BOOSTER VACCINATION AGAINST SARS-CoV-2: CURRENT CHALLENGES AND SOLUTIONS.

The COVID-19 pandemic is going on, which makes it crucial to prevent the spread of coronavirus disease. Vaccination is the only way of specific prevention of COVID-19. The SARS-CoV-2 virus is continuously evolving and new variants appear. Moreover, the effectiveness of protective immunity after vaccination tends to decrease over several months. Booster vaccination may be the solution to these problems. The booster is an extra vaccination that helps to reactivate the immunity against COVID-19. Booster doses can be homologous (the same as the primary vaccine) and heterologous (different from the primary vaccine). It is of current interest to study heterologous vaccination as the injection of different vaccines may result in a more intense immune response. Furthermore, the same vaccine may not be available at the time of booster vaccination. This review is aimed at summarizing the key research findings in the field of booster vaccination against COVID-19.Copyright © 2022 Booster vaccination against. All rights reserved.

Architecture of the SARS-CoV-2-specific T cell repertoire.

The T cell response plays an indispensable role in the early control and successful clearance of SARS-CoV-2 infection. However, several important questions remain about the role of cellular immunity in COVID-19, including the shape and composition of disease-specific T cell repertoires across convalescent patients and vaccinated individuals, and how pre-existing T cell responses to other pathogens-in particular, common cold coronaviruses-impact susceptibility to SARS-CoV-2 infection and the subsequent course of disease. This review focuses on how the repertoire of T cell receptors (TCR) is shaped by natural infection and vaccination over time. We also summarize current knowledge regarding cross-reactive T cell responses and their protective role, and examine the implications of TCR repertoire diversity and cross-reactivity with regard to the design of vaccines that confer broader protection against SARS-CoV-2 variants.

Detection of coronaviruses in insectivorous bats of Fore-Caucasus, 2021.

Coronaviruses (CoVs) pose a huge threat to public health as emerging viruses. Bat-borne CoVs are especially unpredictable in their evolution due to some unique features of bat physiology boosting the rate of mutations in CoVs, which is already high by itself compared to other viruses. Among bats, a meta-analysis of overall CoVs epizootiology identified a nucleic acid observed prevalence of 9.8% (95% CI 8.7-10.9%). The main objectives of our study were to conduct a qPCR screening of CoVs' prevalence in the insectivorous bat population of Fore-Caucasus and perform their characterization based on the metagenomic NGS of samples with detected CoV RNA. According to the qPCR screening, CoV RNA was detected in 5 samples, resulting in a 3.33% (95% CI 1.1-7.6%) prevalence of CoVs in bats from these studied locations. BetaCoVs reads were identified in raw metagenomic NGS data, however, detailed characterization was not possible due to relatively low RNA concentration in samples. Our results correspond to other studies, although a lower prevalence in qPCR studies was observed compared to other regions and countries. Further studies should require deeper metagenomic NGS investigation, as a supplementary method, which will allow detailed CoV characterization.

Bacteriophage Cocktails in the Post-COVID Rehabilitation.

Increasing evidence suggests that gut dysbiosis is associated with coronavirus disease 2019 (COVID-19) infection and may persist long after disease resolution. The excessive use of antimicrobials in patients with COVID-19 can lead to additional destruction of the microbiota, as well as to the growth and spread of antimicrobial resistance. The problem of bacterial resistance to antibiotics encourages the search for alternative methods of limiting bacterial growth and restoring the normal balance of the microbiota in the human body. Bacteriophages are promising candidates as potential regulators of the microbiota. In the present study, two complex phage cocktails targeting multiple bacterial species were used in the rehabilitation of thirty patients after COVID-19, and the effectiveness of the bacteriophages against the clinical strain of Klebsiella pneumoniae was evaluated for the first time using real-time visualization on a 3D Cell Explorer microscope. Application of phage cocktails for two weeks showed safety and the absence of adverse effects. An almost threefold statistically significant decrease in the anaerobic imbalance ratio, together with an erythrocyte sedimentation rate (ESR), was detected. This work will serve as a starting point for a broader and more detailed study of the use of phages and their effects on the microbiome.

BOOSTER VACCINATION AGAINST SARS-CoV-2: CURRENT CHALLENGES AND SOLUTIONS

The COVID-19 pandemic is going on, which makes it crucial to prevent the spread of coronavirus disease. Vaccination is the only way of specific prevention of COVID-19. The SARS-CoV-2 virus is continuously evolving and new variants appear. Moreover, the effectiveness of protective immunity after vaccination tends to decrease over several months. Booster vaccination may be the solution to these problems. The booster is an extra vaccination that helps to reactivate the immunity against COVID-19. Booster doses can be homologous (the same as the primary vaccine) and heterologous (different from the primary vaccine). It is of current interest to study heterologous vaccination as the injection of different vaccines may result in a more intense immune response. Furthermore, the same vaccine may not be available at the time of booster vaccination. This review is aimed at summarizing the key research findings in the field of booster vaccination against COVID-19. © 2022 Booster vaccination against. All rights reserved.

