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Rajeev Chitguppi MDS Profile picture
@chitguppi
Dec 24, 2021 • 39 tweets • 27 min read • Read on X
The story of Omicron so far - virulence, severity, and hospitalisations across the globe.

🧵of tweets from reliable sources
1/ Who is more vulnerable to Omicron infection? @EricTopol

@EricTopol 2/ The lower severity of Omicron cases - Reasons? @RajeevJayadevan

@EricTopol @RajeevJayadevan 3/ Omicron less severe illness #COVID19 - data from South Africa
@EricTopol

@EricTopol @RajeevJayadevan 4/ Two factors: Infection-everted and Re-infections, which may explain why Omicron appears less severe. @nataliexdean

5/ Is Omicron intrinsically less severe? @jburnmurdoch

6/ Cases are rising steeply in London. But what about hospitalisations? @jburnmurdoch

@jburnmurdoch 7/ Share of Omicron cases requiring hospital is lower than for Delta. @jburnmurdoch

@jburnmurdoch 8/ Immune evasion vs Disease progression #Omicron @GuptaR_lab

@jburnmurdoch @GuptaR_lab 9/ CPE & cell-cell fusion #Omicron
@matmartinsvet

Cytopathic effect or cytopathogenic effect (abbreviated CPE) refers to structural changes in host cells that are caused by viral invasion.

@jburnmurdoch @GuptaR_lab @matmartinsvet 10/ Omicron case severity in South Africa & UK. @danielgoyal

@jburnmurdoch @GuptaR_lab @matmartinsvet @danielgoyal 11/ Omicron in London @alexselby1770

@jburnmurdoch @GuptaR_lab @matmartinsvet @danielgoyal @alexselby1770 12/ Age controlled data on Omicron severity. @sailorrooscout

@jburnmurdoch @GuptaR_lab @matmartinsvet @danielgoyal @alexselby1770 @sailorrooscout 13/ People with Omicron are 50- 70% less likely to need hospital care. @BBCBreaking

14/ What to expect from the Omicron wave? @trvrb

@trvrb 15/ Daily hospitalizations and deaths #Gauteng #SouthAfrica #Omicron

@ScottGottliebMD

16/ Rapid turnaround #Omicron #COVID19 @EricTopol

17/ Hospitalizations as per three studies #OmicronVariant @ScottGottliebMD

18/ Lung infectivity
Omicron vs Delta

19/ Severity of Omicron compared to Delta. @AnuragAgrawalMD

20/ Infectivity in hamsters @EricTopol
21/ Omicron - Cross Neutralization - Delta
@sigallab

22/ Extensive mutations in #Omicron might have knocked out a lot of nAb binding sites, but a lot of spike protein is still not mutated, which T cells of vaccinated/ previously infected people recognize easily.

Read this thread by @virusmonologues

23/ Functional preservation of T cell responses against #Omicron

@SetteLab @profshanecrotty

24/ Five independent studies have shown that Omicron cannot infect lung cells as efficiently as the previous variants. @EricTopol

25/ Gauteng, South Africa graphs
#Omicron #Delta #COVID19

26/ Now 6th study shows Omicron affects lungs less - compared to Delta and previous variants of concern. #COVID19 @EricTopol

27/ Ireland cases, positivity are all rising but very few hospitalizations

@EricTopol

28/ South African data @FaheemYounus

29/ Reduced clinical symptoms with Omicron variant #Covid_19 @Marc_Veld

30/ Why is Omicron variant not able to infect lower airway cells?

Why is its infection efficiency limited to upper airway cells?

Why has Omicron's capacity to induce cell-cell fusion & syncytia formation significantly reduced compared to Delta?

Thread:

31/ Syncytia formation is not seen with Omicron, whereas it was a pathogenic characteristic of earlier variants such as D614G and Delta. @juli_bg_bs

32/ Only the immuno-compromised ones are having complications. #Omicron #COVID19 @kit_delgadoMD

33/ There is a drastic difference between the first wave of 2020 and the current Omicron wave in USA.

A thread from the COVID-19 frontlines. @Craig_A_Spencer

34/ Omicron < Substantially milder < Earlier variants @sailorrooscout

35/ The reason behind reduced pathogenicity of Omicron compared to earlier variants

36/ Cases vs mortality in USA #Omicron #COVID19 @sailorrooscout

37/ The UK picture is becoming clearer. Less severity is really a thing. @EricTopol

38/ Less severe disease and fatality rate. #Omicron #COVID19 @EricTopol

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More from @chitguppi

Rajeev Chitguppi MDS Profile picture
Jan 8, 2022
1/ Who gets severe COVID-19?

