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Suspected Long COVID-19 (case definitions, risk factors, sx frequencies)
Case definitions, risk factors CDC case definition:1 - Umbrella term for wide range of health consequences that are present ≥4wk after SARS-CoV-2 infxn
- The ≥4-wk time frame provides a rough approximation of effects that occur beyond the acute period, but the timeframe might change as more is learned about the condition
- Post-COVID conditions can occur in pts who’ve had varying degrees of illness during acute infxn, incl those who had mild or asymptomatic infxns
WHO definition:2 - Post-COVID-19 conditions occur in individuals w/ hx of probable or confirmed SARS-CoV-2 infxn, usually occurring 3mo from onset of COVID-19 sx and lasting ≥2mo; can’t be explained by an alternative dx
- Common sx incl fatigue, SOB, cognitive dysfunction plus others; generally have an impact on everyday functioning
- Sx may be new onset following initial recovery from acute COVID-19 episode or persist from the initial illness
- Sx may also fluctuate or relapse over time
Potential risk factors for long COVID in adults:3-7 - White race
- poor pre-pandemic general/mental health status
- older age, age 40 to 49 yrs
- female sex
- overweight/obesity
- asthma
- severe clinical status
- higher number of comorbidities
- higher symptom load
- hospital admission
- O2 supplementation in acute phase
Nonetheless, recent observational studies suggest that COVID-19 vaccination may protect against development of long COVID8-10 Synonyms: Long COVID is referred to by a wide range of terms, including:1 - Post-acute sequelae of SARS-CoV-2 infection (PASC)
- Post-COVID conditions
- Post-acute COVID
- Long-term effects of COVID
- Post-acute COVID syndrome
- Chronic COVID
- Long-haul COVID
- Late sequelae
Footnotes 1 CDC 2021. Evaluating and Caring for Patients with Post-COVID Conditions: Interim Guidance. Updated 6/14/21. Accessed 3/10/22
2 WHO 2021. World Health Organization. Soriano JB, et al. A Clinical Case Definition of Post COVID-19 Condition by a Delphi Consensus. Lancet Infect Dis. 2022. Apr(22(4):e102-e107. (First published online 12/21/21.) Accessed 3/10/22
3 Cabrera Martimbianco AL, et al. Frequency, signs and symptoms, and criteria adopted for long COVID: a systematic review. Int J Clin Pract. 2021. Oct;75(10):e14357. Free full-text article
4Iqbal FM, et al. Characteristics and predictors of acute and chronic post-COVID syndrome: a systematic review and meta-analysis. EClinicalMedicine. 2021. May 24;36:100899. Free full-text article
5 Aminian A, et al. Association of obesity with postacute sequelae of COVID-19. Diabetes Obes Metab. 2021. Sep;23(9):2183-2188. Free full-text article
6 Thompson EJ, et al. Long COVID burden and risk factors in 10 UK longitudinal studies and electronic health records. Nat Commun. 2022. Jun 28;13(1):3528. Free full-text article
7 Sylvester SV, et al. Sex differences in sequelae from COVID-19 infection and in long COVID syndrome: a review. Curr Med Res Opin. 2022. Jun 20:1-9. Epub ahead of print. Free full-text article
8 Zisis SN, et al. The protective effect of covid-19 vaccination on post-acute sequelae of covid-19 (pasc): a multicenter study from a large health research network. Open Forum Infect Dis. 2022. May 7;ofac228,doi.org/10.1093/ofid/ofac228. Free full-text article
9 Ayoubkhani D, et al. Trajectory of long covid symptoms after covid-19 vaccination: community based cohort study. BMJ. 2022. May 18;377:e069676. Free full-text article
10 10 Ayoubkhani D, et al. Risk of Long Covid in people infected with SARS-CoV-2 after two doses of a COVID-19 vaccine: community-based, matched cohort study. Open Forum Infect Dis. 2022 Sep 12. ofac464. Free full-text article
Reported frequencies of sx:1-10 - Post-exertional malaise: 89%
- Fatigue/asthenia: 7%-72%
- Pain/discomfort: 19%-66%
- Impaired function/mobility/physical dysfxn: 6%-50%
- Weakness: 12%-41%
- Sweating: 17%-24%
- Weight loss: 14%-21%
- Sicca sx: 17%
- Fever: 0%-20%
- Dizziness: 3%-14%
- Swelling/limb edema: 3%-15%
- Lack of appetite: 4%-8%
- Weight gain: 7%
- Chills: 5%-6%
- Flushing: 5%
- Lymphadenopathy: <1%-8%
Footnotes 1 Cabrera Martimbianco AL, et al. Frequency, signs and symptoms, and criteria adopted for long COVID-19: A systematic review. Int J Clin Pract. 2021;75(10):e14357. Free full-text
2 Han Q, et al. Long-Term Sequelae of COVID-19: A Systematic Review and Meta-Analysis of One-Year Follow-Up Studies on Post-COVID Symptoms. Pathogens. 2022. Feb 19;11(2):269. Free full-text
3 Michelen M, et al. Characterising long COVID: a living systematic review. BMJ Glob Health. 2021. Sep;6(9):e005427. Free full-text
4 Wang L, et al. PASCLex: A comprehensive post-acute sequelae of COVID-19 (PASC) symptom lexicon derived from electronic health record clinical notes. J Biomed Inform. 2022. Jan;125:103951. Free full-text
5 Davis HE, et al. Characterizing long COVID in an international cohort: 7 months of symptoms and their impact. EClinicalMedicine. 2021. Aug;38:101019. Free full-text
6 Zhang X, et al. Symptoms and Health Outcomes Among Survivors of COVID-19 Infection 1 Year After Discharge From Hospitals in Wuhan, China. JAMA Netw Open. 2021. Sep 1;4(9):e2127403. Free full-text
7 Carfì A, et al. Persistent Symptoms in Patients After Acute COVID-19. JAMA. 2020. Aug 11;324(6):603-605. Free full-text
8 Ursini F, et al. Fibromyalgia: a new facet of the post-COVID-19 syndrome spectrum? Results from a web-based survey. RMD Open. 2021. Aug;7(3):e001735. Free full-text
9 Halpin SJ, et al. Postdischarge symptoms and rehabilitation needs in survivors of COVID-19 infection: A cross-sectional evaluation. J Med Virol. 2021. Feb;93(2):1013-1022. Free full-text
10 Chen C, et al. Global Prevalence of Post COVID-19 Condition or Long COVID: A Meta-Analysis and Systematic Review. J Infect Dis. 2022. Apr 16:jiac136. Free full-text
Reported frequencies of sx:1-9 - Chest pain/tightness: 0.4%-89%
- Dyspnea/SOB: 6%-66%
- Cough: 2%-59%
- Wheezing: 12%
- Sleep apnea: 5.4%
- Sputum production: 2%-7%
- Hemoptysis: 0.2%
Footnotes 1 Cabrera Martimbianco AL, et al. Frequency, signs and symptoms, and criteria adopted for long COVID-19: A systematic review. Int J Clin Pract. 2021;75(10):e14357. Free full-text
2 Han Q, et al. Long-Term Sequelae of COVID-19: A Systematic Review and Meta-Analysis of One-Year Follow-Up Studies on Post-COVID Symptoms. Pathogens. 2022. Feb 19;11(2):269. Free full-text
3 Michelen M, et al. Characterising long COVID: a living systematic review. BMJ Glob Health. 2021. Sep;6(9):e005427. Free full-text
4 Wang L, et al. PASCLex: A comprehensive post-acute sequelae of COVID-19 (PASC) symptom lexicon derived from electronic health record clinical notes. J Biomed Inform. 2022. Jan;125:103951. Free full-text
5 Davis HE, et al. Characterizing long COVID in an international cohort: 7 months of symptoms and their impact. EClinicalMedicine. 2021. Aug;38:101019. Free full-text
6 Zhang X, et al. Symptoms and Health Outcomes Among Survivors of COVID-19 Infection 1 Year After Discharge From Hospitals in Wuhan, China. JAMA Netw Open. 2021. Sep 1;4(9):e2127403. Free full-text
7 Carfì A, et al. Persistent Symptoms in Patients After Acute COVID-19. JAMA. 2020. Aug 11;324(6):603-605. Free full-text
8 Ursini F, et al. Fibromyalgia: a new facet of the post-COVID-19 syndrome spectrum? Results from a web-based survey. RMD Open. 2021. Aug;7(3):e001735. Free full-text
9 Halpin SJ, et al. Postdischarge symptoms and rehabilitation needs in survivors of COVID-19 infection: A cross-sectional evaluation. J Med Virol. 2021. Feb;93(2):1013-1022. Free full-text
Reported frequencies of sx:1-9 - Chest pain/tightness: 0.4%-89%
- Palpitations/tachy: 5%-62%
- Dizziness: 3%-14%
- New HTN: 1.3%
Footnotes 1 Cabrera Martimbianco AL, et al. Frequency, signs and symptoms, and criteria adopted for long COVID-19: A systematic review. Int J Clin Pract. 2021;75(10):e14357. Free full-text
2 Han Q, et al. Long-Term Sequelae of COVID-19: A Systematic Review and Meta-Analysis of One-Year Follow-Up Studies on Post-COVID Symptoms. Pathogens. 2022. Feb 19;11(2):269. Free full-text
3 Michelen M, et al. Characterising long COVID: a living systematic review. BMJ Glob Health. 2021. Sep;6(9):e005427. Free full-text
4 Wang L, et al. PASCLex: A comprehensive post-acute sequelae of COVID-19 (PASC) symptom lexicon derived from electronic health record clinical notes. J Biomed Inform. 2022. Jan;125:103951. Free full-text
5 Davis HE, et al. Characterizing long COVID in an international cohort: 7 months of symptoms and their impact. EClinicalMedicine. 2021. Aug;38:101019. Free full-text
6 Zhang X, et al. Symptoms and Health Outcomes Among Survivors of COVID-19 Infection 1 Year After Discharge From Hospitals in Wuhan, China. JAMA Netw Open. 2021. Sep 1;4(9):e2127403. Free full-text
7 Carfì A, et al. Persistent Symptoms in Patients After Acute COVID-19. JAMA. 2020. Aug 11;324(6):603-605. Free full-text
8 Ursini F, et al. Fibromyalgia: a new facet of the post-COVID-19 syndrome spectrum? Results from a web-based survey. RMD Open. 2021. Aug;7(3):e001735. Free full-text
9 Halpin SJ, et al. Postdischarge symptoms and rehabilitation needs in survivors of COVID-19 infection: A cross-sectional evaluation. J Med Virol. 2021. Feb;93(2):1013-1022. Free full-text
Reported frequencies of sx:1-10 - Altered cognition/memory impairment/difficulty concentrating (brain fog): 9%-57%
- Headache: 2%-39%
