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1.
Dan Med J ; 69(6)2022 May 16.
Article in English | MEDLINE | ID: covidwho-1877237

ABSTRACT

INTRODUCTION: During the first wave of the COVID-19 pandemic, visits to hospitals were prohibited. Therefore, new ways of communicating with relatives about and with patients were needed. This study aimed to explore experiences made with video calls in an adult ICU. METHODS: This study employed semi-structured group interviews conducted with six registered nurses from the ICU in a large hospital in Denmark who used video calls during the lockdown. Interviews were transcribed verbatim and analysed using systematic text condensation. RESULTS: The analyses indicated that video calls were a useful alternative to physical meetings. The advantages of video calls were that relatives had risk-free access to the ICU and the patient's treatment, whereas patients gained a window into their home, and nurses used less planning time than physical visit. Finally, patients were less distracted by video calls than by visits. The challenges identified with video calls were difficulties for nurses to care for relatives, ethical aspects and technical issues. CONCLUSIONS: Video calls were an effective tool for communication during the COVID-19 lockdown, presenting a number of advantages and challenges compared with in-person visits or telephone calls. By identifying and overcoming these challenges, video calls may become a beneficial supplement to in-person visits or telephone calls. FUNDING: none. TRIAL REGISTRATION: Approved by the Danish Data Protection Agency (P-2020-931).


Subject(s)
COVID-19 , Adult , COVID-19/epidemiology , COVID-19/prevention & control , Communicable Disease Control , Humans , Intensive Care Units , Pandemics/prevention & control , Qualitative Research
2.
Dan Med J ; 69(6)2022 May 19.
Article in English | MEDLINE | ID: covidwho-1876980

ABSTRACT

INTRODUCTION: The coronavirus outbreak causes postponement of elective surgery. We evaluated how pain, function and general health were impacted by postponing elective knee and hip arthroplasty in patients with knee and hip osteoarthritis with no known surgery rescheduling date due to the coronavirus outbreak. METHODS: This study included 194 patients from a Danish public hospital with postponed elective primary knee or hip arthroplasty due to the lockdown. Patients responded to questionnaires when their surgery was cancelled and before surgery. Changes in pain and function were evaluated with the Oxford Knee and Hip Scores (OKS, OHS) and their general health with the EuroQol 5-dimension scale (EQ5D). Additionally, we asked about the patients' concerns and whether they felt improved, unchanged or deteriorated during the waiting period. RESULTS: Complete data were obtained for 110 (57%) patients, 59 and 51 awaiting knee or hip arthroplasty (median age 71 years, 62% were female), respectively. Arthroplasty was postponed for a median (range) 98 (63-161) days. A total of 34% were concerned that the postponement would lead to a poorer outcome. Mean OKS and OHS differences were 0 (95% confidence interval (CI): -1-1) and -1 (95% CI: -2-0) from surgery cancellation to re-scheduled surgery. The mean EQ5D index difference was 0.0 (95% CI: 0.0-0.1) for both groups. A total of 75 (68%) patients felt an important deterioration of their condition. CONCLUSIONS: Pre-operatively, patients worried about experiencing an altered treatment outcome due to postponed surgery and felt that their condition had deteriorated during the waiting period although this was not reflected in patient-reported outcome measures. FUNDING: Department of Orthopaedic Surgery. TRIAL REGISTRATION: not relevant.


Subject(s)
Arthroplasty, Replacement, Hip , Arthroplasty, Replacement, Knee , Osteoarthritis, Hip , Aged , Female , Humans , Male , Osteoarthritis, Hip/surgery , Pain , Patient Reported Outcome Measures
3.
N Engl J Med ; 386(21): 1986-1997, 2022 05 26.
Article in English | MEDLINE | ID: covidwho-1864788

