Development of a Genomics-Based Approach To Identify Putative Hypervirulent Nontyphoidal Salmonella Isolates: Salmonella enterica Serovar Saintpaul as a Model

Not all Salmonella isolates are equally likely to cause human disease, and Salmonella control strategies may unintentionally focus on serovars and subtypes with high prevalence in source populations but are rarely associated with human clinical illness. We describe a framework leveraging WGS data in the NCBI PD database to identify Salmonella subtypes over- and underrepresented among human clinical cases.

Intracranial Hemorrhage Associated with Therapeutic Anticoagulation in Three Critically Ill COVID-19 Patients: A Case Series

Introduction: The COVID-19 pandemic has challenged global health with novel pathogenesis that is both severe and poorly understood. Several mechanisms have been proposed to explain the severity and complexity of the clinical illness including cytokine storm release, thromboembolic microangiopathy, direct cytotoxicity, and post-viral bacterial super infection. Cases: The patients in this case series were all admitted to the intensive care unit with respiratory failure from COVID-19 requiring invasive mechanical ventilation. They were all started on anticoagulation. All three patients developed acute kidney injuries. The first patient had hypertensive emergency at the time of the bleed. The second and third patient both had supratherapeutic heparin levels at the time of the bleed. Methods: We followed patients aged 18 years and above who were admitted to the ICU for COVID-19 during April and May 2020. We then followed those who required therapeutic anticoagulation for any indication and evaluated the ones that developed ICH. Results: Out of the 79 patients admitted to the ICU for COVID-19 related illness during April and May 2020, 31 were placed on therapeutic anticoagulation (intermediate or full-dose) for indications that included hypercoagulable state, ACS, atrial fibrillation, and deep vein thrombosis. 25% of patients on anticoagulation developed bleeding for which the anticoagulation had to be stopped. Three out of these 31 patients developed ICH while on anticoagulation, accounting for 3.8% of our ICU population with COVID-19 Discussion: Activation of coagulation pathways during cytokine storms can result in systemic thromboembolism, in both venous and arterial circulations posing risk of ischemic infarctions to any organ. Supratherapeutic heparin levels and acute kidney injuries are common in COVID-19 patients. The ideal candidates for anticoagulation, the recommended agent and dose, and duration of treatment remain unclear. Conclusion: The benefits of anticoagulation should be weighed against the potential risk of bleeding.

Risk and Predictive Factors of Leptospirosis in Dogs Diagnosed with Kidney and/or Liver Disease in Selangor, Malaysia

Canine leptospirosis is commonly associated with kidney and/or liver disease. It has been widely reported and causes public health concerns due to its zoonotic potential and its re-emergence, resulting from close contact between humans and dogs. The current study identified potential risk and predictive factors for dogs diagnosed with kidney and/or liver disease due to leptospirosis. A total of 124 client-owned dogs were recruited, and information such as signalment, medical history, management, and clinical findings were documented. Samples collected from the recruited dogs were directly tested using polymerase chain reaction (PCR) and subsequently inoculated for bacterial isolation. Statistical analyses were descriptively analyzed, and risk analyses were performed using Pearson chi-square tests and logistic regression. A total of 53 dogs (42.7%) were positive for leptospiral infection based on PCR, and 10 leptospiral isolates were successfully recovered from eight dogs. The mortality rate of infected dogs was 34.0% (18/53). Medium and large dog breeds, with a history of exposure to rats, and managed outdoors had a greater risk for leptospirosis (p < 0.05). The significant predictors for the dogs’ positivity were the presence of rats and acute clinical illness (p < 0.05). Administration of antibiotics and the detection of clinical illness at an early stage of the disease improved the survivability of the dogs (p < 0.05). Identifying the profile of dogs that are at risk to leptospirosis could be useful in the design of diagnostic and treatment strategies, as well as to increase awareness for prevention of the disease.

History of Neuro Rehabilitation in Russia

Medical rehabilitation is a process aimed at promoting and facilitating recovery from physical injury, psychological and mental disorders and clinical illness. The history of medical rehabilitation is a fascinating journey through time, providing insight into many different areas of medicine. When modern rehabilitation emerges in the mid-twentieth century, it stems from a combination of management approaches focusing on orthopedic and biomechanical understanding of movement patterns, on mastering neuropsychological mechanisms, and on an awareness of the socio-professional dimension of everyday reality.

Broad ultra-potent neutralization of SARS-CoV-2 variants by monoclonal antibodies specific to the tip of RBD

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) continue to wreak havoc across the globe. Higher transmissibility and immunologic resistance of VOCs bring unprecedented challenges to epidemic extinguishment. Here we describe a monoclonal antibody, 2G1, that neutralizes all current VOCs and has surprising tolerance to mutations adjacent to or within its interaction epitope. Cryo-electron microscopy structure showed that 2G1 bound to the tip of receptor binding domain (RBD) of spike protein with small contact interface but strong hydrophobic effect, which resulted in nanomolar to sub-nanomolar affinities to spike proteins. The epitope of 2G1 on RBD partially overlaps with ACE2 interface, which gives 2G1 ability to block interaction between RBD and ACE2. The narrow binding epitope but high affinity bestow outstanding therapeutic efficacy upon 2G1 that neutralized VOCs with sub-nanomolar IC50 in vitro. In SARS-CoV-2 and Beta- and Delta- variant-challenged transgenic mice and rhesus macaque models, 2G1 protected animals from clinical illness and eliminated viral burden, without serious impact to animal safety. Mutagenesis experiments suggest that 2G1 could be potentially capable of dealing with emerging SARS-CoV-2 variants in future. This report characterized the therapeutic antibodies specific to the tip of spike against SARS-CoV-2 variants and highlights the potential clinical applications as well as for developing vaccine and cocktail therapy.

