Annals of Neurology: What systems are mainly involved in acute sequelae after COVID-19?

Coronavirus disease 19 ( COVID-19 ), a novel infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has sparked a global pandemic
.
Acute sequelae of COVID-19 (PASC) is provisionally defined as symptoms that persist or worsen for more than 4 weeks, or the onset of new symptoms attributable to COVID-19, affecting 20-60% of patients

Common complaints are fatigue, dyspnea, brain fog, and orthostatic intolerance, as well as various systemic complaints
.
PASC is a multisystem disease, however, the exact pathophysiology remains poorly understood

Symptoms of intravenous immunoglobulin reactivity in PASC patients suggest cerebral hypoperfusion, small fiber neuropathy (SFN), and autonomic dysregulation due to cerebrovascular arterial dysfunction
.

Postural orthostatic tachycardia syndrome (POTS) is characterized by symptoms similar to PASC, including chronic fatigue, orthostatic intolerance, and brain fog associated with decreased orthostatic cerebral blood flow and dysautonomia
.
Therefore, in addition to healthy controls, POTS patients provide a useful comparison group to be able to identify pathophysiologies that differ from PASC

From this, Peter Novak et al.
of Harvard Medical School hypothesized that PASCs are associated with autoimmune/inflammation-mediated widespread cerebrovascular and metabolic dysregulation and neuropathies
.

They retrospectively evaluated consecutive patients with chronic fatigue, brain fog, and normal intolerance consistent with PASC
.
The control group consisted of patients with postural orthostatic tachycardia syndrome (POTS) and healthy participants

They found: Nine patients with PASC were evaluated 0.
8±0.
3 years after mild COVID-19 infection and observed as home
.
Autonomic, pain, brain fog, fatigue, and dyspnea were all abnormal in PASC and POTS (n = 10) compared to controls (n = 15)

Normal CBFv decreased in PASC (-20.
0 ± 13.
4%) and POTS (-20.
3 ± 15.
1%) compared with controls (-3.
0 ± 7.
5%, p = 0.
001), independent of end-tidal carbon dioxide in PASC, but Caused by hypoventilation in POTS
.

Anteroposterior CBFv was decreased in PASC, including subjects without (n = 6) and with (n = 3) anteroposterior tachycardia
.

Autonomic abnormalities were common (100% in both PASC and POTS) but were milder in PASC (P = 0.

The PASC and POTS cohorts differed in frequency of small fiber neuropathy (89% vs 60%), but not in inflammatory markers (67% vs 70%)
.
Supine and orthostatic hypocapnia were observed in PASC

The significance of this study lies in the discovery that PASC following mild COVID-19 infection is associated with multisystem involvement , including: (1) cerebrovascular dysregulation and persistent cerebral arterial vasoconstriction; (2) small fiber neuropathy and related Autonomic nervous system disorders; (3) respiratory system disorders; and (4) chronic inflammation
.

Original source:
Novak P, Mukerji SS, Alabsi HS, et al.
Multisystem Involvement in Post‐Acute Sequelae of Coronavirus Disease 19.
Annals of Neurology .