Impact of COVID-19 in individuals with and without pre-existent digestive disorders with a particular focus on elderly patients

Table 1 Overview of studies evaluating the course of gastrointestinal symptoms during severe acute respiratory syndrome coronavirus 2 infection in the elderly population

Ref.	n	Age (yrs)	GI symptoms	Diarrhoea	Nausea/vomiting	Anorexia	Abdominal pain	Outcomes
de Souza et al[32]	9807	70.21 ± 8	-	2%	-	-	-	No association
Ramos-Rincon et al[34]	2772	86.3 ± 3	-	14%	5%	22%	-	No association
Marziliano et al[33]	4961	77 ± 8	9%	-	-	-	-	No association
Atalla et al[37]	111	87.0 median (IQR: 77.0-92.0)		7% (38% all ages)	2%	17% (61% all ages)	-	Mortality was associated with a disease course beginning with a loss of appetite, and the incidence of diarrhea was more frequent in the deceased
Lanthier et al[35]	50	88 median (IQR: 83-92)	30%	24%	6%	10%	6%	Digestive symptoms were associated with a favorable outcome
Aroniadis et al[9]	434	Age > 70	31%	19%	-	-	-	Older patients were less likely to exhibit gastrointestinal symptoms
Zhan et al[23]	39	Age > 75	36%	-	-	-	-	No association
Vrillon et al[36]	76	90 median (IQR: 86-92)	22%	-	-	-	-	Digestive symptoms were associated with a favorable outcome

The sample’s age was expressed either by the mean or the median in the studies analyzed. For some non-specific studies performed on older people, only the characteristics of the population mentioned above have been shown in the table. However, some of these have yet to express a category-specific significant trend measure. For example, the relationship between the course of the infection and the outcome was reported in the last column. SD: Standard deviation; IQR: Interquartile range; GI: Gastrointestinal.

Table 2 Risk of severe coronavirus disease 2019 in elderly inflammatory bowel disease patients

Ref.	Total number of IBD patients	Number of COVID-19-positive IBD patients	Age threshold considered (yrs)	Risk of severe COVID-19
Ludvigsson et al[45]	67292	179 (hospitalized patients)	60	HR = 1.42; 95%CI: 0.94-2.13
Brenner et al[59]	SECURE-IBD database	525	Increasing age on multivariable analysis	OR = 1.04; 95%CI: 1.01-1.06
Zabana et al[60]	53682	482	60	OR = 4.59, 95%CI: 1.3-15.9, P = 0.02
Wetwittayakhlang et al[61]	3516	82	55	OR = 11.09, 95%CI: 1.81-68.09, P = 0.02

OR: Odds ratio; CI: Confidence interval; IBD: Inflammatory bowel disease; COVID-19: Coronavirus disease 2019; HR: Hazard ratio.

Table 3 Summary of studies on the relationship between liver disease and coronavirus disease 2019 in elderly patients

Ref.	Outcome considered	Results
Khateri et al[108]	Incidence of acute liver injury in patients affected by COVID-19	Acute liver injury has no relationship with age
Metawea et al[110]	Mortality of patients with hepatocellular carcinoma infected with COVID-19	Age is associated with poorer outcomes and higher mortality
Ji et al[111]	Severe COVID-19 in patients affected by NAFLD	Associated in patients older than 60 yr
Zhou et al[112]	Severe COVID-19 in patients affected by NAFLD	Associated in patients younger than 60 yr
Hartl et al[113]	Liver-related death due to COVID-19 between different age groups	More frequent in the 40-69 years old group than in the over 70 years old group (6.5% vs 2.2%)
Ioannou et al[115]	Predictors of mortality among patients with cirrhosis and SARS-CoV-2 infection	Advanced age was one of the main risk factors for mortality among patients with cirrhosis and SARS-CoV-2 infection
Brozat et al[116]	The case fatality rate in patients with cirrhosis and SARS-CoV-2 infection	The case fatality rate in cirrhotic patients and SARS-CoV-2 infection aged 65 yr and older was nearly three times that in patients younger than 65 yr (43.6% vs 16.1%)

SARS-CoV-2: Severe acute respiratory syndrome coronavirus 2; COVID-19: Coronavirus disease 2019; NAFLD: Non-alcoholic fatty liver disease.

