https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7874141/

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Abstract

What is Known and Objective

An extensively documented multisystem inflammatory syndrome (MIS) has been observed in a small but significant percentage of COVID-19 patients, in some adults but primarily in paediatric patients, and for these patients it is sometimes called MIS-C.

Comment

Kawasaki disease has also been observed over the last several decades in patients that tested positive for a variety of very virulent pathogens. Several differences and similarities between MIS-C and Kawasaki disease pathology have been observed. Several puzzling aspects of MIS-C, Kawasaki disease and other Kawasaki-like diseases have been discussed, but not yet explained.

What is New and Conclusion

An explanatory hypothesis has been presented. Using the hypothesis that a transient or permanent inability to quickly phagocytize antigen-antibody immune complexes created by a novel virulent pathogen infection induces a Type III hypersensitivity immune response and the resulting proteinase exposure and expression of new autoantigens are the fundamental steps for MIS and other Kawasaki-like diseases, it is possible to provide straightforward explanations for at least 10 of the most puzzling aspects of these diseases. The validity of the hypothesis itself is also supported by its ability to provide consistent and straightforward explanations for a large number of these disease aspects. Furthermore, these straightforward explanations and the explanatory hypothesis on which they are based also suggest several potential new treatments, which could possibly be more effective than various treatments in current use.

Roe, K: Explanations for 10 of the most puzzling aspects of multisystem inflammatory syndrome and other Kawasaki-like diseases. J. Clin. Pharm. Therapeutics,  47(4): 539-543, https://doi.org/10.1111/jcpt.13560

https://onlinelibrary.wiley.com/doi/full/10.1111/jcpt.13560

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The neuroinflammatory basis of COVID fog has been suggested to involve cytokine-induced activation of regional microglia, causing decreased hippocampal neurogenesis and a loss of myelinated subcortical axons. The findings illustrate similar neuropathophysiology after cancer therapy and respiratory SARS-CoV-2 infection which may contribute to cognitive impairment following even mild COVID.

Kato J, Frankland PW. COVID fog demystified. Cell. 2022 Jun 15;185(14):2391–3. doi: 10.1016/j.cell.2022.06.020. Epub ahead of print. PMID: 35768007; PMCID: PMC9197953.

and

Fernández-Castañeda A, Lu P, Geraghty AC, Song E, Lee MH, Wood J, O’Dea MR, Dutton S, Shamardani K, Nwangwu K, Mancusi R, Yalçın B, Taylor KR, Acosta-Alvarez L, Malacon K, Keough MB, Ni L, Woo PJ, Contreras-Esquivel D, Toland AMS, Gehlhausen JR, Klein J, Takahashi T, Silva J, Israelow B, Lucas C, Mao T, Peña-Hernández MA, Tabachnikova A, Homer RJ, Tabacof L, Tosto-Mancuso J, Breyman E, Kontorovich A, McCarthy D, Quezado M, Vogel H, Hefti MM, Perl DP, Liddelow S, Folkerth R, Putrino D, Nath A, Iwasaki A, Monje M. Mild respiratory COVID can cause multi-lineage neural cell and myelin dysregulation. Cell. 2022 Jun 13;185(14):2452–2468.e16. doi: 10.1016/j.cell.2022.06.008. Epub ahead of print. PMID: 35768006; PMCID: PMC9189143.

https://pubmed.ncbi.nlm.nih.gov/35768007/

https://pubmed.ncbi.nlm.nih.gov/35768006/

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“…In May, the U.S. Centers for Disease Control and Prevention reported that a review of the medical records of nearly 2 million people suggested at least one in five of those diagnosed with COVID-19 had developed conditions characteristic of Long Covid. Other studies have found roughly similar rates. Some recent research suggests the risk for vaccinated people is somewhat lower, but vaccination’s power to head off the syndrome remains uncertain. …”

Couzin-Frankel J.: Clues to long COVID,  Science, 376 (6599), • DOI: 10.1126/science.add429

https://www.science.org/content/article/what-causes-long-covid-three-leading-theories

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https://doi.org/10.1176/appi.ajp.20220445

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Abstract:   A veterinarian in Thailand was diagnosed with COVID-19 after being sneezed on by an infected cat owned by an infected patient. Genetic study supported the hypothesis of SARS-CoV-2 transmission from the owner to the cat, and then from the cat to the veterinarian.

