Proinflammatory IgG Fc structures in patients with severe COVID-19.

Severe acute respiratory syndrome coronavirus 2 infections can cause coronavirus disease 2019 (COVID-19), which manifests with a range of severities from mild illness to life-threatening pneumonia and multi-organ failure. Severe COVID-19 is characterized by an inflammatory signature, including high levels of inflammatory cytokines, alveolar inflammatory infiltrates and vascular microthrombi. Here we show that patients with severe COVID-19 produced a unique serologic signature, including an increased likelihood of IgG1 with afucosylated Fc glycans. This Fc modification on severe acute respiratory syndrome coronavirus 2 IgGs enhanced interactions with the activating Fcγ receptor FcγRIIIa; when incorporated into immune complexes, Fc afucosylation enhanced production of inflammatory cytokines by monocytes, including interleukin-6 and tumor necrosis factor. These results show that disease severity in COVID-19 correlates with the presence of proinflammatory IgG Fc structures, including afucosylated IgG1.

No neonates without adults: A review of adult black soldier fly biology, Hermetia illucens (Diptera: Stratiomyidae): A review of adult black soldier fly biology, Hermetia illucens (Diptera: Stratiomyidae).

With the potential to process the world's agricultural and food waste, provide sustainable fodder for livestock, aquaculture, and pet animals, as well as act as a source of novel biomolecules, the black soldier fly, Hermetia illucens, has been launched into the leading position within the insects as feed industry. Fulfilment of these goals, however, requires mass-rearing facilities to have a steady supply of neonate larvae, which in-turn requires an efficient mating process to yield fertile eggs; yet, little is known about adult reproductive behavior, nor what physiological factors lead to its emergence. Moreover, fertile egg production tends to be highly variable in colony. Therefore, this review brings together what is currently known of the organismal biology of H. illucens, compiling information on adult morphology, physiology, biogeography, genomics, and behavioral ecology. As a holistic synthesis, it highlights several directions of interest for research to follow.

Whole-genome sequencing of two captive black soldier fly populations: Implications for commercial production.

Black soldier fly (BSF; Hermetia illucens) is a promising insect species for food and feed production as its larvae can convert different organic waste to high-value protein. Selective breeding is one way to optimize production, but the potential of breeding is only starting to be explored and not yet utilized for BSF. To assist in monitoring a captive population and implementing a breeding program, genomics tools are imperative. We conducted whole genome sequencing of two captive populations separated by geographical distance - Denmark (DK) and Texas, USA (TX). Various population genetics analyses revealed a moderate genetic differentiation between two populations. Moreover, we observed higher inbreeding in the DK population, and the detection of a subpopulation within DK population aligned well with the recent foundation of the DK population from two captive populations. Additionally, we generated gene ontology annotation and variants annotation for wider potential applications. Our findings establish a robust marker set for research in population genetics, facilitating the monitoring of inbreeding and laying the groundwork for practical breeding programs for BSF.

Recommendations and requirements for the wavelengths in Rayleigh equation anomaloscopes.

DIN 6160:2019 is a technical standard that sets requirements for Rayleigh equation anomaloscopes. Table 1 of the standard contains the limits for centroid wavelengths and spectral half power bandwidths (SHBW). The centroid limits are more restrictive than dominant wavelength recommendations. The SHBW limits have no known evidence base and are inconsistent between colors. The spectral characteristics of three commercial anomaloscopes brands were measured using a telespectroradiometer. Only the oculus instruments complied with DIN 6160 Table 1, but all the anomaloscopes complied with published recommendations. All complied with the DIN 6160 bandwidth requirements. This highlights the need to provide an evidence base for such requirements.

Clinical analysis of the Konan-Waggoner D15 color vision test using the Surface-Pro display.

This work expands on our previous comparison of the Konan-Waggoner D15 (KW-D15) and Farnsworth D15 (F-D15). Sixty subjects with normal color vision and 68 subjects with a red-green color vision defect participated in the study. The KW-D15 had good agreement with the F-D15 for both pass/fail and classification across all failure criteria. The agreement was slightly better if subjects had to pass on 2/3 trials compared with just the first trial. The KW-D15 is an adequate substitute for the F-D15, with the caveat that the KW-D15 might be slightly easier to pass than the F-D15 for deutans.

