scholarly journals A Prenylated dsRNA Sensor Protects Against Severe COVID-19 and is Absent in Horseshoe Bats

2021 ◽  
Author(s):  
Arthur Wickenhagen ◽  
Elena Sugrue ◽  
Spyros Lytras ◽  
Srikeerthana Kuchi ◽  
Matthew L Turnbull ◽  
...  
Keyword(s):  
Disease Severity ◽  
African Descent ◽  
Antiviral Response ◽  
Hospitalized Patients ◽  
Antiviral Defense ◽  
Rnase L ◽  
Splice Acceptor ◽  
Expression Screening ◽  
Horseshoe Bats

Cell autonomous antiviral defenses can inhibit the replication of viruses and reduce transmission and disease severity. To better understand the antiviral response to SARS-CoV-2, we used interferon-stimulated gene (ISG) expression screening to reveal that OAS1, through RNase L, potently inhibits SARS-CoV-2. We show that while some people can express a prenylated OAS1 variant, that is membrane-associated and blocks SARS-CoV-2 infection, other people express a cytosolic, nonprenylated OAS1 variant which does not detect SARS-CoV-2 (determined by the splice-acceptor SNP Rs10774671). Alleles encoding nonprenylated OAS1 predominate except in people of African descent. Importantly, in hospitalized patients, expression of prenylated OAS1 was associated with protection from severe COVID-19, suggesting this antiviral defense is a major component of a protective antiviral response. Remarkably, approximately 55 million years ago, retrotransposition ablated the OAS1 prenylation signal in horseshoe bats (the presumed source of SARS-CoV-2). Thus, SARS-CoV-2 never had to adapt to evade this defense. As prenylated OAS1 is widespread in animals, the billions of people that lack a prenylated OAS1 could make humans particularly vulnerable to the spillover of coronaviruses from horseshoe bats.

scholarly journals Neopterin predicts disease severity in hospitalized patients with COVID-19

2020 ◽  
Author(s):  
Rosa Bellmann-Weiler ◽  
Lukas Lanser ◽  
Francesco Burkert ◽  
Stefanie Seiwald ◽  
Gernot Fritsche ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Retrospective Analysis ◽  
Disease Severity ◽  
Predictive Value ◽  
Clinical Management ◽  
Inflammatory Markers ◽  
Predictive Marker ◽  
Hospitalized Patients ◽  
Icu Admission ◽  
Circulating Inflammatory Markers

Abstract This study evaluates the predictive value of circulating inflammatory markers, especially neopterin, in patients with COVID-19. Within this retrospective analysis of 115 hospitalized COVID-19 patients, elevated neopterin levels upon admission were significantly associated with disease severity, risk for ICU admission, need for mechanical ventilation and death. Therefore, neopterin is a reliable predictive marker in patients with COVID-19 and may help to improve the clinical management of patients.

scholarly journals Author Correction: The U‑shaped association of serum iron level with disease severity in adult hospitalized patients with COVID‑19

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kentaro Tojo ◽  
Yoh Sugawara ◽  
Yasufumi Oi ◽  
Fumihiro Ogawa ◽  
Takuma Higurashi ◽  
...  
Keyword(s):  
Disease Severity ◽  
Serum Iron ◽  
Hospitalized Patients ◽  
Iron Level ◽  
Serum Iron Level

THE IMPACT OF OUTPATIENT INHALED CORTICOSTEROID THERAPY ON DISEASE SEVERITY IN HOSPITALIZED PATIENTS WITH COMMUNITY ACQUIRED PNEUMONIA

CHEST Journal ◽  
2008 ◽  
Vol 134 (4) ◽  
pp. 16S
Author(s):  
Rosa Malo de Molina ◽  
Eric M. Mortensen ◽  
Patricia Castellanos-Matteus ◽  
Antonio Anzueto ◽  
Marcos I. Restrepo
Keyword(s):  
Disease Severity ◽  
Corticosteroid Therapy ◽  
Community Acquired Pneumonia ◽  
Hospitalized Patients ◽  
Inhaled Corticosteroid ◽  
The Impact

scholarly journals Low albumin levels are associated with poorer outcomes in a case series of COVID-19 patients in Spain: a retrospective cohort study

2020 ◽  
Author(s):  
Roberto de la Rica ◽  
Marcio Borges ◽  
María Aranda ◽  
Alberto del Castillo ◽  
Antonia Socias ◽  
...  
Keyword(s):  
Disease Severity ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Case Series ◽  
Hospitalized Patients ◽  
University Hospital ◽  
Limited Information ◽  
Icu Patients ◽  
Epidemiological Features ◽  
Initial Symptoms