ABSTRACT

BACKGROUND: Perioperative bleeding is common in patients undergoing noncardiac surgery. Tranexamic acid is an antifibrinolytic drug that may safely decrease such bleeding. METHODS: We conducted a trial involving patients undergoing noncardiac surgery. Patients were randomly assigned to receive tranexamic acid (1-g intravenous bolus) or placebo at the start and end of surgery (reported here) and, with the use of a partial factorial design, a hypotension-avoidance or hypertension-avoidance strategy (not reported here). The primary efficacy outcome was life-threatening bleeding, major bleeding, or bleeding into a critical organ (composite bleeding outcome) at 30 days. The primary safety outcome was myocardial injury after noncardiac surgery, nonhemorrhagic stroke, peripheral arterial thrombosis, or symptomatic proximal venous thromboembolism (composite cardiovascular outcome) at 30 days. To establish the noninferiority of tranexamic acid to placebo for the composite cardiovascular outcome, the upper boundary of the one-sided 97.5% confidence interval for the hazard ratio had to be below 1.125, and the one-sided P value had to be less than 0.025. RESULTS: A total of 9535 patients underwent randomization. A composite bleeding outcome event occurred in 433 of 4757 patients (9.1%) in the tranexamic acid group and in 561 of 4778 patients (11.7%) in the placebo group (hazard ratio, 0.76; 95% confidence interval [CI], 0.67 to 0.87; absolute difference, -2.6 percentage points; 95% CI, -3.8 to -1.4; two-sided P<0.001 for superiority). A composite cardiovascular outcome event occurred in 649 of 4581 patients (14.2%) in the tranexamic acid group and in 639 of 4601 patients (13.9%) in the placebo group (hazard ratio, 1.02; 95% CI, 0.92 to 1.14; upper boundary of the one-sided 97.5% CI, 1.14; absolute difference, 0.3 percentage points; 95% CI, -1.1 to 1.7; one-sided P = 0.04 for noninferiority). CONCLUSIONS: Among patients undergoing noncardiac surgery, the incidence of the composite bleeding outcome was significantly lower with tranexamic acid than with placebo. Although the between-group difference in the composite cardiovascular outcome was small, the noninferiority of tranexamic acid was not established. (Funded by the Canadian Institutes of Health Research and others; POISE-3 ClinicalTrials.gov number, NCT03505723.).


Subject(s)
Antifibrinolytic Agents , Tranexamic Acid , Antifibrinolytic Agents/adverse effects , Antifibrinolytic Agents/therapeutic use , Canada , Hemorrhage/etiology , Hemorrhage/prevention & control , Humans , Surgical Procedures, Operative , Thrombosis/chemically induced , Thrombosis/drug therapy , Tranexamic Acid/adverse effects , Tranexamic Acid/therapeutic use
4.
Medicine (Baltimore) ; 101(20): e29209, 2022 May 20.
Article in English | MEDLINE | ID: covidwho-1860981

ABSTRACT

ABSTRACT: Coronavirus-2019 (COVID-19) emerged in December 2019, causing significant changes in people's social lives and other human activities. The outbreak halted educational activities throughout the world. The Nigerian experience was unique in that most people were skeptical about the pandemic's existence. This practice contributed to the Nigerian people's fear of the COVID-19 outbreak. However, in Nigeria, there has never been a validated or established Covid-19 phobia scale, necessitating this study.This study was a pure validation study on COVID-19 phobia scale (C19PS). The study area was south-east states and a sample of 386 preschool practitioners in urban and rural communities of South East States, Nigeria participated in the study. The eligibility criteria include being a preschool teacher and demonstrating signs of COVID-19 phobia. The validation of the C19PS was done by subjecting the data gathered to principal axis factoring analysis with varimax rotation. The model fit for the data was tested using root mean square error of approximation and comparative fit index.It was found that the Kaiser-Meyer-Olkin value of .845 for the measure of the adequacy of the sample size. There was also a significant Bartlett's test of sphericity (P < .05). This implies that the correlation matrix for the C19PS is not an identity matrix. It was revealed that C19PS had good overall reliability (α = .896) and model fit (Root mean square error of approximation = .042, comparative fit index = .943) in a sample of Nigerian preschool practitioners.As a result, C19PS was recommended as a trustworthy tool for identifying persons who suffer from COVID-19 phobia.


Subject(s)
COVID-19 , Phobic Disorders , COVID-19/diagnosis , COVID-19/epidemiology , Child, Preschool , Humans , Nigeria/epidemiology , Psychometrics , Reproducibility of Results , Rural Population , School Teachers , Surveys and Questionnaires
5.
Exp Physiol ; 2021 May 31.
Article in English | MEDLINE | ID: covidwho-1807292

