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1.
Perfusion ; 37(4): 350-358, 2022 05.
Article in English | MEDLINE | ID: covidwho-1820033

ABSTRACT

The outbreak of the novel coronavirus pandemic (COVID-19) has resulted in dramatic changes to the conduct of surgery both from a patient management perspective and in protecting healthcare providers. The current study reports on the status of COVID-19 infections in patients presenting for cardiac surgery with cardiopulmonary bypass (CPB) on circuit complications. A tracking process for monitoring the presence of COVID-19 in adult cardiac surgery patients was integrated into a case documentation system across United States hospitals where out-sourced perfusion services were provided. Assessment included infection status, testing technique employed, surgery status and CPB complications. Records from 5612 adult patients who underwent cardiac surgery between November 1, 2020 and January 18, 2021 from 176 hospitals were reviewed. A sub-cohort of coronary artery bypass graft patients (3283) was compared using a mixed effect binary logistic regression analysis. 4297 patients had negative test results (76.6%) while 49 (0.9%) tested positive for COVID-19, and unknown or no results were reported in 693 (12.4%) and 573 (10.2%) respectively. Coagulation complications were reported at 0.2% in the negative test results group versus 4.1% in the positive test result group (p < 0.001). Oxygenator gas exchange complications were 0.2% in the negative test results group versus 2.0% in the positive test results group (p = 0.088). Coronary artery bypass graft patients with a positive test had significantly higher risk for any CPB complication (p = 0.003) [OR 10.38, CI 2.18-49.53] then negative test patients [OR 0.01, CI 0.00-0.20]. The present study has shown that patients undergoing cardiac surgery with CPB who test positive for COVID-19 have higher CPB complication rate than those who test negative.


Subject(s)
COVID-19 , Cardiac Surgical Procedures , Cardiac Surgical Procedures/adverse effects , Cardiopulmonary Bypass/adverse effects , Coronary Artery Bypass/adverse effects , Coronary Artery Bypass/methods , Humans , Postoperative Complications/etiology
2.
JAMA Neurol ; 78(8): 948-960, 2021 08 01.
Article in English | MEDLINE | ID: covidwho-1265359

ABSTRACT

Importance: Myalgia, increased levels of creatine kinase, and persistent muscle weakness have been reported in patients with COVID-19. Objective: To study skeletal muscle and myocardial inflammation in patients with COVID-19 who had died. Design, Setting, and Participants: This case-control autopsy series was conducted in a university hospital as a multidisciplinary postmortem investigation. Patients with COVID-19 or other critical illnesses who had died between March 2020 and February 2021 and on whom an autopsy was performed were included. Individuals for whom informed consent to autopsy was available and the postmortem interval was less than 6 days were randomly selected. Individuals who were infected with SARS-CoV-2 per polymerase chain reaction test results and had clinical features suggestive of COVID-19 were compared with individuals with negative SARS-CoV-2 polymerase chain reaction test results and an absence of clinical features suggestive of COVID-19. Main Outcomes and Measures: Inflammation of skeletal muscle tissue was assessed by quantification of immune cell infiltrates, expression of major histocompatibility complex (MHC) class I and class II antigens on the sarcolemma, and a blinded evaluation on a visual analog scale ranging from absence of pathology to the most pronounced pathology. Inflammation of cardiac muscles was assessed by quantification of immune cell infiltrates. Results: Forty-three patients with COVID-19 (median [interquartile range] age, 72 [16] years; 31 men [72%]) and 11 patients with diseases other than COVID-19 (median [interquartile range] age, 71 [5] years; 7 men [64%]) were included. Skeletal muscle samples from the patients who died with COVID-19 showed a higher overall pathology score (mean [SD], 3.4 [1.8] vs 1.5 [1.0]; 95% CI, 0-3; P < .001) and a higher inflammation score (mean [SD], 3.5 [2.1] vs 1.0 [0.6]; 95% CI, 0-4; P < .001). Relevant expression of MHC class I antigens on the sarcolemma was present in 23 of 42 specimens from patients with COVID-19 (55%) and upregulation of MHC class II antigens in 7 of 42 specimens from patients with COVID-19 (17%), but neither were found in any of the controls. Increased numbers of natural killer cells (median [interquartile range], 8 [8] vs 3 [4] cells per 10 high-power fields; 95% CI, 1-10 cells per 10 high-power fields; P < .001) were found. Skeletal muscles showed more inflammatory features than cardiac muscles, and inflammation was most pronounced in patients with COVID-19 with chronic courses. In some muscle specimens, SARS-CoV-2 RNA was detected by reverse transcription-polymerase chain reaction, but no evidence for a direct viral infection of myofibers was found by immunohistochemistry and electron microscopy. Conclusions and Relevance: In this case-control study of patients who had died with and without COVID-19, most individuals with severe COVID-19 showed signs of myositis ranging from mild to severe. Inflammation of skeletal muscles was associated with the duration of illness and was more pronounced than cardiac inflammation. Detection of viral load was low or negative in most skeletal and cardiac muscles and probably attributable to circulating viral RNA rather than genuine infection of myocytes. This suggests that SARS-CoV-2 may be associated with a postinfectious, immune-mediated myopathy.


