Reactivation of BCG vaccination scars after vaccination with mRNA-Covid-vaccines: two case reports

Abstract Background From May 2020 to January 2021, we enrolled 1233 health care workers (HCW) from Danish Hospitals in a randomized trial evaluating whether Bacille Calmette-Guérin (BCG) provides protection against COVID-19. Participants were randomized 1:1 to BCG vs saline and followed for 6 months. From December 2020, Covid-19 vaccines were offered to the HCW. In most cases, BCG vaccination results in a characteristic scar. Reactivation of the BCG scar has been described in children during viral infections and following influenza vaccination, but is mostly associated to Kawasaki’s disease, a disease entity with pathogenesis likely similar to the child Covid-19 complication MIS-C: Multi-System Inflammatory Syndrome. Reactivation of scars after neonatal BCG vaccination has recently been described in four women after Covid-19 mRNA vaccination. Two of our trial participants experienced reactivation of their novel BCG scars after receiving mRNA Covid-19 vaccination 6 to 8 months post-BCG. Case presentations Two female HCW participants that had been randomly allocated to BCG in the BCG-DENMARK-COVID trial, spontaneously reported itching and secretion at the BCG scar site after having received mRNA Covid-19 vaccination (Moderna and Pfizer-BioNTech) 6 to 8 months following inclusion and BCG vaccination. One participant, who had a larger BCG skin reaction, noticed re-appearing symptoms after both the first and the second COVID-vaccine dose, while the other participant only noted symptoms after the second dose. Both had been BCG vaccinated during childhood, and no reactivation was noted in the older scars. No treatment was needed or provided. Conclusions The reactivation of the BCG scar after receiving mRNA vaccine might have been caused by cross-reactivity between BCG and SARS-CoV-2. In both cases, the symptoms were bothersome, but self-limiting and left no sequelae. The risk of reactivation at the scar site is thus not a reason to avoid vaccination with either vaccine.

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Explore the Possible Impact of BCG Vaccination Policy on the Morbidity, Mortality, and Recovery Rates due to COVID-19 Infection. (Preprint)

10.2196/preprints.22052 ◽

2020 ◽

Author(s):

Yue-Cune Chang

Keyword(s):

Odds Ratio ◽

Randomized Clinical Trials ◽

Vaccination Policy ◽

Bacille Calmette Guerin ◽

Recovery Rates ◽

Bcg Vaccination ◽

The World ◽

New Form ◽

The Relationship ◽

Disease Specific

BACKGROUND The Coronavirus Disease-19 (COVID-19) is the new form of an acute infectious respiratory disease and has quickly spread over most continents in the world. Recently, it has been shown that Bacille Calmette-Guerin (BCG) might protect against COVID-19. This study aims to investigate the possible correlation between BCG vaccination and morbidity/mortality/recovery rate associated with COVID-19 infection. OBJECTIVE Our findings confirm that the BCG vaccination might protect against COVID-19 virus infection. METHODS Data of COVID-19 confirmed cases, deaths, recoveries, and population were obtained from https://www.worldometers.info/coronavirus/ (Accessed on 12 June, 2020). To have meaningful comparisons among countries’ mortality and recovery rates, we only choose those countries with COVID-19 infected cases at least 200. The Poisson regression and logistic regression were used to explore the relationship between BCG vaccination and morbidity, mortality and recovery rates. RESULTS Among those 158 countries with at least 200 COVID-19 infected cases, there were 141 countries with BCG vaccination information available. The adjusted rates ratio of COVID-19 confirmed cases for Current BCG vaccination vs. non-Current BCG vaccination was 0.339 (with 95% CI= (0.338,0.340)). Moreover, the adjusted odds ratio (OR) of death and recovery after coronavirus infected for Current BCG vaccination vs. non-Current BCG vaccination were 0.258 (with 95% CI= (0.254,0.261)) and 2.151 (with 95% CI= (2.140,2.163)), respectively. CONCLUSIONS That data in this study show the BCG might provide the protection against COVID-19, with consequent less COVID-19 infection and deaths and more rapid recovery. BCG vaccine might bridge the gap before the disease-specific vaccine is developed, but this hypothesis needs to be further tested in rigorous randomized clinical trials. INTERNATIONAL REGISTERED REPORT RR2-https://doi.org/10.1101/2020.06.14.20131268

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Prevention of percutaneous injuries with risk of hepatitis B, hepatitis C, or other viral infections for health-care workers

10.1002/14651858.cd007197.pub2 ◽

2011 ◽

Author(s):

Annika Parantainen ◽

Minna Anthoni ◽

America Valdes ◽

Marie-Claude Lavoie ◽

Ulla-Maija Hellgren ◽

...