ABSTRACT

NEW FINDINGS: What is the topic of this review? Lactate is considered an important substrate for mitochondria in the muscles, heart and brain during exercise and is the main gluconeogenetic precursor in the liver and kidneys. In this light, we review the (patho)physiology of lactate metabolism in sepsis and coronavirus disease 2019 (COVID-19). What advances does it highlight? Elevated blood lactate is strongly associated with mortality in septic patients. Lactate seems unrelated to tissue hypoxia but is likely to reflect mitochondrial dysfunction and high adrenergic stimulation. Patients with severe COVID-19 exhibit near-normal blood lactate, indicating preserved mitochondrial function, despite a systemic hyperinflammatory state similar to sepsis. ABSTRACT: In critically ill patients, elevated plasma lactate is often interpreted as a sign of organ hypoperfusion and/or tissue hypoxia. This view on lactate is likely to have been influenced by the pioneering exercise physiologists around 1920. August Krogh identified an oxygen deficit at the onset of exercise that was later related to an oxygen 'debt' and lactate accumulation by A. V. Hill. Lactate is considered to be the main gluconeogenetic precursor in the liver and kidneys during submaximal exercise, but hepatic elimination is attenuated by splanchnic vasoconstriction during high-intensity exercise, causing an exponential increase in blood lactate. With the development of stable isotope tracers, lactate has become established as an important energy source for muscle, brain and heart tissue, where it is used for mitochondrial respiration. Plasma lactate > 4 mM is strongly associated with mortality in septic shock, with no direct link between lactate release and tissue hypoxia. Herein, we provide evidence for mitochondrial dysfunction and adrenergic stimulation as explanations for the sepsis-induced hyperlactataemia. Despite profound hypoxaemia and intense work of breathing, patients with severe coronavirus disease 2019 (COVID-19) rarely exhibit hyperlactataemia (> 2.5 mM), while presenting a systemic hyperinflammatory state much like sepsis. However, lactate dehydrogenase, which controls the formation of lactate, is markedly elevated in plasma and strongly associated with mortality in severe COVID-19. We briefly review the potential mechanisms of the lactate dehydrogenase elevation in COVID-19 and its relationship to lactate metabolism based on mechanisms established in contracting skeletal muscle and the acute respiratory distress syndrome.

6.
Pharm Res ; 39(3): 541-551, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1777764

ABSTRACT

PURPOSE: Intranasally administered unfractionated heparin (UFH) and other sulfated polysaccharides are potential prophylactics for COVID-19. The purpose of this research was to measure the safety and pharmacokinetics of clearance of intranasally administered UFH solution from the nasal cavity. METHODS: Double-blinded daily intranasal dosing in C57Bl6 mice with four doses (60 ng to 60 µg) of UFH was carried out for fourteen consecutive days, with both blood coagulation measurements and subject adverse event monitoring. The pharmacokinetics of fluorescent-labeled UFH clearance from the nasal cavity were measured in mice by in vivo imaging. Intranasal UFH at 2000 U/day solution with nasal spray device was tested for safety in a small number of healthy human subjects. RESULTS: UFH showed no evidence of toxicity in mice at any dose measured. No significant changes were observed in activated partial thromboplastin time (aPTT), platelet count, or frequency of minor irritant events over vehicle-only control. Human subjects showed no significant changes in aPTT time, international normalized ratio (INR), or platelet count over baseline measurements. No serious adverse events were observed. In vivo imaging in a mouse model showed a single phase clearance of UFH from the nasal cavity. After 12 h, 3.2% of the administered UFH remained in the nasal cavity, decaying to background levels by 48 h. CONCLUSIONS: UFH showed no toxic effects for extended daily intranasal dosing in mice as well as humans. The clearance kinetics of intranasal heparin solution from the nasal cavity indicates potentially protective levels for up to 12 h after dosing.


Subject(s)
COVID-19 , Heparin , Animals , Anticoagulants/adverse effects , Humans , Mice , Mice, Inbred C57BL , Partial Thromboplastin Time
7.
Zeitschrift fur Gastroenterologie ; 60(1):e16, 2022.
Article in English | EMBASE | ID: covidwho-1721707

ABSTRACT

Objective Thrombotic-thrombocytopenic events are rare, but life-threatening, complications after ChAdOx1 nCoV-19 vaccination and sometimes present as symptomatic splanchnic vein thrombosis with critical illness. Life-saving aggressive and multimodal treatment is essential in these cases. Design We report on a critically ill 40-year-old male patient with complete splanchnic (portal/mesenteric/splenic) vein thrombosis, becoming symptomatic 7 days after ChAdOx1 nCoV-19 vaccination and diagnosed on day 12. Laparotomy for abdominal compartment syndrome and repeated transjugular/ transhepatic interventional and open surgical thrombectomy procedures were performed. Additional therapy consisted of thrombolysis with recombinant tissue-type plasminogen activator over 5 days, anticoagulation (argatroban), platelet inhibition (Acetylsalicylic acid /clopidogrel), immunoglobulins and steroids. Results This aggressive treatment included 5 laparotomies and 4 angiographic interventions, open abdomen for 8 days, transfusion of 27 units of packed red cells, 9 abdominal and 4 cerebral CT scans, thrombolysis therapy for 5 days, mechanical ventilation for 15 days, and an ICU stay of 25 days. Full patient recovery and near complete recanalization of splanchnic veins was achieved. Conclusion Without treatment, ChAdOx1 nCoV-19 vaccination-induced total splanchnic vein thrombosis has serious consequences with a high risk for death. The case described here shows that an aggressive multimodal surgical-medical treatment strategy in a specialized center can save these patients and achieve a good outcome.

