Epidemiology and Infectious DiseasesEpidemiology and Infectious DiseasesЭпидемиология и инфекционные болезни3034-20073034-2015Eco-Vector10616810.17816/EID106168LecturesЛекцииResearch ArticleAn integrated approach to the differential diagnosis of COVID-19 syndromes and symptomsКомплексный подход к дифференциальной диагностике синдромов и симптомов COVID-19https://orcid.org/0000-0002-4293-3285566995866008775-1299OrlovaNatalia V.ОрловаНаталья Васильевна
Russian Federation

MD, Dr. Sci. (Med.), Professor

д.м.н., профессор

vrach315@yandex.ruhttps://orcid.org/0000-0002-2205-96749044-5289NikiforovVladimir V.НикифоровВладимир Владимирович
Russian Federation

MD, Dr. Sci. (Med.), Professor

д.м.н., профессор

v.v.nikiforov@gmail.comPirogov Russian National Research Medical UniversityРоссийский национальный исследовательский медицинский университет имени Н.И. ПироговаResearch Institute for Systems Biology and MedicineНаучно-исследовательский институт системной биологии и медицины220420221503202126244561104202218042022Copyright ©; 2021, Eco-vectorCopyright ©; 2021, ООО "Эко-вектор"2021Eco-vectorООО "Эко-вектор"https://rjeid.com/1560-9529/article/view/106168

COVID-19 is characterized by a variety of symptoms that are not pathognomonic (hyper-/hypothermia; acute intoxication syndrome; cough; sore throat; enlargement of submandibular lymph nodes; shortness of breath; dyspeptic syndrome; neurological symptoms; ageusia and anosmia, etc.), which determines the need for differential diagnosis. COVID-19 refers to acute respiratory infections, has common transmission routes and similar symptoms, simultaneous infection with other respiratory viruses is possible.

Symptoms of intoxication require differential diagnosis with other infections, cough and shortness of breath may be manifestations of cardiovascular diseases, ageusia and anosmia occur in respiratory viral infections and neurological diseases, skin manifestations are also not specific. Laboratory and radiation diagnostics in COVID-19 reveals frequent changes, which, however, are also not pathognomonic. The article discusses diseases that have similar manifestations to COVID-19.

The greatest difficulties in differential diagnosis are caused by combined conditions ― the development of COVID-19 in patients with cardiovascular diseases, cancer patients, with chronic diseases of the respiratory system and others. Crucial in the differential diagnosis is the conduct of a specific examination ― the determination of the SARS-CoV-2 antigen in smears from the nasopharynx and oropharynx by immunochemical methods.

COVID-19 характеризуется разнообразием симптомов (гипер-/гипотермия; острый интоксикационный синдром; кашель; боли в горле; увеличение подчелюстных лимфатических узлов; одышка; диспепсический синдром; неврологические симптомы; агевзия и аносмия и др.), которые не являются патогномоничными, что определяет необходимость проведения дифференциальной диагностики. COVID-19 относится к острым респираторным инфекциям, имеет общие пути передачи и схожую симптоматику, возможна одновременная инфицированность другими респираторными вирусами.

Симптомы интоксикации требуют проведения дифференциальной диагностики с другими инфекциями. Кашель и одышка могут быть проявлениями сердечно-сосудистых заболеваний, агевзия и аносмия встречаются при респираторных вирусных инфекциях и неврологических заболеваниях, кожные проявления также не являются специфичными. Лабораторная и лучевая диагностика при COVID-19 выявляет часто встречающиеся изменения, которые, однако, также не являются патогномоничными.

В статье рассматриваются заболевания, имеющие схожие с COVID-19 проявления. Наибольшие трудности в дифференциальной диагностике вызывают сочетанные состояния: развитие COVID-19 у больных онкологического профиля, с сердечно-сосудистыми заболеваниями, хроническими заболеваниями дыхательной системы и др. Решающим в дифференциальной диагностике является проведение специфического обследования: определение антигена SARS-CoV-2 в мазках из носо- и ротоглотки иммунохимическими методами.

