Symptoms Of Acute Infection Research Articles

A pilot protocol for surveillance of infection and antibiotic prescribing in primary healthcare across the globe: Antibiotic Prescribing in Primary Healthcare Point Prevalence Survey (APC-PPS)

Little data is available from the primary healthcare setting in low- and middle-income countries to describe the burden of clinical infections and antibiotic prescribing proportions for those infections. The AWaRe Antibiotic Book provides a framework for assessing antibiotic prescribing in primary healthcare but requires understanding both frequency of clinical infections and their antibiotic prescribing proportions. The Antibiotic Prescribing in Primary Healthcare Point Prevalence Survey (APC-PPS) project is a series of point prevalence surveys conducted at primary healthcare facilities in LMICs to capture the frequency of consultation for different clinical infections and diagnoses and the frequency and type of antibiotic prescribing associated with these infections in primary healthcare facilities. This study aims to assess the feasibility of using a PPS methodology to collect data on clinical presentation and antibiotic prescribing in primary healthcare settings. The data collected are necessary to be able to summarise relative rates of presentation of different clinical infections and antibiotic prescribing practices to inform global estimates of antibiotic use and inform the development of surveillance methods and representative sampling frames. Each site will conduct 6-8 point prevalence surveys over the course of 12 months. Completely anonymous data on age, sex, relevant comorbidities, infection symptoms and diagnoses and antibiotic prescription are collected for patients of all ages with acute infection symptoms (up to 14 days of symptoms) who present to the facility on the day of the survey. No identifiable data will be collected from individuals. Data is collected via ODK Collect and stored in a secure ODK Cloud server hosted by City St. George’s, University of London. Sites will be active between early 2023- end 2024, with regular interim data analysis scheduled and final data analysis planned by mid 2025. All required local and national ethical and regulatory approvals will be obtained prior to sites starting.

Long COVID at 3 and 6 months after covid-19 infection in Thailand.

"Long COVID", which describes a diverse set of symptoms or conditions that persist or develop after four weeks from the onset of initial SARS-CoV-2 infection has been introduced. However, the true prevalence varies worldwide. This study aimed to determine the point prevalence and clinical characteristics of long COVID at three and six months after acute COVID-19 infection in Thailand. Methods All adult patients who were diagnosed with COVID-19 by positive nasopharyngeal RT-PCR for SARS-CoV-2 at Thammasat University Hospital between October and December 2021 were recruited and followed for long COVID symptoms by telephone interviews at 3 and 6 months after an acute infection. Among 1,400 eligible COVID-19 cases, interviews were complete for 1,129 and 932 individuals at 3 and 6 months, respectively. Of those, 431 and 314 reported at least one symptom consistent with long COVID. The point prevalence was 38.2% (95% confidence interval: 35.3-41.1%) and 33.7% (95% confidence interval: 30.7-36.7%) respectively. Female gender, disease severity, and symptomatic acute infection were identified as independent risk factors. Conclusion Based on the reported symptoms, long COVID is commonly observed either at 3 or 6 months in our study.

Le viróme humain : un écosystème viral dans notre corps

AbstractThe recent pandemics of H1 N1pdm in 2009 and Sars-CoV-2 in 2020 provide a very negative insight into viruses. However, the advent of new high-throughput sequencing technologies has significantly increased our understanding of these biological entities, revealing that the healthy human body is inhabited by at least ten times more viruses than the cells constituting it. It is therefore necessary to reassess the role of viruses in the physiological balance of the human body, given their omnipresence. The virome, which encompasses all viruses present in a human body, is highly diverse. It consists of viruses infecting our cells, which may or may not cause acute symptomatic infections, or remain in the body for life without clinical signs. However, the majority of the human virome is composed of viruses infecting bacteria, thus forming the phageome. Consequently, the human microbiome itself is subject to viral infections that will have an impact on health. The virome, through its interactions with its host, plays numerous roles within the body: it modulates the abundance of different bacterial species, influences the immune system, and contributes to maintaining health or the onset of diseases.

