The 9th WACEM-ACAIM Joint Special Global Web Conference on Advance therapeutics in COVID19: Opinions from Experts around the World.

The 9^th in the series of WACEM-ACAIM Joint Group Meeting was packed with presentations of important work being done by the group. Our continued gratitude to all presenters and panelists.

COVID19 ~Multi-System Dysfunction Syndrome also called Multi-System Inflammatory Syndrome in Children & Adolescents

We have in detail discussed that COVID is an Immunological Syndrome like HIV and our thought process was further validated by The World Health Organization.

https://www.who.int/publications-detail/multisystem-inflammatory-syndrome-in-children-and-adolescents-with-covid-19

We further profess that there is a strong possibility that COVID will be a chronic immunological disease which will need immunological and anti-viral intervention in combinations rather than individually.

Personalized COVID Therapy Options will need to be devised as COVID generates a personalized reaction in every patient.

The Term “Multi-System Dysfunction” was a term, which was apt for COVID and the personalized response it generates in humans at different ages.

Immunotherapeutic Anti-Virals

COVID and Flu are going to have a devastating effect on population. The synergistic antigenicity will be highlighted by the heightened immune response both by the direct and indirect pathway. IL6 will play a major role and will emerge as a target for therapy.

Immunotherapy Options will need to be addressed aggressively as we near the Flu Season. A detail discussion was held on the role of plasma therapy as well early cell therapy in acute viral diseases with multi-organ failure and shock.

ECMO in COVID

The role of cardiothoracic surgeons supersedes intensivist in the provision of ECMO in COVID. Discussion as regards induction and phase out criteria for ECMO was done.

Supply Chains BioSecurity

Presentations were done on Biosecurity of Medical and Survival supply chains.

It was deducted that a clear focus was to be laid on creating benchmarks to evaluate the security standards of all medical and survival supplies as a part of healthcare and public health.

POC Biomarkers in COVIFLU

Aggressive use of Point of Care Testing was found to be crucial for COVID patient care. Troponin, BNP, ABG and Bedside Chem 8 and lactates were found to not only decrease time but also fasten effective care. New Emerging biomarkers were discussed in detail including immunological markers.

Oxygen Therapeutics

The Group had a detail discussion on the collective wisdom being applied in developing diagnostic, therapeutic as well as home monitoring benchmarks in Oxygenation Therapy.

Our COVID Publications:

Detailed CORONAVIRUS Primer

https://www.researchgate.net/publication/340903626_The_2019-2020_Novel_Coronavirus_Severe_Acute_Respiratory_Syndrome_Coronavirus_2_Pandemic_A_Joint_American_College_of_Academic_International_Medicine-World_Academic_Council_of_Emergency_Medicine_Multid

Silent Hypoxia Algorithm

https://www.researchgate.net/publication/340984601_Management_algorithm_for_subclinical_hypoxemia_in_COVID-19_patients_Intercepting_the_'silent_killer'?_sg=-gsNoFfF4NuezCiRfVgHaOJOEaJ7WBkCCV5eP-8d6OHYe-YODFqNOAwzPZipYqRHna0RhgOHtG0cQdhb3DCZVbjes7B_78MVbP4IxItz.3xTrpdrliCqjnHYNJAzkxNjZPZn-yoODmPq9XDJiaeT6cH4aKgEFglkUG029s4kW9bJbSWxsbjxmJJ80FRHSFA

Crisis TeleMedicine

https://www.researchgate.net/publication/341068835_The_State_of_the_Globe_The_Trials_and_Tribulations_of_the_COVID-19_Pandemic_Separated_but_Together_Telemedicine_Revolution_Frontline_Struggle_against_'Silent_Hypoxia'_the_Relentless_Search_for_Novel_T?_sg=3diYywikltSRusP5JDzbh9ZTLDMhl2RefdKH15C1DOq7zCSkJKnrAQHPtTK7U1qXNfixzhs1tYjSTsAHx4sDPaBo_rVWFcSed7MIWtFm.dMUCuLnOCD_8J-B2HhFbX05ZyKzOVr7Pn-NVM_C_Nnfx_4SaB_ImWLu-RcxDeDkUdUTdU8RLQhsVe4NItwkqnA

The 8th WACEM-ACAIM Joint Special Global Web Conference on Advance therapeutics in COVID19: Opinions from Experts around the World.

The 8th in the series of WACEM-ACAIM Joint Group Meeting was packed with presentations of important work being done by the group. Focus on Immunotherapy and discussion of upcoming publications was the highlight of the meeting.

