Effects of COVID-19 and Social Distancing on Rhinovirus Infections and Asthma Exacerbations.

Since their discovery in the 1950s, rhinoviruses (RVs) have been recognized as a major causative agent of the "common cold" and cold-like illnesses, accounting for more than 50% of upper respiratory tract infections. However, more than that, respiratory viral infections are responsible for approximately 50% of asthma exacerbations in adults and 80% in children. In addition to causing exacerbations of asthma, COPD and other chronic lung diseases, RVs have also been implicated in the pathogenesis of lower respiratory tract infections including bronchiolitis and community acquired pneumonia. Finally, early life respiratory viral infections with RV have been associated with asthma development in children. Due to the vast genetic diversity of RVs (approximately 160 known serotypes), recurrent infection is common. RV infections are generally acquired in the community with transmission occurring via inhalation of aerosols, respiratory droplets or fomites. Following the outbreak of coronavirus disease 2019 (COVID-19), exposure to RV and other respiratory viruses was significantly reduced due to social-distancing, restrictions on social gatherings, and increased hygiene protocols. In the present review, we summarize the impact of COVID-19 preventative measures on the incidence of RV infection and its sequelae.

Kallikreins emerge as new regulators of viral infections.

Kallikrein-related peptidases (KLKs) or kallikreins have been linked to diverse (patho) physiological processes, such as the epidermal desquamation and inflammation, seminal clot liquefaction, neurodegeneration, and cancer. Recent mounting evidence suggests that KLKs also represent important regulators of viral infections. It is well-established that certain enveloped viruses, including influenza and coronaviruses, require proteolytic processing of their hemagglutinin or spike proteins, respectively, to infect host cells. Similarly, the capsid protein of the non-enveloped papillomavirus L1 should be proteolytically cleaved for viral uncoating. Consequently, extracellular or membrane-bound proteases of the host cells are instrumental for viral infections and represent potential targets for drug development. Here, we summarize how extracellular proteolysis mediated by the kallikreins is implicated in the process of influenza (and potentially coronavirus and papillomavirus) entry into host cells. Besides direct proteolytic activation of viruses, KLK5 and 12 promote viral entry indirectly through proteolytic cascade events, like the activation of thrombolytic enzymes that also can process hemagglutinin, while additional functions of KLKs in infection cannot be excluded. In the light of recent evidence, KLKs represent potential host targets for the development of new antivirals. Humanized animal models to validate their key functions in viral infections will be valuable.

The Positive Rhinovirus/Enterovirus Detection and SARS-CoV-2 Persistence beyond the Acute Infection Phase: An Intra-Household Surveillance Study.

We aimed to assess the duration of nasopharyngeal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA persistence in adults self-confined at home after acute infection; and to identify the associations of SARS-CoV-2 persistence with respiratory virus co-detection and infection transmission. A cross-sectional intra-household study was conducted in metropolitan Barcelona (Spain) during the time period of April to June 2020. Every adult who was the first family member reported as SARS-CoV-2-positive by reverse transcription polymerase chain reaction (RT-PCR) as well as their household child contacts had nasopharyngeal swabs tested by a targeted SARS-CoV-2 RT-PCR and a multiplex viral respiratory panel after a 15 day minimum time lag. Four-hundred and four households (404 adults and 708 children) were enrolled. SARS-CoV-2 RNA was detected in 137 (33.9%) adults and 84 (11.9%) children. Rhinovirus/Enterovirus (RV/EV) was commonly found (83.3%) in co-infection with SARS-CoV-2 in adults. The mean duration of SARS-CoV-2 RNA presence in adults' nasopharynx was 52 days (range 26-83 days). The persistence of SARS-CoV-2 was significantly associated with RV/EV co-infection (adjusted odds ratio (aOR) 9.31; 95% CI 2.57-33.80) and SARS-CoV-2 detection in child contacts (aOR 2.08; 95% CI 1.24-3.51). Prolonged nasopharyngeal SARS-CoV-2 RNA persistence beyond the acute infection phase was frequent in adults quarantined at home during the first epidemic wave; which was associated with RV/EV co-infection and could enhance intra-household infection transmission.