Progressive shingles in a toddler due to reactivation of Varicella Zoster vaccine virus four days after infection with SARS-CoV-2; a case report

BackgroundHerpes zoster (HZ) is the clinical syndrome associated with reactivation of latent varicella-zoster virus (VZV). Several factors have been implicated to promote VZV reactivation; these include immunosuppression, older age, mechanical trauma, physiologic stress, lymphopenia, and more recently, infection with severe acute respiratory syndrome coronavirus-2 (SARS- CoV-2). Recent reports suggest an increase in the number of HZ cases in the general population during the global COVID-19 pandemic. However, it is unknown what proportion of HZ during the pandemic is due to reactivation of wild-type or vaccine-strain VZV.CaseHere we report the first known case of HZ concomitant with SARS-CoV2 infection in a 20-month-old female who was treated with a single dose of dexamethasone, due to reactivation of the vaccine-type strain of VZV after presenting with a worsening vesicular rash.ConclusionIn this case, we were able to show vaccine-strain VZV reactivation in the context of a mild acute symptomatic COVID-19 infection in a toddler. Being able to recognize HZ quickly and effectively in a pediatric patient can help stave off the significant morbidity and mortality associated with disease process.

Description of the COVID 2.0 survey in the NAKO and first results

Abstract Introduction The COVID-19 pandemic had a huge impact on society and raised attention to the challenges related to infectious diseases. While a lot of research was initiated during the pandemic, the recruitment of participants in most instances started at the time point of infection. In contrast, the German National Cohort (NAKO Gesundheitsstudie) has the ability to study pre-existing risk factors. In order to obtain information about SARS-CoV-2 infections and the following sequelae a dedicated data collection was conducted. Methods An online survey was conducted in the NAKO between September 2022 and February 2023. Invitation via e-mail was followed by two reminders sent to all NAKO study participants who provided e-mail addresses. The questionnaire was implemented in LimeSurvey and included the following topics: current health status including mental health measurements, restrictions of health services during the pandemic, other collateral effects of the pandemic, reported infections with SARS-CoV-2 and symptoms of acute infection, 4-12 weeks, 12 or more weeks, and one year after infection as well as vaccination status. Results Of 150766 invited NAKO participants, 110362 responded to the second COVID-19 questionnaire. Respondents in 60% reported at least one SARS-CoV-2 infection, 59453 reported one, 6061 two, and 414 three or more infections. The time points of infections followed the general incidence in the German population and thus infections could be mapped to specific variants based on periods of dominance. Of those who reported an infection with SARS-CoV-2, 42% reported symptoms 4 to 12 weeks after infection (ongoing COVID-19), 35% reported symptoms 12 or more weeks after infection (Post-COVID-19), and 37% one year after infection. Conclusions Combined with existing biosamples and measurements prior to infection, NAKO offers an excellent opportunity to study risk factors for infection and post-infection syndromes.

Inhaled Fluticasone Furoate for Outpatient Treatment of Covid-19

BackgroundThe effectiveness of inhaled glucocorticoids in shortening the time to symptom resolution or preventing hospitalization or death among outpatients with mild-to-moderate coronavirus disease 2019 (Covid-19) is unclear.MethodsWe conducted a decentralized, double-blind, randomized, placebo-controlled platform trial in the United States to assess the use of repurposed medications in outpatients with confirmed coronavirus disease 2019 (Covid-19). Nonhospitalized adults 30 years of age or older who had at least two symptoms of acute infection that had been present for no more than 7 days before enrollment were randomly assigned to receive inhaled fluticasone furoate at a dose of 200 μg once daily for 14 days or placebo. The primary outcome was the time to sustained recovery, defined as the third of 3 consecutive days without symptoms. Key secondary outcomes included hospitalization or death by day 28 and a composite outcome of the need for an urgent-care or emergency department visit or hospitalization or death through day 28.ResultsOf the 1407 enrolled participants who underwent randomization, 715 were assigned to receive inhaled fluticasone furoate and 692 to receive placebo, and 656 and 621, respectively, were included in the analysis. There was no evidence that the use of fluticasone furoate resulted in a shorter time to recovery than placebo (hazard ratio, 1.01; 95% credible interval, 0.91 to 1.12; posterior probability of benefit [defined as a hazard ratio >1], 0.56). A total of 24 participants (3.7%) in the fluticasone furoate group had urgent-care or emergency department visits or were hospitalized, as compared with 13 participants (2.1%) in the placebo group (hazard ratio, 1.9; 95% credible interval, 0.8 to 3.5). Three participants in each group were hospitalized, and no deaths occurred. Adverse events were uncommon in both groups.ConclusionsTreatment with inhaled fluticasone furoate for 14 days did not result in a shorter time to recovery than placebo among outpatients with Covid-19 in the United States. (Funded by the National Center for Advancing Translational Sciences and others; ACTIV-6 ClinicalTrials.gov number, NCT04885530.)

