Date/Time 04-27-2020 02:48:57 pm. Local S5a55465643 ‘ocal Name 1 Total Pages Scanned : 38 Wie. [Jeb — [Remote Station far [are0isss ‘Tranemit Header Text ‘This document : Confirmed (reduced sample and details below) Document size : 8.5 GZ Administrative Offices x11" 497 State Stevet, Rochester New York 14608 Phone: (585) 346-7510 (V/TDD) Pax: (585) 546-5643 Ckagerton Program Site 41 Backus Street, Rochester New York 14613. Phone: (585) 458-7994 (V/TDD) Fax: (585) 458-8046 COMMENTS: sds [iob Type [Rene Im GET HORN 00:11 ec | Jer2aeas Abbreviations: 48: Host sand AR: Host racelve (NS: Watting send PL: Polled local (MP: Mailbox print PR: Polled remoto RP: Report MS: Mailbox save FF: Fax Forward ‘TU: Terminated by user TS: Terminated by system G2: Group3 Ec: Error CorrectiZ] Administrative Offices 497 State Street, Rochester New York 14608 Phone: (585) 546-7510 (V/TDD) Fax: (585) 546-5643 Edgerton Program Site 41 Backus Street, Rochester New York 14613 Phone: (585) 458-7994 (V/TDD) Fax: (585) 458-8046 TO: Dr a, FROM _Aruce & Darling CD DATE: _Apri|_ 27. 2020 Re Ae Number of Pages including this coversheet: _ 38 COMMENTS:Center for Disability Rights, In April 27, 2020 Regard Dr. Dear Dr. aaa provider and we have continued our opér we have multiple employees with disabilitie pandemic, we have taken significant steps (attachey )2CDR is an essential health care 's during the Governor's shutdown. Recognizing that efform fun ons on site during the COVID-19 their 1 Ensuring our staff do appropriate mirrors in each af the restroorhs for at least 20 seconds/ ™ [level 2 subheading:] The Patient with [BD wi Is Not Infected with SARS-CoV-2 lt, ‘The available data and exertions suggest that patients with IBD are not at higher A 12. TheFefore, the general recommendation isto stay on IBD. 1g remission, ideally defined as a composite of both risk of infection with SARS-Co\ therapies with a goal of ust = symptomatic tna and objectively confirmed inflammation control (endoscopic improvement and normalized laboratory values). Patients should be advised to maintain their ‘current regimens and to avoid relapse due to non-adherence. Aside from the obvious negative consequences of a relapse, relapsing IBD will strain avallable medical resources, may require steroid therapy or necessitate hospitalization, outcomes that are all much worse than the known risks of existing IBD therapies, Similar to the recommendations to the general Population, patients with IBD should practice strict social distancing, work from home, have. ‘meticulous hand hygiene, and separate themselves from known infected individuals. The 10‘Wuhan 18D Center experience of their 318 patients demonstrates the benefit of this, approach.” The healthcare team there instituted immediate alerts to their population to stay at home and practice strict social distancing. Despite being In the epicenter of COVID-19 in ‘Wuhan, none of their patients subsequently developed COVID-19." Patients with 18D and their providers have expressed concerns about going to infusion centers for delivery of infusible IBD therapies (e.g. infliximab, ustekinufhab, vedolizumat). The eat 10180 consensus supports ongoing use of Infusion centers provided hat the center hada COVID-19 screening protocol In place. Infusion centers shoulda protocol that includes +f bre-screening of patients for exposure or symptoms of COVID-19, fever checks at the door, Le adequate spacing between chairs (nim, of fee masks and gloves used by providers and Provided to patients, and adequate deep cleaning after patient departure. Elective switching to ot Injectable therapies is not recommendedand a prior trial exploring this in patients receiving intima wo were switched. tG-talimumab was asocated with relapses.” In adaltion, switching tohome ihn seem appealing as a way to limit exposure, but this is not ecommended. There are many uncontrolled variables and there is serious risk hata nurse- provider traveling from home to home may become infected and act as a vector to other patients, [level 2 subheading} The Patient with IBD Who Is Infected with SARS-CoV-2 but without Manifestations of COVID-19 Testing for SARS-CoV-2 is becoming more widespread, and point-of-care tests using sensitive nucleic acid detection or serologic antibodies are in development. In addition, there nare discussions about testing patients prior to endoscopic procedures or surgery, even if they have no specific symptoms to suggest