Nausea, Vomiting, and Diarrhea Are Common in Community-Acquired Acute Viral Respiratory Illness.

BACKGROUND: Gastrointestinal (GI) symptoms are recognized sequelae of acute respiratory illness (ARI), but their prevalence is not well documented. Our study aim was to assess the incidence of GI symptoms in community ARI cases for persons of all ages and their association with clinical outcomes. METHODS: We collected mid-nasal swabs, clinical, and symptom data from Seattle-area individuals during the 2018-2019 winter season as part of a large-scale prospective community surveillance study. Swabs were tested by polymerase chain reaction (PCR) for 26 respiratory pathogens. Likelihood of GI symptoms given demographic, clinical, and microbiological covariates were analyzed with Fisher's exact, Wilcoxon-rank-sum, and t-tests and multivariable logistic regression. RESULTS: In 3183 ARI episodes, 29.4% had GI symptoms (n = 937). GI symptoms were significantly associated with pathogen detection, illness interfering with daily life, seeking care for the illness, and greater symptom burden (all p < 0.05). Controlling for age, > 3 symptoms, and month, influenza (p < 0.001), human metapneumovirus (p = 0.004), and enterovirus D68 (p = 0.05) were significantly more likely to be associated with GI symptoms than episodes with no pathogen detected. Seasonal coronaviruses (p = 0.005) and rhinovirus (p = 0.04) were significantly less likely to be associated with GI symptoms. CONCLUSION: In this community-surveillance study of ARI, GI symptoms were common and associated with illness severity and respiratory pathogen detection. GI symptoms did not track with known GI tropism, suggesting GI symptoms may be nonspecific rather than pathogen-mediated. Patients presenting with GI and respiratory symptoms should have respiratory virus testing, even if the respiratory symptom is not the primary concern.

How I prevent viral reactivation in high-risk patients.

Preventing viral infections at an early stage is a key strategy for successfully improving transplant outcomes. Preemptive therapy and prophylaxis with antiviral agents have been successfully used to prevent clinically significant viral infections in hematopoietic cell transplant recipients. Major progress has been made over the past decades in preventing viral infections through a better understanding of the biology and risk factors, as well as the introduction of novel antiviral agents and advances in immunotherapy. High-quality evidence exists for the effective prevention of herpes simplex virus, varicella-zoster virus, and cytomegalovirus infection and disease. Few data are available on the effective prevention of human herpesvirus 6, Epstein-Barr virus, adenovirus, and BK virus infections. To highlight the spectrum of clinical practice, here we review high-risk situations that we handle with a high degree of uniformity and cases that feature differences in approaches, reflecting distinct hematopoietic cell transplant practices, such as ex vivo T-cell depletion.

Acute and Postacute COVID-19 Outcomes Among Immunologically Naive Adults During Delta vs Omicron Waves.

