Deep plasma proteomics with data-independent acquisition: A fastlane towards biomarkers identification. (preprint)

Plasma proteomic is a precious tool in human disease research, but requires extensive sample preparation in order to perform in-depth analysis and biomarker discovery using traditional Data-Dependent Acquisition (DDA). Here, we highlight the efficacy of combining moderate plasma prefractionation and Data-Independent Acquisition (DIA) to significantly improve proteome coverage and depth, while remaining cost- and time-efficient. Using human plasma collected from a 20-patient COVID-19 cohort, our method utilises commonly available solutions for depletion, sample preparation, and fractionation, followed by 3 LC-MS/MS injections for a 360-minutes DIA run time. DIA-NN software was then used for precursor identification, and the QFeatures R package was used for protein aggregation. We detect 1,321 proteins on average per patient, and 2,031 unique proteins across the cohort. Filtering precursors present in under 25% of patients, we still detect 1,230 average proteins and 1,590 unique proteins, indicating robust protein identification. Differential analysis further demonstrates the applicability of this method for plasma proteomic research and clinical biomarker identification. In summary, this study introduces a streamlined, cost- and time-effective approach to deep plasma proteome analysis, expanding its utility beyond classical research environments and enabling larger-scale multi-omics investigations in clinical settings.

The Impact of Non-pharmaceutical Interventions on COVID-19 in Workers and Residents of Nursing Homes in Geneva: A Mixed-Methods Study (preprint)

Non-pharmaceutical interventions (NPIs), including social distancing, wearing personal protective equipment, and lockdown measures, have been at the forefront of outbreak control in nursing homes. We used a mixed methodology to assess which NPIs nursing homes in the canton of Geneva, Switzerland, followed for their staff and residents during the first wave of the pandemic, between March 1, 2020 and June 1, 2020. For the qualitative component, we interviewed the attending physicians and/or director of each nursing home. Based on in-vivo codes, NPIs for nursing home workers and residents in each nursing home were thematically classified as: maximally restrictive, moderately restrictive, and minimally restrictive. In the quantitative component, we calculated incident rate ratios (IRR) for infection between the three levels of COVID-19-related measures taken in these nursing homes. We found an equal distribution of maximally (n=4), moderately (n=4), and minimally (n=4) restrictive NPIs. The extent of restriction did not show to be significantly associated with the cumulative incidence of COVID-19 cases among residents (maximally restrictive IRR = 3.90, 95%CI 0.82-45.54, p = 0.184; moderately restrictive IRR = 3.55, 95%CI 0.75-41.42, p = 0.212 ; minimally restrictive IRR = reference). Variabilities in NPIs adopted by nursing homes, and the number of COVID-19 cases appear to be randomly affected.

Longitudinal Study on Seroprevalence and Immune Response to SARS-CoV-2 in a Population of Food and Retail Workers Through Transformation of ELISA Datasets (preprint)

Since the onset of the global pandemic caused by the emergence and spread of SARS-CoV-2 in early 2020, numerous studies have been conducted worldwide to understand our immune response to the virus. This study investigates the humoral response elicited by vaccination and by SARS-CoV-2 infection in the poorly studied food and retail workers in the Quebec City area. The 1.5-year study period spans from early 2021, when vaccination became available in this region, to mid-2022, following waves of virulence due to the emergence of the first Omicron variants. Cross-correlated with data on workplace protective measures, pre-existing conditions, activities and other potentially relevant factors, this longitudinal study applies recently developed ELISA data transformation to our dataset to obtain normal distribution. This unlocked the possibility to use the ANOVA-Welsh method for statistical analysis to obtain a statistical perspective of the serological response. Our work allows the identification of factors contributing to statistically relevant differences in the humoral response of the cohort and strengthens the utility of the use of decentralized approaches to serological analysis.