Detection of feline morbillivirus in cats with symptoms of acute febrile infection

Feline morbillivirus (FeMV) was identified for the first time in cats in 2012 in Hong Kong. Although its association with chronic kidney disease in cats has attracted the attention of researchers, its clinical significance as an acute infection has not been reported. Previously, we reported FeMV detection using next-generation sequence-based comprehensive genomic analysis of plasma samples from cats with suspected acute febrile infections. Here, we conducted an epidemiological survey to detect FeMV by quantitative reverse transcription polymerase chain reaction (qRT-PCR) using blood samples from cats in Japan. FeMV was detected in 32/102 blood samples (31.4%) from cats with suspected acute viral infections. Most of the FeMV-positive cats had clinical findings consistent with acute viral infections, including fever, leukopenia, thrombocytopenia and jaundice. No FeMV was detected in healthy cats or clinically ill cats that visited veterinary hospitals. Phylogenetic analysis classified FeMV L genes into various FeMV subtypes. We also necropsied a FeMV-positive cat that died of a suspected acute infection. On necropsy, FeMV was detected in systemic organs, including the kidneys, lymph nodes and spleen by qRT-PCR and immunohistochemical staining. These results suggest that FeMV infections may cause acute symptomatic febrile infections in cats. A limitation of this study was that the involvement of other pathogens that cause febrile illnesses could not be ruled out and this prevented a definitive conclusion that FeMV causes febrile disease in infected cats. Further studies that include experimental infections are warranted to determine the pathogenicity of FeMV in cats.

Metabolomic and gut microbiome profiles across the spectrum of community-based COVID and non-COVID disease

Whilst most individuals with SARS-CoV-2 infection have relatively mild disease, managed in the community, it was noted early in the pandemic that individuals with cardiovascular risk factors were more likely to experience severe acute disease, requiring hospitalisation. As the pandemic has progressed, increasing concern has also developed over long symptom duration in many individuals after SARS-CoV-2 infection, including among the majority who are managed acutely in the community. Risk factors for long symptom duration, including biological variables, are still poorly defined. Here, we examine post-illness metabolomic profiles, using nuclear magnetic resonance (Nightingale Health Oyj), and gut-microbiome profiles, using shotgun metagenomic sequencing (Illumina Inc), in 2561 community-dwelling participants with SARS-CoV-2. Illness duration ranged from asymptomatic (n = 307) to Post-COVID Syndrome (n = 180), and included participants with prolonged non-COVID-19 illnesses (n = 287). We also assess a pre-established metabolomic biomarker score, previously associated with hospitalisation for both acute pneumonia and severe acute COVID-19 illness, for its association with illness duration. We found an atherogenic-dyslipidaemic metabolic profile, including biomarkers such as fatty acids and cholesterol, was associated with longer duration of illness, both in individuals with and without SARS-CoV-2 infection. Greater values of a pre-existing metabolomic biomarker score also associated with longer duration of illness, regardless of SARS-CoV-2 infection. We found no association between illness duration and gut microbiome profiles in convalescence. This highlights the potential role of cardiometabolic dysfunction in relation to the experience of long duration symptoms after symptoms of acute infection, both COVID-19 as well as other illnesses.

Peripheral nervous system involvement in SARS-CoV-2 infection: a review of the current pediatric literature.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified as the pathogen responsible for the pandemic health emergency declared by the World Health Organization in March 2020. During the first part of the pandemic, adults showed mild to severe respiratory symptoms. Children seemed initially exempt, both from acute and subsequent complications. Hyposmia or anosmia were promptly identified as the main symptoms of acute infection, so neurotropism of SARS-CoV-2 was immediately suspected. (1, 2). As the emergency progressed, post infectious neurological complications were described also in pediatric population (3). Cases of cranial neuropathy in connection with acute SARS-CoV-2 infection have been reported in pediatric patients, as an isolate post infectious complication or in the context of the multisystem inflammatory syndrome in children (MIS-C) (4-6). Neuroinflammation is thought to be caused by several mechanisms, among which immune/autoimmune reactions (7), but so far, no specific autoantibody has been identified. SARS-CoV-2 can enter the central nervous system (CNS) directly and/or infect it retrogradely, through the peripheral nervous system (PNS), after replicating peripherally; several factors regulate invasion and subsequent neuroinflammation. Indeed, direct/secondary entry and replication can activate CNS-resident immune cells that, together with peripheral leukocytes, induce an immune response and promote neuroinflammation. In addition, as we will discuss in the following review, many cases of peripheral neuropathy (cranial and non-cranial) have been reported during or after SARS-CoV-2 infection. However, some authors have pointed out that the increase of cranial roots and ganglia in neurological imaging is not always observed in children with cranial neuropathy. (8). Even if a variety of case reports were published, opinions about an increased incidence of such neurologic diseases, linked to SARS-CoV-2 infection, are still controversial (9-11). Facial nerve palsy, ocular movements abnormalities and vestibular alterations are among the most reported issues in pediatric population (3-5). Moreover, an increased screen exposure imposed by social distancing led to acute oculomotion's disturbance in children, not primarily caused by neuritis (12, 13). The aim of this review is to suggest food for thought on the role of SARS-CoV-2 in neurological conditions, affecting the peripheral nervous system to optimize the management and care of pediatric patients.

