Tuesday, March 31, 2020

COVID-19: Was SARS-CoV-2 genetically engineered for biological warfare?

An article published in Nature Medicine noted that it is improbable that SARS-CoV-2 emerged through laboratory manipulation of a related SARS-CoV-like coronavirus. This article disproves most conspiracy theories about the artificial origin of the SARS-CoV-2 virus.

I am going to try to explain what the article says in simplified terms but you need to have some background in biochemistry to understand what it says. Let's begin!

COVID-19: Structure of the novel coronavirus (SARS-CoV-2)

Okay, let's start right away.

Molecular structure of SARS-CoV-2

Acute Liver Failure in a nutshell.

Acute Liver Failure is defined as the acute onset of severe liver injury with encephalopathy and ↓ synthetic function (INR ≥ 1.5 ) in a patient without  cirrhosis or underlying known liver disease.

Acute Liver Failure.

COVID-19: Summary of drugs that are under investigation for use as potential treatment options

SARS -CoV-2 that causes the famous disease, COVID-19, has no FDA approved treatment yet. Researchers around the world are using drugs that have previously demonstrated efficacy against similar virus types clinically or based on their in-vitro activity. Many clinical trials are also underway to demonstrate the most efficacious drug which can be used against this disease. Let's go through them today.

COVID-19: Summary of drugs that are under investigation for use as potential treatment options

Rickettsia mnemonic

Hi!

Do you want to learn about Rickettsia today?

Rickettsia mnemonic (Rickettsia typhi, flea vector)

Monday, March 30, 2020

COVID-19: Convalescent plasma as a treatment option

As the pandemic of COVID-19 continues, researchers have been looking at treatment options, most recently the use of convalescent plasma has generated a great deal of interest.

So let's dive in and understand convalescent plasma therapy and its scope:

Convalescent plasma therapy is based on the theory that a patient in the convalescence phase develops antibodies for that disease in their serum, which can be used to treat other patients, after ensuring that safe blood banking practices are being followed.

Historically, convalescent plasma was used as a prophylactic agent against measles. [1] But with the advent of vaccine development and monoclonal antibodies, the use of convalescent plasma went out of practice. It has also been used for scarlet fever [2] and poliomyelitis [3]. The use of convalescent plasma was recommended as an empirical treatment during outbreaks of the Ebola virus in 2014 [4], and a protocol for the treatment of Middle East respiratory syndrome coronavirus with convalescent plasma was established in 2015 [5].

A case series of 5 critically ill patients with laboratory-confirmed COVID-19 and ARDS was done in Shenzhen, China from January 20, 2020, to March 25, 2020. [6] In this study, 5 patients with severe pneumonia (rapid progression and high viral load requiring mechanical ventilation) received SARS-CoV-2 specific antibody (via convalescent plasma), with a binding titer>1:1000 and neutralization titer>40 along with interferon, lopinavir/ritonavir, and methylprednisolone. On 28th March 2020, the FDA gave approval of IND, i.e. Investigatory new drug application to use of convalescent plasma (after approval) to treat critically ill patients. [7]

COVID-19: Pathophysiology and microbiology


COVID-19: Pathophysiology and microbiology

COVID-19: ACE-inhibitors and SARS-Co-V2

Nowadays, many are aware of the pandemic spreading all around the world and causing victims on a daily basis. This infection which appears for the first time at Wuhan in China represents a great concern. Today, let us explore some questions relating to the disease.

1) ACE-inhibitors and SARS-Co-V2, what is the link existing between them?
The angiotensin-converting-enzyme is secreted by pneumocytes 2 of the lungs and allows the conversion of angiotensin 1 to angiotensin 2, a powerful vasoconstrictor. The receptors for this enzyme are found in various places, including the heart and lungs. Normally, the inhibitor of this enzyme is used in case of high blood pressure, coronary heart disease and also diabetes thanks to its protective effect for the kidneys. However, in the context of COVID19 infection, the virus (SARS-Cov2) uses the converting enzyme receptors to enter the lungs. Given the increase in the number of these receptors in the event of therapy based on ACE inhibitors, the maintenance of this drug in patients infected with SARS-Cov2 is controversial.