COVID-19, Therefore, the situation in which a patient is known to have been infected with the virus but does not have the disease Is possible and will Increase. !OIBD specifically explored this scenario in development of their guidance statements.” In this scenario, patients should be actively moved to lower doses of prednisone (<20 soU'ekate, and tofacitinib ethouekake, an tofacitn mg/d) or transition to budesonide when feasible. Thiopurines, should be temporarily held. The available monaclonal ont eas {anti-tumor necrosis € factor (TNF) therapies, ustekinumab, or vedolizumab) should:hiave their dosing delayed for 2 abs ‘weeks while monitoring for development of COVID-18The general considerations here do not fees readily acknowledge the half-lives ofthese therapies a all ofthese medications may continue having systemic or tissue effects dense distontinuation. Restarting therapy after 2 weeks if the Loe patient has not developed manifestations of COVID-19 is reasonable. itis likely that soon we Be will be able to perform serilitesting for SARS-CoV-2 oF look for disappearance of gM and development of ig. antibodies in order to know which phase of infection the patient has entered. This ill provide more precision and comfort regarding the timing of restarting any therapy that has been held. Given that SARS-CoV-2 can persist in stool longer than what is detected from nasopharyngeal swabs, itis not known whether this should be a preferred test. However, from a practical point of view, serial stool testing is not likely to be adopted, Therefore, the clinical significance of stool testing for SARS-CoV-2 in this setting remains to be seen. 32[level 2 subheading] The Patfent with IBD Who Has Confirmed COVID-19 with or without Bowel Inflammation ‘The third scenario is the most challenging, as there are implications for management of ‘the IBD as well as management of COVID-19. Both the BSG and JOIBD statements address the abproach to management of the 180 medications in this scenario, but the details about assessing the state ofthe IBD are complex. We have developed a genefal algorithm for this ‘approach in Figure 2. Pr it a af § For the patent with COVID-18, adjustment of the medial therapy fr IBD is ®ppropriate, based on the understanding ofthe immune adv ofthe therapy and whether abe that therapy may worsen outcomes with COMID- ~s* in emission. Adjustment of 180 therapies is fécused on reducing immune suppression during rst to consider is the patient whose 180 is active viral replication in an attempt to,r@duice the likelihood of complications. It should be known that anti-cytokine-based’t ieatments are being studied for COVID-19 therapy, and itis, possible that we wil teariatptor example, continuing anti-TNF therapies might reduce progression to aes patoy distress syndrome and multi-organ system failure, However, in the absence of those data, guidance is currently based on deciding whether to hold or to continue specific IBD therapies. Of additional interest are the anti-viral therapies and other anti-cytokine therapies that are being studied for COVID-19. Choosing therapies that may have secondary benefit in 180 (or at least do not induce bowel inflammation] would be appropriate to consider, There has been some interesting research Into potential medical therapies to treat patients with COVID-19; in particular there has been attention to a therapy that is used. 2Bved primarily for rheumatoid arthritis, the interleukin-6 blocker tocilizumab. Used in rheumatoid arthritis and giant-cell arteritis, this agent also has proven efficacy (and FDA approval for the treatment of cytokine-release syndrome, a condition that has become more common in the era of chimeric antigen receptor T-cell (CAR-T) cancer therapies.” Tocilizumab had positive phase 2 data published in CO”, and will be actively studied in COVID-19 patients?