Prolonged Infection Research Articles

Emergence of SARS-CoV-2 Spike Mutations during Prolonged Infection in Immunocompromised Hosts.

ABSTRACTImmunocompromised hosts with prolonged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections have been implicated in the emergence of highly mutated SARS-CoV-2 variants. Spike mutations are of particular concern because the spike protein is a key target for vaccines and therapeutics for SARS-CoV-2. Here, we report the emergence of spike mutations in two immunocompromised patients with persistent SARS-CoV-2 reverse transcription (RT)-PCR positivity (>90 days). Whole-genome sequence analysis of samples obtained before and after coronavirus disease 2019 (COVID-19) treatment demonstrated the development of partial therapeutic escape mutations and increased intrahost SARS-CoV-2 genome diversity over time. This case series thus adds to the accumulating evidence that immunocompromised hosts with persistent infections are important sources of SARS-CoV-2 genome diversity and, in particular, clinically important spike protein diversity.IMPORTANCE The emergence of clinically important mutations described in this report highlights the need for sustained vigilance and containment measures when managing immunocompromised patients with persistent COVID-19. Even as jurisdictions across the globe start lifting pandemic control measures, immunocompromised patients with persistent COVID-19 constitute a unique group that requires close genomic monitoring and enhanced infection control measures, to ensure early detection and containment of mutations and variants of therapeutic and public health importance.

Biosafety in Dental Health Care During the COVID-19 Pandemic: A Longitudinal Study.

BackgroundThe coronavirus disease 2019 (COVID-19) pandemic had quite an impact on dental health care. Concerns about the risk of SARS-CoV-2 transmission through contaminant fluids and droplet formation during several dental procedures highly impacted dental health care, drastically reducing the number of dental practices worldwide. To monitor SARS-CoV-2 contamination in dental clinics, a longitudinal study was carried out during the return of dental practice at university.MethodsDental health care professionals [(DHCPs); teachers, undergraduate dental students, and dental assistants] and patients were screened for SARS-CoV-2 RNA in a dental school clinic environment from 11th January to 12th March 2021 (9 weeks). Serological testing was performed on DHCPs in two-time points. Additionally, samples with low Ct values were sequenced to identify the circulating SARS-CoV-2 variant and possible transmission clusters.ResultsWe found a low number of dental staff (5.8%), patients (0.9%), and environment sites (0.8%) positive for SARS-CoV-2. Most positive cases had asymptomatic to mild symptoms, and two asymptomatic DHCPs presented prolonged infection. In the first week after previous exposure to COVID-19, 16.2% of DHCPs had IgM or IgG antibodies against SARS-CoV-2, and 1/3 of them had undetected antibodies in the last weeks. The variant zeta (P.2) could be detected. No cross-infection was observed between participants.ConclusionOur study suggests that dental practice can be safely executed when adequate control measures and biosafety protocols are applied. DHCP and patient testing, patient telemonitoring, proper use of personal protection equipment, and sanitization of surfaces are essential to avoid SARS-CoV-2 cross-infection in dental practice.

Fecal Microbiota Transplantation Alters the Outcome of Hepatitis B Virus Infection in Mice.

The susceptibility of mice to hepatitis B virus (HBV) infection depends on their genetic background. The gut microbiota modulates the antiviral immune response in the liver and plays a protective role against HBV infection. However, whether HBV infection outcomes depend on the gut microbiota remains unclear. In this study, we assessed the gut microbiota composition in naïve BALB/c and C57BL/6 mice using 16S rRNA gene sequencing. The gut microbiota in BALB/c mice was depleted using broad-spectrum antibiotics (ABX) and then reconstituted with fecal microbiota from naïve BALB/c or C57BL/6 mice to evaluate the effect of fecal microbiota transplantation (FMT) on the outcomes of and immune response to HBV infection. We found that HBV infection outcomes and the gut microbiota composition differed between BALB/c and C57BL/6 mice. Commensal bacteria from the fecal microbiota selectively colonized the guts of ABX-treated BALB/c mice. Mice receiving fecal microbiota from BALB/c or C57BL/6 mice displayed different HBV infection outcomes. The fecal microbiota from C57BL/6 mice induced immune tolerance in the liver and prolonged HBV infection. In conclusion, HBV infection outcomes in mice are determined by the host genetic background and gut microbiota composition. Reconstitution of the gut microbiota by FMT can alter the susceptibility to HBV infection in mice.