ABSTRACTOBJECTIVETo describe the clinical characteristics and epidemiological features of severe (non-ICU) and critically patients (ICU) with COVID-19 at triage, prior hospitalization, in one of the main hospitals in The Balearic Islands health care system.DESIGNRetrospective observational studySETTINGSon Llatzer University Hospital in Palma de Mallorca (Spain)PARTICIPANTSAmong a cohort of 52 hospitalized patients as of 31 March 2020, 48 with complete demographic information and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive test, were analyzed. Data were collected between March 15th, 2020, and March 31th 2020, inclusive of these dates.MAIN OUTCOMESClinical, vital signs and routine laboratory outcomes at the time of hospitalization, including symptoms reported prior to hospitalization. Demographics and baseline comorbidities were also collected. Mortality was reported at the end of the study.RESULTS48 patients (27 non-ICU and 21 ICU) resident in Mallorca, Spain (mean age, 66 years, [range, 33-88 years]; 67% males) with positive SARS-CoV-2 infection were analyzed. There were no differences in age or sex among groups (p >.05). Initial symptoms included fever (100%), coughing (85%), dyspnea (76%), diarrhea (42%) and asthenia (21%). The majority of patients in this case series were hospitalized because of low SpO2 (SpO2 below 90%) and presentation of bilateral pneumonia (94%) at triage. ICU patients had a higher prevalence of dyspnea compared to non-ICU patients (95% vs 61%, p = .022). Acute respiratory syndrome (ARDS) was presented in 100% of the ICU-patients. All the patients included in the study required oxygen therapy. ICU-patients had lymphopenia as well as hypoalbuminemia. Inflammatory markers such as lactate dehydrogenase (LDH), C-reactive protein (CRP), and procalcitonin were significantly higher in ICU patients compared to non-ICU (p < .001).Lower albumin levels were associated with poor prognosis measured as longer hospital length (r= −0.472, p <.001) and mortality (r= −0.424, p=.003). Interestingly we also found, that MCV was lower among of those patients who died (p=.0002). As of April 28, 2020, 10 patients (8 ICU and 2 non-ICU) had died (21% mortality) and while 100% of the non-ICU patients had been discharged, 33% of ICU patients still remained hospitalized (5 in ICU and 2 had been transferred to ward).CONCLUSIONCritically ill patients with COVID-19 present lymphopenia, hypoalbuminemia as well high levels of inflammation. Lower levels of albumin were associated with poorer outcomes in COVID-19 patients. Albumin might be of importance because of its association with disease severity in patients infected with SARS-CoV-2.WHAT IS ALREADY KNOWN IN THIS TOPICSpain has been hit particularly hard by the pandemic. By the time that this manuscript was written more than 25.000 deaths related to COVID-19 have been confirmed. There is limited information available describing the clinical and epidemiological features of Spanish patients requiring hospitalization for COVID-19. Also, it is important to know the characteristics of the hospitalized patients who become critically illWHAT THIS STUDY ADDSThis small case series provides the first steps towards a comprehensive clinical characterization of severe and critical COVID-19 adult patients in Spain. The overall mortality in our patients was 21%. To our knowledge this is the first report with reporting these features in Spain. At triage the majority of patients had lower SpO2 (<90%) and bilateral pneumonia. The most common comorbidities were hypertension (70%), dyslipidemia (62%) and cardiovascular disease (30%). Critically ill patients present hypoalbuminemia and lymphopenia, as well as higher levels of inflammation. Albumin might be of importance because of its association with disease severity and mortality in patients infected with SARS-CoV-2.

Introns encode dsRNAs undetected by RIG-I/MDA5/interferons and sensed via RNase L

2021 ◽  
Vol 118 (46) ◽  
pp. e2102134118
Author(s):  
Alisha Chitrakar ◽  
Kristina Solorio-Kirpichyan ◽  
Eliza Prangley ◽  
Sneha Rath ◽  
Jin Du ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Immune Responses ◽  
Innate Immune ◽  
Rna Decay ◽  
Antiviral Defense ◽  
Rnase L ◽  
Innate Immune Responses ◽  
Double Stranded Rna ◽  
Turn On ◽  
Nuclear Rna

Double-stranded RNA (dsRNA), a hallmark viral material that activates antiviral interferon (IFN) responses, can appear in human cells also in the absence of viruses. We identify phosphorothioate DNAs (PS DNAs) as triggers of such endogenous dsRNA (endo-dsRNA). PS DNAs inhibit decay of nuclear RNAs and induce endo-dsRNA via accumulation of high levels of intronic and intergenic inverted retroelements (IIIR). IIIRs activate endo-dsRNA responses distinct from antiviral defense programs. IIIRs do not turn on transcriptional RIG-I/MDA5/IFN signaling, but they trigger the dsRNA-sensing pathways of OAS3/RNase L and PKR. Thus, nuclear RNA decay and nuclear-cytosolic RNA sorting actively protect from these innate immune responses to self. Our data suggest that the OAS3/RNase L and PKR arms of innate immunity diverge from antiviral IFN responses and monitor nuclear RNA decay by sensing cytosolic escape of IIIRs. OAS3 provides a receptor for IIIRs, whereas RNase L cleaves IIIR-carrying introns and intergenic RNAs.

