Ballering, A. V., van Zon, S. K. R., Hartman, T. C. O. & Rosmalen, J. G. M. Persistence of somatic symptoms after COVID-19 in the Netherlands: an observational cohort study. Lancet 400, 452–461 (2022).
Bull-Otterson, L. Post–COVID conditions among adult COVID-19 survivors aged 18–64 and ≥65 years — United States, March 2020–November 2021. MMWR Morb. Mortal. Wkly Rep. 71, 713 (2022).
Ceban, F. et al. Fatigue and cognitive impairment in post-COVID-19 syndrome: a systematic review and meta-analysis. Brain Behav. Immun. 101, 93–135 (2022).
Al-Aly, Z., Bowe, B. & Xie, Y. Long COVID after breakthrough SARS-CoV-2 infection. Nat. Med. https://doi.org/10.1038/s41591-022-01840-0 (2022).
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. Preprint at medRxiv https://doi.org/10.1101/2022.02.23.22271388 (2022).
FAIR Health. Patients Diagnosed with Post-COVID Conditions: An Analysis of Private Healthcare Claims Using the Official ICD-10 Diagnostic Code (FAIR Health, 2022).
Davis, H. E. et al. Characterizing long COVID in an international cohort: 7 months of symptoms and their impact. eClinicalMedicine 38, 101019 (2021).
Xie, Y., Xu, E., Bowe, B. & Al-Aly, Z. Long-term cardiovascular outcomes of COVID-19. Nat. Med. 28, 583–590 (2022).
Xie, Y. & Al-Aly, Z. Risks and burdens of incident diabetes in long COVID: a cohort study. Lancet Diabetes Endocrinol. 10, 311–321 (2022).
Mancini, D. M. et al. Use of cardiopulmonary stress testing for patients with unexplained dyspnea post–coronavirus disease. JACC Heart Fail. 9, 927–937 (2021).
Kedor, C. et al. A prospective observational study of post-COVID-19 chronic fatigue syndrome following the first pandemic wave in Germany and biomarkers associated with symptom severity. Nat. Commun. 13, 5104 (2022).
Larsen, N. W. et al. Characterization of autonomic symptom burden in long COVID: a global survey of 2314 adults. Front. Neurol. 13, 1012668 (2022).
Demko, Z. O. et al. Post-acute sequelae of SARS-CoV-2 (PASC) impact quality of life at 6, 12 and 18 months post-infection. Preprint at medRxiv https://doi.org/10.1101/2022.08.08.22278543 (2022).
Cairns, R. & Hotopf, M. A systematic review describing the prognosis of chronic fatigue syndrome. Occup. Med. Oxf. Engl. 55, 20–31 (2005).
Bach, K. Is ‘long Covid’ worsening the labor shortage? Brookings https://www.brookings.edu/research/is-long-covid-worsening-the-labor-shortage/ (2022).
Swank, Z. et al. Persistent circulating severe acute respiratory syndrome coronavirus 2 spike is associated with post-acute coronavirus disease 2019 sequelae. Clin. Infect. Dis. https://doi.org/10.1093/cid/ciac722 (2022).
Proal, A. D. & VanElzakker, M. B. Long COVID or post-acute sequelae of COVID-19 (PASC): an overview of biological factors that may contribute to persistent symptoms. Front. Microbiol. 12, 698169 (2021).
Klein, J. et al. Distinguishing features of Long COVID identified through immune profiling. Preprint at medRxiv https://doi.org/10.1101/2022.08.09.22278592 (2022).
Glynne, P., Tahmasebi, N., Gant, V. & Gupta, R. Long COVID following mild SARS-CoV-2 infection: characteristic T cell alterations and response to antihistamines. J. Investig. Med. 70, 61–67 (2022).
Phetsouphanh, C. et al. Immunological dysfunction persists for 8 months following initial mild-to-moderate SARS-CoV-2 infection. Nat. Immunol. 23, 210–216 (2022).
Zubchenko, S., Kril, I., Nadizhko, O., Matsyura, O. & Chopyak, V. Herpesvirus infections and post-COVID-19 manifestations: a pilot observational study. Rheumatol. Int. https://doi.org/10.1007/s00296-022-05146-9 (2022).
Peluso, M. J. et al. Evidence of recent Epstein-Barr virus reactivation in individuals experiencing Long COVID. Preprint at medRxiv https://doi.org/10.1101/2022.06.21.22276660 (2022).
Yeoh, Y. K. et al. Gut microbiota composition reflects disease severity and dysfunctional immune responses in patients with COVID-19. Gut 70, 698–706 (2021).
Liu, Q. et al. Gut microbiota dynamics in a prospective cohort of patients with post-acute COVID-19 syndrome. Gut 71, 544–552 (2022).
Mendes de Almeida, V. Gut microbiota from patients with mild COVID-19 cause alterations in mice that resemble post-COVID syndrome. Res. Sq. https://doi.org/10.21203/rs.3.rs-1756189/v1 (2022).
Wallukat, G. et al. Functional autoantibodies against G-protein coupled receptors in patients with persistent long-COVID-19 symptoms. J. Transl Autoimmun. 4, 100100 (2021).
Su, Y. et al. Multiple early factors anticipate post-acute COVID-19 sequelae. Cell 185, 881–895.e20 (2022).
