Severe Respiratory Illness Cases Research Articles

Influenza Virus Infects and Depletes Activated Adaptive Immune Responders.

Influenza infections cause several million cases of severe respiratory illness, hospitalizations, and hundreds of thousands of deaths globally. Secondary infections are a leading cause of influenza's high morbidity and mortality, and significantly factored into the severity of the 1918, 1968, and 2009 pandemics. Furthermore, there is an increased incidence of other respiratory infections even in vaccinated individuals during influenza season. Putative mechanisms responsible for vaccine failures against influenza as well as other respiratory infections during influenza season are investigated. Peripheral blood mononuclear cells (PBMCs) are used from influenza vaccinated individuals to assess antigen‐specific responses to influenza, measles, and varicella. The observations made in humans to a mouse model to unravel the mechanism is confirmed and extended. Infection with influenza virus suppresses an ongoing adaptive response to vaccination against influenza as well as other respiratory pathogens, i.e., Adenovirus and Streptococcus pneumoniae by preferentially infecting and killing activated lymphocytes which express elevated levels of sialic acid receptors. These findings propose a new mechanism for the high incidence of secondary respiratory infections due to bacteria and other viruses as well as vaccine failures to influenza and other respiratory pathogens even in immune individuals due to influenza viral infections.

Relation Between Body Composition, Systemic Inflammatory Response, and Clinical Outcomes in Patients Admitted to an Urban Teaching Hospital with COVID-19.

ABSTRACTBackgroundCOVID-19 has been associated with cases of severe respiratory illness, admissions to intensive therapy units (ITUs), and high mortality rates.ObjectivesThe aim of the present study was to examine the relation between computed tomography- body composition (CT-BC) measurements, systemic inflammation, and clinical outcomes in those with COVID-19.MethodsPatients who presented to our institution between March 17 and May 1, 2020, with a positive PCR test for COVID-19 or characteristic radiological changes, were assessed for inclusion. Data collected included general demographic details, clinicopathological variables, poGPS, NLR , CT-BC measurements, and clinical outcomes including ITU admission and 30-d mortality, of those admitted.ResultsSixty-three patients met the study inclusion criteria. Forty-two patients (67%) were aged ≥70 y, 30 (47.6%) were male and 34.9% ( n = 22) had a poGPS ≥1. ITU admission was significantly associated with a high VFA ( P < 0.05). Thirty-day mortality was associated with high VFA (P < 0.05) and low SMI (P < 0.05).ConclusionsSarcopenia in the presence of obesity was associated with clinical outcomes including greater 30-d mortality.

Comprehensive Characterization of Transcriptional Activity during Influenza A Virus Infection Reveals Biases in Cap-Snatching of Host RNA Sequences

Macrophages in the lung detect and respond to influenza A virus (IAV), determining the nature of the immune response. Using terminal-depth cap analysis of gene expression (CAGE), we quantified transcriptional activity of both host and pathogen over a 24-h time course of IAV infection in primary human monocyte-derived macrophages (MDMs). This method allowed us to observe heterogenous host sequences incorporated into IAV mRNA, "snatched" 5' RNA caps, and corresponding RNA sequences from host RNAs. In order to determine whether cap-snatching is random or exhibits a bias, we systematically compared host sequences incorporated into viral mRNA ("snatched") against a complete survey of all background host RNA in the same cells, at the same time. Using a computational strategy designed to eliminate sources of bias due to read length, sequencing depth, and multimapping, we were able to quantify overrepresentation of host RNA features among the sequences that were snatched by IAV. We demonstrate biased snatching of numerous host RNAs, particularly small nuclear RNAs (snRNAs), and avoidance of host transcripts encoding host ribosomal proteins, which are required by IAV for replication. We then used a systems approach to describe the transcriptional landscape of the host response to IAV, observing many new features, including a failure of IAV-treated MDMs to induce feedback inhibitors of inflammation, seen in response to other treatments.IMPORTANCE Infection with influenza A virus (IAV) infection is responsible for an estimated 500,000 deaths and up to 5 million cases of severe respiratory illness each year. In this study, we looked at human primary immune cells (macrophages) infected with IAV. Our method allows us to look at both the host and the virus in parallel. We used these data to explore a process known as "cap-snatching," where IAV snatches a short nucleotide sequence from capped host RNA. This process was believed to be random. We demonstrate biased snatching of numerous host RNAs, including those associated with snRNA transcription, and avoidance of host transcripts encoding host ribosomal proteins, which are required by IAV for replication. We then describe the transcriptional landscape of the host response to IAV, observing new features, including a failure of IAV-treated MDMs to induce feedback inhibitors of inflammation, seen in response to other treatments.

Influenza virus suppresses the adaptive immune response leaving immune hosts vulnerable to influenza and other respiratory pathogens

Abstract Influenza infections are associated with several million cases of severe respiratory illness, hospitalizations, and hundreds of thousands of deaths globally. Secondary infections further complicate influenza’s high morbidity and mortality, and significantly factored into the severity of the 1918, 1968, and 2009 pandemics. The most common coinfections are bacterial, leading to bacterial pneumonia, though viral secondary infections also occur. Previous studies have shown that influenza can target innate responses and damage affected tissues, allowing for secondary infections. In this study we show that influenza virus targets not only innate immune responses but also the adaptive responses - specifically activated B cells, T cells, and NKT cells. Importantly, we demonstrate that infection with influenza virus can attenuate the adaptive responses to prior influenza vaccination and to other respiratory pathogen vaccinations, in humans and in mouse models. This occurs through a viral hijacking of the normal immune responses by taking advantage of elevated expression of sialic acid receptors on activated lymphocytes to preferentially infect and kill immune responders. Our findings provide a novel potential mechanism for the high incidence of secondary respiratory infections due to bacteria and other viruses, as well as for vaccine failures against other infectious agents during influenza seasons.

Detection of Soluble Oligomers Formed by PB1-F2 Influenza A Virus Protein in vitro

Influenza A viruses (IAV) remain a major cause of respiratory disease worldwide each year and have been responsible for three main pandemics during the last century comprising the Spanish flu which killed up to 50 million of people. IAV are RNA enveloped viruses belonging to the Orthomyxoviridae family. The nature of the genome of IAV favors the constant and hardly predictable emergence of new strains such as highly virulent H5N1 viruses since 2003, or the H1N1 2009 pandemic strain. Recently, new human cases of severe respiratory illness with a new avian influenza A (H7N9) virus have been reported in China (mortality rate of 60%).Thus, researchers maintain their efforts to determine specific markers of virulence and to evaluate the potential of emerging strains to cause new pandemics.

Receptor usage of a newly emergent adenovirus type 14

Recently, cases of severe respiratory illness in military and civilian populations have been associated with a new genomic variant of adenovirus (Ad) serotype 14, designated Ad14a. Compared to the Ad14 reference strain (de Wit), this new virus had a deletion of two amino acid residues in the fiber protein knob. Here we tested whether this mutation changed receptor usage of Ad14a compared to Ad14-de Wit. Competition studies with radio-labeled viruses revealed that both Ad14-de Wit and Ad14a used the same receptor which is hitherto unknown. We also found that recombinant fiber knobs only partially blocked attachment of Ad14a, indicating that virus capsid proteins other than the fiber are involved in infection.