scholarly journals Impact of Smoking Status on Disease Severity and Mortality of Hospitalized Patients With COVID-19 Infection: A Systematic Review and Meta-analysis

2020 ◽  
Vol 22 (9) ◽  
pp. 1657-1659 ◽  
Author(s):  
Antonios Karanasos ◽  
Konstantinos Aznaouridis ◽  
George Latsios ◽  
Andreas Synetos ◽  
Stella Plitaria ◽  
...  
Keyword(s):  
Systematic Review ◽  
Disease Severity ◽  
Smoking Status ◽  
Meta Analysis ◽  
Hospitalized Patients

scholarly journals ICP0 Prevents RNase L-Independent rRNA Cleavage in Herpes Simplex Virus Type 1-Infected Cells

2006 ◽  
Vol 80 (1) ◽  
pp. 218-225 ◽  
Author(s):  
Paul T. Sobol ◽  
Karen L. Mossman
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Viral Infection ◽  
Virus Type ◽  
Herpes Simplex Virus Type ◽  
Antiviral Response ◽  
Rnase L ◽  
Simplex Virus ◽  
Rrna Degradation

ABSTRACT The classical interferon (IFN)-dependent antiviral response to viral infection involves the regulation of IFN-stimulated genes (ISGs), one being the gene encoding cellular endoribonuclease RNase L, which arrests protein synthesis and induces apoptosis by nonspecifically cleaving rRNA. Recently, the herpes simplex virus type 1 (HSV-1) protein ICP0 has been shown to block the induction of ISGs by subverting the IFN pathway upstream of the 2′-5′-oligoadenylate synthetase (OAS)/RNase L pathway. We report that ICP0 also prevents rRNA degradation at late stages of HSV-1 infection, independent of its E3 ubiquitin ligase activity, and that the resultant rRNA degradation is independent of the classical RNase L antiviral pathway. Moreover, the degradation is independent of the viral RNase vhs and is independent of IFN response factor 3. These studies indicate the existence of another, previously unidentified, RNase that is part of the host antiviral response to viral infection.

scholarly journals The Potential Role of Therapeutic Dose of Low Molecular Weight Heparin (LWMH) to Attenuate Hyper-Inflammatory State in Hospitalized COVID-19 Patients

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 11-12
Author(s):  
Mohsin Sheraz Mughal ◽  
Ikwinder Preet Kaur ◽  
Ali R. Jaffery ◽  
Chang Wang ◽  
Muhammad Asif ◽  
...  
Keyword(s):  
Pulmonary Embolism ◽  
Disease Severity ◽  
Inflammatory Markers ◽  
Potential Role ◽  
Hospitalized Patients ◽  
Inflammatory State ◽  
Anti Inflammatory ◽  
D Dimer ◽  
Inflammatory Effect