- Insomnia/sleep disturbance: 11%-53%
- Abnl reflexes: 23%
- Frontal release signs: 15%
- Extremity pain: 11%
- Paresthesia: 9%-11%
- Sensitivity disorder: 7.5%-11%
- Dizziness: 3%-14%
- Swallowing problem: 8%
- Muscle atrophy: 7%
- Limb numbness: 6.6%
- Communication difficulty: 6%
- Vision change: 6%
- Bradykinesia: 5%
- Gait abnormality: 4.2%-5.9%
- Confusion: 3%-5.4%
- Abnormal muscle tone: 4.4%
- Trigeminal neuralgia: 3%
- Tremor: 1.6%-3.5%
- Speech difficulty/dysarthria: 2.22%
- Lack of coordination/dysmetria: 1.5%
- Seizure/cramps: 1.33%
Footnotes 1 Cabrera Martimbianco AL, et al. Frequency, signs and symptoms, and criteria adopted for long COVID-19: A systematic review. Int J Clin Pract. 2021;75(10):e14357. Free full-text
2 Han Q, et al. Long-Term Sequelae of COVID-19: A Systematic Review and Meta-Analysis of One-Year Follow-Up Studies on Post-COVID Symptoms. Pathogens. 2022. Feb 19;11(2):269. Free full-text
3 Michelen M, et al. Characterising long COVID: a living systematic review. BMJ Glob Health. 2021. Sep;6(9):e005427. Free full-text
4 Wang L, et al. PASCLex: A comprehensive post-acute sequelae of COVID-19 (PASC) symptom lexicon derived from electronic health record clinical notes. J Biomed Inform. 2022. Jan;125:103951. Free full-text
5 Davis HE, et al. Characterizing long COVID in an international cohort: 7 months of symptoms and their impact. EClinicalMedicine. 2021. Aug;38:101019. Free full-text
6 Zhang X, et al. Symptoms and Health Outcomes Among Survivors of COVID-19 Infection 1 Year After Discharge From Hospitals in Wuhan, China. JAMA Netw Open. 2021. Sep 1;4(9):e2127403. Free full-text
7 Carfì A, et al. Persistent Symptoms in Patients After Acute COVID-19. JAMA. 2020. Aug 11;324(6):603-605. Free full-text
8 Ursini F, et al. Fibromyalgia: a new facet of the post-COVID-19 syndrome spectrum? Results from a web-based survey. RMD Open. 2021. Aug;7(3):e001735. Free full-text
9 Halpin SJ, et al. Postdischarge symptoms and rehabilitation needs in survivors of COVID-19 infection: A cross-sectional evaluation. J Med Virol. 2021. Feb;93(2):1013-1022. Free full-text
10 Chen C, et al. Global Prevalence of Post COVID-19 Condition or Long COVID: A Meta-Analysis and Systematic Review. J Infect Dis. 2022. Apr 16:jiac136. Free full-text
Reported frequencies of sx:1-9 - Insomnia/sleep disturbance: 11%-53%
- PTSD: 5.8%-57%
- Stress: 15%
- Depression/anxiety: 3%-25%
- Care dependency: 6%
- Low mood/dysphoria: 2%
Footnotes 1 Cabrera Martimbianco AL, et al. Frequency, signs and symptoms, and criteria adopted for long COVID-19: A systematic review. Int J Clin Pract. 2021;75(10):e14357. Free full-text
2 Han Q, et al. Long-Term Sequelae of COVID-19: A Systematic Review and Meta-Analysis of One-Year Follow-Up Studies on Post-COVID Symptoms. Pathogens. 2022. Feb 19;11(2):269. Free full-text
3 Michelen M, et al. Characterising long COVID: a living systematic review. BMJ Glob Health. 2021. Sep;6(9):e005427. Free full-text
4 Wang L, et al. PASCLex: A comprehensive post-acute sequelae of COVID-19 (PASC) symptom lexicon derived from electronic health record clinical notes. J Biomed Inform. 2022. Jan;125:103951. Free full-text
5 Davis HE, et al. Characterizing long COVID in an international cohort: 7 months of symptoms and their impact. EClinicalMedicine. 2021. Aug;38:101019. Free full-text
6 Zhang X, et al. Symptoms and Health Outcomes Among Survivors of COVID-19 Infection 1 Year After Discharge From Hospitals in Wuhan, China. JAMA Netw Open. 2021. Sep 1;4(9):e2127403. Free full-text
7 Carfì A, et al. Persistent Symptoms in Patients After Acute COVID-19. JAMA. 2020. Aug 11;324(6):603-605. Free full-text
8 Ursini F, et al. Fibromyalgia: a new facet of the post-COVID-19 syndrome spectrum? Results from a web-based survey. RMD Open. 2021. Aug;7(3):e001735. Free full-text
9 Halpin SJ, et al. Postdischarge symptoms and rehabilitation needs in survivors of COVID-19 infection: A cross-sectional evaluation. J Med Virol. 2021. Feb;93(2):1013-1022. Free full-text
Reported frequencies of sx:1-9 - Red eyes: 14%
- Anosmia/dysgeusia: 0%-22%
- Laryngeal sensitivity: 12%-25%
- Voice change: 8%-20%
- Rhinitis/nasal congestion: 5%-17%
- Vision changes: 1.6%-25%
- Vertigo: 2.6%-14%
- Dysphagia: 2%-12.5%
- Sore throat: 2%-11%
- Sputum production: 2%-7%
- Hearing loss: 1.1%-5.2%
- Conjunctivitis: 2%
Footnotes 1 Cabrera Martimbianco AL, et al. Frequency, signs and symptoms, and criteria adopted for long COVID-19: A systematic review. Int J Clin Pract. 2021;75(10):e14357. Free full-text
2 Han Q, et al. Long-Term Sequelae of COVID-19: A Systematic Review and Meta-Analysis of One-Year Follow-Up Studies on Post-COVID Symptoms. Pathogens. 2022. Feb 19;11(2):269. Free full-text
3 Michelen M, et al. Characterising long COVID: a living systematic review. BMJ Glob Health. 2021. Sep;6(9):e005427. Free full-text
4 Wang L, et al. PASCLex: A comprehensive post-acute sequelae of COVID-19 (PASC) symptom lexicon derived from electronic health record clinical notes. J Biomed Inform. 2022. Jan;125:103951. Free full-text
5 Davis HE, et al. Characterizing long COVID in an international cohort: 7 months of symptoms and their impact. EClinicalMedicine. 2021. Aug;38:101019. Free full-text
6 Zhang X, et al. Symptoms and Health Outcomes Among Survivors of COVID-19 Infection 1 Year After Discharge From Hospitals in Wuhan, China. JAMA Netw Open. 2021. Sep 1;4(9):e2127403. Free full-text
7 Carfì A, et al. Persistent Symptoms in Patients After Acute COVID-19. JAMA. 2020. Aug 11;324(6):603-605. Free full-text
8 Ursini F, et al. Fibromyalgia: a new facet of the post-COVID-19 syndrome spectrum? Results from a web-based survey. RMD Open. 2021. Aug;7(3):e001735. Free full-text
9 Halpin SJ, et al. Postdischarge symptoms and rehabilitation needs in survivors of COVID-19 infection: A cross-sectional evaluation. J Med Virol. 2021. Feb;93(2):1013-1022. Free full-text
Reported frequencies of sx:1-9 - Arthralgia: 6%-55%
- Fibromyalgia: 30%
- Myalgia: 2%-51%
- Back pain: 4%-17%
- Muscle atrophy: 7%
- Abnl muscle tone: 4.4%
Footnotes 1 Cabrera Martimbianco AL, et al. Frequency, signs and symptoms, and criteria adopted for long COVID-19: A systematic review. Int J Clin Pract. 2021;75(10):e14357. Free full-text
2 Han Q, et al. Long-Term Sequelae of COVID-19: A Systematic Review and Meta-Analysis of One-Year Follow-Up Studies on Post-COVID Symptoms. Pathogens. 2022. Feb 19;11(2):269. Free full-text
3 Michelen M, et al. Characterising long COVID: a living systematic review. BMJ Glob Health. 2021. Sep;6(9):e005427. Free full-text
4 Wang L, et al. PASCLex: A comprehensive post-acute sequelae of COVID-19 (PASC) symptom lexicon derived from electronic health record clinical notes. J Biomed Inform. 2022. Jan;125:103951. Free full-text
5 Davis HE, et al. Characterizing long COVID in an international cohort: 7 months of symptoms and their impact. EClinicalMedicine. 2021. Aug;38:101019. Free full-text
6 Zhang X, et al. Symptoms and Health Outcomes Among Survivors of COVID-19 Infection 1 Year After Discharge From Hospitals in Wuhan, China. JAMA Netw Open. 2021. Sep 1;4(9):e2127403. Free full-text
7 Carfì A, et al. Persistent Symptoms in Patients After Acute COVID-19. JAMA. 2020. Aug 11;324(6):603-605. Free full-text
8 Ursini F, et al. Fibromyalgia: a new facet of the post-COVID-19 syndrome spectrum? Results from a web-based survey. RMD Open. 2021. Aug;7(3):e001735. Free full-text
9 Halpin SJ, et al. Postdischarge symptoms and rehabilitation needs in survivors of COVID-19 infection: A cross-sectional evaluation. J Med Virol. 2021. Feb;93(2):1013-1022. Free full-text
Reported frequencies of sx:1-9 - Alopecia: 7%-29%
- Skin rash/lesion (eg, urticaria)/cutaneous signs: 1.5%-20%
- Itching: 9.4%
- Erythema: 9.2%
- Pernio: 7%
Footnotes 1 Cabrera Martimbianco AL, et al. Frequency, signs and symptoms, and criteria adopted for long COVID-19: A systematic review. Int J Clin Pract. 2021;75(10):e14357. doi:10.1111/ijcp.14357. Epub 2021 Jun 2. PMID: 33977626; PMCID: PMC8236920. Free full-text
2 Han Q, et al. Long-Term Sequelae of COVID-19: A Systematic Review and Meta-Analysis of One-Year Follow-Up Studies on Post-COVID Symptoms. Pathogens. 2022 Feb 19;11(2):269. doi: 10.3390/pathogens11020269. PMID: 35215212; PMCID: PMC8875269. Free full-text
3 Michelen M, et al. Characterising long COVID: a living systematic review. BMJ Glob Health. 2021 Sep;6(9):e005427. doi: 10.1136/bmjgh-2021-005427. PMID: 34580069; PMCID: PMC8478580. Free full-text
4 Wang L, et al. PASCLex: A comprehensive post-acute sequelae of COVID-19 (PASC) symptom lexicon derived from electronic health record clinical notes. J Biomed Inform. 2022 Jan;125:103951. doi: 10.1016/j.jbi.2021.103951. Epub 2021 Nov 13. PMID: 34785382; PMCID: PMC8590503. Free full-text
5 Davis HE, et al. Characterizing long COVID in an international cohort: 7 months of symptoms and their impact. EClinicalMedicine. 2021 Aug;38:101019. doi: 10.1016/j.eclinm.2021.101019. Epub 2021 Jul 15. PMID: 34308300; PMCID: PMC8280690. Free full-text
6 Zhang X, et al. Symptoms and Health Outcomes Among Survivors of COVID-19 Infection 1 Year After Discharge From Hospitals in Wuhan, China. JAMA Netw Open. 2021 Sep 1;4(9):e2127403. doi: 10.1001/jamanetworkopen.2021.27403. PMID: 34586367; PMCID: PMC8482055. Free full-text
7 Carfì A, et al. Persistent Symptoms in Patients After Acute COVID-19. JAMA. 2020 Aug 11;324(6):603-605. doi: 10.1001/jama.2020.12603. PMID: 32644129; PMCID: PMC7349096. Free full-text