Serosurvey of Selected Zoonotic Pathogens in Polar Bears (Ursus maritimus Phipps, 1774) in the Russian Arctic

Antibodies to several pathogens were detected in the serum samples of nine polar bears (Ursus maritimus, Phipps, 1774) from areas of the Russian Arctic. Plasma was studied for antibodies to sixteen infectious and parasitic diseases using indirect Protein-A ELISA. It is known that when using ELISA, the interaction of antibodies with a heterologous antigen is possible due to immunological crossings between antigens. We investigated the plasma for the presence of antibodies to the major pathogens and for the presence of antibodies to pathogens, for which the cross-immunological reactions to these pathogens are described. For example, antibodies to the pathogens of opisthorchiasis, clonorchiasis, and ascariasis were found simultaneously in four polar bears. Antibodies to both anisakidosis and trichinellosis pathogens were found in six animals. The data obtained may also indicate a joint invasion by these pathogens. Unfortunately, due to the small number of animals sampled, it is impossible to carry out statistical processing of the data.

Case Report: COVID-19-Associated ROHHAD-Like Syndrome.

It is known that the SARS-CoV-2 virus may cause neurologic damage. Rapid-onset obesity, hypoventilation, hypothalamus dysfunction, and autonomic dysregulation (ROHHAD) syndrome is a disease of unknown etiology with a progressive course and unclear outcomes. The etiology of ROHHAD syndrome includes genetic, epigenetic, paraneoplastic, and immune-mediated theories, but to our knowledge, viral-associated cases of the disease have not been described yet. Here we present the case of a 4-year-old girl who developed a ROHHAD syndrome-like phenotype after a COVID-19 infection and the results of 5 months of therapy. She had COVID-19 pneumonia, followed by electrolyte disturbances (hypernatremia and hyperchloremia), hypocorticism and hypothyroidism, central hypoventilation-requiring prolonged assisted lung ventilation-bulimia, and progressive obesity with hypertriglyceridemia, dyslipidemia, hyperuricemia, and hyperinsulinemia. The repeated MRI of the brain and hypothalamic-pituitary region with contrast enhancement showed mild post-hypoxic changes. Prader-Willi/Angelman syndrome as well as PHOX2B-associated variants was ruled out. Treatment with non-steroidal anti-inflammatory drugs and monthly courses of intravenous immunoglobulin led to a dramatic improvement. Herein the first description of ROHHAD-like syndrome is timely associated with a previous COVID-19 infection with possible primarily viral or immune-mediated hypothalamic involvement.

Estimating relative abundance of two SARS-CoV-2 variants through wastewater surveillance at two large metropolitan sites (preprint)

Monitoring SARS-CoV-2 variants of concern (VOCs) is critical for public health management of COVID-19. Case isolate sequencing is resource-intensive and not all isolates can be sequenced, and thus are not representative. However, since wastewater SARS-CoV-2 RNA concentrations correlate with COVID-19 case incidence in sewersheds, tracking VOCs through wastewater is appealing. We developed targeted digital RT-PCR assays to monitor abundance of select mutations in Alpha and Delta VOCs in wastewater settled solids, applied these to July 2020-August 2021 samples from two large metropolitan sewersheds, and compared results to estimates of variant abundance from case isolate sequencing. Wastewater measurements tracked closely with case isolate estimates at each site (rp= 0.82, 0.88 for Alpha and rp= 0.97 for Delta). Mutations were detected in wastewater measurements even at levels <5% of circulating virus and in samples available weeks before case isolate results. Therefore, wastewater variant monitoring should be strategically deployed to complement case isolate sequencing.

Isolation of a panel of ultra-potent human antibodies neutralizing SARS-CoV-2 and viral variants of concern.

In the absence of virus-targeting small-molecule drugs approved for the treatment and prevention of COVID-19, broadening the repertoire of potent SARS-CoV-2-neutralizing antibodies represents an important area of research in response to the ongoing pandemic. Systematic analysis of such antibodies and their combinations can be particularly instrumental for identification of candidates that may prove resistant to the emerging viral escape variants. Here, we isolated a panel of 23 RBD-specific human monoclonal antibodies from the B cells of convalescent patients. A surprisingly large proportion of such antibodies displayed potent virus-neutralizing activity both in vitro and in vivo. Four of the isolated nAbs can be categorized as ultrapotent with an apparent IC100 below 16 ng/mL. We show that individual nAbs as well as dual combinations thereof retain activity against currently circulating SARS-CoV-2 variants of concern (such as B.1.1.7, B.1.351, B.1.617, and C.37), as well as against other viral variants. When used as a prophylactics or therapeutics, these nAbs could potently suppress viral replication and prevent lung pathology in SARS-CoV-2-infected hamsters. Our data contribute to the rational development of oligoclonal therapeutic nAb cocktails mitigating the risk of SARS-CoV-2 escape.

