Gastrointestinal disorders and of COVID-19
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Farima Kahe M.D. [2]Tayyaba Ali, M.D.[3]Ifrah Fatima, M.B.B.S[4]
Overview
Transmission of COVID-19 through gastrointestinal route
- Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been detected in non-respiratory specimens, together with stool, blood, ocular secretions, and semen. However, the role of those sites in the transmission is unsure.[1][2][3][4][5][6]
- Several reports are evident for the detection of SARS-CoV-2 RNA from a stool sample, even after no viral RNA is detected from the upper respiratory sample.[7][8]
- According to studies, the SARS-CoV-2 antigen is detected in gastrointestinal epithelial cells of a biopsy sample.[9]
- Live SARS-CoV-2 is also cultured from stool samples in rare cases, providing the evidence that SARS-CoV-2 has the possibility of fecal-oral transmission.[2][10]
- According to a recent investigation, Researchers adopt the method of control volume-based computational fluid dynamics (CFD) to inspect fluid flow characteristics during toilet flushing. Researchers illustrate through computer simulation that toilet flushing can produce plenty of turbulence and vortices above the toilet bowl. These vortices can create a cloud of live virus-containing aerosol droplets that can climb up to 106.5 cm from the ground. These virus-containing droplets can be inhaled and settle onto surfaces.[11] The toilet flushing effect has been studied before for the spread of other diseases. However, the World Health Organization and US Center for Disease Control and Prevention have not verified the transmission of SARS-CoV-2 through this route.[12] [13]
- In spite of the fact that it is hard to affirm, fecal-oral transmission has not been clinically depicted, and as indicated by a joint WHO-China report, didn't have all the earmarks of being a noteworthy factor in the spread of infection. [14]
Gastrointestinal risk factors of COVID-19
- Chronic liver disease like Cirrhosis [15]
- Comorbidities (Type 1 and Type 2 Diabetes) [16]
- Severe obesity, defined as a body mass index (BMI) of 40 or above [17]
- Liver transplantation recipients[18]
Complications
Diarrhea
- Diarrhea is an uncommon gastrointestinal symptom in patients with COVID-19, but may be the presenting symptom in a few patients. The frequency of occurrence of diarrhea varies between 1%-35%. [19]It varies widely between different studies probably due to the different criteria used to define diarrhea.
- Greater percentage of occurrence of diarrhea was noted in patients with severe COVID-19 when compared to non-severe disease. Likewise, patients with gastrointenstinal symptoms were more likely to have severe respiratory disease with ARDS requiring ventilatory support. [20] [21]
Pathophysiology
- SARS-CoV-2 uses the Angiotensin-converting enzyme 2 (ACE2) and the serine protease TMPRSS2 receptors for cell entry. These receptors are presently abundantly not only in the lungs but also in the enterocytes of the small intestinal.[22][23] Other sites of expression of the receptors in the gastrointestinal tract are-the upper esophagus, liver, and colon. [22]
- Entry of the virus causes disruption of the enterocytes and may lead to inflammation and alteration of intestinal permeability.
- COVID- 19 is being treated by atrial of many different antivirals and antibiotics. Diarrhea could also be a result of an alteration of the gut microbiota due to any of these. [24]
Clinical Features of Diarrhea caused by SARS-CoV-2
- According to Jin et al[20], the definition of diarrhea was the passing of loose stools >3 times per day.
- According to this study, 8.1% had diarrhea at onset and the symptoms lasted for approximately 4 days.
- The duration of diarrhea ranged from 2-4 days with 3-8 bowel movements per day, according to various studies. [25][26]
Treatment
- Supportive management is the mainstay of treatment.
- Rehydration, fluid repletion, and potassium monitoring are essential.
- Use of probiotics may have a role if the diarrhea is being caused by alteration of the gut microbiome. This could also be potentially useful in preventing secondary bacterial infections by restoring the gut microbiota. [24]
Nauesa and vomiting
Abdominal pain
Anorexia associated with COVID-19
- According to a recent study by Pan et al, 48.5% presented with digestive symptoms as their chief complaint. Anorexia was the most common (83.8%) of digestive symptoms associated with SARS-Cov2 infection. With COVID-19 primarily being a respiratory disease, surprisingly around 3% cases had just the digestive symptoms but no respiratory symptoms.[27]
Natural history
History of anorexia associated with COVID-19
Diagnosis
Laboratory Findings
Treatment
Oral mucosal lesions associated with COVID-19
- Recently, according to Carreras-Presas et al. oral vesiculobullous lesions associated with COVID-19 infection have been reported in three patients.[28]
Pathophysiology
- An abundant Angiotensin-converting enzyme 2 (ACE2) receptor expression on epithelial cells of the oral cavity plays a pivotal role in allowing COVID-19 virus to enter the epithelial cells and cause infection. There is a strong association between ACE-2 and 2019-nCoV S protein. The presence of coronavirus in human saliva is attributed to the same reason.[29]
Natural history
History of oral mucosal lesions associated with COVID-19
Diagnosis
Laboratory Findings
Treatment
Dysgeusia associated with COVID-19
Hepatic injury associated with COVID-19
- Several studies have reported the incidence of liver injury in COVID-19 infected patients.
