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1.
Int J Mol Sci ; 23(21)2022 Oct 31.
Article in English | MEDLINE | ID: covidwho-2099576

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces immune-mediated type 1 interferon (IFN-1) production, the pathophysiology of which involves sterile alpha motif and histidine-aspartate domain-containing protein 1 (SAMHD1) tetramerization and the cytosolic DNA sensor cyclic-GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway. As a result, type I interferonopathies are exacerbated. Aspirin inhibits cGAS-mediated signaling through cGAS acetylation. Acetylation contributes to cGAS activity control and activates IFN-1 production and nuclear factor-κB (NF-κB) signaling via STING. Aspirin and dapsone inhibit the activation of both IFN-1 and NF-κB by targeting cGAS. We define these as anticatalytic mechanisms. It is necessary to alleviate the pathologic course and take the lag time of the odds of achieving viral clearance by day 7 to coordinate innate or adaptive immune cell reactions.


Subject(s)
COVID-19 , Interferon Type I , Humans , COVID-19/drug therapy , Acetylation , NF-kappa B/metabolism , Drug Repositioning , Membrane Proteins/metabolism , SARS-CoV-2 , Nucleotidyltransferases/metabolism , Interferon Type I/metabolism , Aspirin , Immunity, Innate/genetics
2.
J Korean Med Sci ; 37(42): e303, 2022 Oct 31.
Article in English | MEDLINE | ID: covidwho-2099099

ABSTRACT

BACKGROUND: The risk of severe outcomes with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) delta variant remains low in children and adolescents, but less is known about its effect on the SARS-CoV-2-naïve population. This study evaluated clinical manifestations and risk factors for moderate-to-critical coronavirus disease 2019 (COVID-19) in mostly SARS-CoV-2-naïve children and adolescents in 2021. METHODS: This multicenter retrospective study included patients aged 0-18 years who were hospitalized with COVID-19 at 8 referring hospitals in South Korea during the predelta-predominant and delta-predominant periods in 2021. Each case was labeled as either hospitalization with medical needs or for isolation. Severity was categorized as mild, moderate, severe, or critical with regard to pneumonia presence and illness severity. RESULTS: Among 753 cases, most (99.5%) had no prior history of COVID-19 or vaccination against COVID-19. The proportions of hospitalization with medical needs (3.5% vs. 19.7%), moderate illness (0.9% vs. 4.0%), and severe/critical illness (0.8% vs. 5.3%) increased during delta predominance. The risk of moderate-to-critical COVID-19 among hospitalizations with medical needs was higher among patients aged 12-18 years (adjusted odds ratio [aOR], 4.1; 95% confidence interval [CI], 1.5-11.8) and with obesity (aOR, 6.9; 95% CI, 2.4-19.6) but not among patients infected during delta predominance. However, children with obesity experienced more severe COVID-19 during delta predominance (aOR, 6.1; 95% CI, 1.2-29.6). CONCLUSION: Despite its similar severity among most SARS-CoV-2-naïve children and adolescents, the delta variant may affect COVID-19 severity in those with high-risk underlying medical conditions. Underlying conditions, particularly obesity, may cause severe COVID-19 in children and adolescents, warranting strong consideration for vaccinating high-risk children.


Subject(s)
COVID-19 , SARS-CoV-2 , Child , Humans , Adolescent , Retrospective Studies , Hospitalization , Obesity/complications , Obesity/epidemiology
3.
Emerg Infect Dis ; 28(12)2022 Nov 02.
Article in English | MEDLINE | ID: covidwho-2099066

ABSTRACT

We report results from serologic surveillance for exposure to SARS-CoV-2 among 1,237 wild rodents and small mammals across Europe. All samples were negative, with the possible exception of 1. Despite suspected potential for human-to-rodent spillover, no evidence of widespread SARS-CoV-2 circulation in rodent populations has been reported to date.Esitämme tulokset serologisesta tutkimuksesta, jossa seulottiin SARS-CoV-2 tartuntojen varalta 1,237 luonnonvaraista jyrsijää ja piennisäkästä eri puolilta Eurooppaa. Kaikki näytteet olivat negatiivisia, yhtä näytettä lukuun ottamatta. SARS-CoV-2:n läikkymisen ihmisistä jyrsijöihin on arveltu olevan mahdollista, mutta todisteet viruksen laajamittaisesta leviämisestä jyrsijäpopulaatioissa puuttuvat.

