Threatening drug-drug interaction in a kidney transplant patient with coronavirus disease 2019 (COVID-19).

During the novel coronavirus pandemic, organ transplant recipients represent a frail susceptible category due to long-term immunosuppressive therapy. For this reason, clinical manifestations may differ from general population and different treatment approaches may be needed. We present the case of a 36-year-old kidney-transplanted woman affected by Senior-Loken syndrome diagnosed with COVID-19 pneumonia after a contact with her positive mother. Initial symptoms were fatigue, dry cough, and coryza; she never had fever nor oxygen supplementation. Hydroxychloroquine and lopinavir/ritonavir were started, and the antiviral drug was replaced with darunavir/cobicistat after 2 days for diarrhea. Immunosuppressant levels were closely monitored, and we observed very high tacrolimus trough levels despite initial dose reduction. The patient was left with steroid therapy alone. The peculiarity of clinical presentation and the management difficulties represent the flagship of our case report. We stress the need for guidelines in transplant recipients with COVID-19 infection with particular regard to the management of therapy.

Propolis nasal spray effectively improves recovery from infectious acute rhinitis and common cold symptoms in children: a pilot study.

Currently, treatment for acute rhinitis (AR) is symptomatic but no clear agreement exists to control its development. Propolis extract may appear as a promising natural treatment for AR, but its beneficial effects have not yet been fully tested. Forty children suffering from AR and common cold symptoms aged between 2-12 years were enrolled in a prospective epidemiological multicentre study. A 7-day treatment with propolis nasal spray (3 times/day) was applied and a comparison of symptomatology, subjective global improvement and quality of life (QoL) between baseline (day 1) and final (day 7) visits were performed. The main goal was to evaluate the changes in symptom intensity using the Jackson’s scoring test. After 7 days of treatment there was a significant decrease of symptoms both in the total score (p less than 0.0001) and in regard to each AR symptom (p less than 0.01). On the whole, the sample reported no symptoms by day 7, and the resolution of symptoms occurred approximately at day 4. Furthermore, there was no need for supplementary treatment. Both the subjective global improvement impression and the QoL of patients appeared to significantly improve after treatment. No adverse events (AEs) were found globally. It can be concluded that propolis nasal spray effectively improves recovery from infectious AR and common cold symptoms in children and is an optimal alternative in the treatment of this disease without need for any adjuvant treatment.

Comparison of the Benefit Feeling Rate Based on the Sho of OTC Kakkonto, Cold Remedy and Cold Remedy with Kakkonto Combination Product.

Kakkonto (KK), a traditional Japanese Kampo formulation for cold and flu, is generally sold as an OTC pharmaceuticals used for self-medication. Kampo formulations should be used according to the Sho-symptoms of Kampo medicine. These symptoms refer to the subjective symptoms themselves. Although with OTC pharmaceuticals, this is often not the case. We surveyed the relationship of agreement of Sho with the benefit feeling rate (BFR) of patients who took KK (n=555), cold remedies with KK (CK, n=315), and general cold remedies (GC, n=539) using internet research. BFR of a faster recovery was greater in participants who took the medication early and who had confidence in their physical strength in all treatment groups. BFR was significantly higher in the GC group than in the KK group for patients with headache, runny nose, blocked nose, sneezing, and cough. BFR was also significantly higher in the GC group than in the CK group for headache (males) and cough (females). BFR was the highest in the KK group for stiff shoulders. All cold remedies were more effective when taken early, and the larger the number of Sho that a patient had, the greater the BFR increased. Therefore, a cold remedy is expected to be most effective when there are many cold symptoms and when it is taken at an early stage of the common cold.

Task Engagement and Attentional Resources.

