COVID-19: Coronavirus and hemoglobin

Hello Awesomites!

Please refer to the diagrams for better understanding.

Why do we have abnormal hemoglobin-related biochemical indices in COVID-19 patients?
Reports demonstrate that the hemoglobin and neutrophil counts decrease in most patients with SARS-CoV-2 infection, and values of serum ferritin, erythrocyte sedimentation rate, C-reactive protein, albumin, and lactate dehydrogenase increase significantly.

What makes hemoglobin an attractive molecule for the coronavirus?
Porphyrins!

Porphyrins in the human body are mostly iron porphyrins i.e heme. And a lot of heme is not free, but bound to hemoglobin. Viruses require porphyrins to survive. Therefore, the novel coronavirus targets hemoglobin, attacks heme, and hunts porphyrins.

Structure of SARS-CoV-2

Image by Upasana Yadav

The possible mechanism is that orf1ab bound to the alpha chain and attacks the beta chain, causing conformational changes in the alpha and beta chains; ORF3 attacks the beta chain and exposes heme. ORF10 then quickly attaches to the beta chain and directly impacts the iron atoms on the heme of the beta chain. The heme is dissociated into porphyrin, and orf1ab finally captures porphyrin. Orf1ab plays a vital role throughout the attack. Attack of oxidized hemoglobin by viral proteins leads to less and less hemoglobin that can carry oxygen. The invasion of viral proteins on deoxidized hemoglobin will cause less and less hemoglobin that can carry carbon dioxide.

This study found that ORF8 and surface glycoprotein had a function to combine with porphyrin to form a complex, while orf1ab, ORF10, ORF3a coordinately attack the heme on the 1-beta chain of hemoglobin to dissociate the iron to form the porphyrin. This mechanism of the virus inhibited the normal metabolic pathway of heme, and made people show symptoms of the disease.

What causes the high infectivity of the novel coronavirus?
Medical workers have detected the novel coronavirus from urine, saliva, feces, and blood. The virus can also live in body fluids. In such media, porphyrin is a prevalent substance. At the beginning of life, virus molecules with porphyrins directly move into the original membrane structure by porphyrin permeability. This study showed that the E2 glycoprotein and Envelope protein of the novel coronavirus could bind well to porphyrins. Therefore, the coronavirus may also directly penetrate the human cell membrane through porphyrin. (Means If the virus can bind with porphyrins, it can enter these secretory cells without ACE2 receptors by using the membrane permeability)

What is the importance of knowing the above information?
The drugs based on this mechanism: Chloroquine and Favipiravir.

The primary function of the Envelope protein is to help the virus enter host cells. The primary role of Favipiravir is to prevent the virus from entering host cells and catching free porphyrins. Favipiravir's ability to improve respiratory distress is lower. Favipiravir can only prevent the binding of Envelope protein and porphyrin.

Chloroquine could prevent orf1ab, ORF3a, and ORF10 from attacking the heme to form the porphyrin and inhibit the binding of ORF8 and surface glycoproteins to porphyrins to a certain extent, effectively relieve the symptoms of respiratory distress.

The infectivity of the nCoV pneumonia was not completely prevented by the drugs, because the binding of E2 glycoprotein and porphyrin was not inhibited.

Note for Diabetic patients
Diabetic patients and older people have higher glycated hemoglobin. Glycated hemoglobin was reduced by the attack, which made patients' blood sugar unstable. Since the porphyrin complexes of the virus produced in the human body inhibited the heme anabolic pathway.
Written by Upasana Yadav
(Courtesy:-Thank you Ikan for all the help) 

References:
1. Wenzhong, liu; hualan, Li (2020): COVID-19: Attacks the 1-Beta Chain of Hemoglobin and Captures the Porphyrin to Inhibit Human Heme Metabolism. ChemRxiv. Preprint. https://doi.org/10.26434/chemrxiv.11938173.v5
Link to the article: https://chemrxiv.org/articles/COVID-19_Disease_ORF8_and_Surface_Glycoprotein_Inhibit_Heme_Metabolism_by_Binding_to_Porphyrin/11938173

COVID-19 and Pregnancy: Should Mothers Be Concerned?

Pregnancy is a special phase in a woman’s life, more so because of the various changes which her body undergoes during these 9 months. Perhaps that is why, the concern about the threat of the novel coronavirus is valid- after all pregnancy is a state of slight immunocompromise, and also because there are two lives at stake. WHO declared the COVID-19 outbreak a pandemic on March 11, 2020. Most countries have taken stringent measures to control the spread of this disease, but do pregnant women need to take more measures? So, avid obstetricians out there, let’s find out deeply about the connection between these two:

WHO’s official stand is that there is no higher risk in pregnancy of severe illness BUT because there are trials underway and due to the bodily changes in pregnancy, one can not know the extent of COVID-19 in these patients. [1] Due to the evolving crisis, we are seeing newer studies every day with new results. A study conducted in early February on 38 pregnant women showed that it did not lead to maternal deaths, and neither were there any confirmed cases of intrauterine transmissions, with rt-PCR being negative in all the neonatal specimens tested, hence leading to the belief that there is no intrauterine or transplacental transmission. [2] Even the CT scans done on pregnant women with COVID-19 positive samples, did not show major changes and recovered from pneumonia adequately. [3]

Lysosomal storage diseases mnemonic

COVID-19: Case fatality rate in Italy

Hello everyone, this post explains the factors behind the higher case fatality rate in Italy compared to the other COVID-19 infected countries.