Insights into the reduction of antibiotic-resistant bacteria and mobile antibiotic resistance genes by black soldier fly larvae in chicken manure.

The increasing prevalence of antibiotic-resistant bacteria (ARB) from animal manure has raised concerns about the potential threats to public health. The bioconversion of animal manure with insect larvae, such as the black soldier fly larvae (BSFL, Hermetia illucens [L.]), is a promising technology for quickly attenuating ARB while also recycling waste. In this study, we investigated BSFL conversion systems for chicken manure. Using metagenomic analysis, we tracked ARB and evaluated the resistome dissemination risk by investigating the co-occurrence of antibiotic resistance genes (ARGs), mobile genetic elements (MGEs), and bacterial taxa in a genetic context. Our results indicated that BSFL treatment effectively mitigated the relative abundance of ARB, ARGs, and MGEs by 34.9%, 53.3%, and 37.9%, respectively, within 28 days. Notably, the transferable ARGs decreased by 30.9%, indicating that BSFL treatment could mitigate the likelihood of ARG horizontal transfer and thus reduce the risk of ARB occurrence. In addition, the significantly positive correlation links between antimicrobial concentration and relative abundance of ARB reduced by 44.4%. Moreover, using variance partition analysis (VPA), we identified other bacteria as the most important factor influencing ARB, explaining 20.6% of the ARB patterns. Further analysis suggested that antagonism of other bacteria on ARB increased by 1.4 times, while nutrient competition on both total nitrogen and crude fat increased by 2.8 times. Overall, these findings provide insight into the mechanistic understanding of ARB reduction during BSFL treatment of chicken manure and provide a strategy for rapidly mitigating ARB in animal manure.

Color Vision in the Mountains.

This Lessons from History article uses science, aviation, medicine, and mountaineering sources to describe some of the effects of hypoxia, illumination, and other environmental conditions on the eye, the central nervous system, and light and color perception. The historical perspective is augmented by an analysis of an informal observation of the altered perception of red color on a deck of playing cards while climbing Mera Peak in the Himalaya. The appearance of a grayer red color on the cards was initially attributed to the effects of hypoxia alone. Instead, analysis of cards in combination with the low incidence of protan color vision defects at altitude indicated that glare and contrast effects in the extremely bright lighting environment combined with hypoxia likely caused the perception of a grayer red. The incident provides an educational opportunity for review, analysis, and commentary about some of the complex elements that impact color vision.

Sex Differences in Influenza: The Challenge Study Experience.

BACKGROUND: Preclinical animal studies and retrospective human studies suggest that adult females have worse outcomes from influenza than males. Prospective studies in humans are missing. METHODS: Data from 164 healthy volunteers who underwent influenza A/California/04/2009/H1N1 challenge were compiled to compare differences between sexes. Baseline characteristics, including hormone levels, hemagglutination inhibition (HAI) titers, neuraminidase inhibition (NAI) titers, and outcomes after challenge were compared. Linear and logistic regression models were built to determine significant predictor variables with respect to outcomes of interest. RESULTS: HAI titers were similar between the sexes, but NAI titers were higher in males than females at 4 weeks and 8 weeks postchallenge. Females were more likely to have symptoms (mean, 0.96 vs 0.80; P = .003) and to have a higher number of symptoms (median, 3 vs 4; P = .011) than males. Linear and logistic regression models showed that prechallenge NAI titers, but not HAI titers or sex hormone levels, were predictive of all shedding and symptom outcomes of interest. CONCLUSIONS: Females in our cohorts were more likely to be symptomatic and to have a higher number of symptoms than males. NAI titers predicted all outcomes of interest and may explain differential outcomes between the sexes.

SARS-CoV-2 Cross-Reactivity in Prepandemic Serum from Rural Malaria-Infected Persons, Cambodia.

Inhabitants of the Greater Mekong Subregion in Cambodia are exposed to pathogens that might influence serologic cross-reactivity with severe acute respiratory syndrome coronavirus 2. A prepandemic serosurvey of 528 malaria-infected persons demonstrated higher-than-expected positivity of nonneutralizing IgG to spike and receptor-binding domain antigens. These findings could affect interpretation of large-scale serosurveys.

