Альманах клинической медицины. 2020; 48: 1-10
Коморбидные заболевания и прогнозирование исхода COVID-19: результаты наблюдения 13 585 больных, находившихся на стационарном лечении в больницах Московской области
https://doi.org/10.18786/2072-0505-2020-48-040Аннотация
Актуальность. Пандемия COVID-19 наносит серьезный ущерб обществу и экономике многих стран, включая Российскую Федерацию. Выявление основных факторов риска неблагоприятного исхода может способствовать спасению жизни больных и уменьшению бремени заболевания. Результатов исследований в данном направлении на российском клиническом материале не опубликовано.
Цель - оценка влияния коморбидных состояний на исход (выписка, внутрибольничная летальность) у пациентов, находившихся на стационарном лечении с диагнозом «COVID-19».
Материал и методы. Мы проанализировали базу данных, включающую 13 585 больных, находившихся с 1 апреля по 23 июня 2020 г. на стационарном лечении в 66 больницах, работающих в системе обязательного медицинского страхования Московской области, с диагнозом «COVID-19, вирус идентифицирован» (код U07.1 по МКБ-10). Из них женщин было 53,7%, мужчин - 46,3%; средний возраст составил 56,5 ± 14,9 года (M ± SD, медиана 57 [46; 67] лет). У всех пациентов диагноз COVID-19 был подтвержден с помощью полимеразной цепной реакции на вирус SARS-CoV-2, материал получен с помощью мазка из носоглотки и ротоглотки. У 93,8% больных были выявлены признаки вирусной интерстициальной пневмонии (у 87,9% с помощью компьютерной томографии легких, у 5,9% - стандартной рентгенографии легких). Все пациенты получали стандартное лечение согласно документу Министерства здравоохранения Российской Федерации «Временные методические рекомендации. Профилактика, диагностика и лечение новой коронавирусной инфекции (COVID-19)», версия 7 (03.06.2020). У 1518 (11,2%) больных зафиксировано хотя бы одно коморбидное состояние; наиболее частыми коморбидными заболеваниями были артериальная гипертензия, ишемическая болезнь сердца и сахарный диабет. У 71 пациентки COVID-19 развился во время беременности. К 23 июня 2020 г. 10 761 (79,2%) больной выписан из стационара в состоянии излечения, улучшения или стабилизации (условно благоприятный исход); 1246 умерли, что составило внутрибольничную летальность на уровне 9,2% (неблагоприятный исход); остальные 1578 (11,6%) оставались на лечении или были переведены в другие лечебные учреждения для долечивания. В сравнительный анализ вошли больные (n = 12 007) с благоприятным (n = 10 761) и неблагоприятным (n = 1246) исходами стационарного лечения. Для количественной оценки выраженности коморбидности использовался скорректированный по возрасту индекс Charlson.
Результаты. В отсутствие коморбидных состояний частота летального исхода составила 9,4%. Хотя бы одно коморбидное состояние повышало частоту неблагоприятного исхода до 13,9% (р < 0,001), мультиморбидность - до 24,8% (р < 0,001). Среди конкретных состояний статистически значимо увеличивали вероятность неблагоприятного исхода (р < 0,05) сахарный диабет, психические нарушения, морбидное ожирение, ишемическая болезнь сердца, артериальная гипертензия, острое нарушение мозгового кровообращения (в том числе в анамнезе), острый инфаркт миокарда (в том числе в анамнезе), хроническая сердечная недостаточность, аритмии, онкологические заболевания, хроническая болезнь почек. Туберкулез, СПИД, травмы /хирургическая патология, беременность не были связаны с более частым неблагоприятным исходом, но эти пациенты были значимо моложе по сравнению с пациентами без коморбидных состояний и с таковыми, ассоциированными с летальностью. Скорректированный по возрасту индекс Charlson, начиная с уровня 3 балла, ассоциировался более чем с двукратным ростом внутрибольничной летальности (25,2%, р < 0,001).
