Evaluating the Protective Effect of Intravesical Bacillus Calmette-Guerin against SARS-CoV-2 in Non-Muscle Invasive Bladder Cancer Patients: A Multicenter Observational Trial

Abstract

We aim to evaluate the potential protective role of intravesical Bacillus Calmette-Guerin (BCG) against SARS-CoV-2 in patients with non-muscle invasive bladder cancer (NMIBC). Patients treated with intravesical adjuvant therapy for NMIBC between January 2018 and December 2019 at two Italian referral centers were divided into two groups based on the received intravesical treatment regimen (BCG vs. chemotherapy). The study’s primary endpoint was evaluating SARS-CoV-2 disease incidence and severity among patients treated with intravesical BCG compared to the control group. The study’s secondary endpoint was the evaluation of SARS-CoV-2 infection (estimated with serology testing) in the study groups. Overall, 340 patients treated with BCG and 166 treated with intravesical chemotherapy were included in the study. Among patients treated with BCG, 165 (49%) experienced BCG-related adverse events, and serious adverse events occurred in 33 (10%) patients. Receiving BCG or experiencing systemic BCG-related adverse events were not associated with symptomatic proven SARS-CoV-2 infection (p = 0.9) nor with a positive serology test (p = 0.5). The main limitations are related to the retrospective nature of the study. In this multicenter observational trial, a protective role of intravesical BCG against SARS-CoV-2 could not be demonstrated. These results may be used for decision-making regarding ongoing and future trials.

Intravesical BCG in bladder cancer induces innate immune responses against SARS-CoV-2

“…No differences in the incidence of COVID-19 infections in BCG-treated NMIBC patients could be shown. However, these findings must be interpreted with caution because they did not examine causal and mechanistic associations between intravesical BCG application and immunity against SARS-CoV-2 ( 5 , 38 – 40 ). With regard to severity of the disease, we believe that BCG-induced TI may indeed help prevent detrimental hyperinflammation associated with viremia.…”

“…This prompted us to test whether intravesical BCG might also induce TI-like innate immunity against SARS-CoV-2 in NMIBC. Several observational studies have already attempted to show a possible link between intravesical BCG instillations and COVID-19 infections ( 5 , 38 – 40 ). No differences in the incidence of COVID-19 infections in BCG-treated NMIBC patients could be shown.…”

No Association Between BCG Instillations and COVID-19 Incidence in a Dutch Non-Muscle Invasive Bladder Cancer Cohort

“…COVID-19 data were retrieved via two telephone interviews after the first and second COVID-19 wave in Italy and SARS-CoV-2 infection rates were optionally determined via serology tests. Results indicated no association between BCG instillations and a reduced COVID-19 and SARS-CoV-2 infection rate [ 19 ].…”