clinmedКлиническая медицинаClinical Medicine (Russian Journal)0023-21492412-1339ООО «Медицинское информационное агентство»10.30629/0023-2149-2021-99-7-8-429-435clinmed-284Research ArticleОБЗОРЫ И ЛЕКЦИИREVIEWS AND LECTURESПостковидный синдромPost-COVID-19 syndromehttps://orcid.org/0000-0002-2025-8119АсфандияроваН. С.AsfandiyarovaN. S.

Асфандиярова Наиля Сайфуллаевна, д-р мед. наук, доцент кафедры поликлинической терапии, профилактической медицины и врачебной общей практики 

390026, Рязань

 

Nailya S. Asfandiyarova

390026, Ryazan

n.asfandiyarova2010@yandex.ruФГБОУ ВО «Рязанский государственный медицинский университет имени академика И.П. Павлова» Минздрава РоссииРоссияRyazan State Medical UniversityRussian Federation202104012022997-8429435Copyright © Асфандиярова Н.С., 20222022Асфандиярова Н.С.Asfandiyarova N.S.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.clinmedjournal.com/jour/article/view/284

Заболевание, вызванное новой коронавирусной инфекцией (COVID-19), является глобальной проблемой, и не только по причине широкого распространения, но и в связи с высокой частотой развития постковидного синдрома. В обзоре литературы представлены результаты многочисленных наблюдений за пациентами, перенесшими COVID-19. Описаны наиболее частые симптомы постковидного синдрома, разбираются причины и факторы риска его развития. Отсутствие единства взглядов на термин «постковидный синдром» затрудняет оценку частоты развития тех или иных симптомов. Рассматриваются варианты постковидного синдрома, предлагается разграничить развившийся после острого COVID-19 постковидный синдром длительностью до 12 нед. и продолжительный вариант постковидных клинических симптомов длительностью более 12 нед., которые следует отличать от затяжного COVID-19, его осложнений, последствий интенсивной терапии. Разбираются вопросы прогноза, диагностики, лечения постковидного синдрома.

The disease caused by new coronavirus infection (COVID-19) is a global problem not only because of its wide spread occurrance, but also due to the high incidence of post-COVID syndrome. The literature review presents the results of numerous observations of patients, who undergone COVID-19. The most common symptoms are: general weakness, impaired cognitive functions, memory loss, depression, anosmia, dysgeusia, shortness of breath, cough, chest pain, abdominal pain, anorexia, nausea, vomiting, diarrhea, less often — alopecia, skin rashes, etc. The most frequent symptoms of the post-COVID syndrome are described; the reasons and risk factors for its development are analyzed. The lack of views sameness on the term “postCOVID syndrome” makes it diffi cult to evaluate the frequency of certain symptoms development. Variants of the post-COVID syndrome are considered. It is proposed to distinguish between the post-COVID syndrome, developed after acute COVID-19 that lasts up to 12 weeks, and a prolonged variant of post-COVID clinical symptoms that last longer than 12 weeks, which should be distinguished from lingering COVID-19, its complications, and the consequences of intensive care. The questions of prognosis, diagnostics, and treatment of post-COVID syndrome are discussed.

