[Disseminated infection caused by the bacillus Calmette-Guérin vaccine and SARS-CoV-2 coinfection in a patient with IL-12 receptor ß1 subunit deficiency]. / Infección diseminada por vacuna con bacilo de Calmette-Guérin y coinfección por SARS-CoV-2 en paciente con deficiencia de la subunidad ß1 del receptor de IL-12.

BACKGROUND: Inborn errors of immunity manifest with a greater susceptibility to infections, autoimmunity, autoinflammatory diseases, allergies, or malignancies. One of these is the mendelian susceptibility to mycobacterial disease. The most frequent etiology is the complete autosomal recessive deficiency of the ß1 subunit of the interleukin 12 receptor. CASE REPORT: A female patient who, by the age of six months, started with a nodular lesion in the right shoulder and ipsilateral axillary adenitis after the bacillus Calmette-Guérin vaccine was applied. Later, she developed a cutaneous fistula in the anterior thorax, the inframammary region, and chronic recidivant suppurative lymphadenitis. A disseminated infection caused by Mycobacterium bovis was diagnosed, therefore, individualized pharmacological treatment was required due to failure with the primary treatment. The patient was diagnosed with deficiency in the ß1 subunit of the interleukin 12 receptor at age six. During her last hospitalization, she presented fever, cough, and tachypnea, and SARS-CoV-2 was detected by quantitative polymerase chain reaction. The patient has had a favorable evolution. CONCLUSION: In patients with disseminated infections caused by bacillus Calmette-Guérin vaccination or by environmental mycobacteria, there should be suspicion of an inborn error of immunity and the patient should be referred to a third level hospital for an early immunological assessment.

Antecedentes: Los errores innatos de la inmunidad se manifiestan con una mayor susceptibilidad a infecciones, autoinmunidad, enfermedades autoinflamatorias, alergia o malignidad. Uno de estos es la susceptibilidad mendeliana a infecciones micobacterianas. La etiología más frecuente es la deficiencia completa autosómica recesiva de la subunidad ß1 del receptor de interleucina 12. Caso clínico: Paciente que comenzó a los seis meses de edad con una lesión nodular en hombro derecho y adenitis axilar ipsolateral posterior a la vacuna con bacilo de Calmette-Guérin. Posteriormente desarrolló una fistula cutánea en tórax anterior, región inframamaria y linfadenitis supurativa crónica recidivante. Se diagnosticó infección diseminada por Mycobacterium bovis, por lo que requirió tratamiento farmacológico individualizado debido al fracaso con el tratamiento primario. La paciente fue diagnosticada con deficiencia de la subunidad ß1 del receptor de interleucina 12 a los seis años. Durante su última hospitalización presentó fiebre, tos y taquipnea, detectándose SARS-CoV-2 por reacción en cadena de la polimerasa cuantitativa. La paciente evolucionó favorablemente. Conclusión: En los pacientes con infecciones diseminadas por la vacuna con bacilo de Calmette-Guérin o micobacterias ambientales, debe sospecharse un error innato de la inmunidad y derivarlos a tercer nivel de atención para la evaluación inmunológica temprana.

Previous BCG vaccination is associated with less severe clinical progression of COVID-19.

BACKGROUND: BCG vaccination, originally used to prevent tuberculosis, is known to "train" the immune system to improve defence against viral respiratory infections. We investigated whether a previous BCG vaccination is associated with less severe clinical progression of COVID-19 METHODS: A case-control study comparing the proportion with a BCG vaccine scar (indicating previous vaccination) in cases and controls presenting with COVID-19 to health units in Brazil. Cases were subjects with severe COVID-19 (O2 saturation < 90%, severe respiratory effort, severe pneumonia, severe acute respiratory syndrome, sepsis, and septic shock). Controls had COVID-19 not meeting the definition of "severe" above. Unconditional regression was used to estimate vaccine protection against clinical progression to severe disease, with strict control for age, comorbidity, sex, educational level, race/colour, and municipality. Internal matching and conditional regression were used for sensitivity analysis. RESULTS: BCG was associated with high protection against COVID-19 clinical progression, over 87% (95% CI 74-93%) in subjects aged 60 or less and 35% (95% CI - 44-71%) in older subjects. CONCLUSIONS: This protection may be relevant for public health in settings where COVID-19 vaccine coverage is still low and may have implications for research to identify vaccine candidates for COVID-19 that are broadly protective against mortality from future variants. Further research into the immunomodulatory effects of BCG may inform COVID-19 therapeutic research.

