The panzootic spread of highly pathogenic avian influenza H5N1 sublineage 2.3.4.4b: a critical appraisal of One Health preparedness and prevention.

Changes in the epidemiology and ecology of H5N1 highly pathogenic avian influenza are devastating wild bird and poultry populations, farms and communities, and wild mammals worldwide. Having originated in farmed poultry, H5N1 viruses are now spread globally by wild birds, with transmission to many mammal and avian species, resulting in 2024 in transmission among dairy cattle with associated human cases. These ecological changes pose challenges to mitigating the impacts of H5N1 highly pathogenic avian influenza on wildlife, ecosystems, domestic animals, food security, and humans. H5N1 highly pathogenic avian influenza highlights the need for One Health approaches to pandemic prevention and preparedness, emphasising multisectoral collaborations among animal, environmental, and public health sectors. Action is needed to reduce future pandemic risks by preventing transmission of highly pathogenic avian influenza among domestic and wild animals and people, focusing on upstream drivers of outbreaks, and ensuring rapid responses and risk assessments for zoonotic outbreaks. Political commitment and sustainable funding are crucial to implementing and maintaining prevention programmes, surveillance, and outbreak responses.

Bacteriophage therapy reduces Staphylococcus aureus in a porcine and human ex vivo burn wound infection model.

Burn wounds are a major burden, with high mortality rates due to infections. Staphylococcus aureus is a major causative agent of burn wound infections, which can be difficult to treat because of antibiotic resistance and biofilm formation. An alternative to antibiotics is the use of bacteriophages, viruses that infect and kill bacteria. We investigated the efficacy of bacteriophage therapy for burn wound infections, in both a porcine and a newly developed human ex vivo skin model. In both models, the efficacy of a reference antibiotic treatment (fusidic acid) and bacteriophage treatment was determined for a single treatment, successive treatment, and prophylaxis. Both models showed a reduction in bacterial load after a single bacteriophage treatment. Increasing the frequency of bacteriophage treatments increased bacteriophage efficacy in the human ex vivo skin model, but not in the porcine model. In both models, prophylaxis with bacteriophages increased treatment efficacy. In all cases, bacteriophage treatment outperformed fusidic acid treatment. Both models allowed investigation of bacteriophage-bacteria dynamics in burn wounds. Overall, bacteriophage treatment outperformed antibiotic control underlining the potential of bacteriophage therapy for the treatment of burn wound infections, especially when used prophylactically.

Fourth dose bivalent COVID-19 vaccines outperform monovalent boosters in eliciting cross-reactive memory B cells to Omicron subvariants.

Bivalent COVID-19 vaccines comprising ancestral Wuhan-Hu-1 (WH1) and the Omicron BA.1 or BA.5 subvariant elicit enhanced serum antibody responses to emerging Omicron subvariants. Here, we characterized the RBD-specific memory B cell (Bmem) response following a fourth dose with a BA.1 or BA.5 bivalent vaccine, in direct comparison with a WH1 monovalent fourth dose. Healthcare workers previously immunized with mRNA or adenoviral vector monovalent vaccines were sampled before and one-month after a fourth dose with a monovalent or a BA.1 or BA.5 bivalent vaccine. Serum neutralizing antibodies (NAb) were quantified, as well as RBD-specific Bmem with an in-depth spectral flow cytometry panel including recombinant RBD proteins of the WH1, BA.1, BA.5, BQ.1.1, and XBB.1.5 variants. Both bivalent vaccines elicited higher NAb titers against Omicron subvariants compared to the monovalent vaccine. Following either vaccine type, recipients had slightly increased WH1 RBD-specific Bmem numbers. Both bivalent vaccines significantly increased WH1 RBD-specific Bmem binding of all Omicron subvariants tested by flow cytometry, while recognition of Omicron subvariants was not enhanced following monovalent vaccination. IgG1+ Bmem dominated the response, with substantial IgG4+ Bmem only detected in recipients of an mRNA vaccine for their primary dose. Thus, Omicron-based bivalent vaccines can significantly boost NAb and Bmem specific for ancestral WH1 and Omicron variants, and improve recognition of descendent subvariants by pre-existing, WH1-specific Bmem, beyond that of a conventional, monovalent vaccine. This provides new insights into the capacity of variant-based mRNA booster vaccines to improve immune memory against emerging SARS-CoV-2 variants and potentially protect against severe disease. ONE-SENTENCE SUMMARY: Omicron BA.1 and BA.5 bivalent COVID-19 boosters, used as a fourth dose, increase RBD-specific Bmem cross-recognition of Omicron subvariants, both those encoded by the vaccines and antigenically distinct subvariants, further than a monovalent booster.