OBJECTIVE: Two studies tested multivariate models of relationships between subjective task engagement and vigilance. The second study included a stress factor (cold infection). Modeling tested relationships between latent factors for task engagement and vigilance, and the role of engagement in mediating effects of cold infection. BACKGROUND: Raja Parasuraman's research on vigilance identified several key issues, including the roles of task factors, arousal processes, and individual differences, within the framework of resource theory. Task engagement is positively correlated with performance on various attentional tasks and may serve as a marker for resource availability. METHOD: In the first study, 229 participants performed simultaneous and successive vigilance tasks. In the second study, 204 participants performed a vigilance task and a variable-foreperiod simple reaction-time task on two separate days. On the second day, 96 participants performed while infected with a naturally occurring common cold. Task engagement was assessed in both studies. RESULTS: In both studies, vigilance decrement in hit rate was observed, and task performance led to loss of task engagement. Cold infection also depressed both vigilance and engagement. Fitting structural equation models indicated that simultaneous and successive tasks should be represented by separate latent factors (Study 1), and task engagement fully mediated the impact of cold infection on vigilance but not reaction time (Study 2). CONCLUSIONS: Modeling individual differences in task engagement elucidates the role of resources in vigilance and underscores the relevance of Parasuraman's vision of the field. APPLICATION: Assessment of task engagement may support diagnostic monitoring of operators performing tasks requiring vigilance.

Basal salivary cortisol secretion and susceptibility to upper respiratory infection.

The immunosuppressive effects of glucocorticoids (GCs) are well-established. However, whether the net effect of GC-elicited alterations in immune function is sufficient to influence a clinically relevant outcome in healthy adults has yet to be shown. The aim of the present study was to investigate whether inter-individual differences in basal salivary cortisol production are associated with increased risk and severity of infection and subsequent illness following experimental exposure to a virus that causes the common cold. The present analyses combine archival data from three viral-challenge studies. Participants were 608 healthy adults, aged 18 to 55 years (49.2% female; 65.8% white), who each completed a three-day saliva collection protocol; was subsequently exposed to a virus that causes the common cold; and monitored for 5 days for objective signs of infection (presence of challenge virus in nasal secretions) and clinical illness (mucus weight, mucociliary clearance time). Basal cortisol production (operationalized as the calculated area-under-the-curve averaged across the 3 days) showed a graded association with infection risk, with those producing higher levels of cortisol being at greater risk. Cortisol also showed a continuous association with duration of viral shedding, an indicator of viral replication and continuing infection, such that higher cortisol concentrations predicted more days of shedding. Cortisol was not, however, related to severity of objective illness. These findings are the first to demonstrate in healthy adults an association between basal cortisol production and an objectively measured and clinically relevant infectious disease outcome.

Viral entry pathways: the example of common cold viruses.

For infection, viruses deliver their genomes into the host cell. These nucleic acids are usually tightly packed within the viral capsid, which, in turn, is often further enveloped within a lipid membrane. Both protect them against the hostile environment. Proteins and/or lipids on the viral particle promote attachment to the cell surface and internalization. They are likewise often involved in release of the genome inside the cell for its use as a blueprint for production of new viruses. In the following, I shall cursorily discuss the early more general steps of viral infection that include receptor recognition, uptake into the cell, and uncoating of the viral genome. The later sections will concentrate on human rhinoviruses, the main cause of the common cold, with respect to the above processes. Much of what is known on the underlying mechanisms has been worked out by Renate Fuchs at the Medical University of Vienna.

Infection with Rhinovirus Facilitates Allergen Penetration Across a Respiratory Epithelial Cell Layer.

BACKGROUND: Rhinovirus infections are a major risk factor for asthma exacerbations. We sought to investigate in an in vitro system whether infection with human rhinovirus reduces the integrity and barrier function of a respiratory epithelial cell layer and thus may influence allergen penetration. METHODS: We cultured the human bronchial epithelial cell line 16HBE14o- in a transwell culture system as a surrogate of respiratory epithelium. The cell monolayer was infected with human rhinovirus 14 at 2 different doses. The extent and effects of transepithelial allergen penetration were assessed using transepithelial resistance measurements and a panel of (125)I-labeled purified recombinant respiratory allergens (rBet v 1, rBet v 2, and rPhl p 5). RESULTS: Infection of respiratory cell monolayers with human rhinovirus decreased transepithelial resistance and induced a pronounced increase in allergen penetration. CONCLUSIONS: Our results indicate that infection with rhinovirus damages the respiratory epithelial barrier and allows allergens to penetrate more efficiently into the subepithelial tissues where they may cause increased allergic inflammation.

Stability of cough reflex sensitivity during viral upper respiratory tract infection (common cold).