Establishment of a Pig Influenza Challenge Model for Evaluation of Monoclonal Antibody Delivery Platforms.

mAbs are a possible adjunct to vaccination and drugs in treatment of influenza virus infection. However, questions remain whether small animal models accurately predict efficacy in humans. We have established the pig, a large natural host animal for influenza, with many physiological similarities to humans, as a robust model for testing mAbs. We show that a strongly neutralizing mAb (2-12C) against the hemagglutinin head administered prophylactically at 15 mg/kg reduced viral load and lung pathology after pandemic H1N1 influenza challenge. A lower dose of 1 mg/kg of 2-12C or a DNA plasmid-encoded version of 2-12C reduced pathology and viral load in the lungs but not viral shedding in nasal swabs. We propose that the pig influenza model will be useful for testing candidate mAbs and emerging delivery platforms prior to human trials.

Parenchymal involvement on CT pulmonary angiography in SARS-CoV-2 Alpha variant infection and correlation of COVID-19 CT severity score with clinical disease severity and short-term prognosis in a UK cohort.

AIM: To determine if there is a difference in radiological, biochemical, or clinical severity between patients infected with Alpha-variant SARS-CoV-2 compared with those infected with pre-existing strains, and to determine if the computed tomography (CT) severity score (CTSS) for COVID-19 pneumonitis correlates with clinical severity and can prognosticate outcomes. MATERIALS AND METHODS: Blinded CTSS scoring was applied to 137 hospital patients who had undergone both CT pulmonary angiography (CTPA) and whole-genome sequencing of SARS-CoV-2 within 14 days of CTPA between 1/12/20-5/1/21. RESULTS: There was no evidence of a difference in imaging severity on CTPA, viral load, clinical parameters of severity, or outcomes between Alpha and preceding variants. CTSS on CTPA strongly correlates with clinical and biochemical severity at the time of CTPA, and with patient outcomes. Classifying CTSS into a binary value of "high" and "low", with a cut-off score of 14, patients with a high score have a significantly increased risk of deterioration, as defined by subsequent admission to critical care or death (multivariate hazard ratio [HR] 2.76, p<0.001), and hospital length of stay (17.4 versus 7.9 days, p<0.0001). CONCLUSION: There was no evidence of a difference in radiological severity of Alpha variant infection compared with pre-existing strains. High CTSS applied to CTPA is associated with increased risk of COVID-19 severity and poorer clinical outcomes and may be of use particularly in settings where CT is not performed for diagnosis of COVID-19 but rather is used following clinical deterioration.

In-Orchard Population Dynamics of Erwinia amylovora on Apple Flower Stigmas.

Populations of the fire blight pathogen Erwinia amylovora Ea110 on apple flower stigmas were tracked over the course of apple bloom in field studies conducted between 2016 and 2019. In 18 of 23 experiments, flower stigmas inoculated on the first day of opening were found to harbor large (106 to 107 cells per flower) populations of E. amylovora when assessed 3 to 5 days postinoculation. However, populations inoculated on stigmas of flowers that were already open for 3 days did not reach 106 cells per flower, and populations inoculated on stigmas of flowers that were already open for 5 days never exceeded 104 cells per flower. During this study, ≥10-fold increases in E. amylovora stigma populations in a 24-h time period (termed population surges) were observed on 34.8, 20.0, and 4.0% of possible days on 1-, 3-, and 5-day-open flowers, respectively. Population surges occurred on days with average temperatures as high as 24.5 and as low as 6.1°C. Experiments incorporating more frequent sampling during days and overnight revealed that many population surges occurred between 10:00 p.m. and 2:00 a.m. A Pearson's correlation analysis of weather parameters occurring during surge events indicated that population surges were significantly associated with situations in which overnight temperatures increased or remained constant, in which wind speed decreased, and in which relative humidity increased. This study refines our knowledge of E. amylovora population dynamics and further indicates that E. amylovora is able to infect flowers during exposure to colder field temperatures than previously reported.