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

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.

BCG Vaccination of Health Care Workers Does Not Reduce SARS-CoV-2 Infections nor Infection Severity or Duration: a Randomized Placebo-Controlled Trial.

Bacillus Calmette-Guerin (BCG) vaccination has been hypothesized to reduce severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, severity, and/or duration via trained immunity induction. Health care workers (HCWs) in nine Dutch hospitals were randomized to BCG or placebo vaccination (1:1) in March and April 2020 and followed for 1 year. They reported daily symptoms, SARS-CoV-2 test results, and health care-seeking behavior via a smartphone application, and they donated blood for SARS-CoV-2 serology at two time points. A total of 1,511 HCWs were randomized and 1,309 analyzed (665 BCG and 644 placebo). Of the 298 infections detected during the trial, 74 were detected by serology only. The SARS-CoV-2 incidence rates were 0.25 and 0.26 per person-year in the BCG and placebo groups, respectively (incidence rate ratio, 0.95; 95% confidence interval, 0.76 to 1.21; P = 0.732). Only three participants required hospitalization for SARS-CoV-2. The proportions of participants with asymptomatic, mild, or moderate infections and the mean infection durations did not differ between randomization groups. In addition, unadjusted and adjusted logistic regression and Cox proportional hazards models showed no differences between BCG and placebo vaccination for any of these outcomes. The percentage of participants with seroconversion (7.8% versus 2.8%; P = 0.006) and mean SARS-CoV-2 anti-S1 antibody concentration (13.1 versus 4.3 IU/mL; P = 0.023) were higher in the BCG than placebo group at 3 months but not at 6 or 12 months postvaccination. BCG vaccination of HCWs did not reduce SARS-CoV-2 infections nor infection duration or severity (ranging from asymptomatic to moderate). In the first 3 months after vaccination, BCG vaccination may enhance SARS-CoV-2 antibody production during SARS-CoV-2 infection. IMPORTANCE While several BCG trials in adults were conducted during the 2019 coronavirus disease epidemic, our data set is the most comprehensive to date, because we included serologically confirmed infections in addition to self-reported positive SARS-CoV-2 test results. We also collected data on symptoms for every day during the 1-year follow-up period, which enabled us to characterize infections in detail. We found that BCG vaccination did not reduce SARS-CoV-2 infections nor infection duration or severity but may have enhanced SARS-CoV-2 antibody production during SARS-CoV-2 infection in the first 3 months after vaccination. These results are in agreement with other BCG trials that reported negative results (but did not use serological endpoints), except for two trials in Greece and India that reported positive results but had few endpoints and included endpoints that were not laboratory confirmed. The enhanced antibody production is in agreement with prior mechanistic studies but did not translate into protection from SARS-CoV-2 infection.

Gender, Bladder Cancer Healthcare and Burden of COVID-19.

Bladder cancer as one of the main comorbid diseases might be more susceptible to develop COVID-19 infection with a higher mortality risk during the COVID-19 pandemic. The European Association of Urology (EAU) recommended a comprehensive panel for bladder cancer diagnosis and treatment during this global health problem. The urgent need for treatments of COVID-19 during the pandemic has persuaded researchers to evaluate the different medications, which may lead to drug shortages. Therefore, in this review paper, we have focused on the least recommendations of EAU about bladder cancer during of COVID-19 pandemic to provide a comprehensive panel for high-risk patients.

Bacillus Calmette-Guérin vaccine for prevention of COVID-19 and other respiratory tract infections in older adults with comorbidities: a randomized controlled trial.