Subject(s)
COVID-19/pathology , Muscle, Skeletal/pathology , Myocarditis/pathology , Myocardium/pathology , Myositis/pathology , Aged , Aged, 80 and over , Autopsy , CD8-Positive T-Lymphocytes/pathology , COVID-19/metabolism , COVID-19 Nucleic Acid Testing , COVID-19 Serological Testing , Case-Control Studies , Female , Histocompatibility Antigens Class I/metabolism , Histocompatibility Antigens Class II/metabolism , Humans , Killer Cells, Natural/pathology , Leukocytes/pathology , Macrophages/pathology , Male , Middle Aged , Muscle, Skeletal/metabolism , Myocarditis/metabolism , Myocardium/metabolism , Myositis/metabolism , RNA, Viral/metabolism , SARS-CoV-2 , Sarcolemma/metabolism , Time Factors
3.
Lancet Microbe ; 2(8): e354-e365, 2021 08.
Article in English | MEDLINE | ID: covidwho-1253810

ABSTRACT

BACKGROUND: Microbiological characterisation of co-infections and secondary infections in patients with COVID-19 is lacking, and antimicrobial use is high. We aimed to describe microbiologically confirmed co-infections and secondary infections, and antimicrobial use, in patients admitted to hospital with COVID-19. METHODS: The International Severe Acute Respiratory and Emerging Infections Consortium (ISARIC) WHO Clinical Characterisation Protocol UK (CCP-UK) study is an ongoing, prospective cohort study recruiting inpatients from 260 hospitals in England, Scotland, and Wales, conducted by the ISARIC Coronavirus Clinical Characterisation Consortium. Patients with a confirmed or clinician-defined high likelihood of SARS-CoV-2 infection were eligible for inclusion in the ISARIC WHO CCP-UK study. For this specific study, we excluded patients with a recorded negative SARS-CoV-2 test result and those without a recorded outcome at 28 days after admission. Demographic, clinical, laboratory, therapeutic, and outcome data were collected using a prespecified case report form. Organisms considered clinically insignificant were excluded. FINDINGS: We analysed data from 48 902 patients admitted to hospital between Feb 6 and June 8, 2020. The median patient age was 74 years (IQR 59-84) and 20 786 (42·6%) of 48 765 patients were female. Microbiological investigations were recorded for 8649 (17·7%) of 48 902 patients, with clinically significant COVID-19-related respiratory or bloodstream culture results recorded for 1107 patients. 762 (70·6%) of 1080 infections were secondary, occurring more than 2 days after hospital admission. Staphylococcus aureus and Haemophilus influenzae were the most common pathogens causing respiratory co-infections (diagnosed ≤2 days after admission), with Enterobacteriaceae and S aureus most common in secondary respiratory infections. Bloodstream infections were most frequently caused by Escherichia coli and S aureus. Among patients with available data, 13 390 (37·0%) of 36 145 had received antimicrobials in the community for this illness episode before hospital admission and 39 258 (85·2%) of 46 061 patients with inpatient antimicrobial data received one or more antimicrobials at some point during their admission (highest for patients in critical care). We identified frequent use of broad-spectrum agents and use of carbapenems rather than carbapenem-sparing alternatives. INTERPRETATION: In patients admitted to hospital with COVID-19, microbiologically confirmed bacterial infections are rare, and more likely to be secondary infections. Gram-negative organisms and S aureus are the predominant pathogens. The frequency and nature of antimicrobial use are concerning, but tractable targets for stewardship interventions exist. FUNDING: National Institute for Health Research (NIHR), UK Medical Research Council, Wellcome Trust, UK Department for International Development, Bill & Melinda Gates Foundation, EU Platform for European Preparedness Against (Re-)emerging Epidemics, NIHR Health Protection Research Unit (HPRU) in Emerging and Zoonotic Infections at University of Liverpool, and NIHR HPRU in Respiratory Infections at Imperial College London.


Subject(s)
Anti-Infective Agents , COVID-19 , Coinfection , Respiratory Tract Infections , Aged , Aged, 80 and over , COVID-19/epidemiology , Coinfection/drug therapy , Female , Humans , Male , Middle Aged , Pandemics , Prospective Studies , Respiratory Tract Infections/epidemiology , SARS-CoV-2 , United Kingdom/epidemiology , World Health Organization
4.
Bratisl Lek Listy ; 122(6): 413-417, 2021.
Article in English | MEDLINE | ID: covidwho-1232644

ABSTRACT

OBJECTIVES: This study aims to determine the prognostic significance of the lymphocyte/mean platelet volume ratio (LMR) in terms of the clinical course of the disease in patients with COVID-19. METHODS: Patients over 18 who were evaluated for COVID-19 during the period from April 1, to April 30, 2020 were retrospectively scanned. Patients with at least 1 positive PCR test result were as assigned to Group 1 while patients with negative test results were assigned to Group 2. The LMR ratio was calculated by dividing the lymphocyte value by that of MPV. The relationship between LMR, severity of patients' CT findings and 28-day mortality was evaluated. RESULTS: A total of 938 patients were included in the study. It was observed that the lymphocyte and LMR levels were significantly different in those who died within 28 days (p < 0.001, p ≤ 0.001). In the ROC analysis for the LMR level, the area under the curve (AUC) was found to be 0.737 (95% CI 0.639‒0.834). When the cut­off value of LMR was 0.045, the sensitivity was found to be 99.0 % and specificity was 15.2 %. CONCLUSION: LMR can be a guide in multiple cases of care provided to critical patients, as is the case in the COVID-19 pandemic and can be used in recognizing critical patients (Tab. 5, Fig. 1, Ref. 21).


