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.

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…

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

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.

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.

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

https://twitter.com/chitguppi/status/1381920291815747588?t=8yMTlYwdoK1j5tAn4v1hWA&s=19

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 wishlist two years after 31 December 2019.

On that day WHO was informed of cases of "pneumonia of unknown cause" in Wuhan, China.

Subsequently it was named COVID-19 caused by a novel coronavirus. Earlier we called the virus 2019-nCoV before finalizing the name SARS-COV-2. Since then we have seen 2 to 5 waves in all countries caused by Variants of Concern (VoC), Variants of Interest (VoI) and Variants Under Monitoring (VUM)

Now our understanding of the disease and its management (including prevention) is much better.

(2/n)

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

https://twitter.com/EricTopol/status/1474052582905573377?s=20

A recent breakthrough has identified the molecule responsible for severe disease.

It tells us why some people develop severe disease, complications & hospitalizations, & how to control that.

Before you read the full story, let me name the culprit: ORF 8.

#COVID19 #Omicron 1/n [1] What does SARS-COV-2 do after infecting human cells? (Get the background)

SARS-CoV-2 replicates its RNA genome & produces up to 29 viral proteins

a. Sixteen non-structural proteins (NSP 1 - 16)

b. Four structural proteins- Spike, Membrane, Envelope & Nucleocapsid.

2/n

4-point Summary on the latest evidence available on Masks (N95 and Surgical) and Respirators based on the article published in JAMA Internal Medicine, 11 Aug 2020

Read the thread. #COVID19 #SARSCoV2

jamanetwork.com/journals/jamai… [1] NIOSH -approved N95 respirators are the best.

They outperform alternatives wrt filtration efficiency. Frontline clinicians & health care workers who engage in the highest risk procedures should be afforded the highest level of protection with NIOSH approved N95 respirators.

One article that covers ALL EVIDENCE on masks.

Association of American Physicians & Surgeons (Sept 26, 2020)

It says evidence is not much in favor of use of masks.

Masks may help when used correctly & along with other measures.

#COVID19 #SARSCoV2

aapsonline.org/mask-facts/ The article deals more with cloth masks used by general public in community settings. It's more of a compilation of literature, than a definitive guideline. Not a systematic review. However, many studies in this article DO say that 'masks can help reduce the virus transmission'.

Three genetic risk factors for COVID-19 complications:

[1] A gene cluster on chromosome 3 is a risk locus for #sarscov2 related respiratory failure.

Link: Nature, 30 Sept 2020
nature.com/articles/s4158… [2] A new controlled study of >3000 hospitalized #COVID19 patients has confirmed it as the major genetic risk factor for severe #SARSCoV2 infection and hospitalization.

[3] This genetic risk is conferred by a genomic segment inherited from Neanderthals.

nature.com/articles/s4158…

Now the latest NEJM article (30 Sept) says why we need Rapid Antigen Tests and NOT a standard RT-PCR test. #SARSCoV2 #COVID19 @michaelmina_lab

Read the thread.

[1] By several criteria, the benchmark standard PCR fails when used in a surveillance regimen.
nejm.org/doi/full/10.10… [2] Many people whose infections are detected by PCR are no longer infectious at the time of detection.

[3] >50% infections identified by PCR had their CT values in the higher 30s, indicating low viral loads.

Link: NEJM, 30 Sept 2020
nejm.org/doi/full/10.10…

Most important news (Lancet, 29 Sept, 2020)

Should reduce a lot of #COVID19 anxiety in medical/ dental practice.

[1] LACK of #SARSCoV2 virus being CULTURED from surfaces, fomites, even in the hospital setting, pointing AGAINST this mode of transmission.

thelancet.com/journals/lanin… [2] Environmental contamination leading to SARS-COV-2 transmission is UNKIKELY to occur in real life conditions, provided that standard cleaning procedures & precautions are enforced.