Arthur, J. M. et al. Development of ACE2 autoantibodies after SARS-CoV-2 infection. PLoS ONE 16, e0257016 (2021).
Haffke, M. et al. Endothelial dysfunction and altered endothelial biomarkers in patients with post-COVID-19 syndrome and chronic fatigue syndrome (ME/CFS). J. Transl Med. 20, 138 (2022).
Charfeddine, S. Long COVID 19 syndrome: is it related to microcirculation and endothelial dysfunction? Insights from TUN-EndCOV study. Front. Cardiovasc. Med. https://doi.org/10.3389/fcvm.2021.745758 (2021).
Pretorius, E. et al. Prevalence of symptoms, comorbidities, fibrin amyloid microclots and platelet pathology in individuals with Long COVID/post-acute sequelae of COVID-19 (PASC). Cardiovasc. Diabetol. 21, 148 (2022).
Spudich, S. & Nath, A. Nervous system consequences of COVID-19. Science 375, 267–269 (2022).
Renz-Polster, H., Tremblay, M.-E., Bienzle, D. & Fischer, J. E. The pathobiology of myalgic encephalomyelitis/chronic fatigue syndrome: the case for neuroglial failure. Front. Cell. Neurosci. 16, 888232 (2022).
Merzon, E. et al. Clinical and socio-demographic variables associated with the diagnosis of long COVID syndrome in youth: a population-based study. Int. J. Environ. Res. Public Health 19, 5993 (2022).
CDC. Long COVID – household pulse survey – COVID-19. CDC https://www.cdc.gov/nchs/covid19/pulse/long-covid.htm (2022).
Williamson, A. E., Tydeman, F., Miners, A., Pyper, K. & Martineau, A. R. Short-term and long-term impacts of COVID-19 on economic vulnerability: a population-based longitudinal study (COVIDENCE UK). BMJ Open 12, e065083 (2022).
Ziauddeen, N. et al. Characteristics and impact of Long Covid: findings from an online survey. PLoS ONE 17, e0264331 (2022).
Choutka, J., Jansari, V., Hornig, M. & Iwasaki, A. Unexplained post-acute infection syndromes. Nat. Med. 28, 911–923 (2022).
Komaroff, A. L. & Lipkin, W. I. Insights from myalgic encephalomyelitis/chronic fatigue syndrome may help unravel the pathogenesis of postacute COVID-19 syndrome. Trends Mol. Med. 27, 895–906 (2021).
Schultheiß, C. et al. From online data collection to identification of disease mechanisms: the IL-1ß, IL-6 and TNF-α cytokine triad is associated with post-acute sequelae of COVID-19 in a digital research cohort. SSRN https://doi.org/10.2139/ssrn.3963839 (2021).
Peluso, M. J. et al. Markers of immune activation and inflammation in individuals with postacute sequelae of severe acute respiratory syndrome coronavirus 2 infection. J. Infect. Dis. 224, 1839–1848 (2021).
Fernández-Castañeda, A. et al. Mild respiratory SARS-CoV-2 infection can cause multi-lineage cellular dysregulation and myelin loss in the brain. Preprint at bioRxiv https://doi.org/10.1101/2022.01.07.475453 (2022).
Hornig, M. et al. Distinct plasma immune signatures in ME/CFS are present early in the course of illness. Sci. Adv. 1, e1400121 (2015).
Wang, E. Y. et al. Diverse functional autoantibodies in patients with COVID-19. Nature 595, 283–288 (2021).
Shikova, E. et al. Cytomegalovirus, Epstein-Barr virus, and human herpesvirus-6 infections in patients with myalgic еncephalomyelitis/chronic fatigue syndrome. J. Med. Virol. 92, 3682–3688 (2020).
Schreiner, P. et al. Human herpesvirus-6 reactivation, mitochondrial fragmentation, and the coordination of antiviral and metabolic phenotypes in myalgic encephalomyelitis/chronic fatigue syndrome. Immunohorizons 4, 201–215 (2020).
García-Abellán, J. et al. Antibody response to SARS-CoV-2 is associated with long-term clinical outcome in patients with COVID-19: a longitudinal study. J. Clin. Immunol. 41, 1490–1501 (2021).
Augustin, M. et al. Post-COVID syndrome in non-hospitalised patients with COVID-19: a longitudinal prospective cohort study. Lancet Reg. Health Eur. 6, 100122 (2021).
Talla, A. et al. Longitudinal immune dynamics of mild COVID-19 define signatures of recovery and persistence. Preprint at bioRxiv https://doi.org/10.1101/2021.05.26.442666 (2021).
Peluso, M. J. et al. Long-term SARS-CoV-2-specific immune and inflammatory responses in individuals recovering from COVID-19 with and without post-acute symptoms. Cell Rep. 36, 109518 (2021).
Hu, F. et al. A compromised specific humoral immune response against the SARS-CoV-2 receptor-binding domain is related to viral persistence and periodic shedding in the gastrointestinal tract. Cell. Mol. Immunol. 17, 1119–1125 (2020).
Korte, W. et al. SARS-CoV-2 IgG and IgA antibody response is gender dependent; and IgG antibodies rapidly decline early on. J. Infect. 82, e11–e14 (2021).