9.
Cancer Epidemiology Biomarkers and Prevention ; 31(1 SUPPL), 2022.
Article in English | EMBASE | ID: covidwho-1677445

ABSTRACT

Background: Comprehensive cancer control (CCC) plans are region-specific blueprints that identify cancer priorities and health equity informed strategies to address cancer burden and are supported by the National Comprehensive Cancer Control Program through the Centers for Disease Control and Prevention (CDC). Although CCC plans are created by stakeholder coalitions, few have focused on community engaged approaches, which may diminish their applicability for community members. Thus, in preparation for its forthcoming 2022-2027 CCC plan, the Illinois Comprehensive Cancer Control Program collaborated with the University of Illinois Cancer Center's Community Engagement and Health Equity office to implement a community engagement strategy to address cancer burden. Objective: To describe the development and implementation of a community engagement strategy for the 2022-2027 Illinois CCC plan. Method: The goal of the community engagement strategy was to identify barriers, facilitating factors and recommendations related to cancer burden and equity in Illinois by engaging diverse community stakeholders. A statewide town hall and focus groups (FGs) were implemented in early 2021. Thedevelopment and analysis of the community engagement strategy were guided by the Model for Analysis of Population Health and Health Disparities, CDC's CHANGE Action Guide, and the Community ToolBox. Semistructured guides included questions about fundamental causes of health, social and physical contexts, individual demographics and risk factors, and biologic responses and pathways. The town hall was open to Illinoisians over 18 years of age. FG participants were selected using purposive sampling to maximize group heterogeneity. Eight FGs were held, one each for: rural residents, survivors, young survivors, caregivers, and Spanish speakers, and three that were a mix of community members. Town hall notes and FGs were analyzed using content analysis. Results were synthesized and a final report was included in the forthcoming plan. Results: Town hall and FG (n=8) participants (n=115) included cancer survivors (36%), caregivers (27%), Latinos (17%), African Americans (23%), and rural residents (14%). Throughout the development of the plan, data were continuously reviewed with the coalition developing the CCC Plan. The final report described multi-level factors that contribute to cancer disparities among Illinoisians, proposed recommendations to improve health across the cancer continuum across multiple levels, funding priorities, and the impact of COVID-19 on cancer care. Participant quotes supported strategies throughout the plan. Conclusion: A robust community engagement strategy for the forthcoming 2022-2027 Illinois CCC Plan was implemented through a successful academic-state public health department partnership. This strategy ensures that the plan reflects the expertise and voices of Illinoisians impacted by cancer. This engagement strategy, framed around health determinants that impact cancer risk and outcomes, may be replicated by other coalitions creating CCC plans.

10.
mSphere ; 7(1): e0088321, 2022 02 23.
Article in English | MEDLINE | ID: covidwho-1673356

ABSTRACT

Considering the urgent demand for faster methods to quantify neutralizing antibody titers in patients with coronavirus (CoV) disease 2019 (COVID-19), developing an analytical model or method to replace the conventional virus neutralization test (NT) is essential. Moreover, a "COVID-19 immunity passport" is currently being proposed as a certification for people who travel internationally. Therefore, an enzyme-linked immunosorbent assay (ELISA) was designed to detect severe acute respiratory syndrome CoV 2 (SARS-CoV-2)-neutralizing antibodies in serum, which is based on the binding affinity of SARS-CoV-2 viral spike protein 1 (S1) and the viral spike protein receptor-binding domain (RBD) to antibodies. The RBD is considered the major binding region of neutralizing antibodies. Furthermore, S1 covers the RBD and several other regions, which are also important for neutralizing antibody binding. In this study, we assessed 144 clinical specimens, including those from patients with PCR-confirmed SARS-CoV-2 infections and healthy donors, using both the NT and ELISA. The ELISA results analyzed by spline regression and the two-variable generalized additive model precisely reflected the NT value, and the correlation between predicted and actual NT values was as high as 0.917. Therefore, our method serves as a surrogate to quantify neutralizing antibody titer. The analytic method and platform used in this study present a new perspective for serological testing of SARS-CoV-2 infection and have clinical potential to assess vaccine efficacy. IMPORTANCE Herein, we present a new approach for serological testing for SARS-CoV-2 antibodies using innovative laboratory methods that demonstrate a combination of biology and mathematics. The traditional virus neutralization test is the gold standard method; however, it is time-consuming and poses a risk to medical personnel. Thus, there is a demand for methods that rapidly quantify neutralizing antibody titers in patients with COVID-19 or examine vaccine efficacy at a biosafety level 2 containment facility. Therefore, we used a two-variable generalized additive model to analyze the results of the enzyme-linked immunosorbent assay and found the method to serve as a surrogate to quantify neutralizing antibody titers. This methodology has potential for clinical use in assessing vaccine efficacy.


