Syndromic testing for respiratory pathogens but not National Early Warning Score can be used to identify viral cause in hospitalised adults with lower respiratory tract infections.

BACKGROUND: Community-acquired lower respiratory tract infection (LRTI) is a common reason for hospitalisation. Antibiotics are frequently used while diagnostic microbiological methods are underutilised in the acute setting. OBJECTIVES: We aimed to investigate the relative proportion of viral and bacterial infections in this patient group and explore methods for proper targeting of antimicrobial therapy. METHODS: We collected nasopharyngeal samples prospectively from adults hospitalised with LRTIs during three consecutive winter seasons (2016-2019). Syndromic nasopharyngeal testing was performed using a multiplex PCR panel including 16 viruses and four bacteria. Medical records were reviewed for clinical data. RESULTS: Out of 220 included patients, a viral pathogen was detected in 74 (34%), a bacterial pathogen in 63 (39%), both viral and bacterial pathogens in 49 (22%), while the aetiology remained unknown in 34 (15%) cases. The proportion of infections with an identified pathogen increased from 38% to 85% when syndromic testing was added to standard-of-care testing. Viral infections were associated with a low CRP level and absence of pulmonary infiltrates. A high National Early Warning Score did not predict bacterial infections. CONCLUSIONS: Syndromic testing by a multiplex PCR panel identified a viral infection or viral/bacterial coinfection in a majority of hospitalised adult patients with community-acquired LRTIs.

Risk of pulp necrosis and related complications in the permanent anterior teeth with lateral luxation: A systematic review and meta-analysis.

This systematic review aimed to evaluate the evidence related to the occurrence of pulp necrosis and related complications in permanent anterior teeth with lateral luxation. It was envisaged to address the ambiguity related to the recommendation for pulp extirpation in teeth with mature root apex. An a priori protocol was formulated as per the best practices of evidence-based medicine and registered in PROSPERO. A comprehensive search was performed electronically in PubMed, LILACS, Web of Science, EMBASE, Scopus, and Cochrane on July 10,2023 without any restriction of language or year of publication. The screening of titles and abstracts and later the full-text articles were performed. Later, the data extraction was performed by using a self-designed sheet, risk of bias (ROB) assessment was done, meta-analysis was performed, and the GRADE approach was used to assess the quality of evidence. The qualitative synthesis was performed on 13 studies done from 1985 to 2020 in hospital settings. There was variability in the minimum and total observation periods, sample sizes, and characteristics of the sample population. The overall pooled prevalence of pulp necrosis was found to be 57% (95% CI: 42, 72%). It was 12% (95% CI: 8%, 18%, I2 = 0%) in immature teeth, and 58% (95% CI: 42, 73%, I2 = 86%) in mature teeth. The pooled prevalence of EIRR was found to be 11% (95% CI: 4, 27%, I2 = 95%) with greater risk in teeth with mature root apex (RR: 1.26, 95% CI: 1.12, 1.42, I2 = 0%). The ROB was moderate or high in nine studies and the GRADE of evidence was very low in 14 of 15 outcomes. There are greater chances of pulp necrosis in teeth with lateral luxation, especially with mature apex. However, it can still be less than 60% in most cases with the prevalence of EIRR less than 20%. Hence, an absolute recommendation for endodontic intervention in mature teeth with lateral luxation must be interpreted with slight caution.

Description of the prehospital emergency healthcare system in Norway.

Background: Norway has a long coastline, steep mountains, and wide fjords, which presents some challenges to the prehospital emergency healthcare system. In recent years, the prehospital emergency medical services (EMS) have undergone significant changes, structurally, in terms of professionalisation of the services and in the education level of the personnel. In this article, we aim to describe the current structure for handling prehospital medical emergencies. Methods: For healthcare, Norway is divided into four Regional Health Authorities, consisting of 19 Health Trusts, where 18 have an EMS. There is a dedicated medical emergency number, 113, that terminates in 16 emergency medical communication centres. The use of air and boat ambulances, in addition to traditional ambulances, seeks to meet the challenges in the EMS system. Strengths and limitations: The Norwegian EMS is an advanced system with highly educated staff; however, this level of care comes with an equally high cost. Conclusion: The Norwegian EMS can handle emergencies nationwide, providing advanced care at the scene and during transport. The geography and demography challenge the idea of equal care, but the open publishing of data from national quality registries seeks to identify and address potential differences.