Jo, W. et al. A two-phase, single cohort study of COVID-19 antibody sera-surveillance. Ann. Epidemiol. Public Health 4, 1055 (2021).
Nomura, Y. et al. Attenuation of antibody titers from 3 to 6 months after the second dose of the BNT162b2 vaccine depends on sex, with age and smoking risk factors for lower antibody titers at 6 months. Vaccines 9, 1500 (2021).
Tejerina, F. et al. Post-COVID-19 syndrome. SARS-CoV-2 RNA detection in plasma, stool, and urine in patients with persistent symptoms after COVID-19. BMC Infect. Dis. 22, 211 (2022).
Goh, D. et al. Persistence of residual SARS-CoV-2 viral antigen and RNA in tissues of patients with long COVID-19. Preprint at https://www.researchsquare.com/article/rs-1379777/v1 (2022).
Ceulemans, L. J. et al. Persistence of SARS-CoV-2 RNA in lung tissue after mild COVID-19. Lancet Respir. Med. 9, e78–e79 (2021).
Gaebler, C. et al. Evolution of antibody immunity to SARS-CoV-2. Nature 591, 639–644 (2021).
Menuchin-Lasowski, Y. et al. SARS-CoV-2 infects and replicates in photoreceptor and retinal ganglion cells of human retinal organoids. Stem Cell Rep 17, 789–803 (2022).
Cheung, C. C. L. et al. Residual SARS-CoV-2 viral antigens detected in GI and hepatic tissues from five recovered patients with COVID-19. Gut 71, 226–229 (2022).
Natarajan, A. et al. Gastrointestinal symptoms and fecal shedding of SARS-CoV-2 RNA suggest prolonged gastrointestinal infection. Med 3, 371–387.e9 (2022).
Katsoularis, I. et al. Risks of deep vein thrombosis, pulmonary embolism, and bleeding after covid-19: nationwide self-controlled cases series and matched cohort study. BMJ 377, e069590 (2022).
Pretorius, E. et al. Persistent clotting protein pathology in Long COVID/post-acute sequelae of COVID-19 (PASC) is accompanied by increased levels of antiplasmin. Cardiovasc. Diabetol. 20, 172 (2021).
Kubánková, M. et al. Physical phenotype of blood cells is altered in COVID-19. Biophys. J. 120, 2838–2847 (2021).
Osiaevi, I. et al. Persistent capillary rarefication in long COVID syndrome. Angiogenesis https://doi.org/10.1007/s10456-022-09850-9 (2022).
Patel, M. A. et al. Elevated vascular transformation blood biomarkers in long-COVID indicate angiogenesis as a key pathophysiological mechanism. Mol. Med. 28, 122 (2022).
Puntmann, V. O. et al. Outcomes of cardiovascular magnetic resonance imaging in patients recently recovered from coronavirus disease 2019 (COVID-19). JAMA Cardiol 5, 1265–1273 (2020).
Roca-Fernández, A. et al. Cardiac impairment in Long Covid 1-year post-SARS-CoV-2 infection. Eur. Heart J. 43, ehac544.219 (2022).
Dennis, A. et al. Multiorgan impairment in low-risk individuals with post-COVID-19 syndrome: a prospective, community-based study. BMJ Open 11, e048391 (2021).
Dennis, A. et al. Multi-organ impairment and Long COVID: a 1-year prospective, longitudinal cohort study. Preprint at medRxiv https://doi.org/10.1101/2022.03.18.22272607 (2022).
Bowe, B., Xie, Y., Xu, E. & Al-Aly, Z. Kidney outcomes in Long COVID. J. Am. Soc. Nephrol. 32, 2851–2862 (2021).
Almufarrij, I. & Munro, K. J. One year on: an updated systematic review of SARS-CoV-2, COVID-19 and audio-vestibular symptoms. Int. J. Audiol. 60, 935–945 (2021).
Holdsworth, D. A. et al. Comprehensive clinical assessment identifies specific neurocognitive deficits in working-age patients with long-COVID. PLoS ONE 17, e0267392 (2022).
Cysique, L. A. et al. Post-acute COVID-19 cognitive impairment and decline uniquely associate with kynurenine pathway activation: a longitudinal observational study. Preprint at medRxiv https://doi.org/10.1101/2022.06.07.22276020 (2022).
Crivelli, L. et al. Changes in cognitive functioning after COVID-19: a systematic review and meta-analysis. Alzheimers Dement. 18, 1047–1066 (2022).
Woo, M. S. et al. Frequent neurocognitive deficits after recovery from mild COVID-19. Brain Commun. 2, fcaa205 (2020).
Taquet, M. et al. Neurological and psychiatric risk trajectories after SARS-CoV-2 infection: an analysis of 2-year retrospective cohort studies including 1 284 437 patients. Lancet Psychiatry 9, 815–827 (2022).
Reiken, S. et al. Alzheimer’s-like signaling in brains of COVID-19 patients. Alzheimers Dement. 18, 955–965 (2022).
Charnley, M. et al. Neurotoxic amyloidogenic peptides in the proteome of SARS-COV2: potential implications for neurological symptoms in COVID-19. Nat. Commun. 13, 3387 (2022).
Visser, D. et al. Long COVID is associated with extensive in-vivo neuroinflammation on [18F]DPA-714 PET. Preprint at medRxiv https://doi.org/10.1101/2022.06.02.22275916 (2022).