COVID-19syndromesdifferential diagnosisCOVID-19синдромыдифференциальная диагностиканетHuang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395(10223):497–506. doi: 10.1016/S0140-6736(20)30183-5Huang C., Wang Y., Li X., et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China // Lancet. 2020. Vol. 395, N 10223. Р. 497–506. doi: 10.1016/S0140-6736(20)30183-5Chen N, Zhou M, Dong X, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020;395(10223):507–513. doi: 10.1016/S0140-6736(20)30211-7Chen N., Zhou M., Dong X., et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study // Lancet. 2020. Vol. 395, N 10223. Р. 507–513. doi: 10.1016/S0140-6736(20)30211-7Holshue ML, DeBolt C, Lindquist S, et al. First case of 2019 novel coronavirus in the United States. N Engl J Med. 2020;382(10): 929–936. doi: 10.1056/NEJMoa2001191Holshue M.L., DeBolt C., Lindquist S., et al. First case of 2019 novel coronavirus in the United States // N Engl J Med. 2020. Vol. 382, N 10. Р. 929–936. doi: 10.1056/NEJMoa2001191Solomon DA, Sherman AC, Kanjilal S. Influenza in the COVID-19 Era. JAMA. 2020;324(13):1342–1343. doi: 10.1001/jama.2020.14661Solomon D.A., Sherman A.C., Kanjilal S. Influenza in the COVID-19 Era // JAMA. 2020. Vol. 324, N 13. Р. 1342–1343. doi: 10.1001/jama.2020.14661Krati K, Rizkou J, Errami AA, Essaadouni L. Differential diagnosis of COVID-19 in symptomatic patients at the University Hospital Center Mohammed VI, Marrakesh. Pan Afr Med J. 2020;36:269. doi: 10.11604/pamj.2020.36.269.24558Krati K., Rizkou J., Errami A.A., Essaadouni L. Differential diagnosis of COVID-19 in symptomatic patients at the University Hospital Center Mohammed VI, Marrakesh // Pan Afr Med J. 2020. Vol. 36. Р. 269. doi: 10.11604/pamj.2020.36.269.24558Orlova NV. Gripp. Diagnostics, strategy of choosing antiviral drugs. Medicinskii Sovet. 2017;(20):80–86. (In Russ). doi: 10.21518/2079-701X-2017-20-80-86Орлова Н.В. Грипп. Диагностика, стратегия выбора противовирусных препаратов // Медицинский совет. 2017. № 20. С. 80–86. doi: 10.21518/2079-701X-2017-20-80-86Mao R, Qiu Y, He JS, et al. Manifestations and prognosis of gastrointestinal and liver involvement in patients with COVID-19: a systematic review and meta-analysis. Lancet Gastroenterol Hepatol. 2020;5(7):667–678. doi: 10.1016/S2468-1253(20)30126-6Mao R., Qiu Y., He J.S., et al. Manifestations and prognosis of gastrointestinal and liver involvement in patients with COVID-19: a systematic review and meta-analysis // Lancet Gastroenterol Hepatol. 2020. Vol. 5, N 7. Р. 667–678. doi: 10.1016/S2468-1253(20)30126-6Lechien JR, Chiesa-Estomba CM, De Siati DR. Olfactory and gustatory dysfunctions as a clinical presentation of mild-to-moderate forms of the coronavirus disease (COVID-19): a multicenter European study. Eur Arch Otorhinolaryngol. 2020;277(8):2251–2261. doi: 10.1007/s00405-020-05965-1Lechien J.R., Chiesa-Estomba C.M., de Siati D.R. Olfactory and gustatory dysfunctions as a clinical presentation of mild-to-moderate forms of the coronavirus disease (COVID-19): a multicenter European study // Eur Arch Otorhinolaryngol. 