Risk of ankylosis of avulsed teeth immediately replanted or stored under favorable storage conditions before replantation: A long-term clinical study.

BACKGROUND/AIM: There are few long-term clinical follow-up studies on human teeth replanted immediately or after storage in a suitable storage medium prior to replantation. This study aimed to assess the risk of ankylosis in avulsed human teeth replanted immediately or after storage in physiological media for a short time. MATERIAL: Data from 116 patients with 145 replanted avulsed permanent teeth were selected from a comprehensive dental trauma database in Copenhagen University Hospital. The following teeth were selected: Group 1 comprised 36 teeth replanted immediately (dry time <6 min; wet time <6 min). Group 2 comprised 61 teeth replanted after physiologic storage media (saliva and saline) (dry time <6 min; wet time >5 min; wet time ranged from 7 to 170 min, and mean wet time was 59 min). Group 3 (control) included 48 teeth replanted after dry storage (dry time > 60 min). METHOD: Clinical and radiographic registrations were carried out according to a standardized protocol; follow-up ranged from 7 months to 23 years. Ankylosis was diagnosed by percussion test and radiographs and related to the conditions prior to replantation and stage of root development. RESULTS: The overall risk of ankylosis was 17.2% [95% CI: 4.61; 29.79] for immediately replanted teeth, 55.3% [95% CI: 42.54; 68.00] for teeth stored in physiologic media before replantation, and 85.7% [95% CI: 75.70; 95.73] for teeth stored dry more than 1 h. Mature teeth showed a significantly higher risk of ankylosis than immature teeth. CONCLUSION: This clinical long-term study has verified earlier experimental studies showing that immediate reimplantation has the lowest risk of ankylosis. Physiologic storage media are good alternatives that also reduce the risk of ankylosis compared to dry storage, where ankylosis is more likely although not always seen. Mature teeth are significantly more likely to develop ankylosis.

Low levels of endogenous anabolic androgenic steroids in females with severe asthma taking corticosteroids.

Rationale: Patients with severe asthma are dependent upon treatment with high doses of inhaled corticosteroids (ICS) and often also oral corticosteroids (OCS). The extent of endogenous androgenic anabolic steroid (EAAS) suppression in asthma has not previously been described in detail. The objective of the present study was to measure urinary concentrations of EAAS in relation to exogenous corticosteroid exposure. Methods: Urine collected at baseline in the U-BIOPRED (Unbiased Biomarkers for the Prediction of Respiratory Disease outcomes) study of severe adult asthmatics (SA, n=408) was analysed by quantitative mass spectrometry. Data were compared to that of mild-to-moderate asthmatics (MMA, n=70) and healthy subjects (HC, n=98) from the same study. Measurements and main results: The concentrations of urinary endogenous steroid metabolites were substantially lower in SA than in MMA or HC. These differences were more pronounced in SA patients with detectable urinary OCS metabolites. Their dehydroepiandrosterone sulfate (DHEA-S) concentrations were <5% of those in HC, and cortisol concentrations were below the detection limit in 75% of females and 82% of males. The concentrations of EAAS in OCS-positive patients, as well as patients on high-dose ICS only, were more suppressed in females than males (p<0.05). Low levels of DHEA were associated with features of more severe disease and were more prevalent in females (p<0.05). The association between low EAAS and corticosteroid treatment was replicated in 289 of the SA patients at follow-up after 12-18 months. Conclusion: The pronounced suppression of endogenous anabolic androgens in females might contribute to sex differences regarding the prevalence of severe asthma.

The risk of healing complications in primary teeth with root fractures: A retrospective cohort study.