Guedj, E. et al. 18F-FDG brain PET hypometabolism in patients with long COVID. Eur. J. Nucl. Med. Mol. Imaging 48, 2823–2833 (2021).
Hugon, J. et al. Cognitive decline and brainstem hypometabolism in long COVID: a case series. Brain Behav. 12, e2513 (2022).
Apple, A. C. et al. Risk factors and abnormal cerebrospinal fluid associate with cognitive symptoms after mild COVID-19. Ann. Clin. Transl Neurol. 9, 221–226 (2022).
Douaud, G. et al. SARS-CoV-2 is associated with changes in brain structure in UK Biobank. Nature 604, 697–707 (2022).
Peluso, M. J. et al. SARS-CoV-2 and mitochondrial proteins in neural-derived exosomes of COVID-19. Ann. Neurol. 91, 772–781 (2022).
Villaume, W. A. Marginal BH4 deficiencies, iNOS, and self-perpetuating oxidative stress in post-acute sequelae of Covid-19. Med. Hypotheses 163, 110842 (2022).
Bitirgen, G. et al. Corneal confocal microscopy identifies corneal nerve fibre loss and increased dendritic cells in patients with long COVID. Br. J. Ophthalmol. https://doi.org/10.1136/bjophthalmol-2021-319450 (2021).
Barros, A. et al. Small fiber neuropathy in the cornea of Covid-19 patients associated with the generation of ocular surface disease. Ocul. Surf. 23, 40–48 (2022).
Bitirgen, G. et al. Abnormal quantitative pupillary light responses following COVID-19. Int. Ophthalmol. https://doi.org/10.1007/s10792-022-02275-9 (2022).
Mardin, C. Y. et al. Possible impact of functional active GPCR-autoantibodies on retinal microcirculation in long-COVID. Invest. Ophthalmol. Vis. Sci. 63, 3315–F0124 (2022).
Zhang, B.-Z. et al. SARS-CoV-2 infects human neural progenitor cells and brain organoids. Cell Res. 30, 928–931 (2020).
Sen, S. et al. Retinal manifestations in patients with SARS-CoV-2 infection and pathogenetic implications: a systematic review. Int. Ophthalmol. 42, 323–336 (2022).
Frere, J. J. et al. SARS-CoV-2 infection in hamsters and humans results in lasting and unique systemic perturbations post recovery. Sci. Transl Med. 14, eabq3059 (2022).
Rutkai, I. et al. Neuropathology and virus in brain of SARS-CoV-2 infected non-human primates. Nat. Commun. 13, 1745 (2022).
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 (National Academies Press, 2015).
Bateman, L. et al. Myalgic encephalomyelitis/chronic fatigue syndrome: essentials of diagnosis and management. Mayo Clin. Proc. 96, 2861–2878 (2021).
The ME Association. Index of ME/CFS published research – Nov 2022. 224 Index of ME/CFS Published Research. The ME Association https://meassociation.org.uk/ (2022).
Seltzer, J. & Thomas, J. ME Research Summary 2019 (The ME Association, 2019).
Wong, T. L. & Weitzer, D. J. Long COVID and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)-a systemic review and comparison of clinical presentation and symptomatology. Med. (Kaunas.) 57, 418 (2021).
Twomey, R. et al. Chronic fatigue and postexertional malaise in people living with Long COVID: an observational study. Phys. Ther. 102, pzac005 (2022).
Vernon, S. D. et al. Orthostatic challenge causes distinctive symptomatic, hemodynamic and cognitive responses in Long COVID and myalgic encephalomyelitis/chronic fatigue syndrome. Front. Med. 9, 917019 (2022).
Lam, M. H.-B. et al. Mental morbidities and chronic fatigue in severe acute respiratory syndrome survivors: long-term follow-up. Arch. Intern. Med. 169, 2142–2147 (2009).
Keller, B. A., Pryor, J. L. & Giloteaux, L. Inability of myalgic encephalomyelitis/chronic fatigue syndrome patients to reproduce VO2peak indicates functional impairment. J. Transl Med. 12, 104 (2014).
Saha, A. K. et al. Erythrocyte deformability as a potential biomarker for chronic fatigue syndrome. Blood 132, 4874 (2018).
Díaz-Resendiz, K. J. G. et al. Loss of mitochondrial membrane potential (ΔΨm) in leucocytes as post-COVID-19 sequelae. J. Leukoc. Biol. 112, 23–29 (2022).
Pozzi, A. COVID-19 and mitochondrial non-coding RNAs: new insights from published data. Front. Physiol. 12, 805005 (2022).
Guntur, V. P. et al. Signatures of mitochondrial dysfunction and impaired fatty acid metabolism in plasma of patients with post-acute sequelae of COVID-19 (PASC). Metabolites 12, 1026 (2022).
Paul, B. D., Lemle, M. D., Komaroff, A. L. & Snyder, S. H. Redox imbalance links COVID-19 and myalgic encephalomyelitis/chronic fatigue syndrome. Proc. Natl Acad. Sci. USA 118, e2024358118 (2021).
Wright, J., Astill, S. L. & Sivan, M. The relationship between physical activity and Long COVID: a cross-sectional study. Int. J. Environ. Res. Public Health 19, 5093 (2022).