Impact of a tailored exercise regimen on physical capacity, systemic oxidative stress and plasma proteomic profile in patients affected by post-COVID-19 Condition (PCC) (preprint)

Background: Individuals affected by the post-covid condition (PCC) show an increased fatigue and the so-called post-exertion malaise (PEM) that led health professionals to advise against exercise although accumulating evidence indicates the contrary. The goal of this study is to determine the impact of a closely monitored 8-week mixed exercise program on physical capacity, symptoms, fatigue, systemic oxidative stress and plasma proteomic profiles of PCC cases. Methods: Twenty-five women and men with PCC were assigned sequentially to exercise (n = 15) and non-exercise (n = 10) groups. Individuals with no PCC served as a control group. The exercise program included cardiovascular and resistance exercises. Physical capacity, physical activity level and the presence of common PCC symptoms were measured before and after the intervention. Fatigue was measured the day following each exercise session. Plasma and PBMC samples were collected at the beginning and end of the training program. Glutathione and deoxyguanosine levels in PBMC and plasma proteomic profiles were evaluated. Results: Bicep Curl (p=0.040) and STS-30 (p=0.043) improved to a greater extent in the exercise group than in the non-exercise group. An interaction effect was also observed for the level of physical activity (p=0.007) with a positive effect of the program on their daily functioning and without any adverse effects on general or post-effort fatigue. After exercise, glutathione levels in PBMCs increased in women but remained unchanged in men. Discernable changes were observed in the plasma proteomics profile with certain proteins involved in inflammatory response (SA100A8) decreasing in the exercise group. Conclusions: Supervised exercise adapted to the level of fatigue and ability is safe and effective in PCC patients in improving their general physical capacity and wellbeing. Systemic molecular markers that accompany physical improvement can be monitored by analyzing plasma proteomics and markers of oxidative stress. Large-scale studies will help identify promising molecular markers to objectively monitor patient improvement.

Impact of a tailored exercise regimen on physical capacity, systemic oxidative stress and plasma proteomic profile in PCC patients (preprint)

Background: Individuals affected by the post-covid condition (PCC) show an increased fatigue and the so-called post-exertion malaise (PEM) that led health professionals to advise against exercise although accumulating evidence indicates the contrary. The goal of this study is to determine the impact of a closely monitored 8-week mixed exercise program on physical capacity, symptoms, fatigue, systemic oxidative stress and plasma proteomic profiles of PCC cases.  Methods: Twenty-five women and men with PCC were assigned sequentially to exercise (n = 15) and non-exercise (n = 10) groups. Individuals with no PCC served as a control group. The exercise program included cardiovascular and resistance exercises. Physical capacity, physical activity level and the presence of common PCC symptoms were measured before and after the intervention. Fatigue was measured the day following each exercise session. Plasma and PBMC samples were collected at the beginning and end of the training program. Glutathione and deoxyguanosine levels in PBMC and plasma proteomic profiles were evaluated.   Results: Bicep Curl (p=0.040) and STS-30 (p=0.043) improved to a greater extent in the exercise group than in the non-exercise group. An interaction effect was also observed for the level of physical activity (p=0.007) with a positive effect of the program on their daily functioning and without any adverse effects on general or post-effort fatigue. After exercise, glutathione levels in PBMCs increased in women but remained unchanged in men. Discernable changes were observed in the plasma proteomics profile with certain proteins involved in inflammatory response (SA100A8) decreasing in the exercise group.  Conclusions: Supervised exercise adapted to the level of fatigue and ability is safe and effective in PCC patients in improving their general physical capacity and wellbeing. Systemic molecular markers that accompany physical improvement can be monitored by analyzing plasma proteomics and markers of oxidative stress. Large-scale studies will help identify promising molecular markers to objectively monitor patient improvement.

