Table 4.
IBD-treatment and COVID-19: risks and benefits.
| Author | Patients | Diagnostic Method | Geographic Area | Time/Duration of the Study | Clinic Results | Main Purposes of the Study | Therapy’s Effects |
|---|---|---|---|---|---|---|---|
| Ungaro et al., 2020 [35] |
IBD and COVID-19: 1439 | Laboratory diagnosis | SECURE-IBD (47 countries) | 13 March 2020–09 June 2020 | 112 patients (7.8%) severe form 82 ICU 66 mechanical ventilations 49 (3.4%) deaths |
To evaluate the course of COVID-19 in IBD patients under different therapies | Severe form of disease: patients under anti-TNFs (1.1%) < other patients (4.8%), p < 0.001 Anti-TNF are not associated with COVID-19 severe forms (aOR:0.69). Patients under thiopurine or thiopurine + anti-TNFs (9.2% and 8.8%) > patients under anti-TNFs monotherapy (2.2%), p < 0.001. Risk of COVID-19 severe form is increased in patients under thiopurine treatment (aOR:4.08) or combined therapy (aOR:4.01). Patients under mesalamine (sulfasalazine (13.9%) > other patients (5.2%), p < 0.001 Increased risk of COVID-19 severe forms (aOR: 1.47) |
| Bezzio et al., 2020 [36] |
IBD: 243 COVID-19: 11 (1 confirmed and the other made by contact + clinic) |
Molecular swab in 1 patient Clinic (min 3 symptoms) + contact in 10 patients |
Italy | 10 March 2020–03 May 2020 | 124 patients on biologic therapy (2 COVID-19) 119 patients not on biologic therapy (9 COVID-19) |
To assess the incidence of COVID-19 in IBD patients relating to the use or biologics | COVID-19 incidence: patients on biologic therapy 1.6% < patients not on biologic therapy 7.6% |
| Winthrop et al., 2020 [37] |
COVID-19: 2500, of which 77 on immunomodulator therapy (diagnosis: RA, UC, sarcoidosis and others) | Molecular swab (PCR) | Canada | Until 22 May 2020 | 63 (81.8%) hospitalizations 27 (35.1%) mechanical ventilations 37 (48.1%) ICU 9 (11.7%) deaths |
To report COVID-19 cases among patients assuming immunomodulatory therapies | Hospitalization required in 50% of patients on anti-TNF therapy 73.3% of patients on biologic (non anti-TNFs) therapy 90.9% of patients on DMARDs therapy 100% of patients od DMARDs + corticosteroids or only corticosteroids 66.7% of patients on JAK inhibitors treatment 0 deaths among patients on anti-TNF therapy |
| Rizzello et al., 2020 [12] |
IBD: 1158 COVID-19: 26 (2.2%) |
Molecular swab (PCR) | Italy | 10 March 2020–10 June 2020 | 521 patients on biologic therapy. Treatment interrupted in 85 patients and delayed in 195. Worsening of symptoms in 200 patients on biologic therapy (189 interrupted it) |
To understand the incidence of COVID-19 between IBD patients and to evaluate possible risk factors for the infection | 5 patients on biologics, 16 on mesalazine, 5 on corticosteroids and 1 on thiopurines Hospitalization in 7 patients (none was in biologic therapy) 2 deaths (mesalazine therapy) Anti-TNFs could reduce the infection severity The continuous corticosteroids treatment could represent a risk factor for the infection |
| Burke et al., 2020 [38] |
IBD: 5302 COVID-19: 39 (0.7%) |
Molecular swab (PCR) | Massachusetts | 01 January 2020–25 April 2020 | 7 hospitalized patients 3 ICU 1 death |
To clarify the effect of biologics and immunomodulators on COVID-19 risk | Infection: 0.64% of patients on mesalamine/sulfasalazine therapy, 0.5% of them on immunomodulators, 1% of patients on anti-TNFs, 1% among patients on Vedolizumab therapy. Drug intake does not influence infection risk. Corticosteroids’ or other immunosuppressor’s use have not been associated with a higher infection risk (users 0.37% vs. nonusers 0.36% regarding corticosteroids) |
| Kennedy et al., 2021 [39] |
IBD: 6935 (patients ≥ 5 years under Infliximab or Vedolizumab treatment for at least 6 weeks) | Certain cases: molecular swab (PCR) Highly suspected cases: clinic |