новая коронавирусная инфекцияпостковидный синдромклиникадиагностикалечениеnew coronavirus infectionpost-COVID syndromeclinicdiagnosticstreatmentReferencesKlitzman R.L. Needs to Prepare for «Post-COVID-19 Syndrome». Am. J. Bioeth. 2020;20(11):4–6. Available from: https://doi.org/10.1 080/15265161.2020.1820755Klitzman R.L. Needs to Prepare for «Post-COVID-19 Syndrome». Am. J. Bioeth. 2020;20(11):4–6. Available from: https://doi.org/10.1 080/15265161.2020.1820755Amenta E.M., Spallone A., Rodriguez-Barradas M.C., El Sahly H.M., Atmar R.L., Kulkarni P.A. Post-acute COVID-19: an overview and approach to classifi cation. Open Forum Infect. Dis. [Internet] 2020. [cited 2020 Dec 13]; Available from: https://www.ncbi. nlm.nih.gov/pmc/articles/PMC7665635/Amenta E.M., Spallone A., Rodriguez-Barradas M.C., El Sahly H.M., Atmar R.L., Kulkarni P.A. Post-acute COVID-19: an overview and approach to classifi cation. Open Forum Infect. Dis. [Internet] 2020. [cited 2020 Dec 13]; Available from: https://www.ncbi. nlm.nih.gov/pmc/articles/PMC7665635/Arnold D.T., Hamilton F.W., Milne A., Morley A.J., Viner J., Attwood M. et al. Patient outcomes after hospitalisation with COVID-19 and implications for follow-up: results from a prospective UK cohort. Thorax. 2020; Dec. 3 [Epub ahead of print]. Available from: https://thorax.bmj.com/content/early/2020/12/02/ thoraxjnl-2020-216086Arnold D.T., Hamilton F.W., Milne A., Morley A.J., Viner J., Attwood M. et al. Patient outcomes after hospitalisation with COVID-19 and implications for follow-up: results from a prospective UK cohort. Thorax. 2020; Dec. 3 [Epub ahead of print]. Available from: https://thorax.bmj.com/content/early/2020/12/02/ thoraxjnl-2020-216086Chopra V., Flanders S.A., O’Malley M., Malani A.N., Prescott H.C. Sixty-day outcomes among patients hospitalized with COVID-19. Ann. Intern. Med. 2020; Nov. 11 [Epub ahead of print]. Available from: https://www.acpjournals.org/doi/10.7326/M20-5661Chopra V., Flanders S.A., O’Malley M., Malani A.N., Prescott H.C. Sixty-day outcomes among patients hospitalized with COVID-19. Ann. Intern. Med. 2020; Nov. 11 [Epub ahead of print]. Available from: https://www.acpjournals.org/doi/10.7326/M20-5661Halpin S.J., McIvor C., Whyatt G., Adams A., Harvey O., McLean L. et al. Post discharge symptoms and rehabilitation needs in survivors of COVID-19 infection: a cross-sectional evaluation. J. Med. Virol. 2020; First published: 30 July 2020. Available from: https://doi. org/10.1002/jmv.26368Halpin S.J., McIvor C., Whyatt G., Adams A., Harvey O., McLean L. et al. Post discharge symptoms and rehabilitation needs in survivors of COVID-19 infection: a cross-sectional evaluation. J. Med. Virol. 2020; First published: 30 July 2020. Available from: https://doi. org/10.1002/jmv.26368Moreno-Pérez O., Merino E., Leon-Ramirez J.-M., Andres M., Ramos J.M., Arenas-Jiménez J. et al. Post-acute COVID-19 Syndrome incidence and risk factors: a Mediterranean cohort study. J. Infect. 2021;82(3):378–383. DOI: 10.1016/j.jinf.2021.01.004Moreno-Pérez O., Merino E., Leon-Ramirez J.-M., Andres M., Ramos J.M., Arenas-Jiménez J. et al. Post-acute COVID-19 Syndrome incidence and risk factors: a Mediterranean cohort study. J. Infect. 2021;82(3):378–383. DOI: 10.1016/j.jinf.2021.01.004Willi S., Lüthold R Hunt A Hänggi N.V., Sejdiu D., Scaff C., Bender N. et al. COVID-19 sequelae in adults aged less than 50 years: a systematic review. Travel Med. Infect. Dis. 2021;40:101995. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/ PMC7898978/Willi S., Lüthold R Hunt A Hänggi N.V., Sejdiu D., Scaff C., Bender N. et al. COVID-19 sequelae in adults aged less than 50 years: a systematic review. Travel Med. Infect. Dis. 2021;40:101995. