Therapies for Inflammatory Bowel Disease Do Not Pose Additional Risks for Adverse Outcomes of SARS-CoV-2 Infection

An IG-IBD Study

Cristina Bezzio; Alessandro Armuzzi; Federica Furfaro; Sandro Ardizzone; Monica Milla; Sonia Carparelli; Ambrogio Orlando; Flavio Andrea Caprioli; Fabiana Castiglione; Chiara Viganò; Davide Giuseppe Ribaldone; Fabiana Zingone; Rita Monterubbianesi; Nicola Imperatore; Stefano Festa; Marco Daperno; Ludovica Scucchi; Antonio Ferronato; Luca Pastorelli; Paola Balestrieri; Chiara Ricci; Maria Cappello; Carla Felice; Gionata Fiorino; Simone Saibeni

Disclosures

Aliment Pharmacol Ther. 2021;54(11_12):1432-1441. 

In This Article

Results

We enrolled 937 IBD patients with a confirmed SARS-CoV-2 infection (Table 1) from 47 centres. The study group comprised 446 patients with UC (47.6%) and 491 with CD (52.4%), including 79 patients whom we had already studied.[9] The UC and CD groups differed significantly for age (CD patients were younger), disease activity, and therapies, with salicylates and vedolizumab used more frequently by UC patients and TNF antagonists and ustekinumab used more frequently by CD patients. At least one comorbidity was present in 376 (40.1%) IBD patients [89 (9.5%) had arterial hypertension and 21 were obese (2.2%)]; 116 patients (12.4%) had an IMID other than IBD.

Overall, 809 patients (86.3%) had symptomatic SARS-CoV-2 infection, including 392 UC patients (87.9% of all UC patients) and 417 CD patients (84.9%) (Table S1). The most prevalent class of symptoms was respiratory, registered in 60.8% of UC patients and 48.9% of CD patients. The least prevalent class of symptoms was gastrointestinal in both groups. A favourable course of infection with symptoms resolution was recorded in 664 cases (70.8%).

For the IBD patients with moderate or severe outcomes of COVID-19, 145 (15.5%) had pneumonia, 130 (13.9%) required hospitalisation, 65 (6.9%) required ventilatory support, and 25 (2.7%) died. The rates of all adverse COVID-19 outcomes, but death, were significantly higher in UC patients than in CD patients (Figure S1).

Risk Factors for Moderate or Severe COVID-19 Outcomes

In UC patients, the variables found to be predictive of moderate or severe outcomes at univariable analysis were age (per unit increase, P < 0.001), active disease of any severity (P = 0.001), obesity (P < 0.001), arterial hypertension (P = 0.01), and CCI (per unit increase, P < 0.001) (Table S2). At multivariable analysis, active disease (P < 0.001), obesity (P < 0.001), and CCI (P < 0.001) were significantly associated with a moderate or severe outcome. Univariable analyses in CD patients identified age (P < 0.001), obesity (P = 0.008), IMID (P < 0.001), and CCI (P < 0.001) as associated with moderate or severe outcomes, while multivariable analysis indicated age (P = 0.01), obesity (P = 0.02), and IMID (P = 0.01).

Regression analyses were repeated looking specifically at the risk of COVID-19-related pneumonia (Table 2). For UC patients, univariable analyses identified age ≥60 years, active disease of any severity, obesity, hypertension and CCI ≥2 as associated with the risk of pneumonia, and multivariable analyses found that active disease (OR = 1.88), obesity (OR = 23.76), and CCI ≥2 were associated with the risk of pneumonia. For CD patients, age ≥60 years, obesity, concomitant IMID, and a CCI ≥2 were significantly associated with pneumonia in the univariable analysis, whereas in the multivariable analysis only obesity (OR = 6.54) and concomitant IMID (OR = 3.52) were associated with the risk of pneumonia.

Regarding hospitalisation (Table 2), in UC patients, age ≥60 years, active disease of any severity, obesity, hypertension and CCI ≥2 were found to be associated with risk in univariable analyses. In multivariable analyses adjusted for confounders, only active disease (OR = 1.92), obesity (OR = 22.8) and CCI ≥2 points (OR = 3.97) were found to be associated with the risk of hospitalisation. In CD patients, age ≥60 years, obesity, a concomitant IMID and CCI ≥2 were significantly associated with hospitalisation at the univariable analysis; at the multivariable analysis adjusted for confounders, only concomitant IMID (OR = 2.26) was found to be associated with the risk of hospitalisation.