Importance: The US arrival of the Omicron variant led to a rapid increase in SARS-CoV-2 infections. While numerous studies report characteristics of Omicron infections among vaccinated individuals or persons with previous infection, comprehensive data describing infections among adults who are immunologically naive are lacking. Objectives: To examine COVID-19 acute and postacute clinical outcomes among a well-characterized cohort of unvaccinated and previously uninfected adults who contracted SARS-CoV-2 during the Omicron (BA.1/BA.2) surge, and to compare outcomes with infections that occurred during the Delta wave. Design, Setting, and Participants: This prospective multisite cohort study included community-dwelling adults undergoing high-resolution symptom and virologic monitoring in 8 US states between June 2021 and September 2022. Unvaccinated adults aged 30 to less than 65 years without an immunological history of SARS-CoV-2 who were at high risk of infection were recruited. Participants were followed for up to 48 weeks, submitting regular COVID-19 symptom surveys and nasal swabs for SARS-CoV-2 polymerase chain reaction (PCR) testing. Data were analyzed from May to October 2022. Exposures: Omicron (BA.1/BA.2 lineages) vs Delta SARS-CoV-2 infection, defined as a positive PCR test result that occurred during a period when the variant represented at least 50% of circulating SARS-CoV-2 variants in the participant's geographic region. Main Outcomes and Measure(s): The main outcomes examined were the prevalence and severity of acute (≤28 days after onset) and postacute (≥5 weeks after onset) symptoms. Results: Among 274 participants who were immunologically naive (mean [SD] age, 49 [9.7] years; 186 [68%] female; 19 [7%] Hispanic participants; 242 [88%] White participants), 166 (61%) contracted SARS-CoV-2. Of these, 137 infections (83%) occurred during the Omicron-predominant period and 29 infections (17%) occurred during the Delta-predominant period. Asymptomatic infections occurred among 7% (95% CI, 3%-12%) of Omicron-wave infections and 0% (95% CI, 0%-12%) of Delta-wave infections. Health care use among individuals with Omicron-wave infections was 79% (95% CI, 43%-92%) lower relative to individuals with Delta-wave infections (P = .001). Compared with individuals infected during the Delta wave, individuals infected during the Omicron wave also experienced a 56% (95% CI, 26%-74%, P = .004) relative reduction in the risk of postacute symptoms and a 79% (95% CI, 54%-91%, P < .001) relative reduction in the rate of postacute symptoms. Conclusions and Relevance: These findings suggest that among adults who were previously immunologically naive, few Omicron-wave (BA.1/BA.2) and Delta-wave infections were asymptomatic. Compared with individuals with Delta-wave infections, individuals with Omicron-wave infections were less likely to seek health care and experience postacute symptoms.

Successful treatment of prolonged, severe COVID-19 lower respiratory tract disease in a B-cell ALL patient with an extended course of remdesivir and nirmatrelvir/ritonavir.

A patient with B-cell acute lymphoblastic leukemia (ALL) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had persistent, progressive pneumonia with viremia after 5 months of infection despite monoclonal antibodies, IV remdesivir and prolonged oral steroids. Twenty days of nirmatrelvir/ritonavir and 10 days of IV remdesivir led to full recovery.

Frequently Asked Questions on Coronavirus Disease 2019 Vaccination for Hematopoietic Cell Transplantation and Chimeric Antigen Receptor T-Cell Recipients From the American Society for Transplantation and Cellular Therapy and the American Society of Hematology.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), disproportionately affects immunocompromised and elderly patients. Not only are hematopoietic cell transplantation (HCT) and chimeric antigen receptor (CAR) T-cell recipients at greater risk for severe COVID-19 and COVID-19-related complications, but they also may experience suboptimal immune responses to currently available COVID-19 vaccines. Optimizing the use, timing, and number of doses of the COVID-19 vaccines in these patients may provide better protection against SARS-CoV-2 infection and better outcomes after infection. To this end, current guidelines for COVID-19 vaccination in HCT and CAR T-cell recipients from the American Society of Transplantation and Cellular Therapy Transplant Infectious Disease Special Interest Group and the American Society of Hematology are provided in a frequently asked questions format.

Revised Guidelines for Coronavirus Disease 19 Management in Hematopoietic Cell Transplantation and Cellular Therapy Recipients (August 2022).

This document is intended as a guide for diagnosis and management of Coronavirus Disease 2019 (COVID-19), caused by the virus SARS-CoV-2, in adult and pediatric HCT and cellular therapy patients. This document was prepared using available data and with expert opinion provided by members of the (ASTCT) Infectious Diseases Special Interest Group (ID-SIG) and is an update of pervious publication. Since our original publication in 2020, the NIH and IDSA have published extensive guidelines for management of COVID-19 which are readily accessible ( NIH Guidelines , IDSA Guidelines ). This update focuses primarily on issues pertaining specifically to HCT/cellular therapy recipients. Information provided in this manuscript may change as new information becomes available.

Monoclonal antibodies for prophylaxis and treatment of respiratory viral infections.