8 Ursini F, et al. Fibromyalgia: a new facet of the post-COVID-19 syndrome spectrum? Results from a web-based survey. RMD Open. 2021 Aug;7(3):e001735. doi: 10.1136/rmdopen-2021-001735. PMID: 34426540; PMCID: PMC8384499. Free full-text
9 Halpin SJ, et al. Postdischarge symptoms and rehabilitation needs in survivors of COVID-19 infection: A cross-sectional evaluation. J Med Virol. 2021 Feb;93(2):1013-1022. doi: 10.1002/jmv.26368. Epub 2020 Aug 17. PMID: 32729939. Free full-text
Reported frequencies of sx:1-11 - Acid reflux: 18%-19%
- N/V: 1.3%-33%
- Lack of appetite: 5%-28%
- Diarrhea: 3%-15%
- Constipation: 12%
- Belching: 10%
- Abdo pain/distention: 2%-14%
- Fecal incontinence: 3%
- Bloody stool: 2%
Footnotes 1 Cabrera Martimbianco AL, et al. Frequency, signs and symptoms, and criteria adopted for long COVID-19: A systematic review. Int J Clin Pract. 2021;75(10):e14357. doi:10.1111/ijcp.14357. Epub 2021 Jun 2. PMID: 33977626; PMCID: PMC8236920. Free full-text
2 Han Q, et al. Long-Term Sequelae of COVID-19: A Systematic Review and Meta-Analysis of One-Year Follow-Up Studies on Post-COVID Symptoms. Pathogens. 2022 Feb 19;11(2):269. doi: 10.3390/pathogens11020269. PMID: 35215212; PMCID: PMC8875269. Free full-text
3 Michelen M, et al. Characterising long COVID: a living systematic review. BMJ Glob Health. 2021 Sep;6(9):e005427. doi: 10.1136/bmjgh-2021-005427. PMID: 34580069; PMCID: PMC8478580. Free full-text
4 Wang L, et al. PASCLex: A comprehensive post-acute sequelae of COVID-19 (PASC) symptom lexicon derived from electronic health record clinical notes. J Biomed Inform. 2022 Jan;125:103951. doi: 10.1016/j.jbi.2021.103951. Epub 2021 Nov 13. PMID: 34785382; PMCID: PMC8590503. Free full-text
5 Davis HE, et al. Characterizing long COVID in an international cohort: 7 months of symptoms and their impact. EClinicalMedicine. 2021 Aug;38:101019. doi: 10.1016/j.eclinm.2021.101019. Epub 2021 Jul 15. PMID: 34308300; PMCID: PMC8280690. Free full-text
6 Zhang X, et al. Symptoms and Health Outcomes Among Survivors of COVID-19 Infection 1 Year After Discharge From Hospitals in Wuhan, China. JAMA Netw Open. 2021 Sep 1;4(9):e2127403. doi: 10.1001/jamanetworkopen.2021.27403. PMID: 34586367; PMCID: PMC8482055. Free full-text
7 Carfì A, et al. Persistent Symptoms in Patients After Acute COVID-19. JAMA. 2020 Aug 11;324(6):603-605. doi: 10.1001/jama.2020.12603. PMID: 32644129; PMCID: PMC7349096. Free full-text
8 Ursini F, et al. Fibromyalgia: a new facet of the post-COVID-19 syndrome spectrum? Results from a web-based survey. RMD Open. 2021 Aug;7(3):e001735. doi: 10.1136/rmdopen-2021-001735. PMID: 34426540; PMCID: PMC8384499. Free full-text
9 Halpin SJ, et al. Postdischarge symptoms and rehabilitation needs in survivors of COVID-19 infection: A cross-sectional evaluation. J Med Virol. 2021 Feb;93(2):1013-1022. doi: 10.1002/jmv.26368. Epub 2020 Aug 17. PMID: 32729939. Free full-text
10 Weng J, et al. Gastrointestinal sequelae 90 days after discharge for COVID-19. Lancet Gastroenterol Hepatol. 2021 May;6(5):344-346. doi: 10.1016/S2468-1253(21)00076-5. Epub 2021 Mar 10. PMID: 33711290; PMCID: PMC7943402. Free full-text
11 Chen C, et al. Global Prevalence of Post COVID-19 Condition or Long COVID: A Meta-Analysis and Systematic Review. J Infect Dis. 2022 Apr 16:jiac136. doi: 10.1093/infdis/jiac136. Epub ahead of print. PMID: 35429399. Free full-text
Other (GU, renal, hematologic, etc) Reported frequencies of sx:1-10 - Menstrual irregularity: 25%-28%
- Urinary incontinence: 6%-12.5%
- Bleeding: 15%
- LUTS: 9%
Footnotes 1 Cabrera Martimbianco AL, et al. Frequency, signs and symptoms, and criteria adopted for long COVID-19: A systematic review. Int J Clin Pract. 2021;75(10):e14357. doi:10.1111/ijcp.14357. Epub 2021 Jun 2. PMID: 33977626; PMCID: PMC8236920. Free full-text
2 Han Q, et al. Long-Term Sequelae of COVID-19: A Systematic Review and Meta-Analysis of One-Year Follow-Up Studies on Post-COVID Symptoms. Pathogens. 2022 Feb 19;11(2):269. doi: 10.3390/pathogens11020269. PMID: 35215212; PMCID: PMC8875269. Free full-text
3 Michelen M, et al. Characterising long COVID: a living systematic review. BMJ Glob Health. 2021 Sep;6(9):e005427. doi: 10.1136/bmjgh-2021-005427. PMID: 34580069; PMCID: PMC8478580. Free full-text
4 Wang L, et al. PASCLex: A comprehensive post-acute sequelae of COVID-19 (PASC) symptom lexicon derived from electronic health record clinical notes. J Biomed Inform. 2022 Jan;125:103951. doi: 10.1016/j.jbi.2021.103951. Epub 2021 Nov 13. PMID: 34785382; PMCID: PMC8590503. Free full-text
5 Davis HE, et al. Characterizing long COVID in an international cohort: 7 months of symptoms and their impact. EClinicalMedicine. 2021 Aug;38:101019. doi: 10.1016/j.eclinm.2021.101019. Epub 2021 Jul 15. PMID: 34308300; PMCID: PMC8280690. Free full-text
6 Zhang X, et al. Symptoms and Health Outcomes Among Survivors of COVID-19 Infection 1 Year After Discharge From Hospitals in Wuhan, China. JAMA Netw Open. 2021 Sep 1;4(9):e2127403. doi: 10.1001/jamanetworkopen.2021.27403. PMID: 34586367; PMCID: PMC8482055. Free full-text
7 Carfì A, et al. Persistent Symptoms in Patients After Acute COVID-19. JAMA. 2020 Aug 11;324(6):603-605. doi: 10.1001/jama.2020.12603. PMID: 32644129; PMCID: PMC7349096. Free full-text
8 Ursini F, et al. Fibromyalgia: a new facet of the post-COVID-19 syndrome spectrum? Results from a web-based survey. RMD Open. 2021 Aug;7(3):e001735. doi: 10.1136/rmdopen-2021-001735. PMID: 34426540; PMCID: PMC8384499. Free full-text
9 Halpin SJ, et al. Postdischarge symptoms and rehabilitation needs in survivors of COVID-19 infection: A cross-sectional evaluation. J Med Virol. 2021 Feb;93(2):1013-1022. doi: 10.1002/jmv.26368. Epub 2020 Aug 17. PMID: 32729939. Free full-text
10 Li K, et al. Analysis of sex hormones and menstruation in COVID-19 women of child-bearing age. Reprod Biomed Online. 2021 Jan;42(1):260-267. doi: 10.1016/j.rbmo.2020.09.020. Epub 2020 Sep 29. PMID: 33288478; PMCID: PMC7522626. Free full-text
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Constitutional (fatigue, postural weakness/lightheadedness, etc) Post-COVID fatigue etiology unknown, likely multifactorial; sx may include postexertional malaise similar to post-viral ME/CFS.1,2 (+)COVID test/serology not required to eval/manage sx; lack of abnl labs/imaging doesn’t invalidate sx. Consider return-to-activity program simultaneous w/ eval3 Eval: Consider primary fatigue causes & contributing factors based on hx/signs/sx. 4-12wk out: Explore differential, conservative investigations,3 eg, related to sleep, nutrition, cardiac, respiratory, infxn, autoimmune/inflammatory, psychiatric, malignancy, drug rxn, metabolic, post-ICU syndrome,1 anemia; >12wk: Pursue additional tests3 - Sx timeline. Fatigue common w/ other acute COVID sx; eval further if fatigue severe or affects QoL ≥4wk from onset. Assess whether worse after physical/mental exertion or upon standing; sleep non-refreshing;1 assoc w/ dyspnea, pain, lightheadedness;4 compare w/ pre-COVID functional status1
- PMHx. ✓pre-COVID fatigue, med review;1 COVID pneumonia/hospitalization (post-ICU syndrome),3,5 recent inactivity (deconditioning)5
- Exam. Targeted based on HPI. ✓T, RR, HR, BP (& orthostatic HR/BP);4 resp/CV exam, pulse ox; assess endurance, eg, 30-sec sit-to-stand, 6- or 10-min walk test, 2-min step (seated or standing),1 (✓pulse ox, HR w/ walk test4). Screen for anxiety, depression, PTSD, or other mental health dz if indicated1,3
- Labs. CBC, BMP, CRP, ESR, TSH (& free T43), CK; other tests (BNP, d-dimer) based on sx/signs/comorbidities;1 if mod/high suspicion for cardiac involvement (eg, myocarditis): ✓cTn4
- Imaging/other tests (eg, echo, ECG, CxR or CT chest, PFTs, CPET, holter, CMR): only as indicated by sx/signs/comorbidities1
Sx management - Begin individualized, structured return-to-activity program based on exercise tolerance/comorbidities.1 Be conservative & gradual w/ exercise as tolerated to avoid postexertional malaise.3 Use low-intensity physical exercises unless formal exercise eval done.6 If deconditioning or orthostatic intolerance, start w/ recumbent/semi-recumbent (swim, row, cycle) of short duration (eg, 5-10min/day) before gradual transition to upright exercise & longer durations4
- Refer to PT4 or PM&R if pt unable to start simple activities or unable to advance activities to pre-COVID level1
- Recommend adequate hydration; good nutrition, small frequent meals,1 avoid heavy meals.4 If deconditioning &/or tachycardia, exercise/orthostatic intolerance: consider table salt @ 1-2 tsp/day & 3L/day H2O or electrolyte-balanced fluid, while ensuring BP controlled; avoid dehydration via EtOH, excess caffeine, heat; consider waist-high support stockings4
- Consider whether meds are worsening fatigue. Insufficient evidence on prescription drugs or OTC vitamins/supplements for post-COVID fatigue1
- Counseling or psychiatry co-mgmt for mental health dz1
- Consider whether pts may benefit from ME/CFS sx strategies (eg, pacing activity to avoid postexertional malaise)3,7
Supportive care3 - Ensure full COVID vax; anecdotal reports suggest that some pts w/ post-COVID sx improve after vax; ongoing research needed to verify
- Monitor comorbidities that may impact sx; optimize sleep, nutrition, stress reduction
- Consider online support groups/forums
Footnotes 1 Meds that may be assoc w/ fatigue include antidepressants, anticholinergics, antihistamines, anxiolytics.
