A case report overlapped vaccine and COVID-19 in disseminated atherosclerosis.

Coronavirus disease 2019 (COVID-19) has become a part of our lives now and we have no more effective way of coping than a vaccine. COVID-19 is a disease that causes severe thrombosis outside the respiratory tract. Vaccines also protect us in this respect, but in some rare cases, thrombosis has been found to develop after vaccination (much less frequently than COVID-19). What was interesting in our case was that it showed how a disaster could happen under three factors that predispose to thrombosis. A 65-year-old female patient with disseminated atherosclerosis was admitted to the intensive care unit with complaints of dyspnea and dysphasia. In the evening of the day, the patient had the vaccination 2 weeks ago, she had active COVID-19. On examination, lower extremity pulses could not be detected. The patient's imaging and blood tests were performed. Multiple complications such as embolic stroke, venous and arterial thrombosis, pulmonary embolism, and pericarditis were observed in the patient. This case may give consideration to anticoagulant therapy studies. We give effective anticoagulant therapy in the presence of COVID-19 in patients at risk of thrombosis. Can anticoagulant therapy be considered after vaccination in patients at risk of thrombosis such as disseminated atherosclerosis?

Oral Polio Vaccine to Mitigate the Risk of Illness and Mortality During the Coronavirus Disease 2019 Pandemic: A Cluster-Randomized Trial in Guinea-Bissau.

Background: Oral polio vaccine (OPV) may improve resistance to non-polio-infections. We tested whether OPV reduced the risk of illness and mortality before coronavirus disease 2019 (COVID-19) vaccines were available. Methods: During the early COVID-19 pandemic, houses in urban Guinea-Bissau were randomized 1:1 to intervention or control. Residents aged 50+ years were invited to participate. Participants received bivalent OPV (single dose) or nothing. Rates of mortality, admissions, and consultation for infections (primary composite outcome) during 6 months of follow-up were compared in Cox proportional hazards models adjusted for age and residential area. Secondary outcomes included mortality, admissions, consultations, and symptoms of infection. Results: We followed 3726 participants (OPV, 1580; control, 2146) and registered 66 deaths, 97 admissions, and 298 consultations for infections. OPV did not reduce the risk of the composite outcome overall (hazard ratio [HR] = 0.97; 95% confidence interval [CI], .79-1.18). OPV reduced the risk in males (HR = 0.71; 95% CI, .51-.98) but not in females (HR = 1.18; 95% CI, .91-1.52) (P for same effect = .02). OPV also reduced the risk in Bacillus Calmette-Guérin scar-positive (HR = 0.70; 95% CI, .49-.99) but not in scar-negative participants (HR = 1.13; 95% CI, .89-1.45) (P = .03). OPV had no overall significant effect on mortality (HR = 0.96; 95% CI, .59-1.55), admissions (HR = 0.76; 95% CI, .49-1.17) or recorded consultations (HR = 0.99; 95% CI, .79-1.25), but the OPV group reported more episodes with symptoms of infection (6050 episodes; HR = 1.10 [95% CI, 1.03-1.17]). Conclusions: In line with previous studies, OPV had beneficial nonspecific effects in males.

Trained immunity-related vaccines: innate immune memory and heterologous protection against infections.

The innate immune system is able to build memory-like features in response to certain infections or vaccines, resulting in enhanced responsiveness upon (re)challenge with the same or an unrelated pathogen, a phenomenon termed 'trained immunity'. Compared with antigen-dependent adaptive immune responses triggered by classical vaccines against specific pathogens, trained immunity-related vaccines induce enhanced innate immune responses against unrelated pathogens and provide 'heterologous protection'. Here, we discuss the heterologous effects of vaccines against infections and detail the latest insights into the cellular and molecular mechanisms mediating trained immunity. Additionally, novel vaccine strategies are suggested for fighting new pandemics in the future by taking advantage of the heterologous memory features of trained immunity.

Anticipated reduction in COVID-19 mortality due to population-wide BCG vaccination: evidence from Germany.

Bacillus Calmette-Guérin (BCG) vaccine is known to have "bystander benefits" in protecting against heterologous infections; interim analysis of the "ACTIVATE" trial shows protection against respiratory infections in the elderly population. Epidemiologic studies suggest a potential benefit of BCG vaccination on COVID-19 outcomes. Differential past BCG vaccination policies between the former East and West German states provides a unique natural experiment to assess the potential effect of prior BCG vaccination on COVID-19. We estimated a 5% heterologous vaccine efficacy in the highly vaccinated former East Germany using the COVID-19 International Modeling (CoMo) Consortium model. A comparable BCG vaccination campaign undertaken prior to the pandemic in former West Germany, instituted along with known country-wide transmission reduction measures, is associated with a 37% decrease in projected mortality by mid-summer, 2020. These findings support a combined heterologous vaccine and non-pharmaceutical interventions (HVI+NPI) approach to mitigate the SARS-CoV-2 pandemic until SARS-CoV-2 specific vaccines are widely distributed.

