SARS-CoV-2-Triggered Hemophagocytic Lymphohistiocytosis with Complications of Posterior Reversible Encephalopathy SyndromeRoss M. Perry, M.D. a* | Scott D. Casey, M.D., M.S. b | Alex Q. Lee, M.D.a | Sylvia P. Bowditch, M.D.c | Mary A. Rasmussen, M.D.c | Viyeka Sethi, M.D. d| Arun R. Panigrahi, M.D. eaUniversity of California, Davis, School of Medicine, Sacramento, California, USA; bDepartment of Emergency Medicine, University of California, Davis, Sacramento, California, U.S.A.; cDepartment of Pediatrics, University of California, Davis, Sacramento, California, U.S.A;dDepartment of Pediatric Critical Care Medicine, University of California, Davis, Sacramento, California, U.S.A;eDepartment of Pediatric Hematology & Oncology, University of California, Davis, Sacramento, California, U.S.A*Correspondence to:Ross Perry, M.D., 14 Rock Lane, Berkeley, CA, 94708, Phone: (707) 331-4626, Fax: (510) 752-1571, E-mail: [email protected] Text Word Count: 850Tables: 1; Figures: 1Short Title: SARS-CoV-2-Triggered HLH Complicated by PRESKeywords: SARS-CoV-2, HLH, PRES, MIS-C, corticosteroids, anakinra

The European Medicines Agency (EMA) started operating under its new legal mandate on 1 April 2022. The mandate brings new responsibilities to the Agency in three different areas: • Reinforcement of the role and activities of the EMA pandemic Task Force(which is now known as the Emergency Task Force (ETF)). • A stronger role of EMA in the monitoring of shortages of critical medicines, medical devices and in-vitro diagnostics, both in anticipation of and during a crisis. • A more coordinated mechanism of European Union (EU) experts advice on medical devices classified as high-risk (class IIa and III or class D (1)) and in-vitro diagnostic medical devices. Here we consider the impact of the COVID-19 pandemic on the operations of EMA and the European medicines regulatory network, and how EMA’s new mandate will strengthen the Agency’s and the Network’s ability to face crises. EMA’s extended mandate brings clear benefits in terms of response to public health emergencies at EU level, which ranges from improvements in crisis management to avoiding medicine shortages and improving access to diagnostics and medical devices that are safe and conform to their expected function.

Chinese COVID-19 vaccine named BBIBP-CorV (Sinopharm vaccine) is an inactivated whole virus vaccine to prevent COVID-19 disease. Previous studies concluded that inactivated COVID-19 vaccines do not increase the risk of thrombosis. In this report, we present the first upper limb DVT case after receiving this kind of vaccine.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19. COVID-19 has shown syndromic complexity. COVID-19 effects on the respiratory system have been well described in the literature, but we now recognize that COVID-19 also affects several other organs, including the nervous system. The neurological manifestations of SARS-CoV-2 infection are growing rapidly, as evidenced by several reports. There are several mechanisms responsible for such manifestations in the nervous system. For instance, post-infectious immune-mediated processes, direct virus infection of the central nervous system (CNS), and virus-induced hyper-inflammatory and hypercoagulable states are commonly involved. Due to multifactorial and complicated pathogenic mechanisms, COVID-19 poses a large-scale threat to the whole nervous system. A complete understanding of SARS-CoV-2 neurological impairments is still lacking, but our knowledge base is rapidly expanding. Therefore, we anticipate that this comprehensive review will provide valuable insights in unfolding different neurological dimensions of COVID-19 and other CoV associated abnormalities.

Background Intra-host diversity studies are used to characterise mutational heterogeneity of SARS-CoV-2 infections to understand the impact of virus-host adaptations. This study investigated the frequency and diversity of the spike (S) protein mutations within SARS-CoV-2 infected South African individuals. Methods Single nucleotide polymorphism (SNP) assays and whole genome sequencing were performed on SARS-CoV-2 positive samples. Allele frequency (AF) was determined using TaqMan Genotyper software for SNP analysis and galaxy.eu for analysis of FASTQ reads. Results The SNP assays identified 5.3% (50/948) Delta cases with heterogeneity at delY144 (4%; 2/50), E484Q (6%; 3/50), N501Y (2%; 1/50) and P681H (88%; 44/50). Sequencing identified 9% (210/2381) cases with Beta, Delta, Omicron BA.1, BA.2.15, and BA.4 lineages with heterogeneity in the S protein. Heterogeneity was primarily identified at positions 19 (1.4%) with T19IR (AF 0.2-0.7), 371 (92.3%) with S371FP (AF 0.1-1.0), and 484 (1.9%) with E484AK (0.2-0.7), E484AQ (AF 0.4-0.5) and E484KQ (AF 0.1-0.4). Conclusion Mutations at heterozygous amino acid positions 19, 371 and 484 reduce recognition of neutralising antibodies, however the impact of the multiple substitutions at the same position is unknown. Therefore, we hypothesise that intra-host SARS-CoV-2 quasispecies with heterogeneity in the S protein facilitate competitive advantage of variants that can completely/partially evade host’s natural and vaccine-induced immune responses.

