The association between probable post-COVID-19 condition and sleep-related parameters: a longitudinal study of non-hospitalised patients.

The long-term effects of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection on sleep remain poorly known. We evaluated the association between probable post-COVID-19 condition and changes in sleep quality and quantity before and after SARS-CoV-2 infection in a consecutive sample of non-hospitalized adults. Individuals were identified with SARS-CoV-2 infection in 2020 at the central laboratory of a tertiary hospital in Porto and followed as outpatients. We included patients diagnosed with SARS-CoV-2 infection ≥3 months before this evaluation, with no missing data on key variables (n = 2445). Participants completed a questionnaire that included sociodemographic, clinical, and infection-related questions. We computed changes in sleep-related parameters referred to 1 month before diagnosis and 1 week before the questionnaire. Multinomial logistic regression models were fitted to compute crude and adjusted odds ratios and 95% confidence intervals (95% CIs). Compared to the pre-infection period, those with probable post-COVID-19 condition reported a greater decrease in hours of sleep, had a 2.60 (95% CI 2.02-3.34) higher adjusted odds of perceiving their sleep quality as worsened and experienced a significant increase in number of days with sleeping disturbances as defined according to multiple items. The association between post-COVID-19 condition and indicators of poor sleep health requires special attention from healthcare professionals and services. It is essential that appropriate multidisciplinary care is provided to mitigate the physical, psychological, social, and professional impact of sleeping problems in these already burdened patients.

Cat-scratch disease: a rare cause of osteomyelitis.

Cat-scratch disease is a zoonosis caused by Bartonella henselae, characterised by regional lymphadenopathy. Rarer presentations, such as osteomyelitis, can occur.We present an adolescent girl with severe right lumbar pain and fever, without animal contacts or recent travels. On examination, pain on flexion of torso, movement limitation and marked lordosis were noted, but there were no inflammatory signs, palpable masses or lymph nodes. Serological investigations revealed elevated inflammatory markers. Imaging revealed a paravertebral abscess with bone erosion. Several microbiological agents were ruled out. After a second CT-guided biopsy, PCR for Bartonella spp was positive. At this point, the family recalled having a young cat some time before. Cat-scratch disease was diagnosed, and complete recovery achieved after treatment with doxycycline and rifampicin.Cat-scratch disease is a challenging diagnosis in the absence of typical features. However, B. henselae must be investigated if common pathogens are ruled out and response to therapy is poor.

Endocarditis Without Risk Factors: Clinical Awareness Is Key.

Infective endocarditis (IE) is a relatively common disease that can manifest as a spectrum of clinical findings. Clinical awareness is key for the diagnosis. We present a case of a 14-year-old adolescent with fever, coughing, skin lesions, lip drooping, and quadrantanopia. Lumbar puncture was unremarkable and a head CT scan showed ischemic lesions. Blood cultures were positive for Staphylococcus aureus. A transesophageal echocardiogram showed a 7 x 7 mm mitral valve vegetation. The diagnosis of IE was made and flucloxacillin was initiated. Clinical suspicion was decisive for diagnosis. This case illustrates a serious and atypical presentation of an already uncommon disease in a patient without known risk factors for IE. While the initial cardiology workup was negative, a high clinical suspicion should always motivate further investigation as the consequences of untreated acute endocarditis are serious and life-threatening.

Neuroimaging of central nervous system tuberculosis.

A 20-month-old female, not immunized with Bacillus Calmette-Guérin (BCG) vaccine, was admitted due to a four-day history of fever and cough. In the past three months, she presented respiratory infections, weight loss and enlarged cervical lymph nodes. On day two of admission, she displayed drowsiness and positive Romberg's sign; cerebrospinal fluid (CSF) workout revealed 107/ul cells, low glucose and high protein levels. Ceftriaxone and acyclovir were initiated, and she was transferred to our tertiary hospital. Brain magnetic resonance imaging showed punctiform focal areas of restricted diffusion in left capsular lenticular region suggestive of vasculitis secondary to infection. Tuberculin skin test and interferon-gamma release assay were positive. She started tuberculostatic therapy, but two days later she presented tonic-clonic seizures and impaired consciousness. Cerebral computed tomography (CT) revealed tetrahydrocephalus (Figure 1), needing external ventricular derivation. She had a slow clinical improvement, requiring several neurosurgical interventions and developing a syndrome of inappropriate antidiuretic secretion alternating with cerebral salt wasting. Positive results for Mycobacterium tuberculosis were obtained by CSF culture and by polymerase chain reaction in CSF, bronchoalveolar lavage and gastric aspirate specimens. Repeated brain CT showed a large-vessel vasculitis with basal meningeal enhancement, typical of central nervous system (CNS) tuberculosis (Figure 2). She completed one month of corticosteroids and maintained antituberculosis treatment. At two years of age, she has spastic paraparesis and no language skills. Portugal had 1836 cases of tuberculosis (17.8 per 100000) in 2016 and was considered a low-incidence country; consequently, BCG vaccination is not universal (1). We present a severe case of CNS tuberculosis with intracranial hypertension, vasculitis and hyponatremia, associated with poorer outcomes (2). A high index of suspicion allowed prompt start of antituberculosis treatment. Diagnosis was corroborated by microbiological positivity and a typical triad in neuroimaging (hydrocephalus, vasculitis and basal meningeal enhancement) (3), which we wish to emphasize.