Our continued gratitude to all presenters and panelists.

Pediatric COVID

A lot of discussion was done about the cases of Pediatric COVID. Immunological syndrome simulating Kawasaki disease / vasculitis is being seen in children. It was emphasized that different strains of COVID19 are in circulation and every strain reacts differently in every human being. Response to a foreign organism is always “Personalized”. Hence, therapies need to be personalized.

The Term “Multi-System Dysfunction” was a term, which was apt for COVID and the personalized response it generates in humans at different ages.

Immunotherapy in COVIFLU

The group discussed in detail about human body response when COVID pandemic mixes with the annual FLU outbreaks. The immunological pathway found a common ground on generating an IL6 Response. Monitoring IL6 levels and blocking them relative to the existing levels rather than a 100% blockade could be a possibility. This will need to be looked at carefully.

Additionally aggressive treatment of Flu will be important, as neutralizing the virus is key.

Herd Immunity V/S Herd Infectivity

The group discussed the theory of “Herd Infectivity” which is the complete opposite of Herd Immunity. The spread of Herd Immunity is rapid and effective and from the data at hand, it is very clear that COVID has a “Herd Infectivity” pathway.

Density of people, viral volume of exposure, time / length of exposure are all profound factors in the spread of COVID.

Publications

The group will be soon publishing a Primer on COVID19, The Hypoxia Assessment Pathway, Oxygen and Ventilation Algorithm for COVID Respiratory Distress as well as Home Oxygen Monitoring Guidelines.

Transition to “TeleMedicine Culture” from “Crisis TeleMedicine”

The group confirmed the Four Pillars of TeleMedicine Sciences:
1. Recording of Audio Visual Data as Health Record
2. Reimbursements and Accountability
3. Telemedicine Metrics / Analytics / Reforms
4. Patient Safety & Confidentiality

A working group was created to lead the 4 Pillars.

BioEconomics and BioSecure Supply Chains


Tremendous Discussion was done about the New World of BioSecurity in terms of Food Water and Health Supplies. Stockpiles and Delivery to end users will need more security and testing. Cues from the Cold Chain for Vaccines will serve as a starting point to work on BioSecurity. A new era of BioEconomics are been thrust upon us and we have to work on improvising to respond to the same.

The 7th WACEM-ACAIM Joint Special Global Web Conference on Advance therapeutics in COVID19: Opinions from Experts around the World.

The 7th in the series of WACEM-ACAIM Joint Group Meeting was packed with presentations of important work being done by the group. For this meeting, we were graced by the presence of our first speaker, the honorable Secretary of State at the Ministry of Internal Affairs, Romania, Dr. Raed Arafat, who shared an enlightening glimpse into the Romanian model in this COVID era.

Our continued gratitude to all presenters and panellists.

Romanian Model 

There were a lot of enlightening insights about the successes seen from the Romanian working model for the pandemic, as well as a look into the challenges they faced, as a nation, and on the healthcare front. 

Of particular interest, Dr. Arafat shared that they had conducted table-top exercises geared towards a projected response to biothreat issues, just within a year preceding the pandemic. These exercises highlighted theoretical issues which indeed reflect the challenges being faced now. 

Disaster Preparedness in any place, and at every level (institutional/national/international) is of paramount importance. 

This group hopes that we, collectively around the world, do not have a short-term memory regarding this period of time, and hope to see some constructive and lasting changes emerge amidst the other long-term impacts bound to come. 

Among the challenges they faced were an early closure of the export industry, supply of counterfeit equipment, high rate of HCA infections due to poor preparation and/or compliance with protective protocols. 

They tackled with these challenges very early, in fact having meetings quickly after news of infection first emerged from China. Military personnel were deployed to some areas to assist; there was no institution of a full lockdown, but good general compliance of sensible measures installed early into the local incidence of the disease. 

They learned quickly after instituting the model of: COVID-19 hospitals, Support Hospitals, and Clean Hospitals, that a "clean" hospital would not be an achievable concept practically.

They were able to overcome the hurdle of "admission only after testing for COVID", thus eliminating delays in clinical care of patients, and preventing bottle-necking in the ED. 

Their whole approach to the pandemic saw to the fact that they did not face overwhelming of their critical care units, which was and remains a major problem in the worst affected areas around the globe. 

There is, as there is bound to be, some public unrest, however a good overall compliance. This includes the forethought of delaying re-opening of schools till September: which has been well received by authorities, public, and concerned parents.

We, at WACEM-ACAIM, are looking forward to working together with global leaders in finding successful (and unsuccessful) models, applying lessons learnt from them on an international scale towards the betterment of health sectors globally, and improving disaster preparedness responses.