AAPM&R 2021. The American Academy of Physical Medicine and Rehabilitation. Herrera JE, et al. Multidisciplinary Collaborative Consensus Guidance Statement on the Assessment and Treatment of Fatigue in Postacute Sequelae of SARS-CoV-2 Infection (PASC) Patients. PM&R. 2021. Sept;13(9):1027-1043. Free full-text article
2 Myalgic encephalomyelitis/chronic fatigue syndrome definition:
(1) ≥6mo of impaired physical, occupational, social activity;
(2) post-exertional malaise;
(3) unrefreshing sleep;
(4) and cognitive impairment and/or orthostatic intolerance.
NIH 2015. Committee on the Diagnostic Criteria for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome; Board on the Health of Select Populations; Institute of Medicine. Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness. Washington (DC): National Academies Press (US); 2015. Feb 10. Free full-text article
3 CDC 2021. Postexertional malaise = sx worsening ~12–48h after even minor physical/mental exertion; malaise lasts for days/weeks.
Evaluating and Caring for Patients with Post-COVID Conditions: Interim Guidance. Updated 6/14/21. Accessed 3/10/22
4 ACC 2022.
• Eval suspected PASC (dyspnea, chest pain, palpitations, lightheaded, etc), based on clinical presentation, w/ ECG, cTn, echo, ambulatory rhythm monitor, CXR (+/or non-contrast CT) & PFTs. Cardiology consult for abnl results, if known CV dz, or if sx remain unexplained.
• If PFTs unrevealing: Consider CPET (cardiopulm exercise test) w/ flow-volume loop, if available.
• CMR. Use following abnl echo/cTn/ECG or if cardiopulm sx persist.
• Ischemia eval. If low risk, CAC or exercise test w/o imaging. If higher risk, CTA or stress w/ imaging (echo, PET/SPECT, CMR). Defer max-effort exercise test until myocarditis r/o w/ CMR. Reserve invasive coronary angiographic for pts w/ abnl noninvasive tests or if obstructive CAD or vasospasm very strongly suspected.
Writing Committee, Gluckman TJ, et al. 2022 ACC Expert Consensus Decision Pathway on Cardiovascular Sequelae of COVID-19 in Adults: Myocarditis and Other Myocardial Involvement, Post-Acute Sequelae of SARS-CoV-2 Infection, and Return to Play: A Report of the American College of Cardiology. J Am Coll Cardiol. 2022. Mar 14;S0735-1097(22)00306-0. Free full-text article PDF
5 Persistent cough/dyspnea common months post-d/c.
Baptista da Silva FO, et al. Post-COVID-19 Syndrome: Characterization of a Cohort and Association With Acute Disease Severity. Chest. 2021. Oct;160(4):A561. Free full-text article
6 ATS 2020. Early pulm rehab post-d/c effective for post-ARDS & post-COPD exacerbation, may apply to COVID inpts.
Jenkins A. American Thoracic Society. The Assembly on Pulmonary Rehabilitation (PR) Journal Club. Report of An Ad-Hoc International Task Force on Early and Short-term Rehabilitative Interventions (After the Acute Hospital Setting) in COVID-19 Survivors. Webinar date: 4/9/2020. Accessed 3/10/22
7 Smith ME, et al. Treatment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Systematic Review for a National Institutes of Health Pathways to Prevention Workshop. Ann Intern Med. 2015. Jun 16;162(12):841-50. Free full-text article
Postural sx: weakness, exercise intolerance, lightheadedness, etc Explore broad differential including: - myocarditis: lightheaded/syncope, palp, chest pain/tightness, SOB1
- post-viral POTS (postural orthostatic tachycardia syndrome): weakness, exercise intolerance, fatigue, lightheaded, palp, blurry vision1
- HF, dysrhythmia, deconditioning, post-ICU syndrome,1 dysautonomia,2 medication effect,3 orthostatic hypotension, volume depletion, post-corticosteroid adrenal suppression, etc
POTS diagnostic criteria1 (✓ HR, BP after 5min supine, immediately on stand, & after standing 2, 5, & 10min) - Age >19 yo. HR↑ >30 bpm in pts ≥19 yo (or >40 bpm in pts <19 yo) above supine after 10-min standing &/or HR >120 during 10-min stand test, w/o orthostatic hypotension. Tachycardia lasts >30sec & assoc w/ sx
Eval: Tailor tests per signs/sx. 4-12wk out: Explore differential, conservative investigations based on presentation.2 >12wk, pursue expanded/additional tests;2 (+)COVID test/serology not required to eval/manage sx; lack of abnl lab/imaging doesn’t invalidate sx. Consider return-to-activity program simultaneous w/ eval2 - Sx timeline: new, returning, or persistent since acute COVID.1 Assess current vs pre-COVID functional status, impact on QoL2
- PMHx: ✓hx orthostatic intolerance, review meds,3 ✓hx COVID pneumonia/hospitalization (eg, post-ICU syndrome), inactivity (deconditioning)1
- Exam: ✓T, RR, HR, BP, cardiac & pulm exam; pulse ox;2 10-min stand test (HR, BP after 5min supine, immediately on standing, then 2, 5, 10min); 6-min walk test w/ pulse ox, HR1
- Labs: CBC, BMP, cTn, CRP +/- additional tests (eg, d-dimer, BNP/N-terminal pro-BNP, TSH & free T42), etc, based on clinical presentation1
- Other tests/imaging based on clinical presentation: ECG, echo, ambulatory rhythm monitor, CXR (&/or chest CT), PFTs. Ischemia eval based on risk level1
- Refer to cardiology if abnl cardiac test results, known CV dz w/ new or worsening s/sx, documented cardiac complications during acute infxn, or persistent &/or concerning CV/pulm sx1
Sx management: - Begin individualized, structured return-to-activity program based on identified condition(s), exercise tolerance/comorbidities.1 Refer to PT or PM&R if unable to start simple activities or advance activities to pre-COVID levels; be conservative & gradual w/ exercise as tolerated to avoid postexertional malaise;2 use low-intensity physical exercises unless formal exercise eval done.4 PT or multi-disciplinary team may be required for reconditioning1
- Exercise for pts w/ deconditioning, POTS, or PASC w/ tachycardia, exercise/orthostatic intolerance: recumbent/semi-recumbent exercise (eg, row, swim, cycle) w/ transition to upright as orthostatic intolerance improves. Limit exercise to 5-10min/day initially, gradually increase as tolerated1
- Sx relief for deconditioning (which is assoc w/ plasma volume reduction), POTS, &/or exercise/orthostatic intolerance: Consider table salt @ 1-2 tsp/day & 3L/day H2O or electrolyte-balanced fluid, while ensuring BP controlled; avoid dehydration via EtOH, excess caffeine, heat; consider waist-high support stockings; avoid heavy meals. Consider empiric drug options:1
- low-dose beta-blocker or non-dihydropyridine CCB: titrated gradually to slow HR; nonselective BBs may help control sx of orthostatic intolerance; consider propranolol for pts w/ coexisting anxiety or migraine
- ivabradine can benefit pts w/ severe fatigue exacerbated by BBs or CCBs, may improve POTS
- fludrocortisone (up to 0.2 mg at HS) may be used w/ salt loading to increase blood volume; monitor for hypokalemia
- midodrine (2.5-10 mg) can help w/ orthostatic hypotension; 1st dose taken in am before rising, last dose no later than 4 pm
Supportive care:2 - Ensure full COVID vax; anecdotal reports suggest that some pts w/ post-COVID sx improve after vax; ongoing research needed to verify
- Monitor comorbidities that may impact sx; optimize sleep, nutrition, stress reduction
- Consider online support groups/forums
Footnotes 1 ACC 2022.
Eval for suspected PASC sx (dyspnea, chest pain, palpitations, lightheaded, etc):
• Initial eval based on clinical presentation, w/ ECG, cTn, echo, ambulatory rhythm monitor, CXR (+/or non-contrast CT) & PFTs. Cardiology consult for abnl results, if known CV dz, or if sx remain unexplained.
• If PFTs unrevealing: Consider CPET (cardiopulm exercise test) w/ flow-volume loop, if available.
• CMR. Use following abnl echo/cTn/ECG or if cardiopulm sx persist.
• Ischemia eval. If low risk, CAC or exercise test w/o imaging. If higher risk, CTA or stress w/ imaging (echo, PET/SPECT, CMR). Defer max-effort exercise test until myocarditis r/o w/ CMR. Reserve invasive coronary angiographic for pts w/ abnl noninvasive tests or if obstructive CAD or vasospasm very strongly suspected.
Writing Committee, Gluckman TJ, et al. 2022 ACC Expert Consensus Decision Pathway on Cardiovascular Sequelae of COVID-19 in Adults: Myocarditis and Other Myocardial Involvement, Post-Acute Sequelae of SARS-CoV-2 Infection, and Return to Play: A Report of the American College of Cardiology. J Am Coll Cardiol. 2022. Mar 14;S0735-1097(22)00306-0. Free full-text article PDF
2 CDC 2021. Postexertional malaise = sx worsening ~12–48h after even minor physical/mental exertion; malaise lasts for days/weeks.