Ixodes ricinus as potential vector for Usutu virus.

Usutu virus (USUV) is an emerging flavivirus that is maintained in an enzootic cycle with mosquitoes as vectors and birds as amplifying hosts. In Europe, the virus has caused mass mortality of wild birds, mainly among Common Blackbird (Turdus merula) populations. While mosquitoes are the primary vectors for USUV, Common Blackbirds and other avian species are exposed to other arthropod ectoparasites, such as ticks. It is unknown, however, if ticks can maintain and transmit USUV. We addressed this question using in vitro and in vivo experiments and field collected data. USUV replicated in IRE/CTVM19 Ixodes ricinus tick cells and in injected ticks. Moreover, I. ricinus nymphs acquired the virus via artificial membrane blood-feeding and maintained the virus for at least 70 days. Transstadial transmission of USUV from nymphs to adults was confirmed in 4.9% of the ticks. USUV disseminated from the midgut to the haemocoel, and was transmitted via the saliva of the tick during artificial membrane blood-feeding. We further explored the role of ticks by monitoring USUV in questing ticks and in ticks feeding on wild birds in the Netherlands between 2016 and 2019. In total, 622 wild birds and the Ixodes ticks they carried were tested for USUV RNA. Of these birds, 48 (7.7%) carried USUV-positive ticks. The presence of negative-sense USUV RNA in ticks, as confirmed via small RNA-sequencing, showed active virus replication. In contrast, we did not detect USUV in 15,381 questing ticks collected in 2017 and 2019. We conclude that I. ricinus can be infected with USUV and can transstadially and horizontally transmit USUV. However, in comparison to mosquito-borne transmission, the role of I. ricinus ticks in the epidemiology of USUV is expected to be minor.

Determinants of intended prevention behaviour against mosquitoes and mosquito-borne viruses in the Netherlands and Spain using the MosquitoWise survey: cross-sectional study.

BACKGROUND: Recently, Europe has seen an emergence of mosquito-borne viruses (MBVs). Understanding citizens' perceptions of and behaviours towards mosquitoes and MBVs is crucial to reduce disease risk. We investigated and compared perceptions, knowledge, and determinants of citizens' behavioural intentions related to mosquitoes and MBVs in the Netherlands and Spain, to help improve public health interventions. METHODS: Using the validated MosquitoWise survey, data was collected through participant panels in Spain (N = 475) and the Netherlands (N = 438). Health Belief Model scores measuring behavioural intent, knowledge, and information scores were calculated. Confidence Interval-Based Estimation of Relevance was used, together with potential for change indexes, to identify promising determinants for improving prevention measure use. RESULTS: Spanish participants' responses showed slightly higher intent to use prevention measures compared to those of Dutch participants (29.1 and 28.2, respectively, p 0.03). Most participants in Spain (92.2%) and the Netherlands (91.8%) indicated they used at least one prevention measure, but differences were observed in which types they used. More Spanish participants indicated to have received information on mosquitoes and MBVs compared to Dutch participants. Spanish participants preferred health professional information sources, while Dutch participants favoured government websites. Determinants for intent to use prevention measures included "Knowledge", "Reminders to Use Prevention Measures", and "Information" in the Netherlands and Spain. Determinants for repellent use included "Perceived Benefits" and "Cues to Action", with "Perceived Benefits" having a high potential for behavioural change in both countries. "Self-Efficacy" and "Knowledge" were determinants in both countries for breeding site removal. CONCLUSION: This study found differences in knowledge between the Netherlands and Spain but similarities in determinants for intent to use prevention measures, intent to use repellents and intent to remove mosquito breeding sites. Identified determinants can be the focus for future public health interventions to reduce MBV risks.