Keyword(s):

Health Care ◽

Hepatitis C ◽

Hepatitis B ◽

Health Care Workers ◽

Viral Infections ◽

Care Workers

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Efficacy and safety of intravenous immunoglobulins for the treatment of viral encephalitis: a systematic literature review

Journal of Neurology ◽

10.1007/s00415-021-10494-w ◽

2021 ◽

Author(s):

Judith N. Wagner ◽

Annette Leibetseder ◽

Anna Troescher ◽

Juergen Panholzer ◽

Tim J. von Oertzen

Keyword(s):

Systematic Review ◽

Viral Encephalitis ◽

Viral Infections ◽

Case Reports ◽

Ivig Therapy ◽

Intravenous Immunoglobulins ◽

Efficacy And Safety ◽

Serious Adverse Events ◽

Optimal Dosing ◽

Cochrane Database

Abstract Background For most viral encephalitides, therapy is merely supportive. Intravenous immunoglobulins (IVIG) have been used as a prophylactic and therapeutic approach. We conduct a systematic review on the safety and efficacy of IVIG in viral encephalitis. Methods We conducted a systematic review assessing PubMed, Cochrane Database, Biosis Previews and the ClinicalTrials.gov website to identify all reports on patients with viral encephalitis treated with IVIG as of May 31, 2019. The main outcomes assessed were therapeutic efficacy and safety. For an increased homogeneity of the population, atypical viral infections were excluded, as were reports on prophylactic IVIG use, intrathecal application of immunoglobulins, or use of antibody-enriched IVIG-preparations. Data were extracted from published studies. Descriptive statistics were used. Results We included a total of 44 studies (39 case reports). The case reports cover a total of 53 patients. Our search retrieved two prospective and three retrospective studies. These show heterogeneous results as to the efficacy of IVIG therapy. Only one study reports a significant association between IVIG-use and death (odds ratio 0.032; 95% confidence interval 0.0033–0.3024; p = 0.0027). None of the studies report significant differences in the number of serious adverse events. Conclusion Data on the efficacy of IVIG-therapy is heterogeneous. While it seems generally safe, evident superiority compared to supportive treatment has not been demonstrated so far. Future trials should also investigate the optimal dosing and timing of IVIG and their benefit in the immunosuppressed.

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The vagaries of IgM: a case report of EBV infection with concomitantly false-positive IgM for CMV, VZV, and HSV

The Egyptian Journal of Internal Medicine ◽

10.1186/s43162-020-00006-z ◽

2020 ◽

Vol 32 (1) ◽

Author(s):

Raai Mahmood ◽

Khalid Mohamed ◽

Naba Saeed ◽

Kadhim Al-Banaa ◽

Jonathan Zimmerman ◽

...

Keyword(s):

Infectious Mononucleosis ◽

Total Bilirubin ◽

Viral Infections ◽

Total Bilirubin Level ◽

Peripheral Blood Smear ◽

Cross Reactivity ◽

Immunoglobulin M ◽

Case Presentation ◽

Ebv Infection ◽

Acute Infectious Mononucleosis

Abstract Background Serum IgM (immunoglobulin M) testing is commonly used to diagnose acute viral infections. However, most clinicians are unaware of the vagaries of IgM testing, including antigenic cross-reactivity between multiple viruses and risk misdiagnosis. Case presentation We report a case of infectious mononucleosis with concomitantly positive IgM for EBV, CMV, VZV, and HSV. A 26-year-old man presented with acute infectious mononucleosis picture. His blood work showed a total bilirubin level of 7.7 mg/dl, ALT 1077 U/L, AST 806 U/L, ALP 325 U/L, and INR 1.0. Monospot was positive; peripheral blood smear showed atypical lymphocytes; however, because EBV infectious mononucleosis does not typically cause elevation of liver enzymes over 1000, other etiologies were explored. Tests for hepatitis A, B, C, HIV, ANA, and ASMA returned negative. IgM for EBV-VCA, CMV, HSV, and VZV all returned positive, and the diagnosis of EBV IM was called into question. Subsequent tests of CMV and HSV PCR for viral load were negative (VZV was not clinically suspected), and later on, EBV-EBNA returned negative and EBV-VCA IgM and IgG returned positive, confirming the diagnosis of acute EBV infection. Conclusion We believe that IgM seropositivity can result from cross-reactivity among several viruses (especially herpes viruses), and although often relied on, a positive IgM should not serve as the sole determinant for diagnosis of acute viral infections.

