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1.
Eur J Neurol ; 28(10): 3411-3417, 2021 10.
Article in English | MEDLINE | ID: covidwho-1607226

ABSTRACT

BACKGROUND AND PURPOSE: Since the outbreak of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic, several reports indicated neurological involvement in COVID-19 disease. Muscle involvement has also been reported as evidenced by creatine kinase (CK) elevations and reports of myalgia. METHODS: Creatine kinase, markers of inflammation, pre-existing diseases and statin use were extracted from records of Austrian hospitalised COVID-19 patients. Disease severity was classified as severe in case of intensive care unit (ICU) admission or mortality. COVID-19 patients were additionally compared to an historical group of hospitalised influenza patients. RESULTS: Three hundred fifty-one patients with SARS-CoV-2 and 258 with influenza were included in the final analysis. CK was elevated in 27% of COVID-19 and in 28% of influenza patients. CK was higher in severe COVID-19 as were markers of inflammation. CK correlated significantly with inflammation markers, which had an independent impact on CK when adjusted for demographic variables and disease severity. Compared to influenza patients, COVID-19 patients were older, more frequently male, had more comorbidities, and more frequently had a severe disease course. Nevertheless, influenza patients had higher baseline CK than COVID-19, and 35.7% of intensive care unit (ICU)-admitted patients had CK levels >1,000 U/L compared to only 4.7% of ICU-admitted COVID-19 patients. CONCLUSIONS: HyperCKemia occurs in a similar frequency in COVID-19 and influenza infection. CK levels were lower in COVID-19 than in influenza in mild and severe disease. CK levels strongly correlate with disease severity and markers of inflammation. To date, it remains unclear whether hyperCKemia is due to a virus-triggered inflammatory response or direct muscle toxicity.


Subject(s)
COVID-19 , Influenza, Human , Humans , Influenza, Human/complications , Influenza, Human/epidemiology , Male , Muscles , Pandemics , SARS-CoV-2
2.
Front Public Health ; 9: 773130, 2021.
Article in English | MEDLINE | ID: covidwho-1593754

ABSTRACT

Background: Although coinfection with influenza in COVID-19 patients has drawn considerable attention, it is still not completely understood whether simultaneously infected with these two viruses influences disease severity. We therefore aimed to estimate the impact of coinfected with SARS-CoV-2 and influenza on the disease outcomes compared with the single infection of SARS-CoV-2. Materials and Methods: We searched the PubMed, Web of Science, Embase, Cochrane Library, China National Knowledge Infrastructure Database (CNKI) to identify relevant articles up to July 9, 2021. Studies that assessed the effect of SARS-CoV-2 and influenza coinfection on disease outcomes or those with sufficient data to calculate risk factors were included. Risk effects were pooled using fixed or random effects model. Results: We ultimately identified 12 studies with 9,498 patients to evaluate the risk effects of SARS-CoV-2 and influenza coinfection on disease severity. Results indicated that coinfection was not significantly associated with mortality (OR = 0.85, 95%CI: 0.51, 1.43; p = 0.55, I 2 = 76.00%). However, mortality was found significantly decreased in the studies from China (OR = 0.51, 95%CI: 0.39, 0.68; I 2 = 26.50%), while significantly increased outside China (OR = 1.56, 95%CI: 1.12, 2.19; I 2 = 1.00%). Moreover, a lower risk for critical outcomes was detected among coinfection patients (OR = 0.64, 95%CI: 0.43, 0.97; p = 0.04, I 2 = 0.00%). Additionally, coinfection patients presented different laboratory indexes compared with the single SARS-CoV-2 infection, including lymphocyte counts and APTT. Conclusion: Our study revealed that coinfection with SARS-CoV-2 and influenza had no effect on overall mortality. However, risk for critical outcomes was lower in coinfection patients and different associations were detected in the studies from different regions and specific laboratory indexes. Further studies on influenza strains and the order of infection were warranted. Systematic testing for influenza coinfection in COVID-19 patients and influenza vaccination should be recommended.