Subject(s)
Antibodies, Neutralizing/blood , COVID-19/immunology , Enzyme-Linked Immunosorbent Assay , Models, Immunological , Models, Statistical , Neutralization Tests/methods , SARS-CoV-2/immunology , Biomarkers/blood , COVID-19/blood , COVID-19/diagnosis , Case-Control Studies , Humans , Regression Analysis
11.
Frontiers in sociology ; 6, 2021.
Article in English | EuropePMC | ID: covidwho-1652045

ABSTRACT

During the early months of the COVID-19 pandemic in Germany, social restrictions and social distancing policies forced large parts of social life to take place within the household. However, comparatively little is known about how private living situations shaped individuals experiences of this crisis. To investigate this issue, we analyze how experiences and concerns vary across living arrangements along two dimensions that may be associated with social disadvantage: loneliness and care. In doing so, we employ quantitative text analysis on open-ended questions from survey data on a sample of 1,073 individuals living in Germany. We focus our analyses on four different household structures: living alone, shared living without children, living with a partner and children, and single parents. We find that single parents (who are primarily single mothers) are at high risk of experiencing care-related worries, particularly regarding their financial situation, while individuals living alone are most likely to report feelings of loneliness. Those individuals living in shared houses, with or without children, had the lowest risk of experiencing both loneliness and care-related worries. These findings illustrate that the living situation at home substantially impacts how individuals experienced and coped with the pandemic situation during the first wave of the pandemic.

12.
Mycoses ; 65(1): 103-109, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1470452

ABSTRACT

BACKGROUND: Most COVID-19-associated mucormycosis (CAM) cases are reported from India and neighbouring countries. Anecdotally cases from Europe have been presented. OBJECTIVE: To estimate the disease burden and describe the clinical presentation of CAM in Germany. METHODS: We identified cases through German mycology networks and scientific societies, and collected anonymised clinical information via FungiScope®. RESULTS: We identified 13 CAM cases from six tertiary referral hospitals diagnosed between March 2020 and June 2021. Twelve patients had severe or critical COVID-19, eleven were mechanically ventilated for a median of 8 days (range 1-27 days) before diagnosis of CAM. Eleven patients received systemic corticosteroids. Additional underlying medical conditions were reported for all but one patient, five were immunocompromised because of malignancy or organ transplantation, three were diabetic. Eleven patients developed pneumonia. Mortality was 53.8% with a median time from diagnosis of mucormycosis to death of 9 days (range 0-214 days) despite treatment with liposomal amphotericin B and/or isavuconazole in 10 of 13 cases. CAM prevalence amongst hospitalised COVID-19 patients overall (0.67% and 0.58% in two centres) and those admitted to the intensive care unit (ICU) (1.47%, 1.78% and 0.15% in three centres) was significantly higher compared to non-COVID-19 patients (P < .001 for respective comparisons). CONCLUSION: COVID-19-associated mucormycosis is rare in Germany, mostly reported in patients with comorbidities and impaired immune system and severe COVID-19 treated in the ICU with high mortality compared to mainly rhino-orbito-cerebral CAM in patients with mild COVID-19 in India. Risk for CAM is higher in hospitalised COVID-19 patients than in other patients.