BACKGROUND/AIM: Primary teeth are frequently affected by traumatic dental injuries. Root fractures are rare and have a reported incidence of 2% in the primary dentition. Hence, there is limited evidence on this topic. This study aims to evaluate the risk of healing complications in primary teeth with root fracture and to identify possible sequelae in the permanent dentition following root fracture in the primary dentition. MATERIALS AND METHODS: A retrospective analysis of a cohort of 53 patients with 74 root fractured primary teeth. The standard follow-up program included clinical and radiographic examination after 4 weeks, 8 weeks, 6 months, and 1 year after the trauma and when the patient was 6 years of age. The following complications were registered: pulp necrosis (PN), pulp canal obliteration (PCO), ankylosis with replacement root resorption (ARR), infection-related root resorption (IRR), premature tooth loss (PTL), and repair-related resorption (RRR). STATISTICS: The Kaplan-Meier and Aalen-Johansen estimators were employed. The level of significance was 5%. RESULTS: A total of 74 teeth were included. 42 teeth were extracted at the initial examination. Risks estimated after 3 years: PTL 45.9% [95% CI: 28.8-63.0], PCO 12.9% [95% CI: 2.3-23.4], PN 14.9% [95% CI: 3.9-25.9], RRR 2.6% [95% CI: 0.0-7.5]. No teeth showed ARR or IRR. All complications were diagnosed within the first year. Most common sequelae in the permanent dentition was demarcated opacities, with an estimated risk of 20% [95% CI: 8.2-41.3]. CONCLUSIONS: There is a low risk of healing complications following a root fracture in the primary dentition. Root fractures often result in early extraction of the coronal fragment. The remaining apical fragment will undergo a physiological resorption. Aside from opacities, there is a low risk of sequelae in the permanent dentition.

A novel precision-serology assay for SARS-CoV-2 infection based on linear B-cell epitopes of Spike protein.

Introduction: The COVID-19 pandemic illustrates the need for serology diagnostics with improved accuracy. While conventional serology based on recognition of entire proteins or subunits thereof has made significant contribution to the antibody assessment space, it often suffers from sub-optimal specificity. Epitope-based, high-precision, serology assays hold potential to capture the high specificity and diversity of the immune system, hence circumventing the cross-reactivity with closely related microbial antigens. Methods: We herein report mapping of linear IgG and IgA antibody epitopes of the SARS-CoV-2 Spike (S) protein in samples from SARS-CoV-2 exposed individuals along with certified SARS-CoV-2 verification plasma samples using peptide arrays. Results: We identified 21 distinct linear epitopes. Importantly, we showed that pre-pandemic serum samples contain IgG antibodies reacting to the majority of protein S epitopes, most likely as a result of prior infection with seasonal coronaviruses. Only 4 of the identified SARS-CoV-2 protein S linear epitopes were specific for SARS-CoV-2 infection. These epitopes are located at positions 278-298 and 550-586, just proximal and distal to the RBD, as well as at position 1134-1156 in the HR2 subdomain and at 1248-1271 in the C-terminal subdomain of protein S. To substantiate the applicability of our findings, we tested three of the high-accuracy protein S epitopes in a Luminex assay, using a certified validation plasma sample set from SARS-CoV-2 infected individuals. The Luminex results were well aligned with the peptide array results, and correlated very well with in-house and commercial immune assays for RBD, S1 and S1/S2 domains of protein S. Conclusion: We present a comprehensive mapping of linear B-cell epitopes of SARS-CoV-2 protein S, that identifies peptides suitable for a precision serology assay devoid of cross-reactivity. These results have implications for development of highly specific serology test for exposure to SARS-CoV-2 and other members of the coronaviridae family, as well as for rapid development of serology tests for future emerging pandemic threats.

Plasmablasts in previously immunologically naïve COVID-19 patients express markers indicating mucosal homing and secrete antibodies cross-reacting with SARS-CoV-2 variants and other beta-coronaviruses.

Antigen-specific class-switched antibodies are detected at the same time or even before IgM in serum of non-vaccinated individuals infected with SARS-CoV-2. These derive from the first wave of plasmablasts formed. Hence, the phenotype and specificity of plasmablasts can reveal information about early B-cell activation. Here we have analyzed B cells and plasmablasts circulating in blood of COVID-19 patients not previously exposed to SARS-CoV-2 during and after disease. We find that during infection with the original Wuhan strain, plasmablasts in blood produce IgA1, IgG1, and IgM, and that most express CCR10 and integrin ß1, only some integrin ß7, while the majority lack CCR9. Plasmablast-secreted antibodies are reactive to the spike (S) and nucleocapsid (N) proteins of the Wuhan strain as well as later variants of concern, but also bind S proteins from endemic and non-circulating betacoronaviruses. In contrast, after recovery, antibodies produced from memory B cells target variants of SARS-CoV-2 and SARS-CoV-1 but compared to previously non-infected individuals do not show increased binding to endemic coronaviruses. This suggests that the early antibody response to a large extent stems from pre-existing cross-reactive class-switched memory B cells, and that although newly formed memory cells target the novel SARS-CoV-2 virus the numbers of broadly cross-reactive memory B cells do not increase extensively. The observations give insight into the role of pre-existing memory B cells in early antibody responses to novel pathogens and may explain why class-switched antibodies are detected early in the serum of COVID-19 patients.