OBJECTIVES: To test whether Bacillus Calmette-Guérin (BCG) vaccination would reduce the incidence of COVID-19 and other respiratory tract infections (RTIs) in older adults with one or more comorbidities. METHODS: Community-dwelling adults aged 60 years or older with one or more underlying comorbidities and no contraindications to BCG vaccination were randomized 1:1 to BCG or placebo vaccination and followed for 6 months. The primary endpoint was a self-reported, test-confirmed COVID-19 incidence. Secondary endpoints included COVID-19 hospital admissions and clinically relevant RTIs (i.e. RTIs including but not limited to COVID-19 requiring medical intervention). COVID-19 and clinically relevant RTI episodes were adjudicated. Incidences were compared using Fine-Gray regression, accounting for competing events. RESULTS: A total of 6112 participants with a median age of 69 years (interquartile range, 65-74) and median of 2 (interquartile range, 1-3) comorbidities were randomized to BCG (n = 3058) or placebo (n = 3054) vaccination. COVID-19 infections were reported by 129 BCG recipients compared to 115 placebo recipients [hazard ratio (HR), 1.12; 95% CI, 0.87-1.44]. COVID-19-related hospitalization occurred in 18 BCG and 21 placebo recipients (HR, 0.86; 95% CI, 0.46-1.61). During the study period, 13 BCG recipients died compared with 18 placebo recipients (HR, 0.71; 95% CI, 0.35-1.43), of which 11 deaths (35%) were COVID-19-related: six in the placebo group and five in the BCG group. Clinically relevant RTI was reported by 66 BCG and 72 placebo recipients (HR, 0.92; 95% CI, 0.66-1.28). DISCUSSION: BCG vaccination does not protect older adults with comorbidities against COVID-19, COVID-19 hospitalization, or clinically relevant RTIs.

A case series of bacillus Calmette-Guérin scar reactivation after administration of both mRNA and viral vector COVID-19 vaccines.

AIM: Reactivation of the scar resulting from intradermal injection of bacillus Calmette-Guérin (BCG) is a common specific reaction in Kawasaki's disease. It has also sporadically been associated with viral infections, multisystem inflammatory syndrome in children, influenza vaccination and mRNA COVID-19 vaccination. In this case series, characteristics of BCG scar reactivation after different COVID-19 vaccinations are presented and possible mechanisms are discussed. METHODS: Data were collected from the spontaneous reporting system of the Netherlands Pharmacovigilance Centre Lareb. Descriptives were made for the case reports in which a BCG scar reactivation was detected. RESULTS: Since the start of the COVID-19 vaccination campaign in January 2021, the Netherlands Pharmacovigilance Centre Lareb has received 22 case reports of BCG reactivation after vaccination with a COVID-19 vaccine. In 20 case reports, it concerned mRNA COVID-19 vaccines Moderna (14) and Pfizer (6). In two case reports, the viral vector COVID-19 vaccine AstraZeneca was administered. Erythema and pain were the most frequently reported symptoms and the size of the inflammation was between 1.5 and 5 cm. BCG scar reactivation occurred with a median time to onset of 2 days after the second or booster COVID-19 vaccination, whereas the median time to onset was 7 days after the first COVID-19 vaccination. None of the BCG scar reactivations were treated. CONCLUSIONS: The exact mechanism of the occurrence of BCG scar reactivation remains unknown, but involvement of heat shock protein 65 is suggested. BCG scar reactivation is a nonserious, self-limiting reaction that can occur after vaccination with both mRNA and viral vector COVID-19 vaccines.

Intravesical Bacillus Calmette-Guerin Reduces Lung Involvement in COVID-19 in Patients with Bladder Cancer