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Detection of 30 Fentanyl Analogs by Commercial Immunoassay Kits

Journal of Analytical Toxicology ◽

10.1093/jat/bkaa181 ◽

2021 ◽

Author(s):

Rebekah E Wharton ◽

Jerry Casbohm ◽

Ryan Hoffmaster ◽

Bobby N Brewer ◽

M G Finn ◽

...

Keyword(s):

Alkyl Chain ◽

Cross Reactivity ◽

Overdose Prevention ◽

Drug Enforcement ◽

Drug Enforcement Administration ◽

Preliminary Information ◽

Care Workers ◽

Powder Samples ◽

Fentanyl Analogs ◽

Lateral Flow Assays

Abstract Health-care workers, laboratorians and overdose prevention centers rely on commercial immunoassays to detect the presence of fentanyl; however, the cross-reactivity of fentanyl analogs with these kits is largely unknown. To address this, we conducted a pilot study evaluating the detection of 30 fentanyl analogs and metabolites by 19 commercially available kits (9 lateral flow assays, 7 heterogeneous immunoassays and 3 homogenous immunoassays). The analogs selected for analysis were compiled from the Drug Enforcement Administration and National Forensic Laboratory Information System reports from 2015 to 2018. In general, the immunoassays tested were able to detect their intended fentanyl analog and some closely related analogs, but more structurally diverse analogs, including 4-methoxy-butyryl fentanyl and 3-methylfentanyl, were not well detected. Carfentanil was only detected by kits specifically designed for its recognition. In general, analogs with group additions to the piperidine, or bulky rings or long alkyl chain modifications in the N-aryl or alkyl amide regions, were poorly detected compared to other types of modifications. This preliminary information is useful for screening diagnostic, forensic and unknown powder samples for the presence of fentanyl analogs and guiding future testing improvements.

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Neuroinflammation and Brain Development: Possible Risk Factors in COVID-19-Infected Children

NeuroImmunoModulation ◽

10.1159/000512815 ◽

2021 ◽

pp. 1-7

Author(s):

Luana da Silva Chagas ◽

Poliana Capucho Sandre ◽

Patricia Coelho de Velasco ◽

Henrique Marcondes ◽

Natalia Cristina Aparecida Ribeiro e Ribeiro ◽

...

Keyword(s):

Risk Factors ◽

Fatty Acids ◽

Brain Development ◽

Neural Development ◽

Viral Infections ◽

Additional Risk ◽

Autoimmune Hypothyroidism ◽

Inflammatory Syndrome ◽

Nutritional Imbalance ◽

Synaptic Pruning

COVID-19, a disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) betacoronavirus, affects children in a different way than it does in adults, with milder symptoms. However, several cases of neurological symptoms with neuroinflammatory syndromes, such as the multisystem inflammatory syndrome (MIS-C), following mild cases, have been reported. As with other viral infections, such as rubella, influenza, and cytomegalovirus, SARS-CoV-2 induces a surge of proinflammatory cytokines that affect microglial function, which can be harmful to brain development. Along with the viral induction of neuroinflammation, other noninfectious conditions may interact to produce additional inflammation, such as the nutritional imbalance of fatty acids and polyunsaturated fatty acids and alcohol consumption during pregnancy. Additionally, transient thyrotoxicosis induced by SARS-CoV-2 with secondary autoimmune hypothyroidism has been reported, which could go undetected during pregnancy. Together, those factors may pose additional risk factors for SARS-CoV-2 infection impacting mechanisms of neural development such as synaptic pruning and neural circuitry formation. The present review discusses those conditions in the perspective of the understanding of risk factors that should be considered and the possible emergence of neurodevelopmental disorders in COVID-19-infected children.