Заключение. Коморбидность - один из определяющих факторов прогноза внутрибольничной летальности у госпитализированных пациентов с COVID-19. Однако ее следует рассматривать в контексте возрастных особенностей пациентов. Индекс коморбидности Charlson с поправкой на возраст представляется удобным инструментом для определения прогноза при COVID-19, который можно оценивать как серьезный при значениях индекса 3 балла и более.
Список литературы
1. Министерство здравоохранения Российской Федерации. Коронавирус - симптомы, признаки, общая информация, ответы на вопросы [Интернет]. Доступно на: https://covid19.rosminzdrav.ru.
2. Zaki N, Alashwal H, Ibrahim S. Association of hypertension, diabetes, stroke, cancer, kidney disease, and high-cholesterol with COVID-19 disease severity and fatality: A systematic review. Diabetes Metab Syndr. 2020;14(5):1133-42. Epub ahead of print. doi: 10.1016/j.dsx.2020.07.005.
3. Международная классификация болезней 10-го пересмотра (МКБ-10). Версия 2019 [Интернет]. Доступно на: https://mkb-10.com
4. Министерство здравоохранения Российской Федерации. Временные методические рекомендации: профилактика, диагностика и лечение новой коронавирусной инфекции (COVID-19) [Интернет]. Версия 7 (03.06.2020). Доступно на: https://static-0.rosminzdrav.ru/system/attachments/attaches/000/050/584/original/03062020_%D0%9CR_C0VID-19_v7.pdf.
5. Charlson Comorbidity Index (CCI) [Internet]. Available from: https://www.mdcalc.com/charlson-comorbidity-index-cci#creator-in-sights.
6. Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis. 1987;40(5): 373-83. doi: 10.1016/0021-9681(87)90171-8.
7. Maezawa Y, Aoyama T, Kano K, Tamagawa H, Numata M, Hara K, Murakawa M, Yamada T, Sato T, Ogata T, Oshima T, Yukawa N, Yoshika-wa T, Masuda M, Rino Y. Impact of the Age-adjusted Charlson comorbidity index on the short- and long-term outcomes of patients undergoing curative gastrectomy for gastric cancer. J Cancer. 2019;10(22):5527-35. doi: 10.7150/jca.35465.
8. Palaiodimos L, Kokkinidis DG, Li W, Karamanis D, Ognibene J, Arora S, Southern WN, Mantzoros CS. Severe obesity, increasing age and male sex are independently associated with worse in-hospital outcomes, and higher in-hospital mortality, in a cohort of patients with COVID-19 in the Bronx, New York. Metabolism. 2020;108:154262. doi: 10.1016/j.me-tabol.2020.154262.
9. Sharov KS. Adaptation of a Russian population to SARS-CoV-2: Asymptomatic course, comorbidities, mortality, and other respiratory viruses - A reply to Fear versus Data. Int J Antimicrob Agents. 2020:106093. Epub ahead of print. doi: 10.1016/j.ijantimicag.2020.106093.
10. Wang K, Zuo P, Liu Y, Zhang M, Zhao X, Xie S, Zhang H, Chen X, Liu C. Clinical and laboratory predictors of in-hospital mortality in patients with COVID-19: a cohort study in Wuhan, China. Clin Infect Dis. 2020:ciaa538. Epub ahead of print. doi: 10.1093/cid/ciaa538.
11. Ke C, Yu C, Yue D, Zeng X, Hu Z, Yang C. Clinical Characteristics of confirmed and clinically diagnosed patients with 2019 novel coronavirus pneumonia: a single-center, retrospective, case-control study. Med Clin (Bare). 2020:S0025-7753(20)30564-9. Epub ahead of print. doi: 10.1016/j.medcli.2020.06.055.
