Long-lasting Symptoms Research Articles

Impaired health-related quality of life in long-COVID syndrome after mild to moderate COVID-19

A growing number of patients with SARS-CoV-2 infections experience long-lasting symptoms. Even patients who suffered from a mild acute infection show a variety of persisting and debilitating neurocognitive, respiratory, or cardiac symptoms (Long-Covid syndrome), consequently leading to limitations in everyday life. Because data on health-related quality of life (HRQoL) is scarce, we aimed to characterize the impact of Long-Covid symptoms after a mild or moderate acute infection on HRQoL. In this observational study, outpatients seeking counseling in the interdisciplinary Post-Covid consultation of the University Hospital Zurich with symptoms persisting for more than 4 weeks were included. Patients who received an alternative diagnosis or suffered from a severe acute Covid-19 infection were excluded. St. George’s Respiratory Questionnaire (SGRQ), Euroquol-5D-5L (EQ-5D-5L), and the Short form 36 (SF-36) were distributed to assess HRQoL. 112 patients were included, 86 (76.8%) were female, median (IQR) age was 43 (32.0, 52.5) years with 126 (91, 180) days of symptoms. Patients suffered frequently from fatigue (81%), concentration difficulties (60%), and dyspnea (60%). Patients mostly stated impairment in performing usual activities and having pain/discomfort or anxiety out of the EQ-5D-5L. EQ index value and SGRQ activity score component were significantly lower in females. SF-36 scores showed remarkably lower scores in the physical health domain compared to the Swiss general population before and during the COVID-19 pandemic. Long-Covid syndrome has a substantial impact on HRQoL. Long-term surveillance of patients must provide clarity on the duration of impairments in physical and mental health.Trial registration: The study is registered on www.ClinicalTrials.gov, NCT04793269.