Heerdt, P. M., Shelley, B. & Singh, I. Impaired systemic oxygen extraction long after mild COVID-19: potential perioperative implications. Br. J. Anaesth. 128, e246–e249 (2022).
Novak, P. et al. Multisystem involvement in post-acute sequelae of coronavirus disease 19. Ann. Neurol. 91, 367–379 (2022).
Holmes, E. et al. Incomplete systemic recovery and metabolic phenoreversion in post-acute-phase nonhospitalized COVID-19 patients: implications for assessment of post-acute COVID-19 syndrome. J. Proteome Res. 20, 3315–3329 (2021).
van Campen, C. L. M. C. & Visser, F. C. Orthostatic intolerance in long-haul COVID after SARS-CoV-2: a case-control comparison with post-EBV and insidious-onset myalgic encephalomyelitis/chronic fatigue syndrome patients. Healthcare 10, 2058 (2022).
van Campen, C. L. M. C. & Visser, F. C. Long-Haul COVID patients: prevalence of POTS are reduced but cerebral blood flow abnormalities remain abnormal with longer disease duration. Healthcare 10, 2105 (2022).
Nunes, J. M., Kruger, A., Proal, A., Kell, D. B. & Pretorius, E. The occurrence of hyperactivated platelets and fibrinaloid microclots in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Pharmaceuticals 15, 931 (2022).
Hoad, A., Spickett, G., Elliott, J. & Newton, J. Postural orthostatic tachycardia syndrome is an under-recognized condition in chronic fatigue syndrome. QJM 101, 961–965 (2008).
Shaw, B. H. et al. The face of postural tachycardia syndrome – insights from a large cross‐sectional online community‐based survey. J. Intern. Med. 286, 438–448 (2019).
Raj, S. R. et al. Postural orthostatic tachycardia syndrome (POTS): priorities for POTS care and research from a 2019 National Institutes of Health expert consensus meeting – part 2. Auton. Neurosci. Basic. Clin. 235, 102836 (2021).
Oaklander, A. L. et al. Peripheral neuropathy evaluations of patients with prolonged Long COVID. Neurol. Neuroimmunol. Neuroinflamm. 9, e1146 (2022).
Larsen, N. W. et al. Characterization of autonomic symptom burden in long COVID: a global survey of 2,314 adults. Front. Neurol. 13, 1012668 (2022).
Weinstock, L. B. et al. Mast cell activation symptoms are prevalent in Long-COVID. Int. J. Infect. Dis. 112, 217–226 (2021).
Boneva, R. S. et al. Endometriosis as a comorbid condition in chronic fatigue syndrome (CFS): secondary analysis of data from a CFS case-control study. Front. Pediatr. 7, 195 (2019).
Bragée, B. et al. Signs of intracranial hypertension, hypermobility, and craniocervical obstructions in patients with myalgic encephalomyelitis/chronic fatigue syndrome. Front. Neurol. 11, (2020).
Medina-Perucha, L. et al. Self-reported menstrual alterations during the COVID-19 syndemic in Spain: a cross-sectional study. Int. J. Womens Health 14, 529–544 (2022).
Ding, T. et al. Analysis of ovarian injury associated with COVID-19 disease in reproductive-aged women in Wuhan, China: an observational study. Front. Med. 8, 635255 (2021).
Sharp, G. C. et al. The COVID-19 pandemic and the menstrual cycle: research gaps and opportunities. Int. J. Epidemiol. https://doi.org/10.1093/ije/dyab239 (2021).
Khan, S. M. et al. SARS-CoV-2 infection and subsequent changes in the menstrual cycle among participants in the Arizona CoVHORT study. Am. J. Obstet. Gynecol. 226, 270–273 (2022).
Harlow, B. L., Signorello, L. B., Hall, J. E., Dailey, C. & Komaroff, A. L. Reproductive correlates of chronic fatigue syndrome. Am. J. Med. 105, 94S–99S (1998).
Thomas, N., Gurvich, C., Huang, K., Gooley, P. R. & Armstrong, C. W. The underlying sex differences in neuroendocrine adaptations relevant to myalgic encephalomyelitis chronic fatigue syndrome. Front. Neuroendocrinol. 66, 100995 (2022).
Boneva, R. S., Lin, J.-M. S. & Unger, E. R. Early menopause and other gynecologic risk indicators for chronic fatigue syndrome in women. Menopause 22, 826–834 (2015).
Kresch, E. et al. COVID-19 endothelial dysfunction can cause erectile dysfunction: histopathological, immunohistochemical, and ultrastructural study of the human penis. World J. Mens Health 39, 466–469 (2021).
Maleki, B. H. & Tartibian, B. COVID-19 and male reproductive function: a prospective, longitudinal cohort study. Reproduction 161, 319–331 (2021).
Yu, J. Z. et al. Lung perfusion disturbances in nonhospitalized post-COVID with dyspnea — a magnetic resonance imaging feasibility study. J. Intern. Med. 292, 941–956 (2022).
Cho, J. L. et al. Quantitative chest CT assessment of small airways disease in post-acute SARS-CoV-2 infection. Radiology 304, 185–192 (2022).