Subject(s)
COVID-19 , Coinfection , Influenza, Human , Humans , Influenza, Human/complications , Influenza, Human/epidemiology , SARS-CoV-2 , Severity of Illness Index
3.
Crit Care ; 25(1): 390, 2021 11 15.
Article in English | MEDLINE | ID: covidwho-1518286

ABSTRACT

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a type of respiratory failure characterized by lung inflammation and pulmonary edema. Coronavirus disease 2019 (COVID-19) is associated with ARDS in the more severe cases. This study aimed to compare the specificity of the metabolic alterations induced by COVID-19 or Influenza A pneumonia (IAP) in ARDS. METHODS: Eighteen patients with ARDS due to COVID-19 and twenty patients with ARDS due to IAP, admitted to the intensive care unit. ARDS was defined as in the American-European Consensus Conference. As compared with patients with COVID-19, patients with IAP were younger and received more often noradrenaline to maintain a mean arterial pressure > 65 mm Hg. Serum samples were analyzed by Nuclear Magnetic Resonance Spectroscopy. Multivariate Statistical Analyses were used to identify metabolic differences between groups. Metabolic pathway analysis was performed to identify the most relevant pathways involved in ARDS development. RESULTS: ARDS due to COVID-19 or to IAP induces a different regulation of amino acids metabolism, lipid metabolism, glycolysis, and anaplerotic metabolism. COVID-19 causes a significant energy supply deficit that induces supplementary energy-generating pathways. In contrast, IAP patients suffer more marked inflammatory and oxidative stress responses. The classificatory model discriminated against the cause of pneumonia with a success rate of 100%. CONCLUSIONS: Our findings support the concept that ARDS is associated with a characteristic metabolomic profile that may discriminate patients with ARDS of different etiologies, being a potential biomarker for the diagnosis, prognosis, and management of this condition.


Subject(s)
COVID-19/metabolism , Influenza A Virus, H1N1 Subtype , Influenza, Human/metabolism , Respiratory Distress Syndrome/metabolism , Adult , Aged , COVID-19/complications , Female , Humans , Influenza, Human/complications , Male , Middle Aged , Respiratory Distress Syndrome/virology
4.
BMC Cardiovasc Disord ; 21(1): 528, 2021 11 08.
Article in English | MEDLINE | ID: covidwho-1505900

ABSTRACT

BACKGROUND: The value of mechanical circulatory support (MCS) in cardiogenic shock, especially the combination of the ECMELLA approach (Impella combined with ECMO), remains controversial. CASE PRESENTATION: A previously healthy 33-year-old female patient was submitted to a local emergency department with a flu-like infection and febrile temperatures up to 39 °C. The patient was tested positive for type-A influenza, however negative for SARS-CoV-2. Despite escalated invasive ventilation, refractory hypercapnia (paCO2: 22 kPa) with severe respiratory acidosis (pH: 6.9) and a rising norepinephrine rate occurred within a few hours. Due to a Horovitz-Index < 100, out-of-centre veno-venous extracorporeal membrane oxygenation (vv-ECMO)-implantation was performed. A CT-scan done because of anisocoria revealed an extended dissection of the right vertebral artery. While the initial left ventricular function was normal, echocardiography revealed severe global hypokinesia. After angiographic exclusion of coronary artery stenoses, we geared up LV unloading by additional implantation of an Impella CP and expanded the vv-ECMO to a veno-venous-arterial ECMO (vva-ECMO). Clinically relevant bleeding from the punctured femoral arteries resulted in massive transfusion and was treated by vascular surgery later on. Under continued MCS, LVEF increased to approximately 40% 2 days after the initiation of ECMELLA. After weaning, the Impella CP was explanted at day 5 and the vva-ECMO was removed on day 9, respectively. The patient was discharged in an unaffected neurological condition to rehabilitation 25 days after the initial admission. CONCLUSIONS: This exceptional case exemplifies the importance of aggressive MCS in severe cardiogenic shock, which may be especially promising in younger patients with non-ischaemic cardiomyopathy and potentially reversible causes of cardiogenic shock. This case impressively demonstrates that especially young patients may achieve complete neurological restoration, even though the initial prognosis may appear unfavourable.


Subject(s)
Extracorporeal Membrane Oxygenation/methods , Heart-Assist Devices , Influenza A virus/isolation & purification , Influenza, Human , Respiration, Artificial/methods , Respiratory Insufficiency , Ventricular Dysfunction, Left , Adult , COVID-19/diagnosis , Clinical Deterioration , Critical Care/methods , Echocardiography/methods , Female , Heart Failure/physiopathology , Heart Failure/therapy , Humans , Influenza, Human/complications , Influenza, Human/diagnosis , Influenza, Human/physiopathology , Respiratory Insufficiency/etiology , Respiratory Insufficiency/physiopathology , Respiratory Insufficiency/therapy , SARS-CoV-2 , Serologic Tests/methods , Severity of Illness Index , Shock, Cardiogenic/etiology , Shock, Cardiogenic/physiopathology , Shock, Cardiogenic/therapy , Treatment Outcome , Ventricular Dysfunction, Left/etiology , Ventricular Dysfunction, Left/physiopathology , Ventricular Dysfunction, Left/therapy
5.
BMJ Open ; 11(10): e055435, 2021 10 22.
Article in English | MEDLINE | ID: covidwho-1480255