Monitoring COVID-19 and Influenza: The Added Value of a Severe Acute Respiratory Infection Surveillance System in Portugal.

Background: Severe acute respiratory infections (SARI) surveillance is recommended to assess the severity of respiratory infections disease. In 2021, the National Institute of Health Doutor Ricardo Jorge, in collaboration with two general hospitals, implemented a SARI sentinel surveillance system based on electronic health registries. We describe its application in the 2021/2022 season and compare the evolution of SARI cases with the COVID-19 and influenza activity in two regions of Portugal. Methods: The main outcome of interest was the weekly incidence of patients hospitalized due to SARI, reported within the surveillance system. SARI cases were defined as patients containing ICD-10 codes for influenza-like illness, cardiovascular diagnosis, respiratory diagnosis, and respiratory infection in their primary admission diagnosis. Independent variables included weekly COVID-19 and influenza incidence in the North and Lisbon and Tagus Valley regions. Pearson and cross-correlations between SARI cases, COVID-19 incidence and influenza incidence were estimated. Results: A high correlation between SARI cases or hospitalizations due to respiratory infection and COVID-19 incidence was obtained (ρ = 0.78 and ρ = 0.82, respectively). SARI cases detected the COVID-19 epidemic peak a week earlier. A weak correlation was observed between SARI and influenza cases (ρ = -0.20). However, if restricted to hospitalizations due to cardiovascular diagnosis, a moderate correlation was observed (ρ = 0.37). Moreover, hospitalizations due to cardiovascular diagnosis detected the increase of influenza epidemic activity a week earlier. Conclusion: In the 2021/2022 season, the Portuguese SARI sentinel surveillance system pilot was able to early detect the COVID-19 epidemic peak and the increase of influenza activity. Although cardiovascular manifestations associated with influenza infection are known, more seasons of surveillance are needed, to confirm the potential use of cardiovascular hospitalizations as an indicator of influenza activity.

Evaluation of urinary cysteinyl leukotrienes as biomarkers of severity and putative therapeutic targets in COVID-19 patients.

BACKGROUND: Cysteinyl leukotrienes (CysLT) are potent inflammation-promoting mediators, but remain scarcely explored in COVID-19. We evaluated urinary CysLT (U-CysLT) relationship with disease severity and their usefulness for prognostication in hospitalized COVID-19 patients. The impact on U-CysLT of veno-venous extracorporeal membrane oxygenation (VV-ECMO) and of comorbidities such as hypertension and obesity was also assessed. METHODS: Blood and spot urine were collected in "severe" (n = 26), "critically ill" (n = 17) and "critically ill on VV-ECMO" (n = 17) patients with COVID-19 at days 1-2 (admission), 3-4, 5-8 and weekly thereafter, and in controls (n = 23) at a single time point. U-CysLT were measured by ELISA. Routine markers, prognostic scores and outcomes were also evaluated. RESULTS: U-CysLT did not differ between groups at admission, but significantly increased along hospitalization only in critical groups, being markedly higher in VV-ECMO patients, especially in hypertensives. U-CysLT values during the first week were positively associated with ICU and total hospital length of stay in critical groups and showed acceptable area under curve (AUC) for prediction of 30-day mortality (AUC: 0.734, p = 0.001) among all patients. CONCLUSIONS: U-CysLT increase during hospitalization in critical COVID-19 patients, especially in hypertensives on VV-ECMO. U-CysLT association with severe outcomes suggests their usefulness for prognostication and as therapeutic targets.

Non-COVID-19 respiratory viral infection.

Implemented control measures brought about by the coronavirus disease 2019 (COVID-19) pandemic have changed the prevalence of other respiratory viruses, often relegating them to a secondary plan. However, it must not be forgotten that a diverse group of viruses, including other human coronaviruses, rhinoviruses, respiratory syncytial virus, human metapneumoviruses, parainfluenza and influenza, continue to be responsible for a large burden of disease. In fact, they are among the most common causes of acute upper and lower respiratory tract infections globally. Viral respiratory infections can be categorised in several ways, including by clinical syndrome or aetiological agent. We describe their clinical spectrum. Distinctive imaging features, advances in microbiological diagnosis and treatment of severe forms are also discussed. Educational aims: To summarise the knowledge on the spectrum of disease that respiratory viral infections can cause and recognise how often they overlap.To learn the most common causes of respiratory viral infections and acknowledge other less frequent agents that may target certain key populations (e.g. immunocompromised patients).To improve awareness of the recent advances in diagnostic methods, including molecular assays and helpful features in imaging techniques.To identify supportive care strategies pivotal in the management of severe respiratory viral infections.