PURPOSE OF REVIEW: Monoclonal antibody (mAb) administration represents an important strategy for preventing and treating respiratory viral infections in vulnerable populations, including immunocompromised individuals. The purpose of this review is to provide an overview of mAbs in clinical use against respiratory viruses, highlight factors that modulate mAb clinical efficacy, and provide a perspective on future innovations in the field. This review focuses on publications from the last year. RECENT FINDINGS: Historically, clinical development of a single mAb has taken over a decade. The COVID-19 pandemic has demonstrated that this timeframe can be reduced to less than a year and has catalyzed rapid innovations in the field. Several novel mAbs against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have received emergency use authorization by the Food and Drug Administration (FDA) for the early treatment of mild to moderate COVID-19. However, the majority of these mAbs have ultimately failed due to the emergence of variants, highlighting an important lesson about predicting and countering resistance. Novel mAbs are also in clinical use or in late-stage development for the prevention of infection by SARS-CoV-2 and respiratory syncytial virus (RSV) in vulnerable populations. Several factors can be modulated to improve the clinical efficacy of mAbs. For example, Fc modifications can extend mAb half-life and increase respiratory tract bioavailability, both of which are attractive properties for achieving protection against respiratory viruses. SUMMARY: The mAb landscape is rapidly evolving with numerous examples of success and failure. The armamentarium of clinically-available mAbs to protect vulnerable populations is expected to undergo continued growth.

Genomic surveillance of SARS-CoV-2 Omicron variants on a university campus.

Novel variants continue to emerge in the SARS-CoV-2 pandemic. University testing programs may provide timely epidemiologic and genomic surveillance data to inform public health responses. We conducted testing from September 2021 to February 2022 in a university population under vaccination and indoor mask mandates. A total of 3,048 of 24,393 individuals tested positive for SARS-CoV-2 by RT-PCR; whole genome sequencing identified 209 Delta and 1,730 Omicron genomes of the 1,939 total sequenced. Compared to Delta, Omicron had a shorter median serial interval between genetically identical, symptomatic infections within households (2 versus 6 days, P = 0.021). Omicron also demonstrated a greater peak reproductive number (2.4 versus 1.8), and a 1.07 (95% confidence interval: 0.58, 1.57; P < 0.0001) higher mean cycle threshold value. Despite near universal vaccination and stringent mitigation measures, Omicron rapidly displaced the Delta variant to become the predominant viral strain and led to a surge in cases in a university population.

Structure, receptor recognition, and antigenicity of the human coronavirus CCoV-HuPn-2018 spike glycoprotein.

The isolation of CCoV-HuPn-2018 from a child respiratory swab indicates that more coronaviruses are spilling over to humans than previously appreciated. We determined the structures of the CCoV-HuPn-2018 spike glycoprotein trimer in two distinct conformational states and showed that its domain 0 recognizes sialosides. We identified that the CCoV-HuPn-2018 spike binds canine, feline, and porcine aminopeptidase N (APN) orthologs, which serve as entry receptors, and determined the structure of the receptor-binding B domain in complex with canine APN. The introduction of an oligosaccharide at position N739 of human APN renders cells susceptible to CCoV-HuPn-2018 spike-mediated entry, suggesting that single-nucleotide polymorphisms might account for viral detection in some individuals. Human polyclonal plasma antibodies elicited by HCoV-229E infection and a porcine coronavirus monoclonal antibody inhibit CCoV-HuPn-2018 spike-mediated entry, underscoring the cross-neutralizing activity among ɑ-coronaviruses. These data pave the way for vaccine and therapeutic development targeting this zoonotic pathogen representing the eighth human-infecting coronavirus.

Respiratory viruses in hematopoietic cell transplant candidates: impact of preexisting lower tract disease on outcomes.