COVID-19: Cardiovascular complications

Hi everyone... 

Virus infections are the most common cause of myocarditis. The previous severe acute respiratory syndrome (SARS) beta-coronavirus SARS-CoV-1 was associated with tachyarrhythmias, signs, and symptoms of heart failure.

Let's learn about SARS-CoV-2:
  • COVID-19 patients who died had higher levels of troponin, myoglobin, C-reactive protein, serum ferritin, and IL-6.
  • This is because of the high inflammatory burden in COVID-19.
Let’s find out and understand about CVS complications by COVID-19:
  • Mainly, vascular inflammation, myocarditis, and cardiac arrhythmias
  • The possible late phenomenon of the viral respiratory infection
  • Commonly observed in severe cases
  • Strongly associated with mortality
Cardiovascular complications of COVID-19 



Sunday, March 29, 2020

COVID19 and research: What can I do?

With the COVID19 pandemic hitting us, it is imperative to know where to get our trusted info from. Multiple research papers are emerging these days with one main big goal: Understanding this disease and how to stop it!

In addition to reading and following these research papers, you, yes you, can be a researcher yourself. You can help in fighting this disease and aid humanity.

The studies mentioned below are international studies aiming at understanding COVID19 and its implications:

1- Covidsurg:

Covidsurg is an international cohort study, aiming to assess the outcomes of surgery in patients diagnosed in COVID-19.

It is for patients who undergo surgery with either suspected or confirmed COVID-19 infection (either before or after surgery). Cases can be entered either prospectively or retrospectively.

There is no evidence to inform the management of surgical patients with COVID-19 infection. Capturing real-world data and sharing international experience will support the management of this complex group of patients, improving their clinical care.

To start, register at: http://tiny.cc/covidsurg

==================

2- CovidSurg-Cancer: 

CovidSurg-Cancer is an international cohort study assessing the safety of surgery for all types of cancer during the COVID-19 pandemic and the impact of the pandemic in cancer delay and treatment pathways.

For more info : https://globalsurg.org/cancercovidsurg/

=================

-You can start these studies at your hospital anywhere now! Get the required IRB approval and collect data.

-All publications will be Pub-Med indexed. A corporate authorship model will be used under CovidSurg Collaborative group.


Stay safe

Murad

COVID-19: The journey of a viral pandemic

Modes of transmission of SARS-CoV-2

A novel human coronavirus that emerged in Wuhan, China in the later months of 2019 has now dissipated all around the world, causing a pandemic. Let's analyze how this virus manages to spread so virulently breaching our usual barriers.

Modes of transmission of SARS-CoV-2

Saturday, March 28, 2020

COVID-19: Coping with GRIEF in midst of coronavirus pandemic

The known death toll from the coronavirus has surpassed 25,000 globally. The pandemic has ended communal prayer and congregational funeral gatherings at many major churches, synagogues, mosques, and temples. With these restrictions and isolation measures, dying people can’t see their families at the endpoint of their life. The internet, however, offered some solace to others ( Facebook live streaming, Video calling, etc.) 

Tragic losses of life…Let’s understand grief in the midst of coronavirus.

Normal grief reaction :

Precipitated by the loss of a loved one (bereavement).

Sadness revolves around feelings of loss and typically occurs in "waves" intermixed with positive memories of the deceased.  
Simple hallucinations ( Visual / Auditory ) of the deceased one. 

Thoughts of dying involve wish to join the deceased but active suicidality uncommon 
For most, the natural mourning process lasts 6-12 months 

f/b the integration of grief, in which the individual continues to feel transient but less pronounced sadness, and life plans/routines have adapted to living without the deceased.

There are 5 stages of grief according to the K├╝bler-Ross model are denial, anger, bargaining, depression, and acceptance (may occur in any order).

“Mnemonic” = ABCD 

Wednesday, March 25, 2020

COVID-19: Remdesivir (GS-5734)

Here is a short post about Remdesivir (GS-5734).

Compound:
A '-cyano-substituted adenosine nucleotide analog prodrug.

Mnemonic for TNF-alpha inhibitors



Video by Drashtant

COVID-19: From authors' diary for health care workers

I want to write this post and acknowledge that the pandemic is a very stressful time for healthcare workers. 