Subject(s)
COVID-19 , Mucormycosis , Antifungal Agents/therapeutic use , COVID-19/complications , Germany/epidemiology , Humans , Mucormycosis/diagnosis , Mucormycosis/drug therapy , Mucormycosis/epidemiology , Tertiary Care Centers
13.
J Urban Health ; 98(Suppl 2): 91-102, 2021 10.
Article in English | MEDLINE | ID: covidwho-1405830

ABSTRACT

This manuscript describes a telephone outreach project for members of a research registry program for older adults in Detroit, Michigan. From April until December 2020, the Healthier Black Elders Center designed and implemented a telephone outreach program, calling 1204 older adults utilizing 15 staff and volunteers. The calls served to check in on registry members and collect data on mental health, coping mechanisms, access to services, masks, testing, and tele-health. This paper details the methods of developing and implementing an innovative engagement program that collected time-sensitive data from older Black adults that has directly been applied to create virtual health education programs, share resource information, and create a program to reduce social isolation.


Subject(s)
Empathy , Pandemics , Aged , Humans , Social Isolation , Telephone , Volunteers
14.
PLoS Pathog ; 17(1): e1009161, 2021 01.
Article in English | MEDLINE | ID: covidwho-1388959

ABSTRACT

We report the emergency development and application of a robust serologic test to evaluate acute and convalescent antibody responses to SARS-CoV-2 in Argentina. The assays, COVIDAR IgG and IgM, which were produced and provided for free to health authorities, private and public health institutions and nursing homes, use a combination of a trimer stabilized spike protein and the receptor binding domain (RBD) in a single enzyme-linked immunosorbent assay (ELISA) plate. Over half million tests have already been distributed to detect and quantify antibodies for multiple purposes, including assessment of immune responses in hospitalized patients and large seroprevalence studies in neighborhoods, slums and health care workers, which resulted in a powerful tool for asymptomatic detection and policy making in the country. Analysis of antibody levels and longitudinal studies of symptomatic and asymptomatic SARS-CoV-2 infections in over one thousand patient samples provided insightful information about IgM and IgG seroconversion time and kinetics, and IgM waning profiles. At least 35% of patients showed seroconversion within 7 days, and 95% within 45 days of symptoms onset, with simultaneous or close sequential IgM and IgG detection. Longitudinal studies of asymptomatic cases showed a wide range of antibody responses with median levels below those observed in symptomatic patients. Regarding convalescent plasma applications, a protocol was standardized for the assessment of end point IgG antibody titers with COVIDAR with more than 500 plasma donors. The protocol showed a positive correlation with neutralizing antibody titers, and was used for clinical trials and therapies across the country. Using this protocol, about 80% of convalescent donor plasmas were potentially suitable for therapies. Here, we demonstrate the importance of providing a robust and specific serologic assay for generating new information about antibody kinetics in infected individuals and mitigation policies to cope with pandemic needs.


Subject(s)
COVID-19/virology , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , Adult , Aged , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , Antibody Formation , Argentina/epidemiology , COVID-19/epidemiology , Enzyme-Linked Immunosorbent Assay/methods , Female , Humans , Immunoglobulin G/immunology , Immunoglobulin M/immunology , Longitudinal Studies , Male , Middle Aged , Pandemics , SARS-CoV-2/isolation & purification , Seroepidemiologic Studies
15.
BMC Pregnancy Childbirth ; 21(1): 574, 2021 Aug 21.
Article in English | MEDLINE | ID: covidwho-1374107

ABSTRACT

SARS-Cov-2 (Severe Acute Respiratory Coronavirus 2) infection confers a non-negligible risk for younger pregnant women with diabetes, which is still less well investigated. This topic was recently addressed by a systematic scoping review in BMC Pregnancy and Childbirth, aiming to summarize the complex interaction between SARS-Cov-2 infection, pregnancy and diabetes. This commentary will summarize and discuss the main findings of this article and its implications for future research.


Subject(s)
COVID-19/epidemiology , Infectious Disease Transmission, Vertical/prevention & control , Maternal Health/statistics & numerical data , Pregnancy Complications, Infectious/epidemiology , Pregnancy in Diabetics/epidemiology , Prenatal Care/methods , Female , Humans , Infant, Newborn , Pregnancy , Primary Prevention/methods
16.
Crit Care ; 25(1): 295, 2021 Aug 17.
Article in English | MEDLINE | ID: covidwho-1362062