="5, as will enother anti-IL agent, saritumab.”” Separately, the Janus kinas inhibitor baracitinib (but not tofacitinib}, aay may interfere with the virus entering cels by inhibiting AP2-assoclated rcteinkinose-t (AKI) used for IBD, albelt in uncontrolled fashion 7222 neiibePare encouraged to get the latest ss updates on these and ather anti-inflammatofy therapies at httos://clinicaltrials.zow/. parr Ne In regard to the 18D therapies/artindsalicylates, topical rectal therapy, dietary management, and antibiotics af@ Considered safe and may be continued. Oral budesonide is, likely safe as well and canccBntinue if itis needed for ongoing control of the 18D. Systemic corticosteroids shouldbe avoided ‘and discontinued quickly, if possible, with appropriate ‘caution if there is a concern for adrenel insufficiency from chronie corticosterold use, Thiopurines, methotrexate, and tofacitinib should be discontinued during the acute illness, Anti-INF therapies and ustekinumab should also be held during the viral iness. The 10180 {group was uncertain if holding vedolizumab was necessary inthis situation, but ina patient ‘whose 18D is stable, holding it during the time of vial ilness is appropriate, If the patient has COVID-19 and digestive symptoms, ongoing supportive care of the Primary COVID-19is reasonable but investigating the cause ofthe digestive symptoms in an 8D 1”patient is critically important. First, exclude known enteric infections such as Clostridioides difficile or other Gl pathogens. Second, confirm active inflammation with non-endoscopic approaches including C-reactive protein, fecal calprotectin, or cross-sectional imaging, although. these tests should be interpreted with caution as they may be abnormal due to COVID-19. Ifthe results suggest relapsing IBD, treatment of the IBD should be based on the activity of the inflammation and severity of the 18D. & Per multi-society recommendations on endoscopic proceduts ding the COVID-19 Pandemic, only urgent and emergent endoscopic procedures Should be performed. in the case lations “where [the] of the patient with IBD and patients in general, this appl ahs endoscopic procedure will urgently change management.” Clinical scenarios that might prompt endoscopy during this pandemic include the'Heed to obtain biopsies to diagnose new severe site 180, to exclude cytomegalovirus (CM -nveive tests are equivca, orn patents with aoe severe disease or suspected cafeer where mucosal inspection might drect surgical intervention.” FurthermotSithé AGA Institute presently recommends the use of N9S (or NO ey a or PAPR) masks, instead of surgical masks, and double-gloving as part of appropriate personal protective equipment for health care workers performing both upper and lower GI endoscopies, regardless of COVID-19 status. For mildly active disease, clinicians should utilize the safer therapies mentioned above. For moderately to severely active disease, holding therapies may not be safe or practicable. in this setting, the risks and benefits of escalating 180 therapy must be carefully weighed against the severity of the COVID-19. For an outpatient with mild COVID-19 symptams, IOIBD supports Using any of the usual treatments that would be considered pre-COVID-19. 15For hospitalized patients with severe COVID-19 and risks of poor outcomes, IBD therapy ‘ikely will take a back seat, but choice of therapies for COVID-19 should take into account the ‘co-existing 1BD, if feasible. Its of interest that clearance of CMV is enhanced when IBD therapy is added to ganciclovir and that thiopurines and cyclosporine may have anti-coronavirus properties. 33% a patient is hospitalized for 18D and also has milder or incidentally identified COVID- 19, focus on addressing the severe acute issues from the IBD are neon ‘and standard algorithms applied to the care of hosptallzed patient with wh shots be followed.2* Given the evidence of poor outcomes in SARS and RSV patients t treated sth high-dose corticosteroids, as well as some intriguing data on the possible coles’f éyclosporine™ or tacrolimus™™*” as therapies that interfere with SARS-CoV, irl Féplication, we suggest limiting IV steroids to three days, at which point the decision to pfoeed with a calcineurin inhibitor or infliimab will be made. While urgent endoscoplép Sontures that may change or direct therapy remain “ Inceated, during the pang CMY testing maybe done as serum PCR to ava need for colonoscopic procedures, and ganciclovir startet quantitatively suggestive of active inflammation, Surgical consultation is advised as per standard clinical practice, although the desire to minimize surgical interventions during the pandemic puts more emphasis on finding an effective medical “stop-gap” for these patients. However, there clearly will be some patients that despite medical interventions will still require surgery. ‘Take-Home Points:COVID-19 is the disease caused by the SARS-CoV-2 virus, but patients with IBD do not ‘appear to be at a higher risk for infection with SARS-CoV-2 or development of COVID-19, Patients