UK | 22 September 2020–23 December 2020 | Anti-SARS-CoV-2 antibodies: 4.3% (295) | To study if IBD patients under Infliximab treatment show reduced serological response to the infection | Anti-SARS-CoV-2: 3.4% of patients under Infliximab (161/4685) < 6% of patients under Vedolizumab (134/2250), p < 0.0001 Infliximab is associated to a lower seropositivity level compared to Vedolizumab (OR:0.66, p = 0.0027) or other immunomodulators (OR:0.70, p = 0.012) Among patients with COVID-19 confirmed diagnosis, seroconversion regarded: Infliximab (48%, 39/81) < Vedolizumab (83%, 30/36, p = 0.00044) even though the incidence of symptoms was similar in the two groups Failure of seroconversion has been linked to the concomitant use of immunomodulators: in patients treated with Infliximab only the seroconversion rate was 60% (24/40) while in patients treated with infliximab and immunomodulators it was 37% (15/41, p = 0.046) |
| Bossa et al., 2021 [40] |
IBD: 259 (27 children) Controls: 214 non-IBD patients |
Serologic test | Foggia (Italy) | February 2020–June 2020 | Infection rate (0.77) comparable to general population (0.19), p = 0.5 32 patients (12.3%) developed COVID-like symptoms (1 of them under Infliximab therapy)2 hospitalizations |
To understand the impact of SARS-CoV-2 infection in IBD patients and the serum prevalence of antibodies in IBD patients under biologics | Seroprevalence (anti SARS-CoV-2 antibodies) comparable between IBD patients (0.77) and general population (0.9) No risk associated with biologic therapy (34.4% Adalimumab, 24% Infliximab, 22% Vedolizumab, 10.4% Ustekinumab, 7.7% Golimumab, 1.1% experimental therapy, 0.4% thalidomide) |
| Khan et al., 2021 [41] |
IBD: 30,911 COVID-19: 649 |
Molecular swab (PCR) | USA, VAHS database | 20 January 2020–10 December 2020 | 125 hospitalizations 41 deaths |
To understand the role of IBD therapies in the risk of infection and their impact in the infection course | Vedolizumab is associated with a greater infection risk than mesalazine (HR:1.70, p = 0.006) Corticosteroids are associated with an increased risk of infection and of severe forms (hospitalization or death) No differences in terms of outcome between patients on mesalazine and on anti-TNFs Patients who are not under therapy have a significatively higher risk of severe infection compared to patients under mesalazine |
| Berte et al., 2020 [42] |
IBD: 354 (biologic therapy) COVID-19 IgG: 8 |
Serologic test | Italy and Germany | April 2020–June 2020 | Anti-SARS-CoV-2 IgG have been found in 8 patients (higher incidence of symptoms and contact with positives in these patients) | To determine SARS-CoV-2 infection prevalence in IBD patients under biologics | Seroprevalence (IgG anti SARS-CoV-2) in IBD patients on biologic therapy comparable to that found in general population (Milan 7.5%, Sardinia 0.3% e Germany 0.9%) |
| Agrawal et al., 2021 [43] |
IBD and COVID-19: 3647 patients, of which 457 (12.5%) on Vedolizumab therapy | Laboratory diagnosis | Data from SECURE-IBD database | Until 26 January 2021 | 664 hospitalizations 166 severe forms of infection (ICU admission, mechanical ventilation and/or death) |
To study Vedolizumab effects in IBD patients who undergo COVID-19 | Vedolizumab is safe and it is not associated with hospitalizations or more severe infections compared to other drugs (aOR:0.87 e 0.95) Hospitalization risk (but not the risk of severe forms) is increased in patients on Vedolizumab monotherapy compared to patients on anti-TNFs (aOR:1.38, aOR:2.92, p = 0.049 e p = 0.055) |
| Brenner et al., 2020 [44] |
IBD and COVID-19: 525 (age ≥ 5) | Laboratory diagnosis | Data from SECURE-IBD database | Until May 2020 | Severe forms in 37 patients (ICU, mechanical ventilation, death) Only 3 pediatric patients (10%) hospitalized (none of them in ICU) |
To study the clinical course of COVID-19 in IBD patients and to find eventual associations with clinical and demographic characteristics and with immunosuppressant treatment | Factors that have been connected to severe forms: advanced age, comorbidities, use of systemic corticosteroids (aOR:6.9), sulfasalazine (aOR:3.1) Anti-TNFs (43.4% of patients) are not associated with severe forms (aOR:0.9) |
| Allocca et al., 2020 [20] |
IBD: 23,879 COVID-19: 97 |
Molecular swab in 64 patients Highly suspected (clinic + contact or radiology) 33 patients |