Using BCG vaccine to enhance non-specific protection of health care workers during the COVID-19 pandemic: A structured summary of a study protocol for a randomised controlled trial in Denmark.

OBJECTIVES: The Bacille Calmette-Guérin (BCG) vaccine against tuberculosis is associated with non- specific protective effects against other infections, and significant reductions in all-cause morbidity and mortality have been reported. We aim to test whether BCG vaccination may reduce susceptibility to and/or the severity of COVID-19 and other infectious diseases in health care workers (HCW) and thus prevent work absenteeism.The primary objective is to reduce absenteeism due to illness among HCW during the COVID-19 pandemic. The secondary objectives are to reduce the number of HCW that are infected with SARS-CoV-2, and to reduce the number of hospital admissions among HCW during the COVID-19 pandemic. HYPOTHESIS: BCG vaccination of HCW will reduce absenteeism by 20% over a period of 6 months. TRIAL DESIGN: Placebo-controlled, single-blinded, randomised controlled trial, recruiting study participants at several geographic locations. The BCG vaccine is used in this study on a different indication than the one it has been approved for by the Danish Medicines Agency, therefore this is classified as a phase III study. PARTICIPANTS: The trial will recruit 1,500 HCW at Danish hospitals.To be eligible for participation, a subject must meet the following criteria: Adult (≥18 years); Hospital personnel working at a participating hospital for more than 22 hours per week.A potential subject who meets any of the following criteria will be excluded from participation in this study: Known allergy to components of the BCG vaccine or serious adverse events to prior BCG administration Known prior active or latent infection with Mycobacterium tuberculosis (M. tuberculosis) or other mycobacterial species Previous confirmed COVID-19 Fever (>38 C) within the past 24 hours Suspicion of active viral or bacterial infection Pregnancy Breastfeeding Vaccination with other live attenuated vaccine within the last 4 weeks Severely immunocompromised subjects. This exclusion category comprises: a) subjects with known infection by the human immunodeficiency virus (HIV-1) b) subjects with solid organ transplantation c) subjects with bone marrow transplantation d) subjects under chemotherapy e) subjects with primary immunodeficiency f) subjects under treatment with any anti-cytokine therapy within the last year g) subjects under treatment with oral or intravenous steroids defined as daily doses of 10 mg prednisone or equivalent for longer than 3 months h) Active solid or non-solid malignancy or lymphoma within the prior two years Direct involvement in the design or the execution of the BCG-DENMARK-COVID trial Intervention and comparator: Participants will be randomised to BCG vaccine (BCG-Denmark, AJ Vaccines, Copenhagen, Denmark) or placebo (saline). An adult dose of 0.1 ml of resuspended BCG vaccine (intervention) or 0.1 ml of sterile 0.9% NaCl solution (control) is administered intradermally in the upper deltoid area of the right arm. All participants will receive one injection at inclusion, and no further treatment of study participants will take place. MAIN OUTCOMES: Main study endpoint: Days of unplanned absenteeism due to illness within 180 days of randomisation.Secondary study endpoints: The cumulative incidence of documented COVID-19 and the cumulative incidence of hospital admission for any reason within 180 days of randomisation.Randomisation: Randomisation will be done centrally using the REDCap tool with stratification by hospital, sex and age groups (+/- 45 years of age) in random blocks of 4 and 6. The allocation ratio is 1:1.Blinding (masking): Participants will be blinded to treatment. The participant will be asked to leave the room while the allocated treatment is prepared. Once ready for injection, vaccine and placebo will look similar, and the participant will not be able to tell the difference.The physicians administering the treatment are not blinded.Numbers to be randomised (sample size): Sample size: N=1,500. The 1,500 participants will be randomised 1:1 to BCG or placebo with 750 participants in each group.Trial Status: Current protocol version 5.1, from July 6, 2020.Recruitment of study participants started on May 18, 2020 and we anticipate having finished recruiting by the end of December 2020. TRIAL REGISTRATION: The trial was registered with EudraCT on April 16, 2020, EudraCT number: 2020-001888-90, and with ClinicalTrials.gov on May 1, 2020, registration number NCT04373291.Full protocol: The full protocol is attached as an additional file, accessible from the Trialswebsite (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.