Sila, T., Sunghan, J., Laochareonsuk, W., Surasombatpattana, S., Kongkamol, C., Ingviya, T….Chusri, S. (2022). Suspected Cat-to-Human Transmission of SARS-CoV-2, Thailand, July–September 2021. Emerging Infectious Diseases, 28(7):  1485-1488. https://doi.org/10.3201/eid2807.212605.

https://wwwnc.cdc.gov/eid/article/28/7/21-2605_article

 

 

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Abbreviated Abstract:

Introduction: COVID-19 might affect the incidence of specific neurological diseases, but it is unknown if this differs from the risk following other infections. Here, we characterized the frequency of neurodegenerative, cerebrovascular, and immune-mediated neurological diseases after COVID-19 compared to individuals without COVID-19 and those with other respiratory tract infections.

Methods: This population-based cohort study utilized electronic health records covering ~50% of Denmark’s population (n = 2,972,192). Between 02/2020 and 11/2021, we included individuals tested for COVID-19 or diagnosed with community-acquired bacterial pneumonia in hospital-based facilities. Additionally, we included individuals tested for influenza in the corresponding pre-pandemic period between 02/ 2018 and 11/2019. We stratified cohorts for in- and outpatient status, age, sex, and comorbidities.

Results: In total, 919,731 individuals were tested for COVID-19, of whom 43,375 tested positive. Compared to COVID-negative outpatients, COVID-19 positive outpatients had an increased RR of Alzheimer’s disease, and Parkinson’s disease, ischemic stroke and intracerebral hemorrhage. However, when comparing to other respiratory tract infections, only the RR for ischemic stroke was increased among inpatients with COVID-19 when comparing to inpatients with influenza (RR = 1.7; 95%CI: 1.2–2.4) and only for those >80 years of age when comparing to inpatients with bacterial pneumonia (RR = 2.7; 95%CI: 1.2–6.2). Frequencies of multiple sclerosis, myasthenia gravis, Guillain-Barré syndrome and narcolepsy did not differ after COVID-19, influenza and bacterial pneumonia.

Conclusion: The risk of neurodegenerative and cerebrovascular, but not neuroimmune, disorders was increased among COVID-19 positive outpatients compared to COVID-negative outpatients. However, except for ischemic stroke, most neurological disorders were not more frequent after COVID-19 than after other respiratory infections.

Zarifkar P , Peinkhofer C, Benros ME, Kondziella D: Frequency of Neurological Diseases After COVID-19, Influenza A/B and Bacterial Pneumonia. Front. Neurol. doi: 10.3389/fneur.2022.904796

https://www.frontiersin.org/articles/10.3389/fneur.2022.904796/full

 

 

 

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Abbreviated Abstract:

Importance: Public health measures implemented during the COVID-19 pandemic had widespread effects on population behaviors, transmission of infectious diseases, and exposures to environmental pollutants. This provided an opportunity to study how these factors potentially influenced the incidence of Kawasaki disease (KD), a self-limited pediatric vasculitis of unknown etiology.

Objectives: To examine the change in KD incidence across the United States and evaluate whether public health measures affected the prevalence of KD.

Results: A total of 2461 KD cases were included in the multicenter study (2018: 894; 2019: 905; 2020: 646), and 1461 cases (median [IQR] age, 2.8 years [1.4-4.9 years]; 900 [61.6%] males; 220 [15.1%] Asian, 512 [35.0%] Hispanic, and 338 [23.1%] White children) from RCHSD between 2002 and 2021 were also included. The 28.2% decline in KD cases nationally during 2020 (646 cases) compared with 2018 (894 cases) and 2019 (905 cases) was uneven across the United States. For RCHSD, there was a disproportionate decline in KD cases in 2020 to 2021 compared with the mean (SD) number of cases in earlier years for children aged 1 to 5 years (22 vs 44.9 [9.9]), male children (21 vs 47.6 [10.0]), and Asian children (4 vs 11.8 [4.4]). Mobility data did not suggest that shelter-in-place measures were associated with the number of KD cases. Clinical features including strawberry tongue, enlarged cervical lymph node, and subacute periungual desquamation were decreased during 2020 compared with the baseline period (strawberry tongue: 39% vs 63%; enlarged lymph node: 21% vs 32%; periungual desquamation: 47% vs 58%). School closures, masking mandates, decreased ambient pollution, and decreased circulation of respiratory viruses all overlapped to different extents with the period of decreased KD cases. KD in San Diego rebounded in the spring of 2021, coincident with lifting of mask mandates.