Refining COVID-19 retrospective diagnosis with continuous serological tests: a Bayesian mixture model (preprint)

COVID-19 serological tests with a "positive", "intermediate" or "negative" result according to predefined thresholds cannot be directly interpreted as a probability of having been infected with SARS-CoV-2. Based on 81,797 continuous anti-spike tests collected in France after the first wave, a Bayesian mixture model was developed to provide a tailored infection probability for each participant. Depending on the serological value and the context (age and administrative region), a negative or a positive test could correspond to a probability of infection as high as 61.9% or as low as 68.0%, respectively. In infected individuals, the model estimated a proportion of "non-responders" of 14.5% (95% CI, 11.2-18.1%), corresponding to a sub-group of persons who exhibited a weaker serological response to SARS-CoV-2. This model allows for an individual interpretation of serological results as a probability of infection, depending on the context and without any notion of threshold.

Cohort Profile: Prospective Cohort to Study the COVID-19 Immune Response in Retail Workers in Quebec, Canada (CISACOV) (preprint)

Purpose: Retail workers are an understudied occupational group that may have been at increased risk of contracting SARS-CoV-2 during the COVID-19 pandemic. Therefore, we set up a longitudinal cohort of participants working in this sector to better document the incidence of SARS-CoV-2 infection and the immune response to infection and/or vaccination in this group. Participants: A total of 304 participants were recruited between April 20, 2021 and October 22, 2021. They were invited to attend three visits (each separated by ~12 weeks) during which they provided blood samples and information on participant characteristics, COVID-19 symptoms, and vaccination. An extension phase of two additional visits was carried out between March 15th, 2022 and October 3rd, 2022 to document the impact of the Omicron variant among the 198 participants who were still eligible for recruitment. Participants were aged 18 to 75 and worked in grocery stores, hardware stores, bars or restaurants within the Quebec City metropolitan area (Canada). Findings to date: This article describes participants' demographic, socioeconomic, behavioral, clinical and occupational characteristics, and their COVID-19 symptoms (where applicable). It also describes SARS-CoV-2 vaccination status and any SARS-CoV-2 diagnostic test (i.e., PCR or rapid antigen) performed from the beginning of the pandemic until the last visit. Future plans: The incidence of SARS-CoV-2 infections will be assessed. The immune response (innate and acquired) to SARS-CoV-2 infection or vaccination will be studied using a variety of techniques, including reference and experimental enzyme-linked immunosorbent assays, microneutralization assays with live viruses, experimental pseudoneutralization with an angiotensin-converting enzyme 2-spike assay, peripheral blood mononuclear cells and neutrophil stimulation, and a proliferation assay based on carboxyfluorescein diacetate succinimidyl ester.

An Online Survey of the Perceptions of Clinical and Non-Clinical Professionals on Healthcare for Non-Communicable Diseases and COVID-19 Measures During the Pandemic in Malaysia.

Objectives: This study assesses the opinions of health professionals in Malaysia on the disruption of non-communicable disease (NCD) services during the COVID-19 pandemic from March 2020 to January 2022. Methods: We conducted a cross-sectional online survey with 191 non-clinical public health workers and clinical health service workers in Malaysia from November 2021 to January 2022. Participants were recruited by the Malaysian Ministry of Health using major networks including key experts and practitioners. Secondary respondents were subsequently enrolled through snowballing. Results: The most notable issues raised by the survey participants relate to NCD service disruption, the redirection of NCD care resources, and NCD care being overburdened post-pandemic. Respondents also reported accounts of resilience and prompt reaction from the healthcare system, as well as calls for innovation. Conclusion: Most respondents perceived that the challenges arising from COVID-19 were mostly managed well by the healthcare system, which was able to provide the necessary services to NCD patients during this health emergency. However, the study identifies gaps in the health system response and preparedness capacity, and highlights solutions for strengthening NCD services.

A Pilot Study on Oxidative Stress during the Recovery Phase in Critical COVID-19 Patients in a Rehabilitation Facility: Potential Utility of the PAOT® Technology for Assessing Total Anti-Oxidative Capacity.