Pathophysiology
- The exact mechanism of liver injury is still unclear. There are a few proposed mechanisms by which the SARS-CoV2 virus can infect liver cells causing damage, leading to a rise in hepatic enzymes.
- Hepatic injury directly caused by the viral infection of the liver as the detection of SARS-CoV-2 RNA in stool gives rise to the notion of viral exposure in the liver. [30]
- A preliminary study suggested that Angiotensin-converting enzyme 2 (ACE2) receptor expression is enriched in cholangiocytes and not in hepatocytes, indicating that SARS-CoV-2 might directly bind to ACE2-positive cholangiocytes to dysregulate liver function. The studies have not yet answered about the specific mechanisms of cholangiocyte injury, and how hepatocyte injury occurs as it lacks ACE2 receptor.[31][32]
Natural history
- According to the data available to date, patients with severe disease had increased incidence of abnormal liver function. By Guan et al. of 1099 COVID-19 positive patients, 2.3% had a preexisting liver injury, but elevated levels of AST were observed in 18.2% of the patients with non-severe disease and 39·4% patients with severe disease. Other studies with a lesser sample size had similar findings reported.[30]
Diagnosis
Laboratory Findings
Treatment
References
References
- ↑ Chen, Weilie; Lan, Yun; Yuan, Xiaozhen; Deng, Xilong; Li, Yueping; Cai, Xiaoli; Li, Liya; He, Ruiying; Tan, Yizhou; Deng, Xizi; Gao, Ming; Tang, Guofang; Zhao, Lingzhai; Wang, Jinlin; Fan, Qinghong; Wen, Chunyan; Tong, Yuwei; Tang, Yangbo; Hu, Fengyu; Li, Feng; Tang, Xiaoping (2020). "Detectable 2019-nCoV viral RNA in blood is a strong indicator for the further clinical severity". Emerging Microbes & Infections. 9 (1): 469–473. doi:10.1080/22221751.2020.1732837. ISSN 2222-1751.
- ↑ 2.0 2.1 Wang, Wenling; Xu, Yanli; Gao, Ruqin; Lu, Roujian; Han, Kai; Wu, Guizhen; Tan, Wenjie (2020). "Detection of SARS-CoV-2 in Different Types of Clinical Specimens". JAMA. doi:10.1001/jama.2020.3786. ISSN 0098-7484.
- ↑ Colavita, Francesca; Lapa, Daniele; Carletti, Fabrizio; Lalle, Eleonora; Bordi, Licia; Marsella, Patrizia; Nicastri, Emanuele; Bevilacqua, Nazario; Giancola, Maria Letizia; Corpolongo, Angela; Ippolito, Giuseppe; Capobianchi, Maria Rosaria; Castilletti, Concetta (2020). "SARS-CoV-2 Isolation From Ocular Secretions of a Patient With COVID-19 in Italy With Prolonged Viral RNA Detection". Annals of Internal Medicine. doi:10.7326/M20-1176. ISSN 0003-4819.
- ↑ Cheung, Ka Shing; Hung, Ivan F.N.; Chan, Pierre P.Y.; Lung, K.C.; Tso, Eugene; Liu, Raymond; Ng, Y.Y.; Chu, Man Y.; Chung, Tom W.H.; Tam, Anthony Raymond; Yip, Cyril C.Y.; Leung, Kit-Hang; Fung, Agnes Yim-Fong; Zhang, Ricky R.; Lin, Yansheng; Cheng, Ho Ming; Zhang, Anna J.X.; To, Kelvin K.W.; Chan, Kwok-H.; Yuen, Kwok-Y.; Leung, Wai K. (2020). "Gastrointestinal Manifestations of SARS-CoV-2 Infection and Virus Load in Fecal Samples From a Hong Kong Cohort: Systematic Review and Meta-analysis". Gastroenterology. doi:10.1053/j.gastro.2020.03.065. ISSN 0016-5085.
