EClinicalMedicine

IntroductionOne of the noted features of COVID-19 is the spectrum of expressivity in symptoms among those with the disease, ranging from no or mild symptoms that may last a small number of days, to severe and/or longer lasting symptoms. It is emerging that many patients have long lasting symptoms, several months after initial infection with COVID-19. The aim of this research was to characterize post-acute COVID-19 syndrome (PACS). MethodsThis was a retrospective cross-sectional observational study. Participants were patients recovering from COVID-19 infection, enrolled in Mount Sinai Hospitals COVID-19 Precision Recovery Program (PRP). Inclusion criteria were confirmed or probable (based on World Health Organization criteria) initial diagnosis of COVID-19; post-acute COVID-19 syndrome (defined as experiencing symptoms > 6 weeks since acute symptom onset) and being currently enrolled in the PRP during the months of July and August 2020. Study survey data were collected using REDCap. Demographic data, COVID-19 clinical data and patient-reported outcomes for breathlessness (Medical Research Council Breathlessness Scale), fatigue and quality of life (EuroQoL 5D-5L) were collected. Results84 individuals with PACS were included. Symptoms persisted at mean (range) 151 (54 to 255) days. The most prevalent persistent symptoms were fatigue (92%), loss of concentration/memory (74%), weakness (68%), headache (65%) and dizziness (64%). Most participants reported increased levels of disability associated with breathlessness, increased fatigue and reduced quality of life. ConclusionsPersistent symptoms following COVID-19 infection are prevalent, debilitating and appear to affect individuals regardless of acute infection severity or prior health status. More detailed research is required in order to identify specific symptom clusters associated with PACS, and to devise effective interventional strategies.

BackgroundThe 2019 novel coronavirus (SARS-CoV-2) is reported to result in both respiratory and non-respiratory severe health outcomes, but quantitative assessment of the risk - while adjusting for underlying risk driven by comorbidities - is not yet established. MethodsA retrospective observational study using electronic health records of 9,344,021 individuals across the U.S. with at-least 1 year of clinical history and followed up throughout 2020. Results131,329 individuals were associated with SARS-CoV-2 infection by January 6, 2021 in three distinct surges. While the age and number of preexisting conditions had decreased throughout the pandemic, the characteristics of those who experienced severe health events did not. During the second surge, between June 7 and November 18, 2020, 425,988 individuals in the base cohort were admitted to emergency rooms or hospitals. Among them, 15,486 were detected with SAR-CoV-2 within few days of admission. Significant adjusted odds ratios were observed between SARS-CoV-2 infection and the following severe health events: respiratory (4.38, 95% confidence interval 4.16- 4.62), bacterial pneumonia (3.25, 2.76-3.83), sepsis (1.71, 1.53-1.91), renal (1.69, 1.57-1.83), hematologic/immune (1.32, 1.20-1.45), neurological (1.23, 1.09-1.38). ConclusionsSARS-CoV-2 infection among hospitalized patients is associated with non-negligible increased risk of severe events including multiple non-respiratory ones. These associations, which complement recent studies, are persistent even after accounting for sources of selection and confounding bias, increasing the confidence they are not spurious.

IntroductionMore than 93,000 cases of coronavirus disease (COVID-19) have been reported worldwide. We describe the epidemiology, clinical course, and virologic characteristics of the first 12 U.S. patients with COVID-19. MethodsWe collected demographic, exposure, and clinical information from 12 patients confirmed by CDC during January 20-February 5, 2020 to have COVID-19. Respiratory, stool, serum, and urine specimens were submitted for SARS-CoV-2 rRT-PCR testing, virus culture, and whole genome sequencing. ResultsAmong the 12 patients, median age was 53 years (range: 21-68); 8 were male, 10 had traveled to China, and two were contacts of patients in this series. Commonly reported signs and symptoms at illness onset were fever (n=7) and cough (n=8). Seven patients were hospitalized with radiographic evidence of pneumonia and demonstrated clinical or laboratory signs of worsening during the second week of illness. Three were treated with the investigational antiviral remdesivir. All patients had SARS-CoV-2 RNA detected in respiratory specimens, typically for 2-3 weeks after illness onset, with lowest rRT-PCR Ct values often detected in the first week. SARS-CoV-2 RNA was detected after reported symptom resolution in seven patients. SARS-CoV-2 was cultured from respiratory specimens, and SARS-CoV-2 RNA was detected in stool from 7/10 patients. ConclusionsIn 12 patients with mild to moderately severe illness, SARS-CoV-2 RNA and viable virus were detected early, and prolonged RNA detection suggests the window for diagnosis is long. Hospitalized patients showed signs of worsening in the second week after illness onset.

