GI manifestations in covid 19 patients

1. GI MANIFESTATIONS
IN COVID-19 PATIENTS
DR. KHUSHBOO PRIYA
DM RESIDENT
DEPT. OF GASTROENTEROLOGY

2. Infographic Style
To understand the prognosis of
gastrointestinal and liver
involvement in patients with
COVID-19
To evaluate the GI manifestations in
COVID 19 patients
To understand the modes of
transmission especially feco-oral
route
LEARNING OBJECTIVES
To know the management of GI
complications in COVID 19 patients.

3. STATISTICS OF WORLD
Confirmed
10,79,50,666
Recovered
7,99,91,811
Deaths
23,67,355
Confirmed
Recovered
Deaths
3

4. Nepal STATISTICS
Confimed
2,72,430
Recovered
2,68,660
Deaths 2,052
Confimed
Recovered
Deaths
4

5. CORONAVIRUS
 FAMILY : Coronaviridae
 It is spherical particle with crown like projection
 Average diameter – 125nm
 Viral envelope consists of lipid bilayer with anchored proteins
 Nucleocapsid – N protein and positive sense single stranded
RNA genome
5

6. (Betacorona virus)
6

7. REPLICATION CYCLE
1. ENTRY – S protein +ACE2
2. TRANSLATION : virus particle uncoated and attaches
to ribosome
 Host ribosome translates open reading frames ORF1a
and ORF1b into polyproteins pp1a and pp1b .
 Polyproteins are cleaved by PROTEASES
into 16 nonstructural proteins
 Includes RNA dependent RNA polymerase , RNAhelicase
 Number of nsp’s coalesce to form replicase transcriptase complex (RTC)
 RdRp mediates replication of viral genome
3. TRANSCRIPTION – genomic RNA to mRNAs .
 In host endoplasmic reticulum RNA translation to structural proteins happen.
 In Golgi apparatus assembly of virions happen and forms secretory vesicles
 Progeny virus are released by exocytosis .
7

8. PATHOGENESIS
 Viral antigens presented to APC
 Stimulates cellular and humoral immunity
 IgM and IgG antibodies are formed . They
are S and N protein specific .
 CD4 and CD8 T cells are activated .
 Overproduction of proinflammatory cytokines
 IL-6 , IL-1β, Tumour necrosis factor : CYTOKINE STORM
8

9. CYTOKINE STORM
 Leads to vascular hyperpermeability
 Defective procoagulant – anticoagulant balance
 Leads to formation of thrombin
 Thrombin activates protease activated receptor 1
on platelets and leads to aggregation and
microthrombosis, disseminated intravascular
coagulation, and multiorgan failure.
9

10. HYPERCOAGULABLE STATE
 Endothelial injury : due to direct invasion by virus and
cytokine storm .
 Stasis : immobilization in critically ill patients .
 Decrease in Antithrombin , Protein S and Protein C .
 Elevated factor vш , Fibrinogen , VWF
10

11. INCUBATION PERIOD
 2-14 days
 Mean is 5 days after exposure .
 CDC
11

12.  VIABILITY :
 Aerosols – 3 hours
 Plastic and stainless steel – 72 hours
 Copper – 4 hours
 Cardboard – 24 hours
 Clothes – 8 hours
CDC
12

13. MODES OF TRANSMISSION
 PERSON – PERSON :
 DROPLET transmission
 Infected person coughs , sneezes or talks - direct contact
 Droplets donot travel more than 6 feet .
 Indirect spread – touching an infected surface followed by
eyes , nose or mouth
International pulmonary consensus
13

14. • ACE2 is also expressed and functions in the local RAS of the liver
(cholangiocytes and hepatocytes) and enterocytes of the intestines.
• Secondary site for enteric SARS-CoV-2 infection.
• Continued viral production by host enterocytes perpetuates this
situation and deteriorates conditions in the gut-lung axis.
• Evidence supports that SARS-CoV-2 infection potentially leads to
degeneration of the gut-blood barrier leading to systemic spread of
bacteria, endotoxins, and microbial metabolites likely affecting the
host’s response to COVID-19 infection and cumulating in
multisystem dysfunction and septic shock.
14