Vijayakumar, B. et al. Immuno-proteomic profiling reveals aberrant immune cell regulation in the airways of individuals with ongoing post-COVID-19 respiratory disease. Immunity 55, 542–556.e5 (2022).
Littlefield, K. M. et al. SARS-CoV-2-specific T cells associate with inflammation and reduced lung function in pulmonary post-acute sequalae of SARS-CoV-2. PLOS Pathog. 18, e1010359 (2022).
Meringer, H. & Mehandru, S. Gastrointestinal post-acute COVID-19 syndrome. Nat. Rev. Gastroenterol. Hepatol. 19, 345–346 (2022).
König, R. S. et al. The gut microbiome in myalgic encephalomyelitis (ME)/chronic fatigue syndrome (CFS). Front. Immunol. 12, 628741 (2022).
Zuo, T. et al. Depicting SARS-CoV-2 faecal viral activity in association with gut microbiota composition in patients with COVID-19. Gut 70, 276–284 (2021).
Zollner, A. et al. Postacute COVID-19 is characterized by gut viral antigen persistence in inflammatory bowel diseases. Gastroenterology 163, 495–506.e8 (2022).
Giron, L. B. et al. Markers of fungal translocation are elevated during post-acute sequelae of SARS-CoV-2 and induce NF-κB signaling. JCI Insight https://doi.org/10.1172/jci.insight.160989 (2022).
Jason, L. A. et al. COVID-19 symptoms over time: comparing long-haulers to ME/CFS. Fatigue Biomed. Health Behav. 9, 59–68 (2021).
Tran, V.-T., Porcher, R., Pane, I. & Ravaud, P. Course of post COVID-19 disease symptoms over time in the ComPaRe long COVID prospective e-cohort. Nat. Commun. 13, 1812 (2022).
Walker, A., Kelly, C., Pottinger, G. & Hopkins, C. Parosmia — a common consequence of covid-19. BMJ 377, e069860 (2022).
Jamal, S. M. et al. Prospective evaluation of autonomic dysfunction in post-acute sequela of COVID-19. J. Am. Coll. Cardiol. 79, 2325–2330 (2022).
Stavileci, B., Özdemir, E., Özdemir, B., Ereren, E. & Cengiz, M. De-novo development of fragmented QRS during a six-month follow-up period in patients with COVID-19 disease and its cardiac effects. J. Electrocardiol. 72, 44–48 (2022).
Grist, J. T. et al. Lung abnormalities depicted with hyperpolarized 129Xe MRI in patients with long COVID. Radiology 305, 709–717 (2022).
US ME/CFS Clinician Coalition. Testing Recommendations for Suspected ME/CFS (US ME/CFS Clinician Coalition, 2021).
Galán, M. et al. Persistent overactive cytotoxic immune response in a Spanish cohort of individuals with long-COVID: identification of diagnostic biomarkers. Front. Immunol. 13, 848886 (2022).
Grandjean, D. et al. Screening for SARS-CoV-2 persistence in Long COVID patients using sniffer dogs and scents from axillary sweats samples. Clin. Trials 12, 2 (2022).
Pifarré, F. et al. The use of oxygen as a possible screening biomarker for the diagnosis of chronic fatigue. Apunt. Sports Med 57, 100379 (2022).
Jason, L. A., Kalns, J., Richarte, A., Katz, B. Z. & Torres, C. Saliva fatigue biomarker index as a marker for severe myalgic encephalomyelitis/chronic fatigue syndrome in a community based sample. Fatigue Biomed. Health Behav. 9, 189–195 (2021).
Esfandyarpour, R., Kashi, A., Nemat-Gorgani, M., Wilhelmy, J. & Davis, R. W. A nanoelectronics-blood-based diagnostic biomarker for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Proc. Natl Acad. Sci. USA 116, 10250–10257 (2019).
Nkiliza, A. et al. Sex-specific plasma lipid profiles of ME/CFS patients and their association with pain, fatigue, and cognitive symptoms. J. Transl Med. 19, 370 (2021).
Bolton, M. J., Chapman, B. P. & Van Marwijk, H. Low-dose naltrexone as a treatment for chronic fatigue syndrome. BMJ Case Rep. 13, e232502 (2020).
Pitt, B., Tate, A. M., Gluck, D., Rosenson, R. S. & Goonewardena, S. N. Repurposing low-dose naltrexone (LDN) for the prevention and treatment of immunothrombosis in COVID-19. Eur. Heart J. Cardiovasc. Pharmacother. https://doi.org/10.1093/ehjcvp/pvac014 (2022).
Alper, K. Case report: famotidine for neuropsychiatric symptoms in COVID-19. Front. Med. 7, 614393 (2020).
Hohberger, B. et al. Case report: neutralization of autoantibodies targeting G-protein-coupled receptors improves capillary impairment and fatigue symptoms after COVID-19 infection. Front. Med. 8, 754667 (2021).
Wang, C. et al. Long COVID: the nature of thrombotic sequelae determines the necessity of early anticoagulation. Front. Cell. Infect. Microbiol. 12, 861703 (2022).
The ME Association. A new treatment for Long Covid? The ME Association https://meassociation.org.uk/2021/10/a-new-treatment-for-long-covid/ (2021).