2020. Vol. 277, N 8. Р. 2251–2261. doi: 10.1007/s00405-020-05965-1Li YC, Bai WZ, Hashikawa T. The neuroinvasive potential of SARS-CoV-2 may play a role in the respiratory failure of COVID-19 patients. J Med Virol. 2020;92(6):552–555. doi: 10.1002/jmv.25728Li Y.C., Bai W.Z., Hashikawa T. The neuroinvasive potential of SARS-CoV-2 may play a role in the respiratory failure of COVID-19 patients // J Med Virol. 2020. Vol. 92, N 6. Р. 552–555. doi: 10.1002/jmv.25728Wu Y, Xu X, Chen Z, et al. Nervous system involvement after infection with COVID-19 and other coronaviruses. Brain Behav Immun. 2020;87:18–22. doi: 10.1016/j.bbi.2020.03.031Wu Y., Xu X., Chen Z., et al. Nervous system involvement after infection with COVID-19 and other coronaviruses // Brain Behav Immun. 2020. Vol. 87. Р. 18–22. doi: 10.1016/j.bbi.2020.03.031Wollina U, Karadağ AS, Rowland-Payne C, et al. Cutaneous signs in COVID-19 patients: a review. Dermatol Ther. 2020;33(5):e13549. doi: 10.1111/dth.13549Wollina U., Karadağ A.S., Rowland-Payne C., et al. Cutaneous signs in COVID-19 patients: a review // Dermatol Ther. 2020. Vol. 33, N 5. Р. e13549. doi: 10.1111/dth.13549Suchonwanit P, Leerunyakul K, Kositkuljorn C. Cutaneous manifestations in COVID-19: lessons learned from current evidence. J Am Acad Dermatol. 2020;83(1):e57–e60. doi: 10.1016/j.jaad.2020.04.094Suchonwanit P., Leerunyakul K., Kositkuljorn C. Cutaneous manifestations in COVID-19: lessons learned from current evidence // J Am Acad Dermatol. 2020. Vol. 83, N 1. Р. e57–e60. doi: 10.1016/j.jaad.2020.04.094Galván Casas C, Català A, Carretero Hernández G, et al. Classification of the cutaneous manifestations of COVID-19: a rapid prospective nationwide consensus study in Spain with 375 cases. Br J Dermatol. 2020;183(1):71–77. doi: 10.1111/bjd.19163Galván Casas C., Català A., Carretero Hernández G., et al. Classification of the cutaneous manifestations of COVID-19: a rapid prospective nationwide consensus study in Spain with 375 cases // Br J Dermatol. 2020. Vol. 183, N 1. Р. 71–77. doi: 10.1111/bjd.19163El Hachem M, Diociaiuti A, Concato C, et al. A clinical, histopathological and laboratory study of 19 consecutive Italian paediatric patients with chilblain-like lesions: lights and shadows on the relationship with COVID-19 infection. J Eur Acad Dermatol Venereol. 2020;34(11):2620–2629. doi: 10.1111/jdv.16682El Hachem M., Diociaiuti A., Concato C., et al. A clinical, histopathological and laboratory study of 19 consecutive Italian paediatric patients with chilblain-like lesions: lights and shadows on the relationship with COVID-19 infection // J Eur Acad Dermatol Venereol. 2020. Vol. 34, N 11. Р. 2620–2629. doi: 10.1111/jdv.16682Gianotti R, Veraldi S, Recalcati S, et al. Cutaneous clinico-pathological findings in three COVID-19-positive patients observed in the metropolitan area of Milan, Italy. Acta Derm Venereol. 2020; 100(8):adv00124. doi: 10.2340/00015555-3490Gianotti R., Veraldi S., Recalcati S., et al. Cutaneous clinico-pathological findings in three COVID-19-positive patients observed in the metropolitan area of Milan, Italy // Acta Derm Venereol. 2020. Vol. 100, N 8. Р. adv00124. doi: 10.2340/00015555-3490Feng Z, Diao B, Wang R, et al. The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) directly decimates human spleens and lymph nodes. medRxiv. 