BACKGROUND: Oxidative stress (OS) could cause various COVID-19 complications. Recently, we have developed the Pouvoir AntiOxydant Total (PAOT®) technology for reflecting the total antioxidant capacity (TAC) of biological samples. We aimed to investigate systemic oxidative stress status (OSS) and to evaluate the utility of PAOT® for assessing TAC during the recovery phase in critical COVID-19 patients in a rehabilitation facility. MATERIALS AND METHODS: In a total of 12 critical COVID-19 patients in rehabilitation, 19 plasma OSS biomarkers were measured: antioxidants, TAC, trace elements, oxidative damage to lipids, and inflammatory biomarkers. TAC level was measured in plasma, saliva, skin, and urine, using PAOT and expressed as PAOT-Plasma, -Saliva, -Skin, and -Urine scores, respectively. Plasma OSS biomarker levels were compared with levels from previous studies on hospitalized COVID-19 patients and with the reference population. Correlations between four PAOT scores and plasma OSS biomarker levels were analyzed. RESULTS: During the recovery phase, plasma levels in antioxidants (γ-tocopherol, ß-carotene, total glutathione, vitamin C and thiol proteins) were significantly lower than reference intervals, whereas total hydroperoxides and myeloperoxidase (a marker of inflammation) were significantly higher. Copper negatively correlated with total hydroperoxides (r = 0.95, p = 0.001). A similar, deeply modified OSS was already observed in COVID-19 patients hospitalized in an intensive care unit. TAC evaluated in saliva, urine, and skin correlated negatively with copper and with plasma total hydroperoxides. To conclude, the systemic OSS, determined using a large number of biomarkers, was always significantly increased in cured COVID-19 patients during their recovery phase. The less costly evaluation of TAC using an electrochemical method could potentially represent a good alternative to the individual analysis of biomarkers linked to pro-oxidants.

Long term anti-SARS-CoV-2 antibody kinetics and correlate of protection against Omicron BA.1/BA.2 infection.

Binding antibody levels against SARS-CoV-2 have shown to be correlates of protection against infection with pre-Omicron lineages. This has been challenged by the emergence of immune-evasive variants, notably the Omicron sublineages, in an evolving immune landscape with high levels of cumulative incidence and vaccination coverage. This in turn limits the use of widely available commercial high-throughput methods to quantify binding antibodies as a tool to monitor protection at the population-level. Here we show that anti-Spike RBD antibody levels, as quantified by the immunoassay used in this study, are an indirect correlate of protection against Omicron BA.1/BA.2 for individuals previously infected by SARS-CoV-2. Leveraging repeated serological measurements between April 2020 and December 2021 on 1083 participants of a population-based cohort in Geneva, Switzerland, and using antibody kinetic modeling, we found up to a three-fold reduction in the hazard of having a documented positive SARS-CoV-2 infection during the Omicron BA.1/BA.2 wave for anti-S antibody levels above 800 IU/mL (HR 0.30, 95% CI 0.22-0.41). However, we did not detect a reduction in hazard among uninfected participants. These results provide reassuring insights into the continued interpretation of SARS-CoV-2 binding antibody measurements as an independent marker of protection at both the individual and population levels.

Maternal distress and parenting during COVID-19: differential effects related to pre-pandemic distress?