Transbronchial Lung Cryobiopsy in Patients with Interstitial Lung Disease: A Systematic Review.

Rationale: In 2018, a systematic review evaluating transbronchial lung cryobiopsy (TBLC) in patients with interstitial lung disease (ILD) was performed to inform American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and Asociación Latinoamericana del Tórax clinical practice guidelines on the diagnosis of idiopathic pulmonary fibrosis. Objectives: To perform a new systematic review to inform updated guidelines. Methods: Medline, Excerpta Medica Database, and the Cochrane Central Register of Controlled Trials (CCTR) were searched through June 2020. Studies that enrolled patients with ILD and reported the diagnostic yield or complication rates of TBLC were selected for inclusion. Data was extracted and then pooled across studies via meta-analysis. The quality of the evidence was appraised using the grading of recommendations, assessment, development, and evaluation approach. Results: Histopathologic diagnostic yield (number of procedures that yielded a histopathologic diagnosis divided by the total number of procedures performed) of TBLC was 80% (95% confidence interval [CI], 76-83%) in patients with ILD. TBLC was complicated by bleeding and pneumothorax in 30% (95% CI, 20-41%) and 8% (95% CI, 6-11%) of patients, respectively. Procedure-related mortality, severe bleeding, prolonged air leak, acute exacerbation, respiratory failure, and respiratory infection were rare. The quality of the evidence was very low owing to the uncontrolled study designs, lack of consecutive enrollment, and inconsistent results. Conclusions: Very low-quality evidence indicated that TBLC has a diagnostic yield of approximately 80% in patients with ILD, with manageable complications.

Novel Association of Lyme disease, Age, and Atopic Dermatitis

Abstract Borrelia burgdorferi is a bacterial spirochete that can cause Lyme disease (LD) after infecting a susceptible host. Immune responses to the bacteria are highly variable and host specific. The murine substrain, C3H/HeJ, is a frequently utilized model for LD. Interestingly, over a prolonged infection, mice develop dermatitis on tail skin, which shares critical features with human skin. Female C3H/HeJ mice aged 5–8 weeks, 1 year, or 2 years were infected intraperitoneally with 105 B. burgdorferi. Dermatitis was evaluated by gross examination and histology. Dermatitis worsened over the course of untreated infection, with ulceration, hemorrhaging, flaking, hair loss, and dark lesions as well as spongiosis and acanthosis. These features of dermatitis were present in infected mice after 1 year of age. This relationship among LD, atopic dermatitis, and host age seen in the C3H/HeJ mouse model is consistent with a large pool (342,499) of human epidemiological data from Finland. We identified 5,248 individuals with LD and 17,233 with atopic dermatitis in FinnGen. Retrospective analysis shows LD is associated with atopic dermatitis (OR = 1.91 [1.68 −2.37], P < 2e−16). More visits due to LD complications (3 or more visits versus 1 visit) were associated with atopic dermatitis (OR = 2.19 [1.35–3.55], P = 0.0014) and risk of developing atopic dermatitis over time (HR = 2.26 [1.54–3.95], P = 0.0017). Data from mice and humans reveal a novel relationship among LD, age, and atopic dermatitis. Through defined pathological scoring, we demonstrate the onset of murine atopic dermatitis with B. burgdorferi infection, which is further exacerbated by host age at time of infection, and likewise report a similar association in human epidemiological data from FinnGen. Research was supported by the Fairbairn Family foundation; Bay Area Lyme Foundation; the Younger family foundation; the Robert J. Kleberg, Jr., and Helen C. Kleberg Foundation; the Virginia and D. K. Ludwig Fund for Cancer Research; AML grant R01CA086017; the PCBC from NIHLB U01HL099999; as well as grant U19AI109662. M.C.T. was supported by Stanford Immunology training grant 5T32AI007290, and the NIH NRSA 1 F32 AI124558-01 award. L.B.T.D. was supported by a Stanford Diversifying Academia Recruiting Excellence fellowship. S.G. was supported by the California Institute for Regenerative Medicine. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

HIV and COVID-19: juxtaposition of two pandemics

HIV and COVID-19: juxtaposition of two pandemics

Five-Year PTSD Symptom Remission in Two Patients Following Treatment With Rivastigmine.