A final analysis investigated the risk of severe COVID-19 outcomes (need for ventilatory support or death; Table 2). In UC patients, age ≥60 years, male sex, active disease of any severity, obesity, hypertension and CCI ≥2 were found to be associated with the risk of severe COVID-19; at the multivariable analyses adjusted for confounders, age ≥60 years (OR = 2.57), male sex (OR = 2.85), active disease (OR = 2.03), obesity (OR = 20.34), and CCI ≥2 (OR = 1.53) were associated with the risk of severe COVID-19. In CD patients, age ≥60 years, obesity and CCI ≥2 were significantly associated with severe COVID-19 at univariable analyses; at multivariable analyses adjusted for confounders, only obesity (OR = 12.07) and CCI ≥2 (OR = 1.77) were associated with the risk of severe COVID-19.

Impact of Medications on COVID-19 Outcomes

These results are shown in Table 3.

In the UC population, at univariable analysis, the use of anti-TNF agents was associated with significantly lower risks of COVID-19, pneumonia, and severe COVID-19. Similarly, in CD patients, the use of anti-TNF agents was associated with significantly lower risks of COVID-19, pneumonia, hospitalisation, and severe COVID-19. In contrast, in CD patients, the use of salicylates was associated with higher risks of COVID-19 symptoms, pneumonia, hospitalisation and severe outcomes. The other medications did not have any impact on COVID-19 outcomes.

After adjusting for confounding factors, at multivariable analyses, the use of anti-TNF agents remained significantly associated with a lower risk of pneumonia in UC patients (OR = 0.44; 95% CI, 0.22–0.86) and with lower risks of hospitalisation (OR = 0.46; 95% CI, 0.23–0.92) and severe COVID-19 (OR = 0.31; 95% CI, 0.11–0.88) in CD patients. Salicylates were not confirmed to be associated with the risk of adverse outcomes in CD patients.

Risk Assessment for Moderate-severe COVID-19 in IBD Patients

Based on the multivariable analyses for moderate-severe COVID-19 outcomes, we built two risk indices that sum the contributions of significant variables. For UC patients, the index was calculated with the formula (where yes = 1 and no = 0):

ROC curve analysis (Figure 1A) identified a cut-off ≥0.90 for increased risk of any adverse outcome of SARS-CoV-2 (area under the curve [AUC] = 0.79; 95% CI, 0.75–0.83), with 0.71 sensitivity (95% CI, 0.61–0.80), 0.74 specificity (95% CI, 0.69–0.79), a positive likelihood ratio (+LR) of 2.79, and a negative likelihood ratio (−LR) of 0.39. The same cut-off was found to be the best predictor for the risk of pneumonia (AUC = 0.79; 95% CI, 0.75–0.83), hospitalisation (AUC = 0.81; 95% CI, 0.77–0.85), and severe COVID-19 (AUC = 0.80; 95% CI, 0.76–0.84).

Figure 1.

ROC curve analysis of the IG-IBD COVID-19 index for the risk of moderate-to-severe COVID-19. A, UC patients. B, CD patients

For CD patients, the index was calculated with the formula (where yes = 1 and no = 0):

ROC curve analysis for CD patients identified a cut-off ≥2.20 for increased risk of any adverse outcome of SARS-CoV-2 (AUC = 0.76; 95% CI, 0.72–0.80), with 0.71 sensitivity (95% CI, 0.58–0.82), 0.69 specificity (95% CI, 0.64–0.73), +LR = 2.31, and –LR = 0.41 (Figure 1B). A score of ≥2.50 was the best predictor for the risk of pneumonia (AUC = 0.76; 95% CI, 0.72–0.80) and hospitalisation (AUC = 0.77; 95% CI, 0.73–0.80), whereas a score ≥2.44 was the best predictor for severe COVID-19 (AUC = 0.78; 95% CI, 0.74–0.81).

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