with 18D who do not have infection with SARS-CoV-2 should NOT discontinue thelr 18D theraples and should continue infusion séhedules at appropriate infusion centers, Patients with IBD who have known SARS-CoV-2 but have not déveloped COVID-19 gen should hold thiopurines, methotrexate, and tofacitinib. Dosig of biological therapies should be delayed for 2 weeks monitoring for symptoris Of COVID-19, ™% Patients with 1BD who develop COVID-19 should hold thiopurines, methotrexate, oy tofacitinib, and biological therapies during thé viral iliness, These may be restarted after ep* lable, when follow-up viral testing is negative or complete symptom resolution of, if % Serologic tests demonstrate the convalescent stage of ines Soe, The severity of the COVIb-29 and the severity of the IBD should result in careful rsk- te SS beet assessment eping treatments for COVID-19 and escalating treatments for mt Re ; ‘Bo, i Please submit cases of IBD and confirmed COVID-19 to the SECUREABD registry at covIpIBD. org, 7References: 41. Sultan S, Lim JK, Altayar ©, et al. AGA Institute Rapid Recommendations for Gastrointestinal Procedures During the COVID-19 Pandemic, Gastroenterology. April 2020:50016508520304583. In Press. doi:10.1053/j.gastro.2020.03.072 2. Coronavirus. https://www.who.int/emergencies/diseases/novel-coronavirus-2019. ‘Accessed April 2, 2020, 3. WUC, Chen X, Cai Y, et al. Risk Factors Associated With Acute Respiratory Distress Syndrome and Death in Patlents With Coronavirus Disease 2019 Pneumonia in Wuhan, China. JAMA Intern Med. March 2020, doi:10.1002/jamainternmed:2020.0994 4. Xu, Unvelling the Origin and Transmission of 2019-nCoV. Trends Mievobio 2020;28(4):239-240, dcl:10.1016/).tim.2020.02.001 pate ed 5. van Doremalen N, Bushmaker T, Morris DH, et al. Aerosol and Surface Stability of SARS-CoV- 2 as Compared with SARS-CoV-1. N Engl J Med. 2020;0(0}null. doi:10.1056/NEJMc2004973 ¢ ‘6 Modes of transmission of virus causing COVID-19:implications for 1PC precaution recommendations. https://www.who.int/news-roomn/commentaries/detall/modes-of- transmission-of-virus-causing-covid-15-implications-for-ipc-precautlon-recommendations. Accessed April 3, 2020. a a 7. xiao F, Tang M, Zheng X, Liu Y, Li Shafi. Evidence for gastrointestinal infection of SARS- Cov-2. Gastroenterology. Mareh'2020. dol:10.1053/).gastro.2020.02.055 fy rolonged presence of SARS-CoV-2 viral RNA In faecal samples. |. 2020;0{0). doi:10,1016/52468-1253(20]30083-2 8 WuY, Guo, Tang L, etal Loncet Gnarentera olden 9. Welfel R Cormart Vj Guggemos W, et al. Virological assessment of hospitalized patients with COVID-2019;Nature, April 2020, doi:10.1038/s41586-020-2196-x 10, Hoffmann M, Kleine-Weber H, Schroeder 5, et al. SARS-CoV-2 Cell Entry Depends on ACE2 ‘and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Cell, March 2020. doi:10.1016/}.cell.2020.02.052 41, XuH, Zhong L, Deng J, et al. High expression of ACE2 receptor of 2019-nCoV on the epithelial cells of oral mucosa, Int J Oral Sci. 2020;12(1)'8, dol:10,1038/s41368-020-0074-x 12, Pan L, Mu M, Yang P, et al. Clinical characteristics of COVID-19 patients with digestive ‘symptoms in Hubei, China: a descriptive, cross-sectional, multicenter study. Am J Gastroenterol, 2020. 13. Winthrop KL, Melmed GY, Vermeire S, et al. Herpes Zoster Infection in Patients With Ulcerative Colitis Receiving Tofacitinib. Inflamm Bowel Dis. 2018;24(10}:2258-2265. doi:10.1093/ibd/izy131 1814, Pauly MP, Tucker L-Y, SzpakowskiJ-L, et al. Incidence of Hepatitis B Virus Reactivation and Hepatotoxicity in Patients Recelving Long-term Treatment With Tumor Necrosis Factor Antagonists. Clin Gastroenterol Hepatol Off Clin Pract J Am Gastroenterol Assoc. 2018;16(12):1964-1973.e1. doi:10.1016/.cgh.2018,04.033, 15. 101BD Update on COVID19 for Patients with Crohn’s Disease and Ulcerative Colitis | JOIBD. https://www.ioibd.org/iotbd-update-on-covid19-for-patients-with-crohns-disease-and- leerative-coltis/, Accessed April 1, 2020, 16. Wang D, Hu B, Hu C, et al. Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus—infected Pneumonia in Wuhan, China, JAMA. 2020;323(11):1062-1069. doi:10,1001/jama,2020,1585 x 17, Jin X, Lian JS, Hu J-H, etal Epidemiological, clinical and virologice cases of coronavirus-infected disease 2019 {COVID-19) with gastrointestinal symptoms. Gut, March 2020. doi:i0.1136/gutjnl-2020-320926 * af 19. BSG expanded consensus advice for the'n rahagement of IBD during the COVID-19 pandemic. The British Society of Gastroenterology. https://www.bsg.org.uk/covid-15 advice/bsg-advice-for-management-of inflammatory -bowel-diseases-during-the-covid-19- pandemic/. Published Merch 30, 2020; Accessed March 31, 2020, 20, Rubin DT, Abreu MT, Ral V,, sielta, ‘Management of Patients with Crohn's Disease and Ulcerative Colitis During the COVID-19 Pandemic: Results of an International Meeting. Gastroenterology. 