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

Influence of dietary nutrient balance on aggression and signalling in male field crickets

Indicator models of sexual selection predict that sexually selected trait elaboration should covary positively with condition. However, nutrition might influence the expression of multiple traits, where high-quality diets may result in positive trait correlations and low-quality diets in trade-offs. Although previous studies have examined how diet quantity or single nutrients, such as protein, carbohydrate and phosphorus, influence sexual traits, few have examined how dietary nutrient balance affects sexual trait expression. We therefore investigated how dietary protein:carbohydrate ratio and percentage of phosphorus influence the relationship between investment in mate attraction signalling and aggression. We fought groups of six adult male Gryllus veletis crickets, each consuming a unique diet, while recording their prefight and postfight signalling parameters. We found no evidence that diet influenced aggression or prefight signalling, with the exception that high-phosphorus diets had a negative influence on several signalling effort parameters. Body size was an important predictor of aggressive behaviour and most signalling parameters, suggesting that developmental diet may have a greater influence on these sexual traits. Several prefight signalling parameters were weakly related to aggression, suggesting that signalling may advertise competitive abilities. Males consuming high-carbohydrate and equal protein:carbohydrate diets experienced changes in signalling parameters that represented an overall increase in signalling effort following aggressive contests compared to males consuming high-protein diets, suggesting that dietary effects on signalling may only become apparent following periods of highly energetic activity. Changes in signalling following aggressive contests were also related to aggression levels modulated by dietary phosphorus content, such that only males consuming low-phosphorus diets were able to invest heavily in signalling after investing heavily in aggression. Our findings highlight the importance of research on the interplay between multiple sexually selected traits, and how dietary nutrient balance influences these relationships

How dietary protein and carbohydrate influence field cricket development, size and mate attraction signalling

Researchers examining how nutrition impacts fitness traits usually examine one nutrient at a time, ignoring potential interactions. When researchers simultaneously examine multiple nutrients, their studies often focus on adults, ignoring potential changes in nutritional needs that occur during the transition between juvenile and adult stages. To address these issues, we quantified how dietary nutrient balance (relative amounts of protein and carbohydrate) during development and into adulthood influenced life history and sexually selected traits using male Jamaican field crickets, Gryllus assimilis. Our findings revealed that male crickets developed significantly faster and grew larger when they were reared on a protein-rich diet, but their average daily time spent signalling for mates was significantly higher when they were reared on a carbohydrate-rich diet. Furthermore, while the probability of signalling and daily time spent signalling increased with age, time spent signalling for mates tended to increase at a higher rate with age when males consumed a carbohydrate-rich diet in adulthood. Together our findings suggest that traits may differ in their nutrient requirements, resulting in diet influencing a possible trade-off between traits across different life stages. The ability to locate and consume foods rich in protein during development should impact adult male fitness, as protein availability results in larger males, and larger males typically produce more attractive signals and are preferred by females. Conversely, the ability to locate and consume foods rich in carbohydrate should also impact a male's fitness, as males signal with higher effort when fed carbohydrate-rich diets, and higher signalling effort can directly impact a male's ability to attract a female

Towards a synthesis of frameworks in nutritional ecology: Interacting effects of protein, carbohydrate and phosphorus on field cricket fitness

Phosphorus has been identified as an important determinant of nutritionrelated biological variation. The macronutrients protein (P) and carbohydrates (C), both alone and interactively, are known to affect animal performance. No study, however, has investigated the importance of phosphorus relative to dietary protein or carbohydrates, or the interactive effects of phosphorus with these macronutrients, on fitness-related traits in animals. We used a nutritional geometry framework to address this question in adult field crickets (Gryllus veletis). Our results showed that lifespan, weight gain, acoustic mate signalling and egg production were maximized on diets with different P: C ratios, that phosphorus did not positively affect any of these fitness traits, and that males and females had different optimal macronutrient intake ratios for reproductive performance. When given a choice, crickets selected diets that maximized both lifespan and reproductive performance by preferentially eating diets with low P: C ratios, and females selected diets with a higher P: C ratio than males. Conversely, phosphorus intake was not regulated. Overall, our findings highlight the importance of disentangling the influences of different nutrients, and of quantifying both their individual and interactive effects, on animal fitness traits, so as to gain a more integrative understanding of their nutritional ecology

Calling, Courtship, and Condition in the Fall Field Cricket, Gryllus pennsylvanicus

Theoretically, sexual signals should provide honest information about mating benefits and many sexually reproducing species use honest signals when signalling to potential mates. Male crickets produce two types of acoustic mating signals: a long-distance mate attraction call and a short-range courtship call. We tested whether wild-caught fall field cricket (Gryllus pennsylvanicus) males in high condition (high residual mass or large body size) produce higher effort calls (in support of the honest signalling hypothesis). We also tested an alternative hypothesis, whether low condition males produce higher effort calls (in support of the terminal investment hypothesis). Several components of long-distance mate attraction calls honestly reflected male body size, with larger males producing louder mate attraction calls at lower carrier frequencies. Long-distance mate attraction chirp rate dishonestly signalled body size, with small males producing faster chirp rates. Short-range courtship calls dishonestly reflected male residual mass, as chirp rate and pulse rate were best explained by a curvilinear function of residual mass. By producing long-distance mate attraction calls and courtship calls with similar or higher effort compared to high condition males, low condition males (low residual mass or small body size) may increase their effort in current reproductive success at the expense of their future reproductive success, suggesting that not all sexual signals are honest

