Postexertional malaise (HP:0030973)
Post-exertional symptom exacerbation (PESE), also referred to as post-exertional malaise (PEM), is defined as the worsening of symptoms that can follow minimal cognitive, physical, emotional, or social activity, or activity that could previously be tolerated. Symptoms typically worsen 12 to 72 hours after activity and can last for days or even weeks, sometimes leading to a relapse.
Synonyms: Exercise-induced malaise, Postexertional malaise
Comment: PEM can be observed in individuals with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), as a post-acute sequela of SARS-CoV-2 infection (long COVID), and occasionally in individuals with mitochondrial disorders or cancer related fatigue. It is often accompanied by exacerabtion or new onset of exhaustion, cognitive impairment, muscle pain, muscle weakness, or other manifestations. The onset of PEM may occur hours or even days after exertion, and recovery from PEM is often slow, taking place over days or weeks or longer. PESE can contribute to the episodic nature of disability in post COVID-19 condition, often presenting as unpredictable fluctuations in symptoms and function.
Pubmed References: PMID:25695122 , PMID:26904705 , PMID:32105793 , PMID:33071931
KEGG Pathway
| Index | Name | P-value | Adjusted p-value | Odds Ratio | Combined score |
| 1 | ECM-receptor interaction | 0.0005268 | 0.007568 | 77.16 | 582.42 |
| 2 | Protein digestion and absorption | 0.0007207 | 0.007568 | 65.65 | 474.97 |
| 3 | Starch and sucrose metabolism | 0.01431 | 0.04412 | 81.46 | 345.92 |
| 4 | African trypanosomiasis | 0.01471 | 0.04412 | 79.19 | 334.14 |
| 5 | Regulation of lipolysis in adipocytes | 0.02179 | 0.05721 | 52.75 | 201.82 |
GO: Biological Process
| Index | Name | P-value | Adjusted p-value | Odds Ratio | Combined score |
| 1 | regulation of atrial cardiac muscle cell membrane repolarization (GO:0060372) | 0.000002937 | 0.0003671 | 1332.47 | 16973.13 |
| 2 | urate metabolic process (GO:0046415) | 0.000007686 | 0.0004804 | 740.11 | 8715.63 |
| 3 | positive regulation of action potential (GO:0045760) | 0.001999 | 0.01520 | 713.86 | 4436.86 |
| 4 | bundle of His cell action potential (GO:0086043) | 0.001999 | 0.01520 | 713.86 | 4436.86 |
| 5 | response to denervation involved in regulation of muscle adaptation (GO:0014894) | 0.001999 | 0.01520 | 713.86 | 4436.86 |
GO: Molecular Function
| Index | Name | P-value | Adjusted p-value | Odds Ratio | Combined score |
| 1 | urate transmembrane transporter activity (GO:0015143) | 0.000001399 | 0.00003498 | 2221.00 | 29938.36 |
| 2 | 1,4-alpha-oligoglucan phosphorylase activity (GO:0004645) | 0.001999 | 0.01399 | 713.86 | 4436.86 |
| 3 | voltage-gated sodium channel activity involved in cardiac muscle cell action potential (GO:0086006) | 0.001999 | 0.01399 | 713.86 | 4436.86 |
| 4 | carbohydrate:proton symporter activity (GO:0005351) | 0.002797 | 0.01399 | 475.86 | 2797.66 |
| 5 | nitric-oxide synthase binding (GO:0050998) | 0.002797 | 0.01399 | 475.86 | 2797.66 |
GO: Cellular Component
| Index | Name | P-value | Adjusted p-value | Odds Ratio | Combined score |
| 1 | basement membrane (GO:0005604) | 0.0001838 | 0.004082 | 132.95 | 1143.57 |
| 2 | voltage-gated sodium channel complex (GO:0001518) | 0.006781 | 0.03899 | 178.36 | 890.65 |
| 3 | sodium channel complex (GO:0034706) | 0.009958 | 0.04581 | 118.86 | 547.86 |
| 4 | intercalated disc (GO:0014704) | 0.01233 | 0.04728 | 95.06 | 417.81 |
| 5 | brush border membrane (GO:0031526) | 0.01471 | 0.04832 | 79.19 | 334.14 |
Hub genes predicted as biomarkers & predicted FDA approved drugs
| Hub Genes (ranked) | FDA-Approved Drugs |
| SLC2A9 | – |
| COL9A1 | – |
| SCN5A | INDECAINIDE, BENZONATATE, FOSPHENYTOIN, MORICIZINE, HEXYLCAINE, PROCAINAMIDE, MEXILETINE, DISOPYRAMIDE |
| NPPA | CLORTHALIDONE, AMLODIPINE |
| SLC22A12 | LESINURAD, SULFINPYRAZONE |
| COL9A3 | – |
| PYGM | – |
| SVIL | – |