2020 tn,press. : https://dol.org/10.1053/}.gastro.2020.04.002 ees Outbreak and Rapid Spread of COVID-19 Infection in Wuhan, China, Rochester, NY: Preprints with the Lancet; 2020, dol:10.2139/ssn.3543590 22. Assche GV, Vermeire S, Ballet V, et al. Switch to adalimumab in patients with Crohn's disease controlled by maintenance infliximab: prospective randomised SWITCH trial, Gut, 2012;61(2}:229-234, doi:10.1136/gutjnl-2011-300755, 23. Le RO, LiL, Yuan W, et al, FDA Approval Summary: Tocilizumab for Treatment of Chimeric Antigen Receptor T Cell-nduced Severe or Life-Threatening Cytokine Release Syndrome, The Oncologist. 2018;23(8):943-947, doi:10.1634/theoncologist.2018-0028 24, Danese S, Vermeire S, Hellstern P, et al. Randomised trial and open-label extension study of an ant-interleukin-6 antibody in Crohn’s disease (ANDANTE | and Il). Gut. 2019368(1}:40-48. dok:20.1136/gutjn|-2017-314562 19,25. Tocilizumab in COVID-19 Pneumonia (TOCIVID-19) - Full Text View - ClinicalTrials.gov. https://clinicaltrials gov/ct2/show/NCT04317092, Accessed April 2, 2020. 26. Treatment of COVID-19 Patients With Anti-interleukin Drugs - Full Text View - ClinicatTrials.gav. https://clinicaltrias.gov/ct2/show/NCT04330638, Accessed April 2, 2020, 27. Evaluation of the Efficacy and Safety of Sarilurnab in Hospitalized Patients With COVID-19 - Full Text View - ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCTO4315298. Accessed April 2, 2020, 28. Richardson P, Grifin|, Tucker C, et al. Barcitinib as potential treatmant for 2019-nCoV acute respiratory disease, Lancet Lond Engl. meansesTLOTsH AOR, doi:20.1016/s0140- 16736(20)30304-4 Co 29. Louis E, Belaiche J. Hydroxychloroquine (Plaquenil) for recurfenge prevention of Crohns disease after curative surgery. Gastroenter! Clin Bio, 1995;19(3}:233-234. 5 30. Goenka MK, Kochhar R, Tandia B, Mehta SK. Chloroquinefor mild to moderately active Ulcerative colitis: comparison with sulfasalazine¥Am.J Gastroenterol, 1996;91(5):917-921. 1, 31. Gastroenterology professional society gildgince.on endoscopic procedures during the COVID-19 pandemic | American Gastroéhferological Association, bnttps://www.gastro.org/practice-guldance/practice-updates/covid-19/gastroenterology- professional-society-guidance-or rendoscopic-procedures-during-the-covid-19-pandemic. Accessed April 3, 2020, 32. Park SC, Jeen YM, Jeen YT: Approach to cytomegalovirus infections in patients with Ulcerative colts. Koredin Intern Med, 2017;32(3):383-892, do:10.3904/kjim.2017.087 af 28, Cheng KAW, ches. Se/ hen WY, ea. Thopurnesnalogs and mycophenoic aid synergistically inhibit the papain-lke protease of Middle East respiratory syndrome coronavirus. Antiviral Res, 2015;115:9-16, dl:20.1016/,antvial.2014.12.011 34, de Wilde AH, Zevenhoven-Dobbe JC, van der Meer Y, etal. Cyclosporin A inhibits the replication of diverse coronaviruses. J Gen Virol, 2011;92(Pt 11):2547-2548, doi:40.1099/vir.0.034983-0 35. Kaur M, Dalal AL, Shaffer S, Schwartz DA, Rubin DT. Inpatient Management of Inflammatory Bowel Disease Related Complications. Clin Gastroenterol Hepatol Off Clin Pract J Am Gastroenterol Assoc. January 2020. dol:10.1016/).cgh.2019.12.040 36. Carbajo-Lozoya J, Miller MA, KalliesS, Thiel V, Drosten C, von Brunn A. Replication of human coronaviruses SARS-CoV, HCOV-NLG3 and HCoV-229E is inhibited by the drug FKS06. Virus Res, 2032;165(1}:112-127, dol:10,1016/j.virusres, 2012.02.0237, Carbajo-Lozoya J, Ma-Lauer Y, Malegevié M, et al. Human coronavirus NL63 replication Is. cyclophilin A-dependent and inhibited by non-Immunosuppressive cyclosporine A- derivatives including Alisporivir. Virus Res. 2014;184:44-53, dol:10.1016/} virusres.2014.02.010 a‘+ What Is the risk of infection with SARS-CoV-2 in patients with IBD? ‘+ What is the risk of COVID-19 in patients with IBD? *+ Does bowel inflammation increase risk of infection with SARS-CoV-2? * Do patients with IBD have different outcomes with COVID-19? | + DOIBD therapies increase risk of infection or COVID-197 + Are any IBD therapies protective against COVID-19? ‘+ Should patients with IBD modify their therapies during the pandemic? *+ Should patients with IBD continue going to infusion centers? ., * For patients with IBD exposed to a COVID-19 positive patier wuld their treatments be modified? » * For patients with IBD Infected with SARS-CoV-2 how: should their 180 treatment be modified? + Should patients with IBD with COVID-19 change sho giment? + Does COVID-19 trigger relapses of 1BD? = Does COVID-19 trigger new-onset IBD? IBD = inflammatory bowel disease SARS-CoV-2 = Severe Acute Respiratory Syiidrome of CoronaVirus 2 COVID-19 = COronaVirus Disease 2019.7 . 