The beneficial effect of rivastigmine, an acetylcholinesterase inhibitor (AChEi), which increases levels of acetylcholine (ACh), was first reported in 2013. This paper replicates those findings and reports sustained symptom remission. The high-frequency (HF) component of heart rate variability (HRV) is a measure of cholinergic withdrawal and was measured using a Zephyr Bioharness HR monitor, pre- and post-commencement of treatment. Data analysis was performed using Kubios HRV software. PTSD symptom severity was assessed using the Post-Traumatic Checklist-Civilian (PCL-C). Low HF HRV was observed in both patients before rivastigmine treatment and reductions in PCL-C scores paralleled increases in HF HRV values. Follow-up revealed low HF HRV values in both patients despite PCL-C scores indicating remission. Sympathetic nervous system hyperactivity was observed in one patient, just before a suicide attempt. Following rivastigmine treatment, the patient had no further suicidal ideation or attempts. Another patient reported worsening of her PTSD symptoms in the peri-menstrual period, which was abolished by rivastigmine. She also experienced symptom relapse following prolonged infections. Low HF HRV has been reported in PTSD patients, but findings have been inconsistent. Cholinergic withdrawal could explain the disturbances in sleep, learning, and memory seen in PTSD patients. The relapse of symptoms following prolonged infection implicates the immune system as a possible initiator of the disorder. ACh and estrogen have anti-inflammatory properties, supporting a possible role of inflammation in initiating PTSD. The effect of rivastigmine treatment should be tested in properly controlled clinical trials.

Gastrointestinal symptoms and fecal shedding of SARS-CoV-2 RNA suggest prolonged gastrointestinal infection

BackgroundCOVID-19 manifests with respiratory, systemic, and gastrointestinal (GI) symptoms.1, SARS-CoV-2 RNA is detected in respiratory and fecal samples, and recent reports demonstrate viral replication in both the lung and intestinal tissue.2, 3, 4 Although much is known about early fecal RNA shedding, little is known about long-term shedding, especially in those with mild COVID-19. Furthermore, most reports of fecal RNA shedding do not correlate these findings with GI symptoms.5MethodsWe analyzed the dynamics of fecal RNA shedding up to 10 months after COVID-19 diagnosis in 113 individuals with mild to moderate disease. We also correlated shedding with disease symptoms.FindingsFecal SARS-CoV-2 RNA is detected in 49.2% [95% confidence interval, 38.2%–60.3%] of participants within the first week after diagnosis. Whereas there was no ongoing oropharyngeal SARS-CoV-2 RNA shedding in subjects at 4 months, 12.7% [8.5%–18.4%] of participants continued to shed SARS-CoV-2 RNA in the feces at 4 months after diagnosis and 3.8% [2.0%–7.3%] shed at 7 months. Finally, we found that GI symptoms (abdominal pain, nausea, vomiting) are associated with fecal shedding of SARS-CoV-2 RNA.ConclusionsThe extended presence of viral RNA in feces, but not in respiratory samples, along with the association of fecal viral RNA shedding with GI symptoms suggest that SARS-CoV-2 infects the GI tract and that this infection can be prolonged in a subset of individuals with COVID-19.FundingThis research was supported by a Stanford ChemH-IMA grant; fellowships from the AACR and NSF; and NIH R01-AI148623, R01-AI143757, and UL1TR003142.

Orthotopic Heart Transplantation in Different Categories of Patients. Does It Matter?