ABSTRACT

OBJECTIVES: The steroid hormone vitamin D has roles in immunomodulation and bone health. Insufficiency is associated with susceptibility to respiratory infections. We report 25-hydroxy vitamin D (25(OH)D) measurements in hospitalised people with COVID-19 and influenza A and in survivors of critical illness to test the hypotheses that vitamin D insufficiency scales with illness severity and persists in survivors. DESIGN: Cross-sectional study. SETTING AND PARTICIPANTS: Plasma was obtained from 295 hospitalised people with COVID-19 (International Severe Acute Respiratory and emerging Infections Consortium (ISARIC)/WHO Clinical Characterization Protocol for Severe Emerging Infections UK study), 93 with influenza A (Mechanisms of Severe Acute Influenza Consortium (MOSAIC) study, during the 2009-2010 H1N1 pandemic) and 139 survivors of non-selected critical illness (prior to the COVID-19 pandemic). Total 25(OH)D was measured by liquid chromatography-tandem mass spectrometry. Free 25(OH)D was measured by ELISA in COVID-19 samples. OUTCOME MEASURES: Receipt of invasive mechanical ventilation (IMV) and in-hospital mortality. RESULTS: Vitamin D insufficiency (total 25(OH)D 25-50 nmol/L) and deficiency (<25 nmol/L) were prevalent in COVID-19 (29.3% and 44.4%, respectively), influenza A (47.3% and 37.6%) and critical illness survivors (30.2% and 56.8%). In COVID-19 and influenza A, total 25(OH)D measured early in illness was lower in patients who received IMV (19.6 vs 31.9 nmol/L (p<0.0001) and 22.9 vs 31.1 nmol/L (p=0.0009), respectively). In COVID-19, biologically active free 25(OH)D correlated with total 25(OH)D and was lower in patients who received IMV, but was not associated with selected circulating inflammatory mediators. CONCLUSIONS: Vitamin D deficiency/insufficiency was present in majority of hospitalised patients with COVID-19 or influenza A and correlated with severity and persisted in critical illness survivors at concentrations expected to disrupt bone metabolism. These findings support early supplementation trials to determine if insufficiency is causal in progression to severe disease, and investigation of longer-term bone health outcomes.


Subject(s)
COVID-19 , Influenza A Virus, H1N1 Subtype , Influenza, Human , Vitamin D Deficiency , Critical Illness , Cross-Sectional Studies , Humans , Influenza, Human/complications , Influenza, Human/epidemiology , Pandemics , SARS-CoV-2 , Survivors , Vitamin D , Vitamin D Deficiency/complications , Vitamin D Deficiency/epidemiology
6.
Signal Transduct Target Ther ; 6(1): 367, 2021 10 20.
Article in English | MEDLINE | ID: covidwho-1475287

ABSTRACT

Cytokine release syndrome (CRS) embodies a mixture of clinical manifestations, including elevated circulating cytokine levels, acute systemic inflammatory symptoms and secondary organ dysfunction, which was first described in the context of acute graft-versus-host disease after allogeneic hematopoietic stem-cell transplantation and was later observed in pandemics of influenza, SARS-CoV and COVID-19, immunotherapy of tumor, after chimeric antigen receptor T (CAR-T) therapy, and in monogenic disorders and autoimmune diseases. Particularly, severe CRS is a very significant and life-threatening complication, which is clinically characterized by persistent high fever, hyperinflammation, and severe organ dysfunction. However, CRS is a double-edged sword, which may be both helpful in controlling tumors/viruses/infections and harmful to the host. Although a high incidence and high levels of cytokines are features of CRS, the detailed kinetics and specific mechanisms of CRS in human diseases and intervention therapy remain unclear. In the present review, we have summarized the most recent advances related to the clinical features and management of CRS as well as cutting-edge technologies to elucidate the mechanisms of CRS. Considering that CRS is the major adverse event in human diseases and intervention therapy, our review delineates the characteristics, kinetics, signaling pathways, and potential mechanisms of CRS, which shows its clinical relevance for achieving both favorable efficacy and low toxicity.