Objective Assess whether coronavirus disease 2019 (COVID-19) vaccination impacts menstrual bleeding quantity. Design Retrospective cohort Setting Five global regions Populations Vaccinated and unvaccinated regularly cycling individuals using the digital fertility-awareness application “Natural Cycles”. Methods We used prospectively collected menstrual cycle data and multivariable longitudinal Poisson GEE models, multivariable multinomial logistic regression models, and calculated the adjusted difference between vaccination groups. All regression models were adjusted for confounders. Outcome measures Mean number of heavy bleeding days (fewer, no change, more) and changes in bleeding quantity (less, no change, more) at three time points (first dose, second dose, and post-exposure menses). Results We included 9,555 individuals (7,401 vaccinated, 2,154 unvaccinated). About 2/3 of individuals reported no change in the number of heavy bleeding days regardless of vaccination status. After adjusting for confounders, there were no significant differences in the number of heavy bleeding days by vaccination status. A larger proportion of vaccinated individuals experienced an increase in total bleeding quantity (34.5% unvaccinated, 38.4% vaccinated; 4.0% [0.7, 7.2%] adjusted difference). This translates to an estimated 40 additional people per 1,000 normally cycling individuals who experience more total bleeding quantity following the first vaccine dose due to vaccination. Differences resolved in the cycle post-exposure. Conclusion A small increase in the probability of more total bleeding quantity occurs following the first COVID-19 vaccine dose which resolved the cycle post-vaccination cycle. Total number of heavy bleeding days did not differ by vaccination status. Our findings can reassure the public that any changes are small and transie

A document by Alessandro Farsi. Click on the document to view its contents.

The COVID-19 pandemic has led to an unprecedented change in transportation, including shared mobility services. This study attempted to identify the user group of ride-share services by leveraging daily ride-sharing trip data for the year of 2020 associated with other socio-demographic and built-environment attributes of Chicago, Illinois. The study employed K-means clustering for user group segmentation. Results show: i) the cluster with the largest share of census tracts generate lowest average trips which is clearly an impact of the pandemic; ii) The high-income cluster generates short trip and coupled with high population, land-use, and employment density; iii) The low-income cluster generates longer trips coupled with diversity of land-use mx, employment and population density. Results of this study provide insights for policymakers and ride- sharing operators to ensure access to the services among the population irrespective of spatial diversity.

The present work argues the involvement of zinc chelation ability of some non-steroidal anti-inflammatory drugs as an additive mechanism able to increase their efficacy against COVID-19.

A 57-year-old male known case of diabetes mellitus presented with gradually bilateral decreased vision accompanied by ocular pain two weeks after SARS-CoV-2 infection. Ophthalmic examination and imaging were indicative of bilateral anterior ischemic optic neuropathy and secondary angle-closure glaucoma associated with increased choroidal thickness and hypercoagulable state following COVID-19 infection.

Coronavirus disease is a viral infection affecting different organs with various morbidities and mortality. Vaccines are used to control the disease. COVID-19 vaccines have brought many benefits but their adverse effects should not be ignored. Here, we report a case of Guillain-Barré Syndrome Following Sinopharm COVID-19 Vaccine.

A document by Hubert Blain. Click on the document to view its contents.

Most instances of Guillain-Barré syndrome (GBS) are caused by immunological stimulation and are discovered after vaccinations for tetanus toxoid, oral polio, and swine influenza. This systematic study investigated GBS cases reported after receiving the COVID-19 vaccination.

Background: Following the Coronavirus disease (COVID-19) pandemic, new changes in the transmission of various pathogens have occurred. The environmental changes influenced by the COVID-19 pandemic have affected the flow of human society and the survival environment of other microorganisms. The prevalence of influenza viruses has also changed under this selection pressure. Objective: To investigate the influenza virus’s prevalence, risk factors and symptom characteristics during the outbreak of COVID-19. Methods: Samples and data were collected from outpatients requiring respiratory virus tests in a tertiary hospital. Throat swabs were tested in the immunocolloidal gold method. Characteristics of influenza A and B compared before and after the outbreak of COVID-19. Results: The dominant virus strain in 2020-2022 has gradually changed from influenza A to influenza B. Influenza A is mainly prevalent in 0 to 20 years old (P < 0.05), and influenza B is dominant in all age groups. Most of the patients with positive results were from paediatrics and presented in fever clinics (P < 0.05); Most of the patients were diagnosed with fever and upper respiratory tract infection (P < 0.05). Conclusion: The influenza virus’s positive rate, risk factors and symptom characteristics have changed compared to previous years. It means the epidemic prevention measures have greatly affected the prevalence of the influenza virus since the outbreak of COVID-19.