PurposeThe number of patients undergoing heart transplantation (HT) after a previous sternotomy or LVAD support is increasing. We sought to identify differences in HT outcomes among different preoperative categories of patients.MethodsWe reviewed records of 266 consecutive patients who underwent HT from 10/31/12 to 10/15/20. Patients who had heart and kidney transplantation, re-transplantation, or had total artificial heart were excluded. We compared HT outcomes among 4 groups: patients undergoing HT without previous sternotomy - virgin chest group; redo sternotomy group; patients who had LVAD as a bridge to transplant (BTT); and patients initially deemed as HT ineligible who had LVAD as destination therapy but converted to BTT candidacy (BTTC).ResultsIn 266 patients, 30 day and 1-year HT survival were 97% and 94.7%, respectively. Patients in redo sternotomy group were older in comparison to other groups (P =.015) and had more men (P=.005). Patients in BTTC group had a higher body mass index (29.5±4 kg/m2) in comparison to other groups (27±5 kg/m2), P <.01. Time on LVAD support was comparable between BTT and BTTC groups, 724±576 days vs 716±529 days, respectively. In comparison to virgin chest group, ICU length of stay (LOS) and post HT LOS were longer in other groups (P <0.03). However, posttransplant 30 day and 1-year survivals were comparable. There was a trend to worse survival in the BTTC group in comparison to virgin chest group, but did not reach a significant difference (P =.104).ConclusionPosttransplant survival in BTT patients supported on average 2 years is comparable to survival with conventional virgin chest HT. Although it did not reach statistical significance, lower survival of BTTC patients necessitates consideration of risk factors. Among 4 patients who died in this group, 3 had diabetes mellitus and 2 had prolonged driveline infection. Operative complexity in redo sternotomy patients may affect HT survival as 3 patients died within 30 days and a fourth one died 37 days after procedure. The number of patients undergoing heart transplantation (HT) after a previous sternotomy or LVAD support is increasing. We sought to identify differences in HT outcomes among different preoperative categories of patients. We reviewed records of 266 consecutive patients who underwent HT from 10/31/12 to 10/15/20. Patients who had heart and kidney transplantation, re-transplantation, or had total artificial heart were excluded. We compared HT outcomes among 4 groups: patients undergoing HT without previous sternotomy - virgin chest group; redo sternotomy group; patients who had LVAD as a bridge to transplant (BTT); and patients initially deemed as HT ineligible who had LVAD as destination therapy but converted to BTT candidacy (BTTC). In 266 patients, 30 day and 1-year HT survival were 97% and 94.7%, respectively. Patients in redo sternotomy group were older in comparison to other groups (P =.015) and had more men (P=.005). Patients in BTTC group had a higher body mass index (29.5±4 kg/m2) in comparison to other groups (27±5 kg/m2), P <.01. Time on LVAD support was comparable between BTT and BTTC groups, 724±576 days vs 716±529 days, respectively. In comparison to virgin chest group, ICU length of stay (LOS) and post HT LOS were longer in other groups (P <0.03). However, posttransplant 30 day and 1-year survivals were comparable. There was a trend to worse survival in the BTTC group in comparison to virgin chest group, but did not reach a significant difference (P =.104). Posttransplant survival in BTT patients supported on average 2 years is comparable to survival with conventional virgin chest HT. Although it did not reach statistical significance, lower survival of BTTC patients necessitates consideration of risk factors. Among 4 patients who died in this group, 3 had diabetes mellitus and 2 had prolonged driveline infection. Operative complexity in redo sternotomy patients may affect HT survival as 3 patients died within 30 days and a fourth one died 37 days after procedure.

Penile Invagination and Corporal Excavation for Penile Prosthesis Placement in Severe Corporal Fibrosis

ABSTRACT Introduction The penile prosthesis is a standard treatment for men with erectile dysfunction refractory to vacuum, medical, or injection therapies. In patients with virgin tissue planes and normal anatomy, prosthesis placement can be technically straight forward and associated with minimal morbidity. Patients with corporal fibrosis present a unique surgical challenge for implantation and there is no standardized approach to care. Selection of the appropriate surgical technique can vary depending on the extent of corporal fibrosis and surgeon experience. In this case, our patient's corporal fibrosis resulted from two episodes of prolonged priapism as well as two distal shunts and a failed attempt at inflatable penile prosthesis placement resulting in a prolonged wound infection. Objective We present our unique surgical approach for penile prosthesis implantation in the most severe cases of corporal fibrosis. Methods Video demonstration of corporal excavation and penile prosthesis placement via a perineal incision with complete penile invagination. Results Comprehensive pre-operative planning guided our decision to utilize a malleable prosthesis given the severe degree of corporal fibrosis and higher risk of complications with a three-piece IPP. Our penile invagination technique allowed us to achieve complete longitudinal corporal exposure while avoiding multiple incisions or overlapping incisions near the corporotomy and cylinders. Tachosil or other biologic grafts should be available for use in cases where primary corporotomy closure is not possible. Conclusions We demonstrated that penile invagination, corporal excavation, and implantation with a malleable prosthesis is a safe and effective treatment for patients with the most severe corporal fibrosis. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Coloplast and Boston Scientific