Outdoor Absolute Humidity Predicts the Start of Norovirus GII Epidemics.

Seasonal variation of viral gastroenteritis is related to weather conditions, but the relationship with the incidence of viral gastroenteritis (GE) is not fully understood. This study examined the impact of outdoor climate factors on seasonal variation in detection rates of gastroenteritis viruses, with emphasis on norovirus. Weekly detection rates of norovirus genogroup I (GI) and II (GII), rotavirus, adenovirus, astrovirus, and sapovirus were analyzed in relation to average weekly means of meteorological parameters. Associations between rates of PCR detection of the viral GE pathogens and climate factors were investigated with generalized linear models. Low absolute humidity was correlated with increased detection of adenovirus (P = 0.007), astrovirus (P = 0.005), rotavirus (P = 0.004), norovirus GI (P = 0.001), and sapovirus (P = 0.002). In each investigated season, a drop in absolute humidity preceded the increase in norovirus GII detections. We found a correlation between declining absolute humidity and increasing norovirus GII detection rate. Absolute humidity was a better predictor of gastrointestinal virus seasonality compared to relative humidity. IMPORTANCE Viral gastroenteritis causes considerable morbidity, especially in vulnerable groups such as the elderly and chronically ill. Predicting the beginning of seasonal epidemics is important for the health care system to withstand increasing demands. In this paper we studied the association of outdoor climate factors on the detection rates of gastrointestinal viruses and the association between these factors and the onset of annual norovirus epidemics. Declining absolute humidity preceded the increase in diagnosed norovirus GII cases by approximately 1 week. These findings contribute to the understanding of norovirus epidemiology and allow health care services to install timely preventive measures and can help the public avoid transmission.

COVID-19 is associated with bystander polyclonal autoreactive B cell activation as reflected by a broad autoantibody production, but none is linked to disease severity.

Coronavirus disease 2019 (COVID-19) is associated with autoimmune features and autoantibody production in a small subset of the population. Pre-existing neutralizing antitype I interferons (IFNs) autoantibodies are related to the severity of COVID-19. Plasma levels of IgG and IgM against 12 viral antigens and 103 self-antigens were evaluated using an antibody protein array in patients with severe/critical or mild/moderate COVID-19 disease and uninfected controls. Patients exhibited increased IgGs against Severe acute respiratory syndrome coronavirus-2 proteins compared to controls, but no difference was observed in the two patient groups. 78% autoreactive IgGs and 93% autoreactive IgMs were increased in patients versus controls. There was no difference in the plasma levels of anti-type I IFN autoantibodies or neutralizing anti-type I IFN activity of plasma samples from the two patient groups. Increased anti-type I IFN IgGs were correlated with higher lymphocyte accounts, suggesting a role of nonpathogenic autoantibodies. Notably, among the 115 antibodies tested, only plasma levels of IgGs against human coronavirus (HCOV)-229E and HCOV-NL63 spike proteins were associated with mild disease outcome. COVID-19 was associated with a bystander polyclonal autoreactive B cell activation, but none of the autoantibody levels were linked to disease severity. Long-term humoral immunity against HCOV-22E and HCOV-NL63 spike protein was associated with mild disease outcome. Understanding the mechanism of life-threatening COVID-19 is critical to reducing mortality and morbidity.

Longitudinal single-cell analysis of SARS-CoV-2-reactive B cells uncovers persistence of early-formed, antigen-specific clones.