It has never been more apparent, that the wealth of a country relies heavily on its health.

Silent Hypoxia

It has been a recurring feature in this blog, and in our weekly meetings. Our joint group is in the process of developing a Silent Hypoxia Algorithm, that we hope to share soon. 

A stand-out point today, was the importance of recognizing a subtle minimal-exertional or stress-induced hypoxia in otherwise well-appearing, or imaging-negative patients. It should serve to act as a Red Flag and these patients should be considered for admission, and prophylactic LMWH due to increased thrombogenic potential.

Algorithm

To continue to highlight the importance of the above, and integrate it into practice, 'Silent Hypoxia Algorithm' is in development. 

The group is working on developing a ventilation algorithm to simplify and standardize approach to respiratory management of COVID-19 patients, integrating with the silent hypoxia algorithm.

We are also looking into a biotriage tool. 

COVIFLU 

While we continue to look into the pathophysiology and immune mediated response in COVID-19, we are also hypothesising potential co-infection responses. There is no current evidence of an amnestic response, however, studies are still ongoing.

Policy-making 

The health care sector and governmental response sectors go hand in hand in deciding the outcome of any crisis situation, as is evidenced by varying responses by different nations. 

A close working relationship needs to be developed now, and nurtured going forward, in preparedness, acute crisis response, and crisis recovery phases. 

Suggested model of Home based monitoring

In conjunction with telecommunication and community-based models of care, we suggest developing a model so as to reduce burden of hospitalization and also reduce risk of exposure for the patient where these are preventable.

The 6th WACEM-ACAIM Joint Special Global Web Conference on Advance therapeutics in COVID19: Opinions from Experts around the World.

The 6th in the series of WACEM-ACAIM Joint Group meeting was a very productive conversation that included protocol-sharing, current data sharing, development of algorithms and standards, and expanding our thinking to the future of not just COVID-19, but beyond.

We continue to express our gratitude to all presenters and panellists.

Resource Conscious Approach

We need to be wary when generating data or developing guidelines of the resource-rich and resource-limited environments and institutions of healthcare.

As an example, idealistic practice of medicine would involve the monitoring of P/F ratio (PaO2/FiO2) but a resource-limited institution or patient-centric approach may consider monitoring of S/F ratio (SpO2/FiO2) in prognostication of respiratory optimization.

Standardization and Quantification

Because of limited data and gradual evidence emergence in a new disease, there is a common-sense approach and individualistic approach to monitoring and management of COVID-19. However 5 months into wide knowledge of existence of the disease, and 2 months into declaration of a pandemic, the need of the hour is to develop standardized and quantifiable methods of management of the disease. 

We discussed the use of a modification of the CURB-65 criteria as a clinical prognosticator, with concurrent use of the ROX index when considering invasive ventilation. 

We discussed using awake proning as a rescue therapy or indeed a temporizing measure while making an informed and well-thought decision for invasive ventilation. 

We are working on creating a standardised algorithm.

Immunology and Pathogenesis

A key factor in generating therapeutic regimens and working vaccines is to first understand the immunology and pathogenesis of the disease.

There was a thought-provoking discussion which is beyond the scope of this blog, however to elaborate two take-home messages: 

1) Not every presentation is that of a cytokine storm, there is in fact a preceding step of cytokine release syndrome (CRS). 

2) The goal for management would be to develop an IL-6 immune-modulation treatment rather than suppressing IL-6 altogether, as IL-6 is an expected and needed part of the body's normal immune response.

Crisis Telemedicine

This has to be treated differently to non-crisis telemedicine, especially when considering its role in the future of healthcare management. 

Development of a good model should consider the principles of confidentiality, patient safety, reimbursement, and data storage.

Testing

Antibody testing involves IgG or IgM or a combination of both.

The at-home tests/finger-prick tests utilize lateral assays.

These are not diagnostic, rather their main use is in understanding disease burden. 

The presence of antibodies to a disease does not necessitate the development of immunity to ii. 

Vaccine trials rely on studying both the antibody generation response, as well as immunity-conferred. 

Reinfection

It is important to understand, especially in the era where it is easy to share anecdotal medicine, that there is no known data about re-infection, re-activation, or resurgence of this disease. Studies are ongoing. 

Transformational biosafety in healthcare

Wider experiences shared by this global group led to the observation that this pandemic highlighted compromising of parameters and the onus going forward rests on improving these parameters instead. 

There in ongoing work to elaborate on this. 