Tölle, M. et al. Myalgic encephalomyelitis/chronic fatigue syndrome: efficacy of repeat immunoadsorption. J. Clin. Med. 9, E2443 (2020).
Wood, E., Hall, K. H. & Tate, W. Role of mitochondria, oxidative stress and the response to antioxidants in myalgic encephalomyelitis/chronic fatigue syndrome: a possible approach to SARS-CoV-2 ‘long-haulers’? Chronic Dis. Transl Med. 7, 14–26 (2020).
NICE. Myalgic encephalomyelitis (or encephalopathy)/chronic fatigue syndrome: diagnosis and management. NICE https://www.nice.org.uk/guidance/NG206 (2021).
World Health Organization. Support for Rehabilitation Self-Management After COVID-19 Related Illness (WHO, 2021).
CDC. Treatment of ME/CFS | Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). CDC https://www.cdc.gov/me-cfs/treatment/index.html (2021).
Long COVID Physio. Exercise. Long COVID Physio https://longcovid.physio/exercise (2022).
Geng, L. N., Bonilla, H. F., Shafer, R. W., Miglis, M. G. & Yang, P. C. Case report of breakthrough long COVID and the use of nirmatrelvir-ritonavir. Preprint at https://www.researchsquare.com/article/rs-1443341/v1 (2022).
Xie, Y., Choi, T. & Al-Aly, Z. Nirmatrelvir and the risk of post-acute sequelae of COVID-19. Preprint at medRxiv https://doi.org/10.1101/2022.11.03.22281783 (2022).
Charfeddine, S. et al. Sulodexide in the treatment of patients with long COVID 19 symptoms and endothelial dysfunction: the results of TUN-EndCOV study. Arch. Cardiovasc. Dis. Suppl. 14, 127 (2022).
Thomas, R. et al. A randomised, double-blind, placebo-controlled trial evaluating concentrated phytochemical-rich nutritional capsule in addition to a probiotic capsule on clinical outcomes among individuals with COVID-19 — the UK Phyto-V study. COVID 2, 433–449 (2022).
Zhang, L. et al. Gut microbiota-derived synbiotic formula (SIM01) as a novel adjuvant therapy for COVID-19: an open-label pilot study. J. Gastroenterol. Hepatol. 37, 823–831 (2022).
Liu, L. D. & Duricka, D. L. Stellate ganglion block reduces symptoms of Long COVID: a case series. J. Neuroimmunol. 362, 577784 (2022).
Belcaro, G. et al. Preventive effects of Pycnogenol® on cardiovascular risk factors (including endothelial function) and microcirculation in subjects recovering from coronavirus disease 2019 (COVID-19). Minerva Med. 113, 300–308 (2022).
Crooks, V., Waller, S., Smith, T. & Hahn, T. J. The use of the Karnofsky Performance Scale in determining outcomes and risk in geriatric outpatients. J. Gerontol. 46, M139–M144 (1991).
Ledford, H. Long-COVID treatments: why the world is still waiting. Nature 608, 258–260 (2022).
Toogood, P. L., Clauw, D. J., Phadke, S. & Hoffman, D. Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): where will the drugs come from? Pharmacol. Res. 165, 105465 (2021).
US ME/CFS Clinician Coalition. ME/CFS Treatment Recommendations (US ME/CFS Clinician Coalition, 2021).
Taquet, M., Dercon, Q. & Harrison, P. J. Six-month sequelae of post-vaccination SARS-CoV-2 infection: a retrospective cohort study of 10,024 breakthrough infections. Brain Behav. Immun. 103, 154–162 (2022).
Office for National Statistics. Self-reported long COVID after infection with the Omicron variant in the UK: 6 May 2022. Office for National Statistics https://www.ons.gov.uk/peoplepopulationandcommunity/healthandsocialcare/conditionsanddiseases/bulletins/selfreportedlongcovidafterinfectionwiththeomicronvariant/6may2022 (2022).
Tsuchida, T. et al. Relationship between changes in symptoms and antibody titers after a single vaccination in patients with Long COVID. J. Med. Virol. 94, 3416–3420 (2022).
VA COVID-19 Observational Research Collaboratory. Burden of PCR-confirmed SARS-CoV-2 reinfection in the U.S. Veterans Administration, March 2020 – January 2022. Preprint at medRxiv https://doi.org/10.1101/2022.03.20.22272571 (2022).
Bowe, B., Xie, Y. & Al-Aly, Z. Acute and postacute sequelae associated with SARS-CoV-2 reinfection. Nat. Med. https://doi.org/10.1038/s41591-022-02051-3 (2022).
Blomberg, J., Gottfries, C.-G., Elfaitouri, A., Rizwan, M. & Rosén, A. Infection elicited autoimmunity and myalgic encephalomyelitis/chronic fatigue syndrome: an explanatory model. Front. Immunol. 9, 229 (2018).
Cauchemez, S. & Bosetti, P. A reconstruction of early cryptic COVID spread. Nature 600, 40–41 (2021).
CDC. Estimated COVID-19 burden. Centers for Disease Control and Prevention https://www.cdc.gov/coronavirus/2019-ncov/cases-updates/burden.html (2020).
Kucirka, L. M., Lauer, S. A., Laeyendecker, O., Boon, D. & Lessler, J. Variation in false-negative rate of reverse transcriptase polymerase chain reaction–based SARS-CoV-2 tests by time since exposure. Ann. Intern. Med. 173, 262–267 (2020).