Can Testing Predict SARS-CoV-2 Infectivity? The Potential for Certain Methods to be a Surrogate for Replication-Competent Virus

Since the beginning of the COVID-19 pandemic, molecular methods (e.g., real-time PCR) have been the primary means of diagnosing the disease. It is now well-established that molecular tests can continue to detect SARS-CoV-2 genomic RNA for weeks or months following the resolution of clinical illness. This has prompted public health agencies to recommend a symptom and/or time-based strategy for discontinuation of isolation precautions, which for hospitalized patients, results in significant use of personal protective equipment. Due to the inability of current molecular diagnostic assays to differentiate between the presence of remnant viral RNA (i.e., non-infectious) and replication-competent (i.e., infectious) virus, there has been interest in determining whether laboratory tests can be used to predict an individual’s likelihood of transmitting the virus to others. This review will highlight what is currently known about the potential for existing assays, such as real-time PCR and antigen tests, to predict active viral infection. In addition, data on the performance of new methods, such as molecular tests targeting viral RNA intermediates (e.g., subgenomic RNA), will be discussed.

Serosurveillance among COVID-19 Cases in Ahmedabad Using SARS-COV2 IgG Antibodies

Background: Serosurveillance study focusing on antibodies against SARS-CoV2 among the Covid19 cases can add value in the scientific knowledge & help in formulating valid predictions regarding immunity status in the post-covid period. Objectives: To estimate seropositivity among covid19 cases and to identify various factors affecting seropositivity. Methods: During second half of October 2020, a population based serosurvey on Covid19 cases was carried out in Ahmedabad. Covid-Kavach test kits were used and estimated seroprevalence was compared with available demographic and covid19 case related parameters to identify factors affecting seropositivity in the post-covid period. Simple proportions and Z-test were used as appropriate. Results: As on October 2020, the sero-positivity among Covid19 cases in Ahmedabad was 54.51% [95% Confidence Interval (CI) 52.14-56.86%]. Females have higher positivity (54.78%) as compared to males (54.30%) but the difference was statistically not significant (Z=0.19, P=0.84). Among children and elderly, the positivity is high and from young adults to elderly the seropositivity has an increasing trend. Severity of clinical illness and longer duration of hospitalization are associated with higher seropositivity. Conclusion: With 54.51% seropositivity among covid19 cases, it is clear that all the covid19 cases may not have developed IgG antibodies, have undetectable level or might have disappeared during the post-covid period. Comparison of seropositivity with age group and clinical case details clearly suggest close correlation with the severity of clinical symptoms. The seronegative cases indicate the need for further in-depth scientific research to identify the factors affecting immunity and to uncover the reasons behind the same.

Draft Genome Sequences of Two Enteroinvasive Escherichia coli Strains Representative of Major Enteroinvasive E. coli Clades

There are six described pathotypes of Escherichia coli that cause significant clinical illness in humans. Enteroinvasive E. coli (EIEC) strains have been shown to be separated into three phylogenomic clades. To add to a limited body of EIEC genomic data, we report two high-quality draft genomes representing different EIEC phylogenomic clades.

BET 1: Do homemade or cloth face masks work as a preventive measure for respiratory virus transmission?

A short-cut review of the available medical literature was carried out to establish whether homemade or cloth face masks can prevent respiratory virus transmission or clinical illness. After abstract review, twelve papers were found to answer this clinical question using the detailed search strategy. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of these papers are tabulated. It is concluded that there is currently no direct evidence to support the use of homemade or cloth masks by the general public for protection against viral infections.

Tick-Borne Encephalitis Vaccination Protects from Alimentary TBE Infection: Results from an Alimentary Outbreak

In May 2017, a hospitalized index case of tick-borne encephalitis (TBE) was confirmed by Serology. The case was linked to alimentary infection by raw milk from a goat farm in the region of Tübingen, Baden-Württemberg, Germany, where no previous TBE cases in the area had been reported before. The TBE focus was confirmed by isolation of the TBE virus from ticks and Serological confirmation of past infection in one of the five flock goats. Additional investigations by the local public health office identified 27 consumers of goat milk at the putative period of exposure. For 20/27 exposed persons, anamnestic information was gained by the local public health office. Twelve/fourteen exposed and non-vaccinated people developed clinical illness and were confirmed as TBE cases by Serology. Five/six vaccinated and exposed people did not develop the disease. The one exposed and vaccinated person had their last TBE vaccination booster more than 15 years ago, and therefore a booster was more than 10 years overdue. None of the regularly vaccinated and exposed persons developed clinical overt TBE infection. We report the first known TBE outbreak, during which, protection by TBE vaccination against alimentary TBE infection was demonstrated.