Subject(s)
COVID-19 , Mean Platelet Volume , Humans , Lymphocytes , Monocytes , Pandemics , Prognosis , ROC Curve , Retrospective Studies , SARS-CoV-2
5.
Viruses ; 13(5)2021 04 30.
Article in English | MEDLINE | ID: covidwho-1217119

ABSTRACT

It is unclear whether universal PCR screening for SARS-CoV-2 in asymptomatic individuals prior to admission is useful. From April to December 2020, the positive rate of universal pre-admission screening was 0.005% (4/76,521) in a tertiary care hospital in Korea. The positive rates were not different between the periods (period 1 (daily new patients of <1 per million inhabitants) vs. period 2 (1-8.3 per million inhabitants) vs. period 3 (10.3 to 20 per million inhabitants); P = 0.45). Universal pre-admission screening for SARS-CoV-2 had a lower positive rate than that of symptom-based screening (0.005% vs. 0.049% (53/109,257), p < 0.001). In addition, seven patients with negative pre-admission test results had subsequent positive PCR during hospitalization, and four patients had secondary transmission. Universal pre-admission PCR screening may not be practical in settings of low prevalence of COVID-19, and negative PCR results at admission should not serve as a basis for underestimating the risk of nosocomial spread from asymptomatic patients.


Subject(s)
Asymptomatic Diseases/epidemiology , COVID-19 Nucleic Acid Testing/methods , COVID-19 , Carrier State , Nasopharynx/virology , SARS-CoV-2/isolation & purification , COVID-19/diagnosis , COVID-19/epidemiology , Carrier State/diagnosis , Carrier State/epidemiology , Humans , Prevalence , Republic of Korea/epidemiology , Tertiary Care Centers
6.
Cureus ; 13(3): e14172, 2021 Mar 29.
Article in English | MEDLINE | ID: covidwho-1191510

ABSTRACT

Objective The goal of this study was to investigate whether blood group type caused susceptibility to COVID-19 infection. Methods Two hundred and eleven consecutive patients admitted with various symptoms associated with COVID-19 were included. We compared the AB0 and Rh subgroup distributions between patients with a positive polymerase chain reaction (PCR) test result and the patients without. We compared the AB0 and Rh subgroup distributions between patients with lung involvement and patients without. Additionally, comparisons were performed between the patients both with positive PCR result and lung involvement, and the patients with a negative PCR result. Results No significant difference of ABO and Rh subgroup distributions was evident between patients with and without a positive PCR test result (p=0.632 and p=0.962). No significant difference of ABO and Rh subgroup distributions was evident between the patients with and without lung involvement (p=0.097 and p=0.797). No significant difference of ABO and Rh subgroup distributions was evident among patients both with PCR positivity and lung involvement, patients with only PCR positivity, and the patients with negative PCR test results (p=0.3 and p=0.993). Conclusion All blood group types seem to have an equal risk of COVID-19 infection. Everyone should follow the precautions to avoid the COVID-19 infection.

7.
EClinicalMedicine ; 34: 100793, 2021 Apr.
Article in English | MEDLINE | ID: covidwho-1144586

ABSTRACT

BACKGROUND: Consecutive negative SARS-CoV-2 PCR test results are being considered to estimate viral clearance in COVID-19 patients. However, there are anecdotal reports of hospitalization from protracted COVID-19 complications despite such confirmed viral clearance, presenting a clinical conundrum. METHODS: We conducted a retrospective analysis of 222 hospitalized COVID-19 patients to compare those that were readmitted post-viral clearance (hospitalized post-clearance cohort, n = 49) with those that were not re-admitted post-viral clearance (non-hospitalized post-clearance cohort, n = 173) between February and October 2020. In order to differentiate these two cohorts, we used neural network models for the 'augmented curation' of comorbidities and complications with positive sentiment in the Electronic Hosptial Records physician notes. FINDINGS: In the year preceding COVID-19 onset, anemia (n = 13 [26.5%], p-value: 0.007), cardiac arrhythmias (n = 14 [28.6%], p-value: 0.015), and acute kidney injury (n = 7 [14.3%], p-value: 0.030) were significantly enriched in the physician notes of the hospitalized post-clearance cohort. INTERPRETATION: Overall, this retrospective study highlights specific pre-existing conditions that are associated with higher hospitalization rates in COVID-19 patients despite viral clearance and motivates follow-up prospective research into the associated risk factors. FUNDING: This work was supported by Nference, inc.

