Human rhinovirus (HRV), a non-enveloped RNA virus, was first identified more than 70 years ago. It is highly infectious and easily transmitted through aerosols and direct contact. The advent of multiplex PCR has enhanced the detection of a diverse range of respiratory viruses, and HRV consistently ranks among the most prevalent respiratory pathogens globally. Circulation occurs throughout the year, with peak incidence in autumn and spring in temperate climates. Remarkably, during the SARS-CoV-2 pandemic, HRV transmission persisted, demonstrating its resistance to stringent public health measures aimed at curbing viral transmission.

HRV is characterised by its extensive genetic diversity, comprising three species and more than 170 genotypes. This diversity and substantial number of concurrently circulating strains allows HRVs to frequently escape the adaptive immune system and poses formidable challenges for the development of effective vaccines and antiviral therapies. There is currently a lack of specific treatments. Historically, HRV has been associated with self-limiting upper respiratory infection. However, there is now extensive evidence highlighting its significant role in severe lower respiratory disease in adults, including exacerbations of chronic airway diseases, such as asthma and chronic obstructive pulmonary disease (COPD), as well as pneumonia. These severe manifestations can occur even in immunocompetent individuals, broadening the clinical impact of this ubiquitous virus. Consequently, the burden of rhinovirus infections extends across various healthcare settings, from primary care to general hospital wards and intensive care units. The impact of HRV in adults, in terms of morbidity and healthcare utilisation, rivals that of the other major respiratory viruses, including influenza and respiratory syncytial virus. Recognition of this substantial burden underscores the critical need for novel treatment strategies and effective management protocols to mitigate the impact of HRV infections on public health.

This review examines the epidemiology, clinical manifestations, and risk factors associated with severe HRV infection in adults. By drawing on contemporary literature, we aim to provide a comprehensive overview of the virus's significant health implications. Understanding the scope of this impact is essential for developing new, targeted interventions and improving patient outcomes in the face of this persistent and adaptable pathogen.

Antibiotic resistance is a growing global health threat, and understanding local trends in bacterial isolates and their susceptibility patterns is crucial for effective infection control and antimicrobial stewardship. The coronavirus disease 2019 (COVID-19) pandemic has introduced additional complexities, potentially influencing these patterns.

To analyze trends in bacterial isolates and their antibiotic susceptibility patterns at Salmaniya Medical Complex from 2018 to 2023, with a specific focus on the impact of the COVID-19 pandemic on these trends.

A retrospective analysis of microbiological data was conducted, covering the period from 2018 to 2023. The study included key bacterial pathogens such as Escherichia coli (E. coli), Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Staphylococcus aureus, among others. The antibiotic susceptibility profiles of these isolates were assessed using standard laboratory methods. To contextualize the findings, the findings were compared with similar studies from other regions, including China, India, Romania, Saudi Arabia, the United Arab Emirates, Malaysia, and United States.

The study revealed fluctuating trends in the prevalence of bacterial isolates, with notable changes during the COVID-19 pandemic. For example, a significant increase in the prevalence of Staphylococcus aureus was observed during the pandemic years, while the prevalence of E. coli showed a more variable pattern. Antibiotic resistance rates varied among the different pathogens, with a concerning rise in resistance to commonly used antibiotics, particularly among Klebsiella pneumoniae and E. coli. Additionally, the study identified an alarming increase in the prevalence of multidrug-resistant (MDR) strains, especially within Klebsiella pneumoniae and E. coli isolates. The impact of the COVID-19 pandemic on these trends was evident, with shifts in the frequency, resistance patterns, and the emergence of MDR bacteria among several key pathogens.

This study highlights the dynamic nature of bacterial isolates and their antibiotic susceptibility patterns at Salmaniya Medical Complex, particularly in the context of the COVID-19 pandemic. The findings underscore the need for continuous monitoring and effective anti-microbial stewardship programs to combat the evolving threat of antibiotic resistance. Further research and policy initiatives are required to address the identified challenges and improve patient outcomes in the face of these ongoing challenges.

Bacterial and viral respiratory coinfections are common, but the prevalence of SARS-CoV-2 infections among pertussis cases has not been estimated. We examine the prevalence and temporality of SARS-CoV-2 infections among pertussis patients and describe pertussis clinical severity among patients with and without SARS-CoV-2 coinfections.

Confirmed and probable pertussis cases among individuals with cough onset between January 1, 2020 and February 15, 2023 were identified through surveillance in seven Enhanced Pertussis Surveillance (EPS) sites. Pertussis cases with a laboratory-confirmed SARS-CoV-2 infection detected within 30 days before or after pertussis cough onset were defined as coinfections. We describe patient demographics, symptoms, and severe complications and outcomes (seizures, encephalopathy, pneumonia, hospitalization, or death) by coinfection status.

