Antibody therapy reverses biological signatures of COVID-19 progression

Understanding who is at risk of progression to severe COVID-19 is key to effective treatment. We studied correlates of disease severity in the COMET-ICE clinical trial that randomized 1:1 to placebo or to sotrovimab, a monoclonal antibody for the treatment of SARS-CoV-2 infection. Several laboratory parameters identified study participants at greater risk of severe disease, including a high neutrophil-lymphocyte ratio (NLR), a negative SARS-CoV-2 serologic test and whole blood transcriptome profiles. Sotrovimab treatment in these groups was associated with normalization of NLR and the transcriptomic profile, and with a decrease of viral RNA in nasopharyngeal samples. Transcriptomics provided the most sensitive detection of participants who would go on to be hospitalized or die. To facilitate timely measurement, we identified a 10-gene signature with similar predictive accuracy. In summary, we identified markers of risk for disease progression and demonstrated that normalization of these parameters occurs with antibody treatment of established infection.

Pathology and Immunity After SARS-CoV-2 Infection in Male Ferrets Is Affected by Age and Inoculation Route

Improving COVID-19 intervention strategies partly relies on animal models to study SARS-CoV-2 disease and immunity. In our pursuit to establish a model for severe COVID-19, we inoculated young and adult male ferrets intranasally or intratracheally with SARS-CoV-2. Intranasal inoculation established an infection in all ferrets, with viral dissemination into the brain and gut. Upon intratracheal inoculation only adult ferrets became infected. However, neither inoculation route induced observable COVID-19 symptoms. Despite this, a persistent inflammation in the nasal turbinates was prominent in especially young ferrets and follicular hyperplasia in the bronchi developed 21 days post infection. These effects -if sustained- might resemble long-COVID. Respiratory and systemic cellular responses and antibody responses were induced only in animals with an established infection. We conclude that intranasally-infected ferrets resemble asymptomatic COVID-19 and possibly aspects of long-COVID. Combined with the increasing portfolio to measure adaptive immunity, ferrets are a relevant model for SARS-CoV-2 vaccine research.

Approaches to Integrated Parasite Management (IPM) for Theileria orientalis with an Emphasis on Immunity

Integrated parasite management (IPM) for pests, pathogens and parasites involves reducing or breaking transmission to reduce the impact of infection or infestation. For Theileria orientalis, the critical impact of infection is the first wave of parasitaemia from the virulent genotypes, Ikeda and Chitose, associated with the sequelae from the development of anaemia. Therefore, current control measures for T. orientalis advocate excluding the movement of naïve stock from non-endemic regions into infected areas and controlling the tick Haemaphysalislongicornis, the final host. In Australia, treatment of established infection is limited to supportive therapy. To update and expand these options, this review examines progress towards prevention and therapy for T. orientalis, which are key elements for inclusion in IPM measures to control this parasite.

Pathology and immunity after SARS-CoV-2 infection in male ferrets is affected by age and inoculation route

Improving COVID-19 intervention strategies partly relies on animal models to study SARS-CoV-2 disease and immunity. In our pursuit to establish a model for severe COVID-19, we inoculated young and adult male ferrets intranasally or intratracheally with SARS-CoV-2. Intranasal inoculation established an infection in all ferrets, with viral dissemination into the brain and gut. Upon intratracheal inoculation only adult ferrets became infected. However, neither inoculation route induced observable COVID-19 symptoms. Despite this, a persistent inflammation in the nose was prominent in especially young ferrets and follicular hyperplasia in the bronchi developed 21 days post infection. These effects -if sustained- might resemble long-COVID. Respiratory and systemic cellular responses and antibody responses were induced only in animals with an established infection. We conclude that intranasally-infected ferrets resemble asymptomatic COVID-19 and possibly aspects of long-COVID. Combined with the increasing portfolio to measure adaptive immunity, ferrets are a relevant model for SARS-CoV-2 vaccine research.

Double-Stranded RNA Targeting Dicer-Like Genes Compromises the Pathogenicity of Plasmopara viticola on Grapevine

Downy mildew caused by Plasmopara viticola is one of the most devastating diseases of grapevine, attacking all green parts of the plant. The damage is severe when the infection at flowering stage is left uncontrolled. P. viticola management consumes a significant amount of classical pesticides applied in vineyards, requiring efficient and environmentally safe disease management options. Spray-induced gene silencing (SIGS), through the application of exogenous double-stranded RNA (dsRNA), has shown promising results for the management of diseases in crops. Here, we developed and tested the potential of dsRNA targeting P. viticola Dicer-like (DCL) genes for SIGS-based crop protection strategy. The exogenous application of PvDCL1/2 dsRNA, a chimera of PvDCL1 and PvDCL2, highly affected the virulence of P. viticola. The reduced expression level of PvDCL1 and PvDCL2 transcripts in infected leaves, treated with PvDCL1/2 dsRNA, was an indication of an active RNA interference mechanism inside the pathogen to compromise its virulence. Besides the protective property, the PvDCL1/2 dsRNA also exhibited a curative role by reducing the disease progress rate of already established infection. Our data provide a promising future for PvDCL1/2 dsRNA as a new generation of RNA-based resistant plants or RNA-based agrochemical for the management of downy mildew disease in grapevine.