High frequency, high throughput quantification of SARS-CoV-2 RNA in wastewater settled solids at eight publicly owned treatment works in Northern California shows strong association with COVID-19 incidence (preprint)

A number of recent retrospective studies have demonstrated that SARS-CoV-2 RNA concentrations in wastewater are associated with COVID-19 cases in the corresponding sewersheds. Implementing high-resolution, prospective efforts across multiple plants depends on sensitive measurements that are representative of COVID-19 cases, scalable for high throughput analysis, and comparable across laboratories. We conducted a prospective study across eight publicly owned treatment works (POTWs). A focus on SARS-CoV-2 RNA in solids enabled us to scale-up our measurements with a commercial lab partner. Samples were collected daily and results were posted to a website within 24-hours. SARS-CoV-2 RNA in daily samples correlated to incidence COVID-19 cases in the sewersheds; a 1 log 10 increase in SARS-CoV-2 RNA in settled solids corresponds to a 0.58 log 10 (4X) increase in sewershed incidence rate. SARS-CoV-2 RNA signals measured with the commercial laboratory partner were comparable across plants and to measurements conducted in a university laboratory when normalized by pepper mild mottle virus PMMoV RNA. Results suggest that SARS-CoV-2 RNA should be detectable in settled solids for COVID-19 incidence rates > 1/100,000 (range 0.8 - 2.3 cases per 100,000). These sensitive, representative, scalable, and comparable methods will be valuable for future efforts to scale-up wastewater-based epidemiology. Importance Access to reliable, rapid monitoring data is critical to guide response to an infectious disease outbreak. For pathogens that are shed in feces or urine, monitoring wastewater can provide a cost-effective snapshot of transmission in an entire community via a single sample. In order for a method to be useful for ongoing COVID-19 monitoring, it should be sensitive for detection of low concentrations of SARS-CoV-2, representative of incidence rates in the community, scalable to generate data quickly, and comparable across laboratories. This paper presents a method utilizing wastewater solids to meet these goals, producing measurements of SARS-CoV-2 RNA strongly associated with COVID-19 cases in the sewershed of a publicly owned treatment work. Results, provided within 24 hrs, can be used to detect incidence rates as low as approximately 1/100,000 cases and can be normalized for comparison across locations generating data using different methods.

A Genomic Survey of SARS-CoV-2 Reveals Multiple Introductions into Northern California without a Predominant Lineage (preprint)

The COVID-19 pandemic caused by the novel coronavirus SARS-CoV-2 has spread globally, resulting in >300,000 reported cases worldwide as of March 21st, 2020. Here we investigate the genetic diversity and genomic epidemiology of SARS-CoV-2 in Northern California using samples from returning travelers, cruise ship passengers, and cases of community transmission with unclear infection sources. Virus genomes were sampled from 29 patients diagnosed with COVID-19 infection from Feb 3rd through Mar 15th. Phylogenetic analyses revealed at least 8 different SARS-CoV-2 lineages, suggesting multiple independent introductions of the virus into the state. Virus genomes from passengers on two consecutive excursions of the Grand Princess cruise ship clustered with those from an established epidemic in Washington State, including the WA1 genome representing the first reported case in the United States on January 19th. We also detected evidence for presumptive transmission of SARS-CoV-2 lineages from one community to another. These findings suggest that cryptic transmission of SARS-CoV-2 in Northern California to date is characterized by multiple transmission chains that originate via distinct introductions from international and interstate travel, rather than widespread community transmission of a single predominant lineage. Rapid testing and contact tracing, social distancing, and travel restrictions are measures that will help to slow SARS-CoV-2 spread in California and other regions of the USA.

Biodiversity and epidemic potential of Chiropteran coronaviruses (Nidovirales: Coronaviridae)

Aim. The aim of this review is a comprehensive analysis of current literature data on coronaviruses identified in bats. Discussion. Coronaviruses (Coronaviridae) constitute the most extensive family of viruses of the order Nidovirales. Coronaviruses have a wide range of hosts, including mammals (Alpha coronavirus, Betacoronavirus, Deltacoronavirus, Gamn7acoronavirus) and birds (Deltacoronavirus, Garnmacoronavirus), amphibians (Alphaietovirus) and are pathogens of respiratory, intestinal, cardiovascular. Until the beginning of this century, only etiological agents of mild and moderate respiratory diseases were known among pathogenic coronaviruses for humans. In the 21st century, new highly pathogenic coronaviruses were discovered that caused outbreaks of severe pneumonia with high mortality: the severe acute respiratory syndrome coronavirus (Severe acute respiratory syndrome-related coronavirus, SARS-CoV;2002-2003, southern provinces of China), the Middle East respiratory coronavirus Syndrome (Middle East respiratory syndrome-related coronavirus, MERS-CoV;2012, western part of Saudi Arabia) and type 2 acute respiratory syndrome coronavirus (Severe acute respiratory syndrome-related coronavirus 2, SARS-CoV-2;2019 -..., the eastern part of central China). The natural reservoirs of SARS-CoV, SARS-CoV-2 and MERS-CoV are bats (Chiroptera). Coronaviruses circulating in bat populations are not only phylogenetically close to the currently known especially dangerous human viruses but probably have epidemic potential that can be realized in the future. Conclusion. This review presents current data on coronaviruses of bats: taxonomic status, spectrum of potential hosts, distribution. The ecological features of coronaviruses of bats are considered in the context of their epidemiological significance. The origin of pathogenic human coronaviruses is discussed.