A Case of Prolonged Hospital Acquired COVID-19 Pneumonia in a Lung Transplant Recipient: Management and Outcome

IntroductionLung transplant recipients are at increased risk of SARS-CoV2 infection due to immunosuppression and their management has yet to be standardized. We report a case of prolonged COVID-19 infection in a lung recipient acquired after transplant during the hospital stay.Case ReportA 52-year-old lady with interstitial disease associated to systemic sclerosis underwent bilateral lung transplantation on 04/10/21. Donors and recipient microbiological tests for SARS-CoV2 were negative on molecular swabs performed before transplantation (04/07 and 04/10). Transplantation was uneventful and the recipient was extubated the subsequent day. Twelve days later, a surveillance molecular nose-pharyngeal swab was positive for SARS-CoV2. The positivity for subgenomic analysis revealed productive infection. At first monitoring biopsy, multiple foci of diffuse alveolar damage, significant cytopathic features of pneumocytes, microthrombi of capillaries, and extensive edema were highly suggestive of COVID-19 pneumonia. High viral load was also detected in lung biopsy by RT-PCR. She presented mild respiratory symptoms (cough with low oxygen supplementation) and the CT scan revealed an area of consolidation at the right lower lobe. Monoclonal antibody therapy (Bamlanivimab and Etesevimab) associated with remdesevir was started, IV immunoglobulins were administered while mycophenolate mofetil was discontinued. The patient was closely monitored until the nose-pharyngeal swab turned negative two months after the first positivity associated with a significant clinical improvement. At the last follow-up, five months after transplantation, she had good pulmonary function, no immunological disorders and no signs related to long COVID-19.SummaryThis is a case of prolonged hospital acquired COVID-19 related pneumonia in a lung recipient. Immunocompromized patients present a longer viral clearance. In this fragile population a strict clinical, radiological and histopathological monitoring associated with encouragement of vaccination are mandatory.

Molecular Epidemiology of Rhinovirus/Enterovirus and Their Role on Cause Severe and Prolonged Infection in Hospitalized Patients.

Rhinovirus is one of the most common respiratory viruses, causing both upper and lower respiratory tract infections. It affects mainly children and could cause prolonged infections, especially in immunocompromised patients. Here we report our data on a 15-month surveillance of Rhinovirus seasonality and circulation in Lombardy Region, Italy. All rhinovirus/enterovirus-positive samples were amplified with RT-PCR for the VP4-VP2 region to assign the correct genotype. The median age of RV/EV-positive patients is 9 years, with a range of 0–96. RV-A and RV-C were detected in the majority of cases, while RV-B accounted for less than 10% of cases. An enterovirus species was detected in 6.45% of the cases. A total of 7% of the patients included in this study had a prolonged infection with a median duration of 62 days. All these patients were immunocompromised and most of them were pediatric with an RV-A infection. Two outbreaks were identified, mainly in the neonatal intensive care unit (NICU) and Oncohematology Department, caused by RV A89 and C43, respectively. Nearly 4.5% of the patients were admitted to the ICU requiring mechanical ventilation; all of which had preexisting comorbidities.

Personalized symbionic therapy of campylobacteriosis protracted course in children