8.
Emerg Infect Dis ; 27(5): 1274-1278, 2021 May.
Article in English | MEDLINE | ID: covidwho-1140632

ABSTRACT

The strategy in New Zealand (Aotearoa) to eliminate coronavirus disease requires that international arrivals undergo managed isolation and quarantine and mandatory testing for severe acute respiratory syndrome coronavirus 2. Combining genomic and epidemiologic data, we investigated the origin of an acute case of coronavirus disease identified in the community after the patient had spent 14 days in managed isolation and quarantine and had 2 negative test results. By combining genomic sequence analysis and epidemiologic investigations, we identified a multibranched chain of transmission of this virus, including on international and domestic flights, as well as a probable case of aerosol transmission without direct person-to-person contact. These findings show the power of integrating genomic and epidemiologic data to inform outbreak investigations.


Subject(s)
Air Travel , COVID-19 , Humans , New Zealand/epidemiology , Quarantine , SARS-CoV-2 , Travel
9.
JAMA Intern Med ; 181(5): 672-679, 2021 05 01.
Article in English | MEDLINE | ID: covidwho-1098863

ABSTRACT

Importance: Understanding the effect of serum antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on susceptibility to infection is important for identifying at-risk populations and could have implications for vaccine deployment. Objective: The study purpose was to evaluate evidence of SARS-CoV-2 infection based on diagnostic nucleic acid amplification test (NAAT) among patients with positive vs negative test results for antibodies in an observational descriptive cohort study of clinical laboratory and linked claims data. Design, Setting, and Participants: The study created cohorts from a deidentified data set composed of commercial laboratory tests, medical and pharmacy claims, electronic health records, and hospital chargemaster data. Patients were categorized as antibody-positive or antibody-negative according to their first SARS-CoV-2 antibody test in the database. Main Outcomes and Measures: Primary end points were post-index diagnostic NAAT results, with infection defined as a positive diagnostic test post-index, measured in 30-day intervals (0-30, 31-60, 61-90, >90 days). Additional measures included demographic, geographic, and clinical characteristics at the time of the index antibody test, including recorded signs and symptoms or prior evidence of coronavirus 2019 (COVID) diagnoses or positive NAAT results and recorded comorbidities. Results: The cohort included 3 257 478 unique patients with an index antibody test; 56% were female with a median (SD) age of 48 (20) years. Of these, 2 876 773 (88.3%) had a negative index antibody result, and 378 606 (11.6%) had a positive index antibody result. Patients with a negative antibody test result were older than those with a positive result (mean age 48 vs 44 years). Of index-positive patients, 18.4% converted to seronegative over the follow-up period. During the follow-up periods, the ratio (95% CI) of positive NAAT results among individuals who had a positive antibody test at index vs those with a negative antibody test at index was 2.85 (95% CI, 2.73-2.97) at 0 to 30 days, 0.67 (95% CI, 0.6-0.74) at 31 to 60 days, 0.29 (95% CI, 0.24-0.35) at 61 to 90 days, and 0.10 (95% CI, 0.05-0.19) at more than 90 days. Conclusions and Relevance: In this cohort study, patients with positive antibody test results were initially more likely to have positive NAAT results, consistent with prolonged RNA shedding, but became markedly less likely to have positive NAAT results over time, suggesting that seropositivity is associated with protection from infection. The duration of protection is unknown, and protection may wane over time.


Subject(s)
COVID-19 Nucleic Acid Testing , COVID-19 Serological Testing , COVID-19 , Disease Susceptibility , SARS-CoV-2 , Adult , Age Factors , Antibodies, Viral/isolation & purification , COVID-19/blood , COVID-19/diagnosis , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19 Nucleic Acid Testing/methods , COVID-19 Nucleic Acid Testing/statistics & numerical data , COVID-19 Serological Testing/methods , COVID-19 Serological Testing/statistics & numerical data , Correlation of Data , Disease Susceptibility/diagnosis , Disease Susceptibility/epidemiology , Disease Susceptibility/immunology , Female , Humans , Male , Middle Aged , SARS-CoV-2/immunology , SARS-CoV-2/isolation & purification , Seroepidemiologic Studies , Symptom Assessment/methods , Symptom Assessment/statistics & numerical data , United States/epidemiology , Virus Shedding/immunology
10.
Ann Transl Med ; 9(2): 100, 2021 Jan.
Article in English | MEDLINE | ID: covidwho-1079877

