key: cord-0734600-ts48lmfo
authors: Kumar, Jogender; Meena, Jitendra
title: Demystifying BCG Vaccine and COVID-19 Relationship
date: 2020-04-30
journal: Indian Pediatr
DOI: 10.1007/s13312-020-1872-0
sha: 8951296c19fdb6c794c207234eb8b11e9938079f
doc_id: 734600
cord_uid: ts48lmfo

nan

Efforts for developing vaccines for novel coronavirus disease (COVID-19) are ongoing, but it is unlikely to be available in the immediate future [1] . In the absence of specific therapy, the researchers are exploring other potential preventive and therapeutic options. Recently, there has been a buzz about the protective effect of Bacille Calmette-Guérin (BCG) vaccine in COVID-19. Based on epidemiological correlations, many unpublished preprints hypothesized that the BCG vaccine may offer protection against COVID-19. It gained so much popularity that within 20 days three randomized controlled trials (RCTs) got registered, and many more are in the pipeline [2] . To make an informed decision, we must understand the mechanism of action of BCG, and appraise the robustness of the evidence.

The basis of the possible use of the BCG vaccine against COVID-19 lies in its non-specific effects (NSEs) over the immune system [3] . The NSEs of BCG are mainly mediated by potentiating innate immune response through epigenetic mechanisms.These epigenetic changes within the innate cells act as de novo enhancers to boost the immune response against a secondary challenge [3-5]. This enhancing response is popularly known as 'trained immunity' and is very characteristic of BCG. This trained immunity also offers protection against a variety of pathogens (Salmonella, Shigella, malaria, respiratory viruses, etc.) other than Mycobacterium tuberculosis, and forms the basis of its use in bladder cancer, melanoma etc. However, this non-specific effect is mostly short-lived and wanes soon after the primary BCG stimulus is cleared from the body. By virtue of the NSEs, BCG vaccine has shown to decrease all-cause mortality in children. Though a few observational studies suggest that the NSEs may last till adulthood, but the overall evidence is still inadequate and is of low quality [3, 6, 7] . New cases needing evaluation are also not able to reach some of the major hospitals,which have temporarily closed OPD registrations to focus on COVID patients. There is also risk of new patients being asymptomatic carriers, but the current guidelines do not allow COVID testing for all new hospital admissions even if they are immune-compromised cancer patients.

The pandemic poses a risk of coronavirus infection for all individuals including children. Children with cancer are assumed to be more susceptible to the coronavirus due to inherent suppressed immune function associated with cancer treatment and repeated attendance in health care facilities [2] .

Treatment delay: Children with cancer, already on treatment, were advised to stay indoors and practice social distancing resulting in delay in their treatment. The nationwide lockdown further delayed the treatment due to restricted mobility even within the city or travel from outstation. The bed strength available for in-house admission has also reduced due to diversion to COVID-19 wards, leading to delayed/deferred intensive chemo-

The global pandemic of the novel coronavirus disease (COVID-19) has had a significant impact on adult and pediatric patients with many acute and chronic diseases including cancer. The purpose of this correspondence is to project the challenges faced by both, the children undergoing treatment and the treating pediatric oncologist [1] .

Providing medical care to children with cancer during this pandemic is challenging given the risks of death from cancer versus death or serious complications in the immunocompromised hosts [2, 3] . Hospitals are delaying chemotherapy, radiotherapy and surgery after being overwhelmed by COVID-19 infection. Patients with cancer also fear coming to hospital fearing the risk of infection. There are also limited supplies of personal protective equipment (PPE) for doctors and other personnel, limited beds and ICU facility, limited blood bank facilities and also strained diagnostic facilities. Limited data, though from adults, also suggests that cancer patients with COVID will fare worse [4]. In a study from China, there was a higher risk of severe events in COVID-19 patients with cancer compared with those without cancer. Theoretically, immune therapy can result in cytokine release and worsen the viral injury, which is also believed to be due to a cytokine storm, but this is a theoretical consideration and not proven due to very limited data. Some general guidelines have been provided for children with cancer [5], which include, in addition to

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