“…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


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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.




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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





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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.



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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.


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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.


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Transcriptional profiling has identified a specific population of dopamine neurons in the substantia nigra that is highly susceptible to degeneration in Parkinson disease (PD). Analysis of nearly 400,000 nuclei from patients with PD and healthy individuals showed that a cell population characterized by expression of AGRT1 was more vulnerable to degeneration than nine other dopamine neuron populations that were identified. Spatially confined to the ventral tier of SNpc, it was highly susceptible to loss in PD and showed the strongest upregulation of targets of TP53 and NR2F2, associated with degeneration. This same vulnerable population was specifically enriched for the heritable risk associated with PD, highlighting the importance of cell-intrinsic processes in determining the differential vulnerability of DA neurons to PD-associated degeneration.

Fyfe I. Vulnerable dopamine neurons identified. Nat Rev Neurol. 2022 Jun 8. doi: 10.1038/s41582-022-00682-1. Epub ahead of print. PMID: 35676370.




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Kwon D: Guardians of the Brain: how a special immune system protects our grey matter. Nature 606, 22-24 (2022); doi: https://doi.org/10.1038/d41586-022-01502-8


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Abstract: Long COVID refers to the lingering symptoms which persist or appear after the acute illness. The dominant long COVID symptoms in the two years since the pandemic began (2020-2021) have been depression, anxiety, fatigue, concentration and cognitive impairments with few reports of psychosis. Whether other symptoms will appear later on is not yet known. For example, dopamine-dependent movement disorders generally take many years before first symptoms are seen. Post-stroke depression and anxiety may explain many of the early long COVID cases. Hemorrhagic, hypoxic and inflammatory damages of the central nervous system, unresolved systematic inflammation, metabolic impairment, cerebral vascular accidents such as stroke, hypoxia from pulmonary damages and fibrotic changes are among the major causes of long COVID. Glucose metabolic and hypoxic brain issues likely predispose subjects with pre-existing diabetes, cardiovascular or lung problems to long COVID as well. Preliminary data suggest that psychotropic medications may not be a danger but could instead be beneficial in combating COVID-19 infection. The same is true for diabetes medications such as metformin. Thus, a focus on sigma-1 receptor ligands and glucose metabolism is expected to be useful for new drug development as well as the repurposing of current drugs. The reported protective effects of psychotropics and antihistamines against COVID-19, the earlier reports of reduced number of sigma-1 receptors in post-mortem schizophrenic brains, with many antidepressant and antipsychotic drugs being antihistamines with significant affinity for the sigma-1 receptor, support the role of sigma and histamine receptors in neuroinflammation and viral infections. Literature and data in all these areas are accumulating at a fast rate. We reviewed and discussed the relevant and important literature.

Tang SW, Leonard BE, Helmeste DM. Long COVID, neuropsychiatric disorders, psychotropics, present and future. Acta Neuropsychiatr. 2022 Jun;34(3):109-126. doi: 10.1017/neu.2022.6. Epub 2022 Mar 3. PMID: 35144718.


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