BACKGROUND: Distinguishing whether and how pre-existing characteristics impact maternal responses to adversity is difficult: Does prior well-being decrease the likelihood of encountering stressful experiences? Does it protect against adversity's negative effects? We examine whether the interaction between relatively uniformly experienced adversity (due to COVID-19 experience) and individual variation in pre-existing (i.e., pre-pandemic onset) distress predicted mothers' pandemic levels of distress and insensitive caregiving within a country reporting low COVID-19 death rates, and strict nationwide regulations. METHOD: Fifty-one Singaporean mothers and their preschool-aged children provided data across two waves. Pre- pandemic onset maternal distress (i.e., psychological distress, anxiety, and parenting stress) was captured via self-reports and maternal sensitivity was coded from videos. Measures were repeated after the pandemic's onset along with questionnaires concerning perceived COVID-19 adversity (e.g., COVID-19's impact upon stress caring for children, housework, job demands, etc.) and pandemic-related objective experiences (e.g., income, COVID-19 diagnoses, etc.). Regression analyses (SPSS v28) considered pre-pandemic onset maternal distress, COVID-19 stress, and their interaction upon post-pandemic onset maternal distress. Models were re-run with appropriate covariates (e.g., objective experience) when significant findings were observed. To rule out alternative models, follow up analyses (PROCESS Model) considered whether COVID-19 stress mediated pre- and post-pandemic onset associations. Models involving maternal sensitivity followed a similar data analytic plan. RESULTS: Pre-pandemic maternal distress moderated the association between COVID-19 perceived stress and pandemic levels of maternal distress (ß = 0.22, p < 0.01) but not pandemic assessed maternal sensitivity. Perceived COVID-19 stress significantly contributed to post-pandemic onset maternal distress for mothers with pre-pandemic onset distress scores above (ß = 0.30, p = 0.05), but not below (ß = 0.25, p = 0.24), the median. Objective COVID-19 adversity did not account for findings. Post-hoc analyses did not suggest mediation via COVID-19 stress from pre-pandemic to pandemic maternal distress. CONCLUSIONS: Pre-existing risk may interact with subsequent perceptions of adversity to impact well-being. In combination with existing research, this small study suggests prevention programs should focus upon managing concurrent mental health and may highlight the importance of enhanced screening and proactive coping programs for people entering high stress fields and/or phases of life.

Immunohistologic Features of Cerebral Venous Thrombosis Due to Vaccine-Induced Immune Thrombotic Thrombocytopenia.

OBJECTIVES: Vaccine-induced immune thrombotic thrombocytopenia (VITT), a recently described entity characterized by thrombosis at unusual locations such as cerebral venous sinus and splanchnic vein, has been rarely described after adenoviral-encoded COVID-19 vaccines. In this study, we report the immunohistological correlates in 3 fatal cases of cerebral venous thrombosis related to VITT analyzed at an academic medical center. METHODS: Detailed neuropathologic studies were performed in 3 cases of cerebral venous thrombosis related to VITT after adenoviral COVID-19 vaccination. RESULTS: Autopsy revealed extensive cerebral vein thrombosis in all 3 cases. Polarized thrombi were observed with a high density of neutrophils in the core and a low density in the tail. Endothelial cells adjacent to the thrombus were largely destroyed. Markers of neutrophil extracellular trap and complement activation were present at the border and within the cerebral vein thrombi. SARS-CoV-2 spike protein was detected within the thrombus and in the adjacent vessel wall. DISCUSSION: Data indicate that neutrophils and complement activation associated with antispike immunity triggered by the vaccine is probably involved in the disease process.

Epidemiology and risk factors of 28-day mortality of hospital-acquired bloodstream infection in Turkish intensive care units: a prospective observational cohort study.

