Thread by @zalaly

📣 New in @ScienceMagazine

I teamed up with @EricTopol to write this #SciencePerspective on Long Covid

Solving the puzzle of #LongCovid

A long 🧵

science.org/doi/10.1126/sc…

First, what is Long Covid?

It is a complex nonmonolithic multisystemic disease with sequelae across almost all organ systems

It can manifest across the life span (from children to older adults) and across race & ethnicity, sex, & baseline health status

science.org/doi/10.1126/sc…

Long Covid is likely a disease with many subtypes that may have different risk factors (genetic, environmental, etc.) and distinct biologic mechanisms that may respond differently to treatments.

science.org/doi/10.1126/sc…

More than 90% of cases occur in people who had mild SARS-CoV-2 infection

science.org/doi/10.1126/sc…

Mechanisms of Long Covid include viral persistence, dysregulated immune response, mitochondrial dysfunction, vascular (endothelial) and/or neuronal inflammation and microbiome dysbiosis

science.org/doi/10.1126/sc…

COVID-19 vaccines, COVID-19 antivirals and metformin reduce the risk of Long Covid

science.org/doi/10.1126/sc…

Reinfection contributes additional risks of Long Covid

it can trigger de novo Long Covid or exacerbate its severity.

Efforts to prevent reinfection are critical to reduce the risk of long-term population health loss

science.org/doi/10.1126/sc…

We highlight some challenges

a. Care needs of people with Long Covid must be met

science.org/doi/10.1126/sc…

b. The attribution of #LongCovid symptoms to psychological causes has no scientific support; it perpetuates stigma and disenfranchises patients from accessing the care they need.

This belongs in the dustbin of history.

science.org/doi/10.1126/sc…

c. The lack of consensus on terms, definitions, and clinical trial end points for Long Covid is slowing progress and hampering industry engagement in clinical trials.

Building consensus on these parameters is urgently needed.

science.org/doi/10.1126/sc…

Historical accounts of the Spanish flu of 1918, EBV, poliomyelitis & others taught us that acute infections can have consequences decades later

This highlights the need for studies to identify latent effects of COIVD-19 that may not have materialized

science.org/doi/10.1126/sc…

Registered trials for Long Covid are too small and underpowered to yield conclusive evidence;

they are being conducted at a slow pace that is unlikely to yield answers to inform patient care for years, if not decades.

science.org/doi/10.1126/sc…

Looking ahead:

We must urgently find treatments!!!!

Trials for Long Covid MUST match the scale and urgency of the problem.

science.org/doi/10.1126/sc…

Preventing infections and reinfections is the best way to prevent Long Covid and should remain the foundation of public health policy.

science.org/doi/10.1126/sc…

This includes

➡️masking — especially in high risk places
➡️improved air quality through filtration and ventilation
➡️Updating building codes to require mitigation against airborne pathogens

science.org/doi/10.1126/sc…

Vaccines should be offered more broadly to populations, uptake should be optimized

We also need variant-proof vaccines and vaccines that induce strong mucosal immunity to block infection and transmission

We must broaden the pipeline of antivirals

science.org/doi/10.1126/sc…

Governments and funding agencies should support a comprehensive portfolio of research in infection-associated chronic illnesses

Although SARS-CoV-2 can cause chronic disease, it is not alone. Influenza virus, Epstein-Barr virus, Ebola virus, polio virus, and many others also have long-term health effects.

Myalgic encephalomyelitis/chronic fatigue syndrome is also triggered by infection.

Research in this area has been disproportionately underfunded relative to the burden of long-term disability and disease caused by infections.

science.org/doi/10.1126/sc…

The world has already paid an extraordinarily heavy price for the biggest pandemic of the 21st century so far

In this crisis lies an urgent need to address the challenge of Long Covid

The world must rise to the occasion

Failure must not be an option!

science.org/doi/10.1126/sc…

Thanks to my co-author @EricTopol for working with me on this piece

And thank you @AldertonBiol and your team for all your effort handling this #SciencePerspective

science.org/doi/10.1126/sc…