2Figure 1. Management of Patients with IBD during the COVID-19 Pandemic. Abbreviations: 18D = inflammatory bowel disease, SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2, COVID-19 = COronaVirus Disease 2019, mAbs = monoclonal antibodies, 5-ASA = 5-aminosalicylic acid medications Figure legen * Symptoms and findings of COVID-18: fever (85-99%) cough (59-82%) fatigue (44-70%) mt anorexia (40-84%); shortness of breath (31-40%); sputum production (28-33%); myalgias (11— ee 35%); headache, confusion, rhinorshea, sore throat, hemoptys, vomiting, and diarrhea (<10%); Ps lymphopenia (83%); CT chest: bilateral, peripheral, round co ats i Interim Clinical Guidance for Management of Patignts with Confirmed Coronavirus Disease €2% {COVID-19). htos://www.cde.gov/coronaviris/2019-neov/hep/clinical-guldance-management. atlents.html Accessed April 2, 20204 7 fae ** Clearance of SARS-Cov-2 ma ehable resumption of I60 therapy; role of serologic antibody 98s opacities. Reference: CDC- a testing unclear a the eurrattite. Viral clearance testing may or may not be possible or i anpropriate, given locdl,testing capabilities and health systern-approved epidemiological testing ‘ strategies during the COIVD-19 pande ‘+** Treatment of COVID-19 under investigation, consider therapies that have safety and efficacy in BD. 23gue Menem aah ene CONDE FaneComment *® teeta Mu 3009 egeitrgono6s Implications of COVID-19 for patients with pre-existing digestive diseases ‘The outbreak of coronavirus disease 2019 (COVID-28), ‘caused by severe acute respiratory syndrome coronavirus 2 USA much attention has been pald to the study and reporting of gastrointestinal tract infection of SARS- Sustmsagmames (SARS-CaV-2), ist reported in China inDecember,2019, CoV-2. According to a study including 1099 patients ‘now affects the whole word. As of March 8, 2020, more than 105000 laboratoy-confirmed! cases and. more than3$00 deathsin over100 countries hadbeen reported. Since SARS-COV-2 RNA was fst detectec! in a stool specimen of the fist reported COVID-I8 «ase in the Fert Oientanosne Sail pee With aboratory-confirmed COVID-19 from 52 hospitals In China as of Jan 29,2020, navseaor voraiting, or both, ‘and diarhoea were reported in 55 (546%) and 42 (3.8%) patients, Autopsy studies are crucial to help understand the involvement of COVD-19 In the digestive system, however, to date, there has been oniyone autopsy report? fora man aged 85 yeas with COVID-19, which showed segmental dilation and stenosis in the smal intestine. Whether this finding fs secondary to COVID-19 ora pre- esting gastrointestinal combi is unknown, COVIO-19 has implications for the management of patients with pre-existing digestive dscaes. indeed, ‘the presence and number of comorbidities is associated with poorer ini outcome inpatlets with COVID-29, In the study! of 1099 patients with laboratory confirmed COVID-19, 261 (237%) patients with COVID-29 reported having at least one comorbidity, with hypertension, diabetes, and coronary heart disease being the most common. In this study? 23 (22%) patiants had hepatitis B infection, Severe cases were more likely to have hepatitis 8 infection (2.4% ws 0-63) than non-severe cases. Abnormal lve function tests, including elevated aspartate aminotransferase, alanine aminotransferase, and total bilirubin were noted? Liver abnormaltiesin patients with COVIO-19 might be due to ‘ralinfection in iver cells but couldabo be dve to other ‘causes such as dug toxicity and systemic infarmmation.* ‘ata sugges that ver injury is more prevalent in severe cases than in mild cases of COVID-19.