P63 BREAKTHROUGH COVID-19 IN FULL VACCINATED PATIENTS WITH MULTIPLE MYELOMA: A SINGLE CENTER EXPERIENCE OF 54 PATIENTS

COVID-19-related mortality in the onco-hematological setting is higher than in general population and patients with multiple myeloma (MM) are reported to be particularly vulnerable to SARS-CoV-2 infection, due to compromised humoral and cellular immunity (related to disease itself) and to anti-tumor treatments. Thus, along with general measures, vaccines against SARS-CoV-2 have become, from their approval, the most important strategy to prevent poor outcome from COVID-19 in MM patients. However, limited data have been so far published about epidemiology and outcome of breakthrough COVID-19 in MM patients after three anti-SARS-CoV-2 vaccine doses. We performed a retrospective analysis of 54 consecutive patients with active MM who experienced SARS-CoV-2 infection between December, 2021, and December, 2022 at our Institution (Table 1). Among them, four cases of “reinfection” were documented. All patients had received three doses of anti-SARS-CoV2 vaccines (mostly mRNA) and 6 of them had also received a fourth, “second booster” dose. SARS-CoV-2 infections were diagnosed by RT-PCR or by antigen rapid test on nasopharyngeal swabs. Data about sex, age, ongoing treatment, symptoms, hospitalization, mortality, and additional use of antiviral drugs or monoclonal antibodies for the treatment of COVID-19 were collected. The median age of the whole group was 65 years (IQR: 60-76; range: 39-84), with male preponderance (59.3%). Half of the patients (27) had at least one underlying comorbidity, with chronic cardiopathy (i.e., hypertension, atrial fibrillation) being the most reported. The most frequent isotype was IgG, followed by IgA, light chain and non-secreting subtype. Median number of days between the last dose of vaccine and infection was 136.5 (IQR: 89-199.2; range: 11-381). About disease status at SARS-CoV-2 breakthrough infection, 27 cases (50%) were newly diagnosed/first line MM, 20 (37%) were first relapses, 7 (13%) were further relapsed MM. Forty-eight patients (88.9%) were under treatments including dexamethasone (64.8%), proteosome inhibitors (25.9%), IMiDs (75.9%), anti-CD38 monoclonal antibodies (44.4%) or other therapies (7.4%). Six patients (11.1%) in complete response, three of whom after autologous transplantation and one after CAR-T treatment, were in follow-up, without active therapy. Infection was symptomatic in 35 patients (64.8%) and the most common symptoms were fever, cough, sore throat and runny nose. Overall, 4 patients (7.4%) were hospitalized: among them, 1 (1.8%) was admitted to an intensive care unit (ICU) due to respiratory distress. Fourteen patients (25.9%) received specific anti-SARS-CoV-2 treatment: 7molnupivar, 5 PF-07321332/ritonavir, 1 PF-07321332/ritonavir + sotrovimab, 1 sotrovimab. After a median follow-up of 258 days (IQR: 181-294; range: 43-356), 3 patients (5.6%) had died and no patient reported long-lasting symptoms. Our data indicate that SARS-CoV-2 infection remains frequent even in “triple vaccinated” MM patients, but also that the clinical outcome of COVID-19 appears to be significantly improved by a “booster” dose of vaccine with respect to pre-vaccination era in this high risk population exposed to novel Omicron variants. The role of new antiviral agents and monoclonal antibodies, currently used to reduce the risk of progression of COVID-19 to severe disease, warrants to be further investigated in larger series. Table 1 - Characteristics of 54 full vaccinated MM patients with SARS-CoV-2 infection Age, years Median (IQR)Range 65 (60-76)39-84 Sex, n. (%)MaleFemale 32 (59.3)22 (40.7) Comorbidities, n. (%)012≥3 27 (50)16 (29.7)5 (9.2)6 (11.1) MM subtype, n. (%)IgGIgALight chainNon-secreting 33 (61.1)12 (22.2)7 (13)2 (3.7) Days from last vaccine dose to SARS-CoV-2 infection Median (IQR)Range 136.5 (89-199.2)11-381 Disease status, n. (%)Newly diagnosed/First line1st RelapseRelapse-Refractory 27 (50)20 (37)7 (13) Current MM treatment, n. (%) Dexamethasone Contains Proteosome inhibitor Bortezomib Carfilzomib Ixazomib Contains IMiD (including maintenance therapy) Thalidomide Lenalidomide Pomalidomide Contains CD38 mAb Daratumumab Isatuximab Contains other Elotuzumab, Belantamab Mafodotin Melphalan No therapies 48 (88.9)35 (64.8)14 (25.9)93241 (75.9)632324 (44.4)2224 (7.4)211 6 (11.1) COVID-19 outcome, n. (%)Presence of symptomsHospitalizationHospitalization in ICUDeath to COVID-19 35 (64.8)4 (7.4)1 (1.8)3 (5.6) COVID-19 symptoms, n. (%)FeverCoughSore throatRunny noseFatigueDiarrhea 28 (80)14 (40)11 (31.4)11 (31.4)6 (11.1)3 (8.6) Treatment, n. (%)MolnupiravirPF-07321332/RitonavirPF-07321332/Ritonavir + SotrovimabSotrovimabNone 7 (13)5 (9.3)1 (1.8)1 (1.8)40 (74.1)

Long-Lasting Symptoms in COVID-19 Patients After Hospitalization

Background: Patients with COVID-19 may experience symptoms for a long time. Objectives: The aim of this study is to determine the prevalence of COVID-19 related problems after discharge from the hospital. Methods: This cross-sectional study was conducted on 194 hospitalized COVID-19 patients (110 [56.7%] men and 84 [43.3%] women) using the census method in 2021-2022. The patients were followed up for 4 weeks. Results: The mean age and body mass index (BMI) of the patients were 57.57 ± 16.79 years and 25.9 ± 4.64 kg/m2. The major complaint was fever (75,3%), followed by dyspnea (62%), general weakness (60.8%), cough (59.3%), and anorexia (49%). On admission, lung high-resolution computed tomography (HRCT) scans were normal in 51 patients (26.3%). Regardless of the underlying disease, at least 1 symptom was present in 63 (32%) of patients at the end of the study. Increased appetite was observed in 16 (8.2%) patients at discharge and thereafter. Hair loss was reported in 2% at the beginning and 8% at the end of the study. Conclusions: Prolonged symptoms in COVID-19 patients are common and require long-term care.