Subject(s)
Cytokine Release Syndrome , Signal Transduction/immunology , Acute Disease , Autoimmune Diseases/complications , Autoimmune Diseases/immunology , Autoimmune Diseases/therapy , COVID-19/complications , COVID-19/immunology , COVID-19/therapy , Cytokine Release Syndrome/etiology , Cytokine Release Syndrome/immunology , Cytokine Release Syndrome/therapy , Graft vs Host Disease/complications , Graft vs Host Disease/immunology , Graft vs Host Disease/therapy , Hematopoietic Stem Cell Transplantation , Humans , Immunotherapy, Adoptive/adverse effects , Influenza, Human/complications , Influenza, Human/immunology , Neoplasms/complications , Neoplasms/immunology , Neoplasms/therapy , SARS Virus/immunology , SARS-CoV-2/immunology , Severe Acute Respiratory Syndrome/complications , Severe Acute Respiratory Syndrome/immunology , Severe Acute Respiratory Syndrome/therapy
8.
BMC Infect Dis ; 21(1): 954, 2021 Sep 15.
Article in English | MEDLINE | ID: covidwho-1411524

ABSTRACT

BACKGROUND: In Poland, little is known about the most serious cases of influenza that need admittance to the intensive care unit (ICU), as well as the use of extracorporeal respiratory support. METHODS: This was an electronic survey comprising ICUs in two administrative regions of Poland. The aim of the study was to determine the number of influenza patients with respiratory failure admitted to the ICU in the autumn-winter season of 2018/2019. Furthermore, respiratory support, outcome and other pathogens detected in the airways were investigated. RESULTS: Influenza infection was confirmed in 76 patients. The A(H1N1)pdm09 strain was the most common. 34 patients died (44.7%). The median age was 62 years, the median sequential organ failure assessment (SOFA) score was 11 and was higher in patients who died (12 vs. 10, p = 0.017). Mechanical ventilation was used in 75 patients and high flow nasal oxygen therapy in 1 patient. Extracorporeal membrane oxygenation (ECMO) was used in 7 patients (6 survived), and extracorporeal carbon dioxide removal (ECCO2R) in 2 (1 survived). The prone position was used in 16 patients. In addition, other pathogens were detected in the airways on admittance to the ICU. CONCLUSION: A substantial number of influenza infections occurred in the autumn-winter season of 2018/2019 that required costly treatment in the intensive care units. Upon admission to the ICU, influenza patients had a high degree of organ failure as assessed by the SOFA score, and the mortality rate was 44.7%. Advanced extracorporeal respiratory techniques offer real survival opportunities to patients with severe influenza-related ARDS. The presence of coinfection should be considered in patients with influenza and respiratory failure.


Subject(s)
Influenza A Virus, H1N1 Subtype , Influenza, Human , Respiratory Distress Syndrome , Respiratory Insufficiency , Humans , Infant, Newborn , Influenza, Human/complications , Influenza, Human/epidemiology , Intensive Care Units , Poland/epidemiology , Respiration, Artificial , Respiratory Insufficiency/epidemiology , Respiratory Insufficiency/therapy
9.
Sci Rep ; 11(1): 19713, 2021 10 05.
Article in English | MEDLINE | ID: covidwho-1454811

ABSTRACT

The novel coronavirus disease 2019 (COVID-19) presents with non-specific clinical features. This may result in misdiagnosis or delayed diagnosis, and lead to further transmission in the community. We aimed to derive early predictors to differentiate COVID-19 from influenza and dengue. The study comprised 126 patients with COVID-19, 171 with influenza and 180 with dengue, who presented within 5 days of symptom onset. All cases were confirmed by reverse transcriptase polymerase chain reaction tests. We used logistic regression models to identify demographics, clinical characteristics and laboratory markers in classifying COVID-19 versus influenza, and COVID-19 versus dengue. The performance of each model was evaluated using receiver operating characteristic (ROC) curves. Shortness of breath was the strongest predictor in the models for differentiating between COVID-19 and influenza, followed by diarrhoea. Higher lymphocyte count was predictive of COVID-19 versus influenza and versus dengue. In the model for differentiating between COVID-19 and dengue, patients with cough and higher platelet count were at increased odds of COVID-19, while headache, joint pain, skin rash and vomiting/nausea were indicative of dengue. The cross-validated area under the ROC curve for all four models was above 0.85. Clinical features and simple laboratory markers for differentiating COVID-19 from influenza and dengue are identified in this study which can be used by primary care physicians in resource limited settings to determine if further investigations or referrals would be required.