Monkeypox after Occupational Needlestick Injury from Pustule.

We report a case of monkeypox in a physician after an occupational needlestick injury from a pustule. This case highlights risk for occupational transmission and manifestations of the disease after percutaneous transmission: a short incubation period, followed by a solitary lesion at the injured site and later by systemic symptoms.

[Guidelines for the Treatment and Follow-Up of Patients with Q Fever]. / Recomendações para o Tratamento e Seguimento de Doentes com Febre Q.

Q fever (or query fever) is a zoonotic infectious disease with worldwide distribution transmitted by an intracellular Gram-negative bacterium, Coxiella burnetii. The most common identified sources of human infection are farm animals, such as sheep, goats and cattle. The disease is endemic in mainland Portugal, with most cases notified in the central and southern regions. Q fever is a complex and pleomorphic disease, with those affected presenting with a wide range of manifestations from acute self-limited flu-like symptoms with good prognosis to persistent localized forms that may harbor a poor prognosis. Cases might occur in an isolated fashion or following outbreaks with great public health repercussion, as seen recently in the Netherlands from 2007 to 2010. Given the complexity of this infection, there is no universal consensus to date on the best strategy to manage Q fever patients. These guidelines provide recommendations regarding the treatment and follow-up of these patients, based on studies, on the author's experience and on the opinion of international experts. The aim is to harmonize the management of these patients taking into account not only the clinical manifestations but also the risk factors of the host in order to reduce disease-associated morbidity and mortality.

A febre Q (do inglês query fever) é uma zoonose de distribuição mundial transmitida por uma bactéria intracelular Gram negativo, Coxiella burnetii. Os ruminantes domésticos são os principais reservatórios implicados na transmissão da doença ao ser humano. Em Portugal continental, esta doença é endémica, com o maior número de casos notificados nas regiões Centro e Sul. A doença causada por C. burnetii é complexa e polimórfica, podendo manifestar-se sob uma forma aguda autolimitada do tipo gripal, com um curso ligeiro a moderado e prognóstico benigno, e/ou sob uma forma persistente, geralmente localizada e de evolução grave ou potencialmente fatal. Pode ocorrer em casos isolados ou em contexto de surtos, alguns com importantes implicações em saúde pública, como o verificado na Holanda em 2007 - 2010. Dada a complexidade e espetro clínico da febre Q, não existe um consenso universal sobre a melhor forma de tratamento, gestão e seguimento destes doentes. Este protocolo é uma sugestão de tratamento e seguimento dos doentes com febre Q, compilando a informação de estudos e opiniões de peritos internacionais e a experiência dos autores. Pretende-se assim uniformizar a gestão destes doentes tendo em conta não só o espetro das suas manifestações clínicas, mas também os fatores de risco do hospedeiro, por forma a reduzir morbimortalidade que a doença possa causar.

Brown-Séquard syndrome in a patient with spondyloarthritis after COVID-19 vaccine: a challenging differential diagnosis.

A 41-year-old woman with pre-radiographic axial and peripheric spondyloarthritis, taking adalimumab since 2010, started motor impairment of the right limbs and numbness of the left leg seven days after the administration of COVID-19 mRNA vaccine. Adalimumab was taken 47 days before clinical onset. A comprehensive study for infectious, autoimmune and neoplastic causes were unremarkable. MRI depicted an acute inflammatory lesion at C2 level with gadolinium enhancement. The patient started methylprednisolone with clinical improvement. Three scenarios should be considered: primary CNS inflammatory disorder or a secondary manifestation of the underlying rheumatologic disease; immune-mediated inflammatory lesion triggered by vaccine; demyelinating event due to adalimumab.

Ongoing monkeypox virus outbreak, Portugal, 29 April to 23 May 2022.

Up to 27 May 2022, Portugal has detected 96 confirmed cases of monkeypox. We describe 27 confirmed cases (median age: 33 years (range: 22-51); all males), with an earliest symptom onset date of 29 April. Almost all cases (n = 25) live in the Lisbon and Tagus Valley health region. Most cases were neither part of identified transmission chains, nor linked to travel or had contact with symptomatic persons or with animals, suggesting the possible previously undetected spread of monkeypox.

InfectionCMA: A Cell MicroArray Approach for Efficient Biomarker Screening in In Vitro Infection Assays.