ABSTRACT

BACKGROUND: To investigate the temporal pattern of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presence on ocular surfaces using conjunctival swabs in coronavirus disease 2019 (COVID-19) patients. METHODS: This study included 59 patients (32 newly admitted and 27 hospitalized for ≥2 weeks) with a COVID-19-confirmed diagnosis at the Shanghai Public Health Clinical Center from March 3, 2020, to March 21, 2020. Conjunctival swab samples were collected from both eyes of all the 59 patients and were tested by reverse transcription polymerase chain reaction (RT-PCR) assay. The range of sampling time lies widely between 1 and 50 days since symptom onset. RESULTS: Among the 32 newly admitted patients, positive RT-PCR results for SARS-CoV-2 in conjunctival swab samples were reported in 2 patients (one eye for each) without ocular discomfort, but 1 positive case had conjunctival congestion. The positive results were detected on Day 5 for 1 patient and Day 7 for the other, but repeated tests after 1 week were negative for both patients. All 27 patients who had been hospitalized for ≥2 weeks had negative test results. The mean time from symptom onset to sampling of 2 positive cases was significantly less than that of 57 negative cases (P<0.001). CONCLUSIONS: SARS-CoV-2 on the ocular surface can be detected in the early phase of COVID-19. The risk of ocular transmission remains and might be higher in the early phase.

11.
Scand J Trauma Resusc Emerg Med ; 29(1): 3, 2021 Jan 06.
Article in English | MEDLINE | ID: covidwho-1059735

ABSTRACT

BACKGROUND: The novel coronavirus disease 2019 (Covid-19) pandemic has affected prehospital care systems across the world, but the prehospital presentation of affected patients and the extent to which prehospital care providers are able to identify them is not well characterized. In this study, we describe the presentation of Covid-19 patients in a Swedish prehospital care system, and asses the predictive value of Covid-19 suspicion as documented by dispatch and ambulance nurses. METHODS: Data for all patients with dispatch, ambulance, and hospital records between January 1-August 31, 2020 were extracted. A descriptive statistical analysis of patients with and without hospital-confirmed Covid-19 was performed. In a subset of records beginning from April 14, we assessed the sensitivity and specificity of documented Covid-19 suspicion in dispatch and ambulance patient care records. RESULTS: A total of 11,894 prehospital records were included, of which 481 had a primary hospital diagnosis code related to-, or positive test results for Covid-19. Covid-19-positive patients had considerably worse outcomes than patients with negative test results, with 30-day mortality rates of 24% vs 11%, but lower levels of prehospital acuity (e.g. emergent transport rates of 14% vs 22%). About half (46%) of Covid-19-positive patients presented to dispatchers with primary complaints typically associated with Covid-19. Six thousand seven hundred seventy-six records were included in the assessment of predictive value. Sensitivity was 76% (95% CI 71-80) and 82% (78-86) for dispatch and ambulance suspicion respectively, while specificities were 86% (85-87) and 78% (77-79). CONCLUSIONS: While prehospital suspicion was strongly indicative of hospital-confirmed Covid-19, based on the sensitivity identified in this study, prehospital suspicion should not be relied upon as a single factor to rule out the need for isolation precautions. The data provided may be used to develop improved guidelines for identifying Covid-19 patients in the prehospital setting.


Subject(s)
COVID-19 Testing/methods , COVID-19/diagnosis , Emergency Medical Services/methods , Pandemics , SARS-CoV-2 , Aged , COVID-19/epidemiology , Female , Humans , Male , Middle Aged , ROC Curve , Sweden/epidemiology
12.
Front Med (Lausanne) ; 7: 608525, 2020.
Article in English | MEDLINE | ID: covidwho-1021895

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic continues to have a tremendous impact on patients and healthcare systems around the world. In the fight against this novel disease, there is a pressing need for rapid and effective screening tools to identify patients infected with COVID-19, and to this end CT imaging has been proposed as one of the key screening methods which may be used as a complement to RT-PCR testing, particularly in situations where patients undergo routine CT scans for non-COVID-19 related reasons, patients have worsening respiratory status or developing complications that require expedited care, or patients are suspected to be COVID-19-positive but have negative RT-PCR test results. Early studies on CT-based screening have reported abnormalities in chest CT images which are characteristic of COVID-19 infection, but these abnormalities may be difficult to distinguish from abnormalities caused by other lung conditions. Motivated by this, in this study we introduce COVIDNet-CT, a deep convolutional neural network architecture that is tailored for detection of COVID-19 cases from chest CT images via a machine-driven design exploration approach. Additionally, we introduce COVIDx-CT, a benchmark CT image dataset derived from CT imaging data collected by the China National Center for Bioinformation comprising 104,009 images across 1,489 patient cases. Furthermore, in the interest of reliability and transparency, we leverage an explainability-driven performance validation strategy to investigate the decision-making behavior of COVIDNet-CT, and in doing so ensure that COVIDNet-CT makes predictions based on relevant indicators in CT images. Both COVIDNet-CT and the COVIDx-CT dataset are available to the general public in an open-source and open access manner as part of the COVID-Net initiative. While COVIDNet-CT is not yet a production-ready screening solution, we hope that releasing the model and dataset will encourage researchers, clinicians, and citizen data scientists alike to leverage and build upon them.