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/ PMC7898978/Carfì A., Bernabei R., Landi F. Gemelli against COVID-19 postacute care study group. Persistent symptoms in patients after acute COVID-19. JAMA. 2020;324:603–605 Available from: https://jamanetwork.com/journals/jama/fullarticle/2768351Carfì A., Bernabei R., Landi F. Gemelli against COVID-19 postacute care study group. Persistent symptoms in patients after acute COVID-19. JAMA. 2020;324:603–605 Available from: https://jamanetwork.com/journals/jama/fullarticle/2768351Carvalho-Schneider C., Laurent E., Lemaignen A., Beaufi ls E., Bourbao-Tournois C., Laribi S. et al. Follow-up of adults with noncriti cal COVID-19 two months after symptoms’ onset. Follow-up of adults with non-critical COVID-19 two months after symptoms’ onset. Clin.Microbiol. Infect. 2021;27(2):258–263. DOI: 10.1016/j. cmi.2020.09.052Carvalho-Schneider C., Laurent E., Lemaignen A., Beaufi ls E., Bourbao-Tournois C., Laribi S. et al. Follow-up of adults with noncriti cal COVID-19 two months after symptoms’ onset. Follow-up of adults with non-critical COVID-19 two months after symptoms’ onset. Clin.Microbiol. Infect. 2021;27(2):258–263. DOI: 10.1016/j. cmi.2020.09.052Tenforde M.W., Kim S.S., Lindsell C.J., Rose E.B., Shapiro N.I., Files C. et al. Symptom duration and risk factors for delayed return to usual health among outpatients with COVID-19 in a multistate health care systems network: United States, March-June 2020. Morb. Mortal Wkly. Rep. 2020;69(30):993–998. Available from: https:// www.cdc.gov/mmwr/volumes/69/wr/mm6930e1.htmTenforde M.W., Kim S.S., Lindsell C.J., Rose E.B., Shapiro N.I., Files C. et al. Symptom duration and risk factors for delayed return to usual health among outpatients with COVID-19 in a multistate health care systems network: United States, March-June 2020. Morb. Mortal Wkly. Rep. 2020;69(30):993–998. Available from: https:// www.cdc.gov/mmwr/volumes/69/wr/mm6930e1.htmNalbandian A., Sehgal K., Gupta A., Madhavan M.V., McGro der C., Stevens J.S. et al. Post-acute COVID-19 syndrome. Nat. Med. 2021;27:601–615. Available from: https://doi.org/10.1038/s41591- 021-01283-zNalbandian A., Sehgal K., Gupta A., Madhavan M.V., McGro der C., Stevens J.S. et al. Post-acute COVID-19 syndrome. Nat. Med. 2021;27:601–615. Available from: https://doi.org/10.1038/s41591- 021-01283-zGarrigues E., Janvier P., Kherabi Y., Le Bot A., Hamon A., Gouze H. et al. Post-discharge persistent symptoms and health-related quality of life after hospitalization for COVID-19. J. Infect. 2020;81(6):E4–E6.Garrigues E., Janvier P., Kherabi Y., Le Bot A., Hamon A., Gouze H. et al. Post-discharge persistent symptoms and health-related quality of life after hospitalization for COVID-19. J. Infect. 2020;81(6):E4–E6.Huang C., Huang L., Wang Y., Li X., Ren L., Gu X. et al. 6-month consequences of COVID-19 in patients discharged from hospital: a cohort study (Huang, January 2021). Lancet. 2021;397:220–232.Huang C., Huang L., Wang Y., Li X., Ren L., Gu X. et al. 6-month consequences of COVID-19 in patients discharged from hospital: a cohort study (Huang, January 2021). Lancet. 2021;397:220–232.Ayoubkhani D., Khunti K., Nafi lyan V., Maddox T., Humberstone B., Sir Diamond I., Banerjee A. Epidemiology of post-COVID syndrome following hospitalisation with coronavirus: a retrospective cohort study. MedRxiv: the Preprint Server for Health Sciences. 