ABSTRACT

BACKGROUND: Intensive Care Resources are heavily utilized during the COVID-19 pandemic. However, risk stratification and prediction of SARS-CoV-2 patient clinical outcomes upon ICU admission remain inadequate. This study aimed to develop a machine learning model, based on retrospective & prospective clinical data, to stratify patient risk and predict ICU survival and outcomes. METHODS: A Germany-wide electronic registry was established to pseudonymously collect admission, therapeutic and discharge information of SARS-CoV-2 ICU patients retrospectively and prospectively. Machine learning approaches were evaluated for the accuracy and interpretability of predictions. The Explainable Boosting Machine approach was selected as the most suitable method. Individual, non-linear shape functions for predictive parameters and parameter interactions are reported. RESULTS: 1039 patients were included in the Explainable Boosting Machine model, 596 patients retrospectively collected, and 443 patients prospectively collected. The model for prediction of general ICU outcome was shown to be more reliable to predict "survival". Age, inflammatory and thrombotic activity, and severity of ARDS at ICU admission were shown to be predictive of ICU survival. Patients' age, pulmonary dysfunction and transfer from an external institution were predictors for ECMO therapy. The interaction of patient age with D-dimer levels on admission and creatinine levels with SOFA score without GCS were predictors for renal replacement therapy. CONCLUSIONS: Using Explainable Boosting Machine analysis, we confirmed and weighed previously reported and identified novel predictors for outcome in critically ill COVID-19 patients. Using this strategy, predictive modeling of COVID-19 ICU patient outcomes can be performed overcoming the limitations of linear regression models. Trial registration "ClinicalTrials" (clinicaltrials.gov) under NCT04455451.


Subject(s)
COVID-19/epidemiology , Critical Illness/epidemiology , Electronic Health Records/statistics & numerical data , Intensive Care Units , Machine Learning , Adult , Aged , COVID-19/therapy , Cohort Studies , Critical Illness/therapy , Emergency Service, Hospital , Female , Germany , Humans , Male , Middle Aged , Outcome Assessment, Health Care
17.
Curr Opin Virol ; 50: 49-58, 2021 10.
Article in English | MEDLINE | ID: covidwho-1345304

ABSTRACT

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), like other coronaviruses, relies on a flexible array of entry mechanisms, driven by the spike (S) protein. Entry is dependent on proteolytic priming, activation, and receptor binding; all of which can be variable, dependent on context. Here we review the implications of the complexity of SARS-CoV-2 entry pathways on entry assays that then drive our understanding of humoral immunity, therapeutic efficacy, and tissue restriction. We focus especially on the proteolytic activation of SARS-CoV-2 spike and how this constellation of proteases lends deeper insight to our understanding of arising variants and their putative role transmission or variable pathogenicity in vivo. In this review, we argue for better universal standards to assay virus entry as well as suggest best practices for reporting viral passage number, the cell line used, and proteases present, among other important considerations.


Subject(s)
COVID-19/etiology , Peptide Hydrolases/physiology , SARS-CoV-2/physiology , Virus Internalization , Humans , Mutation , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/genetics
18.
Nat Commun ; 12(1): 4598, 2021 07 26.
Article in English | MEDLINE | ID: covidwho-1327197

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected at least 180 million people since its identification as the cause of the current COVID-19 pandemic. The rapid pace of vaccine development has resulted in multiple vaccines already in use worldwide. The contemporaneous emergence of SARS-CoV-2 'variants of concern' (VOC) across diverse geographic locales underscores the need to monitor the efficacy of vaccines being administered globally. All WHO designated VOC carry spike (S) polymorphisms thought to enable escape from neutralizing antibodies. Here, we characterize the neutralizing activity of post-Sputnik V vaccination sera against the ensemble of S mutations present in alpha (B.1.1.7) and beta (B.1.351) VOC. Using de novo generated replication-competent vesicular stomatitis virus expressing various SARS-CoV-2-S in place of VSV-G (rcVSV-CoV2-S), coupled with a clonal 293T-ACE2 + TMPRSS2 + cell line optimized for highly efficient S-mediated infection, we determine that only 1 out of 12 post-vaccination serum samples shows effective neutralization (IC90) of rcVSV-CoV2-S: B.1.351 at full serum strength. The same set of sera efficiently neutralize S from B.1.1.7 and exhibit only moderately reduced activity against S carrying the E484K substitution alone. Taken together, our data suggest that control of some emergent SARS-CoV-2 variants may benefit from updated vaccines.