We are looking at the epidemiology that shows the increase in mortality related to the COVID-19 disease. Even though we see death everyday, addition of deaths due to SARS-CoV-2 is heartbreaking. Thoughts about not having enough ventilators, not having proven medical therapies, or a vaccine in the near future are distressing. It is in our inherent nature as healthcare professionals to try and help, it's saddening when we can't. 

Hearing the news is also very depressing. Some don't believe it. Some aren't serious enough... Yet. But when you hear the stories instead of looking at the numbers, it becomes real. How strange must it be, to be in quarantine and see your old grandparent go to the hospital alone? How sad must it be to think that it may be the last time that you see them? 

There are concerns about our safety as healthcare workers. We are being exposed on a daily basis and there are concerns about having not enough personal protective equipment such as masks in the future. Even worse, there are concerns about our families safety. We expose them every time we come home. 

I just want to tell you that all your anxieties and concerns are valid. You're not the only one thinking about these things. As we fight this pandemic together, our mental health is important. I'm proud of you for being concerned. I'm proud of you for continuing to fight everyday. 

If you are a health care provider and are distressed by this like I was and want to talk about it, email me at medicowesome@gmail.com. We also have a well being group on Whatsapp to help each other stay strong! 

I was recently talking to a colleague about how we have chosen this profession because this is what we always wanted to do - treat patients. We spoke about the retired physician in Italy who came back to work for his patients. It's noble. It's humbling. If we don't take care of the sick, who will?

-IkaN

COVID-19: Water transmission and the effects of heat on the SARS-CoV-2 virus

Hi!

I am going to be writing a series of COVID-19 posts and answering frequently asked questions by patients. Today's post is about water transmission and the effects of heat on the SARS-CoV-2 virus.

Sunday, March 22, 2020

Recent updates about treatment of COVID19

All things you need to know about COVID19 

Recent Updates: 

At present Best Option = HydroxyCQ +/- Azithromycin 
HydroxyCQ for 10 day ( 200 mg TDS ) 

As ACE 2 enzyme is receptor for SARS-Cov-2 & these RAS inhibitors ⬆️ ACE2 enzyme. So hypothetically, there's an ⬆️ Risk of Covid19. But the guidelines recommend that ACEI / ARBs should not be discontinued. 

Drugs under Clinical Trials:
Remdesivir (USA) 
Ritonavir-Lopinavir 
Tocilizumab (IL6) 
Sarilumab (IL6) 
Favipiravir+ Tocilizumab 
Meplazumab (CD147) 
Fingolimod 
Darunavir + Cobicistat 

Which Rx is used in your country now?  Please comment below ⬇️

Thank you.. 
- Drashtant 


Monday, March 16, 2020

Isatuximab (Novel monoclonal antibody)

Isatuximab (novel monoclonal antibody that binds
selectively to CD38), which is widely expressed on plasma
cells, and kills myeloma cells via multimodal mechanisms
including antibody-dependent cellular cytoxicity,
antibody-dependent cellular phagocytosis, complement-
dependent cellular cytotoxicity, and immune cell
depletion or inhibition of immunosuppressive cells, as has been described with daratumumab.

 Additionally, isatuximab, similar to other CD38 antibodies, modulates
the NADase enzymatic activity of CD38.
However, isatuximab differentiates itself from daratumumab in its
ability to induce direct apoptosis without cross-linking, and in its binding epitope.

Isatuximab is approved in combination with pomalidomide and dexamethasone for adult patients with multiple myeloma who have received at least two prior therapies including lenalidomide and a proteasome inhibitor.

Pretty amazing mechanism, right?


Kirtan

Wednesday, March 11, 2020

How to approach Ankle sprain

Hi!


I sprained my ankle and thought of making a video on it 
-Drashtant

Saturday, March 7, 2020

Layers Of The Abdomen

SUB - Skin
CUTANEOUS- Camper's Fascia
SYSTEM - Scarpa's Fascia
EXITS - External Oblique
INTESTINAL- Internal Oblique
TRANSPORTw/ - Trs Abdominis 
FREE- Fascia Transversalis 
EXIT- Extra Peritoneal C/T 
PASS- Parietal peritoneum 

Everything you need to know about coronavirus COVID-19





Resources: CDC, UpToDate, WHO website.
Video by Drashtant Prajapati, MBBS.

