Gastrointestinal disorders and of COVID-19: Difference between revisions

Revision as of 13:26, 19 June 2020

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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] 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."www.who.int" (PDF).

Gastrointestinal risk factors of COVID-19

Patients with chronic liver disease like Cirrhosis "People Who Are at Higher Risk for Severe Illness | Coronavirus | COVID-19 | CDC".
Comorbidities (Type 1 and Type 2 Diabetes) "People Who Are at Higher Risk for Severe Illness | Coronavirus | COVID-19 | CDC".
Severe obesity, defined as a body mass index (BMI) of 40 or above "People Who Are at Higher Risk for Severe Illness | Coronavirus | COVID-19 | CDC".
Liver transplantation recipients^[11]

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%. ^[12]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. ^[13] ^[14]

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.^[15]^[16] Other sites of expression of the receptors in the gastrointestinal tract are-the upper esophagus, liver, and colon. ^[15]
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. ^[17]

Clinical Features of Diarrhea caused by SARS-CoV-2

According to Jin et al^[13], 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. ^[18]^[19]

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. ^[17]

Nauesa and vomiting

Abdominal pain

Loss of appetite

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).
↑ 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).
↑ ^13.0 ^13.1 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).
↑ ^15.0 ^15.1 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).
↑ ^17.0 ^17.1 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.

[ChenLan2020-1] 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.

[WangXu2020-2] 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.

[ColavitaLapa2020-3] 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.

[CheungHung2020-4] 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.

[ZhengFan2020-5] 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.

[LiJin2020-6] 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.

[pmid32251668-7] 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).

[pmid32317267-8] 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).

[XiaoTang2020-9] 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.

[pmid32421494-10] 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).

[PereiraMohan2020-11] 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.

[pmid32253163-12] 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).

[pmid32213556-13] 13.0 ^13.1 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).

[pmid32109013-14] 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).

[pmid32278065-15] 15.0 ^15.1 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).

[pmid32102928-16] 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).

[pmid32096611-17] 17.0 ^17.1 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).

[pmid32139552-18] 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).

[pmid31986261-19] 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.