OBJECTIVES: To uncover clinical epidemiology, microbiological characteristics and outcome determinants of hospital-acquired bloodstream infections (HA-BSIs) in Turkish ICU patients. METHODS: The EUROBACT II was a prospective observational multicontinental cohort study. We performed a subanalysis of patients from 24 Turkish ICUs included in this study. Risk factors for mortality were identified using multivariable Cox frailty models. RESULTS: Of 547 patients, 58.7% were male with a median [IQR] age of 68 [55-78]. Most frequent sources of HA-BSIs were intravascular catheter [182, (33.3%)] and lower respiratory tract [175, (32.0%)]. Among isolated pathogens (n = 599), 67.1% were Gram-negative, 21.5% Gram-positive and 11.2% due to fungi. Carbapenem resistance was present in 90.4% of Acinetobacter spp., 53.1% of Klebsiella spp. and 48.8% of Pseudomonas spp. In monobacterial Gram-negative HA-BSIs (n = 329), SOFA score (aHR 1.20, 95% CI 1.14-1.27), carbapenem resistance (aHR 2.46, 95% CI 1.58-3.84), previous myocardial infarction (aHR 1.86, 95% CI 1.12-3.08), COVID-19 admission diagnosis (aHR 2.95, 95% CI 1.25-6.95) and not achieving source control (aHR 2.02, 95% CI 1.15-3.54) were associated with mortality. However, availability of clinical pharmacists (aHR 0.23, 95% CI 0.06-0.90) and source control (aHR 0.46, 95% CI 0.28-0.77) were associated with survival. In monobacterial Gram-positive HA-BSIs (n = 93), SOFA score (aHR 1.29, 95% CI 1.17-1.43) and age (aHR 1.05, 95% CI 1.03-1.08) were associated with mortality, whereas source control (aHR 0.41, 95% CI 0.20-0.87) was associated with survival. CONCLUSIONS: Considering high antimicrobial resistance rate, importance of source control and availability of clinical pharmacists, a multifaceted management programme should be adopted in Turkish ICUs.

An exploratory cross-sectional study of the effects of ongoing relationships with accompanying patients on cancer care experience, self-efficacy, and psychological distress.

BACKGROUND: Centre hospitalier de l'Université de Montréal in Canada introduced accompanying patients (APs) into the breast cancer care trajectory. APs are patients who have been treated for breast cancer and have been integrated into the clinical team to expand the services offered to people affected by cancer. This study describes the profiles of the people who received the support and explores whether one-offs vs ongoing encounters with APs influence their experience of care, on self-efficacy in coping with cancer, and on their level of psychological distress. METHODS: An exploratory cross-sectional study was carried out among patients to compare patients who had one encounter with an AP (G1) with those who had had several encounters (G2). Five questionnaires were administered on socio-demographic characteristics, care pathway, evaluation of the support experience, self-efficacy in coping with cancer, and level of psychological distress. Logbooks, completed by the APs, determined the number of encounters. Linear regression models were used to evaluate the associations between the number of encounters, patient characteristics, care pathway, number of topics discussed, self-efficacy measures in coping with cancer, and level of psychological distress. RESULTS: Between April 2020 and December 2021, 60% of 535 patients who were offered support from an AP accepted. Of these, one hundred and twenty-four patients participated in the study. The study aimed to recruit a minimum of 70 patients with the expectation of obtaining at least 50 participants, assuming a response rate of 70%. There were no differences between G1 and G2 in terms of sociodemographic data and care pathways. Statistical differences were found between G1 and G2 for impacts on and the return to daily life (p = 0.000), the return to the work and impacts on professional life (p = 0.044), announcement of a diagnosis to family and friends (p = 0.033), and strategies for living with treatment under the best conditions (p = 0.000). Significant differences were found on the topics of cancer (p = 0.000), genetic testing (p = 0.023), therapeutic options (p = 0.000), fatigue following treatment (p = 0.005), pain and discomfort after treatment or surgery (p = 0.000), potential emotions and their management (p = 0.000) and the decision-making processes (p = 0.011). A significant relationship was found between the two groups for patients' ability to cope with cancer (p = 0.038), and their level of psychological distress at different stages of the care pathway (p = 0.024). CONCLUSIONS: This study shows differences between one-time and ongoing support for cancer patients. It highlights the potential for APs to help patients develop self-efficacy and cope with the challenges of cancer treatment.

Identification of a sub-group of critically ill patients with high risk of intensive care unit-acquired infections and poor clinical course using a transcriptomic score.