2021.01.15.21249885. DOI: 10.1101/2021.01.15.21249885. Now accepted for publication in BMJ.Ayoubkhani D., Khunti K., Nafi lyan V., Maddox T., Humberstone B., Sir Diamond I., Banerjee A. Epidemiology of post-COVID syndrome following hospitalisation with coronavirus: a retrospective cohort study. MedRxiv: the Preprint Server for Health Sciences. 2021.01.15.21249885. DOI: 10.1101/2021.01.15.21249885. Now accepted for publication in BMJ.Sudre C.H., Murray B., Varsavsky T., Graham M.S., Bowyeк R.C., Pujol J.C. et al. Attributes and predictors of long COVID. Nat. Med. 2021;27:626–631. Available from: https://doi.org/10.1038/s41591- 021-01292-ySudre C.H., Murray B., Varsavsky T., Graham M.S., Bowyeк R.C., Pujol J.C. et al. Attributes and predictors of long COVID. Nat. Med. 2021;27:626–631. Available from: https://doi.org/10.1038/s41591- 021-01292-yVanichkachorn G., Newcomb R., Cowl C.T., Murad MH., Breeher L., Miller S. et al. Post COVID-19 Syndrome (Long Haul Syndrome): Description of a Multidisciplinary Clinic at the Mayo Clinic and Characteristics of the Initial Patient Cohort. Mayo Clinic Proceedings. 2021. DOI: 10.1016/j.mayocp.2021.04.024.Vanichkachorn G., Newcomb R., Cowl C.T., Murad MH., Breeher L., Miller S. et al. Post COVID-19 Syndrome (Long Haul Syndrome): Description of a Multidisciplinary Clinic at the Mayo Clinic and Characteristics of the Initial Patient Cohort. Mayo Clinic Proceedings. 2021. DOI: 10.1016/j.mayocp.2021.04.024.Pavli A., Theodoridou M., Maltezou H.C. Post-COVID syndrome: Incidence, clinical spectrum., and challenges for primary healthcare professionals. Arch. Med. Res. 2021. Available from: https://doi. org/10.1016/j.arcmed.2021.03.010Pavli A., Theodoridou M., Maltezou H.C. Post-COVID syndrome: Incidence, clinical spectrum., and challenges for primary healthcare professionals. Arch. Med. Res. 2021. Available from: https://doi. org/10.1016/j.arcmed.2021.03.010Greenhalgh T., Knight M., A’Court С., Buxton M., Husain L. Management of post-acute covid-19 in primary care. BMJ. 2020;370:m3026. DOI: 10.1136/ bmj.m3026.Greenhalgh T., Knight M., A’Court С., Buxton M., Husain L. Management of post-acute covid-19 in primary care. BMJ. 2020;370:m3026. DOI: 10.1136/ bmj.m3026.National Institute for Health and Care Excellence. COVID-19 rapid guideline: managing the long-term eff ects of COVID-19. 2020. Available from: https://www.nice.org.uk/guidance/ng188National Institute for Health and Care Excellence. COVID-19 rapid guideline: managing the long-term eff ects of COVID-19. 2020. Available from: https://www.nice.org.uk/guidance/ng188Maltezou H.C., Pavli A., Tsakris. A. Post-COVID Syndrome: An Insight on Its Pathogenesis. Vaccines. 2021;9:497. Avaliable from: https://doi.org/10.3390/vaccines9050497Maltezou H.C., Pavli A., Tsakris. A. Post-COVID Syndrome: An Insight on Its Pathogenesis. Vaccines. 2021;9:497. Avaliable from: https://doi.org/10.3390/vaccines9050497COVID-19 rapid guideline: managing the long-term eff ects of COVID-19. NICE guideline [NG188]. Published date: 18 December 2020 Available from: https://www.nice.org.uk/guidance/ NG188?utm_sourceCOVID-19 rapid guideline: managing the long-term eff ects of COVID-19. NICE guideline [NG188]. Published date: 18 December 2020 Available from: https://www.nice.org.uk/guidance/ NG188?utm_sourceAugustin M., Schommers Ph., Stecher M., Dewald F., Gieselmann L., Gruell H.et al. Post-COVID syndrome in non-hospitalised patients with COVID-19: a longitudinal prospective cohort study. The Lancet Regional Health – Europe 6. 2021:100122 Science Direct. Available from: http://creativecommons.org/licenses/by-nc-nd/4.0/Augustin M., Schommers Ph., Stecher M., Dewald F., Gieselmann L., Gruell H.et al. Post-COVID syndrome in non-hospitalised patients with COVID-19: a longitudinal prospective cohort study. The Lancet Regional Health – Europe 6. 