12. Ciardullo S, Zerbini F, Perra S, Muraca E, Can-nistraci R, Lauriola M, Grosso P, Lattuada G, Ippoliti G, Mortara A, Manzoni G, Persegh-in G. Impact of diabetes on COVID-19-related in-hospital mortality: a retrospective study from Northern Italy. J Endocrinol Invest. 2020:1-8. Epub ahead of print. doi: 10.1007/s40618-020-01382-7.
13. Laguna-Goya R, Utrero-Rico A, Talayero P, La-sa-Lazaro M, Ramirez-Fernandez A, Naranjo L, Segura-Tudela A, Cabrera-Marante O, Rodriguez de Frias E, Garcia-Garcia R, Fernan-dez-Ruiz M, Aguado JM, Martinez-Lopez J, Lopez EA, Catalan M, Serrano A, Paz-Artal E. IL-6-based mortality risk model for hospitalized patients with COVID-19. J Allergy Clin Immunol. 2020:S0091-6749(20)31027-7. Epub ahead of print. doi: 10.1016/j.jaci.2020.07.009.
14. Richardson S, Hirsch JS, Narasimhan M, Crawford JM, McGinn T, Davidson KW; and the Northwell COVID-19 Research Consortium, Barnaby DP, Becker LB, Chelico JD, Cohen SL, Cookingham J, Coppa K, Diefenbach MA, Dominello AJ, Duer-Hefele J, Falzon L, Gitlin J, Hajizadeh N, Harvin TG, Hirschwerk DA, Kim EJ, Kozel ZM, Marrast LM, Mogavero JN, Osorio GA, Qiu M, Zanos TP. Presenting Characteristics, Comorbidities, and Outcomes Among 5700 Patients Hospitalized With COVID-19 in the New York City Area. JAMA. 2020;323(20): 2052-9. Epub ahead of print. doi: 10.1001/jama.2020.6775. Erratum in: doi: 10.1001/jama.2020.7681.
15. Ji W, Huh K, Kang M, Hong J, Bae GH, Lee R, Na Y, Choi H, Gong SY, Choi YH, Ko KP, Im JS, Jung J. Effect of Underlying Comorbidities on the Infection and Severity of COVID-19 in Korea: a Nationwide Case-Control Study. J Korean Med Sci. 2020;35(25):e237. doi: 10.3346/jkms.2020.35.e237.
16. Egol KA, Konda SR, Bird ML, Dedhia N, Landes EK, Ranson RA, Solasz SJ, Aggarwal VK, Bosco JA 3rd, Furgiuele DL, Ganta A, Gould J, Lyon TR, McLaurin TM, Tejwani NC, Zuckerman JD, Leucht P; NYU COVID Hip Fracture Research Group. Increased Mortality and Major Complications in Hip Fracture Care During the COVID-19 Pandemic: A New York City Perspective. J Orthop Trauma. 2020;34(8):395-402. doi: 10.1097/BOT.0000000000001845.
17. LeBrun DG, Konnaris MA, Ghahramani GC, Premkumar A, DeFrancesco CJ, Gruskay JA, Dvorzhinskiy A, Sandhu MS, Goldwyn EM, Mendias CL, Ricci WM. Hip Fracture Outcomes During the COVID-19 Pandemic: Early Results From New York. J Orthop Trauma. 2020;34(8):403-10. doi: 10.1097/BOT.0000000000001849.
18. Huntley BJF, Huntley ES, Di Mascio D, Chen T, Berghella V, Chauhan SP. Rates of Maternal and Perinatal Mortality and Vertical Transmission in Pregnancies Complicated by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-Co-V-2) Infection: A Systematic Review. Obstet Gynecol. 2020;136(2):303-12. doi: 10.1097/AOG.0000000000004010.
19. Price-Haywood EG, Burton J, Fort D, Seoane L. Hospitalization and Mortality among Black Patients and White Patients with Covid-19. N Engl J Med. 2020;382(26):2534-43. doi: 10.1056/NE-JMsa2011686.