4.
Emerg Infect Dis ; 28(12)2022 Nov 02.
Article in English | MEDLINE | ID: covidwho-2099065

ABSTRACT

We investigated a cluster of SARS-CoV-2 infections in a quarantine hotel in Taiwan in December 2021. The cluster involved 3 case patients who lived in nonadjacent rooms on different floors. They had no direct contact during their stay. By direct exploration of the space above the room ceilings, we found residual tunnels, wall defects, and truncated pipes between their rooms. We conducted a simplified tracer-gas experiment to assess the interconnection between rooms. Aerosol transmission through structural defects in floors and walls in this poorly ventilated hotel was the most likely route of virus transmission. This event demonstrates the high transmissibility of Omicron variants, even across rooms and floors, through structural defects. Our findings emphasize the importance of ventilation and integrity of building structure in quarantine facilities.

5.
BMC Ecol Evol ; 22(1): 123, 2022 10 28.
Article in English | MEDLINE | ID: covidwho-2098309

ABSTRACT

The genome of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) contains many insertions/deletions (indels) from the genomes of other SARS-related coronaviruses. Some of the identified indels have recently reported to involve relatively long segments of 10-300 consecutive bases and with diverse RNA sequences around gaps between virus species, both of which are different characteristics from the classical shorter in-frame indels. These non-classical complex indels have been identified in non-structural protein 3 (Nsp3), the S1 domain of the spike (S), and open reading frame 8 (ORF8). To determine whether the occurrence of these non-classical indels in specific genomic regions is ubiquitous among broad species of SARS-related coronaviruses in different animal hosts, the present study compared SARS-related coronaviruses from humans (SARS-CoV and SARS-CoV-2), bats (RaTG13 and Rc-o319), and pangolins (GX-P4L), by performing multiple sequence alignment. As a result, indel hotspots with diverse RNA sequences of different lengths between the viruses were confirmed in the Nsp2 gene (approximately 2500-2600 base positions in the overall 29,900 bases), Nsp3 gene (approximately 3000-3300 and 3800-3900 base positions), N-terminal domain of the spike protein (21,500-22,500 base positions), and ORF8 gene (27,800-28,200 base positions). Abnormally high rate of point mutations and complex indels in these regions suggest that the occurrence of mutations in these hotspots may be selectively neutral or even benefit the survival of the viruses. The presence of such indel hotspots has not been reported in different human SARS-CoV-2 strains in the last 2 years, suggesting a lower rate of indels in human SARS-CoV-2. Future studies to elucidate the mechanisms enabling the frequent development of long and complex indels in specific genomic regions of SARS-related coronaviruses would offer deeper insights into the process of viral evolution.


Subject(s)
COVID-19 , Chiroptera , SARS Virus , Animals , Humans , Open Reading Frames/genetics , SARS-CoV-2/genetics , Genome, Viral/genetics , SARS Virus/genetics , Evolution, Molecular , Phylogeny , COVID-19/genetics , Chiroptera/genetics , Pangolins
6.
Int J Rheum Dis ; 2022 Oct 29.
Article in English | MEDLINE | ID: covidwho-2097675

ABSTRACT

COVID-19 remains a life-threatening infectious disease worldwide. Several bio-active agents have been tested and evaluated in an effort to contain this disease. Unfortunately, none of the therapies have been successful, owing to their safety concerns and the presence of various adverse effects. Various countries have developed vaccines as a preventive measure; however, they have not been widely accepted as effective strategies. The virus has proven to be exceedingly contagious and lethal, so finding an effective treatment strategy has been a top priority in medical research. The significance of vitamin D in influencing many components of the innate and adaptive immune systems is examined in this study. This review aims to summarize the research on the use of vitamin D for COVID-19 treatment and prevention. Vitamin D supplementation has now become an efficient option to boost the immune response for all ages in preventing the spread of infection. Vitamin D is an immunomodulator that treats infected lung tissue by improving innate and adaptive immune responses and downregulating the inflammatory cascades. The preventive action exerted by vitamin D supplementation (at a specific dose) has been accepted by several observational research investigations and clinical trials on the avoidance of viral and acute respiratory dysfunctions. To assess the existing consensus about vitamin D supplementation as a strategy to treat and prevent the development and progression of COVID-19 disease, this review intends to synthesize the evidence around vitamin D in relation to COVID-19 infection.