Understanding persistence and evolution of B cell clones after COVID-19 infection and vaccination is crucial for predicting responses against emerging viral variants and optimizing vaccines. Here, we collected longitudinal samples from patients with severe COVID-19 every third to seventh day during hospitalization and every third month after recovery. We profiled their antigen-specific immune cell dynamics by combining single-cell RNA-Seq, Cellular Indexing of Transcriptomes and Epitopes by Sequencing (CITE-Seq), and B cell receptor-Seq (BCR-Seq) with oligo-tagged antigen baits. While the proportion of Spike receptor binding domain-specific memory B cells (MBC) increased from 3 months after infection, the other Spike- and Nucleocapsid-specific B cells remained constant. All patients showed ongoing class switching and sustained affinity maturation of antigen-specific cells, and affinity maturation was not significantly increased early after vaccine. B cell analysis revealed a polyclonal response with limited clonal expansion; nevertheless, some clones detected during hospitalization, as plasmablasts, persisted for up to 1 year, as MBC. Monoclonal antibodies derived from persistent B cell families increased their binding and neutralization breadth and started recognizing viral variants by 3 months after infection. Overall, our findings provide important insights into the clonal evolution and dynamics of antigen-specific B cell responses in longitudinally sampled patients infected with COVID-19.

Loss of Y in leukocytes as a risk factor for critical COVID-19 in men.

BACKGROUND: The COVID-19 pandemic, which has a prominent social and economic impact worldwide, shows a largely unexplained male bias for the severity and mortality of the disease. Loss of chromosome Y (LOY) is a risk factor candidate in COVID-19 due to its prior association with many chronic age-related diseases, and its impact on immune gene transcription. METHODS: Publicly available scRNA-seq data of PBMC samples derived from male patients critically ill with COVID-19 were reanalyzed, and LOY status was added to the annotated cells. We further studied LOY in whole blood for 211 COVID-19 patients treated at intensive care units (ICU) from the first and second waves of the pandemic. Of these, 139 patients were subject to cell sorting for LOY analysis in granulocytes, low-density neutrophils (LDNs), monocytes, and PBMCs. RESULTS: Reanalysis of available scRNA-seq data revealed LDNs and monocytes as the cell types most affected by LOY. Subsequently, DNA analysis indicated that 46%, 32%, and 29% of critically ill patients showed LOY above 5% cut-off in LDNs, granulocytes, and monocytes, respectively. Hence, the myeloid lineage that is crucial for the development of severe COVID-19 phenotype is affected by LOY. Moreover, LOY correlated with increasing WHO score (median difference 1.59%, 95% HDI 0.46% to 2.71%, p=0.025), death during ICU treatment (median difference 1.46%, 95% HDI 0.47% to 2.43%, p=0.0036), and history of vessel disease (median difference 2.16%, 95% HDI 0.74% to 3.7%, p=0.004), among other variables. In 16 recovered patients, sampled during ICU stay and 93-143 days later, LOY decreased significantly in whole blood and PBMCs. Furthermore, the number of LDNs at the recovery stage decreased dramatically (median difference 76.4 per 10,000 cell sorting events, 95% HDI 55.5 to 104, p=6e-11). CONCLUSIONS: We present a link between LOY and an acute, life-threatening infectious disease. Furthermore, this study highlights LOY as the most prominent clonal mutation affecting the myeloid cell lineage during emergency myelopoiesis. The correlation between LOY level and COVID-19 severity might suggest that this mutation affects the functions of monocytes and neutrophils, which could have consequences for male innate immunity.

The effect of vitamin B supplementation on neuronal injury in people living with HIV: a randomized controlled trial.

