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Vipin M. Vashishtha

@vipintukur

Oct 13

A new study provides new evidence to help us redefine steroid use in TB care

➡️ Given the renewed interest in the steroid dexamethasone, as a host-directed treatment during the COVID-19 pandemic, the Trinity College Dublin team provides evidence that treating patients with steroids may enhance the function of their macrophages to kill the mycobacteria, while diminishing pathways of inflammatory damage. 1/

The researchers goal was to determine whether dexamethasone impacts the macrophage's ability to fight TB. Although glucocorticoids can reactivate TB, they are paradoxically the only adjunctive host-directed therapies that are recommended by WHO for TB.

Steroids are given to patients alongside antimicrobials in certain circumstances; however, scientists don't fully understand the effect of these drugs on the immune system, especially innate immune cells such as macrophages. 2/

The researchers studied macrophages derived from the blood of healthy volunteers or isolated from lung fluid donated by patients undergoing routine bronchoscopies.

➡️ By treating and infecting these macrophages in the lab with Mtb, the scientists could examine and understand how dexamethasone affects the immune response that protects the lungs during infection. 3/

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Vipin M. Vashishtha

@vipintukur

Oct 7

A NEW review explores how SARS-CoV-2 may influence cancer risk.

➡️ Unlike classical oncogenic viruses, it doesn’t insert viral oncogenes. Instead, its proteins:

-Inhibit tumor suppressors
-Activate growth, survival & inflammation pathways

👉 Potential role in cancer initiation & progression. 1/

Bioinformatic & experimental studies show direct interactions between viral proteins and host cellular components tied to cancer hallmarks.

➡️ These mechanisms could contribute to initiation, promotion, and progression of tumors, raising the possibility that SARS-CoV-2 may act as an oncovirus.

👇The figure illustrates various key oncogenic signaling molecules or pathways targeted by SARS-CoV-2 NSP, N, M and S protein. The activation of oncogenic pathways can lead to the conversion of a normal cell into a cancer cell. 2/

The shared mechanisms between SARS-CoV-2 and key hallmarks of cancer including sustained proliferative signaling, resisting cell death, genomic instability, dysregulated cellular metabolism and epigenetic reprogramming.

👇The figure highlights how SARS-CoV-2 interacts with critical oncogenic signaling molecules or pathways. Specific SARS-CoV-2 proteins involved in these processes are marked. 3/

Read 8 tweets

Vipin M. Vashishtha

@vipintukur

Oct 5

A new study from Karolinska Institutet shows that an unusual heart rhythm disorder, POTS, is particularly common in people with #LongevityPoweredbyGinseng COVID. The majority of those affected are middle-aged women. 1/

Postural orthostatic tachycardia syndrome, or POTS, is a condition where the heart beats abnormally fast when changing position from lying down to standing up. Standing up is a challenge for those affected who feel dizzy and would rather sit or lie down, so-called orthostatic intolerance. Their hearts may also beat faster than normal at rest and during exertion. 2/

Patients experience fatigue and difficulties concentrating, symptoms that are common in longCOVID.

Now, researchers at Karolinska Institutet show that POTS occurs in almost a third of patients with severe longCOVID. By comparison, less than 1% of the Swedish population was affected by POTS before the pandemic. 3/

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Vipin M. Vashishtha

@vipintukur

Sep 24

New insights into #LongCOVID from a hamster model

➡️ Despite LongCOVID’s clinical significance, the mechanisms driving remain poorly understood.

Here, to address this, researchers utilized a Phodopus roborovskii hamster model to investigate the long-term effects of SARS-CoV-2 infection compared with influenza A virus.

➡️ While 46.25–47.50% of hamsters survived SARS-CoV-2 or influenza A virus H1N1 infection, 13.75% of SARS-CoV-2 survivors exhibited impaired weight recovery, severe lung pathology and significant neutrophil accumulation, defining the LongCovid (PAŚĆ) group. 1/

Single-cell RNA sequencing of bronchoalveolar lavage (BAL) fluid, lung and spleen at 30 days post-infection revealed hallmark LongCovid (PASC) gene signatures uniquely upregulated in the PASC group.

➡️ This was accompanied by elevated neutrophil levels and reduced macrophage populations, indicative of disrupted myeloid cell differentiation. 2/

Immunohistochemistry further detected persistent SARS2’s S1 subunit antigen in the lungs of PASC (LongCovid) hamsters at 30 days post-infection, coinciding with marked neutrophil infiltration, which probably drove prolonged inflammatory responses. 3/

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Vipin M. Vashishtha

@vipintukur

Sep 23

It is currently debatable whether mucosal vaccination is still warranted given that most individuals in developed countries have established a hybrid immunity from vaccination and infection.

➡️ In a new study, researchers studied how our immune system in the airways (the “mucosal” immune system) responds to COVID infection, vaccines, and special mucosal booster vaccines. 1/

What they found in people:

➡️ Having both vaccination + prior infection (“hybrid immunity”) gave only a modest increase in protective antibodies (IgA) in the nose and lungs compared to infection or vaccination alone. 2/

What the researchers found in animal models:

➡️ Giving a mucosal booster vaccine (delivered to the airways using an adenovirus-based vaccine) worked much better. It:

-Strongly boosted IgA antibodies in the nose and lungs

-Triggered local T-cells in the airways

-Provided stronger, longer-lasting protection against SARS-CoV-2. 3/

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Vipin M. Vashishtha

@vipintukur

Sep 20

How quickly #mRNA degrades is linked to autoimmune disease risk!

➡️ We usually think of gene activity in terms of how much mRNA is produced. But a new study shows another key factor: how fast mRNA degrades. 1/

UCLA scientists built RNAtracker, a tool to tell whether changes in gene expression are due to production or breakdown of mRNA.

➡️ Testing across 16 human cell types, they found that many “unstable” mRNAs come from innate immunity genes.

➡️ Crucially, UCLA scientists built RNAtracker, a tool to tell whether changes in gene expression are due to production or breakdown of mRNA.

➡️ Crucially, these unstable mRNAs are linked to genetic variants tied to autoimmune diseases like:
•Lupus
•Type 1 diabetes
•Multiple sclerosis
•Allergic rhinitis 2/

The researchers applied RNAtracker to a publicly available dataset of 16 human cell lines, in which newly made mRNAs had been chemically labeled and tracked over time.

This allowed them to identify genes whose stability varies due to specific mutations. Many of these genes are involved in immune system function—especially the innate immune system, the body's first line of defense against infections. 3/

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