7.
ACS Applied Polymer Materials ; JOUR
Article in English | Web of Science | ID: covidwho-2096627

ABSTRACT

Surface dielectric barrier discharge (SDBD) was used to inactivate the infectious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) trapped in a polypropylene (PP) melt-blown filter. We used a dielectric barrier made of polyimide films with hexagonal holes through which air flowed. In a cylindrical wind tunnel, the SDBD device supplied reactive oxygen species such as ozone to the SARS-CoV-2 trapped in the PP filter. A plaque assay showed that SDBD at an ozone concentration of approximately 51.6 ppm and exposure time of 30 min induced more than 99.78% reduction for filter-adhered SARS-CoV-2. A carbon catalyst after SDBD effectively reduced ozone exhaust below 0.05 ppm. The combination of SDBD, PP filter, and catalyst could be a promising way to decrease the risk of secondary infection due to indoor air purifiers.

8.
J Pharm Sci ; 2022 Nov 02.
Article in English | MEDLINE | ID: covidwho-2096154

ABSTRACT

The COVID-19 pandemic outbreak has been overwhelming the healthcare system worldwide. A rapidly growing number of younger pediatric patients in Thailand necessitated the formulation of favipiravir, the most locally accessible antiviral agent against COVID-19, into a child-friendly dosage form as a safer alternative to a dispersion of crushed tablets in simple syrup. While striving to quickly develop a liquid formulation that is feasible for any local hospital production units, an oral solution was chosen due to its simplicity. Despite the large dose and poor aqueous solubility of favipiravir, a combination of pH control and use of poloxamer as a solubilizing agent has enabled us to streamline the manufacturing process of a 200 mg/15 mL oral solution for hospital compounding. To ensure its efficacy and safety, a specification for quality control was also established in accordance with the ICH quality guidelines and USP. The finished product stability was subsequently demonstrated under the conditions of 5°C ± 3°C, 25°C ± 2°C/75% RH ± 5% RH, 30°C ± 2°C/75% RH ± 5% RH, and 40°C ± 2°C/75% RH ± 5% RH. The results indicated that our formulation can be stored at 30°C ± 2°C/75% RH for 30 days, which will very well serve the need to allow drug distribution and patient use during the crisis, while the shelf-life can be extended to 60 days when stored at 5°C ± 3°C. Thus, accessibility to an essential medical treatment has been successfully enhanced for pediatric patients in Thailand and neighboring countries during the COVID-19 outbreak.

9.
JTCVS Open ; 2022 Sep 08.
Article in English | MEDLINE | ID: covidwho-2096151

ABSTRACT

Objective: The COVID -19 pandemic presents a high mortality rate amongst patients who develop severe acute respiratory distress syndrome (ARDS). The purpose of this study was to evaluate the outcomes of venovenous ECMO in COVID-19-related ARDS and identify the patients that benefit the most from this procedure. Methods: Adult COVID-19 patients with severe ARDS requiring VV-ECMO support at four academic insititutions between March and October 2020 were included. Data were collected through retrospective chart reviews. Bivariate and multivariable analysis were performed with the primary outcome of in-hospital mortality. Results: Fifty-one consecutive patients underwent VV-ECMO with a mean age of 50.4 years; 64.7% were male. Survival to hospital discharge was 62.8%. Median ICU and hospitalization duration were 27.4 (IQR:17-37) and 34.5 days (IQR:23-43), respectively. Survivors and non-survivors had a median ECMO cannulation time of 11 days (IQR 8-18) and 17 days (IQR: 12-25). The average post decannulation length of stay was 17.5 days (IQR: 12.4-25) for survivors and 0 days for non-survivors (IQR 0-6 days). Only one non-survivor was able to be decannulated. Clinical characteristics associated with mortality between non-surviors and survivors included increasing age (p=0.0048), hemorrhagic stroke (p=0.0014), and post operative dialysis (p=0.0013)were associated with mortality in a bivariate model and retained statistical significance in a multivariable model. Conclusion: This multicenter study confirms the effectiveness of VV-ECMO in selected critically ill patients with COVID-19-related severe ARDS. The survival of these patients is comparable to non-COVID-19-related ARDS.