Objective: To compare the coronavirus disease-19 (COVID-19) infection, morbidity, and mortality rates of patients who did not receive and received Bacillus Calmette-Guerin (BCG) treatment because of bladder cancer during the COVID-19 pandemic. Material(s) and Method(s): Patients who were followed up for bladder cancer between March 2019 and March 2021 were evaluated. Patients who underwent intravesical BCG instillation (induction or maintenance) and those who did not receive BCG were divided into two groups. The characteris-tics (age, gender, etc.) and COVID-19-related findings (symptoms, comorbidities, lung involvement, and need for patient admission) of the patients were recorded and compared between the groups. Result(s): The present study included 215 patients (85 in Group 1;and 130 in Group 2). Demographic data were similar in both groups (body mass index, age, gender, comorbidities, etc.). COVID-19 incidence was similar in both groups (18 patients in Group 1;21 patients in Group 2;p: 0.350). The number of patients with COVID-19 treated in the hospital was more in Group 1 than in Group 2 (14 patients in Group 1, 7 patients in Group 2, p: 0.006). However, lung involvement and dyspnea were significantly lower in the intravesical BCG Group (p: 0.015;and p: 0.001, respectively). Conclusion(s): Intravesical BCG instillation reduces the morbidity associated with COVID-19. Therefore, the installation schemes should not be delayed due to the pandemic. The current study im-parts preliminary information about the importance of BCG vaccination studies against COVID-19. Copyright © 2022 by Turkish Society of Medical Oncology.

Intravesical BCG immunotherapy for Non-Muscle Invasive Bladder Cancer during COVID-19 pandemic: Mutual impact and implications

Urinary bladder cancer (BC) is the tenth most common malignancy worldwide with 90% of cases diagnosed at >= 55 years of age. An early-stage tumor that invades up to the lamina propria, but not into smooth muscle tissue accounts for 75% of newly diagnosed BCs and is termed as Non muscle invasive bladder cancer (NMIBC). The most effective treatment for NMIBC since many decades is its removal by transurethral resection followed by intravesical immunotherapy with Mycobacterium bovis BCG. The COVID-19 pandemic situation has negatively impacted disease management for many life-threatening diseases, including BC. In order to adapt the clinical practice during pandemic, certain adjustments have been recommended in the BCG therapy regimen of NMIBC. Interestingly, there are certain reports of possible protective role of BCG against COVID-19 in BCG immunotherapy recipients, while others warn of higher cumulative incidence of COVID-19 infection. The study presents an extensive literature review and critical analysis of mutual interplay of BCG immunotherapy for NMIBC and COVID-19 incidence and associated risk. It will not only help us draw conclusions regarding bilateral impact of NMIBC BCG immunotherapy and COVID-19 but also serve as a basis of pragmatic improvisation of guidelines for BCG therapy during COVID-19 crisis.

Current GMP standards for the production of vaccines and antibodies: An overview.

The manufacture of pharmaceutical products made under good manufacturing practices (GMP) must comply with the guidelines of national regulatory bodies based on international or regional compendia. The existence of this type of regulation allows pharmaceutical laboratories to count on the standardization of high-quality production processes, obtaining a safe product for human use, with a positive impact on public health. In addition, the COVID-19 pandemic highlights the importance of having more and better-distributed manufacturing plants, emphasizing regions such as Latin America. This review shows the most important GMP standards in the world and, in particular, their relevance in the production of vaccines and antibodies.

BCG and SARS-CoV-2-What Have We Learned?

Despite controversy over the protective effect of the BCG (Bacille Calmette-Guérin) vaccine in preventing pulmonary tuberculosis (TB) in adults, it has been used worldwide since 1921. Although the first reports in the 1930s had noted a remarkable decrease in child mortality after BCG immunization, this could not be explained solely by a decrease in mortality from TB. These observations gave rise to the suggestion of nonspecific beneficial effects of BCG vaccination, beyond the desired protection against M. tuberculosis. The existence of an innate immunity-training mechanism based on epigenetic changes was demonstrated several years ago. The emergence of the pandemic caused by the severe acute respiratory syndrome coronavirus (SARS-CoV-2) in 2019 revived the debate about whether the BCG vaccine can affect the immune response against the virus or other unrelated pathogens. Due to the mortality of the coronavirus disease (COVID-19), it is important to verify each factor that may have a potential protective value against the severe course of COVID-19, complications, and death. This paper reviews the results of numerous retrospective studies and prospective trials which shed light on the potential of a century-old vaccine to mitigate the pandemic impact of the new virus. It should be noted, however, that although there are numerous studies intending to verify the hypothesis that the BCG vaccine may have a beneficial effect on COVID-19, there is no definitive evidence on the efficacy of the BCG vaccine against SARS-CoV-2.