Live imaging of SARS-CoV-2 infection in mice reveals neutralizing antibodies require Fc function for optimal efficacy

Neutralizing antibodies (NAbs) are effective in treating COVID-19 but the mechanism of immune protection is not fully understood. Here, we applied live bioluminescence imaging (BLI) to monitor the real-time effects of NAb treatment in prophylaxis and therapy of K18-hACE2 mice intranasally infected with SARS-CoV-2-nanoluciferase. We visualized sequential spread of virus from the nasal cavity to the lungs followed by systemic spread to various organs including the brain, culminating in death. Highly potent NAbs from a COVID-19 convalescent subject prevented, and also effectively resolved, established infection when administered within three days of infection. In addition to direct neutralization, in vivo efficacy required Fc effector functions of NAbs, with contributions from monocytes, neutrophils and natural killer cells, to dampen inflammatory responses and limit immunopathology. Thus, our study highlights the requirement of both Fab and Fc effector functions for an optimal in vivo efficacy afforded by NAbs against SARS-CoV-2.

Mechanisms of infection by SARS-CoV-2, inflammation and potential links with the microbiome

The pandemic SARS coronavirus 2 utilizes efficient mechanisms to establish infection and evade the immune system. Established infection leads to severe inflammation in susceptible patients, the main hallmark of progression to severe coronavirus disease (COVID-19). Knowledge of the mechanisms of disease has expanded rapidly. As inflammation emerges as the central pathophysiological feature in COVID-19, elucidating how the immune system, lungs and gut communicate and interact with microbial components of the ecological niches that conform the human microbiome will shed light on how inflammation and disease progression are promoted. Studying the microbiome in COVID-19 could allow scientists to identify novel approaches to prevent severe inflammation by targeting components of the human microbiome. Innovation in the aforementioned is needed to combat this pandemic.

Infection Control in the Era of Antimicrobial Resistance in China: Progress, Challenges, and Opportunities

More than 3 decades have passed since infection control was implemented nationwide in China in 1986. A comprehensive set of regulations and guidelines has been developed, and almost all hospitals have established infection control teams. However, compliance is variable and is usually suboptimal. The incidence of certain multidrug-resistant organisms (MDROs), including carbapenem-resistant Acinetobacter baumannii (CRAB) and carbapenem-resistant Klebsiella pneumoniae (CRKP), is increasing, and associated infections are mainly hospital-acquired in China. Carbapenem-resistant Pseudomonas aeruginosa has remained relatively stable, whereas methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterobacter faecium have been decreasing. The spread of CRAB and CRKP in China is largely mediated by dominant high-risk lineages, namely, clonal complex 92 for CRAB and sequence type 11 for CRKP. However, challenges owing to MDROs bring opportunities for rethinking, taking coordinated action, building capacity, changing behavior, and performing studies that reflect everyday situations in the Chinese healthcare system.

We must rigorously follow basic infection control procedures to protect our healthcare workers from SARS-CoV-2

Because severe acute respiratory coronavirus virus 2 (SARS-CoV-2) spreads easily and healthcare workers are at increased risk of both acquiring and transmitting infection, all healthcare facilities must rapidly and rigorously implement the full hierarchy of established infection controls: source control (removal or mitigation of infection sources), engineering and environmental controls, administrative controls, and personal protective equipment.

Infection

Infection is the most feared and challenging complication in the treatment of open tibial fractures. Microorganisms can adhere as a biofilm on the surface of damaged bone, necrotic tissue, and internal fixation devices, and become resistant to phagocytosis and most antimicrobial agents. Established infection can delay healing and recovery, cause permanent functional loss, and potentially lead to amputation of the affected limb. The incidence of infection after severe open tibial fractures was reported to be over 30% in the 1980s and 1990s. Although there is evidence of a possible reduction in incidence in the past decade, the Lower Extremity Assessment Project (LEAP) study has shown that severe lower extremity trauma continues to be associated with infective complications necessitating additional operative treatment in a significant number of cases. Furthermore, greater bacterial virulence and increasing age and associated co-morbidities of the fracture population ensure that infection after open trauma remains a challenge.