15. • A study by Cai et al. demonstrated that some patients were noted to
have a high frequency of SARS-CoV-2 RNA detection in feces.
• It also confirmed prolonged viral RNA shedding in feces for at least
two weeks and upwards of more than a month, raising suspicion
that the gastrointestinal tract acts as another site of viral replication.
• A study conducted by Xiao et al. demonstrated results favoring
gastrointestinal viral replication with potential fecal-oral route of
transmission.
• Amongst 73 hospitalized COVID-19 patients in China, ranging from
10 months to 78 years old, 53.42 % tested positive for SARS-CoV-2
RNA in the stool.
15

16. • Positive stool results ranged from 1 to 12 days, and 23.29 %
continued to have positive stool results after having negative
respiratory samples.
• Upon endoscopy and biopsy, the study also found that SARS-CoV-2
RNA was detected with positive staining of the viral nucleocapsid
protein in gastric, duodenal, and rectal epithelium.
• These findings further support the evidence of replication of
infectious virions occurring within the gastrointestinal tract .
• Accordingly, fecal-oral transmission must be taken into
consideration. Of great significance is the fact that viral RNA in
feces can remain even after viral RNA in the respiratory tract clears
therefore providing a potential source of spread. Considerations for
testing of viral RNA in feces by rRT-PCR can be taken to monitor for
adequate source and infection control 16

17. CLINICAL PRESENTATION
 Fever (83-99%)  Myalgias(11-35%)
 Cough (59-82%)  Loss of smell ( anosmia )
 Fatigue (44-77%)  Loss of taste (ageusia )
 Anorexia (4-84%)  GI symptoms (15%)
 Shortness of breath (31-40%)  Sore throat
 Nasal congestion
WHO
17

18. Gastrointestinal manifestations
Diarrhea
Vomiting
Abdominal pain
Studies have identified the SARS-CoV-2 RNAin anal/rectal swabs
• Zhang W, Du RH,Li Bet al. Molecular and serological investigation of 2019-nCoV infected
patients: implication of multiple shedding routes. Emerg. Microbes. Infect. 2020; 9: 386–9.
• Xu Y,Li X,Zhu Bet al. Characteristics of pediatric SARS-CoV-2 infection and potential
evidence for persistent fecal viral shedding. Nat. Med. 2020
cohorts have reported frequencies
2.0–10.1%
1.0– 10.1%
2.2–5.8%
18

19. Liver injury in Covid-19 patients
14.8–53.1% of Covid-19 patients had abnormal levels of
alanine aminotransferase (ALT) and aspartate
aminotransferase (AST)
Most of the liver injuries are mild and transient
Mechanism
Direct viral infection of hepatocytes
Immune-related injury
Drug hepatotoxicity
Xu L,Liu J,Lu M, Yang D, Zheng X. Liver injury during highly pathogenic human
coronavirus infections. Liver Int. 2020. 19

20. Pancreas
• In a recent study by Wang et al. examining 52 patients with COVID-
19 pneumonia, 17 % of patients experienced pancreatic injury
defined by any abnormality in amylase or lipase. They did not exhibit
clinical symptoms of severe pancreatitis, however.
• The ACE2 receptor is also highly expressed in pancreatic islet cells,
therefore SARS-CoV-2 infection can theoretically cause islet
damage resulting in acute diabetes.
20

21. Critically ill patients with COVID-19
Bowel ischemia
Transaminitis
Gastrointestinal bleeding
Pancreatitis
Ogilvie syndrome
Severe ileus
Kaafarani HMA, ElMoheb M, Hwabejire JO,et al. Gastrointestinal complications in critically ill
patients with COVID-19.Ann Surg. 2020;272(2)
21

22. Manifestations and prognosis of gastrointestinal and liver
involvement in patients with COVID-19: a systematic review and
meta-analysis
Lancet Gastroenterol Hepatol 2020; 5: 667–78
The pooled estimate of SARS-CoV-2 viral RNApositivity in fecal samples was 54% (95% CI
44–64; I²=28%), with positivity persisting for up to 47 days after symptom onset
Patients with severe COVID-19 were more likely to present with abdominal pain
No significant difference between patients with severe and non-severe disease in loss of
appetite, diarrhea, or nausea or vomiting
Higher risk of abnormal liver chemistry
Gastrointestinal symptoms were reported in 15% of patients with COVID-19 and liver injury
in 19% of patients
22