Subject(s)
COVID-19/pathology , Dengue/pathology , Influenza, Human/pathology , Adult , Area Under Curve , COVID-19/complications , COVID-19/virology , Cohort Studies , Dengue/complications , Dengue/virology , Diagnosis, Differential , Diarrhea/etiology , Female , Fever/etiology , Humans , Influenza, Human/complications , Influenza, Human/virology , Lymphocyte Count , Male , Middle Aged , Platelet Count , RNA, Viral/analysis , RNA, Viral/metabolism , ROC Curve , SARS-CoV-2/genetics , SARS-CoV-2/isolation & purification , Vomiting/etiology , Young Adult
10.
PLoS Med ; 18(9): e1003773, 2021 09.
Article in English | MEDLINE | ID: covidwho-1440981

ABSTRACT

BACKGROUND: Long-COVID refers to a variety of symptoms affecting different organs reported by people following Coronavirus Disease 2019 (COVID-19) infection. To date, there have been no robust estimates of the incidence and co-occurrence of long-COVID features, their relationship to age, sex, or severity of infection, and the extent to which they are specific to COVID-19. The aim of this study is to address these issues. METHODS AND FINDINGS: We conducted a retrospective cohort study based on linked electronic health records (EHRs) data from 81 million patients including 273,618 COVID-19 survivors. The incidence and co-occurrence within 6 months and in the 3 to 6 months after COVID-19 diagnosis were calculated for 9 core features of long-COVID (breathing difficulties/breathlessness, fatigue/malaise, chest/throat pain, headache, abdominal symptoms, myalgia, other pain, cognitive symptoms, and anxiety/depression). Their co-occurrence network was also analyzed. Comparison with a propensity score-matched cohort of patients diagnosed with influenza during the same time period was achieved using Kaplan-Meier analysis and the Cox proportional hazard model. The incidence of atopic dermatitis was used as a negative control. Among COVID-19 survivors (mean [SD] age: 46.3 [19.8], 55.6% female), 57.00% had one or more long-COVID feature recorded during the whole 6-month period (i.e., including the acute phase), and 36.55% between 3 and 6 months. The incidence of each feature was: abnormal breathing (18.71% in the 1- to 180-day period; 7.94% in the 90- to180-day period), fatigue/malaise (12.82%; 5.87%), chest/throat pain (12.60%; 5.71%), headache (8.67%; 4.63%), other pain (11.60%; 7.19%), abdominal symptoms (15.58%; 8.29%), myalgia (3.24%; 1.54%), cognitive symptoms (7.88%; 3.95%), and anxiety/depression (22.82%; 15.49%). All 9 features were more frequently reported after COVID-19 than after influenza (with an overall excess incidence of 16.60% and hazard ratios between 1.44 and 2.04, all p < 0.001), co-occurred more commonly, and formed a more interconnected network. Significant differences in incidence and co-occurrence were associated with sex, age, and illness severity. Besides the limitations inherent to EHR data, limitations of this study include that (i) the findings do not generalize to patients who have had COVID-19 but were not diagnosed, nor to patients who do not seek or receive medical attention when experiencing symptoms of long-COVID; (ii) the findings say nothing about the persistence of the clinical features; and (iii) the difference between cohorts might be affected by one cohort seeking or receiving more medical attention for their symptoms. CONCLUSIONS: Long-COVID clinical features occurred and co-occurred frequently and showed some specificity to COVID-19, though they were also observed after influenza. Different long-COVID clinical profiles were observed based on demographics and illness severity.


Subject(s)
COVID-19/complications , Survivors , Adult , Aged , COVID-19/epidemiology , Cohort Studies , Dyspnea/epidemiology , Dyspnea/etiology , Fatigue/epidemiology , Fatigue/etiology , Female , Gastrointestinal Diseases/epidemiology , Gastrointestinal Diseases/etiology , Humans , Incidence , Influenza, Human/complications , Influenza, Human/epidemiology , Male , Mental Disorders/epidemiology , Mental Disorders/etiology , Middle Aged , Pain/epidemiology , Pain/etiology , Proportional Hazards Models , Retrospective Studies , SARS-CoV-2 , Severity of Illness Index , United States/epidemiology , Young Adult
11.
Respir Investig ; 59(6): 748-756, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1392540

ABSTRACT

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is a valuable rescue therapy to treat refractory hypoxemia caused by influenza. The present meta-analysis aimed to compare the clinical characteristics and outcomes of ECMO between COVID-19 and influenza. METHODS: We searched the PubMed, Cochrane Library, SCOPUS, and Web of Science databases from inception to May 1, 2021. The included studies compared the clinical characteristics and outcomes of ECMO between adults with COVID-19 and those with influenza. RESULTS: The study included four retrospective cohorts involving a total of 129 patients with COVID-19 and 140 with influenza who were treated using ECMO. Clinical characteristics were similar between the COVID-19 and influenza groups, including body mass index (BMI), diabetes mellitus, hypertension, and immunocompromised status. A higher proportion of patients with COVID-19 on ECMO were male (75.9% vs. 62.9%; P = 0.04). There was no difference between the groups in terms of illness severity based on sequential organ failure assessment (SOFA) score or serum pH. Patients with COVID-19 had a longer mean duration of mechanical ventilation before ECMO (6.63 vs. 3.38 days; P < 0.01). The pooled mortality rate was 43.8%. The mean ECMO duration (14.13 vs. 12.55 days; P = 0.25) and mortality rate (42.6% vs. 45.0%; P = 0.99) were comparable between the groups. CONCLUSION: Clinical characteristics, ECMO duration, and mortality were comparable between patients with COVID-19 and those with influenza who required ECMO to treat refractory hypoxemia. The duration of mechanical ventilation before ECMO did not influence outcomes. Patients with COVID-19 benefit from ECMO salvage therapy similarly to those with influenza.


