Influenza & COVID-19 Details

The 1918 influenza pandemic was unusual in that

It was much deadlier and killed healthy young adults in their prime more than children or elderly

Alphainfluenza virus

From the family Orthomyxoviridae

Baltimore Type V enveloped virus

8-segmented DNA

Pleomorphic (round, elongated, or filamentous)

Transmembrane proteins in Influenza A

Hemagglutinin (HA) and Neuraminidase (NA)

Hemagglutinin (HA)

allows the virus to attach to its host cell

Neuraminidase (NA)

Helps the virus escape the host cell after successful replication by cutting off sialic acid residues

Influenza A attaches to

sialic acid residues

Humans and bird sialic acid residue

are differently linked — thus whether alphainfluenza virus infects humans or birds more depends on HA’s preferred linkage

Influenza Sx

Sudden onset of fever, rhinitis, cough, headache, malaise, and prostration lasting 7-10 days

Tissue Tropism

When influenza A infects the epithelial cells lining the respiratory tract

Alphainfluenza virus that replicated high in the respiratory tract are

more transmissible

Alphainfluenza virus replicating low in the respiratory tract cause

more serious disease

The 1918 influenza virus HA

Considered associated with the deadliness in the virus — replacing it caused new strains to be less deadly, but putting it in reference strains had no additional effect

1918 influenza virus Sx

Massive lung damage and severe pneumonia

1918 influenza virus Viral polymerase (PB1)

May play a role in the pathogenicity as it allows the replicate 50x more than reference strains

Alphainfluenza evasion of immune system

Antigenic drift and antigenic shift

Influenza A is spread via

aerosol route — virus laden droplets allow infection from 6ft away

Influenza A can be transmitted (timeline)

1 day before Sx and 5-7 days after Sx

Influenza infection control

Contact avoidance, masking, hand sanitizing, and vaccination

Vaccine strategies for influenza A

Inactive (IIV), recombinant (RIV), and live, attenuated (LAIV)

Inactive influenza vaccine (IIV)

Can be grown in hen eggs or cultured cells. Virus is inactivated and injected into arm

Recombinant influenza vaccine (RIV)

Molecular biology techniques are used to express HA proteins for antibody production

Live, attenuated influenza vaccines (LAIV)

Utilizes the low pathogenic strains which replicate efficiently at cold temperatures. Administered via nasal spray

Influenza viruses are often

quadrivalent — protect against 4 possible strains

Antiviral agents against influenza A

Tamiflu, Relenza, Rapivab, Xofluza

Influenza A antiviral agents that act as neuraminidase inhibitors

Tamiflu (Oseltamivir), Relenza (Zanamivir), and Rapivab (Peramivir)

Xofluza (Baloxavir marboxil)

Acts as an inhibitor of viral polymerase activity to block replication of influenza A

COVID-19 is caused by

SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2)

Coronaviruses

Baltimore Type IV enveloped viruses with the largest ssRNA genome.

Club-shaped projections (spikes) constitute viral attachment protein.

Among common cold viruses

Coronavirus structural proteins

E protein, S protein, M protein, and N protein

E (envelope) protein

Integral membrane protein plays role in viral budding assembly and possibly has a role as an ion channel

S (spike) protein

Viral attachment protein allowing binding to cell and fusion with plasma membrane of target cell

M (membrane) protein

prevents Type I interferon production by interfering with RIG-1-MDA-5 recognition system

N (nucleocapsid) protein

RNA binding protein, protects and packages genome, and may help regulate transcription and replication

Coronavirus cellular receptor

ACE2

Attachment of S protein to ACE2 is facilitated by

a membrane associated protease, TMPRSS2

ACE2 is expressed on

vascular endothelial cells, epithelial cells of oral and nasal mucosa, alveoli cells in lungs, and cells lining stomach and small intestine

ACE2 Fx

regulates renin-angiotensin-aldosterone pathway, controlling BP and is involved in inflammation

Use of ACE2 by SARS-CoV-2 causes

Lung damage d/t build up of angiotensin II and the inflammation it causes

SARS-CoV-2 is more infectious because

S protein has a much higher affinity for ACE2

Severe SARS-CoV-2 infection can cause

pulmonary emboli obstructing main pulmonary arteries, diffuse alveolar damage, abnormal coagulation values, and blood clots in organs and elevated levels of pro-inflammatory cytokines

Remdesivir

Drug used for COVID-19 infection that acts as a small molecular inhibitor of viral RNA polymerase

Dexamethasone

Drug used for COVID-19 infection.

Anti-inflammatory steroid which limits immune over-reaction to virus

Tocilizumab

Drug used for COVID-19 infection.

Monoclonal antibody that neutralizes IL-6

Johnson and Johnson “hybrid” vaccine

Genetically engineered a crippled adenovirus 26 vector that enters a cell to produce the S protein found in SARS-CoV-2 to provoke protective neutralizing antibodies

Moderna and Pfizer RNA-based vaccine approach

Synthetic mRNA is encased in a cationic lipid carrier which is injected intramuscularly and taken across cell membranes where mRNA is translated into an S protein fragment

Long Haul Syndrome

Cases where Sx stay after infection with SARS-CoV-12 subsides

Possibly d/t initial damage being slow to recover or irreparable, low levels of virus still present, or immune system response misdirected to normal tissues

R₀ (Basic reproduction number)

Expression of the contagiousness of an infectious agent

R₀ = 1

Disease will persist in a population infecting at a steady rate

R₀ = 0

Disease will peter out of the population

R₀ > 1

Disease will increase and likely lead to an epidemic

R₀ assumptions

No one has been vaccinated

No one has immunity or is already infected

There are no procedures in place to stop disease from spreading

CoV-2 Delta strain

More infectious and deadly d/t producing a greater viral load allowing easier transmission and more viruses lead to more tissue destruction.

Mutation in P681R in S protein allows direct transmission of virus from an infected cell to an uninfected cell.