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Newly detected rapid eye movement associated sleep apnea after coronavirus disease 2019 as a possible cause for chronic fatigue: two case reports

Journal of Medical Case Reports ◽

10.1186/s13256-021-02819-0 ◽

2021 ◽

Vol 15 (1) ◽

Author(s):

Andreas Rembert Koczulla ◽

Antje Stegemann ◽

Rainer Gloeckl ◽

Sandra Winterkamp ◽

Bernd Sczepanski ◽

...

Keyword(s):

Sleep Apnea ◽

Eye Movement ◽

Case Reports ◽

White Male ◽

Chronic Fatigue ◽

White Female ◽

Rapid Eye Movement ◽

Pressure Therapy ◽

Fatigue Syndrome ◽

Case Presentations

Abstract Background Coronavirus disease 2019 has become a health problem spreading worldwide with pandemic characteristics since March 2020. Post coronavirus disease 2019 symptoms are more frequent than initially expected, with fatigue as an often-mentioned issue. Case presentations We describe a 32-year-old white male and a 55-year-old white female who suffered from post coronavirus disease 2019 fatigue syndrome. On polysomnography, rapid eye movement associated sleep apnea with an increased hypopnea index during rapid eye movement phases of 36.8 and 19.5 events per hour was found. Based on the patients’ burdensome fatigue symptoms, we initiated automatic positive airway pressure therapy, which diminished sleep apnea (rapid eye movement index: 0.0 in both patients) and, consequently, also the fatigue symptoms. Conclusions Since sleep apnea and coronavirus disease 2019 are both associated with fatigue, a screening for sleep apnea might be considered in coronavirus disease 2019 patients with fatigue syndrome.

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COVID-19 in Children: Expressions of Type I/II/III Interferons, TRIM28, SETDB1, and Endogenous Retroviruses in Mild and Severe Cases

International Journal of Molecular Sciences ◽

10.3390/ijms22147481 ◽

2021 ◽

Vol 22 (14) ◽

pp. 7481

Author(s):

Pier-Angelo Tovo ◽

Silvia Garazzino ◽

Valentina Daprà ◽

Giulia Pruccoli ◽

Cristina Calvi ◽

...

Keyword(s):

Viral Infections ◽

Severe Disease ◽

Endogenous Retroviruses ◽

Type I ◽

Human Endogenous Retroviruses ◽

Moderate Disease ◽

Amplification Assay ◽

Positive Correlations ◽

Inducible Genes ◽

Inflammatory Syndrome

Children with the new coronavirus disease 2019 (COVID-19) have milder symptoms and a better prognosis than adult patients. Several investigations assessed type I, II, and III interferon (IFN) signatures in SARS-CoV-2 infected adults, however no data are available for pediatric patients. RIM28 and SETDB1 regulate the transcription of multiple genes involved in the immune response as well as of human endogenous retroviruses (HERVs). Exogenous viral infections can trigger the activation of HERVs, which in turn can induce inflammatory and immune reactions. Despite the potential cross-talks between SARS-CoV-2 infection and TRIM28, SETDB1, and HERVs, information on their expressions in COVID-19 patients is lacking. We assessed, through a PCR real time Taqman amplification assay, the transcription levels of six IFN-I stimulated genes, IFN-II and three of its sensitive genes, three IFN-lIIs, as well as of TRIM28, SETDB1, pol genes of HERV-H, -K, and -W families, and of env genes of Syncytin (SYN)1, SYN2, and multiple sclerosis-associated retrovirus (MRSV) in peripheral blood from COVID-19 children nd in control uninfected subjects. Higher expression levels of IFN-I and IFN-II inducible genes were observed in 36 COVID-19-infected children with mild or moderate disease as compared to uninfected controls, whereas their concentrations decreased in 17 children with severe disease and in 11 with multisystem inflammatory syndrome (MIS-C). Similar findings were found for the expression of TRIM-28, SETDB1, and every HERV gene. Positive correlations emerged between the transcriptional levels of type I and II IFNs, TRIM28, SETDB1, and HERVs in COVID-19 patients. IFN-III expressions were comparable in each group of subjects. This preserved induction of IFN-λs could contribute to the better control of the infection in children as compared to adults, in whom IFN-III deficiency has been reported. The upregulation of IFN-I, IFN-II, TRIM28, SETDB1, and HERVs in children with mild symptoms, their declines in severe cases or with MIS-C, and the positive correlations of their transcription in SARS-CoV-2-infected children suggest that they may play important roles in conditioning the evolution of the infection.

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