Identification of pathogens from the upper respiratory tract of adult emergency department patients at high risk for influenza complications in a pre-Sars-CoV-2 environment.

The emergence of SARS-CoV-2 and subsequent COVID-19 pandemic highlights the morbidity and potential disease severity caused by respiratory viruses. To elucidate pathogen prevalence, etiology of coinfections and URIs from symptomatic adult Emergency department patients in a pre-SARS-CoV-2 environment, we evaluated specimens from four geographically diverse Emergency departments in the United States from 2013-2014 utilizing ePlex RP RUO cartridges (Genmark Diagnostics). The overall positivity was 30.1% (241/799), with 6.6% (16/241) coinfections. Noninfluenza pathogens from most to least common were rhinovirus/enterovirus, coronavirus, human metapneumovirus and RSV, respectively. Broad differences in disease prevalence and pathogen distributions were observed across geographic regions; the site with the highest detection rate (for both mono and coinfections) demonstrated the greatest pathogen diversity. A variety of respiratory pathogens and geographic variations in disease prevalence and copathogen type were observed. Further research is required to evaluate the clinical relevance of these findings, especially considering the SARS-CoV-2 pandemic and related questions regarding SARS-CoV-2 disease severity and the presence of co-infections.

Rhinovirus and asthma: Challenges and opportunities.

Human rhinoviruses (RVs) are the primary aetiological agent of the common cold. Generally, the associated infection is mild and self-limiting, but may also be associated with bronchiolitis in infants, pneumonia in the immunocompromised and exacerbation in patients with pulmonary conditions such as asthma or chronic obstructive pulmonary disease. Viral infection accounts for as many as two thirds of asthma exacerbations in children and more than half in adults. Allergy and asthma are major risk factors for more frequent and severe RV-related illnesses. The prevalence of RV-induced wheezing will likely continue to increase given that asthma affects a significant proportion of the population, with allergic asthma accounting for the majority. Several new respiratory viruses and their subgroups have been discovered, with various degrees of relevance. This review will focus on RV infection in the context of the epidemiologic evidence, genetic variability, pathobiology, clinical studies in the context of asthma, differences with other viruses including COVID-19 and current treatment interventions.

Rhinovirus Type in Severe Bronchiolitis and the Development of Asthma.

BACKGROUND: Respiratory syncytial virus (RSV)- and rhinovirus (RV)-induced bronchiolitis are associated with an increased risk of asthma, but more detailed information is needed on virus types. OBJECTIVE: To study whether RSV or RV types are differentially associated with the future use of asthma control medication. METHODS: Over 2 consecutive winter seasons (2008-2010), we enrolled 408 children hospitalized for bronchiolitis at age less than 24 months into a prospective, 3-center, 4-year follow-up study in Finland. Virus detection was performed by real-time reverse transcription PCR from nasal wash samples. Four years later, we examined current use of asthma control medication. RESULTS: A total of 349 (86%) children completed the 4-year follow-up. At study entry, the median age was 7.5 months, and 42% had RSV, 29% RV, 2% both RSV and RV, and 27% non-RSV/-RV etiology. The children with RV-A (adjusted hazard ratio, 2.3; P = .01), RV-C (adjusted hazard ratio, 3.5; P < .001), and non-RSV/-RV (adjusted hazard ratio, 2.0; P = .004) bronchiolitis started the asthma control medication earlier than did children with RSV bronchiolitis. Four years later, 27% of patients used asthma control medication; both RV-A (adjusted odds ratio, 3.0; P = .03) and RV-C (adjusted odds ratio, 3.7; P < .001) etiology were associated with the current use of asthma medication. The highest risk was found among patients with RV-C, atopic dermatitis, and fever (adjusted odds ratio, 5.0; P = .03). CONCLUSIONS: Severe bronchiolitis caused by RV-A and RV-C was associated with earlier initiation and prolonged use of asthma control medication. The risk was especially high when bronchiolitis was associated with RV-C, atopic dermatitis, and fever.