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@@ Line 7: / Line 7: @@
 ==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.<ref name="ChenLan2020">{{cite journal|last1=Chen|first1=Weilie|last2=Lan|first2=Yun|last3=Yuan|first3=Xiaozhen|last4=Deng|first4=Xilong|last5=Li|first5=Yueping|last6=Cai|first6=Xiaoli|last7=Li|first7=Liya|last8=He|first8=Ruiying|last9=Tan|first9=Yizhou|last10=Deng|first10=Xizi|last11=Gao|first11=Ming|last12=Tang|first12=Guofang|last13=Zhao|first13=Lingzhai|last14=Wang|first14=Jinlin|last15=Fan|first15=Qinghong|last16=Wen|first16=Chunyan|last17=Tong|first17=Yuwei|last18=Tang|first18=Yangbo|last19=Hu|first19=Fengyu|last20=Li|first20=Feng|last21=Tang|first21=Xiaoping|title=Detectable 2019-nCoV viral RNA in blood is a strong indicator for the further clinical severity|journal=Emerging Microbes & Infections|volume=9|issue=1|year=2020|pages=469–473|issn=2222-1751|doi=10.1080/22221751.2020.1732837}}</ref><ref name="WangXu2020">{{cite journal|last1=Wang|first1=Wenling|last2=Xu|first2=Yanli|last3=Gao|first3=Ruqin|last4=Lu|first4=Roujian|last5=Han|first5=Kai|last6=Wu|first6=Guizhen|last7=Tan|first7=Wenjie|title=Detection of SARS-CoV-2 in Different Types of Clinical Specimens|journal=JAMA|year=2020|issn=0098-7484|doi=10.1001/jama.2020.3786}}</ref><ref name="ColavitaLapa2020">{{cite journal|last1=Colavita|first1=Francesca|last2=Lapa|first2=Daniele|last3=Carletti|first3=Fabrizio|last4=Lalle|first4=Eleonora|last5=Bordi|first5=Licia|last6=Marsella|first6=Patrizia|last7=Nicastri|first7=Emanuele|last8=Bevilacqua|first8=Nazario|last9=Giancola|first9=Maria Letizia|last10=Corpolongo|first10=Angela|last11=Ippolito|first11=Giuseppe|last12=Capobianchi|first12=Maria Rosaria|last13=Castilletti|first13=Concetta|title=SARS-CoV-2 Isolation From Ocular Secretions of a Patient With COVID-19 in Italy With Prolonged Viral RNA Detection|journal=Annals of Internal Medicine|year=2020|issn=0003-4819|doi=10.7326/M20-1176}}</ref><ref name="CheungHung2020">{{cite journal|last1=Cheung|first1=Ka Shing|last2=Hung|first2=Ivan F.N.|last3=Chan|first3=Pierre P.Y.|last4=Lung|first4=K.C.|last5=Tso|first5=Eugene|last6=Liu|first6=Raymond|last7=Ng|first7=Y.Y.|last8=Chu|first8=Man Y.|last9=Chung|first9=Tom W.H.|last10=Tam|first10=Anthony Raymond|last11=Yip|first11=Cyril C.Y.|last12=Leung|first12=Kit-Hang|last13=Fung|first13=Agnes Yim-Fong|last14=Zhang|first14=Ricky R.|last15=Lin|first15=Yansheng|last16=Cheng|first16=Ho Ming|last17=Zhang|first17=Anna J.X.|last18=To|first18=Kelvin K.W.|last19=Chan|first19=Kwok-H.|last20=Yuen|first20=Kwok-Y.|last21=Leung|first21=Wai K.|title=Gastrointestinal Manifestations of SARS-CoV-2 Infection and Virus Load in Fecal Samples From a Hong Kong Cohort: Systematic Review and Meta-analysis|journal=Gastroenterology|year=2020|issn=00165085|doi=10.1053/j.gastro.2020.03.065}}</ref><ref name="ZhengFan2020">{{cite journal|last1=Zheng|first1=Shufa|last2=Fan|first2=Jian|last3=Yu|first3=Fei|last4=Feng|first4=Baihuan|last5=Lou|first5=Bin|last6=Zou|first6=Qianda|last7=Xie|first7=Guoliang|last8=Lin|first8=Sha|last9=Wang|first9=Ruonan|last10=Yang|first10=Xianzhi|last11=Chen|first11=Weizhen|last12=Wang|first12=Qi|last13=Zhang|first13=Dan|last14=Liu|first14=Yanchao|last15=Gong|first15=Renjie|last16=Ma|first16=Zhaohui|last17=Lu|first17=Siming|last18=Xiao|first18=Yanyan|last19=Gu|first19=Yaxi|last20=Zhang|first20=Jinming|last21=Yao|first21=Hangping|last22=Xu|first22=Kaijin|last23=Lu|first23=Xiaoyang|last24=Wei|first24=Guoqing|last25=Zhou|first25=Jianying|last26=Fang|first26=Qiang|last27=Cai|first27=Hongliu|last28=Qiu|first28=Yunqing|last29=Sheng|first29=Jifang|last30=Chen|first30=Yu|last31=Liang|first31=Tingbo|title=Viral