Estimating the therapeutic potential of NSAIDs and linoleic acid-isomers supplementation against neuroinflammation.

Nonsteroidal anti-inflammatory drugs (NSAIDs) regulate inflammation, which is associated with their role in preventing neurodegenerative diseases in epidemiological studies. It has sparked interest in their unconventional application for reducing neuroinflammation, opening up new avenues in biomedical research. However, given the pharmacological drawbacks of NSAIDs, the development of formulations with naturally antioxidant/anti-inflammatory dietary fatty acids has been demonstrated to be advantageous for the clinical translation of anti-inflammatory-based therapies. It includes improved blood-brain barrier (BBB) permeability and reduced toxicity. It permits us to speculate about the value of linoleic acid (LA)-isomers in preventing and treating neuroinflammatory diseases compared to NSAIDs. Our research delved into the impact of various factors, such as administration route, dosage, timing of intervention, and BBB permeability, on the efficacy of NSAIDs and LA-isomers in preclinical and clinical settings. We conducted a systematic comparison between NSAIDs and LA-isomers regarding their therapeutic effectiveness, BBB compatibility, and side effects. Additionally, we explored their underlying mechanisms in addressing neuroinflammation. Through our analysis, we've identified challenges and drawn conclusions that could propel advancements in treating neurodegenerative diseases and inform the development of future alternative therapeutic strategies.

Worldwide Trends in COVID-19-Related Attacks Against Healthcare: A Review of the Safeguarding Health in Conflict Coalition Database.

During the COVID-19 pandemic, violence targeting healthcare reportedly increased. Attacks against healthcare can severely hamper the public health response during a pandemic. Descriptive data analysis of these attacks may be helpful to develop prevention and mitigation strategies. This study aimed to investigate trends regarding COVID-19-related attacks against healthcare from January 2020 until January 2023. COVID-19-related incidents occurring between January 2020 and January 2023 were extracted from the Safeguarding Health in Conflict Coalition database and screened for eligibility. Included incidents were linked to COVID-19 health measures or were attacks directly interfering with COVID-19 healthcare, including conflict-related attacks. Data collected per incident included temporal factors; country; setting; attack and weapon type; perpetrator; motive; number of healthcare workers (HCWs) killed, injured, or kidnapped; and health facility damage. The study identified 255 COVID-19-related attacks against healthcare, with 18 HCWs killed, 147 HCWs injured, and 86 facilities damaged. The highest attack frequency was reported during the beginning of the pandemic and predominantly concerned stigma-related attacks against healthcare. Reported incidents in 2021 included attacks targeting vaccination campaigns, as well as conflict-related attacks interfering with COVID-19 healthcare. COVID-19-related attacks against healthcare occurred in heterogeneous contexts throughout the pandemic. Due to underreporting, the data presented are a minimum estimate of the actual magnitude of violence. The findings of this study emphasize the importance of public education campaigns, improved coordination between healthcare organizations and law enforcement, and the possible need to bolster the security of medical facilities and health workers.

SARS-CoV-2-specific immune responses converge in kidney disease patients and controls with hybrid immunity.

Healthy individuals with hybrid immunity, due to a SARS-CoV-2 infection prior to first vaccination, have stronger immune responses compared to those who were exclusively vaccinated. However, little is known about the characteristics of antibody, B- and T-cell responses in kidney disease patients with hybrid immunity. Here, we explored differences between kidney disease patients and controls with hybrid immunity after asymptomatic or mild coronavirus disease-2019 (COVID-19). We studied the kinetics, magnitude, breadth and phenotype of SARS-CoV-2-specific immune responses against primary mRNA-1273 vaccination in patients with chronic kidney disease or on dialysis, kidney transplant recipients, and controls with hybrid immunity. Although vaccination alone is less immunogenic in kidney disease patients, mRNA-1273 induced a robust immune response in patients with prior SARS-CoV-2 infection. In contrast, kidney disease patients with hybrid immunity develop SARS-CoV-2 antibody, B- and T-cell responses that are equally strong or stronger than controls. Phenotypic analysis showed that Spike (S)-specific B-cells varied between groups in lymph node-homing and memory phenotypes, yet S-specific T-cell responses were phenotypically consistent across groups. The heterogeneity amongst immune responses in hybrid immune kidney patients warrants further studies in larger cohorts to unravel markers of long-term protection that can be used for the design of targeted vaccine regimens.