23. GI Surgical Indication and outcome
The overall 14-day patient mortality was 15%.
The mortality rate of the subset of patients who required abdominal surgery was as
high as 40%
Kaafarani HMA, ElMoheb M, Hwabejire JO,et al. Gastrointestinal complications in
critically ill patients with COVID-19.Ann Surg.2020;272(2)
23

24. Categories
A Mild sore throat/ cough/ rhinitis/ diarrhea
B Fever and /or severe sore throat/ cough / diarrhea
or
Cat A + Any of the following
Cardiovascular disease
Uncontrolled DM, HTN, Cancer, HIV, lung, liver, renal or neurological
diseases On steroids/ immunosuppressants
Pregnancy
Age> 60 yrs
C Dyspnoea, chest pain, drowsy, low BP, cyanosis, haemoptysis
Worsening of underlying chronic conditions
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25. 25

26. 26

27. Diagnosis
27

28. Covid suspect:
1. Epidemiological history
• Travel or residence history of the area with COVID-19 case report within 14 days before the onset of
the disease;
• Contact history with the COVID-19 virus infected persons (those with positive nucleic acid test)
within 14 days before the onset of the disease;
• Clustering onset of COVID-19 (2 or more cases of fever and/ or respiratory symptoms within 2 weeks
in small areas such as home, office, school, class, etc.).
2. Clinical manifestations
• Fever and/or respiratory symptoms;
• Pneumonia imaging features of COVID-19 [chest computed tomography (CT) or magnetic
resonance imaging (MRI)];
• Leukocyte normal or decreased, while lymphocyte count normal or decreased in the early stage of
the onset of the disease.
Confirmed case:
A person with laboratory confirmation of COVID-19 infection, irrespective of clinical signs and symptoms
28

29. Samples for analysis
Specimen Positivity
BAL 93%
Sputum 72%
Nasopharyngeal
swab
63%
Oropharyngeal swab 32%
Faeces 29%
Blood 1%
Urine 0%
Detection of SARS-CoV-2 in different types of clinical specimens. Wenling Wang, Yanli Xu.
JAMA.2020. Mar11
Preferred: Throat &
nasal swab
29

30. Diagnostic Test
• RT- PCR(Reverse transcriptase polymerase chain
reaction)
• Gold standard for diagnosis(100% specificity)
• Positive result in early phase, later can be –ve due
to immunity devlopment.
• Expensive, time consuming(6-8 Hr), low
sensitivity(50- 70%)
30

31. Sample – treated with chemicals-
Extract RNA – Reverse transcribed
to DNA – Add a complimentary
DNA fragment to detect Corona
virus- If virus is present, it will
attach to the fragment- fluorescent
material also added for labelling—
RT PCR machine- each cycle
double the DNAA- 35 cycles
minimum- machine detect
florescence- in real time manor.
31

32. • If RT PCR is negative and suspicion is high – test
should be repeated- if possibly from lower resp tract
• Positivity rates >90% on Day 1-3 of ilnness, <80= at
Day6,
<50% after day 14.
32

33. Rapid antibody tests
• ELISA test- IgM(active infection) and IgG(Past
infection)
• Can be used as a screen test
• Point of care test, rapid results
• cheaper
• Blood test
• Combined IgG+IgM – better utility
33

34. Disadvantages:
• Negative in early phase
• Specificity is low ?
• Cross sensitivity to other corona
viruses.
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35. 35

36. GI endoscopy and biopsy findings
• Previously, in the only case who underwent endoscopy because of upper GI
bleeding from the cohort of 73 patients, no abnormalities were observed in the
stomach, duodenum, colon and rectum, with the exception of mucosa damage
in the oesophagus at endoscopy.
• Histology showed numerous infiltrating plasma cells and lymphocytes as well
as interstitial oedema in the lamina propria of the stomach, duodenum and
rectum.
• A recent cohort of 95 COVID-19 patients reported an additional 6 cases who
underwent endoscopy examination, and identified SARS-CoV-2 RNA in the
oesophagus, stomach, duodenum and rectum from two severe COVID-19
patients, whereas only one case out of four non-severe cases were found to
have SARS-CoV-2 in the duodenum.
36