20. Imam Z, Odish F, Gill I, O'Connor D, Armstrong J, Vanood A, Ibironke O, Hanna A, Ranski A, Halalau A. Older age and comorbidity are independent mortality predictors in a large cohort of 1305 COVID-19 patients in Michigan, United States. J Intern Med. 2020:10.1111/joim.13119. Epub ahead of print. doi: 10.1111/joim.13119.
Almanac of Clinical Medicine. 2020; 48: 1-10
Comorbidities and predicting the outcome of COVID-19: the treatment results of 13,585 patients hospitalized in the Moscow Region
https://doi.org/10.18786/2072-0505-2020-48-040Abstract
Background: The COVID-19 pandemic is seriously affecting the society and economy of many countries, including the Russian Federation. Identifying of the major risk factors for an unfavorable outcome could help save lives and reduce the disease burden. Until now, no results of the studies on this issue based on the Russian clinical material have been published. Aim: To evaluate the effects of comorbidities on the outcome (discharge or hospital death rates) in patients hospitalized with a diagnosis of COVID-19.
Materials and methods: We analyzed a database of 13,585 patients who were treated in 66 hospitals functioning under the obligatory health insurance system of the Moscow Region, with a final diagnosis of "COVID-19, virus identified" (ICD 10 code U07.1) from April 1, 2020 to June 23, 2020 (53.7% women, 46.3% men, mean (± SD) age 56.5 ± 14.9 years (median 57 [46; 67])). In all patients, the diagnosis of COVID-19 was confirmed by polymerase chain reaction (PCR) for the SARS-CoV-2 virus in nasopharyngeal or oropharyngeal swabs. 93.8% of the patients showed signs of interstitial viral pneumonia (87.9% confirmed by computed tomography of the lungs, 5.9% by standard chest X-ray). All patients received the standard treatment according to the "Temporary Guidelines on prevention, diagnosis and treatment of the new coronavirus infection (COVID-19), version 7 (03.06.2020)” from the Ministry of Health of the Russian Federation. 1518 (11.2%) patients had at least one comorbid condition, the most frequent being arterial hypertension (AH), ischemic heart disease (IHD), and diabetes mellitus (DM). In 71 female patients, COVID-19 occurred during pregnancy. By June 23, 2020, 10761 (79.2%) patients have been discharged from hospitals with recovery, improvement, or stabilization (the latter was considered a conditionally favorable outcome). 1246 patients died, that transfers into the in-hospital death rates of about 9.2% (unfavorable outcome). The rest of 1578 (11.6%) patients continued their treatment, or were transferred to other medical units for the continuation of care. The comparative analysis included patients (total, n = 12,007) with favorable (n = 10,761) and unfavorable (n = 1246) inpatient outcomes. The age-adjusted Charlson index was used to quantify the severity of comorbidity.
Results: In the patients without any comorbidity, the in-hospital death rate was 9.4%. At least one comorbidity increased the incidence of unfavorable outcome to 13.9% (p < 0.001), and multiple comorbidities to 24.8% (p < 0.001). The following specific conditions significantly increased the likelihood of an unfavorable outcome (p < 0.05): DM, mental disorders, morbid obesity, IHD, AH, stroke (including past history), myocardial infarction (including past history), chronic heart failure, heart arrhythmias, cancer, and chronic kidney disease. Tuberculosis, HIV/AIDS, trauma / surgical disorders, and pregnancy were not associated with higher rates of unfavorable outcomes, but these patients were significantly younger than patients without comorbidities and with comorbidities with higher death rates. The age-adjusted Charlson index of > 3 was associated with a more than 2-fold increase in the in-hospital death rates (25.2%, p < 0.001).
Conclusion: Comorbidity is one of the drivers in the prognosis of in-hospital death rates in patients with COVID-19. However, it should be considered in the context of the patient age-related characteristics. The Charlson Age-Adjusted Comorbidity Index is a useful tool for assessment of the COVID-19 prognosis. The prognosis should be considered serious at a score of 3 or more.