Evaluation of the Third edition of the City University Colour Vision Test.

INTRODUCTION: The 3rd edition of the City University Colour Vision Test (CUT) was originally based on the Farnsworth-Munsell D-15 test (D15). The first part of the test is for detecting a defect, and the second part is used to diagnose the type and severity of the defect. This study evaluates the CUT 3rd edition relative to the Ishihara and the D15 colour vision tests. METHODS: Fifty nine colour vision normal subjects and 60 subjects with a congenital red-green colour vision defect were recruited. Subjects were tested with the Ishihara and CUT tests. Subjects who failed the Ishihara also performed the D15 test. RESULTS: The agreement between the Ishihara and CUT screening plates was marginally higher when using the CUT failure criterion of >1 error compared with using >2 errors. If the diagnostic plates were included with the screening plates in determining the pass/fail outcomes, the agreement between the Ishihara and CUT was high, with a first-order agreement coefficient (AC1) of 0.90. The AC1 coefficient agreement between the D15 and CUT diagnostic plates in terms of pass/fail was 0.81 when using the D15 failure criteria of >1 or >0 crossing. CONCLUSION: The level of agreement between the 3rd edition of the CUT and D15 was lower than the 2nd edition of the CUT. The primary reason for the lower agreement of the 3rd edition of the CUT was that it had a lower specificity relative to the D15 compared to the 2nd edition. Although the CUT predictive value for failing the D15 is over 90%, the predictive value for passing shows that 19%-25% of patients who pass the 3rd edition of the CUT test will fail the D15. The 3rd edition tends to misclassify protans as deutans or cannot classify the type of defect relative to the D15 and Ishihara.

Global population genetic structure and demographic trajectories of the black soldier fly, Hermetia illucens.

BACKGROUND: The black soldier fly (Hermetia illucens) is the most promising insect candidate for nutrient-recycling through bioconversion of organic waste into biomass, thereby improving sustainability of protein supplies for animal feed and facilitating transition to a circular economy. Contrary to conventional livestock, genetic resources of farmed insects remain poorly characterised. We present the first comprehensive population genetic characterisation of H. illucens. Based on 15 novel microsatellite markers, we genotyped and analysed 2862 individuals from 150 wild and captive populations originating from 57 countries on seven subcontinents. RESULTS: We identified 16 well-distinguished genetic clusters indicating substantial global population structure. The data revealed genetic hotspots in central South America and successive northwards range expansions within the indigenous ranges of the Americas. Colonisations and naturalisations of largely unique genetic profiles occurred on all non-native continents, either preceded by demographically independent founder events from various single sources or involving admixture scenarios. A decisive primarily admixed Polynesian bridgehead population serially colonised the entire Australasian region and its secondarily admixed descendants successively mediated invasions into Africa and Europe. Conversely, captive populations from several continents traced back to a single North American origin and exhibit considerably reduced genetic diversity, although some farmed strains carry distinct genetic signatures. We highlight genetic footprints characteristic of progressing domestication due to increasing socio-economic importance of H. illucens, and ongoing introgression between domesticated strains globally traded for large-scale farming and wild populations in some regions. CONCLUSIONS: We document the dynamic population genetic history of a cosmopolitan dipteran of South American origin shaped by striking geographic patterns. These reflect both ancient dispersal routes, and stochastic and heterogeneous anthropogenic introductions during the last century leading to pronounced diversification of worldwide structure of H. illucens. Upon the recent advent of its agronomic commercialisation, however, current human-mediated translocations of the black soldier fly largely involve genetically highly uniform domesticated strains, which meanwhile threaten the genetic integrity of differentiated unique local resources through introgression. Our in-depth reconstruction of the contemporary and historical demographic trajectories of H. illucens emphasises benchmarking potential for applied future research on this emerging model of the prospering insect-livestock sector.

An evaluation of a pilot of daily testing of SARS-CoV-2 contacts in acute hospital and ambulance trusts in England.