Evaluating and Caring for Patients with Post-COVID Conditions: Interim Guidance. Updated 6/14/21. Accessed 3/10/22
3 Meds that may be assoc w/ fatigue include antidepressants, anticholinergics, antihistamines, anxiolytics.
AAPM&R 2021. The American Academy of Physical Medicine and Rehabilitation. Herrera JE, et al. Multidisciplinary Collaborative Consensus Guidance Statement on the Assessment and Treatment of Fatigue in Postacute Sequelae of SARS-CoV-2 Infection (PASC) Patients. PM&R. 2021. Sept;13(9):1027-1043. Free full-text article
4 ATS 2020. Early pulm rehab post-d/c effective for post-ARDS & post-COPD exacerbation, may apply to COVID inpts.
Jenkins A. American Thoracic Society. The Assembly on Pulmonary Rehabilitation (PR) Journal Club. Report of An Ad-Hoc International Task Force on Early and Short-term Rehabilitative Interventions (After the Acute Hospital Setting) in COVID-19 Survivors. Webinar date: 4/9/2020. Accessed 3/10/22
Pulmonary (dyspnea/SOB, cough, chest wall pain) Dyspnea/SOB/↑work of breathing Etiology heterogenous, consider CV cause (myocarditis, PE)1 anemia, drug effect,2 etc (+)COVID test/serology not required to eval/manage sx; lack of abnl labs/imaging doesn’t invalidate sx. Consider rehab plan simultaneous w/ testing1
Eval: If signs/sx of acute/life-threatening dz (related to COVID or not, eg, myocarditis, MI, pericarditis, PE), don’t delay testing.1 Otherwise, 4-12wk out: Explore differential, conservative investigations; >12wk: Pursue additional tests1,3 - Sx timeline of rest/exertion dyspnea, orthopnea relative to any other COVID sx. If new/worsening, consider COVID reinfxn1 (highly unlikely <3mo after resolution)3 or bacterial/viral superinfxn. Assess current vs pre-COVID functional status; consider mMRC1,2 or modified Borg2 dyspnea scales
- PMHx. Smoking, asthma, COPD, chronic bronchitis, interstitial lung dz, CV dz, etc;1 anemia,2 medication effects,2 COVID pneumonia/hospitalization4-6 (eg, post-ICU syndrome, tracheal stenosis s/p intubation)
- Exam. ✓T, RR, HR, BP (incl orthostatic7); resp/CV exam, pulse ox, consider 6-min walk test, 2-min step, 1-min sit-to-stand;1 ✓pulse ox (may be falsely higher in pts w/ darker skin pigmentation2), HR while walking2,7
- Labs. CDC’s basic post-COVID sx labs: CBC, BMP, UA, LFTs (or CMP), CRP, ESR, Ferritin, TSH & free T4, vit D & B12; d-dimer if PE suspected; BNP if HF suspected.1 If mod/high suspicion for cardiac involvement (eg, myocarditis), ✓cTn7
- PFTs. ✓PFTs;7-9 consider full PFTs in adults for breathing discomfort not improving ≥8wk post-acute COVID or if new/worsening sx.2 If PFTs unrevealing, consider CPET;7 cardiac stress test or CPET not routine for isolated post-COVID breathing discomfort, but consider in light of CV signs/sx/rehab plans2
- Imaging. ✓CXR3 +/or non-contrast CT;7 CXR2 appropriate for most pts, including those w/ abnl PFTs/pulm exam, unexplained sx, etc.2 If mod/high suspicion for cardiac involvement (eg, myocarditis), ✓ echo (+ cTn, ECG) then CMR; if PE suspected, V/Q7 or CTPA;9 if interstitial lung dz suspected, ✓ noncontrast2 HRCT;9 ischemia eval depends on CV risk7 level
- Refer pts w/ hypoxemia/severe lung dz signs3 or abnl CV findings.7 Pulm referral for new/progressive abnormalities or abnl PFTs/imaging/exam/sats, etc. ENT referral for stridor/voice changes, etc, esp if hx ET intubation/trach2
Sx management - Drugs (eg, oral/inhaled steroid, bronchodilator inhalers) aren’t routinely recommended absent impaired pulm fxn, though inhaled therapies might be trialed under close supervision for response, side effects, etc2
- O2 to maintain sat >90% for pts w/ PaO2 ≤55 mmHg or sat ≤88% @rest on room air, or if other criteria2 met
- Pulm rehab. Comprehensive rehab plan may include PT/OT; be conservative & gradual w/ exercise as tolerated to avoid postexertional malaise,1 esp if concomitant fatigue or dysautonomia.2 Use low-intensity physical exercises if formal exercise eval not done.9 If deconditioning or orthostatic intolerance, start w/ recumbent/semi-recumbent (swim, row, cycle) of short duration (eg, 5-10min/day) before gradual transition to upright exercise & longer durations.7 Consider virtual rehab10
- Breathing exercises2 (breath control11/diaphragmatic breathing7) may improve sx1,3
- Daily home oximetry may be used, if pt able to use effectively3
- Inform pt when to seek care if signs/sx worsen, consider sx diary1
Supportive care1 - Ensure full COVID vax; anecdotal reports suggest that some pts w/ post-COVID sx improve after vax; ongoing research needed to verify
- Monitor comorbidities that may impact sx; optimize sleep, nutrition, stress reduction
- Consider online support groups/forums
Footnotes 1 CDC 2021. Postexertional malaise = sx worsening ~12–48h after even minor physical/mental exertion; malaise lasts for days/weeks.
Evaluating and Caring for Patients with Post-COVID Conditions: Interim Guidance. Updated 6/14/21. Accessed 3/10/22
2 AAPM&R 2022. The American Academy of Physical Medicine and Rehabilitation. Maley, JH, et al. Multi-disciplinary Collaborative Consensus Guidance Statement on the Assessment and Treatment of Breathing Discomfort and Respiratory Sequelae in Patients With Post-acute Sequelae of SARS-CoV-2 Infection (PASC). PM&R. 2021. Jan;14(1):77-95. Free full-text article
Breathing exercises resources
• Stasis breathing rehab program
• Pulmonary Wellness Foundation Bootcamp
• Coronavirus Recovering Breathing Exercises (Johns Hopkins)
Criteria for O2 (pulse ox may be falsely low in pts w/ darker skin pigmentation)
• PaO 2 ≤55 mmHg or sat ≤88% @ rest on room air
• PaO 2 ≤55 mmHg or sat ≤88% w/ exercise, in pts w/ daytime rest PaO 2 ≥56 mmHg or sat ≥89%
• PaO 2 ≤55 mmHg or sat ≤88% during sleep (despite waking PaO 2 ≥56 mmHg or sat ≥89%) or greater than NL drop during sleep (PaO 2 ↓by >10 mmHg or sat ↓by >5% that is associated w/ hypoxemic signs/sx (cognitive impairment, insomnia, restlessness, etc)
• 56-59 mmHg or sat >89% who have dependent edema suggestive of CHF; evidence of pulm HTN, or cor pulmonale (PA pressure, scans, ECG, etc); or Hct >56%
Imaging. >4-6wk after viral pneumonia, imaging studies may still show residual abnormalities.
3 NICE 2021. CXR: NL plain films don’t r/o lung dz.
National Institute for Health and Care Excellence. COVID-19 Rapid Guideline: Managing the Long-term Effects of COVID-19. Published 12/18/20. Updated 11/11/21. Accessed 3/10/22
4 Table 1. The modified Medical Research Council (mMRC) scale.
Launois C, et al. The Modified Medical Research Council Scale for the Assessment of Dyspnea in Daily Living in Obesity: A Pilot Study. BMC Pulm Med. 2012. Oct 1;12:61. Free full-text article PDF at PubMed®
5 Persistent cough/dyspnea common months post-d/c.
Baptista da Silva FO, et al. Post-COVID-19 Syndrome: Characterization of a Cohort and Association With Acute Disease Severity. Chest. 2021. Oct;160(4):A561. Free full-text article
6 CDC 2021. Post-COVID Conditions: Information for Healthcare Providers. Updated 7/9/21. Accessed 3/10/22
7 ACC 2022.
• Eval suspected PASC (dyspnea, chest pain, palpitations, lightheaded, etc), based on clinical presentation, w/ ECG, cTn, echo, ambulatory rhythm monitor, CXR (+/or non-contrast CT) & PFTs. Cardiology consult for abnl results, if known CV dz, or if sx remain unexplained.
• If PFTs unrevealing: Consider CPET (cardiopulm exercise test) w/ flow-volume loop, if available.
• CMR. Use following abnl echo/cTn/ECG or if cardiopulm sx persist.
• Ischemia eval. If low risk, CAC or exercise test w/o imaging. If higher risk, CTA or stress w/ imaging (echo, PET/SPECT, CMR). Defer max-effort exercise test until myocarditis r/o w/ CMR. Reserve invasive coronary angiographic for pts w/ abnl noninvasive tests or if obstructive CAD or vasospasm very strongly suspected.
Writing Committee, Gluckman TJ, et al. 2022 ACC Expert Consensus Decision Pathway on Cardiovascular Sequelae of COVID-19 in Adults: Myocarditis and Other Myocardial Involvement, Post-Acute Sequelae of SARS-CoV-2 Infection, and Return to Play: A Report of the American College of Cardiology. J Am Coll Cardiol. 2022. Mar 14;S0735-1097(22)00306-0. Free full-text article PDF
8 PFTs. Following COVID pneumonia, lung function recovery initially rapid, but 6-mo post-d/c, recovery slows, w/ 1/3+ pts showing abnl PFTs, per a small study.
Orzes N, et al. Pulmonary Physiology. Chest Annual Meeting Abstracts. Evaluation of Lung Function After SARS-CoV-2 Pneumonia. Chest. 2021. Oct 1;160(4)S:A2157. Free full-text article
9 George PM, et al. State of the Art Review. Respiratory Follow-up of Patients With COVID-19 Pneumonia. Thorax. 2020. Nov;75(11):1009-1016. Free full-text PDF
• Hx severe COVID pneumonia (eg, ICU stay). @12wk post-d/c: ✓CXR, clinical eval. Consider full PFTs, walk test w/ O 2 sats, sputum sample, echo. If imaging/physiological assessment abnl, or evidence of pulm HTN: ✓HRCT and CTPA; consider echo if not already done. If no interstitial lung dz or pulm HTN: Consider other dx.
• Hx mild-to-mod COVID pneumonia (eg, regular hospital ward/community care). @12wk out: ✓CXR; if abnl: Order PFTs. Review PFTs & assess clinically. If suspect PE: ✓CTPA. Otherwise, if pt improving, consider repeat CXR. If repeat CXR is abnl: ✓ both HRCT and CTPA; consider walk test & echo. If no interstitial lung dz or pulm HTN: Consider other dx.
