31 Aug

Diseases

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Content

• Viral Diseaes vs Bacterial Diseases
• COVID-19

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1) VIRAL DISEAES VS BACTERIAL DISEASES

• Why can’t we cure virus infection
  • Bacteria are living cells. They have outer antigens which can be targeted by human immune system and form the basis of vaccines. The cells of a bacteria contain unique (to bacteria) structures which can be disrupted by bactericidal antibiotics without affecting human cells too much; these provide broad targets for therapy. The majority of bacteria find a place to grow inside a human/further invade tissues, but don’t actually enter and live within a human cell. This gives them greater exposure to antibiotics and easier exposure to immune system.
  • Bacteria are virulent by two mechanisms
    • Toxin production
    • Invasion/inflammation
    • Exotoxins in particular are often treated with formaldehyde, acid, or heat in order to convert them into toxoids, which means they are still antigenic but have lost their toxicity.This provides another critical target for vaccine sand treatments of bacteria that doesn’t exist in (most) viruses. Component of bacterial vaccines include these inactivated toxoids, the outer capsular antigens of bacteria without the bacteria inside or other purified bacterial proteins, killed bacteria, or live (attenuated) bacteria.
    • Furthermore, antitoxins (pre-formed immune globulins which will target the bacterial antigens) are available to counteract the toxins of such bacteria as tetanus, diptheria etc.
  • Bacteria can also be targeted by several branches of immune system at its own.
• Viruses on the other hand are not cellular. We can’t kill them simply by disrupting their cells. They are infective nucleic acid that cannot replicate outside living cells.
• Some viruses replicate inside human cells and then bud off from the human cell inside an “envelope” made from the human cell’s membrane, which helps them evade the immune system on their way to infecting another human cell.
• Many viruses are protected by protein capsids, which are extremely protective — unlike a bacterial cell wall or membrane, the virus doesn’t have to be alive inside the capsid or exchange nutrients and waste with environment across the capsid; the capsid is merely there to protect the nucleic acid of the virus.
• Each virus uses a different receptor
  • Viruses need to match some sort of receptor in order to gain entry into human cells, and in some viruses, this receptor is one of the few good targets for drug therapy; however, unlike antibacterial, the drug will only work for that particular virus/receptor, because each virus uses a different receptor

2) COVID-19

1) CORONA VIRUSES

• Coronaviruses are a group of viruses in the subfamily Orthocoronavirinae, in the family Coronaviridae. In humans they are known to cause infection in upper respiratory tract (sinuses, nose and throat) and/or lower respiratory tract (windpipe and lungs).
  • Most of these viruses are harmless, but some can cause less severe common cold to more severe diseases such as severe acute respiratory syndrome (SARS), Middle East Respiratory Syndrome (MERS) and COVID-19.
• Coronaviruses were first identified in the 1960s. Almost everyone gets a coronavirus infection at least once in their life, most likely as a young child. The symptoms of most coronavirus are similar – a runny nose, coughing, sore throat and sometimes a fever.
• Many Coronaviruses are zoonotic i.e., they are transmitted from animals to humans.
  • SARS coronavirus is believed to be an animal virus from an as-yet-uncertain animal reservoir, perhaps bats, that spread to other animals (civet cats) and first infected humans in the Guangdong province of Southern China in 2002.
  • The MERS coronavirus was passed on from dromedary camels to humans in Saudi-Arabia in 2012.
  • SARS-COV-2 also seems to have transmitted from bats to humans (not confirmed yet). Pangolin may have acted as intermediary.
    • Note: SARS-COV-2 is a coronavirus very similar to the one that causes SARS.
• Structure

• • They are enveloped viruses with a positive sense single stranded RNA genome and a nucleocapsid of helical symmetry.
  • The genome size of the coronaviruses ranges from approximately 26 to 32 kilo bases, one of the largest among RNA viruses

2) SARS-COV-2: NAMING, STRUCTURE AND PHYSIOLOGY

• SARS-COV-2 is one of the seven known types of known Corona virus, including SARS and MERS.
  • Naming of the Virus: The Coronavirus Study Group of the International Committee on Taxonomy of Viruses, which had assessed the novelty of the human pathogen, has named the virus as “Severe Acute Respiratory Syndrome Coronavirus 2“, or “SARS-COV-2“.