Subject(s)
COVID-19/complications , Extracorporeal Membrane Oxygenation/adverse effects , Influenza, Human/complications , Pneumonia/therapy , Respiratory Distress Syndrome/therapy , COVID-19/therapy , Humans , Influenza, Human/therapy , Intensive Care Units , Pandemics , Respiratory Distress Syndrome/etiology , SARS-CoV-2 , Treatment Outcome
12.
Pediatrics ; 148(3)2021 09.
Article in English | MEDLINE | ID: covidwho-1394618

ABSTRACT

OBJECTIVES: To characterize the demographics, comorbidities, symptoms, in-hospital treatments, and health outcomes among children and adolescents diagnosed or hospitalized with coronavirus disease 2019 (COVID-19) and to compare them in secondary analyses with patients diagnosed with previous seasonal influenza in 2017-2018. METHODS: International network cohort using real-world data from European primary care records (France, Germany, and Spain), South Korean claims and US claims, and hospital databases. We included children and adolescents diagnosed and/or hospitalized with COVID-19 at age <18 between January and June 2020. We described baseline demographics, comorbidities, symptoms, 30-day in-hospital treatments, and outcomes including hospitalization, pneumonia, acute respiratory distress syndrome, multisystem inflammatory syndrome in children, and death. RESULTS: A total of 242 158 children and adolescents diagnosed and 9769 hospitalized with COVID-19 and 2 084 180 diagnosed with influenza were studied. Comorbidities including neurodevelopmental disorders, heart disease, and cancer were more common among those hospitalized with versus diagnosed with COVID-19. Dyspnea, bronchiolitis, anosmia, and gastrointestinal symptoms were more common in COVID-19 than influenza. In-hospital prevalent treatments for COVID-19 included repurposed medications (<10%) and adjunctive therapies: systemic corticosteroids (6.8%-7.6%), famotidine (9.0%-28.1%), and antithrombotics such as aspirin (2.0%-21.4%), heparin (2.2%-18.1%), and enoxaparin (2.8%-14.8%). Hospitalization was observed in 0.3% to 1.3% of the cohort diagnosed with COVID-19, with undetectable (n < 5 per database) 30-day fatality. Thirty-day outcomes including pneumonia and hypoxemia were more frequent in COVID-19 than influenza. CONCLUSIONS: Despite negligible fatality, complications including hospitalization, hypoxemia, and pneumonia were more frequent in children and adolescents with COVID-19 than with influenza. Dyspnea, anosmia, and gastrointestinal symptoms could help differentiate diagnoses. A wide range of medications was used for the inpatient management of pediatric COVID-19.


Subject(s)
COVID-19 , Adolescent , Age Distribution , COVID-19/complications , COVID-19/diagnosis , COVID-19/drug therapy , COVID-19/epidemiology , Child , Child, Preschool , Cohort Studies , Comorbidity , Databases, Factual , Diagnosis, Differential , Female , France/epidemiology , Germany/epidemiology , Hospitalization/statistics & numerical data , Humans , Infant , Infant, Newborn , Influenza, Human/complications , Influenza, Human/diagnosis , Influenza, Human/epidemiology , Male , Republic of Korea/epidemiology , Spain/epidemiology , Symptom Assessment , Time Factors , Treatment Outcome , United States/epidemiology
14.
Viruses ; 13(7)2021 07 04.
Article in English | MEDLINE | ID: covidwho-1389550

ABSTRACT

Amino acids have been implicated with virus infection and replication. Here, we demonstrate the effects of two basic amino acids, arginine and lysine, and their ester derivatives on infection of two enveloped viruses, SARS-CoV-2, and influenza A virus. We found that lysine and its ester derivative can efficiently block infection of both viruses in vitro. Furthermore, the arginine ester derivative caused a significant boost in virus infection. Studies on their mechanism of action revealed that the compounds potentially disturb virus uncoating rather than virus attachment and endosomal acidification. Our findings suggest that lysine supplementation and the reduction of arginine-rich food intake can be considered as prophylactic and therapeutic regimens against these viruses while also providing a paradigm for the development of broad-spectrum antivirals.


