Evaluation of diarrhea in COVID-19 patients

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OBJECTIVE

To determine the incidence of diarrhea and its epidemiological and clinical features in patients with COVID-19.

MATERIAL AND METHODS

The study included 200 patients with confirmed COVID-19 hospitalized at the Central Clinical Hospital from March 2020 to July 2021.

RESULTS

Diarrhea developed in 61 (30.5%) patients. AAD was detected in 36 (59%), CDI in 15 (24.6%), diarrhea associated with SARS-CoV-2 in 6 (9.8%) patients. 77% of patients had mild diarrhea. The detection of C. difficile toxins is associated with a severe course of the disease (OR=4.38 [95% CI: 1.41—13.13]; p=0.0085) and longer length of stay — 21 [16.5—27, 8] (p<0.0001). Detection C. difficile toxins increased by 5.6% in 2020 compared to 2019 [95% CI: 2.7—8.5, (p=0.0003)]. 46.7% were diagnosed with recurrent CDI within a year after discharge from the hospital. The most reliable indicators of diarrhea severity are CRP, calprotectin, and albumin. The bowel wall thickness on ultrasound in patients with mild diarrhea was <0.4 cm; in patients with severe and moderate diarrhea 0.6—1 cm.

CONCLUSIONS

Diarrhea caused by SARS-CoV-2 is mild and is associated with a more favorable outcome, while CDI is associated with more severe disease. There is an increase in the incidence of CDI in the post-COVID period. According to our data, calprotectin and bowel wall thickness on US can be used as diarrhea severity indicators.

Keywords:

antibiotic-associated diarrhea

clostridium infections

Clostridioides difficile

SARS-CoV-2

COVID-19

Authors:

Zharova M.E.

Pirogov Russian National Research Medical University;
Central Clinical Hospital with Polyclinic of Administrative Directorate of the President of the Russian Federation

Ivanikov I.O.

Pirogov Russian National Research Medical University of the Russian Ministry of Health;
Central Clinical Hospital of Russian Federation Presidential Administration

Grigorieva Yu.V.

Central Clinical Hospital with Polyclinic of Administrative Directorate of the President of the Russian Federation;
Pirogov Russian National Research Medical University

Nikonov E.L.

Pirogov Russian National Research Medical University

Scopus AuthorID: 57216680476
ResearcherID: T-9090-2017
ORCID: 0000-0003-3021-6534

Kirillova N.Ch.

Clinical Hospital of Russian Federation Presidential Administration

Vladimirova N.N.

Central Clinical Hospital of Russian Federation Presidential Administration

Chichva A.N.

Central Clinical Hospital of Russian Federation Presidential Administration

Andreeva O.A.

Central Clinical Hospital of Russian Federation Presidential Administration

Received:

08.09.2022

Accepted:

18.10.2022

List of references:

Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX, Liu L, Shan H, Lei CL, Hui DSC, Du B, Li LJ, Zeng G, Yuen KY, Chen RC, Tang CL, Wang T, Chen PY, Xiang J, Li SY, Wang JL, Liang ZJ, Peng YX, Wei L, Liu Y, Hu YH, Peng P, Wang JM, Liu JY, Chen Z, Li G, Zheng ZJ, Qiu SQ, Luo J, Ye CJ, Zhu SY, Zhong NS. Clinical Characteristics of Coronavirus Disease 2019 in China. New England Journal of Medicine. 2020;382(18):1708-1720. https://doi.org/10.1056/NEJMoa2002032
He J, Tao H, Yan Y, Huang SY, Xiao Y. Molecular Mechanism of Evolution and Human Infection with SARS-CoV-2. Viruses. 2020;12(4):428. https://doi.org/10.3390/v12040428
Wan Y, Shang J, Graham R, Baric RS, Li F. Receptor Recognition by the Novel Coronavirus from Wuhan: an Analysis Based on Decade-Long Structural Studies of SARS Coronavirus. Journal of Virology. 2020;94(7). https://doi.org/10.1128/JVI.00127-20
Cheung KS, Hung IFN, Chan PPY, Lung KC, Tso E, Liu R, Ng YY, Chu MY, Chung TWH, Tam AR, Yip CCY, Leung KH, Fung AY, Zhang RR, Lin Y, Cheng HM, Zhang AJX, To KKW, Chan KH, Yuen KY, Leung WK. Gastrointestinal Manifestations of SARS-CoV-2 Infection and Virus Load in Fecal Samples From a Hong Kong Cohort: Systematic Review and Meta-analysis. Gastroenterology. 2020;159(1):81-95. https://doi.org/10.1053/j.gastro.2020.03.065
Zhao X, Lei Z, Gao F, Xie Q, Jang K, Gong J. The impact of coronavirus disease 2019 (COVID-19) on liver injury in China. Medicine. 2021;100(4):e24369. https://doi.org/10.1097/MD.0000000000024369
Shchikota AM, Pogonchenkova IV, Turova EA, Rassulova MA, Filippov MS. Gastrointestinal tract, liver, and pancreas affected by COVID-19. Russian Journal of Evidence-Based Gastroenterology. 2021;10(1):30-37. (In Russ.). https://doi.org/10.17116/dokgastro20211001130
Groff A, Kavanaugh M, Ramgobin D, McClafferty B, Aggarwal CS, Golamari R, Jain R. Gastrointestinal Manifestations of COVID-19: A Review of What We Know. Ochsner Journal. 2021;21(2):177-180. https://doi.org/10.31486/toj.20.0086
Redd WD, Zhou JC, Hathorn KE, McCarty TR, Bazarbashi AN, Thompson CC, Shen L, Chan WW. Prevalence and Characteristics of Gastrointestinal Symptoms in Patients With Severe Acute Respiratory Syndrome Coronavirus 2 Infection in the United States: A Multicenter Cohort Study. Gastroenterology. 2020;159(2):765-767.e2. https://doi.org/10.1053/j.gastro.2020.04.045
Granata G, Petrosillo N, Al Moghazi S, Caraffa E, Puro V, Tillotson G, Cataldo MA. The burden of Clostridioides difficile infection in COVID-19 patients: A systematic review and meta-analysis. Anaerobe. 2022;74:102484. https://doi.org/10.1016/j.anaerobe.2021.102484
Bentivegna E, Alessio G, Spuntarelli V, Luciani M, Santino I, Simmaco M, Martelletti P. Impact of COVID-19 prevention measures on risk of health care-associated Clostridium difficile infection. American Journal of Infection Control. 2021;49(5):640-642. https://doi.org/10.1016/j.ajic.2020.09.010
Maslennikov R, Ivashkin V, Ufimtseva A, Poluektova E, Ulyanin A. Clostridioides difficile co-infection in patients with COVID-19. Future Microbiology. 2022;17(9):653-663. https://doi.org/10.2217/fmb-2021-0145
Vremennye metodicheskie rekomendacii Ministerstva Zdravoohraneniya RF. Profilaktika, diagnostika i lechenie novoj koronavirusnoj infekcii (COVID-19). Versiya 5 ot 08.04.20. Accessed August 20, 2022. (In Russ.). https://static-1.rosminzdrav.ru/system/attachments/attaches/000/049/951/original/09042020_%D0%9C%D0%A0_COVID-19_v5.pdf
Vremennye metodicheskie rekomendacii Ministerstva Zdravoohraneniya RF. Profilaktika, diagnostika i lechenie novoj koronavirusnoj infekcii (COVID-19). Versiya 6 ot 24.04.20. Accessed August 20, 2022. (In Russ.). https://static-1.rosminzdrav.ru/system/attachments/attaches/000/049/951/original/09042020_%D0%9C%D0%A0_COVID-19_v6.pdf