3) STRUCTURE OF THE VIRUS

• Like other Coronaviruses, SARS-COV-2 virus particles are spherical in shape and have mushroom shaped protein called spikes protruding from their surface. These spikes give the virus appearance of a crown or halo around sun. Therefore, it is called CORONA which is the Latin name for crown.
  • The spike binds and fuses with human cells, allowing the virus to gain entry.
  • The spike protein of the novel coronavirus shares 98% sequence identity with the spike protein of the bat coronavirus.
  • The spike of the virus has something called a receptor binding domain (RBD) which facilitates the virus entry into the target cells by binding with the cellular receptor called Angiotensin Converting Enzyme 2 (ACE2), which serves as the entry point into human cells. SARS corona virus also used the same mechanism for entry into the cells.

• • But unlike SARS the case of SARS Corona, the spike protein of the novel coronavirus binds to the cell receptor with much higher affinity – 10 to 20-fold higher.
  • This much higher binding affinity to the cell receptor explains high human to human transmission of the virus compared to SARS coronavirus.
• The virus (or virus particle) is 50-200 nm in diameter.

4) NAMING OF THE DISEASE – CORONA VIRUS DISEASE-19 (COVID-19)

• On Feb 11, 2020, the WHO officially announced COVID-19 as the name for the disease caused by the n-COV (novel Coronavirus)
  • The name has a standard format to be used in any future corona virus disease.
• Why was it important to name the disease?
  • To prevent the use of other names that can be “inaccurate or stigmatizing”.
• Based on WHO’s May 2015 guidelines.

5) COVID-19 DISEASE CAUSED BY INFECTION OF SARS-COV-2 (2019 N-COV)

• Early symptoms include – Fever, Dry Cough and Fatigue.
• The virus can lead to pneumonia, respiratory failure, septic shock, and death.
• How does SARS-CoV-2 spread?
  • It mainly spreads from person to person.
    • When a sick person coughs or sneezes, droplets containing virus are released in air, on various surfaces. If you inhale or swallow this virus, the virus gets into your body.
• Vertical Transmission across Placenta
  • A study has found evidence that confirms vertical transmission of SARS-CoV-2 virus from the mother to foetus. The route of infection is through the womb (in utero) well before onset of labor and delivery of baby.
• What is community transmission?
• Reproduction Number (Ro) (pronounced R naught) is used to describe the intensity of an infectious disease outbreak.
  • Early studies of COVID-19 in Wuhan estimated the average R0 between 2.2 and 2.7.

6) DIAGNOSIS

• Antibody test
• RTPCR

7) CYTOKINE STORMS AND ITS IMPACT ON COVID-19 DEATHS

• Basics: Understanding how immune system functions:
  • An effective immune system response involves inflammation, an important and indispensable part of the process. This is visible when, for example, you hurt your knee or ankle — the area of this external injury becomes red and swollen, and the immune system in response deploys white blood cells to the injured area to begin work on repairs. Without such an immune response, injuries would not heal, and infections would become deadly.
  • Inflammation has an important protective function. The release of inflammatory mediators increases the blood flow to the area, which allows larger numbers of immune system cells to be carried to the injured tissue, thereby aiding the repairing process.
• What are Cytokines and what is their role in immune system?
  • Cytokines are small proteins released by many different cells in the body, including those of the immune system where they coordinate the body’s response against infection and trigger inflammation.
  • Cytokines are signalling proteins that are released by cells at local high concentration.
• However, sometimes the body’s response to infection can go to overdrive: Cytokine Storm Syndrome
  • In some patients excessive or uncontrolled levels of cytokines are released which then activate more immune cells, resulting into hyper inflammation. Here body’s immune system starts attacking its own cells and tissues rather than just fighting off the virus. This can seriously harm or even kill the patient.
  • Cytokine storms are a common complication in COVID-19, MERS, SARS, and flus. They are also associated with non-infectious diseases such as multiple sclerosis and pancreatitis.
    • For instance, the high fatality rate of 2005 H5N1 influenza, also known as Bird Flu, was linked to an out of control cytokine response.
  • Cytokine storm can explain why some people have severe reaction to coronavirus while others only experience mild symptoms. They could also be the reason why younger people are less affected, as their immune systems are less developed and so produce lower levels of inflammation driving cytokines.

