abstract, an attempt to delve into the minds of those believing in conspiracies, or a a phenomenon, of social isolationism and helplessness, that is universal. This blog runs into 1200 words approximately. I would caution, read when you are at ease. However, it offers an insight on many social phenomenon, little difficult to unravel, but once we understand the underlying dynamics, quite easily revealed.(Reading time 4-5 minutes).

The Kraken Myth and the Safe Harbor

Well, Kraken is a mythical giant octopus, that rose from the bottom of the sea to devour the bad, the malevolent. Let me clarify another term, the Safe Harbor, which talks about conduct that does not violate the rule. Not much of a difference between Kaliya, the serpent demon whom Lord Krishna overpowered in the Yamuna. And what is a safe harbor is a legal provision to reduce or eliminate legal or regulatory liability in certain situations as long as certain conditions are met (Investopedia). 

For many, who are watching with anxiety, the Kraken Conspiracy has added to the folklore of conspiracy theories already pervading the US mythical landscape, the way the Flat Earthers have reigned so far. We all know the several conspiracies around JFK’s assassination. According to Rob Brotherton from Washington Post, over a third of Americans believe that global warming is a hoax, and over half believe that Lee Harvey Oswald did not act alone in the assassination of John F. Kennedy.

It is a famous past time here in the US. Indulging or ruminating the conspiracy theories, that have been recirculated and kept ripe with the grapevine. It’s not just American past time, conspiracies have always evoked interest, possibly because we love some goosebumps. As Rob Brotherton from the Washington Post explains, “But focusing exclusively on unconscious biases and cognitive mistakes overlooks the fact that there is often a kernel of believability at the heart of these theories”.

In rare circumstances, Conspiracy theories can be a bane and pose an existential threat to society. According to Smithsonian, “These new parties, which included the Democrats, the National Republicans, the Anti-Masons, and the Whigs, frequently used conspiracy accusations as a political tool to capture new voters—ultimately bringing about a recession and a collapse of public trust in the democratic process”.

In my view, ‘The Trump Effect’. aka Trumpism is not superfluous, it is deep and taps into the crevices of deep-seated insecurities of a particular set of ethnicities. It is a reflection of isolation, lack of opportunities, of vertical mobility within the society and as a group, of increased isolationism and seclusion. As a group or a part of a clique, people are simply attracted to conspiracy theories when they feel disempowered and helpless, specifically with a frustrating social event.

I believe, to avoid cognitive dissonance, the mind wanders and leans towards cognitive baises, and these biases of causality, which are unsubstantiated and inadequately documented, but supports the internal bias, that requires no evidence, results in subscription to a Conspiracy. Psychodynamically, this avoids greater stress and falling into cognitive dissonance. Anyways, persistent dilemma results in degradation of personality and morale, and this defensive mechanism stops the individual from falling into the vicious trap of dissonance.

Conspiracy theories are universal, across times, cultures, ethnicities, and ideologies often serving irrational delibrations to cater to the rational cravings of the mind. As mentioned earlier, they are enchanting since they evoke goosebumps for many than satisfying the quest of logical reasoning.

Karen Douglas, in her seminal work on ‘The Psychology of Conspiracy Theory’, explains that people like conspiracy theories, when they are anxious, feel powerless, and without control to influence the outcome and a subscription to conspiracies actually disempowers the individual or the group as a whole. What are the immediate implications of these on the outcome?

Impact on the Georgia Run-off

If the Trump or Republican votaries feel disempowered, they are unlikely to vote, because irrespective of their best efforts, they are likely to be robbed by the malevolent force behind the situation. ). It also causes disenchantment with politicians and scientists. the need for people to feel safe and secure in their environment and to exert control over the environment as autonomous individuals and as a clique. People turn to conspiracy theories for compensatory satisfaction when these needs are threatened. For example, people who lack instrumental control may be afforded some compensatory sense of control by conspiracy theories, because they offer them the opportunity to reject official narratives and feel that they possess an alternative account (Goertzel, 1994). Thus, Conspiracy Theories may promise to make people feel safer.

Douglas writes further, that people are clearly attracted to conspiracy theories when their social motivations are frustrated, it is not at all clear that adopting these theories is a fruitful way to fulfill these motivations. A feature of conspiracy theories is their negative, distrustful representation of other people and groups. Thus, it is plausible that they are not only a symptom but also a cause of the feelings of alienation and anomie—a feeling of personal unrest and lack of understanding of the social world—with which they are correlated. Believe in Conspiracies, is generally speculative and contrarian, represent the public as ignorant and at the mercy of unaccountable powers, and impute highly antisocial and cynical motives to other individuals. Studies have shown that people are likely to turn to conspiracy theories when they are anxious (Grzesiak-Feldman, 2013) and feel powerless (Abalakina-Paap, Stephan, Craig, & Gregory, 1999). Other research indicates that conspiracy belief is strongly related to lack of sociopolitical control or lack of psychological empowerment (Bruder et al., 2013). Experiments have shown that compared with baseline conditions, conspiracy belief is heightened when people feel unable to control outcomes and is reduced when their sense of control is affirmed (van Prooijen & Acker, 2015).

COVID-19 as a Myth and a Hoax

Some groups believe COVID-19 is a myth, a hoax. Is it common only in the US? Not at all. I was talking with a friend from central India and when I asked how’s COVID in his city, he said, people are moving around normally. Some even believe that COVID is a myth, a hoax. Why blame America? Well, it is related to all the factors cited above – of cognitively associating the causality of the trigger with an event, of finding inadequate reasoning to substantiate, of deeply inflicted anxiety and helplessness, and finally, a lack of control to fix the situation.

On the contrary, experimental exposure to conspiracy theories appears to immediately suppress people’s sense of autonomy and control (Douglas & Leite, 2017; Jolley & Douglas, 2014a, 2014b). These same studies have also shown that it makes people less inclined to take actions that, in the long run, might boost their autonomy and control. Specifically, they are less inclined to commit to their organizations and to engage in mainstream political processes such as voting and party politics.

History Repeats itself!

The Kraken: What is it and why has Trump’s ex-lawyer released it?
https://www.bbc.co.uk/news/election-us-2020-55090145

The Psychology of Conspiracy Theories
Karen M. Douglas, Robbie M. Sutton, Aleksandra CichockaFirst Published December 7, 2017 Research Article Find in PubMed
https://doi.org/10.1177/0963721417718261

https://onlinelibrary.wiley.com/doi/epdf/10.1111/criq.12578 (worth a read)