load dynamics and disease severity in patients infected with SARS-CoV-2 in Zhejiang province, China, January-March 2020: retrospective cohort study|journal=BMJ|year=2020|pages=m1443|issn=1756-1833|doi=10.1136/bmj.m1443}}</ref><ref name="LiJin2020">{{cite journal|last1=Li|first1=Diangeng|last2=Jin|first2=Meiling|last3=Bao|first3=Pengtao|last4=Zhao|first4=Weiguo|last5=Zhang|first5=Shixi|title=Clinical Characteristics and Results of Semen Tests Among Men With Coronavirus Disease 2019|journal=JAMA Network Open|volume=3|issue=5|year=2020|pages=e208292|issn=2574-3805|doi=10.1001/jamanetworkopen.2020.8292}}</ref> 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.<ref name="pmid32251668">{{cite journal| author=Cheung KS, Hung IFN, Chan PPY, Lung KC, Tso E, Liu R | display-authors=etal| title=Gastrointestinal Manifestations of SARS-CoV-2 Infection and Virus Load in Fecal Samples From a Hong Kong Cohort: Systematic Review and Meta-analysis. | journal=Gastroenterology | year= 2020 | volume=  | issue=  | pages=  | pmid=32251668 | doi=10.1053/j.gastro.2020.03.065 | pmc=7194936 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32251668  }} </ref><ref name="pmid32317267">{{cite journal| author=Zheng S, Fan J, Yu F, Feng B, Lou B, Zou Q | display-authors=etal| title=Viral load dynamics and disease severity in patients infected with SARS-CoV-2 in Zhejiang province, China, January-March 2020: retrospective cohort study. | journal=BMJ | year= 2020 | volume= 369 | issue=  | pages= m1443 | pmid=32317267 | doi=10.1136/bmj.m1443 | pmc=7190077 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32317267  }} </ref>According to studies, the SARS-CoV-2 antigen is detected in gastrointestinal epithelial cells of a biopsy sample.<ref name="XiaoTang2020">{{cite journal|last1=Xiao|first1=Fei|last2=Tang|first2=Meiwen|last3=Zheng|first3=Xiaobin|last4=Liu|first4=Ye|last5=Li|first5=Xiaofeng|last6=Shan|first6=Hong|title=Evidence for Gastrointestinal Infection of SARS-CoV-2|journal=Gastroenterology|volume=158|issue=6|year=2020|pages=1831–1833.e3|issn=00165085|doi=10.1053/j.gastro.2020.02.055}}</ref> Live SARS-CoV-2 is also cultured from  stool samples in rare cases.<ref name="WangXu2020">{{cite journal|last1=Wang|first1=Wenling|last2=Xu|first2=Yanli|last3=Gao|first3=Ruqin|last4=Lu|first4=Roujian|last5=Han|first5=Kai|last6=Wu|first6=Guizhen|last7=Tan|first7=Wenjie|title=Detection of SARS-CoV-2 in Different Types of Clinical Specimens|journal=JAMA|year=2020|issn=0098-7484|doi=10.1001/jama.2020.3786}}</ref><ref name="pmid32421494">{{cite journal| author=Xiao F, Sun J, Xu Y, Li F, Huang X, Li H | display-authors=etal| title=Infectious SARS-CoV-2 in Feces of Patient with Severe COVID-19. | journal=Emerg Infect Dis | year= 2020 | volume= 26 | issue= 8 | pages=  | pmid=32421494 | doi=10.3201/eid2608.200681 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32421494  }} </ref> 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.{{cite web |url=https://www.who.int/docs/default-source/coronaviruse/who-china-joint-mission-on-covid-19-final-report.pdf |title=www.who.int |format= |work= |accessdate=}}