8) MUCORMYCOSIS OR BLACK FUNGUS

• Details
  • The disease is caused by a group of molds known as mucoromycetes present naturally in the environment.
    • It mainly effects people who are on medication for health problems that reduce their ability to fight environmental pathogens. It generally doesn’t pose a serious threat to individuals with healthy immune system.
  • Sinuses or lungs of the infected person get affected after they inhale fungal spores from the air.
  • Symptoms:
    • Warning signs include pain and redness around the eyes or nose, with fever, headache, coughing, shortness of breath, bloody vomits, and altered mental status.
• Treatment:
  • It is treated with antifungal but in worse case it may require surgery.
    • The treatment includes infusion of normal saline (IV) before infusion of amphotericin B and antifungal therapy, for at least 4-6 weeks.
    • It is of utmost importance to control diabetes, reduce steroid use and discontinue immunomodulating drugs.
• Management of COVID-19 patients with Mucormycosis is a team effort involving microbiologists, internal medicine specialists, intensivist neurologist, ENT specialists, ophthalmologists, dentists, surgeons and others.
• Life after Mucormycosis:
  • It can lead to loss of upper jaw and sometimes even the eye.
    • Once the patient stabilizes, prosthetic replacement of the missing facial structures can commence.

9) VARIANTS OF CONCERN

 

A) DETAILS OF DELTA VARIANT

• • The original Wuhan variant mutated into the successively more dangerous Alpha, Beta, Gamma and Delta Variants.
  • Note: All mutations don’t mean that they are more harmful.
  • Variant of Concern: WHO classifies a variant as Variant of Concern when it is associated with an increase in transmissibility or detrimental change in COVID-19 epidemiology; increase in virulence; or decrease in effectiveness of the public health measure or available diagnostics, vaccines, therapeutics.
  • So far, WHO has 5 variants of concerns (Omicron was the fifth one)
• The Delta variant, or the B.1.617.2 lineage was first discovered in Maharashtra, India, in Oct 2020.
  • It has mutation in its spike protein, which helps it bind to the ACE2 receptors present on the surface of the cells more firmly, making it more transmissible and capable of evading the body’s immunity.
• Key characteristics of Delta Variants:
  • Delta variant spreads faster and reduces protection gained from previous infections or vaccines
  • Doesn’t cause more severe illness
  • Vaccines are effective (a bit less) on delta variants. It’s just that delta variant is less sensitive to neutralizing antibodies.
• Why Delta variant spreads faster?
  • Evolution (Class discussion)

 

B) DETAILS OF OMICRON VARIANT (VARIANT 1.1.529)

• • Omicron is WHO’s fifth variant of concern.
  • It was first reported to WHO on 24th Nov 2021 and was classified as a variant of concern by WHO on 26th Nov 2021.
  • It spreads much easily than original virus and the Delta variant.
  • It generally causes less severe disease than infection with prior variants.
  • Symptoms: Similar to previous COVID-19 symptoms.

 

C) RECENT MUTATIONS IN NEWS:

FLip: The omicron subvariant JN.1. is likely to soon become the dominant lineage of the SARS-CoV-2 virus worldwide, according to researchers at the University of Tokyo. The subvariant has a mutation in its spike protein, L455S, also called a “FLip” mutation.