Transmission 3: Repeated infections (e.g. COVID- 19)

Question 1

COVID-19 dynamics (initial confusion)

Answer 1

Alpha -> Beta -> Gamma -> Delta -> Omicron

Individual are infected and can gain immunity to disease but not infectious allowing secondary infection.

COVID-19 initally thought to follow SIR model with herd immunity
- COVID-19 arrived in Manuas, Brazilian Amazon in March and by october there was herd immunity.
- In Novemeber there was a second wave and population very unprepared.

In December further spikes throughout the world.

What lead to these spikes:
* Lose immunity to infection (or v high antibody levels don’t prevent infection)
* New variant arose
-> Evades immunity to previous infection
-> Has higher inherent transmissibility

Question 2

Hypothesis 1: waning immunity

Answer 2

Immunity to Covid-19 is lost

Example: There is now extensive evidence that COVID-19 vaccine-induced antibody titers decline over time. Also found waning of SARS-CoV-2 T-memory-cell populations with a half-life of 3-5 month.

Question 3

Hypothesis 2: Increased transmissibilty

Answer 3

Comparing tranmissibilty of the strains is challenging as the later strains are spreading in a partially immune population so it is not a fair comparison.

Can use multiple strain SIR modelling to compare the transmisibilty of strains and see which strains wins:
- Strain with higher R0 will competitvely exclude the other strain when there is complete cross immunity (gamma= 1)
- Competitive exclusion due to increased transmisbility occured with COVID-19

Example:
- Change in Position 614 changed aspartic acid to glycine leading to a more open spike protein that can attatch to cells more firmly. -> higher R0 and higher transmission

Question 4

Other examples of strain competitive exclusion

Answer 4

Eg. Syphilis (sexually transmitted) replaced other directly transmitted spirochete diseases eg. yaws and bejel (causing skin conditions) when moved to cities with sex-workers as it had a higher R0 therefore more tranmissible.

Eg. tuberculosis reduced leprosy levels as both caused by mycobacteria but TB was more transmissible

Question 5

The relationship between transmissibilty and virulence

Answer 5

Trade-off in virulence & transmission

Virulence can increase transmission rate if pathogens are more virulent due to greater viral load (more viral particles)

Virulence can decrease duration of infection if increased virulence leads to death.

R0 is maxmised at Intermediate virulence with intermediate duration of infection and transmission

Example: . Myxoma virus
- Released in 1950 to control rabbit populations
- Strain selected with intermediate virulance to maximise tranmission.
- Intermediate virulence prevents death, but permits virus to form sores + tumours on faces – sores needed to allow direct transmission

Question 6

Hypothesis 3: increased virulence

Answer 6

It is hard to determine what happened to the virulence characteristics of COVID- 19 as immunity to infection is short-lived but immunity to disease is durable.

Example:
- Omicron may appear less virulent
- First virus to infect Hong Kong and showed same virulence as other variants.

Question 7

Hypothesis 4: evasion of natural immunity/ immunity from previous infection

Answer 7

Variants made by changes to receptor binding site (where spike attaches to cell receptor) -> can escape immunity

New variant have no / reduced neutralisation by antibodies / vaccine specific to different strain
Eg. delta variant has reduced sensitivity to neutralising antibodies if vaccinate using original strain

BUT, protection against death + disease not necessarily mediated by neutralisation, so vaccines to protect against disease + death can remain effective

Question 8

When are vaccines effective and when is there co-existance between strains?

Answer 8

Dominant targets of immunity (epitopes) = conserved
- effective vaccines (herd immunity) + disease eradication
- COMPETITIVE EXLUSION

Dominant targets of immunity = variable
- Unsuccessful vaccines + no disease eradication (eg. smallpox and most strains of polio eradicated, or measles = not eradicated)
- NO competitive exclusion + get COEXISTENCE (Influenza, malaria, Pneumococcus, HIV)

Question 9

Summary

Answer 9

There have been multiple waves of COVID-19 due to:
- Waning immunity
- New strains
- > Increased virulence
- > Increased tranmissibility
- > Evade immunity to previous infection

Important to understand the dynamics of multi-strain pathogens and how they can be modelled:
- No cross immunity (variable epitopes -> ineffective vacination -> co-existance)
- Intermediate cross immunity (sequential replacement)
- High cross immunity (conserved epitopes -> effective vaccination -> competitive exclusion)