Among 765 pertussis cases reported during the study period, the prevalence of SARS-CoV-2 coinfections was 0.78% [6/765]. Among the six patients meeting the coinfection definition, the majority (83.3% [5/6]) had SARS-CoV-2 infections detected following pertussis cough onset. Compared to those with no known coinfection, a higher proportion of those with coinfections reported severe complications or outcomes (50.0% [3/6] vs. 5.2% [36/694]).

Although the prevalence of pertussis patients with SARS-CoV-2 coinfections was low, patients with coinfections reported more severe complications and outcomes compared to those with pertussis alone. Given the decline in reported pertussis cases during the COVID-19 pandemic, continued monitoring of pertussis incidence alongside respiratory viral infections will be important as the pertussis burden returns to pre-pandemic levels.

Human Respiratory Syncytial Virus (HRSV) is a primary cause of severe pediatric respiratory infections, particularly in infants and young children, often resulting in hospitalization. The virus possesses a high degree of mutagenic potential, contributing to significant antigenic diversity, which complicates immune responses and poses challenges for vaccine development and disease management. This study was conducted in Jordan from 2022 to 2023 to epidemiologically determine the prevalence and molecular characteristics of RSV.

A total of 288 nasopharyngeal (NP) swabs were collected from hospitalized children at Prince Hamza Hospital, Amman, Jordan. All samples were screened for common viral and bacterial respiratory pathogens using PCR. A partial segment of the G gene of RSV was amplified for molecular characterization and phylogenetic tree analysis.

Viral and/or bacterial infection was identified in 71.9% (207/288) of the tested specimens. Among these, 35 samples (12.2%, 35/288) tested positive for RSV. Specific subgroup PCR analysis identified (25, 71.4%) RSV-A, (4, 11.4%) RSV-B, and (6, 17.1%) could not be identified using our set of primers. Phylogenetic tree analysis revealed that RSV-A ON1 and RSV-B BA9 genotype strains predominate in Jordan. We observed multiple substitutions in our studied sample which would drive variation in the level of antigenicity and pathogenicity of RSV. Glycosylation sites identified were consistent with previously reported studies.

This study provides updated epidemiological data on the strains circulating in Amman, Jordan and their molecular characteristics. Continuous RSV surveillance informs vaccine development, guides public health interventions, and enables timely administration of prophylactic treatments, reducing the burden of RSV-related illness.

In silico optimization of protein binding has received a great deal of attention in the recent years. Since in silico prefiltering of strong binders is fast and cheap compared to in vitro library screening methods, the advent of powerful hardware and advanced machine learning algorithms has made this strategy more accessible and preferred. These advances have already impacted the global response to pandemic threats. In this study, we proposed and tested a workflow for designing nanobodies targeting the SARS-CoV-2 spike protein receptor binding domain (S-RBD) using machine learning techniques complemented by molecular dynamics simulations. We evaluated the feasibility of this workflow using a test set of 3 different nanobodies and 2 different S-RBD variants, from in silico design and bacterial expression to binding assays of the designed nanobody mutants. We successfully designed nanobodies that were subsequently tested against both the wild-type (Wuhan type) and the delta variant S-RBD and found 2 of them to be stronger binders compared to the wild-type nanobody. We use this case study to describe both the strengths and weaknesses of this in silico assisted nanobody design strategy.

The interplay between SARS-CoV-2 and contemporaneous bacterial or fungal culture growth may have crucial implications for clinical outcomes of hospitalized patients. This study aimed to quantify the effect of microbiological culture positivity on mortality among hospitalized patients with SARS-CoV-2.

In this retrospective cohort study, we included adult hospitalized patients from OPTUM COVID-19 specific data set, who tested positive for SARS-CoV-2 within 14 days of hospitalization between 01/20/2020 and 01/20/2022. We examined outcomes of individuals with organisms growing on cultures from the bloodstream infections (BSIs), urinary tract, and respiratory tract, and a composite of the three sites. We used propensity score matching on covariates included demographics, comorbidities, and hospitalization clinical parameters. In a sensitivity analysis, we included same covariates but excluded critical care variables such as length of stay, intensive care unit stays, mechanical ventilation, and extracorporeal membrane oxygenation.

The cohort included 104,560 SARS-CoV-2 positive adult hospitalized patients across the United States. The unadjusted mortality odds increased significantly with BSIs (98.7%) and with growth on respiratory cultures (RC) (176.6%), but not with growth on urinary cultures (UC). Adjusted analyses showed that BSIs and positive RC independently contribute to mortality, even after accounting for critical care variables.