37. OTHER INVESTIGATIONS
ABNORMALITY POSSIBLE THRESHOLD
D-dimer >1000 ng/ml ( normal < 500 ng/ml
)
CRP > 100 mg /L ( normal < 8 mg/L)
LDH >245 units /L ( 110-210 units /L)
Troponin > 2 times upper limit
Ferritin > 500 mcg/L ( 10-300 mcg/L)
CPK > 2 times upper limit
Neutrophil/lymphocyte ratio >3.5
uptodate
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38. MANAGEMENT
 Isolation protocol
 General measures
 Specific therapy
 Managing chronic conditions
38

39. GENERAL MEASURES
 Empiric antibiotics if secondary bacterial pneumonia is
suspected .
 Avoid nebulized medications .
 Glucocorticoids - WHO strongly recommends that
corticosteroids (i.e. dexamethasone, hydrocortisone or
prednisone) be given orally or intravenously for the
treatment of patients with severe and critical COVID-19.
 Prevention of venous thromboembolism ;
 Prophylactic dose : inj Enoxaparin 40 mg once a day .
 Full dose : Enoxaparin 1 mg / kg every 12 hours .
WHO/CDC
39

40. EMERGENCY USE AUTHORIZATION
MANAGEMENT FOR COVID 19
 1. Remdesivir/ TOCILIZUMAB
 2 . Convalescent plasma
 3. Hyperimmune globulin .
SUPPORTIVE : Zinc, Vitamin C and D important
measure to improve the immune system and to prevent
the development of severe symptoms.
40

41. Effects of SARS-CoV-2 on the Liver and Evaluation of
COVID-19 Patients with Elevated Liver Biochemistries
• The incidence of elevated serum liver biochemistries in hospitalized patients with COVID-19 (primarily elevated AST and ALT, and slightly
elevated bilirubin) ranges from 14% to 53%.
o Liver injury occurs more commonly in more severe COVID-19 cases than in mild cases.
o Liver injury in mild COVID-19 cases is usually transient and does not require specific treatment.
• Lowserum albumin on hospital admission is amarker of COVID-19severity.
•SARS-CoV-2 binds to target cells through angiotensin-converting enzyme 2 (ACE2) (as does SARS-CoV, the virus responsible for
SARS in 2003- 2004).
o Because ACE2 occurs abundantly on liver and biliary epithelial cells, the liver is a potential target for infection.
• Elevated liver biochemistries may reflect a direct virus-induced cytopathic effect and/or immune damage from the provoked
inflammatory response.
• Therapeutic agents usedto managesymptomatic COVID-19may be hepatotoxic. These include statins, remdesivir, and tocilizumab.
•Patients with chronic liver disease, especially viral hepatitis B and/or C, may be more susceptible to liver damage from SARS-CoV-2, as was
the case with SARS-CoV, but supporting data are lacking.
• It is unknown whether SARS-CoV-2 infection exacerbates cholestasis in those with underlying cholestatic liver disease such as PBC
or PSC or with underlying cirrhosis.
• Rarecasesof severeacute liver injury have been described in patients with COVID-19.
•It will be difficult to differentiate whether increases in liver biochemistries are due to SARS-CoV-2 infection itself, its complications, or a
drug- induced liver injury.
• In liver transplant recipients or patients with autoimmune hepatitis on immunosuppressive therapy, acute cellular rejection or disease flare,
respectively, should not be presumed in the face of active COVID-19.
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42. Recommendations
• Serologic testing for hepatitis Band Cis warranted when assessing patients with COVID-19 and elevated liver
biochemistries.
• T
o limit unnecessary transport of patients with COVID-19, ultrasound or other advanced imaging (e.g.,
MRI/MRCP) should be avoided unless there is a clinical suspicion for biliary obstruction, cholangitis, or
venous thrombosis.
The presence of abnormal liver biochemistries should not be a contraindication to using investigational
or off-label therapeutics for COVID-19 (e.g., remdesivir, tocilizumab, chloroquine, hydroxychloroquine,
statins).
• Regular monitoring of liver biochemistries should be performed in all COVID-19 patients, particularly those
treated with remdesivir or tocilizumab, regardless of baseline values.
•Follow guidance in your clinical study protocol and/or by the FDAfor monitoring of liver biochemistries and
discontinuation of study drug used to treat COVID-19.
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43. Management of Patients on Immunosuppressive Agents
• Theeffects of immunosuppression on COVID-19are not well established.
•Rapid pulmonary deterioration in COVID-19is due to a systemic/ pulmonary inflammatory response associated with
increased serum IL-6, IL-8 and TNF-α levels.
•TheWorld Health Organization recommends avoiding corticosteroids for treatment of COVID-19 unless indicated for
another therapeutic purpose.
•Reducing the dosage or stopping immunosuppressants may cause a flare in a patient with autoimmune hepatitis or
precipitate acute rejection in a liver transplant recipient.
•Recommendations
• In immunosuppressed liver disease patients without COVID-19:
oDo not make anticipatory adjustments to current immunosuppressive drugs or dosages.
• In immunosuppressed liver disease patients with COVID-19:
oConsider minimizing the dosage of high-dose prednisone but maintain a dosage of at least 10 mg/day to
avoid adrenal insufficiency.
oConsider reducing azathioprine or mycophenolate dosages, especially in the setting of lymphopenia, fever
or worsening pneumonia attributed to COVID-19.
oConsider reducing but not stopping daily calcineurin inhibitor dosage, especially in the setting of
lymphopenia, fever or worsening pulmonary status attributed to COVID-19.
•In patients with COVID-19, use caution in initiating prednisone or other immunosuppressive therapy where the
potential benefit might be outweighed by the risks (e.g., alcohol-associated hepatitis).
43