We examine the price disorder and market efficiency of five cryptocurrencies (Bitcoin, BNB, Cardano, Ethereum, and XRP) before and during COVID-19 pandemic period. Using permutation entropy and Fisher information measure (FIM), we construct the Shannon-Fisher causality plane (SFCP) to map these cryptocurrencies and their respective locations in a two-dimensional plane and then apply sliding time window approach to study the temporal evolution of efficiency. All cryptocurrencies exhibit high but slightly varying informational efficiency during both periods. Cardano is the most efficient. These results might point to the increasing maturity and lower potential for price predictability, which matter to cryp-tocurrencies usage for liquidity risk diversification strategy.

This research explores the multifractal dynamics of the daily number of vaccinated time series for COVID-19, considering six European countries (Belgium, Denmark, France, Ger-many, Greece, and Italy) using the Multifractal Detrended Fluctuations Analysis (MF-DFA). We calculate the multifractal spectrum í µí±“ (í µí»¼) and apply a fourth-degree polynomial regression fit to estimate the complexity parameters that describe the degree of multifractality of the underlying process. We find that the multifractal dynamics of all these countries are characterized by strongly anti-persistent behaviour or anti-persistent long-term correlations (í µí»¼ 0 < 0.5) a lower degree of multifractality, and small fluctuations are dominant in the mul-tifractal spectrum. Our findings shed light on the period of immunization of the population that adhered to the vaccination campaigns is short and that the application of new doses of vaccines must comply with this phenomenology to keep the people safe.

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from wildlife origins has raised concerns about spillover from humans to animals, the establishment of novel wildlife reservoirs, and the potential for future outbreaks caused by variants of wildlife origin. Norway rats ( Rattus norvegicus) are abundant in urban areas and live in close proximity to humans, providing the opportunity for spillover of SARS-CoV-2. To date, there is no evidence of natural SARS-CoV-2 infection in rats and experimental studies suggest rats are likely not susceptible to ancestral SARS-CoV-2. However, as variants emerge, new species have been identified as competent hosts, as demonstrated by the susceptibility of rats to the SARS-CoV-2 Alpha variant of concern (VOC). We investigated SARS-CoV-2 infection and exposure in Norway rats from southern Ontario, Canada. From October 2019 to June 2021, 224 rats were submitted by collaborating pest control companies. The majority of samples were collected in Windsor (79.9%; n=179), Hamilton (13.8%; n=31), and the Greater Toronto Area (5.8%; n=13). Overall, 50.0% (n=112) were female and most rats were sexually mature (55.8%; n=125). Notably, 202 samples, including the two seropositive samples, were collected prior to the emergence of VOCs, and 22 were collected while the Alpha variant was the predominant circulating VOC in humans. Nasal turbinate (n=164) and small intestinal (n=213) tissue samples were analyzed for SARS-CoV-2 RNA by RT-PCR. Thoracic cavity fluid samples (n=213) were tested for neutralizing antibodies using a surrogate virus neutralization test (sVNT) (GenScript cPass); confirmatory plaque reduction neutralization test (PRNT) testing was conducted on presumptive positive samples. We did not detect SARS-CoV-2 RNA in any samples tested. Two out of eleven samples positive by sVNT had neutralizing antibodies by PRNT (1:40 and 1:320 PRNT70). It is imperative that efforts to control and monitor SARS-CoV-2 include surveillance of rats and other relevant wildlife species as novel variants continue to emerge.

The pandemic situation of the new corona virus (SARS-COV-2) forces drug designers to formulate a new intelligent drug for this disease effective to treat all mutations of the virus. One way to control all mutations of virus is inhibition of spike protein (binding with Angiotensin converting enzyme 2 (ACE-2)) duo to inhibit the viral entry. Viral entry is the first step for virus to start infection. In this work the interactions of SARS-COV-2 spike protein and ACE-2 are evaluated Insilico by docking process and four different Ligands are estimated to simulate those interactions, so as to avoid bindings with ACE-2 needed for viral entry in reality. All Ligand – receptor interactions are considered. Results approves the suggested Ligands in this work, have definite inhibitory effect on SARS-COV-2 spike protein based on the interactions which they make with receptor binding domain (RBD). Docking process are done repeatedly to assure conclusions.