Cardiac injury in children with COVID-19.

There is little known about the spectrum of cardiac injury in acute COVID-19 infection in children. A single-centre, retrospective chart analysis was performed. The protocol was deemed IRB exempt. All patients under the age of 21 years admitted from 20 March, 2020 to 22 June, 2021 for acute symptomatic COVID-19 infection or clinical suspicion of multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19 were included. Past medical history, lab findings, echocardiogram and electrocardiogram/telemetry findings, and clinical outcomes were reviewed. Sixty-six patients with MIS-C and 178 with acute COVID-19 were reviewed. Patients with MIS-C had more cardiac testing than those with acute COVID-19. Inflammatory markers were more likely elevated, and function was more likely abnormal on echocardiogram in those with MIS-C with testing performed. Among patients with MIS-C, 17% had evidence of coronary dilation versus 0% in the acute COVID-19 group. One (0.6%) patient with acute COVID-19 had clinically significant electrocardiogram or telemetry findings, and this was in the setting of prior arrhythmias and CHD. Four (6%) patients with MIS-C had clinically significant findings on electrocardiogram or telemetry. Among patients with acute COVID-19, extracorporeal membrane oxygenation support was required in 0.6% of patients with acute COVID-19, and there was a 2.8% mortality. There were no deaths in the setting of MIS-C. Patients with acute COVID-19 and clinical suspicion of cardiac injury had a lower incidence of abnormal laboratory findings, ventricular dysfunction, or significant arrhythmia than those with MIS-C.

Symptoms compatible with long COVID in an Italian pediatric cohort of Tourette patients with and without SARS‑CoV‑2 infection: a short-term follow-up assessment

BackgroundTourette Syndrome (TS) is a childhood-onset neurodevelopmental disorder with a worldwide prevalence of about 0.3–1% of the population. During the pandemic caused by SARS-CoV-2 infection, the impact on the mental health of children and adolescents was very important. The persistence of symptoms in the post-acute phase of the disease has been termed Long COVID. The neuropsychiatric symptoms seem to be the most common impairment in children and adolescents with long COVID.ObjectivesConsidering the impact of pandemic on mental health, in this study we analyzed the long-term effects of SARS-CoV-2 infection in children and adolescents affected by TS.MethodsWe conducted an online questionnaire covering socio-demographic and clinical data among 158 patients affected by TS or chronic tic disorders (CTD), of which 78 participants reported a positive SARS-CoV-2 infection. Data were collected to investigate tic severity and both the comorbidities, as well as lockdown-related changes to daily life activities and, in case of infection of SARS-CoV-2, possible symptoms of acute infection and long COVID. Markers of systemic inflammation including C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), ferritin, iron, electrolytes, white blood cell counts, platelet cell counts levels, markers of liver, kidney and thyroid function were analyzed. First, all patients were screened with the Schedule for affective disorders and Schizophrenia for School age children—present and lifetime (Kiddie-SADS-PL) to rule out primary psychiatric disorders considered as criteria of exclusion. Then, all patients were clinically assessed at baseline (T0), and after three months (T1) through the administration of Yale Global Tic Severity Rating Scale (YGTSS), Multidimensional Anxiety Scale for Children (MASC), Child Depression Inventory (CDI) and Child Behavior Checklist (CBCL).ResultsAmong the cohort of TS patients that contracted SARS-CoV-2 infection, 84.6% (n = 66) experienced any acute symptoms, and long COVID symptoms occurred in 38.5% (n = 30). A worsening of clinical symptoms of tics and eventually associated comorbidities occurred in 34.6% (n = 27) of TS patients that contracted SARS-CoV-2 infection. TS patients with or without SARS-CoV-2 infection showed an increase in the severity of tics and also behavioral, depressive and anxious symptoms. Instead, this increase was more evident in patients who contracted the infection than in patients who did not contract it.ConclusionsSARS-CoV-2 infection may have a role in the increase of tics and associated comorbidities in TS patients. Despite of these preliminary results, further investigations are necessary to improve knowledge about the acute and long-term impact of SARS-CoV-2 in TS patients.