Vremennye metodicheskie rekomendacii Ministerstva Zdravoohraneniya RF. Profilaktika, diagnostika i lechenie novoj koronavirusnoj infekcii (COVID-19). Versiya 7 ot 03.06.20. Accessed August 20, 2022. (In Russ.). https://static-1.rosminzdrav.ru/system/attachments/attaches/000/049/951/original/09042020_%D0%9C%D0%A0_COVID-19_v7.pdf
Vremennye metodicheskie rekomendacii Ministerstva Zdravoohraneniya RF. Profilaktika, diagnostika i lechenie novoj koronavirusnoj infekcii (COVID-19). Versiya 8 ot 03.09.20. Accessed August 20, 2022. (In Russ.). https://static-1.rosminzdrav.ru/system/attachments/attaches/000/049/951/original/09042020_%D0%9C%D0%A0_COVID-19_v8.pdf
Vremennye metodicheskie rekomendacii Ministerstva Zdravoohraneniya RF. Profilaktika, diagnostika i lechenie novoj koronavirusnoj infekcii (COVID-19). Versiya 9 ot 26.10.20. Accessed August 20, 2022. (In Russ.). https://static-1.rosminzdrav.ru/system/attachments/attaches/000/049/951/original/09042020_%D0%9C%D0%A0_COVID-19_v9.pdf
Vremennye metodicheskie rekomendacii Ministerstva Zdravoohraneniya RF. Profilaktika, diagnostika i lechenie novoj koronavirusnoj infekcii (COVID-19). Versiya 10 ot 08.02.20. Accessed August 20, 2022. (In Russ.). https://static-1.rosminzdrav.ru/system/attachments/attaches/000/049/951/original/09042020_%D0%9C%D0%A0_COVID-19_v10.pdf
Vremennye metodicheskie rekomendacii Ministerstva Zdravoohraneniya RF. Profilaktika, diagnostika i lechenie novoj koronavirusnoj infekcii (COVID-19). Versiya 11 ot 07.05.21. Accessed August 20, 2022. (In Russ.). https://static-1.rosminzdrav.ru/system/attachments/attaches/000/049/951/original/09042020_%D0%9C%D0%A0_COVID-19_v7.pdf
Ivashkin VT, Yushchuk ND, Mayev IV, LapinaTL, Poluektova YeA, Shifrin OS, Tertychny AS, Trukhmanov AS, Sheptulin AA, Baranskaya YeK, Lyashenko OS, Ivashkin KV. Diagnostics and treatment of Clostridium difficile-associated disease: Guidelines of the Russian gastroenterological association. Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2016;26(5):56-65. (In Russ.).
Shelygin YuA, Aleshkin VA, Sukhina MA, Mironov AYU, Briko NI, Kozlov RS, Zverev VV, Achkasov SI, Kovalishena OV, Selkova EP, Safin AL, Grenkova TA, Khalif IL, Frolov SA, Kashnikov VN, Sushkov OI. Klinicheskie rekomendacii Nacional’noj Associacii Specialistov po kontrolyu infekcij, svyazannyh s okazaniem medicinskoj pomoshchi, i Obshcherossijskoj Obshchestvennoj Nekommercheskoj Organizacii «Associaciya Koloproktologov Rossii» po diagnostike, lecheniyu i profilaktike Clostridium Difficile-associirovannoj diarei (CDI). Koloproktologia. 2018;(3):7-23. (In Russ.). https://doi.org/10.33878/2073-7556-2018-0-3-7-23
Lioznov DA, Karnauhova EYu. Klinicheskie rekomendacii (protokol) po okazaniyu skoroj medicinskoj pomoshchi pri sindrome diarei infekcionnogo geneza. Skoraya medicinskaya pomoshch’. Klinicheskie rekomendacii. Pod red. akademika RAN Bagnenko S.F. M.: Izdatel’skaya gruppa «GEOTAR-Media»; 2019:527-543. (In Russ.).
Cheung KS, Hung IFN, Chan PPY, Lung KC, Tso E, Liu R, Ng YY, Chu MY, Chung TWH, Tam AR, Yip CCY, Leung KH, Fung AY, Zhang RR, Lin Y, Cheng HM, Zhang AJX, To KKW, Chan KH, Yuen KY, Leung WK. astrointestinal Manifestations of SARS-CoV-2 Infection and Virus Load in Fecal Samples From a Hong Kong Cohort: Systematic Review and Meta-analysis. Gastroenterology. 2020;159(1):81-95. https://doi.org/10.1053/j.gastro.2020.03.065
Wei XS, Wang X, Niu YR, Ye LL, Peng WB, Wang ZH, Yang WB, Yang BH, Zhang JC, Ma WL, Wang XR, Zhou Q. Diarrhea Is Associated With Prolonged Symptoms and Viral Carriage in Corona Virus Disease 2019. Clinical Gastroenterology and Hepatology. 2020;18(8):1753-1759.e2. https://doi.org/10.1016/j.cgh.2020.04.030