Conclusions and relevance: In this study of epidemiological and clinical features of KD during the COVID-19 pandemic in the United States, KD cases fell and remained low during the period of masking and school closure. Mobility data indicated that differential intensity of sheltering in place was not associated with KD incidence. These findings suggest that social behavior is associated with exposure to the agent(s) that trigger KD and are consistent with a respiratory portal of entry for the agent(s).

Burney JA, Roberts SC, DeHaan LL, Shimizu C, Bainto EV, Newburger JW, Dominguez S, Jone PN, Jaggi P, Szmuszkovicz JR, Rowley AH, Samuy N, Scalici P, Tremoulet AH, Cayan DR, Burns JC; KIDCARE Study Investigators. Epidemiological and Clinical Features of Kawasaki Disease During the COVID-19 Pandemic in the United States. JAMA Netw Open. 2022 Jun 1;5(6):e2217436. doi: 10.1001/jamanetworkopen.2022.17436. PMID: 35713905.

https://pubmed.ncbi.nlm.nih.gov/35713905/

 

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Abbreviated Abstract:  Super antigens are some part of virus or bacteria proteins which stimulate T cells and antigen-presenting cells leading to systemic immune response and inflammation. Super antigens have a possible role in in various inflammatory childhood diseases (i.e. Kawasaki disease, atopic dermatitis, and chronic rhinosinusitis). Occasionally, clinical presentations of some human viruses (eg coronavirus and adenovirus) mimic Kawasaki disease. In addition, coinfection with adenovirus, coronavirus, and para-influenza virus type 3 were observed with Kawasaki disease. This study summarizes the relationship between viral and bacterial super antigens and childhood inflammatory diseases.

Noorbakhsh S, Ashouri S, Moradkhani M. Role of Superantigens In Various Childhood Inflamatory Diseases. Infect Disord Drug Targets. 2022 May 30. doi: 10.2174/1871526522666220530141031. Epub ahead of print. PMID: 35638540.

https://pubmed.ncbi.nlm.nih.gov/35638540/

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Abstract:  Coronavirus disease 2019 (COVID-19), caused by a highly pathogenic emerging virus, is called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Knowledge regarding the pathogenesis of this virus is in infancy; however, investigation on the pathogenic mechanisms of the SARS-CoV-2 is underway. In COVID-19, one of the most remarkable characteristics is the wide range of disease manifestation and severity seen across individuals of different ethnic backgrounds and geographical locations. To effectively manage COVID-19 in the populations, beyond SARS-CoV-2 detection, serological response assessment, and analytic techniques, it is critical to obtain knowledge about at-risk individuals and comprehend the identified variations in the disease’s severity in general and also in the populations’ levels. Several factors can contribute to variation in disease presentation, including population density, gender and age differences, and comorbid circumstances including diabetes mellitus, hypertension, and obesity. Genetic factors presumably influence SARS-CoV-2 infection susceptibility. Besides this, COVID-19 has also been linked with a higher risk of mortality in men and certain ethnic groups, revealing that host genetic characteristics may affect the individual risk of death. Also, genetic variants involved in pathologic processes, including virus entrance into cells, antiviral immunity, and inflammatory response, are not entirely understood. Regarding SARS-CoV-2 infection characteristics, the present review suggests that various genetic polymorphisms influence virus pathogenicity and host immunity, which might have significant implications for understanding and interpreting the matter of genetics in SARS-CoV-2 pathogenicity and customized integrative medical care based on population investigation.

Adli A, Rahimi M, Khodaie R, Hashemzaei N, Hosseini SM. Role of genetic variants and host polymorphisms on COVID-19: From viral entrance mechanisms to immunological reactions. J Med Virol. 2022 May;94(5):1846-1865. doi: 10.1002/jmv.27615. Epub 2022 Feb 8. PMID: 35076118; PMCID: PMC9015257.

https://pubmed.ncbi.nlm.nih.gov/35076118/

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