Cough is among the symptoms most commonly associated with an acute, viral upper respiratory tract infection (URI), such as the common cold. Two previous studies incorporating capsaicin cough challenge methodology have demonstrated that cough reflex sensitivity is transiently enhanced during URI. These studies used single measurements of cough reflex sensitivity during the URI period. To our knowledge, no previous studies have included multiple measurements of cough reflex sensitivity to capsaicin during a URI to evaluate the stability of this measure during the acute viral illness. In the current methodological investigation, we performed capsaicin cough challenges in 42 subjects with URI who were otherwise healthy, adult, nonsmokers (25 female). Subjects were enrolled within 72 h of onset of illness and randomly assigned to 3 groups (n = 14 each) that underwent cough reflex sensitivity measurement (C2 and C5) at days 0 and 1 for group 1; days 2 and 3 for group 2; or days 4 and 5 for group 3. Each subject returned 4-8 weeks post-viral infection to establish a healthy baseline measurement (recovery). Our results support that cough reflex sensitivity to capsaicin, as measured by C5, is a sensitive measure that remains stable during 6 days of a URI. These results suggest that cough reflex sensitivity measures in the presence of a URI provide a sensitive and reproducible approach that could be used in future investigations seeking to test experimental antitussive therapies.

The common cold: potential for future prevention or cure.

The common cold is the most frequent, although generally mild, human disease. Human Rhinoviruses are the prevalent causative agents, but other viruses are also implicated. Being so common, viral colds, have significant implications on public health and quality of life, but may also be life-threatening for vulnerable groups of patients. Specific diagnosis and treatment of the common cold still remain unmet needs. Molecular diagnostic techniques allow specific detection of known pathogens as well as the identification of newly emerging viruses. Although a number of medications or natural treatments have been shown to have some effect, either on the number or on the severity of common colds, no single agent is considerably effective. Virus-specific management remains in most cases a challenging potential as many factors have to be taken into account, including the diversity of the viral genomes, the heterogeneity of affected individuals, as well as the complexity of this long standing host-virus relationship.

Rhinovirus and the developing lung.

Human rhinovirus (HRV) infections are now widely accepted as the commonest cause of acute respiratory illnesses (ARIs) in children. Advanced PCR techniques have enabled HRV infections to be identified as causative agents in most common ARIs in childhood including bronchiolitis, acute asthma, pneumonia and croup. However, the long-term implications of rhinovirus infections are less clear. The aim of this review is to examine the relationship between rhinovirus infections and disorders of the lower airways in childhood.

Consumption of cranberry polyphenols enhances human γδ-T cell proliferation and reduces the number of symptoms associated with colds and influenza: a randomized, placebo-controlled intervention study.

BACKGROUND: Our main objective was to evaluate the ability of cranberry phytochemicals to modify immunity, specifically γδ-T cell proliferation, after daily consumption of a cranberry beverage, and its effect on health outcomes related to cold and influenza symptoms. METHODS: The study was a randomized, double-blind, placebo-controlled, parallel intervention. Subjects drank a low calorie cranberry beverage (450 ml) made with a juice-derived, powdered cranberry fraction (n = 22) or a placebo beverage (n = 23), daily, for 10 wk. PBMC were cultured for six days with autologous serum and PHA-L stimulation. Cold and influenza symptoms were self-reported. RESULTS: The proliferation index of γδ-T cells in culture was almost five times higher after 10 wk of cranberry beverage consumption (p <0.001). In the cranberry beverage group, the incidence of illness was not reduced, however significantly fewer symptoms of illness were reported (p = 0.031). CONCLUSIONS: Consumption of the cranberry beverage modified the ex vivo proliferation of γδ-T cells. As these cells are located in the epithelium and serve as a first line of defense, improving their function may be related to reducing the number of symptoms associated with a cold and flu.

Host and viral factors associated with severity of human rhinovirus-associated infant respiratory tract illness.