Italy, United Kingdom, France, Spain, Portugal, Malta, Kastoria, Attica, Greece, Russia and Israel | 21 February 2020–30 June 2020 | Symptoms in 90% of positives. Pneumonia in 22%. Hospitalization in 24%. 1 death | To study the incidence of COVID-19 and the eventual effects of immunosuppression on the risk of infection | Corticosteroids treatment is associated with an increased risk of hospitalization (OR 7.69, p = 0.015), while the treatment with monoclonal antibodies is associated with a reduced risk of pneumonia and hospitalization (OR 0.15, p = 0.003 e OR 0.31, p = 0.031). |
| Norsa et al., 2020 [21] |
IBD: 522, of which 59 < 18 aa Controls with COVID-19: 479 |
Molecular swab | Hospital “Papa Giovanni XXIII”, Bergamo (Italy) | 19 February 2020–23 March 2020 | To report the experience of this IBD Italian center during the pandemic | 0 COVID-19 cases among IBD patients (despite the therapy with immunomodulators in 22% of them and biologics in 16%) | |
| Hormati et al., 2020 [45] |
IBD (or AIH): 200 (treated with Azathioprine, anti-TNFs and prednisone) COVID-19: 11 (8 with IBD) |
Molecular swab | Iran | Since the beginning of pandemic (publication date): 28 May 2020) | Only mild symptoms that disappears more rapidly compared to general population, as like the RX alterations. 0 deaths | To study the effects of immunosuppressive drugs in SARS-CoV-2 infection | Percentage of positives lower than the general population not receiving immunosuppressors |
| Lukin et al., 2020 [24] |
IBD and COVID-19: 80 (considered positive with both a molecular test or highly suspect clinic) COVID-19 non IBD: 160 |
Molecular swab or highly suspect clinic | New York | 01 February 2020–30 April 2020 | To notice eventual differences between COVID-19 patients with and without IBD in terms of clinical outcomes and to study risk factors for COVID-19 in IBD patients | Use of corticosteroids is higher among patients with COVID-19 than in patients with IBD but not infected No differences regarding biologics and immunomodulators The proportion of patients receiving Vedolizumab or not receiving biological therapy was numerically higher in patients requiring hospitalization (no biologics: 29%, Vedolizumab: 30%, Ustekinumab 8%, anti TNFs (6%) p = 0.197) compared to others |
|
| Khan et al., 2020 [46] |
IBD: 37,857 COVID-19: 36 |
Laboratory diagnosis | USA, VAHS database | 01 January 2020–15 May 2020 | 2391 patients on thiopurine therapy: 2 COVID-19 4920 patients on anti-TNF therapy: 3 COVID-19 |
To study the impact of anti-TNF and thiopurines on SARS-CoV-2 infection | Thiopurines are not connected to an increased risk of infection (OR:0.962, p = 0.9577) Anti-TNFs are not associated with an increased risk of infection (OR:0.581, p = 0.3774) |
| Singh et al., 2020 [27] |
IBD: 196,403 COVID-19: 232 (1901 tests) Controls: 19,776 COVID-19 |
Laboratory diagnosis or diagnostic code for COVID-19 after hospitalization | USA | 26 January 2020–26 May 2020 | Risk of severe infection (hospitalization and/or death within 30 days after diagnosis) similar between IBD patients and controls | To study clinical presentation and outcomes of COVID-19 among IBD patients and compare them to a large control group | Higher risk of severe forms among patients under corticosteroids treatment for at least 3 months (30.98%) compared to other patients (19.25%) RR:1.6, p = 0.4 (univariate analysis) |
| Allocca, Guidelli et al., 2020 [47] |
COVID-19: 41 patients with immune mediated inflammatory diseases (IMID). Among them 12 UC and 9 CD | Molecular swab or highly suspect clinic or chest CT | Italy | N.R. | All patients developed symptoms due to infection: 16 pneumonia (40%), 14 hospitalizations (34%), 0 ICU admissions and 1 death | To report the experience of the Humanitas center (Milan) among patients with IMID | Corticosteroids therapy increases risk of oxygen therapy needing (p = 0.007) Biologics are not associated with hospitalization risk |
IBD: inflammatory bowel disease. TNF: tumor necrosis factor. DMARDs: disease modifying antirheumatic drugs. CS: corticosteroids. RA: rheumatoid arthritis. UC: ulcerative colitis. JAK: Janus kinase. ICU: intensive care unit. AIH: autoimmune hepatitis. IMID: immune mediated inflammatory diseases. CD: Crohn’s disease. UC: ulcerative colitis. PCR: polymerase chain reaction. TC: computed tomography. ICU: intensive care unit.