2020. doi: 10.1101/2020.03.27.20045427Feng Z., Diao B., Wang R., et al. The novel severe acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) directly decimates human spleens and lymph nodes // medRxiv. 2020. doi: 10.1101/2020.03.27.20045427Millan-Oñate J, Millan W, Mendoza LA, et al. Successful recovery of COVID-19 pneumonia in a patient from Colombia after receiving chloroquine and clarithromycin. Ann Clin Microbiol Antimicrob. 2020;19(1):16. doi: 10.1186/s12941-020-00358-yMillan-Oñate J., Millan W., Mendoza L.A., et al. Successful recovery of COVID-19 pneumonia in a patient from Colombia after receiving chloroquine and clarithromycin // Ann Clin Microbiol Antimicrob. 2020. Vol. 19, N 1. Р. 16. doi: 10.1186/s12941-020-00358-yRomán GC, Spencer PS, Reis J, et al. WFN Environmental Neurology Specialty Group. The neurology of COVID-19 revisited: a proposal from the Environmental Neurology Specialty Group of the World Federation of Neurology to implement international neurological registries. J Neurol Sci. 2020;414:116884. doi: 10.1016/j.jns.2020.116884Román G.C., Spencer P.S., Reis J., et al. WFN Environmental Neurology Specialty Group. The neurology of COVID-19 revisited: a proposal from the Environmental Neurology Specialty Group of the World Federation of Neurology to implement international neurological registries // J Neurol Sci. 2020. Vol. 414. Р. 116884. doi: 10.1016/j.jns.2020.116884Driggin E, Madhavan MV, Bikdeli B, et al. Cardiovascular considerations for patients, health care workers, and health systems during the COVID-19 pandemic. J Am Coll Cardiol. 2020;75(18): 2352–2371. doi: 10.1016/j.jacc.2020.03.031Driggin E., Madhavan M.V., Bikdeli B., et al. Cardiovascular considerations for patients, health care workers, and health systems during the COVID-19 pandemic // J Am Coll Cardiol. 2020. Vol. 75, N 18. Р. 2352–2371. doi: 10.1016/j.jacc.2020.03.031Bangash MN, Patel J, Parekh D. COVID-19 and the liver: little cause for concern. Lancet Gastroenterol Hepatol. 2020;5(6):529–530. doi: 10.1016/S2468-1253(20)30084-4Bangash M.N., Patel J., Parekh D. COVID-19 and the liver: little cause for concern // Lancet Gastroenterol Hepatol. 2020. Vol. 5, N 6. Р. 529–530. doi: 10.1016/S2468-1253(20)30084-4Ghayda RA, Lee J, Lee JY, et al. Correlations of clinical and laboratory characteristics of COVID-19: a systematic review and meta-analysis. Int J Environ Res Public Health. 2020;17(14):5026. doi: 10.3390/ijerph17145026Ghayda R.A., Lee J., Lee J.Y., et al. Correlations of clinical and laboratory characteristics of COVID-19: a systematic review and meta-analysis // Int J Environ Res Public Health. 2020. Vol. 17, N 14. Р. 5026. doi: 10.3390/ijerph17145026Zhang C, Shi L, Wang FS. Liver injury in COVID-19: management and challenges. Lancet Gastroenterol Hepatol. 2020;5(5):428–430. doi: 10.1016/S2468-1253(20)30057-1Zhang C., Shi L., Wang F.S. Liver injury in COVID-19: management and challenges // Lancet Gastroenterol Hepatol. 