* However, data about other underlying chronic iver conditions such as non-alcoholic fatty ler disease, aloho-reated liver disease, and autolmmune hepatitis, and their effect on PrognosisofCOVID-19 needsto be further evaluated LUver transplantation might involve a risk of transmission of val infection from danor to ecient, 4s shown in the previous SARS outbreak, ane therefore donor screening and testing fs crudalS Although many patlents had comesbidties in the reported seis? none had been a transplant recipient, Transplant linians are encouraged to follow guidance sued ewan cengeracon WS Hey 2020Comment by The Transplantation Society as well as local health department guidlines for islating,quarantining, testing, and monitoring returned travellers from endemic areas, Patients with cancer in general are more susceptible to infection due to their immunocompromised status caused by the malignancy and anticancer trentments However, whether patients with gastrointestinal cancers are rote likly to be infected with SARS.COV-2 ‘than healthy individuals remains unknown, In a recent nationwide analysis from China? 18 (1x) of 1590 COVID-19 cases had a history of cancer. Among these 18 cases, three had a history of eoloectal cancer one colonic tubular adenocarcinome, one rectal carcinoma, and one colorectal carcinoma)? Patients with COVID-49 and cancer were observed to have a higher risk of severe events; several strategies have been Proposed, such 2s intentional postponing of adjuvant chemotherapy or elective surgery on @ patient-by- Patent basis, stronger personal protection provisions, and more intensive sunveitanceortrestment? Given the use of biologics and immunesuppressive agents, whether patients with inflammatory bowel alsease (IBD) ate more susceptible to SARS-Cov.2 infection has raised great concem, Curently no patients ‘with IBD have been reported to be infected with SARS- CoV-2 in the IBD Elite Union, which incorporates the seven lagest ID referral centesinChinawith morethan 20000 patents with IBD Furthermore, no patients with {BD with SARS-CoV-2 infection have been reported from the three largest tetiaty 18D centres in Wuhan (Tonal Fospital, Union Hospital, and Zhongnan Hospital t the ‘te tat this manuscript was prepared (March 8, 2020}. Several strategies have been implemented in China to minimise the potential rsk of SARS-CoV? infection in patients with IBD since the outbreak of COVID-29. Fist, the Chinese IBD Society issued offal guidelines for managing patients with IBD in early February 20207 ‘The guidelines include practical recommendations on the use of iimmunosuppressive agents and biologic, diet, ancl intentional postponement of elective surgery and endoscopy, as well as personal protection provisions; these aie outined in the panel. Second, the China Crohns & Colitis Foundation has organised a group of volunteer gastroenterologists that specialise in 180 to offer online consultancy to patients with IBD since Jan 29, 2020. Thité, an online virtual IBD visit programme has been initiated in some IBD centves, ontthdsteomigaveyp Ves May 2020 which provides convenient and cost-effective care, and could potentially reduce the risk of SARS-CoV.2 Infection by avoiding close contact with infected patients in public areas. With the increasing concern {rom patients with IBD globally, helpfuloniine resources about COVID-29 have been provided by international on-prafit organisations such as Crohn's Colitis of Foundstion Ametica and Crohns & Colts UK." Such quidance and advice should be delivered urgently to ‘health-care workers as wellas patients with BD. ‘The comorbidity spectrum of digestive conditions ‘and its impact on treatment and outcome of COVID-19 remains largely unknown. Further data need to be ‘analysed from the COVID-19 cohort established by the ‘National Health Connmission of the People’s Republic ‘of China, which would help to more precisely ascertain the tisk oF SARS-COV-2 infection in patients with digestive comorbidities such as 18D. These data and ‘experience with guidance on how to manage patients with undesining comorbidities in China could faclitate integrated care for patients globally. Wedaduenocanatngbnt etki eran of nei ee en, tou Saye IED nl One BD Quy Ce atone aes (00%) te abarton Rand pened fen en Jean, Jon Shen, Subrata Ghosh, tieng Ru 2, Hong Yang, Kl-Chun Wand “in-Hu Chen on behalf of the Chinese Soviet of 80, Chinese ite 18D Union, ond Chinese BD Quably Cre Evlvation Center Commitee chenminhugmalsyiv eden eprtnet f atoet ery The ea Ae Hpac et ‘Une gto ob, hae Saleen! an ogy tan a eer or Dies od ‘fraoptelefOgese Deere toc Uae ee GACH} Ovi of Geer Mato eel Shak ite Sag Tog Use Shang woe! 