Multiple BCG vaccinations for the prevention of COVID-19 and other infectious diseases in type 1 diabetes.

There is a need for safe and effective platform vaccines to protect against coronavirus disease 2019 (COVID-19) and other infectious diseases. In this randomized, double-blinded, placebo-controlled phase 2/3 trial, we evaluate the safety and efficacy of a multi-dose Bacillus Calmette-Guérin (BCG) vaccine for the prevention of COVID-19 and other infectious disease in a COVID-19-unvaccinated, at-risk-community-based cohort. The at-risk population is made of up of adults with type 1 diabetes. We enrolled 144 subjects and randomized 96 to BCG and 48 to placebo. There were no dropouts over the 15-month trial. A cumulative incidence of 12.5% of placebo-treated and 1% of BCG-treated participants meets criteria for confirmed COVID-19, yielding an efficacy of 92%. The BCG group also displayed fewer infectious disease symptoms and lesser severity and fewer infectious disease events per patient, including COVID-19. There were no BCG-related systemic adverse events. BCG's broad-based infection protection suggests that it may provide platform protection against new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants and other pathogens.

Higher BCG-induced trained immunity prevalence predicts protection from COVID-19: Implications for ongoing BCG trials.

Endeavors to identify potentially protective variables for COVID-19 impact on certain populations have remained a priority. Multiple attempts have been made to attribute the reduced COVID-19 impact on populations to their Bacillus-Calmette-Guérin (BCG) vaccination coverage ignoring the fact that the effect of childhood BCG vaccination wanes within 5 years while most of the COVID-19 cases and deaths have occurred in aged with comorbidities. Since the supposed protection being investigated could come from heterologous 'trained immunity' (TI) conferred by exposure to Mycobacterium spp. (i.e., environmental and BCG), it is argued that the estimates of the prevalence of TI in populations currently available as latent tuberculosis infection (LTBI) prevalence would be a better variable to evaluate such assertions. Indeed, when we analyze the European populations (24), and erstwhile East and West Germany populations completely disregarding their BCG vaccination coverage, the populations with higher TI prevalence consistently display reduced COVID-19 impact as compared to their lower TI prevalence neighbors. The TI estimates of the populations not the BCG coverage per se, negatively correlated with pandemic phase-matched COVID-19 incidences (r(24): -0.79 to -0.57; p-value < .004), mortality (r(24): -0.63 to -0.45; p-value < .03), and interim case fatality rates (i-CFR) data. To decisively arrive at dependable conclusions about the potential protective benefit gained from BCG vaccination in COVID-19, the ongoing or planned randomized controlled trials should consciously consider including measures of TI as: (a) all individuals immunized do not respond equally, (b) small study groups from higher background TI could fail to indicate any protective effect.

The Potential Roles of BCG Vaccine in the Prevention or Treatment of COVID-19.

Coronavirus disease 2019 (COVID-19), which broke out at the end of 2019, is a global pandemic and seriously threatens human health. Vaccination is the most effective way to prevent and control COVID-19. At present, more than 13 COVID-19 vaccines have been urgently authorized for use, but the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants has brought unprecedented challenges to the protective efficiency of these COVID-19 vaccines. In particular, the recent emergence of Delta and Omicron variants, which are rapidly spreading worldwide, may bring many challenges to the medical systems. Interestingly, previous studies have shown that the Bacillus Calmette-Guerin (BCG) vaccine used to prevent tuberculosis can induce non-specific trained immunity, protecting against infectious diseases caused by respiratory viruses. Therefore, there is a hypothesis that BCG plays an essential role in reducing the incidence, severity, hospitalization, and mortality of COVID-19 and enhancing the protection efficiency of the COVID-19 vaccine. To confirm this hypothesis, 56 clinical trials have been conducted globally to assess BCG's protective effectiveness against COVID-19 infection. Herein, this review discussed the trained immunity induced by BCG and its underlying mechanisms and summarised BCG's latest research progress in preventing COVID-19, especially the ongoing clinical trials. We hope this review will provide new strategies for fighting against COVID-19.

SARS-CoV-2 variants and COVID-19 vaccines: Current challenges and future strategies.