References
1. Ministerstvo zdravookhraneniya Rossiiskoi Federatsii. Koronavirus - simptomy, priznaki, obshchaya informatsiya, otvety na voprosy [Internet]. Dostupno na: https://covid19.rosminzdrav.ru.
2. Zaki N, Alashwal H, Ibrahim S. Association of hypertension, diabetes, stroke, cancer, kidney disease, and high-cholesterol with COVID-19 disease severity and fatality: A systematic review. Diabetes Metab Syndr. 2020;14(5):1133-42. Epub ahead of print. doi: 10.1016/j.dsx.2020.07.005.
3. Mezhdunarodnaya klassifikatsiya boleznei 10-go peresmotra (MKB-10). Versiya 2019 [Internet]. Dostupno na: https://mkb-10.com
4. Ministerstvo zdravookhraneniya Rossiiskoi Federatsii. Vremennye metodicheskie rekomendatsii: profilaktika, diagnostika i lechenie novoi koronavirusnoi infektsii (COVID-19) [Internet]. Versiya 7 (03.06.2020). Dostupno na: https://static-0.rosminzdrav.ru/system/attachments/attaches/000/050/584/original/03062020_%D0%9CR_C0VID-19_v7.pdf.
5. Charlson Comorbidity Index (CCI) [Internet]. Available from: https://www.mdcalc.com/charlson-comorbidity-index-cci#creator-in-sights.
6. Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis. 1987;40(5): 373-83. doi: 10.1016/0021-9681(87)90171-8.
7. Maezawa Y, Aoyama T, Kano K, Tamagawa H, Numata M, Hara K, Murakawa M, Yamada T, Sato T, Ogata T, Oshima T, Yukawa N, Yoshika-wa T, Masuda M, Rino Y. Impact of the Age-adjusted Charlson comorbidity index on the short- and long-term outcomes of patients undergoing curative gastrectomy for gastric cancer. J Cancer. 2019;10(22):5527-35. doi: 10.7150/jca.35465.
8. Palaiodimos L, Kokkinidis DG, Li W, Karamanis D, Ognibene J, Arora S, Southern WN, Mantzoros CS. Severe obesity, increasing age and male sex are independently associated with worse in-hospital outcomes, and higher in-hospital mortality, in a cohort of patients with COVID-19 in the Bronx, New York. Metabolism. 2020;108:154262. doi: 10.1016/j.me-tabol.2020.154262.
9. Sharov KS. Adaptation of a Russian population to SARS-CoV-2: Asymptomatic course, comorbidities, mortality, and other respiratory viruses - A reply to Fear versus Data. Int J Antimicrob Agents. 2020:106093. Epub ahead of print. doi: 10.1016/j.ijantimicag.2020.106093.
10. Wang K, Zuo P, Liu Y, Zhang M, Zhao X, Xie S, Zhang H, Chen X, Liu C. Clinical and laboratory predictors of in-hospital mortality in patients with COVID-19: a cohort study in Wuhan, China. Clin Infect Dis. 2020:ciaa538. Epub ahead of print. doi: 10.1093/cid/ciaa538.
11. Ke C, Yu C, Yue D, Zeng X, Hu Z, Yang C. Clinical Characteristics of confirmed and clinically diagnosed patients with 2019 novel coronavirus pneumonia: a single-center, retrospective, case-control study. Med Clin (Bare). 2020:S0025-7753(20)30564-9. Epub ahead of print. doi: 10.1016/j.medcli.2020.06.055.
12. Ciardullo S, Zerbini F, Perra S, Muraca E, Can-nistraci R, Lauriola M, Grosso P, Lattuada G, Ippoliti G, Mortara A, Manzoni G, Persegh-in G. Impact of diabetes on COVID-19-related in-hospital mortality: a retrospective study from Northern Italy. J Endocrinol Invest. 2020:1-8. Epub ahead of print. doi: 10.1007/s40618-020-01382-7.