OBJECTIVES: Healthcare worker (HCW) SARS-CoV-2 contacts in England have been required to quarantine, creating staff shortages. We piloted daily contact testing (DCT) to assess its feasibility as an alternative. STUDY DESIGN: Observational service evaluation. METHODS: We conducted an observational service evaluation of 7-day DCT using antigen lateral flow devices (LFDs) at four acute hospital trusts and one ambulance trust in England. Mixed methods were used, using aggregate and individual-level test monitoring data, semi-structured interviews, and a survey of eligible contacts. RESULTS: In total, 138 HCWs were identified as contacts of a confirmed SARS-CoV-2 case. Of these, 111 (80%) consented to daily LFD testing, of whom 82 (74%) completed the required programme without interruption and 12 (11%) completed with interruption. Fifty-eight participants (52%) and two non-participants (7.4%) completed the survey. In total, 28 interviews were conducted with participants, site and infection control leads, and union representatives. One participant tested positive on LFD and polymerase chain reaction (PCR) test. Three participants tested positive on PCR but not LFD. DCT was well-accepted by trusts and staff. Participants reported no relaxation of their infection prevention and control behaviours. No incidents of transmission were detected. An estimated 729 potential days of work absence were averted. CONCLUSIONS: DCT can be acceptably operated in a healthcare setting, averting quarantine-related work absences in HCW SARS-CoV-2 contacts.

Black soldier fly larvae effectively degrade lincomycin from pharmaceutical industry wastes.

Lincomycin fermentation residues (LFR) are the byproducts from the pharmaceutical industry, and contain high concentrations of antibiotics that could pose a threat to the environment. Here, we report that black soldier fly larvae (BSFL) and associated microbiota can effectively degrade LFR and accelerate the degradation of lincomycin in LFR. The degradation rate of lincomycin in LFR can reach 84.9% after 12 days of BSFL-mediated bioconversion, which is 3-fold greater than that accomplished with natural composting. The rapid degradation was partially carried out by the BSFL-associated microbiota, contributing 22.0% of the degradation in the final composts. Based on microbiome analysis, we found that the structure of microbiota from both BSFL guts and BSFL composts changed significantly during the bioconversion, and that several bacterial genera were correlated with lincomycin degradation. The roles of the associated microbiota in the degradation were further verified by the ability of two larval intestinal bacterial isolates and one bacterial isolate from BSFL composts to lincomycin degradation. The synergy between BSFL and the isolated strains resulted in a 2-fold increase in degradation compared to that achieved by microbial degradation alone. Furthermore, we determined that the degradation was correlated with the induction of several antibiotic resistant genes (ARGs) associated with lincomycin degradation in larval guts and BSFL composts. Moreover, the environmental conditions in the BSFL composts were found to be conducive to the degradation. In conclusion, these findings demonstrate that the BSFL-mediated bioconversion of LFR could effectively reduce residual lincomycin and that the associated microbiota play crucial roles in the process.

Safety and Efficacy of CR6261 in an Influenza A H1N1 Healthy Human Challenge Model.

BACKGROUND: It is imperative to identify new targets for improved vaccines and therapeutics against influenza. One such target is the relatively conserved stalk region of the influenza A hemagglutinin (HA) surface protein. METHODS: We conducted a randomized, double-blind, phase 2, placebo-controlled trial of a monoclonal antibody that targets the HA stalk (CR6261) in a H1N1pdm09 healthy volunteer human challenge model. A single 50 mg/kg dose of CR6261 was infused 24 hours after challenge. The primary efficacy outcome was area under the curve (AUC) of viral RNA detection over time. RESULTS: Ninety-one healthy volunteers were randomized and underwent influenza challenge; 49 received CR6261 and 42 received placebo. CR6261 had no statistically significant effect on AUC (AUC, 48.56 log [copies/mL] × days, interquartile range [IQR], 202 vs AUC, 25.53 log [copies/mL] × days, IQR, 155; P = .315) and no clinically significant effect on influenza disease measures including number of symptoms, duration of symptoms, or inFLUenza Patient-Reported Outcome (FLU-PRO) scores. Preexisting anti-NA antibody titers were most predictive of reduced influenza disease. CR6261 reached a mean peak serum concentration of 1 × 106 ng/mL 15 minutes after infusion and a mean peak of 5.97 × 102 ng/mL in the nasal mucosa 2-3 days after infusion. CONCLUSIONS: The results of this study suggest that a monoclonal anti-stalk approach to prevent or treat influenza infection may be limited in efficacy. Future approaches should consider including and evaluating anti-stalk antibodies as part of a multifaceted strategy rather than as a stand-alone therapeutic. CLINICAL TRIALS REGISTRATION: NCT02371668.