ImportanceInformation about the severity of Omicron is scarce. ObjectiveTo report the respective risk of ICU admission in patients hospitalized with Delta and Omicron variants and to compare the characteristics and disease severity of critically ill patients infected with both variants according to vaccination status. DesignAnalysis from the APHP database, called Reality, prospectively recording the following information in consecutive patients admitted in the ICU for COVID-19: age, sex, immunosuppression, vaccination, pneumonia, need for invasive mechanical ventilation, time between symptom onset and ICU admission, and in-ICU mortality. Retrospective analysis on an administrative database, "Systeme dInformation pour le Suivi des Victimes" (SI-VIC), which lists hospitalized COVID-19 patients. Setting39 hospitals in the Paris area from APHP group. ParticipantsPatients hospitalized from December 1, 2021 to January 18, 2022 for COVID-19. Main outcomes and measuresRisk of ICU admission was evaluated in 3761 patients and Omicron cases were compared to Delta cases in the ICU in 888 consecutive patients. ResultsOn January 18, 45% of patients in the ICU and 63.8% of patients in conventional hospital units were infected with the Omicron variant (p < 0.001). The risk of ICU admission with Omicron was reduced by 64% than with Delta (9.3% versus 25.8% of cases, respectively, p < 0.001). In critically ill patients, 400 had the Delta variant, 229 the Omicron variant, 98 had an uninformative variant screening test and 161 did not have information on variant screening test. 747 patients (84.1%) were admitted for pneumonia. Compared to patients infected with Delta, Omicron patients were more vaccinated (p<0.001), even with 3 doses, more immunocompromised (p<0.001), less admitted for pneumonia (p<0.001), especially when vaccinated (62.1% in vaccinated versus 80.7% in unvaccinated, p<0.001), and less invasively ventilated (p=0.02). Similar results were found in the subgroup of pneumonia but Omicron cases were older. Unadjusted in-ICU mortality did not differ between Omicron and Delta cases, neither in the overall population (20.0% versus 27.9%, p = 0.08), nor in patients with pneumonia (31.6% versus 29.7%, respectively) where adjusted in-ICU mortality did not differ according to the variant (HR 1.43 95%CI [0.89;2.29], p=0.14). Conclusion and relevanceCompared to the Delta variant, the Omicron variant is less likely to result in ICU admission and less likely to be associated with pneumonia. However, when patients with the Omicron variant are admitted for pneumonia, the severity seems similar to that of patients with the Delta variant, with more immunocompromised and vaccinated patients and no difference in adjusted in-ICU mortality. Further studies are needed to confirm our results.

BackgroundStudies on long COVID differ in the selection of symptoms used to define the condition. We aimed to assess to what extent symptom selection impacts prevalence estimates of long COVID. MethodsIn a prospective cohort of patients who experienced mild to critical coronavirus disease 2019 (COVID-19), we used longitudinal data on the presence of 20 different symptoms to evaluate changes in the prevalence of long COVID over time when altering symptom selection. ResultsChanging symptom selection resulted in wide variation in long COVID prevalence, even within the same study population. Long COVID prevalence at 12 months since illness onset ranged from 39.6% (95%CI=33.4-46.2) when using a limited selection of symptoms to 80.6% (95%CI=74.8-85.4) when considering any reported symptom to be relevant. ConclusionsComparing the occurrence of long COVID is already complex due to heterogeneity in study design and population. Disparate symptom selection may further hamper comparison of long COVID estimates between populations. Harmonised data collection tools could be one means to achieve greater reproducibility and comparability of results.

Background and purposeTo test the hypothesis that the incidence of Creutzfeldt-Jakob disease (CJD) has remained constant, we calculated the rate of hospitalizations for CJD in the United States using the National Inpatient Sample (NIS) from 2000 to 2019. MethodsWe used ICD-9 and ICD-10 codes to identify people hospitalized with presumed CJD in the National Inpatient Sample (NIS) from 2000 to 2019. Survey weights were used to calculate nationally representative estimates. We used 2000 census data to calculate age-adjusted standardized rates of CJD hospitalizations by sex and race-ethnicity and then used Joinpoint regression to evaluate changes in those rates. ResultsFrom 2000 to 2019, there were 11,064 admissions for CJD across the U.S. Across this period, the age-adjusted rate of CJD-related hospitalizations increased significantly from 1.25 (95% CI, 1.25-1.26) to 1.98 (95% CI, 1.98-1.99) per million U.S. adults per year, with a significant annual percentage change between 2004 and 2013 of 7.6% (95% CI, 4.4%-10.9%). ConclusionsThe incidence of CJD increased in the United States from 2000 to 2019, with a significant increase specifically between 2004 and 2013, though the overall case rate remains low.