BACKGROUND: The development of stratification tools based on the assessment of circulating mRNA of genes involved in the immune response is constrained by the heterogeneity of septic patients. The aim of this study is to develop a transcriptomic score based on a pragmatic combination of immune-related genes detected with a prototype multiplex PCR tool. METHODS: As training cohort, we used the gene expression dataset obtained from 176 critically ill patients enrolled in the REALISM study (NCT02638779) with various etiologies and still hospitalized in intensive care unit (ICU) at day 5-7. Based on the performances of each gene taken independently to identify patients developing ICU-acquired infections (ICU-AI) after day 5-7, we built an unweighted score assuming the independence of each gene. We then determined the performances of this score to identify a subgroup of patients at high risk to develop ICU-AI, and both longer ICU length of stay and mortality of this high-risk group were assessed. Finally, we validated the effectiveness of this score in a retrospective cohort of 257 septic patients. RESULTS: This transcriptomic score (TScore) enabled the identification of a high-risk group of patients (49%) with an increased rate of ICU-AI when compared to the low-risk group (49% vs. 4%, respectively), with longer ICU length of stay (13 days [95% CI 8-30] vs. 7 days [95% CI 6-9], p < 0.001) and higher ICU mortality (15% vs. 2%). High-risk patients exhibited biological features of immune suppression with low monocytic HLA-DR levels, higher immature neutrophils rates and higher IL10 concentrations. Using the TScore, we identified 160 high-risk patients (62%) in the validation cohort, with 30% of ICU-AI (vs. 18% in the low-risk group, p = 0.06), and significantly higher mortality and longer ICU length of stay. CONCLUSIONS: The transcriptomic score provides a useful and reliable companion diagnostic tool to further develop immune modulating drugs in sepsis in the context of personalized medicine.

Detection of Influenza D-Specific Antibodies in Bulk Tank Milk from Swedish Dairy Farms.

Influenza D virus (IDV) has been detected in bovine respiratory disease (BRD) outbreaks, and experimental studies demonstrated this virus's capacity to cause lesions in the respiratory tract. In addition, IDV-specific antibodies were detected in human sera, which indicated that this virus plays a potential zoonotic role. The present study aimed to extend our knowledge about the epidemiologic situation of IDV in Swedish dairy farms, using bulk tank milk (BTM) samples for the detection of IDV antibodies. A total of 461 and 338 BTM samples collected during 2019 and 2020, respectively, were analyzed with an in-house indirect ELISA. In total, 147 (32%) and 135 (40%) samples were IDV-antibody-positive in 2019 and 2020, respectively. Overall, 2/125 (2%), 11/157 (7%) and 269/517 (52%) of the samples were IDV-antibody-positive in the northern, middle and southern regions of Sweden. The highest proportion of positive samples was repeatedly detected in the south, in the county of Halland, which is one of the counties with the highest cattle density in the country. In order to understand the epidemiology of IDV, further research in different cattle populations and in humans is required.

[Post-COVID-19 syndrome]. / Syndrome post-COVID-19.

In the aftermath of acute infection with the severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2), a large number of symptoms persist or appear, constituting a real syndrome called "long COVID-19" or "post-COVID- 19" or "post-acute COVID-19 syndrome". Its incidence is very high, half of patients showing at least one symptom at 4-6 months after Coronarovirus infectious disease 2019 (COVID-19). They can affect many organs. The most common symptom is persistent fatigue, similar to that seen after other viral infections. Radiological pulmonary sequelae are relatively rare and not extensive. On the other hand, functional respiratory symptoms, primarily dyspnoea, are much more frequent. Dysfunctional breathing is a significant cause of dyspnoea. Cognitive disorders and psychological symptoms are also very common, with anxiety, depression and post-traumatic stress symptoms being widely described. On the other hand, cardiac, endocrine, cutaneous, digestive or renal sequelae are rarer. The symptoms generally improve after several months, even if their prevalence at two years remains significant. Most of the symptoms are favored by the severity of the initial illness, and the psychic symptoms by the female sex. The pathophysiology of most symptoms is poorly understood. The influence of the treatments used in the acute phase is also important. Vaccination, on the other hand, seems to reduce their incidence. The sheer number of affected patients makes long-term COVID-19 syndrome a public health challenge.