Campylobacteriosis is one of the most common bacterial intestinal infections with high risks of severe and prolonged infection in childhood. The growing incidence of campylobacteriosis, the variety of clinical forms of the disease, the difficulties of timely diagnosis of the infection against the background of a high level of resistance of the microorganism to a number of antibacterial drugs determine the need to optimize the rational tactics of treating this infectious disease. One of the possible ways to overcome these difficulties is to further expand the use of probiotics and autoprobiotics. Aim: to reveal the features of the influence of autoprobiotic and probiotic E. faecium strains on clinical and laboratory parameters in children with non-smooth forms of campylobacteriosis .. Materials and methods: In the period from 2018 to 2020. In DNCIB FMBA, a comprehensive single-center prospective dynamic open observational study of 34 children with an uneven course of campylobacteriosis was carried out. For therapeutic purposes, patients were prescribed an autoprobiotic (group A; n = 15) or a probiotic strain E. faecium (group P; n = 19). Clinical and laboratory parameters and indicators of the intestinal microbiocenosis composition were assessed by real-time PCR. Results: Studies of the effect of two different approaches to prescribing probiotic strains of enterococcus to children with a protracted course of campylobacteriosis - a conditionally “reference” industrial strain E. faecium L3 and autoprobiotic strains with a comparable frequency (88.9% and 93.3% of cases, respectively) revealed their significant positive impact on the course of protracted forms of campylobacteriosis, which was expressed by the disappearance of abdominal pain syndrome, normalization of the frequency and consistency of stools, relief of hemocolitis in the absence of undesirable side effects. Analysis of the dynamics of coprograms before and after taking autoprobiotics and probiotic E. faecium L3 also did not reveal significant differences: there was an equivalent positive dynamics in the form of improvement in most of the macroscopic and microscopic characteristics of the stool. The study of the composition of the intestinal microbiota showed that after the course of administration of autoprobiotic strains of E. faecium, there was a significant increase in the content of butyrate-producing indigenous representative - F. prausnitzii, which promotes the repair of the intestinal mucosa. The studies also showed that the course use of autoprobiotic strains of enterococcus contributed to a decrease in the frequency of convalescent release of campylobacter, which suggests a sanitizing effect of autoprobiotics and does not exclude a similar effect in relation to other bacterial pathogens of intestinal infections in children.

Exploring a prolonged enterovirus C104 infection in a severely ill patient using nanopore sequencing

Chronic enterovirus infections can cause significant morbidity, particularly in immunocompromised patients. This study describes a fatal case associated with a chronic untypeable enterovirus infection in an immunocompromised patient admitted to a Dutch university hospital over nine months. We aimed to identify the enterovirus genotype responsible for the infection and to determine potential evolutionary changes. Long-read sequencing was performed using viral targeted sequence capture on four respiratory and one faecal sample. Phylogenetic analysis was performed using a maximum likelihood method, along with a root-to-tip regression and time-scaled phylogenetic analysis to estimate evolutionary changes between sample dates. Intra-host variant detection, using a Fixed Ploidy algorithm, and selection pressure, using a Fixed Effect Likelihood and a Mixed Effects Model of Evolution, were also used to explore the patient samples. Near-complete genomes of enterovirus C104 (EV-C104) were recovered in all respiratory samples but not in the faecal sample. The recovered genomes clustered with a recently reported EV-C104 from Belgium in August 2018. Phylodynamic analysis including ten available EV-C104 genomes, along with the patient sequences, estimated the most recent common ancestor to occur in the middle of 2005 with an overall estimated evolution rate of 2.97 × 10−3 substitutions per year. Although positive selection pressure was identified in the EV-C104 reference sequences, the genomes recovered from the patient samples alone showed an overall negative selection pressure in multiple codon sites along the genome. A chronic infection resulting in respiratory failure from a relatively rare enterovirus was observed in a transplant recipient. We observed an increase in single-nucleotide variations between sample dates from a rapidly declining patient, suggesting mutations are weakly deleterious and have not been purged during selection. This is further supported by the persistence of EV-C104 in the patient, despite the clearance of other viral infections. Next-generation sequencing with viral enrichment could be used to detect and characterise challenging samples when conventional workflows are insufficient.

Transcriptomics of rhinovirus persistence reveals sustained expression of RIG-I and interferon-stimulated genes in nasal epithelial cells in vitro.