- ↑ Zheng, Shufa; Fan, Jian; Yu, Fei; Feng, Baihuan; Lou, Bin; Zou, Qianda; Xie, Guoliang; Lin, Sha; Wang, Ruonan; Yang, Xianzhi; Chen, Weizhen; Wang, Qi; Zhang, Dan; Liu, Yanchao; Gong, Renjie; Ma, Zhaohui; Lu, Siming; Xiao, Yanyan; Gu, Yaxi; Zhang, Jinming; Yao, Hangping; Xu, Kaijin; Lu, Xiaoyang; Wei, Guoqing; Zhou, Jianying; Fang, Qiang; Cai, Hongliu; Qiu, Yunqing; Sheng, Jifang; Chen, Yu; Liang, Tingbo (2020). "Viral load dynamics and disease severity in patients infected with SARS-CoV-2 in Zhejiang province, China, January-March 2020: retrospective cohort study". BMJ: m1443. doi:10.1136/bmj.m1443. ISSN 1756-1833.
- ↑ Li, Diangeng; Jin, Meiling; Bao, Pengtao; Zhao, Weiguo; Zhang, Shixi (2020). "Clinical Characteristics and Results of Semen Tests Among Men With Coronavirus Disease 2019". JAMA Network Open. 3 (5): e208292. doi:10.1001/jamanetworkopen.2020.8292. ISSN 2574-3805.
- ↑ Cheung KS, Hung IFN, Chan PPY, Lung KC, Tso E, Liu R; et al. (2020). "Gastrointestinal Manifestations of SARS-CoV-2 Infection and Virus Load in Fecal Samples From a Hong Kong Cohort: Systematic Review and Meta-analysis". Gastroenterology. doi:10.1053/j.gastro.2020.03.065. PMC 7194936 Check
|pmc=value (help). PMID 32251668 Check|pmid=value (help). - ↑ Zheng S, Fan J, Yu F, Feng B, Lou B, Zou Q; et al. (2020). "Viral load dynamics and disease severity in patients infected with SARS-CoV-2 in Zhejiang province, China, January-March 2020: retrospective cohort study". BMJ. 369: m1443. doi:10.1136/bmj.m1443. PMC 7190077 Check
|pmc=value (help). PMID 32317267 Check|pmid=value (help). - ↑ Xiao, Fei; Tang, Meiwen; Zheng, Xiaobin; Liu, Ye; Li, Xiaofeng; Shan, Hong (2020). "Evidence for Gastrointestinal Infection of SARS-CoV-2". Gastroenterology. 158 (6): 1831–1833.e3. doi:10.1053/j.gastro.2020.02.055. ISSN 0016-5085.
- ↑ Xiao F, Sun J, Xu Y, Li F, Huang X, Li H; et al. (2020). "Infectious SARS-CoV-2 in Feces of Patient with Severe COVID-19". Emerg Infect Dis. 26 (8). doi:10.3201/eid2608.200681. PMID 32421494 Check
|pmid=value (help). - ↑ Li, Yun-yun; Wang, Ji-Xiang; Chen, Xi (2020). "Can a toilet promote virus transmission? From a fluid dynamics perspective". Physics of Fluids. 32 (6): 065107. doi:10.1063/5.0013318. ISSN 1070-6631.
- ↑ "Modes of transmission of virus causing COVID-19: implications for IPC precaution recommendations".
- ↑ "Coronavirus (COVID-19) frequently asked questions | CDC".
- ↑ "www.who.int" (PDF).
- ↑ "People Who Are at Higher Risk for Severe Illness | Coronavirus | COVID-19 | CDC".
- ↑ "People Who Are at Higher Risk for Severe Illness | Coronavirus | COVID-19 | CDC".
- ↑ "People Who Are at Higher Risk for Severe Illness | Coronavirus | COVID-19 | CDC".
- ↑ Pereira, Marcus R.; Mohan, Sumit; Cohen, David J.; Husain, Syed A.; Dube, Geoffrey K.; Ratner, Lloyd E.; Arcasoy, Selim; Aversa, Meghan M.; Benvenuto, Luke J.; Dadhania, Darshana M.; Kapur, Sandip; Dove, Lorna M.; Brown, Robert S.; Rosenblatt, Russell E.; Samstein, Benjamin; Uriel, Nir; Farr, Maryjane A.; Satlin, Michael; Small, Catherine B.; Walsh, Thomas J.; Kodiyanplakkal, Rosy P.; Miko, Benjamin A.; Aaron, Justin G.; Tsapepas, Demetra S.; Emond, Jean C.; Verna, Elizabeth C. (2020). "COVID‐19 in solid organ transplant recipients: Initial report from the US epicenter". American Journal of Transplantation. doi:10.1111/ajt.15941. ISSN 1600-6135.