OBJECTIVENeurological complications can worsen outcomes in COVID-19. We defined the prevalence of a wide range of neurological conditions among patients hospitalized with COVID-19 in geographically diverse multinational populations. METHODSUsing electronic health record (EHR) data from 348 participating hospitals across 6 countries and 3 continents between January and September 2020, we performed a cross-sectional study of hospitalized adult and pediatric patients with a positive SARS-CoV-2 reverse transcription polymerase chain reaction test, both with and without severe COVID-19. We assessed the frequency of each disease category and 3-character International Classification of Disease (ICD) code of neurological diseases by countries, sites, time before and after admission for COVID-19, and COVID-19 severity. RESULTSAmong the 35,177 hospitalized patients with SARS-CoV-2 infection, there was increased prevalence of disorders of consciousness (5.8%, 95% confidence interval [CI]: 3.7%-7.8%, pFDR<.001) and unspecified disorders of the brain (8.1%, 95%CI: 5.7%-10.5%, pFDR<.001), compared to pre-admission prevalence. During hospitalization, patients who experienced severe COVID-19 status had 22% (95%CI: 19%-25%) increase in the relative risk (RR) of disorders of consciousness, 24% (95%CI: 13%-35%) increase in other cerebrovascular diseases, 34% (95%CI: 20%-50%) increase in nontraumatic intracranial hemorrhage, 37% (95%CI: 17%-60%) increase in encephalitis and/or myelitis, and 72% (95%CI: 67%-77%) increase in myopathy compared to those who never experienced severe disease. INTERPRETATIONUsing an international network and common EHR data elements, we highlight an increase in the prevalence of central and peripheral neurological phenotypes in patients hospitalized with SARS-CoV-2 infection, particularly among those with severe disease.

Pneumocystis jirovecii Pneumonia (PJP) is a potentially life-threatening fungal infection occurring in immunocompromised individuals, particularly those receiving anti-cancer treatment. However, the incidence of PJP among children and young people (CYP) with cancer, cancer-like conditions or haematopoietic stem cell transplant (HSCT) recipients is unclear. This systematic review aimed to determine the incidence and impact of PJP in this population. Twelve databases were searched in November 2024. Any study reporting the incidence of PJP in CYP<18 years old with cancer, a cancer-like condition or having received a HSCT were included. Screening, data extraction and quality assessment (using a modified JBI critical appraisal tool for prevalence studies) were conducted in duplicate. Meta-analyses using GLMM methods were used. Of 7,194 records screened, 106 studies were included. Interpretation of the results of many studies was hindered by limited reporting. For the acute lymphoblastic leukaemia meta-analyses using confirmed events, higher pooled cumulative incidence rates were seen in the no prophylaxis group than in the prophylaxis group (2.86% vs 0.04%). Rates increased to 5.41% in the no prophylaxis group when studies reporting unconfirmed cases were included. Subgroup analyses suggested lower incidence rates in cohorts taking first-line PJP prophylaxis, compared to second-line. The cumulative incidence rate using confirmed events was 0.16% for HSCT patients receiving prophylaxis; data were not available for a no prophylaxis analysis. Only three studies were available for the HSCT total events analysis, producing a rate of 4.27%. Several analyses were subject to some uncertainty due to their high heterogeneity estimates. PROSPERO registration: CRD42025628682

BackgroundEthnic minorities living in high-income countries have been disproportionately affected by COVID-19 in terms of infection rates and hospitalisations; however, less is known about long COVID in this population. Our aim was to examine the risk of long COVID and associated symptoms among ethnic minorities. Methods and FindingsA Danish nationwide register-based cohort study of individuals diagnosed with COVID-19 aged [&ge;]18 years (n=2 334 271) between January 2020 and August 2022. We calculated the risk of long COVID diagnosis and long COVID symptoms among ethnic minorities compared with native Danes using multivariable Cox proportional hazard regression and logistic regression, respectively. Ethnic minorities from North Africa (adjusted hazard ratio [aHR] 1.41; 95% CI 1.12-1.79), Middle East (aHR 1.38; 95% CI 1.24-1.55), Eastern Europe (aHR 1.35; 95% CI 1.22-1.49), and Asia (aHR 1.23; 95% CI 1.09-1.40) had significantly greater risk of long COVID diagnosis than native Danes in both unadjusted and adjusted models. In the analysis by largest countries of origin, the greater risks of long COVID diagnosis were found in Iraqis (aHR 1.56; 95% CI 1.30- 1.88), Turks (aHR 1.42; 95% CI 1.24-1.63), and Somalis (aHR 1.42; 95% CI 1.07-1.91) after adjustment for confounders. Significant factor associated with an increased risk of long COVID diagnosis was COVID-19 hospitalisation. Furthermore, the odds of reporting cardiopulmonary symptoms (including dyspnoea, cough, and chest pain) and any long COVID symptoms were higher among North African, Middle Eastern, Eastern European, and Asian than among native Danes in both unadjusted and adjusted models. ConclusionsBelonging to an ethnic minority group was significantly associated with an increased risk of long COVID indicating the need to better understand long COVID drivers and address care and treatment strategies in this population.