BACKGROUND: Risk factors for severe human rhinovirus (HRV)-associated infant illness are unknown. OBJECTIVES: We sought to examine the role of HRV infection in infant respiratory tract illness and assess viral and host risk factors for HRV-associated disease severity. METHODS: We used a prospective cohort of term, previously healthy infants enrolled during an inpatient or outpatient visit for acute upper or lower respiratory tract illness during the fall-spring months of 2004-2008. Illness severity was determined by using an ordinal bronchiolitis severity score, with higher scores indicating more severe disease. HRV was identified by means of real-time RT-PCR. The VP4/VP2 region from HRV-positive specimens was sequenced to determine species. RESULTS: Of 630 infants with bronchiolitis or upper respiratory tract illnesses (URIs), 162 (26%) had HRV infection; HRV infection was associated with 18% of cases of bronchiolitis and 47% of cases of URI. Among infants with HRV infection, 104 (64%) had HRV infection alone. Host factors associated with more severe HRV-associated illness included a maternal and family history of atopy (median score of 3.5 [interquartile range [IQR], 1.0-7.8] vs 2.0 [IQR, 1.0-5.2] and 3.5 [IQR, 1.0-7.5] vs 2.0 [IQR, 0-4.0]). In adjusted analyses maternal history of atopy conferred an increase in the risk for more severe HRV-associated bronchiolitis (odds ratio, 2.39; 95% CI, 1.14-4.99; P = .02). In a similar model maternal asthma was also associated with greater HRV-associated bronchiolitis severity (odds ratio, 2.49, 95% CI, 1.10-5.67; P = .03). Among patients with HRV infection, 35% had HRVA, 6% had HRVB, and 30% had HRVC. CONCLUSION: HRV infection was a frequent cause of bronchiolitis and URIs among previously healthy term infants requiring hospitalization or unscheduled outpatient visits. Substantial viral genetic diversity was seen among the patients with HRV infection, and predominant groups varied by season and year. Host factors, including maternal atopy, were associated with more severe infant HRV-associated illness.

Anesthesia in children with a cold.

PURPOSE OF REVIEW: Common colds are infections of mostly viral origin that frequently occur in childhood. The overall anesthetic risk in children with respiratory tract infections is increased because of the increased incidence of perioperative respiratory adverse events (PRAEs). Although the morbidity and mortality of PRAE are low when managed by experienced anesthesiologists, careful preoperative assessment and perioperative anesthetic care are indispensable. RECENT FINDINGS: This review summarizes recent studies to give a brief overview and background information with regard to the pathophysiological mechanisms of upper respiratory tract infections, risk factors for PRAE in children with a cold, management of anesthesia and prevention and treatment of frequently observed adverse events as well as a proposal for a decision algorithm. SUMMARY: Children with a cold can be safely anesthetized under certain circumstances; however, anesthesia in children with symptomatic infections with wheezing, purulent secretion, fever and reduced general condition should be postponed for at least 2 weeks. Anesthetic treatment options for children with infection of the upper airway with a runny nose and cough include preoperative inhalational therapy with salbutamol, avoidance of endotracheal intubation whenever possible, use of a face mask or laryngeal mask, intravenous induction with propofol and avoidance of desflurane. Prevention, early recognition and immediate treatment of complications by an experienced anesthesiologist are crucial.

May nasal hyperreactivity be a sequela of recurrent common cold?

Respiratory viral infections may worsen bronchial hyperreactivity. However, there is no data on the possible role of recurrent infectious rhinitis in nose hyperreactivity. This study was therefore designed to investigate whether subjects suffering from recurrent common cold have nasal hyperreactivity, assessed by histamine nasal challenge. This study included a group of 40 patients (19 males, mean age 34.1 years) with history of at least five episodes of common cold in the previous year, but without documented allergy, and twenty healthy subjects (8 males, mean age 32.3 years) were enrolled as control group, all of whom were non-allergic. Nasal provocation test with histamine was performed in all subjects. Nasal provocation test with histamine induced a 200% increase in nasal resistance after provocation in 24 (60%) patients suffering from recurrent viral rhinitis. No normal subject had an increase >180% in nasal resistance. There was a significant difference between the patient group and the control group (p<0.05). In conclusion, this study shows that nasal hyperreactivity might be a sequela of recurrent common cold. Further studies should be conducted to confirm this preliminary finding.

Mechanism of Rhinovirus Immunity and Asthma.