Original COVID-19 priming regimen impacts the immunogenicity of bivalent BA.1 and BA.5 boosters.

Waning antibody responses after COVID-19 vaccination combined with the emergence of the SARS-CoV-2 Omicron lineage led to reduced vaccine effectiveness. As a countermeasure, bivalent mRNA-based booster vaccines encoding the ancestral spike protein in combination with that of Omicron BA.1 or BA.5 were introduced. Since then, different BA.2-descendent lineages have become dominant, such as XBB.1.5, JN.1, or EG.5.1. Here, we report post-hoc analyses of data from the SWITCH-ON study, assessing how different COVID-19 priming regimens affect the immunogenicity of bivalent booster vaccinations and breakthrough infections (NCT05471440). BA.1 and BA.5 bivalent vaccines boosted neutralizing antibodies and T-cells up to 3 months after boost; however, cross-neutralization of XBB.1.5 was poor. Interestingly, different combinations of prime-boost regimens induced divergent responses: participants primed with Ad26.COV2.S developed lower binding antibody levels after bivalent boost while neutralization and T-cell responses were similar to mRNA-based primed participants. In contrast, the breadth of neutralization was higher in mRNA-primed and bivalent BA.5 boosted participants. Combined, our data further support the current use of monovalent vaccines based on circulating strains when vaccinating risk groups, as recently recommended by the WHO. We emphasize the importance of the continuous assessment of immune responses targeting circulating variants to guide future COVID-19 vaccination policies.

A pilot study of a virtually delivered dissonance-based eating disorder prevention program for young women with type 1 diabetes: within-subject changes over 6-month follow-up.

INTRODUCTION: In an uncontrolled study, we previously demonstrated the feasibility and preliminary efficacy of our virtual diabetes-specific version (Diabetes Body Project) of the eating disorder (ED) prevention program the Body Project. The aim of the current study was to evaluate further this program for women with type 1 diabetes (T1D) by assessing within-subject changes in outcomes from pretest over 6-month follow-up. METHODS: Young women with T1D aged 16-35 years were invited to participate in Diabetes Body Project groups. A total of 35 participants were allocated to five Diabetes Body Project groups (six meetings over 6 weeks). Primary outcome measures included ED risk factors and symptoms, and secondary outcomes included three T1D-specific constructs previously found to be associated with ED pathology: glycemic control as measured by HbA1c level, diabetes distress, and illness perceptions. RESULTS: Within-subject reductions, with medium-to-large effect sizes, were observed for the primary (ED pathology, body dissatisfaction, thin-ideal internalization, and appearance ideals and pressures) and secondary outcomes (within-condition Cohen's ds ranged from .34 to 1.70). CONCLUSION: The virtual Diabetes Body Project appears to be a promising intervention worthy of more rigorous evaluation. A randomized controlled trial with at least a 1-year follow-up is warranted to determine its efficacy compared to a control condition.

Species-specific responses during Seoul orthohantavirus infection in human and rat lung microvascular endothelial cells.