BackgroundThe novel coronavirus disease 2019 (COVID-19) outbreak presents a significant threat to global health. A better understanding of patient clinical profiles is essential to drive efficient and timely health service strategies. In this study, we aimed to identify risk factors for a higher susceptibility to symptomatic presentation with COVID-19 and a transition to severe disease. MethodsWe analysed data on 2756 patients admitted to Chelsea & Westminster Hospital NHS Foundation Trust between 1st January and 23rd April 2020. We compared differences in characteristics between patients designated positive for COVID-19 and patients designated negative on hospitalisation and derived a multivariable logistic regression model to identify risk factors for predicting risk of symptomatic COVID-19. For patients with COVID-19, we used univariable and multivariable logistic regression to identify risk factors associated with progression to severe disease defined by: 1) admission to the hospitals AICU, 2) the need for mechanical ventilation, 3) in-hospital mortality, and 4) at least one measurement of elevated D-dimer ([&ge;]1,000 g/L) indicative of increased risk of venous thromboembolism. ResultsThe patient population consisted of 1148 COVID-19 positive and 1608 COVID-19 negative patients. Age, sex, self-reported ethnicity, C-reactive protein, white blood cell count, respiratory rate, body temperature, and systolic blood pressure formed the most parsimonious model for predicting risk of symptomatic COVID-19 at hospital admission. Among 1148 patients with COVID-19, 116 (10.1%) were admitted to the AICU, 71 (6.2%) required mechanical ventilation, 368 (32.1%) had at least one record of D-dimer levels [&ge;]1,000 g/L, and 118 patients died. In the multivariable logistic regression, age (OR = 0.953 per 1 year, 95% CI: 0.937-0.968) C-reactive protein (OR = 1.004 per 1 mg/L, 95% CI: 1.002-1.007), and white blood cell counts (OR = 1.059 per 109/L, 95% CI: 1.010-1.111) were found to be associated with admission to the AICU. Age (OR = 0.973 per 1 year, 95% CI: 0.955-0.990), C-reactive protein (OR = 1.003 per 1 mg/L, 95% CI: 1.000-1.006) and sodium (OR = 0.915 per 1 mmol/L, 0.868-0.962) were associated with mechanical ventilation. Age (OR = 1.023 per 1 year, 95% CI: 1.004-1.043), CRP (OR = 1.004 per 1 mg/L, 95% CI: 1.002-1.006), and body temperature (OR = 0.723 per 1{degrees}C, 95% CI: 0.541-0.958) were associated with elevated D-dimer. For mortality, we observed associations with age (OR = 1.060 per 1 year, 95% CI: 1.040-1.082), female sex (OR = 0.442, 95% CI: 0.442, 95% CI: 0.245-0.777), Asian ethnic background (OR = 2.237 vs White ethnic background, 95% CI: 1.111-4.510), C-reactive protein (OR = 1.004 per 1 mg/L, 95% CI: 1.001-1.006), sodium (OR = 1.038 per 1 mmol/L, 95% CI: 1.001-1.006), and respiratory rate (OR = 1.054 per 1 breath/min, 95% CI: 1.024-1.087). ConclusionOur analysis suggests there are several demographic, clinical and laboratory findings associated with a symptomatic presentation of COVID-19. Moreover, significant associations between patient deterioration were found with age, sex and specific blood markers, chiefly C-reactive protein, and could help early identification of patients at risk of poorer prognosis. Further work is required to clarify the extent to which our observations are relevant beyond current settings.

ObjectiveTo assess whether severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is associated with changes in plasma levels of neurofilament light chain (NfL), an extremely sensitive marker of neuroaxonal damage, in community-dwelling individuals. SettingThis study was embedded within the Rhineland Study, an ongoing community-based cohort study in Bonn, Germany DesignCross-sectional nested case-control study. ParticipantsParticipants were selected based on results from a previously conducted seroprevalence survey within the framework of the Rhineland Study. Cases were defined as those individuals who had had two positive confirmatory test results, including a recombinant spike-based immunofluorescence assay and a plaque reduction neutralization test (N=21). As controls, a random sample of individuals with a negative ELISA test result (Controls I, N=1117), and those with a borderline or positive ELISA test result who failed confirmatory testing (Controls II, N=68), were selected. Outcome measuresPlasma levels of NfL at the time of measurement, as well as change in plasma NfL levels compared to previously measured pre-pandemic levels ResultsAfter adjustment for age, sex and batch effects, serologically confirmed SARS-CoV-2 infection was neither associated with cross-sectional NfL levels, nor with the magnitude of change from pre-pandemic levels, compared to either of the two control groups. Similarly, after adjustment for age, sex and batch effects, self-reported neurological symptoms - including altered sense of smell or taste, headache, myalgia and fever - were not associated with changes in NfL levels in participants with a serologically confirmed SARS-CoV-2 infection (all p [&ge;] 0.56). ConclusionsOur findings indicate that mild-to-moderate coronavirus disease-19 is unlikely to be associated with a clinically relevant degree of neuroaxonal damage, even in those cases associated with neurological symptoms.