2021:100122 Science Direct. Available from: http://creativecommons.org/licenses/by-nc-nd/4.0/Azer S.A. COVID-19: pathophysiology., diagnosis., complications and investigationaltherapeutics. New Microbes. New Infect. 2020;37:100738. DOI: 10.1016/j.nmni.2020.100738. PMID: 32834902; PMCID: PMC7403867.Azer S.A. COVID-19: pathophysiology., diagnosis., complications and investigationaltherapeutics. New Microbes. New Infect. 2020;37:100738. DOI: 10.1016/j.nmni.2020.100738. PMID: 32834902; PMCID: PMC7403867.COVID-19: Clinical management. WHO. 25.01.2021. Available from: https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-1COVID-19: Clinical management. WHO. 25.01.2021. Available from: https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-1Профилактика, диагностика и лечение новой коронавирусной инфекции (COVID-19). Временные методические рекомендации. Версия 11 (07.05.2021). Министерство здравоохранения Российской Федерации. 225 с.Prevention, diagnosis and treatment of new coronavirus infection (COVID-19). Temporary methodological recommendations. Version 11 (07.05.2021). Ministry of Health of the Russian Federation (in Russian). ttps://edu-rosminzdrav.ru.com/ profi laktika-diagnostika-i-lechenie-covid-19/Козлов И.А., Тюрин И.Н. Сердечно-сосудистые осложнения COVID-19. Вестник анестезиологии и реаниматологии. 2020;17(4):14–22. DOI: 10.21292/2078-5658- 2020-17-4-14-22.Kozlov I.А., Tyurin I.N. Cardiovascular complications of COVID-19. Messenger of Anesthesiology and Resuscitation.2020;17(4):14–22. (in Russian). DOI: 10.21292/2078-5658- 2020-17-4-14-22.Смирнова Е.А., Седых Е.В. Острая декомпенсация сердечной недостаточности: актуальные вопросы эпидемиологии, диагностики, терапии. Наука молодых (Eruditio Juvenium). 2021;9(2):289–300. DOI:10.23888/HMJ202192289-300.Smirnova E.A., Sedykh E.V. Acute decompensation of heart failure: current issues of epidemiology, diagnostics, therapy. Science of the young (Eruditio Juvenium). 2021;9(2):289– 300. (in Russian). DOI:10.23888/HMJ202192289-300.Aghagoli G., Gallo Marin B., Soliman LB., Sellke F.W. Cardiac involvement in COVID-19 patients: Risk factors., predictors., and complications: A review. J. Card. Surg. 2020;35:1302–1305.Aghagoli G., Gallo Marin B., Soliman LB., Sellke F.W. Cardiac involvement in COVID-19 patients: Risk factors., predictors., and complications: A review. J. Card. Surg. 2020;35:1302–1305.Chen C., Zhou Y., Wang D.W. SARS-CoV-2: a potential novel etiology of fulminant myocarditis. Herz. 2020;45(3):230–232. DOI:10.1007/s00059-020-04909-zChen C., Zhou Y., Wang D.W. SARS-CoV-2: a potential novel etiology of fulminant myocarditis. Herz. 2020;45(3):230–232. DOI:10.1007/s00059-020-04909-zKochi A.N., Tagliari A.P., Forleo G.B.Fassini G.M., Tondo C. Cardiac and arrhythmic complications in patients with COVID-19. J. Cardiovasc. Electrophysiol. 2020;31(5):1003–1008. DOI: 10.1111/ jce.14479Kochi A.N., Tagliari A.P., Forleo G.B.Fassini G.M., Tondo C. Cardiac and arrhythmic complications in patients with COVID-19. J. Cardiovasc. Electrophysiol. 2020;31(5):1003–1008. DOI: 10.1111/ jce.14479Kunutsor S.K., Laukkanen J.A. Cardiovascular complications in COVID-19: A systematic review and meta-analysis. J. Infect. 2020;81(2):e139–e141. DOI: 10.1016/j.jinf.2020.05.068. Epub 2020 Jun 3. PMID: 32504747; PMCID: PMC7832225Kunutsor S.K., Laukkanen J.A. Cardiovascular complications in COVID-19: A systematic review and meta-analysis. J. Infect. 