Pretransplant respiratory virus infections (RVIs) have been shown to negatively affect hematopoietic cell transplantation (HCT) outcomes. The impact of and need for delay of HCT for pretransplant infection with human rhinovirus (HRV) or endemic human coronavirus (HCoV; 229E, OC43, NL63, and HKU1) remain controversial. We analyzed the impact of symptomatic RVI within ≤90 days before HCT on overall mortality, posttransplant lower respiratory tract disease (LRD), and days alive and out of hospital (DAOH) by day 100 post-HCT in multivariable models. Among 1,643 adult HCT recipients (58% allogeneic recipients), 704 (43%) were tested for RVI before HCT, and 307 (44%) tested positive. HRV was most commonly detected (56%). Forty-five (15%) of 307 HCT recipients had LRD with the same virus early after HCT. Pretransplant upper respiratory tract infection (URI) with influenza, respiratory syncytial virus, adenovirus, human metapneumovirus, parainfluenza virus, HRV, or endemic HCoV was not associated with increased overall mortality or fewer DAOH. However, in allogeneic recipients who received myeloablative conditioning, LRD due to any respiratory virus, including HRV alone, was associated with increased overall mortality (adjusted hazard ratio, 10.8 [95% confidence interval, 3.29-35.1] for HRV and 3.21 [95% confidence interval, 1.15-9.01] for all other viruses). HRV LRD was also associated with fewer DAOH. Thus, the presence of LRD due to common respiratory viruses, including HRV, before myeloablative allogeneic HCT was associated with increased mortality and hospitalization. Pretransplant URI due to HRV and endemic HCoV was not associated with these outcomes. Improved management strategies for pretransplant LRD are warranted.

Phylogenomics of Severe Acute Respiratory Syndrome Coronavirus 2 in Emergency Shelters for People Experiencing Homelessness.

BACKGROUND: Residents and staff of emergency shelters for people experiencing homelessness (PEH) are at high risk of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The importance of shelter-related transmission of SARS-CoV-2 in this population remains unclear. It is also unknown whether there is significant spread of shelter-related viruses into surrounding communities. METHODS: We analyzed genome sequence data for 28 SARS-CoV-2-positive specimens collected from 8 shelters in King County, Washington between March and October, 2020. RESULTS: We identified at least 12 separate SARS-CoV-2 introduction events into these 8 shelters and estimated that 57% (16 of 28) of the examined cases of SARS-CoV-2 infection were the result of intrashelter transmission. However, we identified just a few SARS-CoV-2 specimens from Washington that were possible descendants of shelter viruses. CONCLUSIONS: Our data suggest that SARS-CoV-2 spread in shelters is common, but we did not observe evidence of widespread transmission of shelter-related viruses into the general population.

Remote Household Observation for Noninfluenza Respiratory Viral Illness.

BACKGROUND: Noninfluenza respiratory viruses are responsible for a substantial burden of disease in the United States. Household transmission is thought to contribute significantly to subsequent transmission through the broader community. In the context of the coronavirus disease 2019 (COVID-19) pandemic, contactless surveillance methods are of particular importance. METHODS: From November 2019 to April 2020, 303 households in the Seattle area were remotely monitored in a prospective longitudinal study for symptoms of respiratory viral illness. Enrolled participants reported weekly symptoms and submitted respiratory samples by mail in the event of an acute respiratory illness (ARI). Specimens were tested for 14 viruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), using reverse-transcription polymerase chain reaction. Participants completed all study procedures at home without physical contact with research staff. RESULTS: In total, 1171 unique participants in 303 households were monitored for ARI. Of participating households, 128 (42%) included a child aged <5 years and 202 (67%) included a child aged 5-12 years. Of the 678 swabs collected during the surveillance period, 237 (35%) tested positive for 1 or more noninfluenza respiratory viruses. Rhinovirus, common human coronaviruses, and respiratory syncytial virus were the most common. Four cases of SARS-CoV-2 were detected in 3 households. CONCLUSIONS: This study highlights the circulation of respiratory viruses within households during the winter months during the emergence of the SARS-CoV-2 pandemic. Contactless methods of recruitment, enrollment, and sample collection were utilized throughout this study and demonstrate the feasibility of home-based, remote monitoring for respiratory infections.

Trends in COVID-19 vaccination intent and factors associated with deliberation and reluctance among adult homeless shelter residents and staff, 1 November 2020 to 28 February 2021 - King County, Washington.