In SARS-CoV-2-positive hospitalized patients, positive bacterial and fungal microbiological cultures, especially BSIs and RC, are associated with an increased risk of mortality even after accounting for critical care variables associated with disease severity. These findings underscore the importance of stringent infection control and the effective management of secondary infections to improve patient outcomes.

The coronavirus disease (COVID-19) led to a global health crisis. Inappropriate use of antibiotics in COVID-19 patients has been a concern, leading to antimicrobial resistance. This study evaluated the patterns and predictors of empirical antibiotic therapy in COVID-19 patients and associated outcomes.

A hospital-based retrospective study was conducted with 525 patients admitted to Kasturba Hospital, Manipal, India, with moderate and severe COVID-19 from 1 March to 1 August 2021. They were divided based on empirical therapy, and predictors of antibiotic usage were assessed by logistic regression.

Four hundred and eighty (91.4%) COVID-19 patients received at least one course of antibiotics, with 440 (83.8%) initiating empirical therapy. Patients with severe COVID-19 manifestations were more likely to be prescribed empirical antibiotics. Multivariable analysis showed that patients initiated on empirical antibiotics had significantly elevated levels of procalcitonin [OR: 3.91 (95% CI: 1.66-9.16) (p = 0.001)], invasive ventilation [OR: 3.93 (95% CI: 1.70-9.09) (p = 0.001)], shortness of breath [OR: 2.25 (95% CI: 1.30-3.89) (p = 0.003)] and higher CRP levels [OR: 1.01 (95% CI: 1.00-1.01) (p = 0.005)]. Most antibiotics (65.9%) were prescribed from the 'Watch' group, the highest being ceftriaxone. Only 23.8% of the patients had microbiologically confirmed infections.

The study identified predictors for initiating empirical antibacterial therapy in our setting.

This exploratory post hoc analysis assessed the incidence of respiratory viral coinfections and their impact on clinical outcomes in non-hospitalized adults with mild-to-moderate coronavirus disease-2019 (COVID-19) treated with molnupiravir versus placebo for 5 days in the Phase 2/3 MOVe-OUT trial (NCT04575597), which took place in October 2020 to January 2021 (Phase 2, n = 302) and May 2021 to October 2021 (Phase 3, n = 1,433). Among 1,735 total randomized participants, 1,674 had a baseline respiratory pathogen panel (NxTAG Respiratory Pathogen Panel for the Luminex MAGPIX instrument) performed and 69 (4.1%) were coinfected with at least one additional respiratory viral pathogen. Human rhinovirus/enterovirus (39/69, 56.5%) was the most common coinfection detected at baseline. In the modified intention-to-treat population, two participants with coinfecting respiratory RNA viruses were hospitalized and received respiratory interventions through Day 29, and none died; one participant in the molnupiravir group was coinfected with human rhinovirus/enterovirus, and one participant in the placebo group was coinfected with human metapneumovirus. Hospitalization or death occurred in 6.2% and 9.0% of non-coinfected participants in the molnupiravir versus placebo group, respectively, and over 90% did not require respiratory interventions. Most coinfecting respiratory RNA viruses detected at baseline were not detected at the end of therapy in both the molnupiravir and placebo groups. In summary, participants coinfected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and another respiratory RNA virus were not more likely to be hospitalized or die, or require respiratory interventions, compared to participants who were not coinfected with another respiratory RNA virus at baseline in both groups.

Respiratory viral coinfections are known to occur with coronavirus disease-2019 (COVID-19). In a cohort of non-hospitalized adults with mild-to-moderate COVID-19 treated with molnupiravir versus placebo in the MOVe-OUT trial during October 2020 to October 2021, 4.1% of participants had a documented viral coinfection; human rhinovirus/enterovirus was the most common pathogen detected with the NxTAG Respiratory Pathogen Panel assay. Participants who had a coinfection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and another respiratory RNA virus were not more likely to have worse clinical outcomes compared to those participants without a viral coinfection, and many coinfecting respiratory RNA viruses were no longer detected at the end of the 5-day treatment period in both groups.

Hypercytokinemia, the renin-angiotensin system, hypoxia, immune dysregulation, and vasculopathy with evidence of immune-related damage are implicated in brain morbidity in COVID-19 along with a wide variety of genomic and environmental influences. There is relatively little evidence of direct SARS-CoV-2 brain infection in COVID-19 patients.