+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.<ref name="ChenLan2020">{{cite journal|last1=Chen|first1=Weilie|last2=Lan|first2=Yun|last3=Yuan|first3=Xiaozhen|last4=Deng|first4=Xilong|last5=Li|first5=Yueping|last6=Cai|first6=Xiaoli|last7=Li|first7=Liya|last8=He|first8=Ruiying|last9=Tan|first9=Yizhou|last10=Deng|first10=Xizi|last11=Gao|first11=Ming|last12=Tang|first12=Guofang|last13=Zhao|first13=Lingzhai|last14=Wang|first14=Jinlin|last15=Fan|first15=Qinghong|last16=Wen|first16=Chunyan|last17=Tong|first17=Yuwei|last18=Tang|first18=Yangbo|last19=Hu|first19=Fengyu|last20=Li|first20=Feng|last21=Tang|first21=Xiaoping|title=Detectable 2019-nCoV viral RNA in blood is a strong indicator for the further clinical severity|journal=Emerging Microbes & Infections|volume=9|issue=1|year=2020|pages=469–473|issn=2222-1751|doi=10.1080/22221751.2020.1732837}}</ref><ref name="WangXu2020">{{cite journal|last1=Wang|first1=Wenling|last2=Xu|first2=Yanli|last3=Gao|first3=Ruqin|last4=Lu|first4=Roujian|last5=Han|first5=Kai|last6=Wu|first6=Guizhen|last7=Tan|first7=Wenjie|title=Detection of SARS-CoV-2 in Different Types of Clinical Specimens|journal=JAMA|year=2020|issn=0098-7484|doi=10.1001/jama.2020.3786}}</ref><ref name="ColavitaLapa2020">{{cite journal|last1=Colavita|first1=Francesca|last2=Lapa|first2=Daniele|last3=Carletti|first3=Fabrizio|last4=Lalle|first4=Eleonora|last5=Bordi|first5=Licia|last6=Marsella|first6=Patrizia|last7=Nicastri|first7=Emanuele|last8=Bevilacqua|first8=Nazario|last9=Giancola|first9=Maria Letizia|last10=Corpolongo|first10=Angela|last11=Ippolito|first11=Giuseppe|last12=Capobianchi|first12=Maria Rosaria|last13=Castilletti|first13=Concetta|title=SARS-CoV-2 Isolation From Ocular Secretions of a Patient With COVID-19 in Italy With Prolonged Viral RNA Detection|journal=Annals of Internal Medicine|year=2020|issn=0003-4819|doi=10.7326/M20-1176}}</ref><ref name="CheungHung2020">{{cite journal|last1=Cheung|first1=Ka Shing|last2=Hung|first2=Ivan F.N.|last3=Chan|first3=Pierre P.Y.|last4=Lung|first4=K.C.|last5=Tso|first5=Eugene|last6=Liu|first6=Raymond|last7=Ng|first7=Y.Y.|last8=Chu|first8=Man Y.|last9=Chung|first9=Tom W.H.|last10=Tam|first10=Anthony Raymond|last11=Yip|first11=Cyril C.Y.|last12=Leung|first12=Kit-Hang|last13=Fung|first13=Agnes Yim-Fong|last14=Zhang|first14=Ricky R.|last15=Lin|first15=Yansheng|last16=Cheng|first16=Ho Ming|last17=Zhang|first17=Anna J.X.|last18=To|first18=Kelvin K.W.|last19=Chan|first19=Kwok-H.|last20=Yuen|first20=Kwok-Y.|last21=Leung|first21=Wai K.|title=Gastrointestinal Manifestations of SARS-CoV-2 Infection and Virus Load in Fecal Samples From a Hong Kong Cohort: Systematic Review and Meta-analysis|journal=Gastroenterology|year=2020|issn=00165085|doi=10.1053/j.gastro.2020.03.065}}</ref><ref name="ZhengFan2020">{{cite journal|last1=Zheng|first1=Shufa|last2=Fan|first2=Jian|last3=Yu|first3=Fei|last4=Feng|first4=Baihuan|last5=Lou|first5=Bin|last6=Zou|first6=Qianda|last7=Xie|first7=Guoliang|last8=Lin|first8=Sha|last9=Wang|first9=Ruonan|last10=Yang|first10=Xianzhi|last11=Chen|first11=Weizhen|last12=Wang|first12=Qi|last13=Zhang|first13=Dan|last14=Liu|first14=Yanchao|last15=Gong|first15=Renjie|last16=Ma|first16=Zhaohui|last17=Lu|first17=Siming|last18=Xiao|first18=Yanyan|last19=Gu|first19=Yaxi|last20=Zhang|first20=Jinming|last21=Yao|first21=Hangping|last22=Xu|first22=Kaijin|last23=Lu|first23=Xiaoyang|last24=Wei|first24=Guoqing|last25=Zhou|first25=Jianying|last26=Fang|first26=Qiang|last27=Cai|first27=Hongliu|last28=Qiu|first28=Yunqing|last29=Sheng|first29=Jifang|last30=Chen|first30=Yu|last31=Liang|first31=Tingbo|title=Viral