INTRODUCTION: Little is known about COVID-19 vaccination intent among people experiencing homelessness. This study assesses surveyed COVID-19 vaccination intent among adult homeless shelter residents and staff and identifies factors associated with vaccine deliberation (responded "undecided") and reluctance (responded "no"), including time trends. METHODS: From 11/1/2020-2/28/21, we conducted repeated cross-sectional surveys at nine shelters in King County, WA as part of ongoing community-based SARS-CoV-2 surveillance. We used a multinomial model to identify characteristics associated with vaccine deliberation and reluctance. RESULTS: A total of 969 unique staff (n = 297) and residents (n = 672) participated and provided 3966 survey responses. Among residents, 53.7% (n = 361) were vaccine accepting, 28.1% reluctant, 17.6% deliberative, and 0.6% already vaccinated, whereas among staff 56.2% were vaccine accepting, 14.1% were reluctant, 16.5% were deliberative, and 13.1% already vaccinated at their last survey. We observed higher odds of vaccine deliberation or reluctance among Black/African American individuals, those who did not receive a seasonal influenza vaccine, and those with lower educational attainment. There was no significant trend towards vaccine acceptance. CONCLUSIONS: Strong disparities in vaccine intent based on race, education, and prior vaccine history were observed. Increased vaccine intent over the study period was not detected. An intersectional, person-centered approach to addressing health inequities by public health authorities planning vaccination campaigns in shelters is recommended. Clinical Trial Registry Number: NCT04141917.

Guidelines for COVID-19 Management in Hematopoietic Cell Transplantation and Cellular Therapy Recipients

There are currently limited data on the epidemiology, clinical manifestations, and optimal management of Coronavirus Disease 2019 (COVID-19) in hematopoietic cell transplantation and cellular therapy recipients. Given the experience with other respiratory viruses, we anticipate that patients may develop severe clinical disease and thus provide the following general principles for cancer centers across the nation. These guidelines were developed by members of the American Society for Transplantation and Cellular Therapy Infectious Diseases Special Interest Group. Specific practices may vary depending on local epidemiology and testing capacity, and the guidance provided in this document may change as new information becomes available.

Reliability of Self-Sampling for Accurate Assessment of Respiratory Virus Viral and Immunologic Kinetics.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic demonstrates the need for accurate and convenient approaches to diagnose and therapeutically monitor respiratory viral infections. We demonstrated that self-sampling with mid-nasal foam swabs is well-tolerated and provides quantitative viral output concordant with flocked swabs. Using longitudinal home-based self-sampling, we demonstrate that nasal cytokine levels correlate and cluster according to immune cell of origin. Periods of stable viral loads are followed by rapid elimination, which could be coupled with cytokine expansion and contraction. Nasal foam swab self-sampling at home provides a precise, mechanistic readout of respiratory virus shedding and local immune responses.

Point-of-care molecular testing and antiviral treatment of influenza in residents of homeless shelters in Seattle, WA: study protocol for a stepped-wedge cluster-randomized controlled trial.

INTRODUCTION: Influenza is an important public health problem, but data on the impact of influenza among homeless shelter residents are limited. The primary aim of this study is to evaluate whether on-site testing and antiviral treatment of influenza in residents of homeless shelters reduces influenza spread in these settings. METHODS AND ANALYSIS: This study is a stepped-wedge cluster-randomized trial of on-site testing and antiviral treatment for influenza in nine homeless shelter sites within the Seattle metropolitan area. Participants with acute respiratory illness (ARI), defined as two or more respiratory symptoms or new or worsening cough with onset in the prior 7 days, are eligible to enroll. Approximately 3200 individuals are estimated to participate from October to May across two influenza seasons. All sites will start enrollment in the control arm at the beginning of each season, with routine surveillance for ARI. Sites will be randomized at different timepoints to enter the intervention arm, with implementation of a test-and-treat strategy for individuals with two or fewer days of symptoms. Eligible individuals will be tested on-site with a point-of-care influenza test. If the influenza test is positive and symptom onset is within 48 h, participants will be administered antiviral treatment with baloxavir or oseltamivir depending upon age and comorbidities. Participants will complete a questionnaire on demographics and symptom duration and severity. The primary endpoint is the incidence of influenza in the intervention period compared to the control period, after adjusting for time trends. TRIAL REGISTRATION: ClinicalTrials.gov NCT04141917 . Registered 28 October 2019. Trial sponsor: University of Washington.