Agglomerative Hierarchical Clustering of Long-Lasting Post-Concussive Symptoms: Symptom-Centric Association with Functional Impairments (P8-1.001)

<h3>Objective:</h3> The aim of this study was to characterize the underlying clusters of prolonged post-concussive symptoms lasting more than 12 months, and to investigate their association with functional impairments. <h3>Background:</h3> Following a concussion, approximately 15% of individuals experience persistent symptoms that can lead to functional deficits. However, underlying symptom-clusters that persist beyond 12 months have not been adequately characterized, and their relevance to functional deficits are unclear. <h3>Design/Methods:</h3> Although hierarchical clustering is ideally suited in evaluating subjective symptom severities, it has not been applied to post-concussive symptoms or the Rivermead Post-Concussion Questionnaire (RPQ). The RPQ and functional impairments questions were administered via a smartphone application to 445 individuals who self-reported prolonged post-concussive symptoms. Symptom-clusters were obtained using agglomerative hierarchical clustering, and their association with functional deficits were investigated with sensitivity analyses, and corrected for multiple comparisons. <h3>Results:</h3> Five symptom-clusters were identified: headache-related, sensitivity to light and sound, cognitive, mood-related, and sleep-fatigue. Individuals with more severe RPQ symptoms were more likely to report functional deficits (p&lt;0.0001). Whereas the headache and sensitivity clusters were associated with at most one impairment, at-least-mild sleeping difficulties and fatigue were associated with four, and moderate-to-severe cognitive difficulties with five functional impairments (all p&lt;0.01). <h3>Conclusions:</h3> Symptom-clusters may be clinically useful for functional outcome stratification and for targeted rehabilitation therapies, for example directed towards mild trouble sleeping. Further studies are required to replicate these findings in other cohorts and questionnaires, and to ascertain the effects of symptomatic intervention on functional outcomes. <b>Disclosure:</b> Mr. Kuleindiren has nothing to disclose. Mr. Tiersen has received personal compensation for serving as an employee of Mindstep. Mr. Tiersen has stock in Mindstep. Mr. Tiersen has received research support from Imperial College London. Dr. Johal has nothing to disclose. Dr. Lin has nothing to disclose. Mr. Selim has received personal compensation in the range of $500-$4,999 for serving as an officer or member of the Board of Directors for Mindstep . Mr. Selim has stock in Mindstep. Dr. Rifkin-Zybutz has received personal compensation for serving as an employee of Mindset Technologies Ltd. Dr. Rifkin-Zybutz has received research support from National Institute for Health and Care Research. Mr. Mahmud has received personal compensation for serving as an employee of Mindset Technologies Ltd .

Apractical approach for the treatment of post-COVID symptoms.

For the past 3years, our daily lives have been largely dictated by the coronavirus disease 2019 (COVID-19) pandemic. In many people, this infectious disease leads to long-lasting symptoms, which can vary greatly in form and intensity between individuals. This report describes the case of ayoung patient who had no health restrictions until she came into contact with severe acute respiratory syndrome coronavirus2 (SARS-CoV-2). As part of apost-COVID syndrome, she not only temporarily lost her ability to work, but was also no longer able to manage her daily life independently. Acrucial therapeutic approach, in this case, was the use of heparin-induced extracorporeal LDL/fibrinogen precipitation (H.E.L.P.) apheresis.

Impairment of quality of life due to COVID-19-induced long-term olfactory dysfunction.

Olfactory dysfunction is one of many long-lasting symptoms associated with COVID-19, estimated to affect approximately 60% of individuals and often lasting several months after infection. The associated daily life problems can cause a decreased quality of life. Here, we assessed the association between perceived quality of life and both qualitative and quantitative olfactory function (distorted and weakened sense of smell, respectively) in 58 individuals who had undergone confirmed SARS-CoV-2 infection and who complained about olfactory dysfunction. Participants with large quantitative olfactory dysfunction experienced a greater reduction in their quality of life. Moreover, our participants had a high prevalence of qualitative olfactory dysfunction (81%) with a significant correlation between qualitative olfactory dysfunction and daily life impairment. Strong drivers of low quality of life assessments were lack of enjoyment of food as well as worries related to coping with long-term dysfunctions. These results stress the clinical importance of assessing qualitative olfactory dysfunction and the need to develop relevant interventions. Given the poor self-rated quality of life observed, healthcare systems should consider developing support structures, dietary advice, and guidelines adapted to individuals experiencing qualitative olfactory dysfunction.