Sequelae of long COVID, known and unknown: A review of updated information

Over three years have passed since the COVID-19 pandemic started. The dangerousness and impact of COVID-19 should definitely not be ignored or underestimated. Other than the symptoms of acute infection, the long-term symptoms associated with SARS-CoV-2 infection, which are referred to here as "sequelae of long COVID (LC)", are also a conspicuous global public health concern. Although such sequelae were well-documented, the understanding of and insights regarding LC-related sequelae remain inadequate due to the limitations of previous studies (the follow-up, methodological flaws, heterogeneity among studies, etc.). Notably, robust evidence regarding diagnosis and treatment of certain LC sequelae remain insufficient and has been a stumbling block to better management of these patients. This awkward situation motivated us to conduct this review. Here, we comprehensively reviewed the updated information, particularly focusing on clinical issues. We attempt to provide the latest information regarding LC-related sequelae by systematically reviewing the involvement of main organ systems. We also propose paths for future exploration based on available knowledge and the authors' clinical experience. We believe that these take-home messages will be helpful to gain insights into LC and ultimately benefit clinical practice in treating LC-related sequelae.

Effect of Higher-Dose Ivermectin for 6 Days vs Placebo on Time to Sustained Recovery in Outpatients With COVID-19

It is unknown whether ivermectin, with a maximum targeted dose of 600 μg/kg, shortens symptom duration or prevents hospitalization among outpatients with mild to moderate COVID-19. To evaluate the effectiveness of ivermectin at a maximum targeted dose of 600 μg/kg daily for 6 days, compared with placebo, for the treatment of early mild to moderate COVID-19. The ongoing Accelerating COVID-19 Therapeutic Interventions and Vaccines 6 (ACTIV-6) platform randomized clinical trial was designed to evaluate repurposed therapies among outpatients with mild to moderate COVID-19. A total of 1206 participants older than 30 years with confirmed COVID-19 experiencing at least 2 symptoms of acute infection for less than or equal to 7 days were enrolled at 93 sites in the US from February 16, 2022, through July 22, 2022, with follow-up data through November 10, 2022. Participants were randomly assigned to receive ivermectin, with a maximum targeted dose of 600 μg/kg (n = 602) daily, or placebo (n = 604) for 6 days. The primary outcome was time to sustained recovery, defined as at least 3 consecutive days without symptoms. The 7 secondary outcomes included a composite of hospitalization, death, or urgent/emergent care utilization by day 28. Among 1206 randomized participants who received study medication or placebo, the median (IQR) age was 48 (38-58) years, 713 (59.1%) were women, and 1008 (83.5%) reported receiving at least 2 SARS-CoV-2 vaccine doses. The median (IQR) time to sustained recovery was 11 (11-12) days in the ivermectin group and 11 (11-12) days in the placebo group. The hazard ratio (posterior probability of benefit) for improvement in time to recovery was 1.02 (95% credible interval, 0.92-1.13; P = .68). Among those receiving ivermectin, 34 (5.7%) were hospitalized, died, or had urgent or emergency care visits compared with 36 (6.0%) receiving placebo (hazard ratio, 1.0 [95% credible interval, 0.6-1.5]; P = .53). In the ivermectin group, 1 participant died and 4 were hospitalized (0.8%); 2 participants (0.3%) were hospitalized in the placebo group and there were no deaths. Adverse events were uncommon in both groups. Among outpatients with mild to moderate COVID-19, treatment with ivermectin, with a maximum targeted dose of 600 μg/kg daily for 6 days, compared with placebo did not improve time to sustained recovery. These findings do not support the use of ivermectin in patients with mild to moderate COVID-19. ClinicalTrials.gov Identifier: NCT04885530.

Direct impact of COVID-19 by estimating disability-adjusted life years at national level in France in 2020.