Influenza Virus Hemagglutinins H2, H5, H6, and H11 Are Not Targets of Pulmonary Surfactant Protein D: N-Glycan Subtypes in Host-Pathogen Interactions.

Seasonal influenza carrying key hemagglutinin (HA) head region glycosylation sites can be removed from the lung by pulmonary surfactant protein D (SP-D). Little is known about HA head glycosylation of low-pathogenicity avian influenza virus (LPAIV) subtypes. These can pose a pandemic threat through reassortment and emergence in human populations. Since the presence of head region high-mannose glycosites dictates SP-D activity, the ability to predict these glycosite glycan subtypes may be of value. Here, we investigate the activities of two recombinant human SP-D forms against representative LPAIV strains, including H2N1, H5N1, H6N1, H11N9, an avian H3N8, and a human seasonal H3N2 subtype. Using mass spectrometry, we determined the glycan subclasses and heterogeneities at each head glycosylation site. Sequence alignment and molecular structure analysis of the HAs were performed for LPAIV strains in comparison to seasonal H3N2 and avian H3N8. Intramolecular contacts were determined between the protein backbone and glycosite glycan based on available three-dimensional structure data. We found that glycosite "N165" (H3 numbering) is occupied by high-mannose glycans in H3 HA but by complex glycans in all LPAIV HAs. SP-D was not active on LPAIV but was on H3 HAs. Since SP-D affinity for influenza HA depends on the presence of high-mannose glycan on the head region, our data demonstrate that SP-D may not protect against virus containing these HA subtypes. Our results also demonstrate that glycan subtype can be predicted at some glycosites based on sequence comparisons and three-dimensional structural analysis.IMPORTANCE Low-pathogenicity avian influenza virus (LPAIV) subtypes can reassort with circulating human strains and pandemic viruses can emerge in human populations, as was seen in the 1957 pandemic, in which an H2 virus reassorted with the circulating H1N1 to create a novel H2N2 genotype. Lung surfactant protein D (SP-D), a key factor in first-line innate immunity defense, removes influenza type A virus (IAV) through interaction with hemagglutinin (HA) head region high-mannose glycan(s). While it is known that both H1 and H3 HAs have one or more key high-mannose glycosites in the head region, little is known about similar glycosylation of LPAIV strains H2N1, H5N1, H6N1, or H11N9, which may pose future health risks. Here, we demonstrate that the hemagglutinins of LPAIV strains do not have the required high-mannose glycans and do not interact with SP-D, and that sequence analysis can predict glycan subtype, thus predicting the presence or absence of this virulence marker.

A Centenary Tale of Two Pandemics: The 1918 Influenza Pandemic and COVID-19, Part I.

Separated by a century, the influenza pandemic of 1918 and the COVID-19 pandemic of 2019-2021 are among the most disastrous infectious disease emergences of modern times. Although caused by unrelated viruses, the two pandemics are nevertheless similar in their clinical, pathological, and epidemiological features, and in the civic, public health, and medical responses to combat them. Comparing and contrasting the two pandemics, we consider what lessons we have learned over the span of a century and how we are applying those lessons to the challenges of COVID-19.

A Centenary Tale of Two Pandemics: The 1918 Influenza Pandemic and COVID-19, Part II.

Both the 1918 influenza pandemic and the 2019‒2021 COVID-19 pandemic are among the most disastrous infectious disease emergences of modern times. In addition to similarities in their clinical, pathological, and epidemiological features, the two pandemics, separated by more than a century, were each met with essentially the same, or very similar, public health responses, and elicited research efforts to control them with vaccines, therapeutics, and other medical approaches. Both pandemics had lasting, if at times invisible, psychosocial effects related to loss and hardship. In considering these two deadly pandemics, we ask: what lessons have we learned over the span of a century, and how are we applying those lessons to the challenges of COVID-19?