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29th Napa Pain Conference Sessions

Neurological Consequences of COVID-19 & Post-Acute Sequelae of COVID (PASC)

Aug 20, 2022 8:45am ‐ Aug 20, 2022 9:30am


Among evaluated patients with long COVID, prolonged, often disabling, small-fiber neuropathy after mild SARS-CoV-2 was most common, beginning within 1 month of COVID-19 onset. Various evidence suggested infection-triggered immune dysregulation as a common mechanism. - Nath, 2022

Symptoms of long COVID are reported to be on-and-off, cyclic or multiphasic. A meta-analysis of pain-related symptoms reported for patients with long-term PASC determined that every one month of follow-up corresponded to a 45% increase in prevalence in patients who developed neuralgia after acute COVID-19 infection.

Weakness, often accompanied by myalgia and arthralgia, is a musculoskeletal manifestation of SARS-CoV-2 infection.

Central and peripheral nerve systems are one of the most susceptible targets for SARS-CoV-2 virus (neurotropism).

As well, a prolonged period of mechanical ventilation in the ICU may cause what is called “post intensive care syndrome” or “ICU-acquired weakness”, manifesting as cognitive dysfunction, muscle atrophy, sensory disruption and joint-related pain.

Residual effects from SARS-CoV-2 virus include fatigue, dyspnea, chest pain, persistent loss of taste and/or smell, cognitive changes, arthralgias, and decreased quality of life.

Additional Reading

  • Oaklander, A. L., Mills, A. J., Kelley, M., Toran, L. S., Smith, B., Dalakas, M. C., & Nath, A. (2022). Peripheral Neuropathy Evaluations of Patients With Prolonged Long COVID. Neurology-Neuroimmunology Neuroinflammation, 9(3).
  • Chrousos, G. P., & Kaltsas, G. (2005). Post‐SARS sickness syndrome manifestations and endocrinopathy: how, why, and so what?. Clinical Endocrinology, 63(4), 363.
  • Nath, A. (2020). Long-haul COVID. Neurology, 95(13), 559-560.
  • Shiers, S., Ray, P. R., Wangzhou, A., Sankaranarayanan, I., Tatsui, C. E., Rhines, L. D., ... & Price, T. J. (2020). ACE2 and SCARF expression in human DRG nociceptors: implications for SARS-CoV-2 virus neurological effects. Pain, 161(11), 2494.
  • Attal, N., Martinez, V., & Bouhassira, D. (2021). Potential for increased prevalence of neuropathic pain after the COVID-19 pandemic. Pain reports, 6(1).
  • Lancet, T. (2021). Understanding long COVID: a modern medical challenge. Lancet (London, England), 398(10302), 725.
  • Cascella, M., Del Gaudio, A., Vittori, A., Bimonte, S., Del Prete, P., Forte, C. A., ... & De Blasio, E. (2021). COVID-Pain: Acute and Late-Onset Painful Clinical Manifestations in COVID-19–Molecular Mechanisms and Research Perspectives. Journal of Pain Research, 14, 2403.
  • Dani, M., Dirksen, A., Taraborrelli, P., Torocastro, M., Panagopoulos, D., Sutton, R., & Lim, P. B. (2021). Autonomic dysfunction in ‘long COVID’: rationale, physiology and management strategies. Clinical Medicine, 21(1), e63.
  • Raveendran, A. V., Rajeev Jayadevan, and S. Sashidharan. "Long COVID: an overview." Diabetes & Metabolic Syndrome: Clinical Research & Reviews 15, no. 3 (2021): 869-875.
  • Nath, A., & Smith, B. (2021). Neurological issues during COVID-19: An overview. Neuroscience Letters, 742, 135533.
  • Goss, A. L., Samudralwar, R. D., Das, R. R., & Nath, A. (2021). ANA investigates: neurological complications of COVID‐19 vaccines. Annals of Neurology, 89(5), 856.
  • Bierle, D. M., Aakre, C. A., Grach, S. L., Salonen, B. R., Croghan, I. T., Hurt, R. T., & Ganesh, R. (2021). Central sensitization phenotypes in post acute sequelae of SARS-CoV-2 infection (PASC): defining the post COVID syndrome. Journal of Primary Care & Community Health, 12, 21501327211030826.
  • Groff, D., Sun, A., Ssentongo, A. E., Ba, D. M., Parsons, N., Poudel, G. R., ... & Chinchilli, V. M. (2021). Short-term and long-term rates of postacute sequelae of SARS-CoV-2 infection: a systematic review. JAMA Network Open, 4(10)
  • Hoshijima, H., Mihara, T., Seki, H., Hyuga, S., Kuratani, N., & Shiga, T. (2021). Incidence of Long-term Post-acute Sequelae of SARS-CoV-2 Infection Related to Pain and Other Symptoms: A Living Systematic Review and Meta-analysis. medRxiv.


  • Dr. Avindra Nath, MD, Chief, Section for Infections of the Nervous System; Clinical Director, Translational Neuroscience Center, NIH - National Institute of Neurological Disorders and Stroke (NINDS)
Category: General Session

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