Seoul orthohantavirus (SEOV) is a rat-borne zoonotic virus that is transmitted via inhalation of aerosolized infectious excreta, and can cause hemorrhagic fever with renal syndrome (HFRS) in humans worldwide. In rats, SEOV predominantly exists as a persistent infection in the absence of overt clinical signs. Lack of disease in rats is attributed to downregulation of pro-inflammatory and upregulation of regulatory host responses. As lung microvascular endothelial cells (LMECs) represent a primary target of infection in both human and rats, infections in these cells provide a unique opportunity to study the central role of LMECs in the dichotomy between pathogenicity in both species. In this study, host responses to SEOV infection in primary human and rat LMECs were directly compared on a transcriptional level. As infection of rat LMECs was more efficient than human LMECs, the majority of anti-viral defense responses were observed earlier in rat LMECs. Most prominently, SEOV-induced processes in both species included responses to cytokine stimulus, negative regulation of innate immune responses, responses to type I and II interferons, regulation of pattern recognition receptor signaling and MHC-I signaling. However, over time, in the rat LMECs, responses shifted from an anti-viral state towards a more immunotolerant state displayed by a PD-L1, B2M-, JAK2-focused interaction network aiding in negative regulation of cytotoxic CD8-positive T cell activation. This suggests a novel mechanism by which species-specific orthohantavirus-induced endothelium and T cell crosstalk may play a crucial role in the development of acute disease in humans and persistence in rodents.

Six dilemmas for stakeholders inherently affecting data sharing during a zoonotic (re-)emerging infectious disease outbreak response.

BACKGROUND: Timely access to outbreak related data, particularly in the early events of a spillover, is important to support evidence based control measures in response to outbreaks of zoonotic Emerging Infectious Diseases (EID). Yet, this is impeded by several barriers that need to be understood to promote timely sharing of data. Using the MERS epidemic as a model for a zoonotic EID outbreak, this study sought to provide an in-depth understanding of data sharing practices. METHODS: Semi-structured interviews with 25 experts were conducted, along with Focus Group Discussions with 15 additional experts. A root-cause analysis was performed to examine the causal relationships between barriers. Enablers were mapped to the root-cause analysis to understand their influence on the barriers. Finally, root causes were placed in context of core dilemmas identified from the qualitative analysis. FINDINGS: Eight barriers to data sharing were identified, related to collaboration, technical preparedness, regulations, and (conflict of) interests, and placed in the context of six dilemmas inherent to the multi-stakeholder collaboration required for a zoonotic outbreak response. Fourteen identified enablers showed the willingness of stakeholders to overcome or circumvent these barriers, but also indicated the inherent trial and error nature of implementing such enablers. INTERPRETATION: Addressing the barriers requires solutions that must consider the complexity and interconnectedness of the root causes underlying them, and should consider the distinct scopes and interests of the different stakeholders. Insights provided by this study can be used to encourage data sharing practices for future outbreaks FUNDING: Wellcome Trust and UK Aid; EU-H2020 Societal Challenges (grant agreement no. 643476), Nederlandse Organisatie voor Wetenschappelijk Onderzoek (VI.Veni.201S.044).

West Nile virus spread in Europe: Phylogeographic pattern analysis and key drivers.

BACKGROUND: West Nile virus (WNV) outbreaks in birds, humans, and livestock have occurred in multiple areas in Europe and have had a significant impact on animal and human health. The patterns of emergence and spread of WNV in Europe are very different from those in the US and understanding these are important for guiding preparedness activities. METHODS: We mapped the evolution and spread history of WNV in Europe by incorporating viral genome sequences and epidemiological data into phylodynamic models. Spatially explicit phylogeographic models were developed to explore the possible contribution of different drivers to viral dispersal direction and velocity. A "skygrid-GLM" approach was used to identify how changes in environments would predict viral genetic diversity variations over time. FINDINGS: Among the six lineages found in Europe, WNV-2a (a sub-lineage of WNV-2) has been predominant (accounting for 73% of all sequences obtained in Europe that have been shared in the public domain) and has spread to at least 14 countries. In the past two decades, WNV-2a has evolved into two major co-circulating clusters, both originating from Central Europe, but with distinct dynamic history and transmission patterns. WNV-2a spreads at a high dispersal velocity (88km/yr-215 km/yr) which is correlated to bird movements. Notably, amongst multiple drivers that could affect the spread of WNV, factors related to land use were found to strongly influence the spread of WNV. Specifically, the intensity of agricultural activities (defined by factors related to crops and livestock production, such as coverage of cropland, pasture, cultivated and managed vegetation, livestock density) were positively associated with both spread direction and velocity. In addition, WNV spread direction was associated with high coverage of wetlands and migratory bird flyways. CONCLUSION: Our results suggest that-in addition to ecological conditions favouring bird- and mosquito- presence-agricultural land use may be a significant driver of WNV emergence and spread. Our study also identified significant gaps in data and the need to strengthen virological surveillance in countries of Central Europe from where WNV outbreaks are likely seeded. Enhanced monitoring for early detection of further dispersal could be targeted to areas with high agricultural activities and habitats of migratory birds.

