Reduced

binding to receptors in the lower respiratory tract, limiting severe disease

Increased

binding to receptors predominantly found in the lower respiratory tract,

enhancing tissue invasion

Increased

binding to receptors predominantly found in the upper respiratory tract,

facilitating efficient person-to-person spread

Acquisition

of multiple basic amino acids in the haemagglutinin cleavage site, increasing

intracellular activation

Activation

of autoreactive B cells alone is sufficient to sustain chronic autoimmune

pathology

Inflammation

lowers activation thresholds and promotes inappropriate activation of self‑reactive immune cells

Universal

loss of regulatory T cells serves as the initiating event in all autoimmune

diseases

Autoimmune diseases are intrinsically restricted to specific organs regardless of inflammatory context

Shared

involvement of autoantibodies implies that therapeutic strategies should be

interchangeable

Broad

immunosuppression is generally more effective than targeting specific immune

pathways

Individual

genetic variation shapes how environmental triggers are translated into

distinct immunopathological outcomes

Autoimmune

diseases inevitably evolve into one another if left untreated

Maintaining

dominance of a single optimal B‑cell clone throughout the immune response

Generating

receptor diversity through mutation, allowing selection of variants with

progressively improved antigen binding

Mandating

differentiation of all activated B cells into long‑lived plasma cells

Ensuring

that only high‑affinity B cells are initially recruited into

immune responses

T-cell

immunity from previous variants was completely ineffective against Omicron

Mutations

in the spike protein allowed infection via ACE2 but eliminated the need for

TMPRSS2

Mutations

in the spike protein allowed more efficient infection of lung cells by

interacting with both ACE2 and TMPRSS2

Pre-existing

immunity from prior infection or vaccination was evaded, allowing the virus to

infect people who were previously protected

SARS-CoV-2’s

spike protein contains a polybasic cleavage site that facilitates more

efficient entry into human cells

Only

SARS-CoV-2 uses ACE1 as its cellular receptor

Only

SARS-CoV-2 uses ACE2 as its cellular receptor

SARS-CoV’s

spike protein contains a polyacidic cleavage site that facilitates less efficient

entry into human cells

The

infection stimulated only antibody‑mediated immunity without cellular responses

The

virus was poorly adapted to infect human cells

An

unusually weak innate immune response that prevented inflammation

Partial

immunity from exposure to antigenically related influenza strains in the past

Their

mild clinical presentation allows undetected community spread

They

currently transmit poorly between humans but could acquire mutations that

enhance upper airway replication

They

already circulate efficiently among humans without causing symptoms

Their

lethality in humans guarantees widespread global outbreaks

Moderate

cases show reduced interferon expression, which protects lung tissue from

damage

Severe

cases show reduced interferon production, limiting early antiviral defence and

allowing extensive viral replication and tissue injury

Downregulation

of interferons is a normal cellular response to all viral infections and is not

linked to pathology

Severe

cases exhibit excessive activation of inflammatory pathways, resulting in

immune-mediated lung damage

HA

molecules assemble into pores that directly transport viral RNA into the

cytoplasm

Individual

HA subunits independently penetrate the membrane to deliver genetic material

HA

remains structurally rigid while host enzymes actively transport the viral

genome into the cell

Change

in pH triggers HA to change shape, exposing fusion machinery that merges viral

and host membranes