Comparison of Symptoms and RNA Levels in Children and Adults With SARS-CoV-2 Infection in the Community Setting.

Importance: The association between COVID-19 symptoms and SARS-CoV-2 viral levels in children living in the community is not well understood. Objective: To characterize symptoms of pediatric COVID-19 in the community and analyze the association between symptoms and SARS-CoV-2 RNA levels, as approximated by cycle threshold (Ct) values, in children and adults. Design, Setting, and Participants: This cross-sectional study used a respiratory virus surveillance platform in persons of all ages to detect community COVID-19 cases from March 23 to November 9, 2020. A population-based convenience sample of children younger than 18 years and adults in King County, Washington, who enrolled online for home self-collection of upper respiratory samples for SARS-CoV-2 testing were included. Exposures: Detection of SARS-CoV-2 RNA by reverse transcription-polymerase chain reaction (RT-PCR) from participant-collected samples. Main Outcomes and Measures: RT-PCR-confirmed SARS-CoV-2 infection, with Ct values stratified by age and symptoms. Results: Among 555 SARS-CoV-2-positive participants (mean [SD] age, 33.7 [20.1] years; 320 were female [57.7%]), 47 of 123 children (38.2%) were asymptomatic compared with 31 of 432 adults (7.2%). When symptomatic, fewer symptoms were reported in children compared with adults (mean [SD], 1.6 [2.0] vs 4.5 [3.1]). Symptomatic individuals had lower Ct values (which corresponded to higher viral RNA levels) than asymptomatic individuals (adjusted estimate for children, -3.0; 95% CI, -5.5 to -0.6; P = .02; adjusted estimate for adults, -2.9; 95% CI, -5.2 to -0.6; P = .01). The difference in mean Ct values was neither statistically significant between symptomatic children and symptomatic adults (adjusted estimate, -0.7; 95% CI, -2.2 to 0.9; P = .41) nor between asymptomatic children and asymptomatic adults (adjusted estimate, -0.6; 95% CI, -4.0 to 2.8; P = .74). Conclusions and Relevance: In this community-based cross-sectional study, SARS-CoV-2 RNA levels, as determined by Ct values, were significantly higher in symptomatic individuals than in asymptomatic individuals and no significant age-related differences were found. Further research is needed to understand the role of SARS-CoV-2 RNA levels and viral transmission.

Risk factors for seasonal human coronavirus lower respiratory tract infection after hematopoietic cell transplantation.

Data are limited regarding risk factors for lower respiratory tract infection (LRTI) caused by seasonal human coronaviruses (HCoVs) and the significance of virologic documentation by bronchoalveolar lavage (BAL) on outcomes in hematopoietic cell transplant (HCT) recipients. We retrospectively analyzed patients undergoing allogeneic HCT (4/2008-9/2018) with HCoV (OC43/NL63/HKU1/229E) detected by polymerase chain reaction during conditioning or post-HCT. Risk factors for all manifestations of LRTI and progression to LRTI among those presenting with HCoV upper respiratory tract infection (URTI) were analyzed by logistic regression and Cox proportional hazard models, respectively. Mortality rates following HCoV LRTI were compared according to virologic documentation by BAL. A total of 297 patients (61 children and 236 adults) developed HCoV infection as follows: 254 had URTI alone, 18 presented with LRTI, and 25 progressed from URTI to LRTI (median, 16 days; range, 2-62 days). Multivariable logistic regression analyses showed that male sex, higher immunodeficiency scoring index, albumin <3 g/dL, glucose >150 mg/dL, and presence of respiratory copathogens were associated with occurrence of LRTI. Hyperglycemia with steroid use was associated with progression to LRTI (P < .01) in Cox models. LRTI with HCoV detected in BAL was associated with higher mortality than LRTI without documented detection in BAL (P < .01). In conclusion, we identified factors associated with HCoV LRTI, some of which are less commonly appreciated to be risk factors for LRTI with other respiratory viruses in HCT recipients. The association of hyperglycemia with LRTI might provide an intervention opportunity to reduce the risk of LRTI.