Aim: To investigate prevention measures of hospital-acquired infection and clinical features of suspicious COVID-19 patients in the pediatric respiratory ward. Methods: Patients with fever and cough or fever accompanied by vomiting and diarrhea were given pre-isolation measures. The medical records of the patients were collected and analyzed to summarize the pre-isolation measures and patients’ clinical features. Results: A total of 50 pre-isolated children with suspicious COVID-19 hospitalized between January 28 and March 5, 2020 were included in. Pre-isolation measures combined with epidemiological history and pathogen screenings were used to rule out COVID-19 patients. No definite COVID-19 cases were detected, while 2(4%) patients were suspected of having COVID-19. The pathogenic results mainly included Mycoplasma pneumonia (35, 70%).Thirty-five (70%) patients had bronchopneumonia. The pre-isolation patients had the common clinical epidemiological characteristics as patients with fever and cough, vomiting, and diarrhea. Discussion: Pre-isolation measures could prevent suspicious COVID-19 patients from coming in contact with other patients before definite exclusion. Clinical analysis of the patients was helpful for clinical nursing management. Conclusions: Pre-isolation measures combined with epidemiological history and pathogen screening (novel coronavirus nucleic acid and general pathogen) can help to minimize the risk of COVID-19 as a hospital-acquired infection.

Background and Purpose Codonopsis lanceolata (CL) has long been used as a medicinal herb in East Asian countries to treat inflammatory diseases of the respiratory system but its antiviral activity has not been investigated. Here, we evaluated the potential inhibitory activity of CL extracts and their active compounds on SARS-CoV-2. Experimental Approach Pseudotyped SARS-CoV-2 entry assay and dose-response curve analysis with authentic SARS-CoV-2 and recombinant SARS-CoV-2 reporter virus expressing the nanoluciferase were carried out to investigate the effects of compounds against SARS-CoV-2 entry into host cells. Filipin cholesterol staining, SARS-CoV-2 Spike (S)-ACE2 binding assay, and S-mediated cell fusion assay using time-lapse imaging, flow cytometry, and split-GFP fusion were conducted to understand the inhibitory mechanisms. Key Results Lancemaside A (LA), a triterpenoid saponin isolated from CL, impeded the endosomal entry pathway of SARS-CoV-2 and its variants including Alpha, Beta, Delta, and Omicron with similar IC50 values of 2.23 ~ 3.37 μM as well as the TMPRSS2-mediated viral entry pathway with IC50 value of 3.92 μM. LA was also able to prevent the formation of S-induced multinucleated syncytia. Mechanically, LA altered the distribution of host cell membrane cholesterol and blocked the membrane fusion between SARS-CoV-2 and host cells. Conclusion and implications LA can be a broad-spectrum antiviral drug not only against SARS-CoV-2 but also against other novel enveloped viral pathogens that might arise in the future by targeting viral envelope fusion with the host cell membrane. Keywords SARS-CoV-2, Omicron, COVID-19, Lancemaside A, triterpenoid saponin, membrane fusion

In this work, we show the spatiotemporal spread and replacement of different Variant of Concern (VOC) of SARS-COV-2. We define a metric to quantify the spread speed of each COV. We discuss the basic reproductive number of these VOC’s and possible impact of travel ban.

This work presents a novel perfect reconstruction filter bank decomposition (PRFBD) for nonlinear and nonstationary time series and image data representation and analysis. The Fourier decomposition method (FDM), an adaptive approach wholly based on the Fourier representation, is shown to be a special case of the proposed PRFBD. The adaptive Fourier–Gauss decomposition (FGD) proposed in this work is a variation of the FDM, which is based on the FR and Gaussian filtering. Similarly, we also consider Butterworth filtering to develop adaptive Fourier–Butterworth decomposition (FBD). The proposed theory can decompose any signal (time series, image, or other data) into a set of the desired number of Fourier intrinsic band functions (FIBFs), which follow the amplitude-modulation and frequency-modulation (AM-FM) representations. A generic filterbank representation is also provided, where perfect reconstruction can be ensured for any given set of lowpass or highpass filters. We have performed an extensive analysis of both simulated and real-life data (COVID-19 pandemic, Earthquake and Gravitational waves) to demonstrate the efficacy of the proposed method. The resolution results in the time-frequency representation demonstrate that the proposed method is more promising than the state-of-the-art approaches.

The Human Monkeypox virus belongs to the Poxvirdiae family of the Orthopoxvirus genus. This virus is seen to get transmitted to humans predominantly by contact transmission via infected animals and humans. It exhibits a range of clinical features apart from the common rash, swollen lymph nodes, and flu-like symptoms.

Specific background information on cancer patients affected more severely by crisis and disasters is lacking. We experienced an advanced breast cancer patient whose hospital visits were interrupted for two years due to multiple internal and external factors. These factors need to be taken more into account for breast cancer management.