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Multisystem Involvement in Long Covid



Published five days ago in a Neurology journal "Multisystem Involvement in Post-acute Sequelae of COVID-19 (PASC)" by a Boston collaborative team.

PASC refers to Post-Acute Sequalae of Covid -19 and Long Covid.


Quick summary for Fatigues/Cognitives:

PASC following mild COVID-19 infection is associated with multisystem involvement including:

  • 100% with PASC had reduced cerebral blood flow velocity/ dysregulation even in those who did not have post-COVID POTS

  • 100% with PASC had dysautonomia

  • 89% with PASC had small fibre neuropathy which leads to dysautonomia/ POTS

  • Respiratory dysregulation was seen

  • Chronic inflammation was seen with 67% having inflammatory markers.




What was their objective?

To describe cerebrovascular, neuropathic and autonomic features of post-acute sequelae of COVID-19 (PASC) /Long Covid.


What did they do? This was a retrospective (looking back) study evaluating consecutive patients with chronic fatigue, brain fog and orthostatic intolerance consistent with PASC.

Controls included postural tachycardia syndrome patients (POTS) and healthy participants.


They analyzed data including:

  • Patient surveys

  • Autonomic nervous system tests including Valsalva manoeuvre, deep breathing, sudomotor and tilt tests

  • Cerebrovascular (brain blood flow) tests including cerebral blood flow velocity (CBFv) monitoring in middle cerebral artery.

  • Respiratory tests including Capnography monitoring - capnography is a non-invasive measurement during inspiration and expiration of the partial pressure of CO2 from the airway. It provides physiologic information on ventilation, perfusion, and metabolism,

  • Neuropathic tests including skin biopsies for assessment of small fibre neuropathy

  • Inflammatory and autoimmune markers.

(So far in the UK I have ONLY ONE of these tests. I am sure most of you have had none, well maybe the patient surveys.....)

What did they find?

  • Nine PASC patients were evaluated 0.7±0.3 years after a mild COVID-19 infection, treated as home observations.

  • Autonomic, pain, brain fog, fatigue and dyspnea surveys were abnormal in PASC (n=9) and POTS (n=10), compared to controls (n=15).

  • Tilt table test reproduced the majority of PASC symptoms.

  • Orthostatic CBFv declined in PASC (-20.0±13.4%) and POTS (-20.3±15.1%), compared to controls (-3.0±7.5%,p=0.001) and was independent of end-tidal carbon dioxide in PASC, but caused by hyperventilation in POTS.

  • Reduced orthostatic CBFv in PASC included both subjects without (n=6) and with (n=3) orthostatic tachycardia.

  • Dysautonomia was frequent (100% in both PASC and POTS) but was milder in PASC (p=0.013).

  • PASC and POTS cohorts diverged in frequency of small fibre neuropathy (89% vs. 60%)

  • Inflammatory markers for PASC and POTS (67% vs. 70%).

  • Supine (lying down) and orthostatic (standing up) hypocapnia (low CO2 levels) was observed in PASC.


What did they conclude?

PASC following mild COVID-19 infection is associated with multisystem involvement including:

  • Cerebrovascular dysregulation with persistent cerebral arteriolar vasoconstriction

  • Small fibre neuropathy and related dysautonomia

  • Respiratory dysregulation

  • Chronic inflammation.


This was only a small study but I think the results are pretty hard hitting both in the severity of the sequelae of PASC but also in the fact that we are being completely mismanaged by Long Covid Clinics who have NO expertise in dysautonomia its consequences - POTS, orthostatic intolerance, reduced cerebral blood flow, respiratory dysregulation, chronic inflammation, peripheral and central neuropathy. Something needs to change and soon.




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