10 Rehab. Early pulm rehab post-d/c effective for post-ARDS & post-COPD exacerbation, so may apply to COVID inpts.
Jenkins A. American Thoracic Society. The Assembly on Pulmonary Rehabilitation (PR) Journal Club. Report of An Ad-Hoc International Task Force on Early and Short-term Rehabilitative Interventions (After the Acute Hospital Setting) in COVID-19 Survivors. Webinar date: 4/9/2020. Accessed 3/10/22
11 NHS 2022. National Health Service. Scottish Government. Long COVID: Breathlessness. Updated 3/9/22. Accessed 3/10/22
Consider wide differential for dry/wet cough. Evidence of (+)COVID test/serology not required to eval/manage sx. Lack of abnl labs/imaging doesn’t invalidate sx1 Eval: Tailor tests per signs/sx to r/o acute/life-threatening dz that may/may not be COVID related,2 exac of previous dz, or post-infectious cough causes. 4-12wk out: explore differential, conservative investigations1 - Sx timeline relative to any other COVID sx. If new/worsening, consider COVID reinfxn1 (highly unlikely <3mo after resolution) or superinfxn (flu, viral bronchitis, etc), or complication (PE, tracheal stenosis s/p intubation, etc). Assess impact on daily activities1
- PMHx. ✓hx smoking, allergy, pneumonia, bronchiectasis, ACEI use, etc
- Post-infectious cough may be from new-onset or acute exac of: postnasal drip/UACS, asthma (incl cough-variant), nonasthmatic eosinophilic bronchitis, chronic bronchitis, COPD, GERD.3 Eval per guideline: Cough ≥15 yo
- Exam. ✓RR, temp, chest & ENT exam, ✓pulse ox (may be falsely higher in pts w/ darker skin pigmentation), HR while walking4
- Labs. CDC’s basic post-COVID sx labs: CBC, BMP, UA, LFTs (or CMP), CRP, ESR, ferritin, TSH & free T4, vit D & B12; d-dimer if PE suspected
- PFTs. Consider full PFTs if breathing discomfort not improving ≥8wk post-acute COVID or if new/worsening sx;4 some groups recommend full PFTs (eg, @12wk5 for persistent sx)6
- Imaging. CXR appropriate for most pts, including those w/ persistent cough/abnl PFTs/pulm exam, unexplained sx, etc.4 Timing: CXR @12wk recommended by several groups5 for persistent pulm sx.2 If ongoing signs/test abnl or to F/U on abnl CXR or unexplained sx, consider noncontrast HRCT (eg, for interstitial lung dz);4,5 if concern for PE, use CTPA4
- Refer pts w/ hypoxemia/severe lung dz signs.2 Pulmonary referral for unexplained cough, new/progressive abnormalities, abnl PFTs/imaging/exam/sats, or secretion clearance issues. ENT referral for stridor/voice changes, etc, esp if hx ET intubation/trach5
Sx management - Drugs (eg, oral/inhaled steroid, bronchodilator inhalers) aren’t routinely recommended absent impaired pulm fxn;4 however, If no other cause identified despite eval, some groups suggest empiric inhaled steroids trial for persistent post-COVID cough.6 Tx other cough causes per guideline: Cough ≥15 yo
- OTC sx relief guidance differs: ACCP is against OTC antitussives, expectorants, NSAIDs, antihistamines, mucolytics, or combos.7 ACP suggests using OTC antitussives, analgesics; but notes antihistamines alone8 have more side effects than benefits
- O2 to maintain sat >90% for pts w/ PaO2 ≤55 mmHg or sat ≤88% @rest on room air, or if other criteria4 met
- Dry cough self-mgmt tips.9 Hydrate throughout day, warm drink (eg, honey10 w/ lemon). If about to cough: small sips of liquid, suck sugary sweet, or dry swallow repeatedly. If nasal congestion, blow nose rather than sniff. Avoid irritants (smoke, strong scents). Optimize comfortable sleeping position9
- Wet cough self-mgmt tips.9 Hydrate, inhale steam, lie on one side, avoid mouth breathing, slow nasal breaths when transitioning to area w/ temp difference. If difficulty clearing secretions, consider airway clearance techniques/devices4
- Inform pt when to seek care if signs/sx worsen, consider sx diary1
Supportive care1 - Ensure full COVID vax; anecdotal reports suggest that some pts w/ post-COVID sx improve after vax; ongoing research needed to verify
- Monitor comorbidities that may impact sx
- Optimize sleep, nutrition, stress reduction
- Consider online support groups/forums
Footnotes 1 CDC 2021. Evaluating and Caring for Patients with Post-COVID Conditions: Interim Guidance. Updated 6/14/21. Accessed 3/10/22
2 NICE 2021. CXR: NL plain films don’t r/o lung dz.
National Institute for Health and Care Excellence. COVID-19 Rapid Guideline: Managing the Long-term effects of COVID-19. Published 12/18/20. Updated 11/11/21. Accessed 3/10/22
3 ACCP 2006. Irwin RS, et al. Diagnosis and Management of Cough Executive Summary: ACCP Evidence-Based Clinical Practice Guidelines. Chest. 2006. Jan;129:1S-23S. Free full-text PDF
4 AAPM&R 2022. The American Academy of Physical Medicine and Rehabilitation. Maley, JH, et al. Multi-disciplinary Collaborative Consensus Guidance Statement on the Assessment and Treatment of Breathing Discomfort and Respiratory Sequelae in Patients With Post-acute Sequelae of SARS-CoV-2 Infection (PASC). PM&R. 2021. Jan;14(1):77-95. Free full-text article
Imaging. >4-6wk after viral pneumonia, imaging studies may still show residual abnormalities.
Criteria for O2 (pulse ox may be falsely low in pts w/ darker skin pigmentation)
• PaO 2 ≤55 mmHg or sat ≤88% @rest on room air
• PaO 2 ≤55 mmHg or sat ≤88% with exercise, in pts w/ daytime rest PaO 2 ≥56 mmHg or sat ≥89%
• PaO 2 ≤55 mmHg or sat ≤88% during sleep (despite waking PaO 2 ≥56 mmHg or sat ≥89%) or greater than NL drop during sleep (PaO 2 ↓by >10 mmHg or sat ↓by >5% that is associated w/ hypoxemic signs/sx (cognitive impairment, insomnia, restlessness, etc)
• 56-59 mmHg or sat >89% who have dependent edema suggestive of CHF; evidence of pulm HTN, or cor pulmonale (PA pressure, scans, ECG, etc); or Hct >56%
5 George PM, et al. State of the Art Review. Respiratory Follow-up of Patients With COVID-19 Pneumonia. Thorax. 2020. Nov;75(11):1009-1016. Free full-text PDF
• Hx severe COVID pneumonia (eg, ICU stay). @12wk post-d/c: ✓CXR, clinical eval. Consider full PFTs, walk test w/ O 2 sats, sputum sample, echo. If imaging/physiological assessment abnl, or evidence of pulm HTN: ✓HRCT and CTPA; consider echo if not already done. If no interstitial lung dz or pulm HTN, consider other dx.
• Hx mild-to-mod COVID pneumonia (eg, regular hospital ward/community care). @12wk out: ✓CXR. If abnl, order PFTs. Review PFTs & assess clinically. If suspect PE, ✓CTPA. Otherwise, if pt improving, consider repeat CXR. If repeat CXR abnl, ✓ both HRCT & CTPA; consider walk test & echo. If no interstitial lung dz or pulm HTN, consider other dx.
6 SLG/SSP 2021. SSP reached “moderate” consensus for empiric inhaled steroids for post-COVID persistent cough.
Swiss COVID Lung Study group and Swiss Society for Pulmonology. Funke-Chambour M, et al. Swiss COVID Lung Study Group. Swiss Recommendations for the Follow-Up and Treatment of Pulmonary Long COVID. Respiration. 2021;100(8):826-841. Free full-text article
7 ACCP 2017. Malesker MA, et al. Pharmacologic and Nonpharmacologic Treatment for Acute Cough Associated With the Common Cold: CHEST Expert Panel Report. Chest. 2017. Nov;152(5):1021-1037. Free full-text PDF
8 ACP/CDC 2016. OTC cough relief: Although antihistamines alone have more side effects than benefits, relief was seen in 1/4 pts on antihistamine/analgesic/decongestant combo.
Harris AM, et al. Appropriate Antibiotic Use for Acute Respiratory Tract Infection in Adults: Advice for High-Value Care From the American College of Physicians and the Centers for Disease Control and Prevention. Ann Intern Med. 2016. Mar 15;164(6):425-34. Free full-text article
9 NHS 2022. National Health Service. Scottish Government. Long COVID: Cough. Updated 3/9/22. Accessed 3/10/22
10 CDC 2021. Avoid honey in infants <1 yo (botulism risk).
Botulism. Prevention. Many Cases of Botulism Are Preventable. Updated 6/1/21. Accessed 3/10/22
Consider wide differential: CV (PE, myocarditis, pericarditis, CAD, etc), pneumonia, pleurisy, esophageal, costochondritis,1 panic, etc. (+)COVID test/serology not required to eval/manage sx; lack of abnl labs/imaging doesn’t invalidate sx2 Eval: Tailor tests per signs/sx to r/o acute or life-threatening dz that may/may not be related to COVID3 (CV, PE, pneumonia, MI, etc). 4-12wk out: Explore differential, conservative investigations - Pain location/quality/triggers; sx timeline relative to any other COVID sx (cough, SOB, etc). If new/worsening, consider COVID reinfxn2 (highly unlikely <3mo after resolution) or bacterial/viral superinfxn. Assess impact on QoL2
- PMHx. Smoking, CV dz/risks, asthma, COPD, chronic bronchitis,2 GERD, anxiety, etc; ✓hx COVID pneumonia/hospitalization2,4
- Exam. ✓T, RR, HR; chest/resp/CV exam, pulse ox (may be falsely higher in pts w/ darker skin pigmentation5); consider 6-min walk test, 2-min step, 1-min sit-to-stand2 (✓pulse ox, HR w/ walk test)1,5
- Labs. CDC’s basic post-COVID sx labs: CBC, BMP, UA, LFTs (or CMP), CRP, ESR, Ferritin, TSH & free T4, vit D & B12; d-dimer if PE suspected; BNP if HF suspected.2 If mod/high suspicion for cardiac involvement, ✓cTn1
- PFTs. ✓PFTs;1,4,6 consider full PFTs if breathing discomfort not improving ≥8wk post-acute COVID or if new/worsening sx5 (some groups recommend full PFTs @12wk6 for persistent sx)
- Imaging. ✓CXR3 +/or non-contrast CT; if mod/high suspicion for cardiac involvement (eg, myocarditis), ✓echo (+ ECG, cTn) then CMR; if PE suspected, V/Q1 or CTPA;6 if interstitial lung dz suspected, ✓ noncontrast5 HRCT;6 ischemia eval depends on CV risk1 level
- Refer pts w/ hypoxemia/severe lung dz signs3 or abnl CV findings.1 Pulm referral for new/progressive abnormalities or abnl PFTs/imaging/exam/sats, etc
Sx management - Noncardiac pain sx relief.1 If pleuritic or inflammatory, consider 1-2wk NSAID trial (if sx worsen, consider esophageal dz)
- Inform pt when to seek care if signs/sx worsen, consider sx diary2
Supportive care2 - Ensure full COVID vax; anecdotal reports suggest that some pts w/ post-COVID sx improve after vax; ongoing research needed to verify
- Monitor comorbidities that may impact sx; optimize sleep, nutrition, stress reduction
- Consider online support groups/forums
Footnotes 1 ACC 2022.