10.
EJIFCC ; 33(2): 105-120, 2022 Aug.
Article in English | MEDLINE | ID: covidwho-2092464

ABSTRACT

COVID-19 is an acute respiratory infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To date, more than 550 million cases and 6 million deaths have been reported worldwide. This study investigated the laboratory features in hospitalised patients with COVID-19 and determined risk factors for in-hospital mortality. This retrospective observational study included laboratory results of confirmed cases of hospitalised patients with SARS-CoV-2 infection in Jersey (UK) between March-December 2020 (subject to inclusion criteria), and a control group. Furthermore, COVID-19 patients were split into two sub-groups, based on outcome (non-survivors vs. survivors). Logistic regression was used to determine risk factors for in-hospital mortality. A total of 81 COVID-19 cases and 100 controls were included in this study. In the COVID-19 group, 59.3% of subjects were male, and the overall mortality was 33.3%. The main laboratory changes were the following: 95.1% of patients presented with raised C-reactive protein (p<0.001), 85% showed increased fibrinogen (p<0.001), 70% had prolonged prothrombin time (p=0.014), 51.9% suffered from lymphopenia (p<0.001), 42% had elevated gamma glutamyl transferase (p=0.011) and 35.8% demonstrated raised creatinine concentration (p=0.002). Non-survivors were older than survivors (median age: 82 vs. 74 years, p=0.003) with substantial lymphopenia (p=0.018), high creatinine level (p=0.009), and leukocytosis (p=0.018). Increased in-hospital mortality risk was 6.7-fold in patients presenting with a lymphocyte count <0.85 x109/L, 5.3-fold with red blood cell distribution width >14%, 4.9-fold with white cell count >9.5 x109/L, and 3.3-fold for those presenting with creatinine >100 µmol/L. Age ≥82 years was significantly associated with death, and male gender a risk factor for hospital admission in COVID-19. These results demonstrate that routine haematology and biochemistry tests may allow for risk-stratification of hospitalised patients with COVID-19.

11.
Zhongguo Dang Dai Er Ke Za Zhi ; 24(10): 1092-1097, 2022 Oct 15.
Article in Chinese | MEDLINE | ID: covidwho-2090827

ABSTRACT

OBJECTIVES: To study the clinical features of children infected with the Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: The medical data of 19 children who were diagnosed with SARS-CoV-2 Omicron variant infection from January 28 to March 3, 2022 in Hangzhou were retrospectively reviewed. RESULTS: Among the 19 children, there were 7 boys (37%) and 12 girls (63%), and their age ranged from 6 months to 16 years, with a median age of 2 years and 1 month. Most of these children were infants and young children (aged ≤3 years, accounting for 53%). Among these children, 11 (58%) were unvaccinated with SARS-CoV-2 vaccine and 8 (42%) were vaccinated with SARS-CoV-2 vaccine, and 3 children (16%) had a history of underlying diseases. All 19 children had a clear history of close contact with persons infected with SARS-CoV-2, and 10 children (53%) were involved in the cluster outbreak in a maternal and infant care center. In terms of clinical classification, 13 children (68%) had mild coronavirus disease 2019 (COVID-19) and 6 (32%) had common COVID-19, with no severe cases of COVID-19. The most common clinical symptoms were cough (100%) and fever (63%). The children with a normal peripheral white blood cell count accounted for 84%, and those with a normal lymphocyte count accounted for 68%. There were no significant abnormalities in platelet count, procalcitonin, liver function parameters (alanine aminotransferase and aspartate aminotransferase), and renal function parameters (creatinine and urea). Six children (32%) had obvious signs of pneumonia on chest CT. All 19 children were given symptomatic treatment, and 12 children (63%) were given aerosol inhalation of interferon α. All children were cured and discharged. CONCLUSIONS: Children infected with Omicron variant strains are more common in infants and young children, with mild symptoms and good prognosis. Most of the children have a history of close contact with persons infected with SARS-CoV-2, and epidemic prevention and control should be strengthened in places with many infants and children, such as maternal and infant care centers.