Sex-specific effects of psychedelic drug exposure on central amygdala reactivity and behavioral responding

Psilocybin and its active metabolite psilocin have been shown to elicit rapid and long-lasting symptom improvements in a variety of affective psychiatric illnesses. However, the region-specific alterations underlying these therapeutic effects remain relatively unknown. The central amygdala (CeA) is a primary output region within the extended amygdala that is dysregulated in affective psychiatric disorders. Here, we measured CeA activity using the activity marker c-Fos and CeA reactivity using fiber photometry paired with an aversive air-puff stimulus. We found that psilocin administration acutely increased CeA activity in both males and females and increased stimulus specific CeA reactivity in females, but not males. In contrast, psilocin produced time-dependent decreases in reactivity in males, but not in females, as early as 2 days and lasting to 28 days post administration. We also measured behavioral responses to the air-puff stimulus and found sex-dependent changes in threat responding but not exploratory behavior or general locomotion. Repeated presentations of the auditory component of the air-puff were also performed and sex-specific effects of psilocin on CeA reactivity to the auditory-alone stimulus were also observed. This study provides new evidence that a single dose of psilocin produces sex-specific, time-dependent, and enduring changes in CeA reactivity and behavioral responding to specific components of an aversive stimulus.

Long-Term Consequences of COVID-19: A 1-Year Analysis.

Long-lasting symptoms after SARS-CoV-2 infection have been described many times in the literature and are referred to as Long COVID. In this prospective, longitudinal, monocentric, observational study, we collected the health complaints of 474 patients (252 ambulatory and 222 hospitalized) at Lausanne University Hospital 1 year after COVID-19 diagnosis. Using a self-reported health survey, we explored cardiopulmonary, vascular, neurological, and psychological complaints. Our results show that age, Charlson comorbidity index, and smoking habits were associated with hospital admission. Regarding the vascular system, we found that having had thromboembolism before SARS-CoV-2 infection was significantly associated with a higher risk of recurrence of thromboembolism at 1 year. In the neurologic evaluation, the most frequent symptom was fatigue, which was observed in 87.5% of patients, followed by "feeling slowed down", headache, and smell disturbance in 71.5%, 68.5%, and 60.7% of cases, respectively. Finally, our cohort subjects scored higher overall in the STAI, CESD, Maastricht, and PSQI scores (which measure anxiety, depression, fatigue, and sleep, respectively) than the healthy population. Using cluster analysis, we identified two phenotypes of patients prone to developing Long COVID. At baseline, CCS score, prior chronic disease, stroke, and atrial fibrillation were associated with Long COVID. During COVID infection, mechanical ventilation and five neurological complaints were also associated with Long COVID. In conclusion, this study confirms the wide range of symptoms developed after COVID with the involvement of all the major systems. Early identification of risk factors associated with the development of Long COVID could improve patient follow-up; nevertheless, the low specificity of these factors remains a challenge to building a systematic approach.

«Long COVID»: the current state of the problem. A review of foreign scientific and medical publications

Not all the patients diagnosed with COVID-19 can completely recover; some of them experience various persistent symptoms which wax and wane. As the COVID-19 pandemic continues, the number of people with long-term symptoms is rapidly increasing, adding to the burden on the healthcare and society.&#x0D; The prevalence of the COVID-19 consequences varies between studies, with some researchers reporting that more than half of hospitalized patients suffer from long-lasting symptoms for at least 6 months after the acute SARS-CoV-2 infection, and others observing such symptoms for more than 12 months. The overall prevalence of residual symptoms in patients infected with SARS-CoV-2 is currently estimated as 1030%. This clinical syndrome is commonly referred to as post-acute COVID syndrome (PACS) or long COVID.&#x0D; This multifactorial syndrome is characterised by a variety of debilitating symptoms, including fatigue, brain fog, postural hypotension with tachycardia, and post-exertional malaise. Many of the post COVID-19 condition observations, including changes in the immune, cardiovascular, gastrointestinal, nervous and autonomic systems, are shared with those for myalgic encephalitis/chronic fatigue syndrome (ME/CFS) patients. A comprehensive longitudinal symptom monitoring is required to confirm the diagnosis, uncover the mechanisms of post-COVID-19-associated ME/CFS, and develop the prevention and treatment measures. The current absence of an effective treatment reflects the unclear causes of the post COVID-19 conditions which cannot be targeted properly until the mechanism is established and confirmed.&#x0D; The multisystem aspects of long COVID remain poorly understood. The COVID-19 pandemic has exposed a significant gap in the knowledge about the post-acute consequences of infectious diseases and the need for a unified nomenclature and classification, diagnostic criteria, and a reliable assessment of post-COVID conditions. Unraveling the complex biology of PACS relies on the identification of biomarkers in the plasma and tissue samples harvested from individuals infected with SARS-CoV-2 that will allow classification of the phenotypes of patients who develop PACS.&#x0D; For a comprehensive treatment of patients with post-COVID syndrome, multidisciplinary therapy and rehabilitation are required. Understanding the physiological mechanisms underlying the long-term clinical manifestations of COVID-19 and the post-COVID-19 state is vital for the development of appropriate effective therapies.