The World Health Organization declared a pandemic of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), on March 11, 2020. The standardized approach of disability-adjusted life years (DALYs) allows for quantifying the combined impact of morbidity and mortality of diseases and injuries. The main objective of this study was to estimate the direct impact of COVID-19 in France in 2020, using DALYs to combine the population health impact of infection fatalities, acute symptomatic infections and their post-acute consequences, in 28 days (baseline) up to 140 days, following the initial infection. National mortality, COVID-19 screening, and hospital admission data were used to calculate DALYs based on the European Burden of Disease Network consensus disease model. Scenario analyses were performed by varying the number of symptomatic cases and duration of symptoms up to a maximum of 140 days, defining COVID-19 deaths using the underlying, and associated, cause of death. In 2020, the estimated DALYs due to COVID-19 in France were 990 710 (1472 per 100 000), with 99% of burden due to mortality (982 531 years of life lost, YLL) and 1% due to morbidity (8179 years lived with disability, YLD), following the initial infection. The contribution of YLD reached 375%, assuming the duration of 140 days of post-acute consequences of COVID-19. Post-acute consequences contributed to 49% of the total morbidity burden. The contribution of YLD due to acute symptomatic infections among people younger than 70 years was higher (67%) than among people aged 70 years and above (33%). YLL among people aged 70 years and above, contributed to 74% of the total YLL. COVID-19 had a substantial impact on population health in France in 2020. The majority of population health loss was due to mortality. Men had higher population health loss due to COVID-19 than women. Post-acute consequences of COVID-19 had a large contribution to the YLD component of the disease burden, even when we assume the shortest duration of 28 days, long COVID burden is large. Further research is recommended to assess the impact of health inequalities associated with these estimates.

Epstein-Barr virus and multiple sclerosis: moving from questions of association to questions of mechanism.

The link between Epstein-Barr virus (EBV) and multiple sclerosis (MS) has puzzled researchers since it was first discovered over 40 years ago. Until that point, EBV was primarily viewed as a cancer-causing agent, but the culmination of evidence now shows that EBV has a pivotal role in development of MS. Early MS disease is characterised by episodic neuroinflammation and focal lesions in the central nervous system (CNS) that over time develop into progressive neurodegeneration and disability. Risk of MS is vanishingly low in EBV seronegative individuals, history of infectious mononucleosis (acute symptomatic primary infection with EBV) significantly increases risk and elevated antibody titres directed against EBV antigens are well-characterised in patients. However, the underlying mechanism - or mechanisms - responsible for this interplay remains to be fully elucidated; how does EBV-induced immune dysregulation either trigger or drive MS in susceptible individuals? Furthermore, deep understanding of virological and immunological events during primary infection and long-term persistence in B cells will help to answer the many questions that remain regarding MS pathogenesis. This review discusses the current evidence and mechanisms surrounding EBV and MS, which have important implications for the future of MS therapies and prevention.

LB1528A. Fluvoxamine for Outpatient Treatment of Covid-19: A Decentralized, Placebo-controlled, Randomized, Platform Clinical Trial

Abstract Background The effectiveness of fluvoxamine to shorten symptom duration or prevent hospitalization among outpatients with mild-to-moderate coronavirus 2019 (COVID-19) is unclear. Tolerability has also been identified as a potential limiting factor for 100 mg twice daily of fluvoxamine. We evaluated the efficacy of low-dose fluvoxamine 50 mg twice daily for 10 days compared with placebo for the treatment of early mild-to-moderate COVID-19. Methods ACTIV-6 is an ongoing, decentralized, double-blind, randomized, placebo-controlled platform trial testing repurposed medications in outpatients with confirmed SARS-CoV-2 infection. Non-hospitalized adults aged ≥ 30 years, experiencing ≥ 2 symptoms of acute infection for ≤ 7 days were randomized to fluvoxamine 50 mg twice daily for 10 days or placebo. The primary outcome was time to sustained recovery, defined as the third of 3 consecutive days without symptoms. Secondary outcomes included composites of hospitalization or death with or without urgent care or emergency department visit by day 28. Results Of those eligible for the fluvoxamine arm, 675 were randomized to and received fluvoxamine; 619 received concurrent placebo. Sixty-six percent of the study population reported at least 2 doses of a COVID-19 vaccine. There was no evidence of improvement in time to recovery with fluvoxamine compared with placebo (hazard ratio [HR] 0.96, 95% credible interval [CrI] 0.86–1.06; posterior probability for benefit [HR > 1]=0.2). Sixteen participants (2.4%) in the fluvoxamine arm had urgent care or emergency department visits or were hospitalized compared with 11 (1.8%) in the pooled, concurrent placebo arm (HR 1.5, 95% CrI 0.5–3.0; posterior probability for benefit [HR < 1]=0.1725). No participant in either arm was hospitalized, and no deaths occurred. Adverse events were uncommon in both arms. Conclusion Treatment with low-dose fluvoxamine 50 mg dosed twice daily for 10 days did not result in improved time to recovery among outpatients with COVID-19 in the United States during the delta and omicron variant surges. Disclosures All Authors: No reported disclosures.