The ongoing COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global threat. Despite strict control measures implemented worldwide and immunization using novel vaccines, the pandemic continues to rage due to emergence of several variants of SARS-CoV-2 with increased transmission and immune escape. The rapid spread of variants of concern (VOC) in the recent past has created a massive challenge for the control of COVID-19 pandemic via the currently used vaccines. Vaccines that are safe and effective against the current and future variants of SARS-CoV-2 are essential in controlling the COVID-19 pandemic. Rapid production and massive rollout of next-generation vaccines against the variants are key steps to control the COVID-19 pandemic and to help us return to normality. Coordinated surveillance of SARS-CoV-2, rapid redesign of new vaccines and extensive vaccination are needed to counter the current SARS-CoV-2 variants and prevent the emergence of new variants. In this article, we review the latest information on the VOCs and variants of interest (VOIs) and present the information on the clinical trials that are underway on evaluating the effectiveness of COVID-19 vaccines on VOCs. We also discuss the current challenges posed by the VOCs in controlling the COVID-19 pandemic and future strategies to overcome the threat posed by the highly virulent and rapidly transmissible variants of SARS-CoV2.

The COVID-19 is a contagious respiratory disease caused by a virus known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that emerged in 2019. The COVID-19 has now spread to all part of the world and has become a global threat. Even after the strict control measures and immunization programs to prevent the disease, COVID-19 is still causing destruction due to appearance of new strains of SARS-CoV-2 that transmit faster and capable of escaping the immunity. The faster spread of the new strains of viruses that cause more severe disease is the biggest challenge to control the COVID-19 pandemic by using the presently available vaccines. To control the COVID-19 pandemic we urgently need safe and effective vaccines against the corona viral variants. This can be achieved by tracking the appearance of new viral types, design and rapid production and supply of new vaccines against the virus. This article presents the latest information on the new types of SARS-CoV-2, and on the status of vaccine trials and their effectiveness against these viruses. Similarly, the information on the challenges posed by the new viral strains in controlling the COVID-19 and future strategies to overcome the threat posed by corona viruses is also provided.

Epidemiological characteristics, clinical course, and laboratory investigation of pediatric COVID-19 patients in a tertiary care center in Saudi Arabia.

Background: Since the initial emergence of the novel SARS-CoV-2 coronavirus responsible for the 2019 coronavirus disease (COVID-19) pandemic, many studies have been exploring the nature and characteristics of this virus and its associated clinical manifestations. The present study aimed to describe the clinical presentation and outcomes of COVID-19 infections in pediatric patients. Methods: A retrospective review of findings associated with 143 pediatric patients (age <14 years) with a confirmed COVID-19 diagnosis who had undergone inpatient or outpatient treatment at King Faisal Specialist Hospital and Research Center in Riyadh, Saudi Arabia, between March 2020 and October 2020, was conducted. The analyzed data included patient demographic information, pre-existing medical conditions, symptoms, interventions, and outcomes. Results: The median age of this patient population was 7 years. Of these 143 patients, 67 (46.8%) had known pre-existing medical conditions including bronchial asthma (12.8%), chronic lung disease (CLD) (3%), congenital heart disease (CHD) (17%), primary immunodeficiencies (1.5%), malignancies (9.8%), and 7.5% were post-transplant patients. Thirty-seven patients (26%) were overweight or obese. Sixty-three of these patients (51%) were symptomatic, with the most common symptom being fever (55%). Ultimately, 45 patients (31%) required admission to the hospital, with a median duration of hospitalization of 9.6 days for admitted patients. There were no documented cases of infection-related mortality among this pediatric cohort, although 11 patients experienced post-infectious complications that primarily manifested as a loss of taste and smell. Conclusion: These findings suggest that pediatric COVID-19 patients tend to experience mild forms of the disease, without any significant differences in disease severity as a function of patient gender or immune status.

Severe Respiratory Failure Due to Pulmonary BCGosis in a Patient Treated for Superficial Bladder Cancer.