Effective antiretroviral therapy has radically changed the course of the HIV pandemic. However, despite efficient therapy, milder forms of neurocognitive symptoms are still present in people living with HIV. Plasma homocysteine is a marker of vitamin B deficiency and has been associated with cognitive impairment. People living with HIV have higher homocysteine concentrations than HIV-negative controls, and we have previously found an association between plasma homocysteine concentration and CSF concentration of neurofilament light protein, a sensitive marker for ongoing neuronal injury in HIV. This prompted us to perform this randomized controlled trial, to evaluate the effect of vitamin B supplementation on neuronal injury in a cohort of people living with HIV on stable antiretroviral therapy. At the Department of Infectious Diseases at Sahlgrenska University Hospital in Gothenburg, Sweden, 124 virally suppressed people living with HIV were screened to determine eligibility for this study. Sixty-one fulfilled the inclusion criteria by having plasma homocysteine levels at or above 12 µmol/l. They were randomized (1:1) to either active treatment (with cyanocobalamin 0.5 mg, folic acid 0.8 mg and pyridoxine 3.0 mg) q.d. or to a control arm with a cross over to active treatment after 12 months. Cognitive function was measured repeatedly during the trial, which ran for 24 months. We found a significant correlation between plasma neurofilament light protein and plasma homocysteine at screening (n = 124, r = 0.35, P < 0.0001). Plasma homocysteine levels decreased by 35% from a geometric mean of 15.7 µmol/l (95% confidence interval 14.7-16.7) to 10.3 µmol/l (95% confidence interval 9.3-11.3) in the active treatment arm between baseline and Month 12. No significant change was detected in the control arm during the same time period [geometric mean 15.2 (95% confidence interval 14.3-16.2) versus geometric mean 16.5 µmol/l (95% confidence interval 14.7-18.6)]. A significant difference in change in plasma homocysteine levels was seen between arms at 12 months [-40% (95% confidence interval -48 to -30%), P < 0.001]. However, no difference between arms was seen in either plasma neurofilament light protein levels [-6.5% (-20 to 9%), P = 0.39], or cognitive measures [-0.08 (-0.33 to 0.17), P = 0.53]. Our results do not support a vitamin B-dependent cause of the correlation between neurofilament light protein and homocysteine. Additional studies are needed to further elucidate this matter.

Nonlinear Radiation Gauge for Near Kerr Spacetimes.

In this paper, we introduce and explore the properties of a new gauge choice for the vacuum Einstein equation inspired by the ingoing and outgoing radiation gauges (IRG, ORG) for the linearized vacuum Einstein equation introduced by Chrzanowski in his work on metric reconstruction (Chrzanowski in Phys Rev D 11:2042-2062, 1975) on the Kerr background. It has been shown by Price et al. (Class Quantum Gravity 24:2367-2388, 2007) that the IRG/ORG are consistent gauges for the linearized vacuum Einstein equation on Petrov type II backgrounds. In (Andersson et al. Stability for linearized gravity on the Kerr spacetime, 2019), the ORG was used in proving linearized stability for the Kerr spacetime, and the new non-linear radiation gauge introduced here is a direct generalization of that gauge condition, and is intended to be used to study the stability of Kerr black holes under the evolution generated by the vacuum Einstein equation.

Long-term functional consequences of cranial nerve injuries after carotid endarterectomy.

BACKGROUND: The aim of the study was to investigate long-term patient consequences of cranial nerve injury (CNI) caused by carotid endarterectomy (CEA) in patients with identified CNI at the 30-day follow-up. METHODS: Consecutive patients operated for symptomatic carotid artery stenosis 2015-2019 with a documented CNI at the 30-day follow-up after CEA were recruited to this cross-sectional survey. Telephone interviews were conducted >1 year after CEA utilizing survey instruments developed to uncover CNI symptoms. Patients graded their symptoms on a 4-point scale: 1) no symptoms; 2) mild symptoms; 3) moderate symptoms; and 4) severe symptoms. RESULTS: Altogether, 477 patients underwent CEA, of which 82 were diagnosed with CNI; 70/82 patients remained alive at the time for the survey and 68 patients completed the interview. The mean follow-up time was 3.7 years. Severe persistent CNI symptoms were reported in 2/68 (2.9%), moderate symptoms in 1/68 (1.5%) and mild symptoms in 14/68 (21%) whereas 51/68 patients (75%) reported no residual symptoms. When extrapolating these findings to all patients, approximately 4.4% reported persistent symptoms at the long-term follow-up and only 0.8% reported moderate or severe symptoms. CONCLUSIONS: The long-term consequences of CNI following CEA are benign in most patients, with a high rate of symptom resolution and a very low rate of persistent clinically significant symptoms.

Comparison of SARS-CoV-2 spike RNA sequences in feces and nasopharynx indicates intestinal replication.