• Eval suspected PASC (dyspnea, chest pain, palpitations, lightheaded, etc), based on clinical presentation, w/ ECG, cTn, echo, ambulatory rhythm monitor, CXR (+/or noncontrast CT) & PFTs. Cardiology consult for abnl results, if known CV dz, or if sx remain unexplained.
• CMR. Use following abnl echo/cTn/ECG or if cardiopulm sx persist.
• Ischemia eval. If low risk: CAC or exercise test w/o imaging. If higher risk: CTA or stress w/ imaging (echo, PET/SPECT, CMR). Defer max-effort exercise test until myocarditis r/o w/ CMR. Reserve invasive coronary angiographic for pts w/ abnl noninvasive tests or if obstructive CAD or vasospasm very strongly suspected.
Writing Committee, Gluckman TJ, et al. 2022 ACC Expert Consensus Decision Pathway on Cardiovascular Sequelae of COVID-19 in Adults: Myocarditis and Other Myocardial Involvement, Post-Acute Sequelae of SARS-CoV-2 Infection, and Return to Play: A Report of the American College of Cardiology. J Am Coll Cardiol. 2022. Mar 14;S0735-1097(22)00306-0. Free full-text article PDF
2 CDC 2021. Evaluating and Caring for Patients with Post-COVID Conditions: Interim Guidance. Updated 6/14/21. Accessed 3/10/22
3 NICE 2021. CXR: NL plain films don’t r/o lung dz.
National Institute for Health and Care Excellence. COVID-19 Rapid Guideline: Managing the Long-term Effects of COVID-19. Published 12/18/20. Updated 11/11/21. Accessed 3/10/22
4 PFTs. Following COVID pneumonia, lung function recovery initially rapid, but 6-mo post-d/c, recovery slows, w/ 1/3+ pts showing abnl PFTs, per a small study.
Orzes N, et al. Pulmonary Physiology. Chest Annual Meeting Abstracts. Evaluation of Lung Function After SARS-CoV-2 Pneumonia. Chest. 2021. Oct 1;160(4)S:A2157. Free full-text article
5 AAPM&R 2022. The American Academy of Physical Medicine and Rehabilitation. Maley, JH, et al. Multi-disciplinary Collaborative Consensus Guidance Statement on the Assessment and Treatment of Breathing Discomfort and Respiratory Sequelae in Patients With Post-acute Sequelae of SARS-CoV-2 Infection (PASC). PM&R. 2021. Jan;14(1):77-95. Free full-text article
Imaging. >4-6wk after viral pneumonia, imaging studies may still show residual abnormalities.
6 George PM, et al. State of the Art Review. Respiratory Follow-up of Patients With COVID-19 Pneumonia. Thorax. 2020. Nov;75(11):1009-1016. Free full-text PDF
• Hx severe COVID pneumonia (eg, ICU stay). @12wk post-d/c: ✓CXR, clinical eval. Consider full PFTs, walk test w/ O 2 sats, sputum sample, echo. If imaging/ physiological assessment abnl, or evidence of pulm HTN: ✓HRCT and CTPA; consider echo if not already done. If no interstitial lung dz or pulm HTN: Consider other dx.
• Hx mild-to-mod COVID pneumonia (eg, regular hospital ward/community care). @12wk out: ✓CXR. If abnl: Order PFTs. Review PFTs & assess clinically. If suspect PE: ✓CTPA. Otherwise, if pt improving, consider repeat CXR. If repeat CXR is abnl: ✓both HRCT and CTPA; consider walk test & echo. If no interstitial lung dz or pulm HTN: Consider other dx.
Cardiovascular (chest pain, dyspnea, palpitations, syncope) CV sx, including new, returning, or persistent ≥4wk after SARS-CoV-2 infxn may be due to various conditions, eg, myocarditis/myocardial involvement, pericarditis, new/worsening myocardial ischemia, microvasc coronary artery dysfxn, nonischemic CM, thromboembolism, CV sequelae of pulm dz, arrhythmia.1 When evaluating possible PASC pt, be aware that previously unrecognized cardiac dz may become clinically evident in acute illness setting. (+)COVID test/serology not required to eval/manage sx; lack of abnl labs/imaging doesn’t invalidate sx. Consider rehab plan simultaneous w/ testing2 Eval: If signs/sx of acute/life-threatening dz (related to COVID or not, eg, myocarditis, MI, pericarditis, PE), don’t delay testing.2 Otherwise, 4-12wk out: Explore differential, conservative investigations; >12wk: Pursue additional tests2 Work-up1 - Sx timeline: Cardiac sx (eg, chest pain, SOB, fatigue, palpitations) may persist for months after SARS-CoV-2 infxn
- PMHx: baseline health status; known CV comorbidities (HTN, hyperlipidemia, DM); ✓FHx of premature CAD, CM, SCD
- HPI: ✓primary sx (eg, chest pain, dyspnea, palpitations, tachy, lightheadedness); most bothersome sx; impact on QoL, clinical presentation of acute infxn (sx type/duration/severity; hx hospitalization, organ injury); ✓exercise intolerance, tachy, orthostasis, autonomic dysfxn sx (eg, GI dysmotility, urinary retention/incontinence, sexual dysfxn)
- Exam: Temp, cardiac & pulm exam; orthostatic vitals, 10-min active stand test, 6-min walk test (✓pulse ox, HR w/ walk test)
- Labs: CBC, BMP, cTn, CRP +/- additional tests (eg, d-dimer, BNP/N-terminal pro-BNP, thyroid fxn tests) based on clinical presentation
- Other tests/imaging based on clinical presentation:
- Chest pain, dyspnea, palpitations, and/or syncope in setting of acute SARS-CoV-2 infxn (suspected myocarditis): Order ECG, cTn, and echo (triad test)
- Tachycardia & exercise intolerance: orthostatic vitals, autonomic testing, CPET, active stand test
- Palpitations: ambulatory rhythm monitor
- Chest pain: stress test, echo, CMR,1 coronary CTA, invasive coronary angiography (ischemia eval based on risk level)
- Dyspnea: echo, stress test, CPET (may differentiate CV vs pulm etiologies), stress PET/CT
- Refer to cardiology if abnl cardiac test results, known CV dz w/ new or worsening signs/sx, documented cardiac complications during acute infxn, or persistent &/or concerning CV/pulm sx
Sx management1 - PASC w/ tachycardia, exercise/orthostatic intolerance, &/or deconditioning: recumbent/semi-recumbent exercise (eg, row, swim, cycle) w/ transition to upright as orthostatic intolerance improves. Limit exercise to 5-10min/day initially, gradually increase as tolerated (avoid postexertional malaise). If deconditioning (which is assoc w/ plasma volume reduction) or orthostatic sx: consider table salt @ 1-2 tsp/day & 3 L/day H2O or electrolyte-balanced fluid, while ensuring BP controlled; avoid dehydration via EtOH, excess caffeine, heat; consider waist-high support stockings; avoid heavy meals. Consider empiric drug options:
- low-dose beta-blocker or non-dihydropyridine CCB: titrated gradually to slow HR; nonselective BBs may help control sx of orthostatic intolerance; consider propranolol for pts w/ coexisting anxiety or migraine
- ivabradine can benefit pts w/ severe fatigue exacerbated by BBs or CCBs, may improve POTS
- fludrocortisone (up to 0.2 mg at HS) may be used w/ salt loading to increase blood volume; monitor for hypokalemia
- midodrine (2.5-10 mg) can help w/ orthostatic hypotension; 1st dose taken in am before rising, last dose no later than 4pm
- Chest pain: If ischemia ruled out, and pain is pleuritic or underlying inflammation present (eg, costochondritis): 1-2wk trial of NSAIDS, w/ colchicine added prn. If sx worsen w/ NSAID, consider esophagitis, esophageal spasm. If suspected endothelial dysfxn: consider CCB, long-acting nitrate, or ranolazine. For underlying ASCVD: aspirin and high-intensity statin. If persistent chest pain refractory to other tx or if microvascular dysfxn suspected: some supplements may help. Beetroot extract taken 1h before exercise for max vasodilation, or L-arginine 4 mg bid.
- Mild/moderate myocarditis: Manage in hospital w/ advanced cardiac expertise. If concurrent lung injury: steroids. If pericardial involvement: NSAIDs, colchicine, or prednisone. If reduced LVEF: tx HF. Avoid vigorous physical activity x3-6mo; repeat cardiac testing (ECG, echo, ambulatory rhythm monitor, CMR) @ 3-6mo
- Severe myocarditis: Manage in hospital w/ advanced cardiac expertise. If severe concurrent lung injury, hemodynamic compromise, MIS-A, or severe myocardial infiltrates/fulminant myocarditis on bx: steroids (balanced against infxn risk). If reduced LVEF: tx HF. If cardiogenic shock: mechanical circ support. Avoid vigorous physical activity x3-6mo. Repeat cardiac testing (ECG, echo, ambulatory rhythm monitor, CMR) @ 3-6mo
- Suspected pericardial involvement w/o myocarditis: Can likely manage as out-pt, if chest pain is only sx, LV systolic fxn preserved, no ventricular arrhythmias. Treat w/ NSAIDs, colchicine, or prednisone. Monitor closely. Consider repeat cardiac testing (ECG, echo, ambulatory rhythm monitor, CMR) @ 3-6mo
Supportive care2 - Inform pt when to seek care if signs/sx worsen, consider sx diary
- Ensure full COVID vax; anecdotal reports suggest that some pts w/ post-COVID sx improve after vax; ongoing research needed to verify
- Monitor comorbidities that may impact sx; optimize sleep, nutrition, stress reduction
- Consider online support groups/forums
Footnotes 1 ACC 2022.
Myocarditis defined by: a) cardiac sx (eg, chest pain, dyspnea, palpitations, syncope); b) elevated cTn; and c) abnormal ECG, echo, CMR, and/or bx findings or postmortem eval.
Ischemia eval. If low risk, CAC or exercise test w/o imaging. If higher risk, CTA or stress w/ imaging (echo, PET/SPECT, CMR). Defer max-effort exercise test until myocarditis r/o w/ CMR. Reserve invasive coronary angiographic for pts w/ abnl noninvasive tests or if obstructive CAD or vasospasm very strongly suspected.
CMR usually ordered by cardiologist if abnl triad testing (ECG/cTn/echo) or if CV/pulm sx persist.