Momentary skills use predicts decreased binge eating and purging early in day treatment: An ecological momentary assessment study.

OBJECTIVE: Emerging research indicates that skills acquisition may be important to behavior change in cognitive behavior therapy (CBT) for eating disorders. This study investigated whether skills use assessed in real time during the initial 4 weeks of CBT-based day treatment was associated with momentary eating disorder behavior change and rapid response to treatment. METHODS: Participants with DSM-5 bulimia nervosa or purging disorder (N = 58) completed ecological momentary assessments (EMA) several times daily for the first 28 days of treatment. EMA assessed skills use, the occurrence of binge eating and/or purging, and state negative affect. Rapid response was defined as abstinence from binge eating and/or purging in the first 4 weeks of treatment. RESULTS: Greater real-time skills use overall, and use of "planning ahead," "distraction," "social support," and "mechanical eating" skills in particular, were associated with a lower likelihood of engaging in binge eating or purging during the same period. After controlling for baseline group differences in overall difficulties with emotion regulation, rapid and non-rapid responders did not differ in overall skills use, or skills use at times of higher negative affect, during the EMA period. DISCUSSION: Momentary use of skills appears to play an important role in preventing binge eating and purging, and certain skills appear to be particularly helpful. These findings contribute to the literature elucidating the processes by which CBT treatments for eating disorders work by providing empirical evidence that skills use helps to prevent binge eating and purging behaviors. PUBLIC SIGNIFICANCE: Individuals with eating disorders learn new skills during treatment to help them improve their symptoms. This study shows that for people with eating disorders, using skills helps prevent eating disorder behaviors in the moment. Certain skills may be particularly helpful, including planning ahead, distracting activities, support from others, and focusing on eating meals and snacks regardless of how one is feeling. These findings help us better understand how treatments work.

Development and validation of the MosquitoWise survey to assess perceptions towards mosquitoes and mosquito-borne viruses in Europe.

Due to climate change and the expanding geographical ranges of key mosquito species, several mosquito-borne viruses (MBVs) have recently emerged in Europe. Understanding people's perceptions and behaviours towards these viruses and the mosquitoes capable of transmitting them is crucial for implementing effective prevention measures and targeted communication campaigns. However, there is currently no appropriate validated survey for European populations to assess this. This study developed and validated a standardized survey, based on the Health Belief Model (HBM), to assess perceptions of mosquitoes and MBVs among Europe's residents. The survey was distributed online to United Kingdom (UK), Dutch and Spanish participants through panel providers. Survey validity and reliability were tested using confirmatory factor analysis (CFA) and Cronbach's alpha. The optimised survey was completed by 336 UK, 438 Dutch and 475 Spanish residents, respectively, and the HBM items passed our validity and reliability testing in all three countries. The final survey has 57 questions, including 19 validated HBM items, and questions to assess demographic characteristics, knowledge, prevention measures and behavioural determinants. Our MosquitoWise survey bridges researchers' understandings of European residents' perceptions and knowledge as a first step to improve preventive behaviour towards mosquitoes and MBVs and guide prevention and communication initiatives.

Seroprevalence of SARS-CoV-2 antibodies among healthcare workers in Dutch hospitals after the 2020 first wave: a multicentre cross-sectional study with prospective follow-up.

