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29th Napa Pain Conference Sessions

How Do We Manage Pain Syndromes Related to Post Acute Sequela of COVID-19 (PASC)?

Aug 21, 2022 9:00am ‐ Aug 21, 2022 10:30am


"Long-Haul COVID is our calling and we should take the lead" - Avindra Nath, MD  2020, Editorial, American Academy of Neurology

Even mild COVID-19 infection may lead to persistent and potentially incapacitating clinical manifestations (Postacute Sequelae of SARS-CoV-2 Infection (PASC)).

It is estimated that anywhere from 10% to 30% of patients might experience long COVID after recovering. 

Among pain-related symptoms, chest pain, headaches, arthralgia, neuralgia, and abdominal pain are most persistent. Central and peripheral nerve systems are one of the most susceptible targets for SARS-CoV-2 virus. 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.

This session will address:

  • possible pathophysiology, 
  • risk factors, and 
  • treatment strategies for pain-related symptoms in long COVID

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-analyisis 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”,9
manifesting as cognitive dysfunction, muscle atrophy, sensory disruption and joint-related

more than half of COVID-19 survivors experienced PASC 6 months after recovery

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

  • Steroid-Induced Avascular Necrosis

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.
  • Moldofsky, H., & Patcai, J. (2011). Chronic widespread musculoskeletal pain, fatigue, depression and disordered sleep in chronic post-SARS syndrome; a case-controlled study. BMC neurology, 11(1), 1-7.
  • Attal, N., Martinez, V., & Bouhassira, D. (2021). Potential for increased prevalence of neuropathic pain after the COVID-19 pandemic. Pain reports, 6(1).
  • Chrousos, G. P., & Kaltsas, G. (2005). Post‐SARS sickness syndrome manifestations and endocrinopathy: how, why, and so what?. Clinical endocrinology, 63(4), 363.
  • Liu, Y., Sawalha, A. H., & Lu, Q. (2021). COVID-19 and autoimmune diseases. Current Opinion in Rheumatology, 33(2), 155.
  • Faye, A. S., Lee, K. E., Laszkowska, M., Kim, J., Blackett, J. W., McKenney, A. S., ... & Lebwohl, B. (2021). Risk of adverse outcomes in hospitalized patients with autoimmune disease and COVID-19: a matched cohort study from New York City. The Journal of Rheumatology, 48(3), 454-462.
  • Hong, N., & Du, X. K. (2004). Avascular necrosis of bone in severe acute respiratory syndrome. Clinical Radiology, 59(7), 602-608.
  • Zhang, S., Wang, C., Shi, L., & Xue, Q. (2021). Beware of Steroid-Induced Avascular Necrosis of the Femoral Head in the Treatment of COVID-19—Experience and Lessons from the SARS Epidemic. Drug Design, Development and Therapy, 15, 983.
  • Michelen, M., Manoharan, L., Elkheir, N., Cheng, V., Dagens, A., Hastie, C., ... & Stavropoulou, C. (2021). Characterising long COVID: a living systematic review. BMJ global health, 6(9), e005427.
  • 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.
  • de Araújo, A. L., da Silva Duarte, A. J., Levin, A. S., Guedes, B. F., Kallas, E. G., Pinna, F. R., ... & HCFMUSP PASC Initiative. (2021). Post-acute sequelae of SARS-CoV-2 infection (PASC): a protocol for a multidisciplinary prospective observational evaluation of a cohort of patients surviving hospitalisation in Sao Paulo, Brazil. BMJ Open, 11(6), e051706.
  • 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. Monica Verduzco–Gutierrez, MD, Professor and Chair of the Department of Rehabilitation Medicine, Long School of Medicine at UT Health San Antonio
  • 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)

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