Cognition and Mental Health in Pediatric Patients Following COVID-19.

The global coronavirus pandemic has significantly impacted public health and has been a research subject since its emergence in 2019. The acute phase of the disease leads to pulmonary and non-pulmonary manifestations, which in some individuals may progress to long-lasting symptoms. In this article, we conducted a narrative review of the current literature to summarize current knowledge regarding long COVID syndrome in children, focusing on cognitive symptoms. The review included a search of three databases (PubMed, Embase, and Web of Science) using the key phrases "post COVID-19 cognitive pediatric", "long COVID pediatric", "mental health long COVID children", and "COVID-19 cognitive symptoms". A total of 102 studies were included. The review revealed that the main long-term cognitive symptoms following COVID-19 were memory and concentration deficits, sleep disturbances, and psychiatric states such as anxiety and stress. In addition to the direct physiological effects of a viral infection, there are psychological, behavioral, and social factors contributing to cognitive impairment, which should be addressed regarding the pediatric population. The high prevalence of neurocognitive symptoms in children following COVID-19 emphasizes the importance of understanding the mechanisms of nervous system involvement.

Quality of life and ability to work of patients with Post-COVID syndrome in relation to the number of existing symptoms and the duration since infection up to 12 months: a cross-sectional study

PurposeFollowing SARS-CoV-2 virus infection, patients may suffer from long-lasting symptoms regardless of disease severity. Preliminary results show limitations in health-related quality of life (HRQoL). The aim of this study is to show a possible change depending on the duration since infection and the accumulation of symptoms. Additionally, other possible influencing factors will be analyzed.MethodsThe study population consisted of patients (18–65 years) presenting to the Post-COVID outpatient clinic of the University Hospital Jena, Germany, between March and October 2021. The HRQoL was assessed by the use of the RehabNeQ and the SF-36. Data analysis was descriptive with frequencies, means, and/or percentages. In addition, a univariate analysis of variance was performed to show the dependence of physical and psychological HRQoL on specific factors. This was finally tested for significance at an alpha level of 5%.ResultsData from 318 patients were analyzed, most of whom had 3–6 months of infection (56%) and 5–10 symptoms persisted (60.4%). Both mental (MCS) and physical sum score (PCS) of HRQoL were significantly lower than those of the German normal population (p < .001). The number of remaining symptoms (MCS p = .0034, PCS p = .000) as well as the perceived ability to work (MCS p = .007, PCS p = .000) influenced the HRQoL.ConclusionThe HRQoL of patients with Post-COVID-syndrome is still reduced months after infection and so is their occupational performance. In particular, the number of symptoms could have an influence on this deficit, which would need to be further investigated. Further research is needed to detect other factors influencing HRQoL and to implement appropriate therapeutic interventions.

Behavioral and biochemical effects of alcohol withdrawal in female C3H/HeNRj and C57BL/6JRj mice.