load dynamics and disease severity in patients infected with SARS-CoV-2 in Zhejiang province, China, January-March 2020: retrospective cohort study|journal=BMJ|year=2020|pages=m1443|issn=1756-1833|doi=10.1136/bmj.m1443}}</ref><ref name="LiJin2020">{{cite journal|last1=Li|first1=Diangeng|last2=Jin|first2=Meiling|last3=Bao|first3=Pengtao|last4=Zhao|first4=Weiguo|last5=Zhang|first5=Shixi|title=Clinical Characteristics and Results of Semen Tests Among Men With Coronavirus Disease 2019|journal=JAMA Network Open|volume=3|issue=5|year=2020|pages=e208292|issn=2574-3805|doi=10.1001/jamanetworkopen.2020.8292}}</ref> 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.<ref name="pmid32251668">{{cite journal| author=Cheung KS, Hung IFN, Chan PPY, Lung KC, Tso E, Liu R | display-authors=etal| title=Gastrointestinal Manifestations of SARS-CoV-2 Infection and Virus Load in Fecal Samples From a Hong Kong Cohort: Systematic Review and Meta-analysis. | journal=Gastroenterology | year= 2020 | volume=  | issue=  | pages=  | pmid=32251668 | doi=10.1053/j.gastro.2020.03.065 | pmc=7194936 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32251668  }} </ref><ref name="pmid32317267">{{cite journal| author=Zheng S, Fan J, Yu F, Feng B, Lou B, Zou Q | display-authors=etal| title=Viral load dynamics and disease severity in patients infected with SARS-CoV-2 in Zhejiang province, China, January-March 2020: retrospective cohort study. | journal=BMJ | year= 2020 | volume= 369 | issue=  | pages= m1443 | pmid=32317267 | doi=10.1136/bmj.m1443 | pmc=7190077 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32317267  }} </ref>According to studies, the SARS-CoV-2 antigen is detected in gastrointestinal epithelial cells of a biopsy sample.<ref name="XiaoTang2020">{{cite journal|last1=Xiao|first1=Fei|last2=Tang|first2=Meiwen|last3=Zheng|first3=Xiaobin|last4=Liu|first4=Ye|last5=Li|first5=Xiaofeng|last6=Shan|first6=Hong|title=Evidence for Gastrointestinal Infection of SARS-CoV-2|journal=Gastroenterology|volume=158|issue=6|year=2020|pages=1831–1833.e3|issn=00165085|doi=10.1053/j.gastro.2020.02.055}}</ref> 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..<ref name="WangXu2020">{{cite journal|last1=Wang|first1=Wenling|last2=Xu|first2=Yanli|last3=Gao|first3=Ruqin|last4=Lu|first4=Roujian|last5=Han|first5=Kai|last6=Wu|first6=Guizhen|last7=Tan|first7=Wenjie|title=Detection of SARS-CoV-2 in Different Types of Clinical Specimens|journal=JAMA|year=2020|issn=0098-7484|doi=10.1001/jama.2020.3786}}</ref><ref name="pmid32421494">{{cite journal| author=Xiao F, Sun J, Xu Y, Li F, Huang X, Li H | display-authors=etal| title=Infectious SARS-CoV-2 in Feces of Patient with Severe COVID-19. | journal=Emerg Infect Dis | year= 2020 | volume= 26 | issue= 8 | pages=  | pmid=32421494 | doi=10.3201/eid2608.200681 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32421494  }} </ref> 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.{{cite web |url=https://www.who.int/docs/default-source/coronaviruse/who-china-joint-mission-on-covid-19-final-report.pdf |title=www.who.int |format= |work= |accessdate=}}
 ==Gastrointestinal risk factors of COVID-19==