Post-Covid Long-Term Effects

Aka: Post-Covid Long-Term Effects, Long COVID, COVID Long Hauler, Postacute Sequelae of COVID-19, PASC

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II. Epidemiology

  1. Incidence
    1. Adult: 10% of Covid Patients (up to 19 to 30% in some studies)
    2. Child: 8% (e.g. persistent Fatigue)

III. Pathophysiology

  1. Although there are many Chronic Complications of ICU Care, Post-Covid effects are often seen in less severe cases
  2. Proposed Mechanisms
    1. Residual tissue injury from acute infection
    2. Persistent smoldering viral activity from a host reservoir
    3. Hyperinflammatory state complications (Multisystem Inflammatory Syndrome)
    4. Immune dysfunction
    5. Preexisting comorbid conditions that are unmasked or provoked by Covid infection

IV. Risk Factors

  1. Age over 50 years old
  2. Female gender
  3. Obesity
  4. Severe acute infection (or more than 5 symptoms in the first week of illness)
  5. Unvaccinated or incompletely vaccinated with Covid19 Vaccine (<3 Vaccine doses)
  6. Type 2 Diabetes Mellitus
  7. Immunocompromised patient
  8. Hypertension
  9. Psychiatric Conditions
  10. Earlier strains of Covid
  11. Azzolini (2022) JAMA 328(7): 676-8 [PubMed]

V. Symptoms

  1. General
    1. Fatigue (<58%)
      1. Similar to Chronic Fatigue Syndrome
      2. Common in post-covid symptoms >6 months
    2. Night Sweats (<24%)
    3. Appetite change (<17%)
    4. Weight loss (<21%)
  2. Cardiopulmonary
    1. Chest Pain (<16%)
    2. Palpitations (<14%)
    3. Dyspnea (<30%)
    4. Cough (<15%)
    5. Autonomic Dysfunction (e.g. Postural Orthostatic Tachycardia Syndrome or POTS Syndrome)
      1. POTS Syndrome demonstrates Orthostatic Intolerance with Tachycardia, without significant Orthostatic Hypotension
      2. Mast Cell Activation Syndrome (Hypotension, Palpitations, Urticaria, Wheezing, Rhinitis, Pharyngitis, Conjunctivitis)
    6. Decreased Exercise tolerance (<15%)
    7. Post-exertional malaise
      1. Common, hallmark symptom in post-covid symptoms >6 months
      2. Exhaustion and prolonged recovery, requiring days to weeks, starting 12 to 72 hours after activity
  3. Musculoskeletal
    1. Decreased mobility (<20%)
    2. Arthralgias and myalgias (<14%)
  4. Neurologic
    1. Headache (12 to 44%)
    2. Cognitive dysfunction (common in post-covid symptoms >6 months)
      1. Attention disorder, difficulty concentrating or brain fog (<27%)
      2. Memory deficit (<19%)
    3. Altered taste, Ageusia, parageusia, dysguesia (<23%)
    4. Altered Sense of Smell, Anosmia or Parosmia (<21%)
      1. Otte (2020) J Infect 81(3):e58 +PMID: 32592702 [PubMed]
  5. Skin
    1. Alopecia (<25%)
  6. Psychiatric
    1. Anxiety (<30%)
    2. Depression (<23%)
    3. Post-Traumatic Stress Disorder (<13%)
    4. Insomnia or other sleep disorder (<27%)

VI. Associated Conditions

  1. Respiratory
    1. DLCO Decreased on Pulmonary Function Testing
    2. Decreased lower respiratory Muscle Strength
    3. Persistently abnormal CT Chest
    4. Huang (2020) Respir Res 21(1):163 +PMID: 32600344 [PubMed]
    5. Lerum TV (2020) Eur Respir J +PMID: 33303540 [PubMed]
  2. Cardiovascular
    1. Persistent Myocarditis
    2. Puntmann (2020) JAMA Cardiol 5(11):1265-73 [PubMed]
    3. Rajpal (2021) JAMA Cardiol 6(1):116-8 [PubMed]