Subject(s)
Antibodies, Neutralizing/immunology , COVID-19 Vaccines/immunology , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , Adult , COVID-19 Vaccines/administration & dosage , COVID-19 Vaccines/genetics , Female , HEK293 Cells , Humans , Immune Sera/immunology , Male , Middle Aged , Mutation , Neutralization Tests , SARS-CoV-2/genetics , SARS-CoV-2/physiology , Spike Glycoprotein, Coronavirus/genetics , Vaccination/methods , Vesicular stomatitis Indiana virus/genetics , Vesicular stomatitis Indiana virus/immunology , Virus Internalization/drug effects , Virus Replication/drug effects , Virus Replication/genetics , Virus Replication/immunology
19.
Blood ; 138(14): 1269-1277, 2021 10 07.
Article in English | MEDLINE | ID: covidwho-1317119

ABSTRACT

Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a severe adverse effect of ChAdOx1 nCoV-19 COVID-19 vaccine (Vaxzevria) and Janssen Ad26.COV2.S COVID-19 vaccine, and it is associated with unusual thrombosis. VITT is caused by anti-platelet factor 4 (PF4) antibodies activating platelets through their FcγRIIa receptors. Antibodies that activate platelets through FcγRIIa receptors have also been identified in patients with COVID-19. These findings raise concern that vaccination-induced antibodies against anti-SARS-CoV-2 spike protein cause thrombosis by cross-reacting with PF4. Immunogenic epitopes of PF4 and SARS-CoV-2 spike protein were compared using in silico prediction tools and 3D modeling. The SARS-CoV-2 spike protein and PF4 share at least 1 similar epitope. Reactivity of purified anti-PF4 antibodies from patients with VITT was tested against recombinant SARS-CoV-2 spike protein. However, none of the affinity-purified anti-PF4 antibodies from 14 patients with VITT cross-reacted with SARS-CoV-2 spike protein. Sera from 222 polymerase chain reaction-confirmed patients with COVID-19 from 5 European centers were tested by PF4-heparin enzyme-linked immunosorbent assays and PF4-dependent platelet activation assays. We found anti-PF4 antibodies in sera from 19 (8.6%) of 222 patients with COVID-19. However, only 4 showed weak to moderate platelet activation in the presence of PF4, and none of those patients developed thrombotic complications. Among 10 (4.5%) of 222 patients who had COVID-19 with thrombosis, none showed PF4-dependent platelet-activating antibodies. In conclusion, antibodies against PF4 induced by vaccination do not cross-react with the SARS-CoV-2 spike protein, indicating that the intended vaccine-induced immune response against SARS-CoV-2 spike protein is not the trigger of VITT. PF4-reactive antibodies found in patients with COVID-19 in this study were not associated with thrombotic complications.


Subject(s)
Antibodies/adverse effects , COVID-19 Vaccines/adverse effects , Cross Reactions/immunology , Platelet Factor 4/immunology , Purpura, Thrombocytopenic, Idiopathic/etiology , Purpura, Thrombocytopenic, Idiopathic/immunology , Spike Glycoprotein, Coronavirus/immunology , Adult , Aged , Aged, 80 and over , Blood Platelets/immunology , COVID-19/immunology , Cohort Studies , Epitopes/immunology , Female , Heparin/metabolism , Humans , Immunoglobulin G/immunology , Male , Middle Aged , Protein Binding , Protein Domains , Purpura, Thrombocytopenic, Idiopathic/blood , Spike Glycoprotein, Coronavirus/chemistry , Young Adult
20.
Preprint in English | medRxiv | ID: ppmedrxiv-21259936

ABSTRACT

PurposeIntranasally administered unfractionated heparin (UFH) and other sulfated polysaccharides are potential prophylactics for COVID-19. The purpose of this research was to measure the safety and pharmacokinetics of clearance of intranasally administered UFH solution from the nasal cavity. MethodsDouble-blinded daily intranasal dosing in C57Bl6 mice with four doses (60 ng to 60 g) of UFH was carried out for fourteen consecutive days, with both blood coagulation measurements and subject adverse event monitoring. The pharmacokinetics of fluorescent-labeled UFH clearance from the nasal cavity were measured in mice by in vivo imaging. Intranasal UFH at 2000 U/day solution with nasal spray device was tested for safety in a small number of healthy human subjects. ResultsUFH showed no evidence of toxicity in mice at any dose measured. No significant changes were observed in activated partial thromboplastin time (aPTT), platelet count, or frequency of minor irritant events over vehicle-only control. Human subjects showed no significant changes in aPTT time, international normalized ratio (INR), or platelet count over baseline measurements. No serious adverse events were observed. In vivo imaging in a mouse model showed a single phase clearance of UFH from the nasal cavity. After 12 hours, 3.2% of the administered UFH remained in the nasal cavity, decaying to background levels by 48 hours. ConclusionsUFH showed no toxic effects for extended daily intranasal dosing in mice as well as humans. The clearance kinetics of intranasal heparin solution from the nasal cavity indicates potentially protective levels for up to 12 hours after dosing.

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