Emerging Viruses: Coming in on a Wrinkled Wing and a Prayer

The role that bats have played in the emergence of several new infectious diseases has been under review. Bats have been identified as the reservoir hosts of newly emergent viruses such as Nipah virus, Hendra virus, and severe acute respiratory syndrome–like coronaviruses. This article expands on recent findings about bats and viruses and their relevance to human infections. It briefly reviews the history of chiropteran viruses and discusses their emergence in the context of geography, phylogeny, and ecology. The public health and trade impacts of several outbreaks are also discussed. Finally, we attempt to predict where, when, and why we may see the emergence of new chiropteran viruses

Cefiderocol for the Treatment of Adult and Pediatric Patients with Cystic Fibrosis and Achromobacter xylosoxidans Infections

Treatment options for Achromobacter xylosoxidans are limited. Eight cystic fibrosis patients with A. xylosoxidans were treated with 12 cefiderocol courses. Pretreatment in vitro resistance was seen in 3 of 8 cases. Clinical response occurred after 11 of 12 treatment courses. However, microbiologic relapse was observed after 11 of 12 treatment courses, notably without emergence of resistance

SARS-CoV-2-specific nasal IgA wanes 9 months after hospitalisation with COVID-19 and is not induced by subsequent vaccination

BACKGROUND: Most studies of immunity to SARS-CoV-2 focus on circulating antibody, giving limited insights into mucosal defences that prevent viral replication and onward transmission. We studied nasal and plasma antibody responses one year after hospitalisation for COVID-19, including a period when SARS-CoV-2 vaccination was introduced. METHODS: In this follow up study, plasma and nasosorption samples were prospectively collected from 446 adults hospitalised for COVID-19 between February 2020 and March 2021 via the ISARIC4C and PHOSP-COVID consortia. IgA and IgG responses to NP and S of ancestral SARS-CoV-2, Delta and Omicron (BA.1) variants were measured by electrochemiluminescence and compared with plasma neutralisation data. FINDINGS: Strong and consistent nasal anti-NP and anti-S IgA responses were demonstrated, which remained elevated for nine months (p < 0.0001). Nasal and plasma anti-S IgG remained elevated for at least 12 months (p < 0.0001) with plasma neutralising titres that were raised against all variants compared to controls (p < 0.0001). Of 323 with complete data, 307 were vaccinated between 6 and 12 months; coinciding with rises in nasal and plasma IgA and IgG anti-S titres for all SARS-CoV-2 variants, although the change in nasal IgA was minimal (1.46-fold change after 10 months, p = 0.011) and the median remained below the positive threshold determined by pre-pandemic controls. Samples 12 months after admission showed no association between nasal IgA and plasma IgG anti-S responses (R = 0.05, p = 0.18), indicating that nasal IgA responses are distinct from those in plasma and minimally boosted by vaccination. INTERPRETATION: The decline in nasal IgA responses 9 months after infection and minimal impact of subsequent vaccination may explain the lack of long-lasting nasal defence against reinfection and the limited effects of vaccination on transmission. These findings highlight the need to develop vaccines that enhance nasal immunity. FUNDING: This study has been supported by ISARIC4C and PHOSP-COVID consortia. ISARIC4C is supported by grants from the National Institute for Health and Care Research and the Medical Research Council. Liverpool Experimental Cancer Medicine Centre provided infrastructure support for this research. The PHOSP-COVD study is jointly funded by UK Research and Innovation and National Institute of Health and Care Research. The funders were not involved in the study design, interpretation of data or the writing of this manuscript

Large-scale phenotyping of patients with long COVID post-hospitalization reveals mechanistic subtypes of disease