Subject(s)
Amino Acids, Basic/pharmacology , COVID-19/drug therapy , Influenza A virus/drug effects , Influenza, Human/drug therapy , SARS-CoV-2/drug effects , A549 Cells , Amino Acids, Basic/chemistry , Angiotensin-Converting Enzyme 2/metabolism , Antiviral Agents/pharmacology , COVID-19/complications , COVID-19/prevention & control , COVID-19/virology , HEK293 Cells , Humans , Influenza, Human/complications , Influenza, Human/prevention & control , Influenza, Human/virology , SARS-CoV-2/metabolism , Spike Glycoprotein, Coronavirus/metabolism , Virus Attachment/drug effects , Virus Replication/drug effects
16.
Front Immunol ; 12: 720363, 2021.
Article in English | MEDLINE | ID: covidwho-1376702

ABSTRACT

Severe coronavirus disease 2019 (COVID-19) can manifest as a viral-induced hyperinflammation with multiorgan dysfunction. It has been documented that severe COVID-19 is associated with higher levels of inflammatory mediators than a mild disease, and tracking these markers may allow early identification or even prediction of disease progression. It is well known that C-reactive protein (CRP) is the acute-phase protein and the active regulator of host innate immunity, which is highly predictive of the need for mechanical ventilation and may guide escalation of treatment of COVID-19-related uncontrolled inflammation. There are numerous causes of an elevated CRP, including acute and chronic responses, and these can be infectious or non-infectious in etiology. CRP are normally lacking in viral infections, while adaptive immunity appears to be essential for COVID-19 virus clearance, and the macrophage activation syndrome may explain the high serum CRP contents and contribute to the disease progression. Nevertheless, for the assessment of host inflammatory status and identification of viral infection in other pathologies, such as bacterial sepsis, the acute-phase proteins, including CRP and procalcitonin, can provide more important information for guiding clinical diagnosis and antibiotic therapy. This review is aimed to highlight the current and most recent studies with regard to the clinical significance of CRP in severe COVID-19 and other viral associated illnesses, including update advances on the implication of CRP and its form specifically on the pathogenesis of these diseases. The progressive understanding in these areas may be translated into promising measures to prevent severe outcomes and mitigate appropriate treatment modalities in critical COVID-19 and other viral infections.


Subject(s)
C-Reactive Protein/metabolism , COVID-19/blood , COVID-19/complications , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/complications , Humans , Inflammation/blood , Influenza A Virus, H1N1 Subtype , Influenza, Human/blood , Influenza, Human/complications , Stroke/blood , Virus Diseases
17.
Front Immunol ; 12: 716075, 2021.
Article in English | MEDLINE | ID: covidwho-1359192

ABSTRACT

The existence of asymptomatic and re-detectable positive coronavirus disease 2019 (COVID-19) patients presents the disease control challenges of COVID-19. Most studies on immune responses in COVID-19 have focused on moderately or severely symptomatic patients; however, little is known about the immune response in asymptomatic and re-detectable positive (RP) patients. Here we performed a comprehensive analysis of the transcriptomic profiles of peripheral blood mononuclear cells (PBMCs) from 48 COVID-19 patients which included 8 asymptomatic, 13 symptomatic, 15 recovered and 12 RP patients. The weighted gene co-expression network analysis (WGCNA) identified six co-expression modules, of which the turquoise module was positively correlated with the asymptomatic, symptomatic, and recovered COVID-19 patients. The red module positively correlated with symptomatic patients only and the blue and brown modules positively correlated with the RP patients. The analysis by single sample gene set enrichment analysis (ssGSEA) revealed a lower level of IFN response and complement activation in the asymptomatic patients compared with the symptomatic, indicating a weaker immune response of the PBMCs in the asymptomatic patients. In addition, gene set enrichment analysis (GSEA) analysis showed the enrichment of TNFα/NF-κB and influenza infection in the RP patients compared with the recovered patients, indicating a hyper-inflammatory immune response in the PBMC of RP patients. Thus our findings could extend our understanding of host immune response during the progression of COVID-19 disease and assist clinical management and the immunotherapy development for COVID-19.