Subject(s)
COVID-19 , SARS-CoV-2 , Child , Infant , Male , Female , Humans , Child, Preschool , Retrospective Studies , COVID-19 Vaccines , China/epidemiology
12.
J Korean Med Sci ; 37(41): e297, 2022 Oct 24.
Article in English | MEDLINE | ID: covidwho-2089755

ABSTRACT

BACKGROUND: This study aimed to describe the maternal, obstetrical, and neonatal outcomes in pregnant women with coronavirus disease 2019 (COVID-19) and identify the predictors associated with the severity of COVID-19. METHODS: This multicenter observational study included consecutive pregnant women admitted because of COVID-19 confirmed using reverse transcriptase-polymerase chain reaction (RT-PCR) test at 15 hospitals in the Republic of Korea between January 2020 and December 2021. RESULTS: A total of 257 women with COVID-19 and 62 newborns were included in this study. Most of the patients developed this disease during the third trimester. Nine patients (7.4%) developed pregnancy-related complications. All pregnant women received inpatient treatment, of whom 9 (3.5%) required intensive care, but none of them died. The gestational age at COVID-19 diagnosis (odds ratio [OR], 1.096, 95% confidence interval [CI], 1.04-1.15) and parity (OR, 1.703, 95% CI, 1.13-2.57) were identified as significant risk factors of severe diseases. Among women who delivered, 78.5% underwent cesarean section. Preterm birth (38.5%), premature rupture of membranes (7.7%), and miscarriage (4.6%) occurred, but there was no stillbirth or neonatal death. The RT-PCR test of newborns' amniotic fluid and umbilical cord blood samples was negative for severe acute respiratory syndrome coronavirus 2. CONCLUSION: At the time of COVID-19 diagnosis, gestational age and parity of pregnant women were the risk factors of disease severity. Vertical transmission of COVID-19 was not observed, and maternal severity did not significantly affect the neonatal prognosis.


Subject(s)
COVID-19 , Pregnancy Complications, Infectious , Premature Birth , Infant, Newborn , Female , Humans , Pregnancy , COVID-19 Testing , Cesarean Section , Pregnant Women , Pregnancy Complications, Infectious/diagnosis , Pregnancy Outcome , Infectious Disease Transmission, Vertical , RNA-Directed DNA Polymerase
13.
Emerg Infect Dis ; 28(12)2022 Oct 26.
Article in English | MEDLINE | ID: covidwho-2089724

ABSTRACT

SARS-CoV-2 likely emerged from an animal reservoir. However, the frequency of and risk factors for interspecies transmission remain unclear. We conducted a community-based study in Idaho, USA, of pets in households that had >1 confirmed SARS-CoV-2 infections in humans. Among 119 dogs and 57 cats, clinical signs consistent with SARS-CoV-2 were reported for 20 dogs (21%) and 19 cats (39%). Of 81 dogs and 32 cats sampled, 40% of dogs and 43% of cats were seropositive, and 5% of dogs and 8% of cats were PCR positive. This discordance might be caused by delays in sampling. Respondents commonly reported close human‒animal contact and willingness to take measures to prevent transmission to their pets. Reported preventive measures showed a slightly protective but nonsignificant trend for both illness and seropositivity in pets. Sharing of beds and bowls had slight harmful effects, reaching statistical significance for sharing bowls and seropositivity.

14.
Emerg Infect Dis ; 28(11): 2270-2280, 2022 Nov.
Article in English | MEDLINE | ID: covidwho-2089723

ABSTRACT

Since the COVID-19 pandemic began, different SARS-CoV-2 variants have been identified and associated with higher transmissibility than the ancestral nonvariant strain. During January 1, 2021-January 15, 2022, we assessed differences in clinical and viral parameters in a convenience sample of COVID-19 outpatients and inpatients 0-21 years of age in Columbus, Ohio, USA, according to the infecting variant, identified using a mutation-specific reverse transcription PCR assay. Of the 676 patients in the study, 17.75% were infected with nonvariant strains, 18.49% with the Alpha variant, 41.72% with Delta, and 16.42% with Omicron. Rates of SARS-COV-2/viral co-infections were 15.66%-29.41% and were comparable across infecting variants. Inpatients with acute Delta and Omicron infections had lower SARS-CoV-2 cycle threshold values and more frequent fever and respiratory symptoms than those with nonvariant strain infections. In addition, SARS-COV-2/viral co-infections and the presence of underlying conditions were independently associated with worse clinical outcomes, irrespective of the infecting variant.


Subject(s)
COVID-19 , Coinfection , Child , Humans , Adolescent , SARS-CoV-2/genetics , Pandemics , Severity of Illness Index
15.
Emerg Infect Dis ; 28(11): 1-8, 2022 Nov.
Article in English | MEDLINE | ID: covidwho-2089722

ABSTRACT

During 2020-2021, countries in Latin America and the Caribbean reported clinical emergence of carbapenemase-producing Enterobacterales that had not been previously characterized locally, increased prevalence of carbapenemases that had previously been detected, and co-production of multiple carbapenemases in some isolates. These increases were likely fueled by changes related to the COVID-19 pandemic, including empirical antibiotic use for potential COVID-19-related bacterial infections and healthcare limitations resulting from the rapid rise in COVID-19 cases. Strengthening antimicrobial resistance surveillance, epidemiologic research, and infection prevention and control programs and antimicrobial stewardship in clinical settings can help prevent emergence and transmission of carbapenemase-producing Enterobacterales.