One in ten severe acute respiratory syndrome coronavirus 2 infections result in prolonged symptoms termed long coronavirus disease (COVID), yet disease phenotypes and mechanisms are poorly understood1. Here we profiled 368 plasma proteins in 657 participants ≥3 months following hospitalization. Of these, 426 had at least one long COVID symptom and 233 had fully recovered. Elevated markers of myeloid inflammation and complement activation were associated with long COVID. IL-1R2, MATN2 and COLEC12 were associated with cardiorespiratory symptoms, fatigue and anxiety/depression; MATN2, CSF3 and C1QA were elevated in gastrointestinal symptoms and C1QA was elevated in cognitive impairment. Additional markers of alterations in nerve tissue repair (SPON-1 and NFASC) were elevated in those with cognitive impairment and SCG3, suggestive of brain–gut axis disturbance, was elevated in gastrointestinal symptoms. Severe acute respiratory syndrome coronavirus 2-specific immunoglobulin G (IgG) was persistently elevated in some individuals with long COVID, but virus was not detected in sputum. Analysis of inflammatory markers in nasal fluids showed no association with symptoms. Our study aimed to understand inflammatory processes that underlie long COVID and was not designed for biomarker discovery. Our findings suggest that specific inflammatory pathways related to tissue damage are implicated in subtypes of long COVID, which might be targeted in future therapeutic trials

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

The interaction effect of carbon dioxide and ethylene in the storage atmosphere on potato fry color is dose-related

Previous studies have shown that the fry color of stored potatoes (Solanum tuberosum L.) can be negatively affected by an interaction between elevated CO2 (2 kPa) and ethylene gas (0.5 mLL–1) from various sources. Two consecutive trials were conducted during each of two storage seasons (2006 and 2007) to study the effects of varying concentrations of these two gases. In each year, CO2 at 0, 0.5, 1.0, or 2.0 kPa plus 0, 0.25, or 0.5 mLL–1 ethylene was applied in a factorial design to ‘Russet Burbank’ tubers for 9 weeks. Trials that began in Jan. 2006 and Jan. 2007 comprised the dormanttuber experiment; trials that began in Apr. 2006 and Apr. 2007 comprised the nondormant-tuber experiment. Fry color of the tubers was evaluated at the start of each trial and thereafter at intervals of 3 weeks. In all trials, when tubers were exposed to different concentrations of CO2 but without ethylene, fry color was the same as in untreated controls. When only ethylene was applied, the fry color was 7 to 22 Agtron percent reflectance units darker than the controls. In the nondormant-tuber experiment, the darkening resulting from ethylene was dose-related, in agreement with previous research. When the tubers were exposed to both CO2 and ethylene, dose-related responses to both gases were observed in the nondormant-tuber experiment, i.e., fry color was darker with an increase in either CO2 or ethylene when both gases were present. Neither the dose–response to ethylene nor the interaction between ethylene and CO2 was statistically significant in the dormant-tuber experiment. In both experiments, the darkest color was observed when both gases were present at the highest concentrations. A dose–response of potato fry color to CO2 in the presence of ethylene has not been reported previously

The interaction effect of carbon dioxide and ethylene in the storage atmosphere on potato fry color is dose-related

Previous studies have shown that the fry color of stored potatoes (Solanum tuberosum L.) can be negatively affected by an interaction between elevated CO2 (2 kPa) and ethylene gas (0.5 mLL–1) from various sources. Two consecutive trials were conducted during each of two storage seasons (2006 and 2007) to study the effects of varying concentrations of these two gases. In each year, CO2 at 0, 0.5, 1.0, or 2.0 kPa plus 0, 0.25, or 0.5 mLL–1 ethylene was applied in a factorial design to ‘Russet Burbank’ tubers for 9 weeks. Trials that began in Jan. 2006 and Jan. 2007 comprised the dormanttuber experiment; trials that began in Apr. 2006 and Apr. 2007 comprised the nondormant-tuber experiment. Fry color of the tubers was evaluated at the start of each trial and thereafter at intervals of 3 weeks. In all trials, when tubers were exposed to different concentrations of CO2 but without ethylene, fry color was the same as in untreated controls. When only ethylene was applied, the fry color was 7 to 22 Agtron percent reflectance units darker than the controls. In the nondormant-tuber experiment, the darkening resulting from ethylene was dose-related, in agreement with previous research. When the tubers were exposed to both CO2 and ethylene, dose-related responses to both gases were observed in the nondormant-tuber experiment, i.e., fry color was darker with an increase in either CO2 or ethylene when both gases were present. Neither the dose–response to ethylene nor the interaction between ethylene and CO2 was statistically significant in the dormant-tuber experiment. In both experiments, the darkest color was observed when both gases were present at the highest concentrations. A dose–response of potato fry color to CO2 in the presence of ethylene has not been reported previously