BackgroundMany hospitalised patients require rehabilitation during recovery from acute illness. We use routine data from electronic health records (EHR) to report the quantity and intensity of rehabilitation and compared this in patients with and without COVID-19. MethodsWe performed a retrospective cohort study of consecutive adults in whom COVID-19 testing was undertaken between March 2020 and August 2021 across three acute hospitals in Scotland. We defined rehabilitation contacts (physiotherapy, occupational therapy, dietetics and speech and language therapy) from timestamped EHR data and determined contact time from a linked workforce planning dataset. We included survivors to hospital discharge who received at least two rehabilitation contacts. The primary outcome was total rehabilitation time. Secondary outcomes included the number of contacts, time to first contact, and rehabilitation minutes per day. A multivariate regression analysis for predictors of rehabilitation time included age, sex, comorbidities, and socioeconomic status. FindingsWe included 11,591 consecutive unique patient admissions (76 [63,85] years, 56% female), of which 651 (6%) were with COVID-19, and 10,940 (94%) were admissions with negative testing. There were 128,646 rehabilitation contacts. Patients with COVID-19 received more than double the rehabilitation time compared to those without (365 [165,772] vs 170 [95,350] mins, p<0.001), and this was delivered over more specialist contacts (12 [6,25] vs 6 [3,11], p<0.001). Time to first rehabilitation contact was later in patients with COVID-19 (3 [1,5] vs 2 [1,4] days from admission). Overall, patients with COVID-19 received fewer minutes of rehabilitation per day of admission (14.1 [9.8,18.7] vs 15.6 [10.6,21.3], p<0.001). In our regression analyses, older age and COVID-19 were the most important predictors of increased rehabilitation time. InterpretationPatients with COVID received more rehabilitation contact time than those without COVID, but this was delivered less intensively. Rehabilitation data derived from the EHR represents a novel measure of delivered hospital care.

Post-acute sequalae of Coronavirus disease-19 (COVID-19 [PASC]) are defined as the persistence of existing or new symptoms for a period extending beyond initial COVID-19 infection. Post COVID Neurological Syndrome (PCNS) relates to the persistent cognitive and neurological deficits characteristic of PASC. This includes significant changes in attention and memory function in adult and geriatric populations, with such impairments notably impacting quality of life. However, despite reports of similar cognitive changes in paediatric patients, this issue is yet to be systematically investigated. This systematic review and meta-analysis synthesised literature reporting on the prevalence of clinically significant cognitive impairment in paediatric PASC using DSM-5 cognitive domains to categorise study outcomes. Final literature searching was completed on 15th of November, 2024 across four databases combining the following keywords: COVID-19, cognition and paediatric. Included studies examined standardised psychometric or parent report measures of cognition in children and adolescents with a PASC diagnosis. Studies were excluded if participants had prior cognitive impairments or comorbidities. Risk of bias was assessed using Joanna Briggs Institute Critical Appraisal Tools Checklist for Analytical Cross-sectional Studies. Results revealed that between 35-55% of paediatric PASC patients were at risk of impairment or showed clinically significant impairment in complex attention, learning and memory, working memory and executive function. Further research is needed to assess impacts of infection severity and repeated infection. However, this meta-analysis provides insights into the nature of PCNS-associated complications to aid more detailed management strategies for children and adolescents.

IntroductionCryptococcal meningitis remains a leading cause of HIV-related mortality in sub-Saharan Africa despite expanded antiretroviral therapy coverage. Evidence on the burden of disease and inpatient mortality among people living with HIV (PLHIV) in routine care settings in Uganda remains limited. This study assessed the proportion of cryptococcal meningitis among HIV-related admissions and examined clinical factors associated with inpatient mortality. MethodsWe conducted a retrospective cohort study of adult PLHIV admitted with cryptococcal meningitis between January 2017 and December 2022 at a national referral hospital in Uganda. Diagnosis was based on cerebrospinal fluid cryptococcal antigen or India ink positivity. Data were abstracted from medical records and analysed using descriptive statistics and multivariable logistic regression to identify factors associated with inpatient mortality. Multiple imputation was used to address missing data. ResultsOf 3,042 HIV-related admissions, cryptococcal meningitis accounted for 21.4% (650/3,042). Medical records for 634 patients were analysed, among whom 39.3% (249/634) died during hospitalization. Factors independently associated with higher odds of inpatient mortality included convulsions, headache, vomiting, cryptococcal meningitis-associated immune reconstitution inflammatory syndrome, concurrent opportunistic infections, chronic kidney disease, anaemia, and severe immunosuppression (CD4 <200 cells/{micro}L). Longer duration of hospitalization ([&ge;]7 days) and symptom duration of one to two weeks before admission were associated with lower odds of mortality. ConclusionCryptococcal meningitis continues to account for a substantial proportion of HIV-related hospital admissions and inpatient deaths in Uganda. Mortality is associated with identifiable clinical and health-system factors, underscoring the need for early diagnosis, risk stratification, and optimized inpatient management for PLHIV with cryptococcal meningitis in resource-limited settings.