BACKGROUND: We aimed to estimate the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seroprevalence and describe its determinants and associated symptoms among unvaccinated healthcare workers (HCWs) after the first wave of the pandemic. METHODS: HCWs from 13 Dutch hospitals were screened for antibodies against the spike protein of SARS-CoV-2 in June-July 2020 and after three months. Participants completed a retrospective questionnaire on determinants for occupational and community exposure to SARS-CoV-2 and symptoms suggestive of COVID-19 experienced since January 2020. The seroprevalence was calculated per baseline characteristic and symptom at baseline and after follow-up. Adjusted odds ratios (aOR) for seropositivity were determined using logistic regression. RESULTS: Among 2328 HCWs, 323 (13.9%) were seropositive at enrolment, 49 of whom (15%) reported no previous symptoms suggestive of COVID-19. During follow-up, only 1% of the tested participants seroconverted. Seroprevalence was higher in younger HCWs compared to the mid-age category (aOR 1.53, 95% CI 1.07-2.18). Nurses (aOR 2.21, 95% CI 1.34-3.64) and administrative staff (aOR 1.87, 95% CI 1.02-3.43) had a higher seroprevalence than physicians. The highest seroprevalence was observed in HCWs in the emergency department (ED) (aOR 1.79, 95% CI 1.10-2.91), the lowest in HCWs in the intensive, high, or medium care units (aOR 0.47, 95% CI 0.31-0.71). Chronic respiratory disease, smoking, and having a dog were independently associated with a lower seroprevalence, while HCWs with diabetes mellitus had a higher seroprevalence. In a multivariable model containing all self-reported symptoms since January 2020, altered smell and taste, fever, general malaise/fatigue, and muscle aches were positively associated with developing antibodies, while sore throat and chills were negatively associated. CONCLUSIONS: The SARS-CoV-2 seroprevalence in unvaccinated HCWs of 13 Dutch hospitals was 14% in June-July 2020 and remained stable after three months. A higher seroprevalence was observed in the ED and among nurses, administrative and young staff, and those with diabetes mellitus, while a lower seroprevalence was found in HCWs in intensive, high, or medium care, and those with self-reported lung disease, smokers, and dog owners. A history of altered smell or taste, fever, muscle aches and fatigue were independently associated with the presence of SARS-CoV-2 antibodies in unvaccinated HCWs.

Immunological profiling in long COVID: overall low grade inflammation and T-lymphocyte senescence and increased monocyte activation correlating with increasing fatigue severity.

Background: Many patients with SARS-CoV-2 infection develop long COVID with fatigue as one of the most disabling symptoms. We performed clinical and immune profiling of fatigued and non-fatigued long COVID patients and age- and sex-matched healthy controls (HCs). Methods: Long COVID symptoms were assessed using patient-reported outcome measures, including the fatigue assessment scale (FAS, scores ≥22 denote fatigue), and followed up to one year after hospital discharge. We assessed inflammation-related genes in circulating monocytes, serum levels of inflammation-regulating cytokines, and leukocyte and lymphocyte subsets, including major monocyte subsets and senescent T-lymphocytes, at 3-6 months post-discharge. Results: We included 37 fatigued and 36 non-fatigued long COVID patients and 42 HCs. Fatigued long COVID patients represented a more severe clinical profile than non-fatigued patients, with many concurrent symptoms (median 9 [IQR 5.0-10.0] vs 3 [1.0-5.0] symptoms, p<0.001), and signs of cognitive failure (41%) and depression (>24%). Immune abnormalities that were found in the entire group of long COVID patients were low grade inflammation (increased inflammatory gene expression in monocytes, increased serum pro-inflammatory cytokines) and signs of T-lymphocyte senescence (increased exhausted CD8+ TEMRA-lymphocytes). Immune profiles did not significantly differ between fatigued and non-fatigued long COVID groups. However, the severity of fatigue (total FAS score) significantly correlated with increases of intermediate and non-classical monocytes, upregulated gene levels of CCL2, CCL7, and SERPINB2 in monocytes, increases in serum Galectin-9, and higher CD8+ T-lymphocyte counts. Conclusion: Long COVID with fatigue is associated with many concurrent and persistent symptoms lasting up to one year after hospitalization. Increased fatigue severity associated with stronger signs of monocyte activation in long COVID patients and potentially point in the direction of monocyte-endothelial interaction. These abnormalities were present against a background of immune abnormalities common to the entire group of long COVID patients.