Introduction:The underlying pathophysiology of severe COVID-19 involves cytokine storm syndrome that is associated with an elevation of immunoinflammatory cytokines [1]. This hyper-inflammatory state has been implicated with coagulopathy among severely sick patients with COVID-19. Inflammation and coagulopathy are interlinked processes [2]. Coagulopathy has been associated with high mortality in COVID-19 patients [3]. LMWH is traditionally used for its anticoagulant and antithrombotic properties, however, its anti-inflammatory effect has not been fully elucidated. A study done by Shastri et al. suggested that LMWH can inhibit the release of different cytokines (IL-4, IL-5, IL-13, and TNF-α) [4]. Recent retrospective studies on COVID-19 illustrated that the LMWH (40-60 mg, subcutaneously every day) was associated with better prognosis as measured by (28 days of survival) in severely sick patients meeting sepsis-induced coagulopathy (SIC≥4) criteria compared to nonusers [5]. The potential role of escalated/therapeutic LMWH (1mg/kg/subcutaneously every 12 hours) remains unclear. This study involves a retrospective analysis of the potential role of an escalated dose of LMWH to alter the hyper-inflammatory state in hospitalized patients with COVID-19 and compared outcomes to those patients who received a low dose (40-60 mg, subcutaneously every day) of LMWH. Methods:Adult patients with confirmed SARS-CoV-2 infection by nasopharyngeal (NP) polymerase chain reaction (PCR) who were hospitalized from March 1st to April 20, 2020, were included. They were divided into two cohorts based on the dose of LMWH; cohort 1 (40-60 mg, subcutaneously every day) and cohort 2 (1mg/kg/subcutaneously every 12 hours). Categorical variables were compared by conducting a chi-square test or Fisher's exact test while continuous ones were compared by conducting a median two-sample test. Results:The median values of PT, PTT, INR, CRPmax, LDHmax, ferritinmax, D-dimermax, are mentioned in table 1. Incidence of thrombotic events (deep venous thrombosis, ischemic stroke, pulmonary embolism) was higher in cohort 1 (n=3, 4.8%) compared to cohort 2 (n=1, 2.6%). Cohort 2 had a higher number of patients who received ICU level of care (n=24) compared to the 6 patients in cohort 1. Out of 24 patients in cohort 2, 18 patients received invasive mechanical ventilation. The median value of length of stay in the hospital (10.0 days) and all-cause mortality (31.6 %) were higher in cohort 2 as compared to cohort 1 (p&lt;0.05). Discussion:Infections have the ability to trigger systemic inflammation [6]. The interplay between the host system and its response to foreign pathogens can lead to the activation of coagulation pathways. SARS-CoV-2 entry via ACE-2 receptors on endothelial cells is likely associated with endothelial dysfunction. This endotheliopathy plays a significant role in COVID-19 related microcirculatory changes [7]. Severe COVID-19, a hyperinflammatory state, is marked by elevated inflammatory markers including D-dimer, ferritin, IL-6, LDH, and CRP levels. Elevated D-dimer levels have been correlated with disease severity and poor outcomes in hospitalized patients with COVID-19 [8]. The incidence of VTE and pulmonary embolism among COVID-19 ICU patients was higher in a study from France [9]. The patient population who received the escalated dose of LMWH in our study either had SIC score ≥ 4 or D-dimer ≥ 2.2 (FEU). This data indicated that the median value of peak inflammatory markers in cohort 1 was lower (p&lt;0.05) when compared to cohort 2. Patients in cohort 2 were sicker than cohort 1, as evidenced by a statistically significant longer length of hospital stay and a higher rate of ICU admission. However, the potential dose-dependent anti-inflammatory effect of LMWH was not observed. Additional studies evaluating comorbidities and disease severity in both cohorts may yield different results. Conclusion:Aside from the known anticoagulant benefit of LMWH, there was no additional anti-inflammatory role with higher doses (1mg/kg/subcutaneously every 12 hours) of LMWH. Disclosures No relevant conflicts of interest to declare.

scholarly journals FRAILTY AND MORTALITY RISK IN PATIENTS WITH SEVERE COVID-19: PROGNOSIS BEYOND THE AGE CRITERION

2021 ◽  
Author(s):  
Márlon Juliano Romero Aliberti ◽  
Claudia Szlejf ◽  
Claudia Kimie Suemoto ◽  
Murilo Bacchini Dias ◽  
Wilson Jacob-Filho ◽  
...  
Keyword(s):  
Disease Severity ◽  
Scale Score ◽  
Mortality Risk ◽  
Frailty Index ◽  
Hazard Ratio ◽  
Hospitalized Patients ◽  
Adjusted Hazard Ratio ◽  
Acute Disease ◽  
Clinical Frailty Scale ◽  
Risk Of Death

OBJECTIVE: To investigate the association between frailty and death in hospitalized patients with COVID-19. METHODOLOGY: Prospective cohort study with patients ≥ 50 years hospitalized with COVID-19. Frailty was assessed using the Clinical Frailty Scale and the frailty index. Patients with a Clinical Frailty Scale score ≥ 5 were considered frail. The primary endpoints were mortality at 30 and 100 days after hospital admission. We used Cox proportional hazard models to investigate the association between frailty and mortality. We also explored whether frailty predicted different mortality levels among patients within strata of similar age and acute disease severity (Sequential Organ Failure Assessment score). RESULTS: A total of 1,830 patients were included (mean age 66 years; 58% men; 27% frail according to Clinical Frailty Scale score). The mortality risk at 30 days (adjusted hazard ratio = 1.7; 95% CI 1.4 - 2.1; p <0.001) and 100 days (adjusted hazard ratio = 1.7; 95% CI 1.4 - 2.1; p <0.001) was almost double for frail patients. The Clinical Frailty Scale also predicted different mortality levels among patients within strata of similar age and acute disease severity. Frailty intensified the effect of acute disease severity on the risk of death (p for interaction = 0.01). Of note, the Clinical Frailty Scale achieved outstanding accuracy to identify frailty according to the frailty index (area under the ROC curve = 0.94; 95% CI 0.93 - 0.95). CONCLUSIONS: Our results encourage the use of the Clinical Frailty Scale in association with measures of acute disease severity to determine prognosis and promote adequate resource allocation in hospitalized patients with COVID-19.

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