BackgroundKRAS mutation status, stage and tumor size at the time of diagnosis are well-established independent prognostic factors in non-small cell lung cancer (NSCLC). Here, we investigate the prognostic value of combining survival data on KRAS mutation status and tumor size in early-stage NSCLC. MethodsWe studied the combined impact of KRAS mutational status and tumor size on overall survival (OS) and risk of death in patients with stage I-II NSCLC. We performed a retrospective study including 310 consecutively diagnosed patients with early (stage I-II) NSCLCs. All consecutive patients molecularly assessed and diagnosed between 2016-2018 with stage I-II NSCLC in the Vastra Gotaland region of western Sweden were included in this multi-center retrospective study. The primary study outcome was OS and risk of death (hazard ratio). ResultsOut of 310 patients with stage I-II NSCLC, 37% harbored an activating mutation in the KRAS gene. Our study confirmed staging and tumor size as prognostic factors. However, KRAS mutational status was not found to impact OS and there was no difference in the risk of death when combining KRAS mutational status and primary tumor size. ConclusionsIn our patient cohort, KRAS mutations in combination with primary tumor size are not associated with a worse prognosis in stage I-II NSCLC.

IntroductionCOVID-19 infection caused by SARS-CoV-2 has led to significant long-term health challenges, including Long COVID or Post-COVID condition, that can include symptoms such as cognitive decline, memory loss, and concentration issues. This study investigates the prevalence and risk factors of post-COVID cognitive symptoms among individuals tested for COVID-19. MethodsA cross-sectional study was conducted in Lisbon and Tagus Valley, targeting individuals tested for COVID-19 in August 2022. Participants were selected from a random sample of 10,000 individuals. Data were collected via computer-assisted telephone interviews at 9 and 12 months post-test, covering sociodemographic details, health behaviors, pre-existing conditions, and COVID-19 symptoms. The primary outcome was the presence of at least one cognitive symptom (memory loss and/or concentration issues) at 9 and 12 months. Additionally, each symptom was assessed individually, along with a composite outcome of both symptoms concurrently. ResultsAt 9 months, memory loss was reported by 24.87% of COVID-19 positive cases versus 10.20% of negatives, and concentration issues by 15.45% of positives versus 7.45% of negatives. At 12 months, memory loss prevalence was 16.67% for positives and 9.45% for negatives, while concentration issues were 9.82% for positives and 2.99% for negatives. Additionally, the prevalence of at least one cognitive symptom was 28.24% in positive cases at 9 months compared to 12.16% in negatives, and 17.81% versus 9.95% at 12 months. Female sex was significantly associated with a higher prevalence of cognitive symptoms at both time points. DiscussionThese findings underscore the enduring cognitive impact of COVID-19, with significant disparities in cognitive symptoms between COVID-19 positive and negative individuals observed at both 9 and 12 months post-infection. The higher prevalence of memory loss and concentration issues among COVID-19 positives suggests potential neurological sequelae linked to SARS-CoV-2 infection. Notably, the association of female sex with increased cognitive symptom prevalence warrants further investigation into gender-specific vulnerabilities or biological mechanisms underlying these disparities. Addressing these persistent cognitive symptoms is crucial for long-term patient management and underscores the need for targeted interventions and comprehensive post-COVID care strategies to mitigate long-lasting health implications.