The recently emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has forced the scientific community to acquire knowledge in real-time, when total lockdowns and the interruption of flights severely limited access to reagents as the global pandemic became established. This unique reality made researchers aware of the importance of designing efficient in vitro set-ups to evaluate infectious kinetics. Here, we propose a histology-based method to evaluate infection kinetics grounded in cell microarray (CMA) construction, immunocytochemistry and in situ hybridization techniques. We demonstrate that the chip-like organization of the InfectionCMA has several advantages, allowing side-by-side comparisons between diverse cell lines, infection time points, and biomarker expression and cytolocalization evaluation in the same slide. In addition, this methodology has the potential to be easily adapted for drug screening.

SARS-CoV-2 reinfection in a healthcare worker: First case in Portugal confirmed by viral genome sequencing.

Few reports of SARS-CoV-2 reinfection by antigenically similar variants are well documented. The interplay between natural acquired immunity, escape by emerging variants, and protective measures in the healthcare setting is considered in this description of the first phylogenetically confirmed SARS-CoV-2 reinfection in Portugal.

Safety of Rifampicin at High Dose for Difficult-to-Treat Tuberculosis: Protocol for RIAlta Phase 2b/c Trial.

Previous clinical trials for drug-susceptible tuberculosis (DS-TB) have shown that first-line treatment with doses of rifampicin up to 40 mg/kg are safe and increase the early treatment response for young adults with pulmonary tuberculosis. This may lead to a shorter treatment duration for those persons with TB and a good baseline prognosis, or increased treatment success for vulnerable subgroups (age > 60, diabetes, malnutrition, HIV, hepatitis B or hepatitis C coinfection, TB meningitis, stable chronic liver diseases). Here, we describe the design of a phase 2b/c clinical study under the hypothesis that rifampicin at 35 mg/kg is as safe for these vulnerable groups as for the participants included in previous clinical trials. RIAlta is an interventional, open-label, multicenter, prospective clinical study with matched historical controls comparing the standard DS-TB treatment (isoniazid, pyrazinamide, and ethambutol) with rifampicin at 35 mg/kg (HR35ZE group) vs. rifampicin at 10 mg/kg (historical HR10ZE group). The primary outcome is the incidence of grade ≥ 3 Adverse Events or Severe Adverse Events. A total of 134 participants will be prospectively included, and compared with historical matched controls with at least a 1:1 proportion. This will provide a power of 80% to detect non-inferiority with a margin of 8%. This study will provide important information for subgroups of patients that are more vulnerable to TB bad outcomes and/or treatment toxicity. Despite limitations such as non-randomized design and the use of historical controls, the results of this trial may inform the design of future more inclusive clinical trials, and improve the management of tuberculosis in subgroups of patients for whom scientific evidence is still scarce. Trial registration: EudraCT 2020-003146-36, NCT04768231.

Development of the HIV360 international core set of outcome measures for adults living with HIV: A consensus process.

OBJECTIVES: HIV outcomes centre primarily around clinical markers with limited focus on patient-reported outcomes. With a global trend towards capturing the outcomes that matter most to patients, there is agreement that standardizing the definition of value in HIV care is key to their incorporation. This study aims to address the lack of routine, standardized data in HIV care. METHODS: An international working group (WG) of 37 experts and patients, and a steering group (SG) of 18 experts were convened from 14 countries. The project team (PT) identified outcomes by conducting a literature review, screening 1979 articles and reviewing the full texts of 547 of these articles. Semi-structured interviews and advisory groups were performed with the WG, SG and people living with HIV to add to the list of potentially relevant outcomes. The WG voted via a modified Delphi process - informed by six Zoom calls - to establish a core set of outcomes for use in clinical practice. RESULTS: From 156 identified outcomes, consensus was reached to include three patient-reported outcomes, four clinician-reported measures and one administratively reported outcome; standardized measures were included. The WG also reached agreement to measure 22 risk-adjustment variables. This outcome set can be applied to any person living with HIV aged > 18 years. CONCLUSIONS: Adoption of the HIV360 outcome set will enable healthcare providers to record, compare and integrate standardized metrics across treatment sites to drive quality improvement in HIV care.

Field and Molecular Epidemiology: How Viral Sequencing Changed Transmission Inferences in the First Portuguese SARS-CoV-2 Infection Cluster.

Field epidemiology and viral sequencing provide a comprehensive characterization of transmission chains and allow a better identification of superspreading events. However, very few examples have been presented to date during the COVID-19 pandemic. We studied the first COVID-19 cluster detected in Portugal (59 individuals involved amongst extended family and work environments), following the return of four related individuals from work trips to Italy. The first patient to introduce the virus would be misidentified following the traditional field inquiry alone, as shown by the viral sequencing in isolates from 23 individuals. The results also pointed out family, and not work environment, as the primary mode of transmission.