Subject(s)
Asymptomatic Diseases , COVID-19/immunology , Carrier State/immunology , Leukocytes, Mononuclear/immunology , SARS-CoV-2/immunology , Transcriptome/genetics , Adult , Carrier State/virology , Complement Activation/immunology , Female , Gene Expression Profiling , Humans , Inflammation/immunology , Influenza, Human/complications , Interferons/blood , Interferons/immunology , Male , Middle Aged , NF-kappa B/metabolism , Transcriptome/immunology , Tumor Necrosis Factor-alpha/metabolism , Young Adult
18.
J Card Surg ; 36(10): 3740-3746, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1348154

ABSTRACT

PURPOSE: Extracorporeal membrane oxygenation (ECMO) is a refractory treatment for acute respiratory distress syndrome (ARDS) due to influenza and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, also referred to as coronavirus disease 2019 [COVID-19]). We conducted this study to compare the outcomes of influenza patients treated with veno-venous-ECMO (VV-ECMO) to COVID-19 patients treated with VV-ECMO, during the first wave of COVID-19. METHODS: Patients in our institution with ARDS due to COVID-19 or influenza who were placed on ECMO between August 1, 2010 and September 15, 2020 were included in this comparative, retrospective study. To improve homogeneity, only VV-ECMO patients were analyzed. The clinical characteristics and outcomes were extracted and analyzed. RESULTS: A total of 28 COVID-19 patients and 17 influenza patients were identified and included. ECMO survival rates were 68% (19/28) in COVID-19 patients and 94% (16/17) in influenza patients (p = .04). Thirty days survival rates after ECMO decannulation were 54% (15/28) in COVID-19 patients and 76% (13/17) in influenza patients (p = .13). COVID-19 patients spent a longer time on ECMO compared to flu patients (21 vs. 12 days; p = .025), and more COVID-19 patients (26/28 vs. 2/17) were on immunomodulatory therapy before ECMO initiation (p < .001). COVID-19 patients had higher rates of new infections during ECMO (50% vs. 18%; p = .03) and bacterial pneumonia (36% vs. 6%; p = .024). CONCLUSIONS: COVID-19 patients who were treated in our institution with VV-ECMO had statistically lower ECMO survival rates than influenza patients. It is possible that COVID-19 immunomodulation therapies may increase the risk of other superimposed infections.


Subject(s)
COVID-19 , Extracorporeal Membrane Oxygenation , Influenza, Human , Humans , Influenza, Human/complications , Influenza, Human/therapy , Retrospective Studies , SARS-CoV-2
19.
Am J Cardiol ; 159: 129-137, 2021 Nov 15.
Article in English | MEDLINE | ID: covidwho-1347476

ABSTRACT

During the clinical care of hospitalized patients with COVID-19, diminished QRS amplitude on the surface electrocardiogram (ECG) was observed to precede clinical decompensation, culminating in death. This prompted investigation into the prognostic utility and specificity of low QRS complex amplitude (LoQRS) in COVID-19. We retrospectively analyzed consecutive adults admitted to a telemetry service with SARS-CoV-2 (n = 140) or influenza (n = 281) infection with a final disposition-death or discharge. LoQRS was defined as a composite of QRS amplitude <5 mm or <10 mm in the limb or precordial leads, respectively, or a ≥50% decrease in QRS amplitude on follow-up ECG during hospitalization. LoQRS was more prevalent in patients with COVID-19 than influenza (24.3% vs 11.7%, p = 0.001), and in patients who died than survived with either COVID-19 (48.1% vs 10.2%, p <0.001) or influenza (38.9% vs 9.9%, p <0.001). LoQRS was independently associated with mortality in patients with COVID-19 when adjusted for baseline clinical variables (odds ratio [OR] 11.5, 95% confidence interval [CI] 3.9 to 33.8, p <0.001), presenting and peak troponin, D-dimer, C-reactive protein, albumin, intubation, and vasopressor requirement (OR 13.8, 95% CI 1.3 to 145.5, p = 0.029). The median time to death in COVID-19 from the first ECG with LoQRS was 52 hours (interquartile range 18 to 130). Dynamic QRS amplitude diminution is a strong independent predictor of death over not only the course of COVID-19 infection, but also influenza infection. In conclusion, this finding may serve as a pragmatic prognostication tool reflecting evolving clinical changes during hospitalization, over a potentially actionable time interval for clinical reassessment.


Subject(s)
Arrhythmias, Cardiac/physiopathology , Arrhythmias, Cardiac/virology , COVID-19/complications , Electrocardiography , Influenza, Human/complications , Pneumonia, Viral/complications , Aged , COVID-19/mortality , Female , Hospital Mortality , Hospitalization , Humans , Influenza, Human/mortality , Male , Middle Aged , New York City/epidemiology , Pneumonia, Viral/mortality , Pneumonia, Viral/virology , Prognosis , Retrospective Studies , SARS-CoV-2
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