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Gee on owenef doen 04) {G05 oranges pea Cae pdt gate n 019: croton 2S ‘warplane, 2020) 7 VagW Gan Cent Cnc ants SARC ene ‘atl aa Chin tae E303 pire FO doraoamsiare-aowsaepoose 6 Mook cen Mt lead Ciel ty celabrton on niratry ‘eldbenin Ce knee SRE 9 iseSoetcf 8,Naang pars ingeotaskof i 390g 30248 30-isps cotiseun Wh 0 poe sould koa te 018 ‘ow roe (CMD 39) Mi weesesNoonong) ‘hat dato shoe sneer cod 19 (cred ae. 200) 21Gb acs tern COM 9) ae ia Schrag eontpied ha ar erat iecasedbarSo). Liver injury in COVID-19: management and challenges In December, 2019, an outbreak of a novel coronavirus (Severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2], previously 2019-nCoV) started in Wuhan, China, and has since become a global threat to human health. The number of confirmed cases ‘of 2019 coronavirus disease (COVID-19) has reached £87137 worldwide as of March 4, 2020, according to i» WHO COVID-29 situation report 41; most of these patients are in Wuhan, China. Many cazes of COVID-29 are acute and resolve quickly, but the disease can also be fatal, with a mortality rate of around 3%? Onset of severe disease can result in death due to massive alveolar damage and progressive respiratory faire? SARS-CoV-2 shares 82% genome sequence similarity to SARS-COV and 50% genome sequence homology to Middle East respiratory syndrome. coronavius ((nERS-CoV)—all thre coronaviruses are known to cause severe respiratory syrnptons. Live impairment has been reported in upto 60% of patients with SARSPand has also ‘been reported in patints infected with MERS-CoV. ‘At least seven relatively large-scale casestudies have reported the lnial features of patients with COVID-19.% inthis Comment, we assess how the liver is affected using the available case studies and data fom ‘The Fifth Medical Center of PLS General Hospital, Bojng, China. These data indicate that 2-11% of patients with COvID-19 had liver comorbidities and 14-53% cases reported abnormal levels of alanine aminotransferase and aspartate aminotransferase (AST) during disease rogession (table). Patients with severe COVID-29 seem to have higher ates of liver dysfunction. tna study in The Loncet by Huang and colleagues? elevation of AST was observed in eight (623) of 13 patients inthe intensive cre unit (CU) compared with seven (255) ‘of 28 patients who did not require care in the ICU. -Moreove in a large cohort including 1099 patients fom $552 hosptalsin 31 provinces ox provincial municipalities, mote severe patients with dsease had abnormal liver aminotransferase levels than did non-sevre patients ‘with disease? Furthermore, in another stody* patients who had a diagnosis of COVID-19 confirmed by CT scan \while in the subclinical phase i, before symptom onset) had significantly lower incidence of AST sbnormalty than did potent diagnosed after the onset of symptoms ‘Therefore, liver injny is mote prevalent in severe cases than in mildcases of COVID9. Liver damage in patients with coronavius infections might direct caused by the vil nfectionof liver cel, Approximately 2-10% of patients with COVID-19 present with diarchoes, and SARS-CoV-2 RNA hasbeen detected instool and blood samples This evidence implicates the possibilty of viral eqposure in the iver. Both SARS-CoV.2 and SARS-CoV bind to the angiotersin-converting ‘eye 2 (ACE2) receptor to enter the target cll? where ‘the vrs cepicates and subsequent infects other cells in the upper respiratory tract and lung tissue patients then begin to have cinical symptoms and manifestations, Pathological studies in patients with SARS. confirmed the presence ofthe virus ver tsue, although the viral titre was relatively low because vial incisions were not ‘observe. In patients with MERS, viral particles were not detectable in ver tise Gamma-ghitamy/ transferase (66M), a diagnostic biomasker for cholangocyt injury. has not been seported in the exiting COVID-A9 case studies; we found that it was elevated in 30 (54%) cf 55 patients with COVID-19 during hospitalisation jn our centre (unpublished). We also found that tlevated alkaline phosphatase levels were observed in one (183) of 56 patients with COVID-19. during hospitalisation, A preliminary study (albeit not peer- reviewed) suggested that ACE2 receptor expression is cenvichad in cholangiogytes,” indicating that SARS-CoV-2 ‘night tetly bind to ACE2-postve cholanglogtes to dysegulete liver function. Nevertheless, pathological rthcnomipstihey Vt May 2000