Same-sex sexual behaviour in crickets: Understanding the paradox

Same-sex sexual behaviour (SSSB) occurs in animals ranging from insects to mammals, yet its evolutionary origins remain enigmatic. Is it adaptive, or has it evolved as a by-product of selection for other traits? Using data from two experiments on male spring field crickets, Gryllus veletis, we tested whether SSSB is socially adaptive, sexually adaptive, correlated with other sexual behaviours and/or a result of sex misidentification. By identifying how sexual experience, audience composition, mate attraction signalling time, body size/mass, food composition and aggression levels correlated with levels of SSSB, we found support for the misidentification and phenotypic correlation hypotheses. More aggressive males were more likely to court other males, and males who spent the most time signalling to attract mates tended to spend the most time courting other males, suggesting that aggression, mate signalling effort and same-sex courtship may all be phenotypically correlated. However, the positive relationship between mate attraction signalling effort and probability of expressing same-sex courtship only occurred in males on a high-carbohydrate, low-protein food, suggesting that the expression of such a phenotypic correlation may be constrained by dietary carbohydrate availability. Finally, males were more likely to be courted if they were less aggressive and spent little time signalling for mates, but, for the latter, only if they were on high-carbohydrate foods, suggesting that together, diet, which may alter chemical cues involved in sex identification, and behavioural cues may lead to sex misidentification. Thus, SSSB in male G. veletis does not appear to be adaptive, probably evolving instead as a by-product of selection for other sexually selected traits. By investigating both proximate and ultimate factors contributing to the evolutionary enigma of SSSB, we may gain important insights into the selective forces shaping aggression, social interactions and reproductive strategies in social animals

Choosy males in Jamaican field crickets

Male mate choice is an often neglected aspect of sexual selection studies. While theory predicts that females should exhibit mate choice due to their comparatively greater investment in gametes, males may also exhibit mate choice for a variety of reasons, including seeking mates with greater fecundity. Furthermore, males may exhibit discriminant or indiscriminate mate choice as a function of their own intrinsic characteristics, such as body size or condition. Here we experimentally evaluated male Jamaican field cricket, Gryllus assimilis, mating preferences using randomly selected females and determined how both male and female morphology (body size and residual mass) and male signalling behaviour influence male mate preference. Results show that male crickets exhibit mating preferences, with larger males tending to exhibit more consistent mate preferences than smaller males. Contrary to predictions, males did not prefer larger or relatively heavier females, suggesting that males may not be basing their choosiness on these proxy measures of female fecundity. Our findings highlight the need for continued research on male mate ch

What is driving male mate preference evolution in Jamaican field crickets?

Male mating preferences are often a neglected aspect of studies on sexual selection. Male mating preferences may evolve if they provide males with direct-fitness benefits such as increased opportunity to fertilize more eggs or indirect-fitness benefits such as enhanced offspring survival. We tested these ideas using Jamaican field crickets, Gryllus assimilis, previously shown to exhibit male mating preferences. We randomly mated males to either their preferred or non-preferred potential mates and then asked whether mating treatment influenced egg oviposition or offspring viability. Preferred females were not significantly more fecund and did not produce more viable eggs or offspring than non-preferred females. Male mate preferences were therefore inconsistent with both the direct- and indirect-fitness benefits hypotheses under the conditions of our experiment. Our null results leave us with an open question about what is driving the evolution of m

Linking mating preferences to sexually selected traits and offspring viability: good versus complementary genes hypotheses

Indirect fitness benefits hypotheses suggest that offspring of preferred mates should exhibit greater survival or reproductive success. For example, good genes hypotheses propose that female mating preferences are mediated by secondary sexual traits because they honestly reflect the ability to pass on genes that will enhance offspring survival or reproduction. Conversely, complementary genes hypotheses propose that mating preferences are mediated by complementary genes because they enhance offspring viability. While these two research traditions are not strict alternatives and both may operate simultaneously, they have never been tested together. Here we explore the multiple potential underlying factors influencing mating preference ev

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

Altres ajuts: Department of Health and Social Care (DHSC); Illumina; LifeArc; Medical Research Council (MRC); UKRI; Sepsis Research (the Fiona Elizabeth Agnew Trust); the Intensive Care Society, Wellcome Trust Senior Research Fellowship (223164/Z/21/Z); BBSRC Institute Program Support Grant to the Roslin Institute (BBS/E/D/20002172, BBS/E/D/10002070, BBS/E/D/30002275); UKRI grants (MC_PC_20004, MC_PC_19025, MC_PC_1905, MRNO2995X/1); UK Research and Innovation (MC_PC_20029); the Wellcome PhD training fellowship for clinicians (204979/Z/16/Z); the Edinburgh Clinical Academic Track (ECAT) programme; the National Institute for Health Research, the Wellcome Trust; the MRC; Cancer Research UK; the DHSC; NHS England; the Smilow family; the National Center for Advancing Translational Sciences of the National Institutes of Health (CTSA award number UL1TR001878); the Perelman School of Medicine at the University of Pennsylvania; National Institute on Aging (NIA U01AG009740); the National Institute on Aging (RC2 AG036495, RC4 AG039029); the Common Fund of the Office of the Director of the National Institutes of Health; NCI; NHGRI; NHLBI; NIDA; NIMH; NINDS.Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care or hospitalization 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