Sunday, March 1, 2020

Acquired coagulopathy


Apart from congenital disorders, various clinical scenarios can give rise to altered hemostatic patterns leading to the state of so called "acquired coagulopathy".

1.) Due to Factor inhibitors:
Classically it is seen in pregnant patients and those with lymphoproliferative disorders like CLL. However it could be idiopathic.
Usually it leads to the acquired factor Vlll and V deficiency.
Mixing studies are employed to differentiate between acquired and congenital factor deficiency. Failure of correction of clotting assays after mixing studies suggests the presence of inhibitors.

2.) Amyloidosis
Sequestration of Factor X by amyloid fibrils leads to acquired deficiency like state. Amyloid vasculopathy along with factor X deficiency often leads to purpura and ecchymosis in these patients.

3.) Myeloproliferative neoplasms
Apart from acquired vWD due to loss of HMW vWF multimers, acquired factor V deficiency can also be seen. This has been attributed to adherence of Factor V to megakaryoblasts similar to the  relation between factor X and amyloid fibrils. However, severe clinical manifestations might not necessarily reflect upon clotting assays or factor levels with latter suggesting functional factor V deficiency.

3.) Thrombotic microangiopathies and DIC
Usually leads to both thrombotic and bleeding manifestations. Spectrum of TMA includes HUS, aHUS, TTP, HELLP syndrome, DIC, cAPLA, scleroderma renal crisis, malignant hypertension and radiation or HSCT induced vasculopathy.

4.) Coagulopathy of liver failure
Classically seen in setting of fulminant liver injury which may be due to the infections, drugs, autoimmune hepatitis, ischemic hepatitis/shock liver or rarely in Wilson's disease due to massive hepatocyte destruction.
One of the hallmark lab findings includes normal factor VIII levels. This is due to the fact that factor VIII, unlike other factors, is chiefly produced by endothelial cells rather than by hepatocytes. In fact, due to it's reduced metabolism by hepatocytes in state of liver failure, factor VIIl levels are often elevated.

Other miscellaneous causes include Acute fatty liver of pregnancy, fat embolism syndrome, amniotic fluid embolism and other pregnancy associated complications.

Kirtan Patolia

Acquired Von willebrand disease

Von willebrand disease is one of the most commonly encountered congenital bleeding disorder in clinical practice. Broadly speaking they are classified as type 1, 2A, 2B, 2M, 2N and 3. Each one of them are distinct from each other in subtle ways.

However, it could be acquired in number of ways.

 a.) In patients with thrombocytosis > 1 million cells/ microliter, especially in essential thrombocythemia, loss of HMW  vWD multimers leads to reduced vWF Ristocetin activity : vWF antigen ratio (<0.6)  suggesting type 2 like pattern.

 b.) In patients with aortic stenosis, due to extreme shear stress, vWF unfolds prematurely at the site of valve revealing ADAMTS13 binding sites, ultimately resulting in it's cleavage and loss of HMW multimers. So basically, it could be visualized as the pattern that is just opposite to TTP where in defective ADAMTS13 activity results in excess of HMW vWF multimers.

It is often associated with either angiodysplasia or AVMs of GI tract that further predisposes to bleeding. Although exact pathogenesis of these lesions is not understood, one postulated mechanism suggests chronic colonic ischemia leading to sympathetic nervous system induced vasodilation as potential culprit.
 In this context it is also known as Heyde's syndrome.

c.) Sometimes in severe hypothyroidism, often the production of vWF by endothelial cells itself is markedly reduced.

d.) Rarely in the setting of multiple myeloma and various other neoplasms, tumor cells express excess of Gpllb/llla leading to enhanced clearance of vWF from circulation.

One of the common lab finding in acquired vWD is reduced vWF Ristocetin activity : vWF antigen ratio pointing to the disproportionate decrease in activity compared to antigen levels.
It is due to the loss of HMW  multimers.

Kirtan Patolia