Tian Y, Rong L, Nian W, He Y. Review article: gastrointestinal features in COVID-19 and the possibility of faecal transmission. Alimentary Pharmacology & Therapeutics. 2020;51(9):843-851. https://doi.org/10.1111/apt.15731
Schettino M, Pellegrini L, Picascia D, Saibeni S, Bezzio C, Bini F, Omazzi BF, Devani M, Arena I, Bongiovanni M, Manes G, Della Corte CMR. Clinical Characteristics of COVID-19 Patients With Gastrointestinal Symptoms in Northern Italy: A Single-Center Cohort Study. American Journal of Gastroenterology. 2021;116(2):306-310. https://doi.org/10.14309/ajg.0000000000000965
Slimings C, Riley TV. Antibiotics and healthcare facility-associated Clostridioides difficile infection: systematic review and meta-analysis 2020 update. Journal of Antimicrobial Chemotherapy. 2021;76(7):1676-1688. https://doi.org/10.1093/jac/dkab091
Kovačević N, Lendak D, Popović M, Plećaš Đuric A, Pete M, Petrić V, Sević S, Tomić S, Alargić J, Damjanov D, Kosjer D, Lekin M. Clinical Presentations, Predictive Factors, and Outcomes of Clostridioides difficile Infection among COVID-19 Hospitalized Patients-A Single Center Experience from the COVID Hospital of the University Clinical Center of Vojvodina, Serbia. Medicina (Kaunas, Lithuania). 2022;58(9). https://doi.org/10.3390/medicina58091262
Reveles KR, Frei AL, Strey KA, Young EH. Prevalence and Health Outcomes of Clostridioides difficile Infection During the Coronavirus Disease 2019 Pandemic in a National Sample of United States Hospital Systems. Open Forum Infectious Diseases. 2022;9(9):ofac441. https://doi.org/10.1093/ofid/ofac441
Vázquez-Cuesta S, Olmedo M, Reigadas E, Alcalá L, Marín M, Muñoz P, Bouza E. Clostridioides difficile infection epidemiology and clinical characteristics in COVID-19 pandemic. Frontiers in Medicine. 2022;9:953724. https://doi.org/10.3389/fmed.2022.953724
Wen BJ, Te LG, Liu XX, Zhao JH. The value of fecal calprotectin in Clostridioides difficile infection: A systematic review. Frontiers in Physiology. 2022;13:881816. https://doi.org/10.3389/fphys.2022.881816
Kelly CR, Fischer M, Allegretti JR, LaPlante K, Stewart DB, Limketkai BN, Stollman NH. ACG Clinical Guidelines: Prevention, Diagnosis, and Treatment of Clostridioides difficile Infections. American Journal of Gastroenterology. 2021;116(6):1124-1147. https://doi.org/10.14309/ajg.0000000000001278
Wiener-Well Y, Kaloti S, Hadas-Halpern I, Munter G, Yinnon AM. Ultrasound diagnosis of Clostridium difficile-associated diarrhea. European Journal of Clinical Microbiology & Infectious Diseases. 2015;34(10):1975-1978. https://doi.org/10.1007/s10096-015-2439-1
Nylund K, Hausken T, Gilja OH. Ultrasound and Inflammatory Bowel Disease. Ultrasound Quarterly. 2010;26(1):3-15. https://doi.org/10.1097/RUQ.0b013e3181ce0929
Allocca M, Furfaro F, Fiorino G, Peyrin-Biroulet L, Danese S. Point-of-Care Ultrasound in Inflammatory Bowel Disease. Journal of Crohn’s and Colitis. 2021;15(1):143-151. https://doi.org/10.1093/ecco-jcc/jjaa151
Sagami S, Kobayashi T, Miyatani Y, Okabayashi S, Yamazaki H, Takada T, Kinoshita K, Allocca M, Kunisaki R, Ramaswamy PK, Shiraki M, Hibi T, Kataoka Y. Accuracy of Ultrasound for Evaluation of Colorectal Segments in Patients With Inflammatory Bowel Diseases: A Systematic Review and Meta-analysis. Clinical Gastroenterology and Hepatology. 2021;19(5):908-921.e6. https://doi.org/10.1016/j.cgh.2020.07.067
Goodsall TM, Nguyen TM, Parker CE, Ma C, Andrews JM, Jairath V, Bryant RV. Systematic Review: Gastrointestinal Ultrasound Scoring Indices for Inflammatory Bowel Disease. Journal of Crohn’s and Colitis. 2021;15(1):125-142. https://doi.org/10.1093/ecco-jcc/jjaa129
COVID-19 data in the WHO European Region. 08/20/22. Accessed August 20, 2022. https://who.maps.arcgis.com/apps/dashboards/a19d5d1f86ee4d99b013eed5f637232d

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