VII. Labs

  1. General Testing in Most Cases (Identify Reversible Causes)
    1. Complete Blood Count
    2. Comprehensive Metabolic Panel
    3. Serum Magnesium
    4. C-Reactive Protein
    5. Erythrocyte Sedimentation Rate (ESR)
    6. Serum Ferritin
    7. Thyroid Stimulating Hormone (TSH)
    8. Serum Vitamin D
    9. Serum Vitamin B12
  2. Autonomic Dysfunction Additional Testing (e.g. POTS Syndrome)
    1. Orthostatic Blood Pressure and pulse
    2. Electrocardiogram (EKG)
    3. Consider Gluten Sensitive Enteropathy testing
    4. Consider Echocardiogram
    5. Consider autonomic reflex testing
    6. Consider ambulatory Heart Rate monitoring (e.g. zio monitor)
  3. Neurocognitive Additional Testing (e.g. Brain Fog)
    1. See Cognitive Impairment
    2. Cognitive assessment tools (e.g. Montreal Cognitive Assessment)
    3. Consider Neuropsychological Testing
    4. Consider Thiamine replacement
    5. Consider MRI Brain
  4. Dyspnea Additional Testing
    1. Chest XRay
    2. B-Type Natriuretic Peptide (BNP)
    3. Pulmonary Function Tests
    4. Electrocardiogram (EKG)
    5. Consider D-Dimer
    6. Consider CT Chest
    7. Consider Sleep Study for Obstructive Sleep Apnea (if suspected by history)
    8. Consider Echocardiogram
    9. Consider home Pulse Oximetry
    10. Consider Cortisol
  5. Chronic Fatigue Additional Testing
    1. Functional Capacity Testing
    2. Consider Respiratory Additional Testing as above
    3. Consider Antinuclear Antibody testing
  6. Mast Cell Activation Additional Testing (Hypotension, Palpitations, Urticaria, Wheezing, Rhinitis, Pharyngitis, Conjunctivitis)
    1. Serum Tryptase (baseline and within <4 hours of symptom onset)
    2. N-Methylhistamine 24 hour Urine Collection
    3. Prostaglandin D2 24 hour Urine Collection

VIII. Differential Diagnosis

  1. Chronic Complications of ICU Care (or prolonged illness or hospitalization)
  2. New illness
  3. Exacerbation of comorbid conditions
    1. Chronic Kidney Disease
    2. Diabetes Mellitus
    3. Chronic lung disease (e.g. Asthma, COPD)
    4. Cardiomyopathy (e.g. CHF)
    5. Mood Disorders (e.g. Major Depression, Anxiety Disorder)
  4. Altered Smell or Taste
    1. See Smell Dysfunction
    2. See Taste Dysfunction
    3. Allergic Rhinitis
    4. Sinusitis
  5. Dyspnea
    1. See Dyspnea Causes
    2. Obstructive Lung Disease (Asthma, COPD)
    3. Restrictive Lung Disease (e.g. pulmonary fibrosis)
    4. Cardiomyopathy (e.g. Congestive Heart Failure, Myocarditis)
    5. Pneumonia
    6. Coronary Artery Disease
    7. Pulmonary Embolism
    8. Anemia
  6. Autonomic Dysfunction (Dysautonomia)
    1. See Autonomic Dysfunction
    2. POTS Syndrome
    3. Hyperthyroidism
    4. Cardiac Arrhythmia
    5. Inappropriate Sinus Tachycardia
  7. Mast Cell Activation Syndrome (Hypotension, Palpitations, Urticaria, Wheezing, Rhinitis, Pharyngitis, Conjunctivitis)
    1. POTS Syndrome
    2. Multisystem Inflammatory Syndrome
    3. Diabetes Mellitus
    4. Porphyria
    5. Celiac Disease
    6. Vasculitis
  8. Cognitive Dysfunction
    1. See Dementia Differential Diagnosis
    2. Cerebrovascular Accident
    3. Multiple Sclerosis
    4. Sleep Disorder (e.g. Obstructive Sleep Apnea)
    5. Major Depression
    6. Traumatic Brain Injury
  9. Chronic Fatigue Syndrome
    1. See Fatigue Differential Diagnosis

IX. Diagnosis

  1. New, recurrent or ongoing Covid19 symptoms persisting >28 days (per CDC) or >2 months (WHO)
  2. Covid19 diagnosis may be a clinical diagnosis despite negative PCR or other testing
    1. Of those with known Covid19 infection, 10-20% will have subsequent negative Antibody testing