BackgroundPneumonia is a leading cause of childhood morbidity and mortality. Hospital re-admission may signify missed opportunities for care or undiagnosed comorbidities. MethodsWe conducted a retrospective cohort study including children aged [&ge;]2 months to 14 years hospitalised with severe pneumonia between 2013 and 2021 in a network of 22 primary referral hospitals in Kenya. Severe pneumonia was defined using the World Health Organization criteria, and re-admission was based on clinical documentation from individual patient case notes. We estimated the prevalence of re-admission, described clinical management practices, and modelled risk factors for re-admission and inpatient mortality. ResultsAmong 20,603 children diagnosed with severe pneumonia, 2,274 (11.0%, 95% confidence interval (CI) 10.62 to 11.47) were readmitted. Re-admission was independently associated with age (12-59 months vs 2-11 months: adjusted odds ratio (aOR) 1.70, 95% confidence interval (CI) 1.55 to 1.88; >5 years vs 2-11 months: aOR 1.86, 95% CI 1.55 to 2.23), malnutrition (weight for age z-score (WAZ) < -3SD vs WAZ > -2SD: aOR 2.03, 95%1.83 to 2.28); WAZ -2 to -3 SD vs WAZ> -2SD: aOR 1.37, 95% CI 1.20 to 1.56) and presence of a concurrent neurological disorder (aOR 4.04, 95% CI 1.57 to 10.42) . Chest radiography was ordered more frequently among those readmitted (540/2,274 vs 3,102/18,329, p<0.001). Readmitted patients were more likely to receive second-line antibiotics (808/2,256 vs 5,538/18,173 p<0.001), TB medication (69/2,256 vs 298/18,173 p<0.001), salbutamol (530/2,256 vs 3,707/18,173 p=0.003), and prednisolone (157/2,256 vs 764/18,173 p<0.001). Inpatient mortality was 2,354/18,329 (12.8%) among children admitted with a first episode of severe pneumonia and 269/2,274 (11.8%) among those who were readmitted (adjusted hazard ratio (aHR) 0.94, 95% CI 0.82-1.07). Age (12-59 months vs 2-11 months: aHR 0.62, 95% 0.57 to 0.67), female sex (aHR 1.23, 95% 1.14 to 1.33), malnutrition (WAZ <-3SD vs WAZ> -2SD: aHR 1.90 95% CI 1.74 to 2.08); WAZ -2 to -3 SD vs WAZ> -2SD: aHR 1.48, 95% CI 1.32 to 1.65), incomplete vaccination (aHR 1.43, 95% CI 1.16 to 1.75), and anaemia (aHR 2.16, 95% CI 1.90 to 2.45) were independently associated with mortality. ConclusionsChildren readmitted with severe pneumonia account for a substantial proportion of pneumonia hospitalisations and deaths. Further research is required to develop evidence-based approaches to screening, case management, and follow-up of children with severe pneumonia, prioritising those with underlying risk factors for readmission and mortality.

ImportanceRecent reports have highlighted an intense influenza activity related to the circulation of the influenza A(H3N2) subclade k variant. There is no data available on the impact of the emergence of H3N2 subclade k on the severity of the 2025-2026 epidemic or on the clinical phenotype of patients requiring admission to the intensive care unit (ICU). ObjectiveTo compare the clinical presentation, hospital mortality and virological characteristics of patients with laboratory-confirmed influenza infection included in French intensive care units during the 2025-2026 epidemic season with those of patients admitted during the 2024-2025 season. We also aimed at measuring the impact of the A(H3N2) subtype on hospital mortality during the 2025-2026 season. DesignProspective, multicenter, observational SEVARVIR cohort study including patients admitted during the 2024-2025 and 2025-2025 influenza seasons. SettingForty-two French ICUs ParticipantsAdult patients with laboratory-confirmed influenza infection Interventionsnone Main Outcomes and MeasuresThe primary outcome measure was in-hospital mortality. ResultsPatients admitted in intensive care units for influenza in 2024-2025 (n=360) and 2025-2026 (n=325) were included in the French nationwide prospective multicentre SEVARVIR study. There was no significant difference in day-28 mortality between the seasons (12.7%, n=45/355 vs 16.5% n=28/170; p=0.28). In the 2025-26 season, 49% had the A(H1N1) subtype and 51% the A(H3N2) subtype (k subclade: 77%). The univariable Cox analysis revealed that patients infected with A(H3N2) viruses were at greater risk of death over time. Multivariable Cox analysis revealed that during the 2025-2026 season, age (adjusted hazard ratio, aHR=1.05 [1.00;1.11]; p=0.046) and the clinical frailty scale (aHR=1.82 [1.26;2.72]; p=0.001) were associated with an increased risk of death. The A(H3N2) subtype was not associated with an increased risk of death (aHR=1.13 [0.32;4.51]; p=0.85). Phylogenetic analyses from our ICU cohort together with 300 contextual sequences from community-acquired influenza cases collected during the same period showed no clustering according to severity. Conclusions and RelevanceThis French national prospective observational study, found that the emergence of the influenza A(H3N2) subclade K was associated with an increased risk of death in univariable but not multivariable analysis, adjusting for host-related factors. Trial RegistrationNCT051625 Key PointsQuestion: What impact did the 2025-26 influenza epidemic and the A(H3N2) variant have on the mortality of patients admitted to intensive care units? Findings: In this prospective, nationwide cohort study of 685 patients admitted to intensive care units with severe influenza during the 2024-25 or 2025-26 seasons, no difference in hospital mortality was observed between the two seasons. Patients infected with the A(H3N2) virus, 77% of which corresponded to clade k, were at higher risk of death in univariable but not in multivariable analysis after adjusting for age and clinical frailty scale. Meaning: Patients in intensive care units with severe A(H3N2) infection during the 2025/2026 season were not at higher risk of death after adjusting for confounding variables.