- ↑ Li XY, Dai WJ, Wu SN, Yang XZ, Wang HG (2020). "The occurrence of diarrhea in COVID-19 patients". Clin Res Hepatol Gastroenterol. doi:10.1016/j.clinre.2020.03.017. PMC 7270575 Check
|pmc=value (help). PMID 32253163 Check|pmid=value (help). - ↑ 20.0 20.1 Jin X, Lian JS, Hu JH, Gao J, Zheng L, Zhang YM; et al. (2020). "Epidemiological, clinical and virological characteristics of 74 cases of coronavirus-infected disease 2019 (COVID-19) with gastrointestinal symptoms". Gut. 69 (6): 1002–1009. doi:10.1136/gutjnl-2020-320926. PMC 7133387 Check
|pmc=value (help). PMID 32213556 Check|pmid=value (help). - ↑ Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX; et al. (2020). "Clinical Characteristics of Coronavirus Disease 2019 in China". N Engl J Med. 382 (18): 1708–1720. doi:10.1056/NEJMoa2002032. PMC 7092819 Check
|pmc=value (help). PMID 32109013 Check|pmid=value (help). - ↑ 22.0 22.1 D'Amico F, Baumgart DC, Danese S, Peyrin-Biroulet L (2020). "Diarrhea During COVID-19 Infection: Pathogenesis, Epidemiology, Prevention, and Management". Clin Gastroenterol Hepatol. doi:10.1016/j.cgh.2020.04.001. PMC 7141637 Check
|pmc=value (help). PMID 32278065 Check|pmid=value (help). - ↑ Liang W, Feng Z, Rao S, Xiao C, Xue X, Lin Z; et al. (2020). "Diarrhoea may be underestimated: a missing link in 2019 novel coronavirus". Gut. 69 (6): 1141–1143. doi:10.1136/gutjnl-2020-320832. PMID 32102928 Check
|pmid=value (help). - ↑ 24.0 24.1 Gao QY, Chen YX, Fang JY (2020). "2019 Novel coronavirus infection and gastrointestinal tract". J Dig Dis. 21 (3): 125–126. doi:10.1111/1751-2980.12851. PMC 7162053 Check
|pmc=value (help). PMID 32096611 Check|pmid=value (help). - ↑ Song Y, Liu P, Shi XL, Chu YL, Zhang J, Xia J; et al. (2020). "SARS-CoV-2 induced diarrhoea as onset symptom in patient with COVID-19". Gut. 69 (6): 1143–1144. doi:10.1136/gutjnl-2020-320891. PMID 32139552 Check
|pmid=value (help). - ↑ Chan JF, Yuan S, Kok KH, To KK, Chu H, Yang J; et al. (2020). "A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster". Lancet. 395 (10223): 514–523. doi:10.1016/S0140-6736(20)30154-9. PMC 7159286 Check
|pmc=value (help). PMID 31986261. - ↑ Pan L, Mu M, Yang P, Sun Y, Wang R, Yan J, Li P, Hu B, Wang J, Hu C, Jin Y, Niu X, Ping R, Du Y, Li T, Xu G, Hu Q, Tu L (May 2020). "Clinical Characteristics of COVID-19 Patients With Digestive Symptoms in Hubei, China: A Descriptive, Cross-Sectional, Multicenter Study". Am. J. Gastroenterol. 115 (5): 766–773. doi:10.14309/ajg.0000000000000620. PMC 7172492 Check
|pmc=value (help). PMID 32287140 Check|pmid=value (help). - ↑ Al-Khatib A (June 2020). "Oral manifestations in COVID-19 patients". Oral Dis. doi:10.1111/odi.13477. PMID 32521067 Check
|pmid=value (help). - ↑ Baghizadeh Fini M (May 2020). "Oral saliva and COVID-19". Oral Oncol. 108: 104821. doi:10.1016/j.oraloncology.2020.104821. PMC 7250788 Check
|pmc=value (help). PMID 32474389 Check|pmid=value (help). - ↑ 30.0 30.1 Zhang C, Shi L, Wang FS (May 2020). "Liver injury in COVID-19: management and challenges". Lancet Gastroenterol Hepatol. 5 (5): 428–430. doi:10.1016/S2468-1253(20)30057-1. PMC 7129165 Check
|pmc=value (help). PMID 32145190 Check|pmid=value (help). - ↑ Lee IC, Huo TI, Huang YH (June 2020). "Gastrointestinal and liver manifestations in patients with COVID-19". J Chin Med Assoc. 83 (6): 521–523. doi:10.1097/JCMA.0000000000000319. PMC 7176263 Check
|pmc=value (help). PMID 32243269 Check|pmid=value (help). - ↑ Kumar, Pramod; Sharma, Mithun; Kulkarni, Anand; Rao, Padaki N. (2020). "Pathogenesis of Liver Injury in Coronavirus Disease 2019". Journal of Clinical and Experimental Hepatology. doi:10.1016/j.jceh.2020.05.006. ISSN 0973-6883.