Table 4 Evidence regarding pancreatic involvement in coronavirus disease 2019 patients

Ref.	Study design	No. of patients with pancreatic injury/total no. of patients	Remarks
Wang et al[122]	CHS	9/52 (4.68%)	Potential mild pancreatic involvement in patients with COVID-19 pneumonia
Bruno et al[124]	CHS	6/70 (8.5%)	Pancreatic involvement in hospitalized patients with documented COVID-19
Liu et al[125]	RS	13/121 (10.74%)	Pancreatic enzyme alteration incidence was higher in patients with severe COVID-19-related conditions than those with the non-severe disease. However, only a minority of patients with pancreatic enzyme alteration had a confirmed diagnosis of AP as defined by the AC
Stephens et al[126]	RS	158/234 (67.5%)	Raised serum amylase in patients with COVID-19 may not be associated with pancreatitis
Akkus et al[127]	RS	127/309 (15.7%)	Pancreatic injuries or AP are frequent during COVID-19 infection, especially in those with pre-existing DM
McNabb-Baltar et al[128]	RS	9/71 (12.1%)	Although a mild elevation in serum lipase was observed in some patients with COVID-19, acute clinical pancreatitis was not seen, according to the AC
Bansal et al[129]	RS	14/42 (33%), 7/29 patients (24.1%)	Pancreatic injury showed no statistically significant relation to the severity or outcome of COVID-19
Rasch et al[130]	CHS	22/38 (57.8%)	Patients with lipasemia needed more extended periods of mechanical ventilation than patients with COVID-19-associated ARDS
Barlass et al[131]	CCS	14/83 (16.8%)	Elevated lipase is associated with worse disease outcomes and increased ICU admission and intubation
Bacaksiz et al[132]	RS	316/1378 (23%)	Hyperamilasemia was significantly associated with COVID-19 severity
Magro et al[86]	Review	NA	Increased amylase or lipase levels might not be associated with AP in COVID-19 and may be a consequence of concurrent clinical conditions
Hunt et al[133]	Review	NA	No direct correlation between COVID-19 and pancreatic impairment could be established
Singh et al[134]	MS	1406/435731 (0.32%)	Worse clinical outcomes
Inamdar et al[135]	MS	189/11.883 (0.01%)	COVID-19 patients with pancreatitis were more likely to require mechanical ventilation and had a more extended hospital stay than patients without COVID-19
Karaali and Topal[136]	RS	189/562 (33.6%)	COVID-19 patients with AP had a higher rate of severe AP and a higher need for ICU admission
Dirweesh et al[137]	RS	75/339 (22.1%)	Higher mortality, MOF, and POF rates were registered in patients with AP and coexisting COVID-19
Pandanaboyana et al[138]	CHS	149/1777 (8.3%)	SARS-CoV-2 infection in acute pancreatitis increases 30-d mortality and disease severity
Mirò et al[140]	MS	45/63.822 (0.0007%)	Higher need for hospitalisation in COVID-19 patients with pancreatitis
Akarsu et al[141]	CCS	40/316 (12.6%)	Higher mortality rate and increased need for hospitalisation in COVID-19 patients with pancreatitis
Gubatan et al[62]	RS	100% total population 14235	Patients with a history of pancreatitis may be more susceptible to COVID-19
Huang et al[142]	RCS	4706/326993 (1.4%)	Pre-existing pancreatitis was associated with an increased risk of COVID-19–related hospitalisation and mortality
Hadi et al[143]	CS	2/3 (66.6%)	COVID-19 patients with CP bear higher hospitalisation rates
Georgakopoulou et al[144]	RS	100%	COVID-19-associated acute pancreatitis affected primarily females with a median age of 53.5 yr

CS: Case series; CR: Case reports; RS: Retrospective studies; RCS: Retrospective cohort study; MS: Multicentric study; CCS: Case-control study; CHS: Cohort study; CSS: Cross-sectional study; NA: Not available; SARS-CoV-2: Severe acute respiratory syndrome coronavirus 2; COVID-19: Coronavirus disease 2019; AC: Atlanta criteria; CP: Convalescent plasma; ICU: Intensive care unit; MOF: Multiple-organ failure; POF: Persistent organ failure; ARDS: Acute respiratory distress syndrome.