2020;81(2):e139–e141. DOI: 10.1016/j.jinf.2020.05.068. Epub 2020 Jun 3. PMID: 32504747; PMCID: PMC7832225Long B., Brady W.J., Koyfman A., Gotleb M. Cardiovascular complications in COVID-19. Am. J. Emerg. Med. 2020;38(7);1504– 1507. DOI: 10.1016/j.ajem.2020.04.048Long B., Brady W.J., Koyfman A., Gotleb M. Cardiovascular complications in COVID-19. Am. J. Emerg. Med. 2020;38(7);1504– 1507. DOI: 10.1016/j.ajem.2020.04.048Zhu H., Rhee J-W., Cheng P., Waliany S., Chang A., Witteles R.M. et al. Cardiovascular complications in patients with COVID-19: consequences of viral toxicities and host immune response. Curr. Cardiol. Rep. 2020;22(5):32. DOI: 10.1007/s11886-020-01292-3Zhu H., Rhee J-W., Cheng P., Waliany S., Chang A., Witteles R.M. et al. Cardiovascular complications in patients with COVID-19: consequences of viral toxicities and host immune response. Curr. Cardiol. Rep. 2020;22(5):32. DOI: 10.1007/s11886-020-01292-3Belopasov V.V., Yachou Y., Samoilova E.M., Baklaushev V.P. The Nervous System Damage in COVID-19. J. Clin. Practice. 2020;11(2):60–80. (in Russian). DOI: 10.17816/clinpract34851Belopasov V.V., Yachou Y., Samoilova E.M., Baklaushev V.P. The Nervous System Damage in COVID-19. J. Clin. Practice. 2020;11(2):60–80. (in Russian). DOI: 10.17816/clinpract34851Терновых И.К., Топузова М.П., Чайковская А.Д., Исабе кова П.Ш., Алексеева Т.М. Неврологические проявления и осложнения у пациентов с COVID-19. Трансляционная медицина. 2020;7(3):21–29. Available from: https:// doi.org/10.18705/2311-4495-2020-7-3-21-29Ternovyh I.K., Topuzova M.P., Chaykovskaya A.D., Isabekova P.S., Alekseeva T.M. Neurological manifestations and complications in patients with COVID-19. Translational Medicine. 2020;7(3):21–29. (in Russian). Available from: https:// doi.org/10.18705/2311-4495-2020-7-3-21-29Maiti T., Essam L., Orsolini L., Ramalho R., El Halabi S., Nguyen V. et al. COVID-19-индуцированные психозы: новые вызовы для начинающих карьеру психиатров. Российский медико-биологический вестник им. академика И.П. Павлова. 2021;29(2):325–331. Available from: https: //journals.eco-vector.com/pavlovj/indexMaiti T., Essam L., Orsolini L., Ramalho R., El Halabi S., Nguyen V. et al. COVID-19-induced psychoses: new chal lenges for aspiring psychiatric careers. IP Pavlov Russian Medical Biological Herald. 2021;29(2):325-331. (in Russian). Available from: https: //journals.eco-vector.com/pavlovj/indexLi G., Yang Y., Gao D., XuY., GuJ., Liu P. Is liver involvement overestimated in COVID-19 patients? A meta-analysis. Int. J. Med Sci. 2021;18(5):1285–1296. Available from: https://www.medsci.org/ v18p1285.htmLi G., Yang Y., Gao D., XuY., GuJ., Liu P. Is liver involvement overestimated in COVID-19 patients? A meta-analysis. Int. J. Med Sci. 2021;18(5):1285–1296. Available from: https://www.medsci.org/ v18p1285.htmWang F., Wang H., Fan J., Zhang Y., Wang H., Zhao Q. Pancreatic injury patterns in patients with COVID-19 pneumonia. Gastroenterology. 2020;159(1):367–370. Available from: https://www.ncbi. nlm.nih.gov/pmc/articles/PMC7118654/Wang F., Wang H., Fan J., Zhang Y., Wang H., Zhao Q. Pancreatic injury patterns in patients with COVID-19 pneumonia. Gastroenterology. 2020;159(1):367–370. Available from: https://www.ncbi. nlm.nih.gov/pmc/articles/PMC7118654/Kirkey S. It’s only ‘the end of the beginning.’ COVID-19 will be with us for years. NATIONAL POST. Feb 16 2021. Available from: https://nationalpost.com/news/postpandemic/its-only-the-end-ofthe-beginning-of-covid-19Kirkey S. It’s only ‘the end of the beginning.’ COVID-19 will be with us for years. NATIONAL POST. Feb 16 2021. Available from: https://nationalpost.com/news/postpandemic/its-only-the-end-ofthe-beginning-of-covid-19

The authors declare that there are no conflicts of interest present.