13.
Trials ; 22(1): 9, 2021 Jan 06.
Article in English | MEDLINE | ID: covidwho-1011237

ABSTRACT

OBJECTIVES: 1. To assess the efficacy of Mesenchymal Stromal Cells (MSC) versus a control arm as described in the primary endpoint. 2. To evaluate the effects of MSC on the secondary efficacy endpoints. 3. To evaluate the safety and tolerability profiles of MSC. 4. To study soluble and cellular biomarkers that might be involved in the course of the disease and the response to the investigational product. TRIAL DESIGN: A double-blind, randomized, controlled, trial to evaluate the efficacy and safety of MSC intravenous administration in patients with COVID-induced Acute Respiratory Distress Syndrome (ARDS) compared to a control arm. PARTICIPANTS: The trial is being conducted at a third level hospital, Hospital Universitario Puerta de Hierro, in Majadahonda, Madrid (Spain). Inclusion criteria 1. Informed consent prior to performing study procedures (witnessed oral consent with written consent by representatives will be accepted to avoid paper handling). Written consent by patient or representatives will be obtained whenever possible. 2. Adult patients ≥18 years of age at the time of enrolment. 3. Laboratory-confirmed SARS-CoV-2 infection as determined by Polymerase Chain Reaction (PCR), in oropharyngeal swabs or any other relevant specimen obtained during the course of the disease. Alternative tests (e.g., rapid antigen tests) are also acceptable as laboratory confirmation if their specificity has been accepted by the Sponsor. 4. Moderate to severe ARDS (PaO2/FiO2 ratio equal or less than 200 mmHg) for less than 96 hours at the time of randomization. 5. Patients requiring invasive ventilation are eligible within 72 hours from intubation. 6. Eligible for ICU admission, according to the clinical team. Exclusion criteria 1. Imminent and unavoidable progression to death within 24 hours, irrespective of the provision of treatments (in the opinion of the clinical team). 2. "Do Not Attempt Resuscitation" order in place. 3. Any end-stage organ disease or condition, which in the investigator's opinion, makes the patient an unsuitable candidate for treatment. 4. History of a moderate/severe lung disorder requiring home-based oxygen therapy. 5. Patient requiring Extracorporeal Membrane Oxygenation (ECMO), haemodialysis or hemofiltration at the time of treatment administration. 6. Current diagnosis of pulmonary embolism. 7. Active neoplasm, except carcinoma in situ or basalioma. 8. Known allergy to the products involved in the allogeneic MSC production process. 9. Current pregnancy or lactation (women with childbearing potential should have a negative pregnancy test result at the time of study enrolment). 10. Current participation in a clinical trial with an experimental treatment for COVID-19 (the use of any off-label medicine according to local treatment protocols is not an exclusion criteria). 11. Any circumstances that in the investigator's opinion compromises the patient's ability to participate in the clinical trial. INTERVENTION AND COMPARATOR: - Experimental treatment arm: Allogeneic MSC (approximately 1 x 106 cells/kg). - Control arm: placebo solution (same composition as the experimental treatment, without the MSC). One single intravenous dose of the assigned treatment will be administered on Day 0 of the study. All trial participants will receive standard of care (SOC). In the context of the current worldwide pandemic, SOC can include medicines that are being used in clinical practice (e.g. lopinavir/ritonavir; hydroxy/chloroquine, tocilizumab, etc.), as well as those authorised for COVID (e.g., remdesivir). MAIN OUTCOMES: Primary endpoint: Change in the PaO2/FiO2 ratio from baseline to day 7 of treatment administration, or to the last available PaO2/FiO2 ratio if death occurs before day 7. Secondary endpoints: - All-cause mortality on days 7, 14, and 28 after treatment. - PaO2/FiO2 ratio at baseline and days 2, 4, 7, 14 and 28 after treatment. - Oxygen saturation (by standardized measurement) at baseline, daily until day 14, and on day 28 after treatment. - Time to PaO2/FiO2 ratio greater than 200 mmHg. - Subjects' clinical status on the WHO 7-point ordinal scale at baseline, daily until day 14, and on day 28 after treatment. - Time to an improvement of one category from admission on the WHO 7-point ordinal scale. - Percentage of patients that worsen at least one category on the WHO 7-point ordinal scale. - Percentage of patients that improve at least one category (maintained 48h) on the WHO 7-point ordinal scale. - Sequential Organ Failure Assessment (SOFA) scale at baseline and days 2, 4, 7, 14 and 28 after treatment. - Duration of hospitalization (days). - Duration of ICU stay (days). - Oxygen therapy-free days in the first 28 days after treatment. - Duration of supplemental oxygen. - Incidence of and duration of non-invasive and invasive mechanical ventilation in the first 28 days after treatment. - Mechanical ventilation-free days in the first 28 days after treatment. - Ventilation parameters. - Incidence of new onset pulmonary fibrosis at 3 and 12 months after treatment, based on CT scan and pulmonary function tests. - Survival at 3 and 12 months. - Cumulative incidence of Serious Adverse events (SAEs) and Grade 3 and 4 Adverse Events (AEs). - Cumulative incidence of Adverse Drug Reactions (ADR) in the experimental treatment arm. - Cumulative incidence of AEs of special interest. - Levels of analytical markers (C-Reactive Protein, lymphocyte and neutrophil counts, lymphocyte subpopulations, LDH, ferritin, D-dimer, coagulation tests and cytokines...) at baseline and days 2, 4, 7, 14 and 28 after treatment. - Other soluble and cellular biomarkers that might be involved in the course of the disease and the response to MSC. RANDOMISATION: The assignment to treatment will be carried out randomly and blinded, with a 1:1 allocation. Randomization will be done through a centralized system embedded in the electronic Case Report Form (CRF). BLINDING (MASKING): To ensure blinding, treatments will be prepared for administration at the Cell Production Unit and the administration of the treatment will be masked, not allowing the identification of the Investigational Medicinal Product (IMP). NUMBERS TO BE RANDOMISED (SAMPLE SIZE): A total of 20 participants are planned to be randomized, 10 to each treatment group. TRIAL STATUS: Protocol version: 1.2, dated October 14th, 2020 Start of recruitment: 01/10/2020 End of recruitment (estimated): December 2020. TRIAL REGISTRATION: EudraCT Number: 2020-002193-27 , registered on July 14th, 2020. NCT number: NCT04615429 , registered on November 4th, 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.