Table 5 Case reports regarding pancreatic involvement in old coronavirus disease 2019 patients

Ref.	Study design	Age (yrs)	Remarks
Meyers et al[151]	CR	67	COVID-19 can cause clinical AP. Typical abdominal pain radiating to the back. Increase lipase serum level. Evidence of AP in abdominal CT scan. Glasgow Acute Pancreatitis Score: NA
Karimzadeh et al[152]	CR	65	COVID-19 presents as mild AP. Typical abdominal pain radiating to the back. Increase lipase serum level. Negative abdominal CT scan. Glasgow Acute Pancreatitis Score: 1 point
Gadiparthi et al[153]	CR	74	AP in a patient with COVID-19 with SARS-CoV-2 as the possible etiological agent. Typical abdominal pain radiating to the back. Increase lipase serum level. Evidence of AP in abdominal CT scan. Glasgow Acute Pancreatitis Score: 1 point
Wifi et al[154]	CR	72	Emphasises the importance of measuring serum amylase and lipase in patients with COVID-19. Typical abdominal pain radiating to the back. Increase lipase and amylase serum levels. Negative abdominal CT scan. Glasgow Acute Pancreatitis Score: 3 points
Gonzalo-Voltas et al[155]	CR	76	A case of AP that could be related to COVID-19 infection. Typical abdominal pain radiating to the back. Increase amylase serum level. Evidence of AP in abdominal CT scan. Glasgow Acute Pancreatitis Score: NA
Reick-Mitrisin et al[156]	CR	71	AP should be considered in differential abdominal pain in patients with active or recent SARS-CoV-2 infection. Typical abdominal pain. Increase lipase serum level. Evidence of AP in abdominal CT scan. Glasgow Acute Pancreatitis Score: 3 points
Brikman et al[163]	CR	61	Unresolved abdominal pain occurring late during COVID-19 warrants a thorough workup. Typical abdominal pain. Increase lipase serum level. Evidence of AP in abdominal CT scan. Glasgow Acute Pancreatitis Score: 2 points
Acherjya et al[157]	CR	57	Pay attention to the atypical presentations of SARS-CoV-2, including AP. Typical abdominal pain radiating to the back. Increase lipase serum level. Evidence of AP in abdominal CT scan. Glasgow Acute Pancreatitis Score: 4 points
Alves et al[158]	CR	56	Physicians should be aware that asymptomatic or mildly gastrointestinal symptomatic patients with COVID-19 require pancreatic enzymes and even abdomen imaging to diagnose pancreatitis. Typical abdominal pain. Increase lipase and amylase serum levels. Evidence of AP in abdominal CT scan. Glasgow Acute Pancreatitis Score: 3 points
Shinohara et al[159]	CR	58	Extrapulmonary clinical characteristics of COVID-19 remain unclear. Typical abdominal pain. Increase amylase serum level. Evidence of AP in abdominal CT scan. Glasgow Acute Pancreatitis Score: NA
Kumaran et al[160]	CR	67	Importance of considering COVID-19 as a potential cause in patients presenting with idiopathic pancreatitis. Typical abdominal pain. Increase amylase serum level. Evidence of AP in abdominal CT scan. Glasgow Acute Pancreatitis Score: 2 points

AP: Acute pancreatitis; CR: Case reports; CT: Computed tomography; NA: Not available; SARS-CoV-2: Severe acute respiratory syndrome coronavirus 2.