44. Procedures
• Thereis potential for fecal-oral SARS-CoV-2 transmission and the virus is detected in saliva.
• Thejoint GIsocieties recommend to “strongly consider rescheduling non-urgent endoscopicprocedures.”
• Endoscopic procedures should be considered aerosol-generating.
•When performing procedures, in addition to standard PPE(gloves, gown, eyewear), the Association for Operating Room Nurses
recommends headwear and masks for those with potential droplet exposure during endoscopic procedures.
Recommendations
• Cancelall elective/non-urgent procedures (e.g., endoscopy, liver biopsy).
•Some procedures may need to be performed, e.g., liver biopsy to rule out rejection or diagnose autoimmune hepatitis,
therapeutic paracentesis, TIPS, endoscopy for variceal bleeding, follow-up band ligation in those with history of
variceal bleeding, biliary procedures (IR or endoscopic).
•Designated hats and surgical masks should be made available to all healthcare staff involved with performing procedures.
Gloves, gowns, and masks should be changed for each case. Hats may be worn for the entire day. Eyewear (personal
or disposable) should be cleaned with an alcohol wipe between cases. Disposable eyewear should be disposed of at
the end of the day unless visibly soiled, in which case it should be immediately discarded.
• Consider limiting the involvement of fellows in endoscopies and other procedures to conserve PPE.
• Follow CDCrecommendations for cleaning and disinfecting rooms or areas visited by individuals with suspected orconfirmed
COVID-19.
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45. 45

46. Conclusions
• While SARS-CoV-2 has been established as a respiratory tract
pathogen, its pathogenesis may also be responsible for the
gastrointestinal manifestations that accompany COVID-19. Some
patients have experienced symptoms such as diarrhea, nausea,
vomiting, and abdominal pain. Additionally, laboratory abnormalities,
hepatic injury, and pancreatic injury have been evident in a subset
of patients, ranging on a spectrum with the severity of disease.
• As the viral receptor ACE2 is present in the gastrointestinal tract, it
may play a role in the virus’s ability to dysregulate the digestive
system, hepatobiliary function, and pancreatic function, thereby
resulting in gastrointestinal symptoms.
46

47. REFERANCES
 UPTODATE
 WHO guidelines on clinical management of COVID 19
 International pulmonologist’s consensus on COVID 19
 Centers for disease control and prevention .
 WORLD HEALTH ORGANIZATION
 AASLD guidelines for GI Manifestation in COVID 19 patient
47

48. THANK YOU