Intra-vesical instillations with bacillus Calmette-Guerin (BCG) are the established adjuvant therapy for superficial bladder cancer. Although generally safe and well tolerated, they may cause a range of different, local, and systemic complications. We present a patient treated with BCG instillations for three years, who was admitted to our hospital due to fever, hemoptysis, pleuritic chest pain and progressive dyspnea. Chest computed tomography (CT) showed massive bilateral ground glass opacities, partly consolidated, localized in the middle and lower parts of the lungs, bronchial walls thickening, and bilateral hilar lymphadenopathy. PCR tests for SARS-CoV-2 as well as sputum, blood, and urine for general bacteriology-were negative. Initial empiric antibiotic therapy was ineffective and respiratory failure progressed. After a few weeks, a culture of M. tuberculosis complex was obtained from the patient's specimens; the cultured strain was identified as Mycobacterium bovis BCG. Anti-tuberculous treatment with rifampin (RMP), isoniazid (INH) and ethambutol (EMB) was implemented together with systemic corticosteroids, resulting in the quick improvement of the patient's clinical condition. Due to hepatotoxicity and finally reported resistance of the BCG strain to INH, levofloxacin was used instead of INH with good tolerance. Follow-up CT scans showed partial resolution of the pulmonary infiltrates. BCG infection in the lungs must be taken into consideration in every patient treated with intra-vesical BCG instillations and symptoms of protracted infection.

Erythema and Induration of Bacillus Calmette-Guérin Scar Associated With Multisystem Inflammatory Syndrome in Children in Japan: A Case Report.

Multisystem Inflammatory Syndrome in Children (MIS-C) is a rare febrile disorder with multisystem organ involvement temporally associated with coronavirus 2019 infection (COVID-19) and frequently exhibits features mimicking Kawasaki disease (KD), another febrile disorder in children. The pathogenesis and the full clinical spectrum of MIS-C is poorly understood: It is still unclear whether MIS-C and KD are different syndromes or represent a common spectrum. The erythema and induration of Bacillus Calmette-Guérin (BCG) scar is one of the characteristic findings of KD, and is useful for the diagnosis in countries where BCG vaccination is mandated in infancy. Furthermore, such findings in BCG scar were also reported after SARS-CoV-2 vaccination, which may be related to molecular mimicry. However, there are no reports of changes at the BCG scar in MIS-C cases. Here, we report a case of MIS-C in a 3-year-old Hispanic boy in Japan, with erythema and induration at the BCG scar. The patient received BCG vaccination at 16 months of age in Japan. Four weeks before the onset, he had positive polymerase chain reaction (PCR) results for SARS-CoV-2 following household outbreak, although he was asymptomatic. He presented with fever and gastrointestinal symptoms, followed by the appearance of all six principal findings of complete KD. He exhibited congestive heart failure, following intravenous immunoglobulin (IVIG) therapy. He was diagnosed with MIS-C based on characteristic mucocutaneous and gastrointestinal symptoms, decreased cardiac function, and coagulopathy, in addition to laboratory data consistent with MIS-C. The BCG finding was present from the early stage of the disease. The patient was refractory to two doses of IVIGs, and the third IVIG plus prednisolone resulted in defervescence and improvement in heart failure. No coronary involvement was observed. This is the first case of erythema and induration at the BCG scar associated with MIS-C accompanied by KD features, which may give clinical and mechanistic insights in the understanding of the disease. Since the full spectrum of MIS-C is still evolving and both of them are syndromes with overlapped clinical features, further studies are warranted for deep phenotyping of MIS-C with KD features relative to KD in countries with mandatory BCG programs in infancy.

Tuberculosis and COVID-19: A combined global threat to human civilization.

A new era has begun with the discovery of SARS-CoV-2 in a seafood market in Wuhan, China. The SARS-CoV-2 outbreak has wreaked havoc on health systems and generated worldwide attention. The world's attention was diverted from the treatment of the leading chronic infectious illness, Mycobacterium tuberculosis. The similarities in the performance of the two infectious species had obvious repercussions. Administrative efforts to combat SARS-CoV-2 have weakened the tuberculosis control chain. As a result, progress against tuberculosis has slowed. Thus, the goal of this review is to examine the impact of SARS- CoV-2 on a chronic public health issue: tuberculosis.