Human rhinoviruses (HRVs) are frequently associated with asthma exacerbations, and have been found in the airways of asthmatic patients. While HRV-induced acute infection is well-documented, it is less clear whether the nasal epithelium sustains prolonged HRV infections along with the associated activation of host immune responses. To investigate sustainably regulated host responses of human nasal epithelial cells (hNECs) during HRV persistence. Using a time-course study, HRV16 persistence and viral replication dynamics were established using an in vitro infection model of hNECs. RNA sequencing was performed on hNECs in the early and late stages of infection at 3 and 14days post-infection (dpi), respectively. The functional enrichment of differentially expressed genes (DEGs) was evaluated using gene ontology (GO) and Ingenuity pathway analysis. HRV RNA and protein expression persisted throughout prolonged infections, even after decreased production of infectious virus progeny. GO analysis of unique DEGs indicated altered regulation of pathways related to ciliary function and airway remodeling at 3 dpi and serine-type endopeptidase activity at 14 dpi. The functional enrichment of shared DEGs between the two time-points was related to interferon (IFN) and cytoplasmic pattern recognition receptor (PRR) signaling pathways. Validation of the sustained regulation of candidate genes confirmed the persistent expression of RIG-I and revealed its close co-regulation with interferon-stimulated genes (ISGs) during HRV persistence. The persistence of HRV RNA does not necessarily indicate an active infection during prolonged infection. The sustained expression of RIG-I and ISGs in response to viral RNA persistence highlights the importance of assessing how immune-activating host factors can change during active HRV infection and the immune regulation that persists thereafter.

Monitoring and managing SARS-CoV-2 evolution in immunocompromised populations

Monitoring and managing SARS-CoV-2 evolution in immunocompromised populations

SARS-CoV-2 transmission: time to rethink public health strategy

SARS-CoV-2 transmission: time to rethink public health strategy

Emergence of Progressive Mutations in SARS-CoV-2 From a Hematologic Patient With Prolonged Viral Replication.

We documented a hematologic patient with prolonged SARS-CoV-2 viral replication in whom emergence of viral mutations was documented after the consecutive use of antivirals and convalescent plasma. The virus detected in the last of 12 clinical samples (day 237) had accumulated 22 changes in amino acids and 29 in nucleotides. Some of these changes, such as the E484Q, were mutations of concern as defined by WHO. This finding represents an enormous epidemiological threat and poses a major clinical challenge. Combined antiviral strategies, as well as specific strategies related to the diagnostic approach of prolonged infections for this specific population, may be needed.

Electrospun PLGA Membranes with Incorporated Moxifloxacin-Loaded Silica-Based Mesoporous Nanocarriers for Periodontal Regeneration.

Engineered electrospun membranes have emerged as promising materials in guided tissue regeneration, as they provide an appropriate framework for the formation of new functional periodontal tissues. The development of multifunctional local drug delivery systems with sustained release of drugs for prolonged infection control can be used in periodontal surgical interventions to simultaneously prohibit epithelium downgrowth and ensure proper healing and regeneration of damaged periodontal tissues. The aim of the present study was the fabrication of novel composite membranes from PLGA/moxifloxacin-loaded mesoporous nanocarriers through electrospinning and the evaluation of their drug release profiles. The addition of moxifloxacin-loaded mesoporous nanocarriers in PLGA yielded a sustained and prolonged drug release, while maintaining satisfactory mechanical strength. The freshly fabricated membranes were found to be biocompatible at masses less than 1 mg after exposure to healthy erythrocytes. Increase in the amount of polymer led to more uniform fibers with large diameters and pores. The study of the parameters of the electrospinning process indicated that increase in the applied voltage value and rotation speed of the collector led to more uniform fibers with higher diameter and larger pores, suitable for tissue regeneration applications, such as periodontal tissue regeneration.

Rare Cases of Filarial Chyluria in Children

BackgroundLymphatic filariasis leading to the passage of white urine or chyle is a rare manifestation in children. Filarial parasite infiltration leading to abnormal lymphatic–urinary communication occurs with prolonged infection. The incubation period ranges from 5 to 20 yrs., thus relatively infrequent in the pediatric age group. Index of suspicion should be high when a child presents with the passage of white urine because the subclinical manifestation of filarial infection is difficult to recognize. Moreover, more pathognomonic clinical manifestations such as lymphoedema or hydrocoele are present in adulthood. It should also be differentiated from non-parasitic causes like nephrotic syndrome, urates and phosphates in urine, and congenital lymphatic-urinary communication.Case PresentationWe report two pediatric cases with the intermittent passage of milky white urine since one year. Institutional ethical committee approved the study. In both patients, urine triglycerides were high, and the presence of positive filarial antigen test confirmed the diagnosis. Medical management showed remission of symptoms. Our cases highlight the rare presentation of LF in children and the use of point of care diagnostic tests, management, and outcome in them.ConclusionLF is a rare condition in children, and the index of suspicion should be high for early management.