Subject(s)
Antiviral Agents/administration & dosage , COVID-19/therapy , Mesenchymal Stem Cell Transplantation/methods , Respiratory Distress Syndrome/therapy , Administration, Intravenous , Adult , Biomarkers/blood , COVID-19/complications , COVID-19/diagnosis , COVID-19/virology , Clinical Trials, Phase II as Topic , Combined Modality Therapy/adverse effects , Combined Modality Therapy/methods , Double-Blind Method , Female , Humans , Male , Mesenchymal Stem Cell Transplantation/adverse effects , Randomized Controlled Trials as Topic , Respiration, Artificial , Respiratory Distress Syndrome/blood , Respiratory Distress Syndrome/diagnosis , Respiratory Distress Syndrome/virology , SARS-CoV-2/isolation & purification , SARS-CoV-2/pathogenicity , Severity of Illness Index , Spain , Standard of Care , Transplantation, Homologous/adverse effects , Transplantation, Homologous/methods
14.
Eur J Clin Invest ; 51(3): e13474, 2021 Mar.
Article in English | MEDLINE | ID: covidwho-991347

ABSTRACT

INTRODUCTION: Despite being widely used as a screening tool, a rigorous scientific evaluation of infrared thermography for the diagnosis of minimally symptomatic patients suspected of having COVID-19 infection has not been performed. METHODS: A consecutive sample of 60 adult individuals with a history of close contact with COVID-19 infected individuals and mild respiratory symptoms for less than 7 days and 20 confirmed COVID-19 negative healthy volunteers were enrolled in the study. Infrared thermograms of the face were obtained with a mobile camera, and RT-PCR was used as the reference standard test to diagnose COVID-19 infection. Temperature values and distribution of the face of healthy volunteers and patients with and without COVID-19 infection were then compared. RESULTS: Thirty-four patients had an RT-PCR confirmed diagnosis of COVID-19 and 26 had negative test results. The temperature asymmetry between the lacrimal caruncles and the forehead was significantly higher in COVID-19 positive individuals. Through a random forest analysis, a cut-off value of 0.55°C was found to discriminate with an 82% accuracy between patients with and without COVID-19 confirmed infection. CONCLUSIONS: Among adults with a history of COVID-19 exposure and mild respiratory symptoms, a temperature asymmetry of ≥ 0.55°C between the lacrimal caruncle and the forehead is highly suggestive of COVID-19 infection. This finding questions the widespread use of the measurement of absolute temperature values of the forehead as a COVID-19 screening tool.


Subject(s)
Body Temperature , COVID-19/diagnosis , Eye , Forehead , Thermography/methods , Adult , COVID-19/physiopathology , COVID-19 Nucleic Acid Testing , Case-Control Studies , Female , Humans , Infrared Rays , Machine Learning , Male , Middle Aged , Multivariate Analysis , Prospective Studies , SARS-CoV-2 , Severity of Illness Index
15.
Am J Clin Pathol ; 154(5): 575-584, 2020 10 13.
Article in English | MEDLINE | ID: covidwho-965750

ABSTRACT

OBJECTIVES: To illustrate how patient risk and clinical costs are driven by false-positive and false-negative results. METHODS: Molecular, antigen, and antibody testing are the mainstay to identify infected patients and fight the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To evaluate the test methods, sensitivity (percent positive agreement [PPA]) and specificity (percent negative agreement [PNA]) are the most common metrics utilized, followed by the positive and negative predictive value-the probability that a positive or negative test result represents a true positive or negative patient. The number, probability, and cost of false results are driven by combinations of prevalence, PPA, and PNA of the individual test selected by the laboratory. RESULTS: Molecular and antigen tests that detect the presence of the virus are relevant in the acute phase only. Serologic assays detect antibodies to SARS-CoV-2 in the recovering and recovered phase. Each testing methodology has its advantages and disadvantages. CONCLUSIONS: We demonstrate the value of reporting probability of false-positive results, probability of false-negative results, and costs to patients and health care. These risk metrics can be calculated from the risk drivers of PPA and PNA combined with estimates of prevalence, cost, and Reff number (people infected by 1 positive SARS-CoV-2 carrier).


