Long Covid: where we stand and challenges ahead, Mantovani et al 2022


This is a review article but it is really super in terms of its breadth, how seriously it takes the issue, and how much is actually known now. I can't help but be grateful for this major wave of research into Long Covid, hoping and indeed expecting that they will really come to understand certain aspects of it properly in due course.

Having a neatly defined abundant cohort is an enormous difference to me/cfs. If this is where we stand after just 2.5 years of covid being in circulation, and perhaps 2 years after long covid came to be understood, imagine where we will be in another 5 years. Being able to use other scientists findings to focus their own research is going to be an enormous boost - perhaps there are not 'shoulders of giants' to stand on yet, but shoulders nonetheless. Whereas - if you'll permit a contorted metaphor - most original mecfs researchers have had to try to stand on their own shoulders!

The research environment is strong-looking, global and motivated. I am pleased.

Cell Death Differ. 2022 Sep 7 : 1–10.
doi: 10.1038/s41418-022-01052-6 [Epub ahead of print]
PMCID: PMC9449925
PMID: 36071155
Long Covid: where we stand and challenges ahead
Alberto Mantovani,
1,2,3 Maria Concetta Morrone,4,5 Carlo Patrono,6 M. Gabriella Santoro,7,8 Stefano Schiaffino,9 Giuseppe Remuzzi,10 Giovanni Bussolati,
11,12 and On behalf of the Covid-19 Commission of the Accademia Nazionale dei Lincei



  • PASC is a frequent legacy of acute SARS-CoV-2 infection, affecting over 10% of patients with different signs and symptoms across a wide range of organs and systems.
  • The most frequent manifestations of PASC, in addition to compromised lung functions, include: neurocognitive alterations; alterations of cardiovascular functions and increased risk of acute events; fatigue.
  • The SARS-CoV-2 virus seeds and persists in different organs and tissues.
  • The pathogenesis of PASC is multifactorial and includes: virus seeding and persistence in different organs; activation and response to unrelated viruses (e.g., EBV); autoimmunity; uncontrolled inflammation.
  • Biomarkers of clinical PASC include levels of IgG, cytokines, chemokines, PTX3, and interferons.
  • Vaccination reduces PASC after breakthrough infection.

Open questions

  • Occurrence, mechanism, and significance of SARS-CoV-2 persistence in different organs.
  • Mechanisms, targets, and significance of autommune reactions.
  • Role of other viruses.
  • Impact of host genetics and microbiome.
  • Actual impact of vaccination in people who get breakthrough infections and its duration.
  • Occurrence and severity of PASC after infection with future variants.
  • Preventive and therapeutic approaches.