LB1528B. Inhaled Fluticasone for Outpatient Treatment of Covid-19: A Decentralized, Placebo-controlled, Randomized, Platform Clinical Trial

Abstract Background The effectiveness of inhaled corticosteroids to shorten time to symptom resolution or prevent hospitalization or death among outpatients with mild-to-moderate coronavirus 2019 (Covid-19) is unclear. Methods ACTIV-6 is an ongoing, decentralized, double-blind, randomized, placebo-controlled platform trial testing repurposed medications in outpatients with confirmed SARS-CoV-2 infection. Non-hospitalized adults aged ≥ 30 years, experiencing ≥ 2 symptoms of acute infection for ≤ 7 days were randomized to inhaled fluticasone furoate 200 μg once daily for 14 days or placebo. The primary outcome was time to sustained recovery, defined as the third of 3 consecutive days without symptoms. Secondary outcomes included composites of hospitalization or death with or without urgent care or emergency department visit by day 28. Results Of those eligible for the fluticasone arm, 656 were randomized to and received inhaled fluticasone; 621 received concurrent placebo. There was no evidence of improvement in time to recovery with fluticasone compared with placebo (hazard ratio [HR] 1.01, 95% credible interval [CrI] 0.91–1.12; posterior probability for benefit [HR > 1]=0.56). Twenty-four participants (3.7%) in the fluticasone arm had urgent care or emergency department visits or were hospitalized compared with 13 (2.1%) in the pooled, concurrent placebo arm (HR 1.9, 95% CrI 0.8–3.5; posterior probability for benefit [HR< 1]=0.03). Three participants in each arm were hospitalized, and no deaths occurred. Adverse events were uncommon in both arms. Conclusion Treatment with inhaled fluticasone furoate for 14 days did not result in improved time to recovery among outpatients with Covid-19 in the United States during the delta and omicron variant surges. Disclosures All Authors: No reported disclosures.

LB1528. Results from ACTIV-6: A Decentralized, Double-Blinded, Randomized, Placebo-Controlled Platform Trial of Repurposed Drugs for the Treatment of Mild-to-Moderate COVID-19

Abstract Background The effectiveness of fluvoxamine to shorten symptom duration or prevent hospitalization among outpatients with mild-to-moderate coronavirus 2019 (COVID-19) is unclear. Tolerability has also been identified as a potential limiting factor for 100 mg twice daily of fluvoxamine. We evaluated the efficacy of low-dose fluvoxamine 50 mg twice daily for 10 days compared with placebo for the treatment of early mild-to-moderate COVID-19. Methods ACTIV-6 is an ongoing, decentralized, double-blind, randomized, placebo-controlled platform trial testing repurposed medications in outpatients with confirmed SARS-CoV-2 infection. Non-hospitalized adults aged ≥ 30 years, experiencing ≥ 2 symptoms of acute infection for ≤ 7 days were randomized to fluvoxamine 50 mg twice daily for 10 days or placebo. The primary outcome was time to sustained recovery, defined as the third of 3 consecutive days without symptoms. Secondary outcomes included composites of hospitalization or death with or without urgent care or emergency department visit by day 28. Results Of those eligible for the fluvoxamine arm, 675 were randomized to and received fluvoxamine; 619 received concurrent placebo. Sixty-six percent of the study population reported at least 2 doses of a COVID-19 vaccine. There was no evidence of improvement in time to recovery with fluvoxamine compared with placebo (hazard ratio [HR] 0.96, 95% credible interval [CrI] 0.86–1.06; posterior probability for benefit [HR > 1]=0.2). Sixteen participants (2.4%) in the fluvoxamine arm had urgent care or emergency department visits or were hospitalized compared with 11 (1.8%) in the pooled, concurrent placebo arm (HR 1.5, 95% CrI 0.5–3.0; posterior probability for benefit [HR < 1]=0.1725). No participant in either arm was hospitalized, and no deaths occurred. Adverse events were uncommon in both arms. Conclusion Treatment with low-dose fluvoxamine 50 mg dosed twice daily for 10 days did not result in improved time to recovery among outpatients with COVID-19 in the United States during the delta and omicron variant surges. Disclosures All Authors: No reported disclosures.