Levine-Tiefenbrun, M. et al. SARS-CoV-2 RT-qPCR test detection rates are associated with patient age, sex, and time since diagnosis. J. Mol. Diagn. 24, 112–119 (2022).
Jarvis, K. F. & Kelley, J. B. Temporal dynamics of viral load and false negative rate influence the levels of testing necessary to combat COVID-19 spread. Sci. Rep. 11, 9221 (2021).
Dattner, I. et al. The role of children in the spread of COVID-19: using household data from Bnei Brak, Israel, to estimate the relative susceptibility and infectivity of children. PLoS Comput. Biol. 17, e1008559 (2021).
Langeland, N. & Cox, R. J. Are low SARS-CoV-2 viral loads in infected children missed by RT-PCR testing? Lancet Reg. Health Eur. 5, 100138 (2021).
Van Elslande, J. et al. Longitudinal follow-up of IgG anti-nucleocapsid antibodies in SARS-CoV-2 infected patients up to eight months after infection. J. Clin. Virol. 136, 104765 (2021).
Liu, W. et al. Predictors of nonseroconversion after SARS-CoV-2 infection. Emerg. Infect. Dis. 27, 2454–2458 (2021).
Toh, Z. Q. et al. Comparison of seroconversion in children and adults with mild COVID-19. JAMA Netw. Open 5, e221313 (2022).
Peterson, T. M., Peterson, T. W., Emerson, S., Meredyth, A. Evans, E. R. & Jason, L. A. Coverage of CFS within U.S. medical schools. Univers. J. Public Health 1, 177–179 (2013).
Rowe, P. C. et al. Orthostatic intolerance and chronic fatigue syndrome associated with Ehlers-Danlos syndrome. J. Pediatr. 135, 494–499 (1999).
Nguyen, T. et al. Novel characterisation of mast cell phenotypes from peripheral blood mononuclear cells in chronic fatigue syndrome/myalgic encephalomyelitis patients. Asian Pac. J. Allergy Immunol. 35, 75–81 (2017).
Wagner, C., Isenmann, S., Ringendahl, H. & Haensch, C.-A. Anxiety in patients with postural tachycardia syndrome (POTS). Fortschr. Neurol. Psychiatr. 80, 458–462 (2012).
Grayson, D. A., Mackinnon, A., Jorm, A. F., Creasey, H. & Broe, G. A. Item bias in the center for epidemiologic studies depression scale: effects of physical disorders and disability in an elderly community sample. J. Gerontol. Ser. B 55, P273–P282 (2000).
Twisk, F. N. M. & Maes, M. A review on cognitive behavorial therapy (CBT) and graded exercise therapy (GET) in myalgic encephalomyelitis (ME) / chronic fatigue syndrome (CFS): CBT/GET is not only ineffective and not evidence-based, but also potentially harmful for many patients with ME/CFS. Neuro Endocrinol. Lett. 30, 284–299 (2009).
Vink, M. & Vink-Niese, F. Is it useful to question the recovery behaviour of patients with ME/CFS or Long COVID? Healthcare 10, 392 (2022).
Dysautonomia International. What is dysautonomia? Dysautonomia International http://www.dysautonomiainternational.org/page.php?ID=34 (2022).
CDC. Epidemiology | Presentation and clinical course | Healthcare providers | Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). CDC https://www.cdc.gov/me-cfs/healthcare-providers/presentation-clinical-course/epidemiology.html (2021).
Sørensen, A. I. V. et al. A nationwide questionnaire study of post-acute symptoms and health problems after SARS-CoV-2 infection in Denmark. Nat. Commun. 13, 4213 (2022).
Berg, S. K. et al. Long COVID symptoms in SARS-CoV-2-positive children aged 0–14 years and matched controls in Denmark (LongCOVIDKidsDK): a national, cross-sectional study. Lancet Child Adolesc. Health 6, 614–623 (2022).
Morrow, A. K. et al. Long-term COVID 19 sequelae in adolescents: the overlap with orthostatic intolerance and ME/CFS. Curr. Pediatr. Rep. 10, 31–44 (2022).
Cooper, S. et al. Long COVID-19 liver manifestation in children. J. Pediatr. Gastroenterol. Nutr. https://doi.org/10.1097/MPG.0000000000003521 (2022).
Kompaniyets, L. Post–COVID-19 symptoms and conditions among children and adolescents — United States, March 1, 2020–January 31, 2022. MMWR Morb. Mortal. Wkly Rep. 71, 993–999 (2022).
Edlow, A. G., Castro, V. M., Shook, L. L., Kaimal, A. J. & Perlis, R. H. Neurodevelopmental outcomes at 1 year in infants of mothers who tested positive for SARS-CoV-2 during pregnancy. JAMA Netw. Open 5, e2215787 (2022).
Morand, A. et al. Similar patterns of [18F]-FDG brain PET hypometabolism in paediatric and adult patients with long COVID: a paediatric case series. Eur. J. Nucl. Med. Mol. Imaging 49, 913–920 (2022).
Heiss, R. et al. Pulmonary dysfunction after pediatric COVID-19. Radiology https://doi.org/10.1148/radiol.221250 (2022).