X. Management

  1. General
    1. Goals of management is improved function and quality of life
    2. Lifestyle Interventions (non-medication therapy)
      1. Limit Alcohol and Caffeine
      2. Tobacco Cessation
      3. Insomnia Nonpharmacologic Management
      4. Meditation and MindfulnessExercises
    3. Multi-specialty support
      1. Support groups
      2. Physical Therapy
      3. Specialists (cardiology, pulmonology, ent) as needed
    4. Follow-up every 2-3 months
  2. Altered Smell or Taste
    1. See Smell Dysfunction
    2. See Taste Dysfunction
    3. Smell Training
    4. No treatment (e.g. Intranasal Steroids) found effective in speeding olfactory recovery
    5. Improves or resolves more quickly than other causes of Olfactory Dysfunction
    6. Resolution by 7 days in a majority of patients and by 3 months in 80%
      1. Course prolonged in more severe disease
      2. Ferrell (2022) Eur Arch Otorhinolaryngol 279(9): 4633-40 [PubMed]
  3. Autonomic Dysfunction (Dysautonomia)
    1. See Autonomic Dysfunction
    2. Eat smaller, more frequent meals
    3. Increase volume status
    4. Consider increased dietary salt when appropriate
    5. Consider Compression Stockings
    6. Sleep with head of bed elevated
    7. Perform Isometric Exercises
    8. Avoid triggers of Orthostatic Intolerance (e.g. excessive heat, Alcohol)
    9. Consider medication management starting at low dose and titrating as needed (e.g. Propranolol, Fludrocortisone, Midodrine)
      1. Local expert Consultation recommended
  4. Cognitive dysfunction
    1. Neuropsychiatric Consultation
    2. Eliminate contributing factors (e.g. Polypharmacy, medications impacting attention)
    3. Ensure adequate sleep
    4. Consider neurology Consultation
    5. Consider occupational therapy
    6. Consider speech pathologist
    7. Gradual return to cognitive activities
  5. Dyspnea
    1. Pulmonary Rehabilitation and breathing Exercises
    2. Gradual return to activity
  6. Chronic Fatigue Syndrome
    1. Lifestyle changes (adequate sleep, Healthy Diet, adequate hydration)
    2. Energy conservation (e.g. 4Ps - Plan, Pace, Prioritize, Position)
    3. Avoid relapse triggers (emotional stress, strenuous activity)
    4. Gradual return to activity
  7. Mast Cell Activation Syndrome (Hypotension, Palpitations, Urticaria, Wheezing, Rhinitis, Pharyngitis, Conjunctivitis)
    1. Cromolyn or Mast Cell Stabilizers
    2. Antihistamines

XI. Prognosis

  1. Symptom peak timing may predict duration
    1. Recovery by 90 days: Symptoms peak at 2 weeks
    2. Not recovered by 90 days: Symptoms peak at 2 months
  2. Relapses after 6 months (Fatigue, post-exertional malaise, cognitive dysfunction) have common triggers
    1. Physical Activity or Exercise
    2. Emotional stress
    3. Cognitive activity
  3. Patients should expect continued gradual improvement with periodic relapses and set backs
    1. Outcomes vary from patient to patient and longterm data is limited
    2. More than half of patients will have symptoms >6 months, but these symptoms decrease over time
    3. Most patients with persistent Dyspnea following covid improve without chronic lung disease
    4. Most patients recover from Cognitive Impairment

XII. Prevention

  1. Covid-19 Vaccine
    1. Most effective prevention of Long COVID (pre-exposure)
  2. COVID-19 Treatment
    1. Paxlovid started within 5 days of Covid onset may reduce the risk of developing Long COVID

XIII. Resources

  1. Post-Covid (CDC)
    1. https://www.cdc.gov/coronavirus/2019-ncov/hcp/clinical-care/post-covid-conditions.html
  2. SurvivorCorps
    1. https://www.survivorcorps.com/

XIV. References

  1. (2023) Presc Lett 30(4): 20-1
  2. Alkodaymi (2022) Clin Microbiol Infect 28(5): 657-66 [PubMed]
  3. Fernandez (2021) Sao Paulo Med. J. 139 +PMID:33656121 [PubMed]
  4. Herman (2022) Am Fam Physician 106(5): 523-32 [PubMed]
  5. Lopez-Leon (2021) medRxiv +PMID: 33532785 [PubMed]
  6. Sneller (2022) Ann Intern Med 175(7): 969-79 [PubMed]
  7. Michelen (2021) BMJ Glob Health 6(9): e005427 [PubMed]

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