As of today, there are 937,941 coronavirus cases in the world with 47,273 deaths; that comes down to a mortality rate of around 5%. On the other hand, China, the former epicenter of the disease has a COVID-19 case fatality rate of approximately 4%; while Italy has a much higher rate of 11.897%.

COVID-19: Vaccines under development

COVID-19 pandemic has led researchers around the world to work on developing a safe and effective vaccine. At present, there are 5 agents which are being extensively tested as potential vaccines. Here is some information about them.

1. mRNA- 1273 

Trial: Safety and Immunogenicity Study of 2019-nCoV Vaccine (mRNA-1273) for Prophylaxis SARS CoV-2 Infection

   

- novel lipid nanoparticle encapsulated mRNA based vaccine that encodes for spike protein of SARS-CoV-2

- an open-label phase I dose-ranging clinical trial in the United States

- Study Population: 45 healthy people, males and non-pregnant women aged 18-55

    - enrolled in one of three cohorts - 25mcg, 100mcg, 250mcg

    - IM injection of the vaccine on Day 1 and 29 in deltoid

    - Follow up: 1,2,4 weeks post each vaccination, 3,6,12 months post second vaccine

- Objective

    - To evaluate the safety and reactogenicity of a 2-dose vaccination schedule of mRNA-1273, given 28 days apart, across 3 dosages in healthy adults 

    - To evaluate the immunogenicity as measured by Immunoglobulin G (IgG) enzyme-linked immunosorbent assay ELISA to the SARS-CoV-2 S (spike) protein following a 2-dose vaccination schedule of mRNA-1273 at Day 57

2. BCG Vaccine

BCG vaccine — developed for Tuberculosis. It has favorable in vitro or in vivo effect against RSV, Yellow fever, HSV, HPV. The hypothesis is that it may induce partial protection against the susceptibility to and/or severity of SARS-CoV-2 infection

Trial 1: BCG-CORONA reducing health care workers absenteeism in SARS-CoV-2 pandemic through Bacillus Calmette-Guérin vaccination, a randomized controlled trial (BCG-CORONA)

- RCT in the Netherlands 

- Study population: 1000 Health care workers with direct COVID-infected patient      

  contact

- Study duration: 6 months

- Objective: 

    - To reduce absenteeism among HCW with direct patient contacts during the epidemic phase of COVID19

    - To reduce hospital admission, ICU admission or death in HCW with direct patient contacts during the epidemic phase of COVID19

Trial 2: BRACE - BCG Vaccination to Reduce the Impact of COVID-19 in Australian Healthcare Workers Following Coronavirus Exposure (BRACE) Trial

- Open-label two group phase III RCT in Australia

- Study population: 4170 Healthcare workers

- Study duration: 12 months

- Objective:

    - COVID 19 disease incidence over 6 months, by 12 months

    - severe COVID 19 disease incidence over 6 months, by 12 months

3. Synthetic Minigene Vaccine

Artificial antigen-presenting cell Vaccine - a synthetic minigene that has been engineered based on conserved domains of the viral structural proteins and a polyprotein protease. The vaccine will be produced using a vector system to express viral proteins and immune modulators genes to modify artificial antigen-presenting cells (APC) and to activate T cells

Trial 1: Safety and Immunity of COVID-19 aAPC Vaccine

- Open-label phase I study in China

- Study population: 100 participants aged 6months to 80 years

- Objective: 

    - Injection of COVID-19/aAPC vaccine to volunteers to evaluate the safety

- To evaluate the anti- COVID-19 reactivity of the COVID-19/aAPC vaccine

Trial 2: Phase I/II Multicenter Trial of Lentiviral Minigene Vaccine (LV-SMENP) of COVID-19 Coronavirus

- Open-label Phase I/II study in China

-Study population: 100 participants aged 6months to 80 years

- Objective:

    - Injection and infusion of LV-SMENP DC and antigen-specific cytotoxic T cell vaccines to  

healthy volunteers and COVID-19 infected patients to evaluate the safety

- To evaluate the anti- COVID-19 efficacy of the LV-SMENP DC and antigen-specific  

cytotoxic T cell vaccines

4. ChAdOx1 nCoV-19 Vaccine

Trial: A Phase I/II Study to Determine Efficacy, Safety, and Immunogenicity of the Candidate Coronavirus Disease (COVID-19) Vaccine ChAdOx1 nCoV-19 in UK Healthy Adult Volunteers

- Single-blinded, Randomized Phase I/II study in UK

-Study population: 510 participants aged 18 to 55 years

- Objective: 

    - To assess efficacy of the candidate ChAdOx1 nCoV-19 against COVID-19

    - To assess safety of the candidate ChAdOx1 nCoV

5. Recombinant Novel Coronavirus Vaccine (Adenovirus Type 5 Vector)

Trial: A Single-center,Open-label，Dose-escalating Phase I Clinical Trial to Evaluate Recombinant Novel Coronavirus Vaccine (Adenovirus Type 5 Vector) in Healthy Adults Aged 18-60 Years Old

- Open label, dose-escalating Phase I study in China

-Study population: 108 participants aged 18 to 60 years

- Objective:

    - To evaluate the safety, reactogenicity and immunogenicity of Recombinant Novel Coronavirus Vaccine (Adenovirus Type 5 Vector)

Written by Devi Bavishi

Reference: clincialtrials.gov

COVID-19: App based clinical trials

Let’s see how scientists are using app technology to generate data for research on COVID-19.

COVID-19: Lessons from coronavirus outbreak in China and formulating a strategy

Hello awesomites!

The following information is regarding the situation of COVID19 in China and how did China manage to reduce the incidence of new cases.

Image by  Nakeya. Medicowesome 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)

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]