More than 30 percent of the over 70 million individuals in the United States who
experienced an acute COVID-19 infection as a result of severe acute respiratory
coronavirus-2 (SARS-CoV2), have variety of lingering and disabling symptoms that last
beyond the acute phase of the illness. [1]This condition is referred to as Post-Acute
Sequalae SARS-CoV-2 infection (PASC). Symptoms (including fatigue, post-exertional
malaise (PEM), cardiovascular dysfunction, respiratory distress, gastrointestinal
disturbances, and dermatologic issues) associated with PASC vary and can affect multiple
organ systems. These symptoms are similar to, in extent and degree, to other neuro-immune
conditions such as Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). PASC, as
with ME/CFS, is likely to pose a significant impact on the healthcare system and
patient's quality of life. An unmet need exists as the susceptibility and pathogenesis of
PASC remains yet to be fully elucidated. Emerging evidence suggests that existing
interventions widely used for other neuro-immune conditions may prove equally effective
in the treatment of PASC. Repurposing of drugs or identification of new drugs will take
time. Still, there is growing evidence of the mind-body connection in modulating the
autonomic, central and peripheral nervous systems as well as the immune system and the
gastrointestinal tract. Recent studies have documented that holistic strategies such as
mindfulness, meditation, and amygdala and insula retraining (AIR) have an objective
measurable effect on heart rate variability, fatigue, pain, quality of life, depression,
anxiety, and gastrointestinal symptoms. The mechanisms proposed include activation of
vagus nerve, balancing the autonomic nervous system, reducing stress, and improving
immune function. AIR is based on the principle that viral, bacterial, or environmental
insults can sensitize the amygdala, which becomes hypervigilant and unleashes a cascade
of hormonal responses that perpetuate a state of neuroinflammation and dysautonomia. AIR
de-sensitizes the amygdala, breaking vicious cycles and reducing the maladaptive release
of hormones and cytokines. Our clinical group has already recommended the use of AIR with
great anecdotical response in clinical practice. This strategy is readily available and
has no contraindications or risks. We aim to conduct a pilot study of AIR to generate
preliminary data for a larger, federally funded trial. Our specific aims are:

1. Identify 130 subjects within the Miami Veteran's Administration (VA) Medical Center
who experienced an acute COVID-19 infection and continue to experience persistent
moderate fatigue (using standard questionnaires). Subjects will be randomized to
either 1. AIR + standard of care or 2. Standard of care/wait list. Individuals in
this latter arm will be waitlisted to receive the AIR intervention after they
complete the study.

2. Collect standard questionnaires recommended by the Veterans Affairs Healthcare
System at baseline, three, and six months to capture levels of fatigue (primary
outcome), post exertional malaise (PEM), brain fog, pain, and other symptoms and
compare changes over time across the two study arms.

3. Collect objective biometric data in a sample of patients at baseline and at three
and six months to explore potential mediating mechanisms: heart rate variability,
heart rate and blood pressure sitting and standing, inflammatory markers (c-reactive
protein, cortisol, and Epstein Barr viral reactivation. The laboratory tests will
not be collected for research purposes as they are collected for clinical purposes.