COVID-19 is a double-defect disease:

1. A defective early control of the virus by type I / III Interferons (IFN)

2. An impaired ability to control proinflammatory activities.

Only when both these checkpoints fail will critical disease develop.
2/ Interferons (IFN)

SARS-CoV-2 is a poor inducer of IFN:

Triggers limited & delayed type I / III IFN responses.

On the other hand, the virus is highly sensitive to IFN treatment similar to other coronaviruses.
3/ Despite modest IFN induction, this innate antiviral response is critical for infection control. #COVID19

@SciImmunology 7 Jan 2022

science.org/doi/10.1126/sc…
Read 6 tweets
Rajeev Chitguppi MDS Profile picture
Jan 8, 2022
Neutralizing antibodies are a good indicator of protection,
- not only against severe disease
- but also (if amounts are very high) against viral replication in the mucosa (with or without symptoms), thereby reducing transmission. #COVID19

However... 1/n science.org/doi/10.1126/sc…
However, this does not mean that it is circulating antibody that is causing protection:

- Antibody in the serum does not normally diffuse (or get transported) into mucosal fluids.

- Also... (2/n)
science.org/doi/10.1126/sc…
Also, protection against superficial infection depends on

- mucosal antibodies [including immunoglobulin A (IgA)],

and possibly on

- antiviral T cells that reside within the linings of the respiratory tract. (3/n)
science.org/doi/10.1126/sc…
Read 5 tweets
Rajeev Chitguppi MDS Profile picture
Jan 4, 2022
1/ Which oral/ periodontal pathogen acts similar to viruses when it comes to suppressing host immunity?

Background:

Anatomical (mucosal/ epithelial) barriers confer antiviral immunity via interferon (IFN) production.

IFNs function like antiviral cytokines...
2/ IFNs function as antiviral cytokines and restrict viral infection, replication, and release.

Oral epithelial cells fight viral infections by inducing Type III IFNs (IFN-λ) preferentially.

Latest evidence:

Recent study PNAS, 21 Dec 2021
3/ A recent study showed that IFN production and antiviral immunity are severely compromised by one oral bacterial pathogen.

And that is Porphyromonas gingivalis (Pg).

Molecular pathways employed by Pg are strikingly parallel to those utilized by viruses for IFN suppression.
Read 4 tweets
Rajeev Chitguppi MDS Profile picture
Jan 4, 2022
1/ Delta variant was highly pathogenic due to its ability to cause cell-cell fusion & syncytia formation.

But this pathogenicity came with Terms & Conditions.

"S1/2 cleavage should be optimal for cells expressing TMPRSS2 (lower airway)"

Omicron #COVID19 story is different.
2/ Cell-cell fusion mediated by spike glycoprotein requires S1/S2 cleavage, but is also dependent on TMPRSS2 presence.

Omicron spike is relatively poorly cleaved.

Way suboptimal compared to Delta

Due to this suboptimal cleavage lower airway infection is less with Omicron.
3/ So, Omicron shows impaired entry & replication in lung cells that express TMPRSS2 (a serine protease enriched in lung alveolar type 1 & 2 cells).

This reduced cleavage is also associated with poorer cell-cell fusion and syncytia formation.

This tells us about upper airway
Read 5 tweets
Rajeev Chitguppi MDS Profile picture
Jan 3, 2022
1/ Omicron's 3 mutations (P681H, H655Y, N679K) in furin cleavage site region were initially predicted to favor its pathogenicity: cell-cell fusion & syncytia formation.

But reality is different.

Omicron's cleavage efficiency is substantially lower than Delta variant. #COVID19
2/ Omicron spike is relatively poorly cleaved.

It shows impaired entry & replication in lung cells that express TMPRSS2, a serine protease enriched in lung alveolar type 1 & 2 cells.

This reduced cleavage is also associated with poorer cell-cell fusion and syncytia formation.
3/ Cell-cell fusion mediated by spike glycoprotein requires S1/S2 cleavage, but is also dependent on TMPRSS2 presence.

Fusogenicity of Omicron spike was severely impaired despite TMPRSS2 expression, leading to marked reduction in syncytium formation compared to Delta spike.
Read 4 tweets
Rajeev Chitguppi MDS Profile picture
Jan 3, 2022
Omicron infects throat more & lungs less compared to earlier variants.

Simple strategy: As soon as you get sore throat start with Chlorhexidine (CHX) mouthwash for throat gargling

Study: 4 day CHX use eliminated #SARSCOV2 virus from oropharynx. #COVID19
All studies done on Chlorhexidine and its antiviral actions esp. against SARS-COV-2 summarized in my blog

"Chlorhexidine gluconate — the most effective antiviral mouthwash in COVID-19 pandemic"

chitguppi.medium.com/chlorhexidine-…
My earlier thread on Chlorhexidine mouthwash and its antiviral effects against SARS-COV-2

Read 5 tweets

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