Alcohol use disorder (AUD) is a major problem of our society and is often characterized and worsened by relapse. Prolonged alcohol exposure leads to numerous biochemical alterations that, upon cessation of alcohol intake, cause an array of immediate and lasting withdrawal symptoms. Acute withdrawal and neuroinflammation can be harmful in themselves, and lasting withdrawal symptoms contribute to relapse. Here, we conducted an initial feasibility study assessing several behavioral and neurochemical factors in female C3H/HeNRj (C3H) and C57BL/6JRj (B6) mice to determine which strain showed the clearest alcohol withdrawal symptoms during long-term abstinence and neurochemical alterations following re-exposure. Female C3H and B6 mice (n = 12 per group/strain) were intermittently exposed to alcohol-containing or control liquid diets for 3 weeks. Acute and prolonged withdrawal symptoms were assessed over a period of 3 weeks using a battery of behavioral test, comprised of alcohol self-administration, anhedonia, hyperalgesia, anxiety-like and depressive-like disturbances. Brain inflammation was measured by multiplex cytokine assay. Monoamine levels in the hippocampus and striatum, as well as exploratory analyses of cations levels in the cerebellum, were assessed by High-Performance Liquid Chromatography (HPLC). Both C3H and B6 alcohol-exposed mice displayed decreased saccharin intake or preference and higher stress levels assessed by ultrasonic vocalizations (USVs) recordings. B6 but not C3H alcohol-exposed mice also exhibited a slower decline of alcohol oral self-administration (OSA), hyperalgesia, elevated brain TNF-α and elevated serotonin turnover. Our findings highlight the suitability of the B6 strain to study the behavioral and neurochemical alterations caused by alcohol withdrawal and the potential efficacy of experimental treatments, not only in early detoxification, but also in prolonged abstinence. The feasibility of these assays is important because long-lasting withdrawal symptoms are often the main cause of relapse in alcohol-dependent patients.

The Impact of SARS-CoV-2 on the Brain: It Is All in Your Head

What is going on with SARS-CoV-2 infection and your brain? Even in mild infection there may be neurological injury that affects recovery. In our study, brain tissue recovered from SARS-CoV-2 infected non-human primates revealed microbleeds, neuron injury and death, and evidence of brain hypoxia, all of which may cause long-lasting neurological symptoms after infection.

Persistent short nighttime sleep duration is associated with a greater post-COVID risk in fully mRNA-vaccinated individuals

Short nighttime sleep duration impairs the immune response to virus vaccination, and long nighttime sleep duration is associated with poor health status. Thus, we hypothesized that short (<6 h) and long (>9 h) nighttime sleepers have a higher post-COVID risk than normal nighttime sleepers, despite two doses of mRNA vaccine (which has previously been linked to lower odds of long-lasting COVID-19 symptoms). Post-COVID was defined as experiencing at least one core COVID-19 symptom for at least three months (e.g., shortness of breath). Multivariate logistic regression adjusting for age, sex, BMI, and other factors showed in 9717 respondents (age span 18–99) that two mRNA vaccinations lowered the risk of suffering from post-COVID by about 21% (p < 0.001). When restricting the analysis to double-vaccinated respondents (n = 5918), short and long sleepers exhibited a greater post-COVID risk than normal sleepers (adjusted OR [95%-CI], 1.56 [1.29, 1.88] and 1.87 [1.32, 2.66], respectively). Among respondents with persistent sleep duration patterns during the pandemic compared to before the pandemic, short but not long sleep duration was significantly associated with the post-COVID risk (adjusted OR [95%-CI], 1.59 [1.24, 2.03] and 1.18 [0.70, 1.97], respectively). No significant association between sleep duration and post-COVID symptoms was observed in those reporting positive SARS-CoV-2 test results (n = 538). Our findings suggest that two mRNA vaccinations against SARS-CoV-2 are associated with a lower post-COVID risk. However, this protection may be less pronounced among those sleeping less than 6 h per night. Our findings warrant replication in cohorts with individuals with confirmed SARS-CoV-2 infection.