13. Laguna-Goya R, Utrero-Rico A, Talayero P, La-sa-Lazaro M, Ramirez-Fernandez A, Naranjo L, Segura-Tudela A, Cabrera-Marante O, Rodriguez de Frias E, Garcia-Garcia R, Fernan-dez-Ruiz M, Aguado JM, Martinez-Lopez J, Lopez EA, Catalan M, Serrano A, Paz-Artal E. IL-6-based mortality risk model for hospitalized patients with COVID-19. J Allergy Clin Immunol. 2020:S0091-6749(20)31027-7. Epub ahead of print. doi: 10.1016/j.jaci.2020.07.009.
14. Richardson S, Hirsch JS, Narasimhan M, Crawford JM, McGinn T, Davidson KW; and the Northwell COVID-19 Research Consortium, Barnaby DP, Becker LB, Chelico JD, Cohen SL, Cookingham J, Coppa K, Diefenbach MA, Dominello AJ, Duer-Hefele J, Falzon L, Gitlin J, Hajizadeh N, Harvin TG, Hirschwerk DA, Kim EJ, Kozel ZM, Marrast LM, Mogavero JN, Osorio GA, Qiu M, Zanos TP. Presenting Characteristics, Comorbidities, and Outcomes Among 5700 Patients Hospitalized With COVID-19 in the New York City Area. JAMA. 2020;323(20): 2052-9. Epub ahead of print. doi: 10.1001/jama.2020.6775. Erratum in: doi: 10.1001/jama.2020.7681.
15. Ji W, Huh K, Kang M, Hong J, Bae GH, Lee R, Na Y, Choi H, Gong SY, Choi YH, Ko KP, Im JS, Jung J. Effect of Underlying Comorbidities on the Infection and Severity of COVID-19 in Korea: a Nationwide Case-Control Study. J Korean Med Sci. 2020;35(25):e237. doi: 10.3346/jkms.2020.35.e237.
16. Egol KA, Konda SR, Bird ML, Dedhia N, Landes EK, Ranson RA, Solasz SJ, Aggarwal VK, Bosco JA 3rd, Furgiuele DL, Ganta A, Gould J, Lyon TR, McLaurin TM, Tejwani NC, Zuckerman JD, Leucht P; NYU COVID Hip Fracture Research Group. Increased Mortality and Major Complications in Hip Fracture Care During the COVID-19 Pandemic: A New York City Perspective. J Orthop Trauma. 2020;34(8):395-402. doi: 10.1097/BOT.0000000000001845.
17. LeBrun DG, Konnaris MA, Ghahramani GC, Premkumar A, DeFrancesco CJ, Gruskay JA, Dvorzhinskiy A, Sandhu MS, Goldwyn EM, Mendias CL, Ricci WM. Hip Fracture Outcomes During the COVID-19 Pandemic: Early Results From New York. J Orthop Trauma. 2020;34(8):403-10. doi: 10.1097/BOT.0000000000001849.
18. Huntley BJF, Huntley ES, Di Mascio D, Chen T, Berghella V, Chauhan SP. Rates of Maternal and Perinatal Mortality and Vertical Transmission in Pregnancies Complicated by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-Co-V-2) Infection: A Systematic Review. Obstet Gynecol. 2020;136(2):303-12. doi: 10.1097/AOG.0000000000004010.
19. Price-Haywood EG, Burton J, Fort D, Seoane L. Hospitalization and Mortality among Black Patients and White Patients with Covid-19. N Engl J Med. 2020;382(26):2534-43. doi: 10.1056/NE-JMsa2011686.
20. Imam Z, Odish F, Gill I, O'Connor D, Armstrong J, Vanood A, Ibironke O, Hanna A, Ranski A, Halalau A. Older age and comorbidity are independent mortality predictors in a large cohort of 1305 COVID-19 patients in Michigan, United States. J Intern Med. 2020:10.1111/joim.13119. Epub ahead of print. doi: 10.1111/joim.13119.