BACKGROUND: Little is known of possible selection and replication of SARS-CoV-2 in the intestines and if viral load in feces is associated with severity of disease. Therefore, sequence variations of the spike region in strains collected from feces and nasopharynx (NPH) from the same patients were compared. It was also investigated whether viral load in feces related to severity of COVID-19 in hospitalized patients. RESULTS: SARS-CoV-2 RNA was found in 88 (79%) fecal samples from 112 patients. The complete spike region could be sequenced in 15 fecal and 14 NPH samples. Fourteen Alpha-variants and one Beta-variant of SARS-CoV-2 were identified. The majority of the viral genetic variants (viral populations) in two fecal samples, but none in NPH, had a reversion of the H69/V70 amino acid deletion normally seen in the Alpha variants. Nine fecal samples contained up to nine minority variants, each which may constitute a separate viral population. Five NPH samples had one genetic variant each, and one NPH sample contained nine minority populations of SARS-CoV-2 spike genes. CONCLUSIONS: The higher genomic diversity of SARS-CoV-2 in feces compared to NPH, and the reversion of the H69/V70 deletion in Alpha variants from feces indicate a selection of viral strains and replication of SARS-CoV-2 in the gastrointestinal tract.

No effect of remdesivir or betamethasone on upper respiratory tract SARS-CoV-2 RNA kinetics in hospitalised COVID-19 patients: a retrospective observational study.

BACKGROUND: The viral kinetics of SARS-CoV-2 has been considered clinically important. While remdesivir and corticosteroids are recommended for COVID-19 patients requiring oxygen support, there is a limited number of published reports on viral kinetics in hospitalised patients with COVID-19 treated with remdesivir or corticosteroids. METHODS: We conducted a retrospective study by collecting longitudinal samples from the nasopharynx/throat of 123 hospitalised patients (median age 55 years, 74% male) with COVID-19, to evaluate the effects of remdesivir and corticosteroid treatment on viral RNA levels. The subjects were divided into four groups: those receiving remdesivir (n = 25), betamethasone (n = 41), both (n = 15), or neither (n = 42). Time to viral RNA clearance was analysed using Kaplan-Meier plots, categorical data were analysed using Fisher's exact test, and Kruskal-Wallis for continuous data. Viral RNA decline rate was analysed using a mixed effect model. RESULTS: We found no significant difference in SARS-CoV-2 RNA decline rate or time to SARS-CoV-2 RNA clearance between the groups. Moreover, clinical status at baseline was not correlated with time to viral clearance. CONCLUSIONS: Since SARS-CoV-2 RNA kinetics was not affected by treatment, repeated sampling from the upper respiratory tract cannot be used to evaluate treatment response.

System dynamic modelling of healthcare associated influenza -a tool for infection control.

BACKGROUND: The transmission dynamics of influenza virus within healthcare settings are not fully understood. Capturing the interplay between host, viral and environmental factors is difficult using conventional research methods. Instead, system dynamic modelling may be used to illustrate the complex scenarios including non-linear relationships and multiple interactions which occur within hospitals during a seasonal influenza epidemic. We developed such a model intended as a support for health-care providers in identifying potentially effective control strategies to prevent influenza transmission. METHODS: By using computer simulation software, we constructed a system dynamic model to illustrate transmission dynamics within a large acute-care hospital. We used local real-world clinical and epidemiological data collected during the season 2016/17, as well as data from the national surveillance programs and relevant publications to form the basic structure of the model. Multiple stepwise simulations were performed to identify the relative effectiveness of various control strategies and to produce estimates of the accumulated number of healthcare-associated influenza cases per season. RESULTS: Scenarios regarding the number of patients exposed for influenza virus by shared room and the extent of antiviral prophylaxis and treatment were investigated in relation to estimations of influenza vaccine coverage, vaccine effectiveness and inflow of patients with influenza. In total, 680 simulations were performed, of which each one resulted in an estimated number per season. The most effective preventive measure identified by our model was administration of antiviral prophylaxis to exposed patients followed by reducing the number of patients receiving care in shared rooms. CONCLUSIONS: This study presents an system dynamic model that can be used to capture the complex dynamics of in-hospital transmission of viral infections and identify potentially effective interventions to prevent healthcare-associated influenza infections. Our simulations identified antiviral prophylaxis as the most effective way to control in-hospital influenza transmission.