2020. Vol. 5, N 5. Р. 428–430. doi: 10.1016/S2468-1253(20)30057-1Guan WJ, Ni ZY, Hu Y, et al. China Medical Treatment Expert Group for COVID-19. Clinical Characteristics of Coronavirus Disease 2019 in China. N Engl J Med. 2020;382(18):1708–1720. doi: 10.1056/NEJMoa2002032Guan W.J., Ni Z.Y., Hu Y., et al. China medical treatment expert group for COVID-19. Clinical characteristics of Coronavirus Disease 2019 in China // N Engl J Med. 2020. Vol. 382, N 18. Р. 1708–1720. doi: 10.1056/NEJMoa2002032Zhou F, Yu T, Du R, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020;395(10229):1054–1062. doi: 10.1016/S0140-6736(20)30566-3Zhou F., Yu T., Du R., et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study // Lancet. 2020. Vol. 395, N 10229. Р. 1054–1062. doi: 10.1016/S0140-6736(20)30566-3Wu C, Chen X, Cai Y, et al. Risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease 2019 pneumonia in wuhan, China. JAMA Intern Med. 2020; 180(7):934–943. doi: 10.1001/jamainternmed.2020.0994Wu C., Chen X., Cai Y., et al. Risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease 2019 pneumonia in wuhan, China // JAMA Intern Med. 2020. Vol. 180, N 7. Р. 934–943. doi: 10.1001/jamainternmed.2020.0994Valeri AM, Robbins-Juarez SY, Stevens JS, et al. Presentation and outcomes of patients with ESKD and COVID-19. J Am Soc Nephrol. 2020;31(7):1409–1415. doi: 10.1681/ASN.2020040470Valeri A.M., Robbins-Juarez S.Y., Stevens J.S., et al. Presentation and outcomes of patients with ESKD and COVID-19 // J Am Soc Nephrol. 2020. Vol. 31, N 7. Р. 1409–1415. doi: 10.1681/ASN.2020040470Akalin E, Azzi Y, Bartash R, et al. COVID-19 and kidney transplantation. N Engl J Med. 2020;382(25):2475–2477. doi: 10.1056/NEJMc2011117Akalin E., Azzi Y., Bartash R., et al. COVID-19 and kidney transplantation // N Engl J Med. 2020. Vol. 382, N 25. Р. 2475–2477. doi: 10.1056/NEJMc2011117Rismanbaf A, Zarei S. Liver and kidney injuries in COVID-19 and their effects on drug therapy; a letter to editor. Arch Acad Emerg Med. 2020;8(1):e17. doi: 10.22037/aaem.v8i1.590Rismanbaf A., Zarei S. Liver and kidney injuries in COVID-19 and their effects on drug therapy; a letter to editor // Arch Acad Emerg Med. 2020. Vol. 8, N 1. Р. e17. doi: 10.22037/aaem.v8i1.590Dai WC, Zhang HW, Yu J, et al. ct imaging and differential diagnosis of COVID-19. Can Assoc Radiol J. 2020;71(2):195–200. doi: 10.1177/0846537120913033Dai W.C., Zhang H.W., Yu J., et al. CT imaging and differential diagnosis of COVID-19 // Can Assoc Radiol J. 2020. Vol. 71, N 2. Р. 195–200. doi: 10.1177/0846537120913033Duzgun SA, Durhan G, Demirkazik FB, et al. COVID-19 pneumonia: the great radiological mimicker. Insights Imaging. 2020;11(1):118. doi: 10.1186/s13244-020-00933-zDuzgun S.A., Durhan G., Demirkazik F.B., et al. COVID-19 pneumonia: the great radiological mimicker // Insights Imaging. 2020. Vol. 11, N 1. Р. 118. doi: 10.1186/s13244-020-00933-zPetrovichev VS, Melekhov AV, Sayfullin MA, et al. Computed tomography for coronavirus infection: differential diagnosis on clinical examples. Archiv of Internal Medicine. 2020;10(5):357–371. (In Russ). doi: 10.20514/2226-6704-2020-10-5-357-371Петровичев В.С., Мелехов А.В., Сайфуллин М.А., и др. Компьютерная томография при коронавирусной инфекции: дифференциальный диагноз на клинических примерах // Архивъ внутренней медицины. 2020. Т. 10, № 5. С. 357–371. doi: 10.20514/2226-6704-2020-10-5-357-371