Brain histopathology of 36 consecutive autopsies of patients who were RT-PCR positive for SARS-CoV-2 was studied along with findings from contemporary and pre-pandemic historical control groups. Immunostaining for serum and blood cell proteins and for complement components was employed. Microcirculatory wall complement deposition in the COVID-19 cohort was compared to historical control cases. Comparisons also included other relevant clinicopathological and microcirculatory findings in the COVID-19 cohort and control groups.

The COVID-19 cohort and both the contemporary and historical control groups had the same rate of hypertension, diabetes mellitus, and obesity. The COVID-19 cohort had varying amounts of acute neutrophilic vasculitis with leukocytoclasia in the microcirculation of the brain in all cases. Prominent vascular neutrophilic transmural migration was found in several cases and 25 cases had acute perivasculitis. Paravascular microhemorrhages and petechial hemorrhages (small brain parenchymal hemorrhages) had a slight tendency to be more numerous in cohort cases that displayed less acute neutrophilic vasculitis. Tissue burden of acute neutrophilic vasculitis with leukocytoclasia was the same in control cases as a group, while it was significantly higher in COVID-19 cases. Both the tissue burden of acute neutrophilic vasculitis and the activation of complement components, including membrane attack complex, were significantly higher in microcirculatory channels in COVID-19 cohort brains than in historical controls.

Acute neutrophilic vasculitis with leukocytoclasia, acute perivasculitis, and associated paravascular blood extravasation into brain parenchyma constitute the first phase of an immune-related, acute small-vessel inflammatory condition often termed type 3 hypersensitivity vasculitis or leukocytoclastic vasculitis. There is a higher tissue burden of acute neutrophilic vasculitis and an increased level of activated complement components in microcirculatory walls in COVID-19 cases than in pre-pandemic control cases. These findings are consistent with a more extensive small-vessel immune-related vasculitis in COVID-19 cases than in control cases. The pathway(s) and mechanism for these findings are speculative.

To estimate the prevalence of influenza coinfection in COVID-19 patients and investigate its association with severe clinical outcomes.

We systematically searched the Web of Science, PubMed, Scopus, Embase, The Cochrane Library, and CNKI for studies published between January 01, 2020, and May 31, 2023. Meta-analysis was performed to estimate the pooled prevalence of coinfection and the impact on clinical outcomes. Systematic review registered in PROSPERO (CRD42023423113).

A total of 95 studies involving 62,107 COVID-19 patients were included. The pooled prevalence of coinfection with influenza virus was 2.45% (95% confidence interval [CI]: 1.67-3.58%), with a high proportion of influenza A. Compared with mono-infected patients (COVID-19 only), the odds ratio (OR) for severe outcomes (including intensive care unit admission [OR = 2.20, 95% CI: 1.68-2.87, P < 0.001], mechanical ventilation support [OR = 2.73, 95% CI: 1.46-5.10, P = 0.002], and mortality [OR = 2.92, 95% CI: 1.16-7.30, P = 0.022]) was significantly higher among patients coinfected influenza A.

Although the prevalence of coinfection is low, coinfected patients are at higher risk of severe outcomes. Enhanced identification of both viruses, as well as individualized treatment protocols for coinfection, are recommended to reduce the occurrence of serious disease outcomes in the future.

As the transmission of endemic respiratory pathogens returns to prepandemic levels, understanding the epidemiology of respiratory coinfections in children with SARS-CoV-2 is of increasing importance.

We performed a retrospective analysis of all pediatric patients 0-21 years of age who had a multiplexed BioFire Respiratory Panel 2.1 test performed at Children's Healthcare of Atlanta, Georgia, from January 1 to December 31, 2021. We determined the proportion of patients with and without SARS-CoV-2 who had respiratory coinfections and performed Poisson regression to determine the likelihood of coinfection and its association with patient age.

Of 19,199 respiratory panel tests performed, 1466 (7.64%) were positive for SARS-CoV-2, of which 348 (23.74%) also had coinfection with another pathogen. The most common coinfection was rhino/enterovirus (n = 230, 15.69%), followed by adenovirus (n = 62, 4.23%), and RSV (n = 45, 3.507%). Coinfections with SARS-CoV-2 were most commonly observed in the era of Delta (B.1.617.2) predominance (190, 54.60%), which coincided with periods of peak rhino/enterovirus and RSV transmission. Although coinfections were common among all respiratory pathogens, they were significantly less common with SARS-CoV-2 than other pathogens, with exception of influenza A and B. Children <2 years of age had the highest frequency of coinfection and of detection of any pathogen, including SARS-CoV-2. Among children with SARS-CoV-2, for every 1-year increase in age, the rate of coinfections decreased by 8% (95% CI, 6-9).

Respiratory coinfections were common in children with SARS-CoV-2. Factors associated with the specific pathogen, host, and time period influenced the likelihood of coinfection.