Coming up next...

Our next meeting will recap on the work currently in development by the WACEM-ACAIM team, more on telemedicine, immunology and COVIFLU - anticipating and preparing for concurrent infection. 

The 5th WACEM-ACAIM Joint Special Global Web Conference on Advance therapeutics in COVID19: Opinions from Experts around the World.

Date: 18^th April 2020

Inter Facility and In-Hospital Patient Transfers:

A detail discussion was held based on the HMC Qatar model about strict protocols for donning and doffing of protective clothing and gadgets when conducting COVID19 Patient Transfers. 

Various Videos are shared:

https://www.youtube.com/watch?v=-JHk9-IT4X0

https://www.youtube.com/watch?v=KwUqoq3VqWs

https://www.youtube.com/watch?v=Q_uZv-XwKdI

Lung Management Algorithms

Currently there are no objective recommendations / criteria about prone ventilation. There are no directives as regards duration, and monitoring and when does one intubate. There is no recommendation about ventilation settings. The WACEM Task force will soon come up with the recommendations, which will be a consensus document.

Telemedicine

One aspect, which stood out, clearly was that there was a stark difference between Crisis Telemedicine and Culture of Telemedicine. 
Patient Confidentiality, Patient Safety, Care Reimbursements and Tele medical records will need to be addressed very technically and systematically as Telemedicine becomes the new norm. 
In Crisis allied tools and platforms are used with very little recording of summaries of communication. If Crisis Telemedicine proceeds to be cultural telemedicine then a lot of thought will have to be put in to the four pillars of confidentiality, safety , records and reimbursements.

Immunology of COVID

Data on Immune Mechanisms of COVID was presented and on  discussion it was hypothesized that COVID Storm was a hyper immune reaction where there was some role played by IL-6. A detail discussion on Immunotherapy will be done in the Next Conference.

Anti COVID Therapeutics:

Currently some drugs are showing hope and so is the vaccine development. The data is enough to suggest compassionate use only. The group could not mention anything about Definitive EBM use of any therapy.

WACEM-ACAIM Survey Research

Leaders of WACEM have undertaken Path breaking Research and present surveys for open participation.

EMERGE Study: 

https://umich.qualtrics.com/jfe/form/SV_6X8DWxqrOiza6G1?Q_DL=d85sCfEE1TIGrwJ_6X8DWxqrOiza6G1_MLRP_bd3T4VM5hhN3Yqh&Q_CHL=gl

University of South Alabama Study 

https://southalabama.az1.qualtrics.com/jfe/form/SV_eIPk3lA4rDZ6ZqB

HCQ Study                                                                                                                                                        https://docs.google.com/forms/d/e/1FAIpQLScCCZNNUbcDH_7-V7d-TV522CwgXV5HNg8Qf5ra_KErAYqMtA/viewform?usp=sf_link

Post COVID Era

If Post COVID becomes the New Norm Process of Medical Care will change. Detail discussion on the above area will be done in the next meeting.

The WACEM-ACAIM Joint 4th Special Global Web Conference on Case Based Lessons from COVID19 patients across the World

Transplant recipients in COVID-19

It is still early for statistical data on the prognosis of transplant recipients with COVID-19, however anecdotally kidney transplant patients are showing poorer outcomes. 

Linked is an open access case study: https://onlinelibrary.wiley.com/doi/full/10.1111/ajt.15874 which also suggests having a lower threshold for suspicion of COVID-19 in kidney transplant patients with non-specific or atypical symptoms.

Differing treatment for immunocompromised individuals?

General global consensus is that the initial algorithm of management in patients with and without immunocompromise remains the same, though data suggests that outcomes are worse in immunocompromised individuals, putting them in a higher risk bracket. There is benefit to be had in conducting early transparent discussions with immunocompromised individuals about available modalities of treatment, and regular review of ceiling of care based on expected outcomes tailored to individual cases.

Telemedicine

As evident from this point being regularly reiterating during these meetings, telemedicine is playing a major role during this pandemic. There was some advocacy for use of telemedicine before the COVID-19 era, however several different models of care have unintentionally found the impetus needed to take off from a hypothetical to practical stage. There are advocates who hope to see telemedicine continue where appropriate to reduce unnecessary risk and/or need for physical clinical visits.

Oncology

There is evolving guidance being generated as in all aspects of medicine during the pandemic. ( eg: https://www.england.nhs.uk/coronavirus/wp-content/uploads/sites/52/2020/03/specialty-guide-acute-treatment-cancer-23-march-2020.pdf ) Oncologists are stopping cancer therapies with the goal to minimize harm where appropriate, or stopping immunocompromising medications. This requires regular review and consideration by oncologists on an individual patient basis. 