LB1528C. Ivermectin for Treatment of Mild-to-Moderate COVID-19 in the Outpatient Setting A Decentralized, Placebo-controlled, Randomized, Platform Clinical Trial

Abstract Background The effectiveness of ivermectin to shorten symptom duration or prevent hospitalization among outpatients in the United States with mild-to-moderate symptomatic coronavirus disease 2019 (COVID-19) is unknown. We evaluated the efficacy of ivermectin 400 µg/kg daily for 3 days compared with placebo for the treatment of early mild-to-moderate COVID-19. Methods ACTIV-6 is an ongoing, decentralized, double-blind, randomized, placebo-controlled platform trial to evaluate repurposed therapies in outpatients with mild-to-moderate COVID-19. Non-hospitalized adults age ≥ 30 years with confirmed COVID-19, experiencing ≥ 2 symptoms of acute infection for ≤ 7 days were randomized to receive ivermectin 400 µg/kg daily for 3 days or placebo. The main outcome measure was time to sustained recovery, defined as achieving at least 3 consecutive days without symptoms. Secondary outcomes included a composite of hospitalization or death by day 28. Results Of the 3457 participants who consented to be evaluated for inclusion in the ivermectin arm, 1591 were eligible for this study arm, randomized to receive ivermectin 400 µg/kg (n=817) or placebo (n=774), and received study drug. Of those enrolled, 47% reported receiving at least 2 doses of SARS-CoV-2 vaccination. The posterior probability for any improvement in time to recovery was 0.91 (hazard ratio 1.07, 95% credible interval 0.96–1.17). The posterior probability of this benefit exceeding 24 hours was less than 0.01, as measured by the difference in mean time unwell. Hospitalizations or deaths were uncommon (ivermectin [n=10]; placebo [n=9]). Ivermectin at 400 µg/kg was safe and without serious adverse events as compared with placebo (ivermectin [n=10]; placebo [n=9]). Conclusion Ivermectin dosed at 400 µg/kg daily for 3 days resulted in less than one day of shortening of symptoms and did not lower incidence of hospitalization or death among outpatients with COVID-19 in the United States during the delta and omicron variant time periods. Disclosures Susanna Naggie, MD/MHS, AbbVie: Grant/Research Support|BMS/PRA: Event adjudication|Gilead Sciences: Grant/Research Support|Pardes Biosciences: Advisor/Consultant|Personal Health Insights, Inc: Data Safety Monitoring Board Member|Silverback Therapeutics: Advisor/Consultant|Vir Biotechnology: Advisor/Consultant|Vir Biotechnology: Stocks/Bonds.

250. Clinical Disease in Pediatric Long Covid

Abstract Background Even weeks and months after initial infection, full recovery from a Covid-19 infection is elusive for some pediatric patients. Long Covid is now recognized as a chronic condition with a constellation of lingering health problems. As the long term sequala of Covid-19 continue to become apparent, it is imperative to study this emerging disease in the pediatric population. Methods The University of Minnesota Pediatric Covid Clinic has been receiving referrals since April 2020. The clinic is participating in a national registry (PIDTRAN-6_Covid-19), facilitating IRB approved collection of anonymized clinical data from children diagnosed with Long Covid syndrome. Results We have identified 47 children (female 28, male 19) who were diagnosed with Long Covid at the University of Minnesota Covid Clinic. The majority were previously healthy (40) and the average age was 14.7 years (4-18yr). Acute symptomatic infection preceded the diagnosis in 41 children and 6 children were asymptomatic. Common symptoms reported by the patients included: fatigue (35), dizziness and/or lightheadedness and/or palpitation (16), abnormal taste/smell (15), headache (14), difficulty concentrating/focusing [brain fog] (13), myalgia/arthralgia (15), dyspnea (12), abdominal pain (10), and sleep disturbance (6). Clinical Symptoms of Long Covid The nine most common clinical symptoms of Long Covid are shown in the chart above with the numbers corresponding to the number of patients who reported experiencing each symptom. Demographics of Long Covid The above graphic depicts the demographics of patients seen at the University of Minnesota Pediatric Long Covid Clinic. Conclusion Pediatric populations, like adult populations, have patients who suffer from the lingering health effects of what is now termed Long Covid. The majority of patients presenting with Long Covid are teenagers, with females being more commonly affected than males. These patients often suffer from fatigue and are experiencing a constellation of symptoms that are reminiscent of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and positional orthostatic tachycardia syndrome (POTS). This suggests a post-viral autoimmune injury as the likely pathophysiology for Long Covid syndrome. Further population based studies are needed to better understand the extent and prevalence of this debilitating disease. Disclosures All Authors: No reported disclosures.