The majority of asthma exacerbations in children are caused by Rhinovirus (RV), a positive sense single stranded RNA virus of the Picornavirus family. The host has developed virus defense mechanisms that are mediated by the upregulation of interferon-activated signaling. However, the virus evades the immune system by inducing immunosuppressive cytokines and surface molecules like programmed cell death protein 1 (PD-1) and its ligand (PD-L1) on immunocompetent cells. Initially, RV infects epithelial cells, which constitute a physiologic mucosal barrier. Upon virus entrance, the host cell immediately recognizes viral components like dsRNA, ssRNA, viral glycoproteins or CpG-DNA by host pattern recognition receptors (PRRs). Activation of toll like receptors (TLR) 3, 7 and 8 within the endosome and through MDA-5 and RIG-I in the cytosol leads to the production of interferon (IFN) type I and other antiviral agents. Every cell type expresses IFNAR1/IFNAR2 receptors thus allowing a generalized antiviral activity of IFN type I resulting in the inhibition of viral replication in infected cells and preventing viral spread to non-infected cells. Among immune evasion mechanisms of the virus, there is downregulation of IFN type I and its receptor as well as induction of the immunosuppressive cytokine TGF-ß. TGF-ß promotes viral replication and is associated with induction of the immunosuppression signature markers LAP3, IDO and PD-L1. This article reviews the recent advances on the regulation of interferon type I expression in association with RV infection in asthmatics and the immunosuppression induced by the virus.

Common cold decreases lung function in infants with recurrent wheezing.

BACKGROUND: Common acute viral respiratory infections (colds) are the most frequent cause of exacerbations in infants with recurrent wheezing (RW). However, there is no quantitative information about the effect of colds on the lung function of infants with RW. This study was undertaken to determine the effect of common cold on forced expiratory parameters measured from raised lung volume in infants with RW. METHODS: Spirometric lung function (expiratory flows from raised lung volume) was randomly assessed in 28 infants with RW while they had a common cold and when asymptomatic. RESULTS: It was found that during colds there was a significant decrease in all forced expiratory parameters and this was much more evident for flows (FEF(50%), FEF(75%) and FEF(25-75%)) which were definitively abnormal (less than -1.65 z-score) in the majority of infants. There was not association between family asthma, tobacco exposure, and other factors, with the extent of lung function decrease during colds. Tobacco during pregnancy but not a history of family asthma was significantly associated to lower expiratory flows; however, the association was significant only when infants were asymptomatic. CONCLUSION: This study shows that common colds cause a marked reduction of lung function in infants with RW.

Development and Content Validity Testing of Patient-Reported Outcome Items for Children to Self-Assess Symptoms of the Common Cold.

BACKGROUND AND OBJECTIVE: No pediatric patient-reported outcome instruments specific to the common cold are found in the literature. This study involved development and content validity testing of patient-reported outcome items (questions and response options) assessing cold symptoms in children aged 6-11 years. METHODS: Draft patient-reported outcome instructions, items, response scales, and recall periods were developed based on the literature and existing measures. Qualitative interviews were conducted with children (n = 39) who were currently (n = 31) or had recently (n = 8) experienced a cold and ten parents of a subset of children aged 6-8 years. The interviews were conducted over two rounds and included open-ended concept elicitation questioning, a free-drawing task, a card sorting task, and a task involving circling parts of the body, followed by cognitive debriefing of draft items. Thematic analysis of verbatim transcripts was performed to analyze the qualitative data. The findings were used to support revisions to the draft patient-reported outcome. RESULTS: Ten symptom concepts were reported by the children during concept elicitation. The creative tasks helped the children to describe their symptoms, generally using consistent language to do so, irrespective of age. Nineteen patient-reported outcome items were developed and subject to cognitive debriefing. Debriefing with both children and parents informed several small revisions and provided evidence that the majority of children found most patient-reported outcome items easy to understand, and that the items were mainly interpreted consistently and as intended. CONCLUSIONS: This in-depth qualitative study has supported identification of relevant symptom concepts and the development and refinement of patient-reported outcome items to assess those concepts. The findings support the content validity of the items and suggest that they can be used with confidence in children aged 9 years and older. For children aged 6-8 years, it is recommended the items are administered with initial adult supervision to explain the more difficult concepts or through parent/interviewer administration.

25-Hydroxyvitamin D variability within-person due to diurnal rhythm and illness: a case report.