Link: The Lancet 29 Sept 2020
thelancet.com/journals/lanin…

Early decline of neutralizing Ab levels shouldn't be a concern. The key is at what levels Ab titers stabilize after natural infection/ vaccination. This represents the generation of long-lived plasma cells to protect against subsequent infection. #COVID19
jamanetwork.com/journals/jama/… Individuals with mild or asymptomatic disease have shown robust memory T-cell responses months after COVID-19 infection.

However, it is unknown whether memory T cells in the absence of detectable circulating antibodies protect against SARS-CoV-2.

jamanetwork.com/journals/jama/…

#SARSCoV2 virus spread via speech droplets. My FB post covers the full story of all four articles in 7 images. #COVID19

Fig 1,2,3 - Latest study by Bax et al (PNAS, June 2020)
Fig 4, 5 - Their earlier study (NEJM, May 2020) and a supporting letter.

m.facebook.com/story.php?stor… Fig 6 - Arguement (by Abbas & Pittet) on the design flaws of above studies (Lancet, 30 Jun 2020)
Fig 7 - Authors' response to the above arguement (Lancet, Sept 2020)

m.facebook.com/story.php?stor…

On day 1 of exposure, chances of RT PCR result coming negative are 100% (95% confidence interval [CI], 100%-100%).

Chances reduce as days pass.

On day 4 after exposure, chances of false negative decrease to 67% (CI, 27%-94%), but still big. #covid19
acc.org/latest-in-card… Day 5: On the day of symptom onset (typically day 5), false-negative rate was 38% (CI, 18%-65%).

Day 8 (3 days after symptom onset)
chaces are the lowest- at 20% (CI, 12%-30%)

Then increase again.

Day 9: 21% (CI, 13%-31%)

Day 21: 66% (CI, 54%-77%)
acc.org/latest-in-card…

Bradykinin Storm rather than Cytokine storm:

Explains almost every symptom of Covid-19. Offers hope for the use of many already approved drugs.

Analysis of 2.5 billion genetic combinations of 40,000 genes from 17,000 genetic samples related to COVID-19.

biospace.com/article/-oak-r… This great analysis resulted in the "bradykinin hypothesis" on how COVID-19 affects the body.

Bradykinin storm hypothesis says it causes the blood vessels to leak, allowing fluid to accumulate in organs and tissues, like the lung alveoli.

biospace.com/article/-oak-r…

BIG BREAKING | BCG VACCINE for #COVID19

[1] Double-blind, randomized controlled trial in elderly patients (n=198).

[2] BCG vaccination is safe and can protect the elderly against infections.

Link: Cell, 31 Aug 2020
cell.com/cell/fulltext/… [3] BCG vaccination significantly increased the time to first infection (test 16 weeks: placebo 11 weeks).

[4] Incidence of new infections was less after BCG vaccination (Test 25%: Placebo 42.3%)

Link: Cell, 31 Aug 2020
cell.com/cell/fulltext/…

ACE2 receptors in multiple cell types act as entry points for #SARSCoV2

[1] Apart from respiratory, cardiovascular, GI-tract, renal-excretory and reproductive systems there is a significant ACE2 expression in brain/ CNS.

Cell & Mol Neurobiol 25, Aug 2020
link.springer.com/article/10.100… [2] ACE2 receptor expression detected in multiple brain regions. Highest levels detected in pons / medulla oblongata - respiratory centers of brain. This may in part explain the respiratory distress.

Link: Cell & Mol Neurobiology 25, Aug 2020
link.springer.com/article/10.100…

#SARSCoV2 infections among doctors:
Frontline Health Care Personnel (HCP) getting infected with #SARSCoV2

[1] A high proportion of #SARSCoV2 infections among HCP appear to go undetected

Link: CDC (31 Aug 2020)
cdc.gov/mmwr/volumes/6… [2] Most HCP who had antibodies, had no symptoms.

[3] Two potential reasons for HCP infections:
(a) PPE shortages and
(b) interacting with patients without wearing a face covering.

cdc.gov/mmwr/volumes/6…