Complex network analysis of arboviruses in the same geographic domain: Differences and similarities

Arbovirus can cause diseases with a broad spectrum from mild to severe and long-lasting symptoms, affecting humans worldwide and therefore considered a public health problem with global and diverse socio-economic impacts. Understanding how they spread within and across different regions is necessary to devise strategies to control and prevent new outbreaks. Complex network approaches have widespread use to get important insights on several phenomena, as the spread of these viruses within a given region. This work uses the motif-synchronization methodology to build time varying complex networks based on data of registered infections caused by Zika, chikungunya, and dengue virus from 2014 to 2020, in 417 cities of the state of Bahia, Brazil. The resulting network sets capture new information on the spread of the diseases that are related to the time delay in the synchronization of the time series among different municipalities. Thus the work adds new and important network-based insights to previous results based on dengue dataset in the period 2001–2016. The most frequent synchronization delay time between time series in different cities, which control the insertion of edges in the networks, ranges 7 to 14 days, a period that is compatible with the time of the individual-mosquito-individual transmission cycle of these diseases. As the used data covers the initial periods of the first Zika and chikungunya outbreaks, our analyses reveal an increasing monotonic dependence between distance among cities and the time delay for synchronization between the corresponding time series. The same behavior was not observed for dengue, first reported in the region back in 1986, either in the previously 2001–2016 based results or in the current work. These results show that, as the number of outbreaks accumulates, different strategies must be adopted to combat the dissemination of arbovirus infections.

The trajectory of two negative symptom dimensions in first-episode psychosis and the role of cannabis use: A 10-year follow-up study

ObjectiveTo investigate the trajectories of diminished expression and apathy over 10 years. Further, to explore the effects of baseline- and persistent cannabis use on the development of diminished expression and apathy during follow-up, while controlling other potential sources and predictors of secondary negative symptoms. Methods351 participants with a first episode of non-affective psychosis were examined at baseline and invited to follow-up at one year and 10 years. The trajectories of diminished expression and apathy were investigated using linear mixed models. Subsequently, cannabis use and other potential predictors and sources of secondary negative symptoms were added to the model to investigate the respective impact on their trajectories. ResultsThe severity of both diminished expression and apathy decreased during the follow-up period after the first episode of psychosis, with the most improvement observed from baseline to 1-year follow-up. Cannabis use at baseline was associated with a long-lasting higher symptom load for diminished expression, but not apathy. Introducing persistent cannabis use to the model further strengthened the association with diminished expression. ConclusionBoth cannabis use at baseline and persistent cannabis use after a first episode of psychosis were associated with more severe symptoms of diminished expression. Our results imply a causal relationship between cannabis use and diminished expression and suggest that measures to reduce cannabis use both before and after psychosis onset may reduce expressive negative symptoms.

Clinical Outcomes of SARS-CoV-2 Breakthrough Infections in Liver Transplant Recipients during the Omicron Wave.

At the start of the pandemic, liver transplant recipients (LTR) were at high risk of developing severe COVID-19. Here, the outcomes of breakthrough infections in fully vaccinated LTR (n = 98) during the Omicron wave were assessed. In most patients, a mild disease course was observed, but 11 LTR (11.2%) required hospitalization for COVID-19-related complications. All patients survived. The LTR requiring hospitalization were older (67 years vs. 54 years; p < 0.001), had a higher Charlson comorbidity index (9 vs. 5; p < 0.001), and a lower anti-S RBD titer (Roche Elecsys) prior to infection (508.3 AU/mL vs. 2044 AU/mL; p = 0.03). Long-lasting symptoms for ≥4 weeks were reported by 37.5% of LTR (30/80). Risk factors in LTR included female sex (p = 0.01; Odds Ratio (OR) = 4.92 (95% confidence interval (CI) (1.5-16.5)) and dyspnea (p = 0.009; OR = 7.2 (95% CI (1.6-31.6)) during infection. Post-infection high anti-S RBD antibody levels were observed in LTR, and healthy controls (HC), while the cellular immune response, assessed by interferon-gamma release assay (EUROIMMUN), was significantly lower in LTR compared with HC (p < 0.001). In summary, in fully vaccinated LTR, SARS-CoV-2 breakthrough infections during the Omicron wave led to mild disease courses in the majority of patients and further boosted the humoral and cellular hybrid anti-SARS-CoV-2-directed immune response. While all patients survived, older and multimorbid LTR with low baseline antibody titers after vaccination still had a substantial risk for a disease course requiring hospitalization due to COVID-19-related complications.

Two-Years Follow-Up of Symptoms and Return to Work in Complex Post-COVID-19 Patients.