Writing Committee, Gluckman TJ, et al. 2022 ACC Expert Consensus Decision Pathway on Cardiovascular Sequelae of COVID-19 in Adults: Myocarditis and Other Myocardial Involvement, Post-Acute Sequelae of SARS-CoV-2 Infection, and Return to Play: A Report of the American College of Cardiology. J Am Coll Cardiol. 2022. Mar 14;S0735-1097(22)00306-0. Free full-text article PDF
2 CDC 2021. Postexertional malaise = sx worsening ~12–48h after even minor physical/mental exertion; malaise lasts for days/weeks.
Evaluating and Caring for Patients with Post-COVID Conditions: Interim Guidance. Updated 6/14/21. Accessed 3/22/22
3 AAP 2021. American Academy of Pediatrics. Post-COVID-19 Conditions in Children and Adolescents. Updated 12/17/21. Accessed 3/10/22
Neurocognitive dysfunction/“brain fog” Post-COVID cognitive fatigue1 & cognitive dysfunction (eg, “brain fog” affecting processing speed, exec. fxn, etc2); etiology unknown, likely multifactorial; may overlap w/ mood disorders, physical fatigue. Sx may include postexertional malaise3 after mental/physical exertion, similar to ME/CFS.4 (+)COVID test/serology not required to eval/manage sx; lack of abnl labs/imaging doesn’t invalidate sx. Consider return-to-activity program and cognitive rehab interventions simultaneous w/ eval3 Eval: Consider primary causes of cognitive impairment and contributing factors based on hx/signs/sx. 4-12wk out: Explore differential, conservative investigations,3 including related to sleep, psych (depression, anxiety, PTSD), fatigue, endocrine, autoimmune;1 >12wk: Pursue additional tests3 - Sx timeline. Cognitive issues common w/ acute COVID sx.1 Eval if cognitive sx severe or affect QoL ≥4wk from onset. Assess current vs pre-COVID functional status3
- PMHx. ✓pre-COVID cognitive status issues, current cognitive sx severity & impact on daily activities/QoL, ROS, med review;1 COVID severity/hospitalization3 (eg, post-ICU syndrome)
- Exam. Targeted exam based on HPI. ✓RR, HR, BP (& orthostatic HR/BP if postural sx);5 resp/CV exam, pulse ox. If assoc. fatigue, assess endurance, eg, 30-sec sit-to-stand, 6- or 10-min walk test, 2-min step (seated or standing),5 (✓pulse ox, HR w/ walk test).5 Neuro exam, use validated cognitive sx screening tool (Montreal Cognitive Assessment, MMSE, St. Louis University Mental Status Exam, Mini-Cog, Short Test of Mental Status);1 screen for anxiety, depression, PTSD, and other mental health dz if indicated3,5
- Labs. CBC, CMP, B12, thiamine, folate, homocysteine, 1,25-dihydroxy vit D, magnesium, LFTs, TSH, free T3, free T4; if high-risk, consider syphilis and HIV testing; other tests based on specific signs/sx1
- Brain imaging. Consider neuroimaging for new/ worsening focal neuro deficits/cognitive sx1
- Refer to neurology if neurosigns/sx (urgent eval for focal or progressive features). Refer pts w/ (+)screen for cognitive sx to specialist (neuropsych, speech-language path, OT) w/ expertise in formal cognitive assessment & tx.1 Consider sleep specialty referral if needed1
Sx management - Begin individualized, titrated, structured return-to-activity program based on exercise tolerance/comorbidities; conserve energy initially.1,5 Once back to normal activities, stay active (aerobic activity 2-3x/wk);5 however, to avoid postexertional malaise from mental/physical exertion, return to physical exercise slowly (eg, 5-10min/day to start)6
- Memory/organization compensation techniques.1 Treat as concussion/TBI: Take notes via notebook/filing system/to-do lists/calendars on paper or phone app, set electronic reminders/alarms. Break tasks into manageable components. Practice skills until automatic. Create routines; consistently place items. If slowed motor fxn, consider voice dictation. Use word assoc for word-finding, self-talk for active problem-solving
- Recommend good sleep hygiene (ideally 7-8h/night);1 consistent sleep/wake schedule. If dysautonomia sx, good hydration & increased salt intake if not contraindicated.5 Address pain control if required; reduce screen time1
- Avoid meds1 that can worsen cognitive sx
- Counseling or psych co-management for mental health dz1
Supportive care3 - Ensure full COVID vax; anecdotal reports suggest that some pts w/ post-COVID sx improve after vax; ongoing research needed to verify
- Monitor comorbidities that may impact sx; optimize nutrition, stress reduction
- Consider online support groups/forums
Footnotes 1 AAPM&R 2021 Cognitive.
Mental/cognitive fatigue definition: progressive ↓cognitive resources over time while performing tasks that require sustained attention & executive function (outside of deficits related to motivation or inadequate sleep)
Meds that may worsen cognitive sx include antihistamines, anticholinergics, antidepressants, anxiolytics, hypnotics, muscle relaxants, antipsychotics, etc.
Fine JS, et al. Multi-disciplinary collaborative consensus guidance statement on the assessment and treatment of cognitive symptoms in patients with post-acute sequelae of SARS-CoV-2 infection (PASC). PM&R. 2022. Jan;14(1):96-111. Free full-text article
2 Brain fog definition: Common self-reported cognitive dysfunction in adults includes: processing speed, executive functioning, phonemic & category fluency, category fluency, & memory encoding/recall. Memory recognition was relatively spared. Hospitalized pts had higher likelihood of impaired attention, exec fxn, category fluency, and memory encoding/recall vs outpts.
Becker JH, et al. Assessment of Cognitive Function in Patients After COVID-19 Infection. JAMA Netw Open. 2021. Oct 1;4(10):e2130645. Free full-text research letter
3 CDC 2021.
Postexertional malaise = sx worsening ~12–48h after even minor physical/mental exertion; malaise lasts for days/weeks.
Evaluating and Caring for Patients with Post-COVID Conditions: Interim Guidance. Updated 6/14/21. Accessed 3/10/22
4 ACC 2022. Gluckman TJ, et al. 2022 ACC Expert Consensus Decision Pathway on Cardiovascular Sequelae of COVID-19 in Adults: Myocarditis and Other Myocardial Involvement, Post-Acute Sequelae of SARS-CoV-2 Infection, and Return to Play: A Report of the American College of Cardiology. J Am Coll Cardiol. 2022. Mar 14;S0735-1097(22)00306-0. Free full-text article PDF
5 Definition: myalgic encephalomyelitis/chronic fatigue syndrome:
(1) ≥6mo of impaired physical, occupational, social activity;
(2) post-exertional malaise (PEM);
(3) unrefreshing sleep;
(4) and cognitive impairment and/or orthostatic intolerance.
NIH 2015. Committee on the Diagnostic Criteria for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome; Board on the Health of Select Populations; Institute of Medicine. Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness. Washington (DC): National Academies Press (US); 2015. Feb 10. Free full-text article
6 AAPM&R 2021 Fatigue.
Herrera JE, et al. Multidisciplinary Collaborative Consensus Guidance Statement on the Assessment and Treatment of Fatigue in Postacute Sequelae of SARS-CoV-2 Infection (PASC) Patients. PM&R. 2021. Sep;13(9):1027-1043. Free full-text article
Regaining smell/taste occurs w/in several months post-COVID in most pts;1 (+)COVID test/serology not required to eval/manage sx. Lack of abnl labs/imaging doesn’t invalidate sx,2 but CT or endoscopy may help confirm inflammatory, structural dz3 Eval: Tailor tests per signs/sx per clinical presentation. 4-12wk out: explore differential (rhinitis, meds, etc3), conservative investigations2 - Sx timeline relative to any other COVID sx. If new/worsening, consider COVID reinfxn2 or superinfxn (flu, sinusitis, etc). Assess impact on QoL2
- PMHx. ✓hx smoking, allergy, meds, head trauma, etc3
- Exam. ✓ENT exam, CN I, VII, IX, X3
- Labs/imaging. If persistent, consider further eval, eg, labs, etc to r/o underlying dz.3 In general, nasal endoscopy, then CT may be used to explore sinonasal pathology/structural dz; consider ENT or neuro consult based on signs/sx3
Sx management - Post-viral infxn smell retraining tx: start w/ 4 diff memorable scents (most rec’d: rose, lemon, cloves, eucalyptus). Sniff each scent x10-20sec qd-bid. Focus on memory of that smell. After each scent, take a few breaths, move on to next scent. Duration of tx: ≥12wk1
- Nasal rinses, intranasal steroids may also help1
Supportive care - Ensure proper chemical detectors (gas and CO) in the home1
- Ensure full COVID vax; anecdotal reports suggest that some pts w/ post-COVID sx improve after vax; ongoing research needed to verify2
- Monitor comorbidities that may impact sx; optimize sleep, nutrition, stress reduction1
- Consider online support groups/forums1
Footnotes 1 AAO-HNS 2022. ENThealth.org Conditions: Hyposmia and Anosmia https://www.enthealth.org/conditions/hyposmia-and-anosmia/
2 CDC 2021. Evaluating and Caring for Patients with Post-COVID Conditions: Interim Guidance. Updated 6/14/21. Accessed 3/10/22
3 AAFP 2013. Malaty J, et al. Smell and Taste Disorders in Primary Care. Am Fam Physician. 2013. Dec 15;88(12):852-859. Accessed 4/16/20
Meds w/ anosmia as potential adverse rxn:
• chemo
• ACEI
• ARB
• dihydropyridine CCB
• diuretics
• intranasal zinc
• antibiotics (macrolides, FQ, PCNs, tetracyclines, metronidazole)
• other antimicrobials (terbinafine, protease inhibitors, griseofulvin)
• antiarrhythmics
• anti-thyroid agents
• antidepressants
• anticonvulsants
• lipid-lowering agents
Other etiologies of olfactory dysfxn:
- • Most common: URI (esp viral), allergic rhinitis, chronic sinusitis, nasal polyps
- • More common: head trauma; neurodegenerative disorders (Parkinson dz, Alzheimer dz, mild cognitive impairment, MS)
- • Less common:
- ° Meds: see above
- ° Illicit substances: EtOH, cocaine
- ° Toxins: ammonia, hairstyling chemicals, gasoline, formaldehyde, etc.
- ° Chronic medical conditions: renal/liver failure, DM2, cancer, HIV
- ° Structural/mechanical conditions: stroke, SAH/ICH, brain or sinonasal tumor
- ° Nutritional deficiencies: malnutrition, pernicious anemia, deficiencies of vit B12, B6, A, niacin, zinc, copper
- ° Postsurgical: ENT surgeries
- ° Congenital: Kallmann syndrome
- ° Psychiatric: anorexia nervosa, depression, bipolar, schizophrenia
- ° Endocrine: pregnancy, hypothyroidism, Addison dz, Cushing syndrome
- ° Autoimmune/inflammatory: Sjogren syndrome, SLE, sarcoidosis, herpes encephalitis
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