Subject(s)
COVID-19 , Humans , COVID-19/epidemiology , Pandemics , Latin America/epidemiology , beta-Lactamases/genetics , Bacterial Proteins/genetics , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Bacteria
16.
Intern Med ; 61(8): 1219-1223, 2022 Apr 15.
Article in English | MEDLINE | ID: covidwho-2089579

ABSTRACT

A 44-year-old man developed coronavirus disease 2019 (COVID-19) pneumonia during immunochemotherapy consisting of carboplatin, paclitaxel, and pembrolizumab for non-small cell lung cancer. Low-grade fever, followed by mild hypoxemia, and febrile neutropenia, were observed, and granulocyte colony-stimulating factor (G-CSF) was administered until the recovery of neutropenia, when he developed a high fever, severe hypoxemia, and hypotension accompanied by consolidation in the bilateral lungs. His conditions promptly improved after treatment including hydrocortisone and the primary and metastatic tumors remained regressed for 10 months without further treatment. Post-COVID-19 organizing pneumonia during cancer immunochemotherapy can be aggravated by immune-checkpoint inhibitors and G-CSF.


Subject(s)
COVID-19 , Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Adult , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Carcinoma, Non-Small-Cell Lung/drug therapy , Granulocyte Colony-Stimulating Factor/therapeutic use , Humans , Hypoxia/drug therapy , Lung Neoplasms/complications , Lung Neoplasms/drug therapy , Male
17.
Crit Care Explor ; 4(10): e0773, 2022 Oct.
Article in English | MEDLINE | ID: covidwho-2087871

ABSTRACT

Respiratory virus infections cause significant morbidity and mortality ranging from mild uncomplicated acute respiratory illness to severe complications, such as acute respiratory distress syndrome, multiple organ failure, and death during epidemics and pandemics. We present a protocol to systematically study patients with severe acute respiratory infection (SARI), including severe acute respiratory syndrome coronavirus 2, due to respiratory viral pathogens to evaluate the natural history, prognostic biomarkers, and characteristics, including hospital stress, associated with clinical outcomes and severity. DESIGN: Prospective cohort study. SETTING: Multicenter cohort of patients admitted to an acute care ward or ICU from at least 15 hospitals representing diverse geographic regions across the United States. PATIENTS: Patients with SARI caused by infection with respiratory viruses that can cause outbreaks, epidemics, and pandemics. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Measurements include patient demographics, signs, symptoms, and medications; microbiology, imaging, and associated tests; mechanical ventilation, hospital procedures, and other interventions; and clinical outcomes and hospital stress, with specimens collected on days 0, 3, and 7-14 after enrollment and at discharge. The primary outcome measure is the number of consecutive days alive and free of mechanical ventilation (VFD) in the first 30 days after hospital admission. Important secondary outcomes include organ failure-free days before acute kidney injury, shock, hepatic failure, disseminated intravascular coagulation, 28-day mortality, adaptive immunity, as well as immunologic and microbiologic outcomes. CONCLUSIONS: SARI-Preparedness is a multicenter study under the collaboration of the Society of Critical Care Medicine Discovery, Resilience Intelligence Network, and National Emerging Special Pathogen Training and Education Center, which seeks to improve understanding of prognostic factors associated with worse outcomes and increased resource utilization. This can lead to interventions to mitigate the clinical impact of respiratory virus infections associated with SARI.