BackgroundPolicymakers need robust data to respond to the COVID-19 pandemic. We describe demographic features, treatments and clinical outcomes in the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) COVID-19 cohort, the worlds largest international, standardised cohort of hospitalised patients. MethodsThe dataset analysed includes COVID-19 patients hospitalised between January 2020 and May 2021. We investigated how symptoms on admission, comorbidities, risk factors, and treatments varied by age, sex, and other characteristics. We used Cox proportional hazards models to investigate associations between demographics, symptoms, comorbidities, and other factors with risk of death, admission to intensive care unit (ICU), and invasive mechanical ventilation (IMV). Findings439,922 patients with laboratory-confirmed (91.7%) or clinically-diagnosed (8.3%) SARS-CoV-2 infection from 49 countries were enrolled. Age (adjusted hazard ratio [HR] per 10 years 1.49 [95% CI 1.49-1.50]) and male sex (1.26 [1.24-1.28]) were associated with a higher risk of death. Rates of admission to ICU and use of IMV increased with age up to age 60, then dropped. Symptoms, comorbidities, and treatments varied by age and had varied associations with clinical outcomes. Tuberculosis was associated with an 86% higher risk of death, and HIV with an 87% higher risk of death. Case fatality ratio varied by country partly due to differences in the clinical characteristics of recruited patients. InterpretationThe size of our international database and the standardized data collection method makes this study a reliable and comprehensive international description of COVID-19 clinical features. This is a viable model to be applied to future epidemics. FundingUK Foreign, Commonwealth and Development Office, the Bill & Melinda Gates Foundation and Wellcome. See acknowledgements section for funders of sites that contributed data. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSTo identify large, international analyses of hospitalised COVID-19 patients that used standardised data collection, we conducted a systematic review of the literature from 1 Jan 2020 to 28 Apr 2020. We identified 78 studies, with data from 77,443 people (1) predominantly from China. We could not find any studies including data from low and middle-income countries. We repeated our search on 18 Aug 2021 but could not identify any further studies that met our inclusion criteria. Added value of this studyOur study uses standardised clinical data collection to collect data from a vast number of patients across the world, including patients from low-, middle-, and high-income countries. The size of our database gives us great confidence in the accuracy of our descriptions of the global impact of COVID-19. We can confirm findings reported by smaller, country-specific studies and compare clinical data between countries. We have demonstrated that it is possible to collect large volumes of standardised clinical data during a pandemic of a novel acute respiratory infection. The results provide a valuable resource for present policymakers and future global health researchers. Implications of all the available evidencePresenting symptoms of SARS-CoV-2 infection in patients requiring hospitalisation are now well-described globally, with the most common being fever, cough, and shortness of breath. Other symptoms also commonly occur, including altered consciousness in older adults and gastrointestinal symptoms in younger patients, and age can influence the likelihood of a patient having symptoms that match one or more case definitions. There are geographic and temporal variations in the case fatality rate (CFR), but overall, CFR was 20.6% in this large international cohort of hospitalised patients with a median age of 60 years (IQR: 45 to 74 years).

BACKGROUNDTB meningitis (TBM) has up to 50% mortality in people living with HIV. We investigated differences in cerebrospinal fluid (CSF) host immune responses associated with acute mortality. METHODSWe enrolled a prospective cohort of adults with definite, probable and possible HIV-related TBM, without evidence of co-infection, in Kampala, Uganda. We performed metagenomic next-generation sequencing (mNGS) of bulk CSF RNA to profile host gene expression and exclude participants with co-infecting or alternate central nervous system pathogens. We then assessed host differential gene expression based on 14-day mortality within the refined cohort. RESULTSAmong the 110 patients included in the transcriptomic analysis, 22.7% (n=25) died within 14 days of enrollment. More than 2000 genes were differentially expressed in the CSF based on 14-day mortality (adjusted p-value < 0.05). Genes upregulated in TBM-survivors included genes related to T-cell receptor signaling (LCK, FYN, LAT), T-cell survival and differentiation (IL7, CD27, IL12RB1), B-cell receptor signaling (BCR, CD81, PLCG2), and TNF signaling. Survivors demonstrated downregulation in the neutrophil chemoattractant gene CXCL1, and classical complement pathway genes C4A and C4B. CONCLUSIONSA regulated immune response in which T-cell, B-cell, and microglial signaling are upregulated, but also in which certain neutrophil and complement genes are downregulated, was associated with short-term TBM survival in this population with HIV-related TBM. This finding provides context for the nuanced immunologic response and suggests that certain targeted immunomodulatory agents may be more effective as adjunctive therapy in HIV-related TBM compared to broad spectrum agents such as glucocorticoids.