Stem Cell Trial

Placental stem cell trial was brought up as another emerging modality of treatment currently in trial phases. Unfortunately I could find limited information about this. 

Link: https://www.webmd.com/lung/news/20200403/fda-oks-1st-stem-cell-human-trial-for-covid-19

Link: https://medicalxpress.com/news/2020-03-stem-cells-combat-covid-pneumonia.html 

Link: https://www.geekwire.com/2020/celularity-infectious-disease-research-institute-win-fdas-ok-try-covid-19-cell-therapy/

However expect more articles to emerge.

Transfer procedures

The presence of both symptomatic and asymptomatic COVID-19 cases generates the important question of safe transfers. Transfer guidance differs in various institutions, and perhaps has some inter-institution variability, but developing set criteria during this period is critical to maintain in-hospital and inter-hospital safety of both patients and providers. 

Some hospitals are conducting "box-transfers" and in other cases, have protective plastic covers. PPE guidance for transferring team varies by institution and case. There must be due consideration for the safety of, and clear communication to the team receiving the transfer/referral.

Link: NHS England's guidance document on transfers: https://www.england.nhs.uk/coronavirus/wp-content/uploads/sites/52/2020/04/C0199-Specialty-guide_specialist-rehabilitation-v1-03-April_.pdf

Test Value

Though there is value to positive tests, there are several reports of delayed positive testing. Thus a negative test in a symptomatic patient carries little value and onus of decision making must rest upon the clinical picture. 

Bottom-line is: guided testing is carried out for symptomatic individuals (whether mild or otherwise), therefore regardless of the test results, the individual must follow self-isolation advice.

Another point of discussion, was the purchase and use of commercial testing by private companies outside the remit of hospital based or clinician based management. Commercial tests lack standardisation both in the kind of tests available as well as their legitimacy and accountability.

Pooled PCR

Theoretically, this is the collection of multiple samples, pooled together for PCR testing. If none of the samples contain the virus, then the result of the test is negative. If the result is positive, then further testing on an individual level can be conducted. This is of particular benefit in resource-limited and/or population dense areas. 

Link: https://www.cerberus.co.nz/covid-19-pooled-pcr-testing

Medical Ethics during the pandemic

Every hospital/clinical establishment should have an ethic and medicolegal team to provide guidance and support at all times, but especially during a pandemic. In the context of COVID-19, ethics come into play on both an individual patient basis, as well as institutional basis. If there aren't already, then there will be high stakes decisions in emotionally charged situations that can impact provider and patients, and these must not be dismissed. 

Upcoming: 

Discussions involving anticoagulation in COVID-19, ACAIM/WACEM multidisciplinary working group statement, and more.

The WACEM-ACAIM Joint 3rd Special Global Web Conference on Case Based Lessons from COVID19 patients across the World

4th April 2020

Telemedicine

Telemedicine for home monitoring of discharged patients and other complaints is in full use as numbers in Italy start to trend south.

Hypoxia

Point of Care Pulse Ox assessment at triage should identify silent Hypoxia Assessment via rest and stress check after one-minute walk.

Order Labs and X-ray Chest.

An inconclusive chest X-ray should prompt plain CT of the chest. If the CT is positive then the patient is admitted.

Negative CT Chest should prompt an evaluation to rule out COVID Myocarditis / PE as COVID has shown to have cardiac effects and thrombotic tendencies.

CTA is done when there is a high suspicion for PE. Additional POCUS Cardiac exam is done. D-Dimer routinely is high in COVID patients.

The PE algorithm should be followed keeping in mind that AKI and dehydration can be present.

Kidney Dysfunction

GFR and trending the creatinine in last 7 weeks is good enough to evaluate the kidney status in addition to creatinine.

Myocarditis

High Sensitivity Troponin is an efficient marker to r/o myocarditis.

Non-COVID Pathologies:

The emphasis was that other pathologies do exist and we have to keep that in mind as we evaluate COVID patients and vice versa.

Hematological / Metabolic Markers

Neutropenia, Lymphopenia, Hypokalemia and High Fibrinogen levels have been found in COVID19 patients.

LMWH

Routine dosing that the experts recommended for patients admitted.

Extra-Pulmonary manifestations of COVID19

AMS / Seizures / Delirium / Encephalopathy / Myocarditis / N / V/ D / Rhabdomyolysis / AKI / Thrombosis / Embolism were the major manifestations mentioned by experts.