18.
ACS Appl Mater Interfaces ; 14(43): 48464-48475, 2022 Nov 02.
Article in English | MEDLINE | ID: covidwho-2087121

ABSTRACT

Rapid and precise serum cytokine quantification provides immense clinical significance in monitoring the immune status of patients in rapidly evolving infectious/inflammatory disorders, examplified by the ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. However, real-time information on predictive cytokine biomarkers to guide targetable immune pathways in pathogenic inflammation is critically lacking, because of the insufficient detection range and detection limit in current label-free cytokine immunoassays. In this work, we report a highly sensitive localized surface plasmon resonance imaging (LSPRi) immunoassay for label-free Interleukin 6 (IL-6) detection utilizing rationally designed peptide aptamers as the capture interface. Benefiting from its characteristically smaller dimension and direct functionalization on the sensing surface via Au-S bonding, the peptide-aptamer-based LSPRi immunoassay achieved enhanced label-free serum IL-6 detection with a record-breaking limit of detection down to 4.6 pg/mL, and a wide dynamic range of ∼6 orders of magnitude (values from 4.6 to 1 × 106 pg/mL were observed). The immunoassay was validated in vitro for label-free analysis of SARS-CoV-2 induced inflammation, and further applied in rapid quantification of serum IL-6 profiles in COVID-19 patients. Our peptide aptamer LSPRi immunoassay demonstrates great potency in label-free cytokine detection with unprecedented sensing capability to provide accurate and timely interpretation of the inflammatory status and disease progression, and determination of prognosis.


Subject(s)
Aptamers, Peptide , Biosensing Techniques , COVID-19 , Humans , SARS-CoV-2 , Cytokines/analysis , Interleukin-6 , Immunoassay/methods , Inflammation
19.
Virol Sin ; 2022 Oct 26.
Article in English | MEDLINE | ID: covidwho-2086828

ABSTRACT

The spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from cold-chain foods to frontline workers poses a serious public health threat during the current global pandemic. There is an urgent need to design concise approaches for effective virus inactivation under different physicochemical conditions to reduce the risk of contagion through viral contaminated surfaces of cold-chain foods. By employing a time course of electron beam exposure to a high titer of SARS-CoV-2 at cold-chain temperatures, a radiation dose of 2 â€‹kGy was demonstrated to reduce the viral titer from 104.5 to 0 median tissue culture infectious dose (TCID50)/mL. Next, using human coronavirus OC43 (HCoV-OC43) as a suitable SARS-CoV-2 surrogate, 3 â€‹kGy of high-energy electron radiation was defined as the inactivation dose for a titer reduction of more than 4 log units on tested packaging materials. Furthermore, quantitative reverse transcription PCR (RT-qPCR) was used to test three viral genes, namely, E, N, and ORF1ab. There was a strong correlation between TCID50 and RT-qPCR for SARS-CoV-2 detection. However, RT-qPCR could not differentiate between the infectivity of the radiation-inactivated and nonirradiated control viruses. As the defined radiation dose for effective viral inactivation fell far below the upper safe dose limit for food processing, our results provide a basis for designing radiation-based approaches for the decontamination of SARS-CoV-2 in frozen food products. We further demonstrate that cell-based virus assays are essential to evaluate the SARS-CoV-2 inactivation efficiency for the decontaminating strategies.

20.
Smart Health (Amst) ; 26: 100323, 2022 Dec.
Article in English | MEDLINE | ID: covidwho-2086730

ABSTRACT

The large amount of data generated during the COVID-19 pandemic requires advanced tools for the long-term prediction of risk factors associated with COVID-19 mortality with higher accuracy. Machine learning (ML) methods directly address this topic and are essential tools to guide public health interventions. Here, we used ML to investigate the importance of demographic and clinical variables on COVID-19 mortality. We also analyzed how comorbidity networks are structured according to age groups. We conducted a retrospective study of COVID-19 mortality with hospitalized patients from Londrina, Parana, Brazil, registered in the database for severe acute respiratory infections (SIVEP-Gripe), from January 2021 to February 2022. We tested four ML models to predict the COVID-19 outcome: Logistic Regression, Support Vector Machine, Random Forest, and XGBoost. We also constructed a comorbidity network to investigate the impact of co-occurring comorbidities on COVID-19 mortality. Our study comprised 8358 hospitalized patients, of whom 2792 (33.40%) died. The XGBoost model achieved excellent performance (ROC-AUC = 0.90). Both permutation method and SHAP values highlighted the importance of age, ventilatory support status, and intensive care unit admission as key features in predicting COVID-19 outcomes. The comorbidity networks for old deceased patients are denser than those for young patients. In addition, the co-occurrence of heart disease and diabetes may be the most important combination to predict COVID-19 mortality, regardless of age and sex. This work presents a valuable combination of machine learning and comorbidity network analysis to predict COVID-19 outcomes. Reliable evidence on this topic is crucial for guiding the post-pandemic response and assisting in COVID-19 care planning and provision.

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