Many COVID-19 patients present with severe long-lasting symptoms. They might benefit from a coordination team to manage such complex situations, but late efficacy still needs to be determined. Out of 105 contacts, 45 patients had two phone consultations separated by personalized support 15 and 22 months, respectively, after COVID infection. Self-reported symptoms, feelings of improvement and ability to return to work allowed us to determine the efficacy of the therapeutic strategy proposed. Unlike what was expected, many post-COVID-19 patients directly contacted the coordination team and had significant pre-existing comorbidities. Despite exercise, respiratory, olfactory rehabilitations, cognition/speech therapy and/or psychological support, the more frequent self-reported symptoms (fatigue, neurocognitive disorders, muscles and joint pain) did not resolve. However, dyspnea, anxiety and chest pain were significantly reduced. Finally, 2/3 of the patients felt some degree of improvement and returned to work either partially or fully, but 1/3 remained complaining of symptoms and out of work as late as 22 months after COVID occurrence. All patients greatly appreciated the second phone consultation. In such complex situations, besides early and adapted rehabilitations and psychological help allowing better symptom management, relatively simple actions such as a phone call might be very useful to reduce patients' feelings of abandonment.

Decoding the role of loratadine in optimally managing and in alleviating the burden of allergic rhinitis

Despite an alarmingly rise in prevalence of allergic rhinitis in the last 2 decades, yet till date it remains underdiagnosed, undertreated, or mistreated in India. The distinguishing features of allergic rhinitis are commonly misinterpreted with the common cold and thus early detection of allergic rhinitis is often delayed in primary care. Poorly controlled allergic rhinitis adversely impairs overall long-term productivity at work or school, quality of life (QoL) and can also trigger underlying comorbidities like asthma. Thus, early diagnosis and timely referral is the need of the hour for more effective management which will reduce the overall burden of allergic rhinitis in India. As allergic rhinitis needs long-term management, it is also paramount to prescribe highly efficacious, cost-effective treatment with minimal side effects like drowsiness to prevent disruption of patient’s QoL. However, current therapies including intranasal corticosteroids have adverse long-term complications and antihistamines like cetirizine, levocetirizine, and fexofenadine have varying degrees of sedation.With these concerns, a management algorithm was developed to aid for early diagnosis in primary care which provides cost effective option of right medication for a proper duration of time to optimize overall patient care. After a thorough discussion of key opinion leaders and evidence-based recommendations, it was highlighted that loratadine deserves to be considered as a first-line antihistamine therapy due to its rapid and long-lasting symptom relief, non drowsy, and low complication rate for long-term management of allergic rhinitis.

Inflammatory markers and pulmonary function in adolescents and young adults 6 months after mild COVID-19.

Both public and scientific attention have shifted from the acute COVID-19 illness to the chronic disability experienced by a proportion of COVID-19 convalescents. Post COVID-19 condition, a term used for long-lasting symptoms after COVID-19, can affect individuals across all disease severity and age groups. Data on post-COVID-19 symptomatology, epidemiology and pathophysiology in adolescents and young adults are scarce. To date, little is known on the immunological and pulmonary trends in these patients after COVID-19. This study investigated immunological markers and pulmonary function in non-hospitalized patients in this group at 6 months after initial mild COVID-19 infection. Non-hospitalized SARS-CoV-2 positive (n = 405) and SARS-CoV-2 negative (n = 111) adolescents and young adults (aged 12-25 years) were followed prospectively for six months after SARS-CoV-2 PCR testing. At baseline and at six months follow-up, all participants underwent an assessment including clinical examination, questionnaires, spirometry, and blood sampling. Cross-sectional comparisons of blood biomarkers; including white blood cell counts, CRP, GDF-15, a 27-multiplex cytokine assay, complement activation products and SARS-CoV-2 antibodies; and spirometry measures were performed after classification of all participants according to their COVID-19 status and adherence to post-COVID-19 case criteria. Associations between biomarkers and COVID-19 symptoms were explored. No difference in pulmonary function was detected between the groups. COVID-19 convalescents had higher levels of chemokines eotaxin, MCP-1 and IP-10 than non-infected controls. The increase was modest and not associated with long-lasting COVID-19 symptoms. Elevated inflammatory mediators were found in adolescents and young adults six months after mild COVID-19, but there was no association with post-COVID-19 condition.