BACKGROUND: Vitamin D nutrition research requires accurate measures of circulating 25-hydroxyvitamin D. Our objectives were to test whether a diurnal fluctuation in blood-spot concentrations of 25-hydroxyvitamin D can be demonstrated statistically in a single individual, and whether such fluctuation is affected by the pre-dose versus post-dose timing of the blood draw. CASE PRESENTATION: The participant in this case study was a generally healthy Caucasian woman in her 40s who has taken 5000 IU vitamin D3 supplement at midday for over 1 year. Each blood sample was drawn individually from a finger prick onto filter paper at morning, midday, or night, on 4 days (three groups of five individual blood samples per collection day). On days 1 and 2, the midday samples were collected approximately 1 hour after the supplement was taken; on days 3 and 4, the midday samples were collected within an hour prior to supplementation (the classical, daily "trough" value for a drug). There was a significant daily pattern of variation in 25-hydroxyvitamin D concentrations (analysis of variance p ≤ 0.02 for 3 of the 4 days): peak midday mean 25-hydroxyvitamin D was approximately 20% higher than in the morning, and approximately 13% higher than in the evening. Trough sampling produced no significant difference in 25-hydroxyvitamin D compared to sampling an hour after the dose. An incidental finding was that acute illness during the study was related to acutely lower 25-hydroxyvitamin D at every sampling time in the day (p < 0.00001). CONCLUSIONS: There was a consistent diurnal variation in 25-hydroxyvitamin D, with the peak at midday. There was no difference between trough versus post-dose blood draws. Acute illness may acutely lower serum 25-hydroxyvitamin D levels. Because within-person, within-day variability in 25-hydroxyvitamin D is approximately 20%, sampling time introduces systematic error in vitamin D nutritional assessment that is bigger than random analytical error or choice of assay method.

Association of Daily Workload, Wellness, and Injury and Illness During Tours in International Cricketers.

PURPOSE: To examine the relationship between player internal workloads, daily wellness monitoring, and injury and illness in a group of elite adolescent cricketers during overseas competitions. METHODS: A total of 39 male international adolescent cricketers (17.5 [0.8] y) took part in the study. Data were collected over 5 tours across a 3-y period (2014-2016). Measures of wellness were recorded and daily training loads were calculated using session rating of perceived exertion. The injury and illness status of each member of the squad was recorded daily. Acute and chronic workloads were calculated using 3-d and 14-d moving averages. Acute workloads, chronic workloads, and acute chronic workload ratios were independently modeled as fixed effects predictor variables. RESULTS: In the subsequent week, a high 3-d workload was significantly associated with an increased risk of injury (relative risk = 2.51; CI = 1.70-3.70). Similarly, a high 14-d workload was also associated with an increased risk of injury (relative risk = 1.48; CI = 1.01-2.70). Individual differences in the load-injury relationship were also found. No clear relationship between the acute chronic workload ratios and injury risk was found, but high chronic workloads combined with high or low acute chronic workload ratios showed an increased probability of injury compared with moderate chronic workloads. There were also trends for sleep quality and cold symptoms worsening the week before an injury occurred. CONCLUSION: Although there is significant individual variation, short-term high workloads and change in wellness status appear to be associated with injury risk.

Binafuxi granules in the treatment of common cold with heat syndrome based on traditional Uighur medicine: study protocol for a multicenter randomized controlled trial.

BACKGROUND: The common cold is a highly prevalent illness with significant impact on society and health care. Common cold with heat syndrome (CCHS) is one of the most common types based on syndrome differentiation by traditional Uighur medicine (TUM), which is widely used in Central Asia. The study is designed to explore the efficacy, safety and optimal therapeutic dosage of Binafuxi granules in treating CCHS. METHODS: This is a multicenter, randomized, double-blind, placebo-controlled, phase II clinical trial. Participants (n = 240) will be enrolled from five centers across China and randomly assigned to the high-dose group, low-dose group or placebo control group in a 1:1:1 ratio. All eligible patients will receive test drugs twice daily for 3 days. The primary outcome is the time to fever relief. Secondary outcomes include the time to fever clearance, duration of primary symptoms and each symptom and change in TUM symptom score. DISCUSSION: This is the first placebo-controlled randomized clinical trial of a Uighur medicine in treating common cold. It will provide robust evidence on the efficacy and safety of Binafuxi granules in the treatment of CCHS. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR-IIR-17013379 . Registered on 14 November 2017.