Subject(s)
Betacoronavirus/pathogenicity , Clinical Laboratory Techniques , Coronavirus Infections/diagnosis , Pneumonia, Viral/diagnosis , Sensitivity and Specificity , COVID-19 , COVID-19 Testing , Clinical Laboratory Techniques/methods , False Negative Reactions , Humans , Pandemics , Risk , SARS-CoV-2
16.
J Clin Med ; 9(11)2020 Nov 04.
Article in English | MEDLINE | ID: covidwho-908922

ABSTRACT

This study was designed to examine maternal-perinatal outcomes in pregnant women with suspected coronavirus disease 2019 (COVID-19) according to the result of a real-time reverse transcription polymerase chain reaction (RT-PCR) test and to investigate possible variables that could be useful for predicting a negative RT-PCR result. Participants of this retrospective cohort study were obstetrics patients with suspected COVID-19 who underwent an RT-PCR test in a tertiary hospital in Madrid, Spain. Maternal-perinatal features were analysed according to the results of this test. Clinical, radiological and analytical characteristics that could be associated with a negative result were also explored. In a final subgroup analysis, patients were included if they had pneumonia and a negative test result for the virus. Out of the 111 obstetric patients with suspected COVID-19 that were enrolled, 38.7% returned a negative result. In this RT-PCR-negative group, we recorded lower rates of pneumonia (21.4% vs. 45.6%, p = 0.009), severe or critical clinical features (4.7% vs. 11.8% and 0.0% vs. 5.9%, p = 0.02, respectively), lower lactate dehydrogenase (LDH) levels (168 UI/L vs. 224.5 UI/L, p = 0.003), a greater need for maternal treatment (60.3% vs 24.4%, p < 0.001), a reduced need for oxygen therapy (2.4% vs 28.8%, p < 0.001) and a lower rate of intensive care unit admission (0.0% vs. 3.7%, p = 0.046) than the RT-PCR-positive group. While no differences were found in other variables, the monocyte count was higher (946.2/µL vs. 518.8/µL, p = 0.022) in this group. The predictive model for a negative test result included the monocyte count, LDH level and no need for oxygen therapy. This model was able to identify 73.5% of patients with a negative RT-PCR result. Only 11% of the patients with pneumonia testing negative for the virus had IgG antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The proportion of pregnant women with suspected COVID-19 and a negative RT-PCR result was nearly 39%. In these patients, the symptoms were mild and the systemic severity of the disease was lower. The monocyte count, LDH level and no need for oxygen therapy were the factors that were more related to a negative test result in this group. These variables could be used to guide the management of patients with suspected COVID-19, mainly while waiting for RT-PCR results or in settings where this test is not available.

17.
Cureus ; 12(10): e11044, 2020 Oct 19.
Article in English | MEDLINE | ID: covidwho-890671

ABSTRACT

One of the biggest challenges during the coronavirus disease 2019 (COVID-19) pandemic continues to be the detection of asymptomatic and presymptomatic persons infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Persons infected with SARS-CoV-2 who do not have symptoms of COVID-19 may transmit the virus to others and may have subclinical lung abnormalities. Some hospitals use SARS-CoV-2 antigen tests for pre-admission screening testing because they are relatively inexpensive, have a rapid turnaround time, and can be performed at the point of care; however, antigen tests are generally less sensitive than nucleic acid amplification tests with reverse transcription polymerase chain reaction (RT-PCR) assay. Moreover, as the local COVID-19 prevalence increases, the negative predictive value of antigen tests may decrease, meaning that the probability of having false-negative results may increase. We present a case of a patient who, prior to admission for a surgical procedure, had a negative antigen test result for SARS-CoV-2, had no respiratory symptoms, and had no suspected or known exposure to SARS-CoV-2; however, she tested positive for SARS-CoV-2 RNA after admission. The only factor that led the healthcare team to suspect SARS-CoV-2 infection was an unexpected finding of bilateral ground-glass opacities on an abdominopelvic computed tomography (CT), which was performed to assess the extent of a perianal abscess the patient presented. This case highlights the importance of using highly sensitive SARS-CoV-2 tests for pre-admission screening testing in the hospital setting.

18.
World J Clin Cases ; 8(19): 4360-4369, 2020 Oct 06.
Article in English | MEDLINE | ID: covidwho-819329

ABSTRACT

BACKGROUND: The global outbreak of human severe acute respiratory syndrome coronavirus (SARS-CoV)-2 infection represents an urgent need for readily available, accurate and rapid diagnostic tests. Nucleic acid testing of respiratory tract specimens for SARS-CoV-2 is the current gold standard for diagnosis of coronavirus disease 2019 (COVID-19). However, the diagnostic accuracy of reverse transcription polymerase chain reaction (RT-PCR) tests for detecting SARS-CoV-2 nucleic acid may be lower than optimal. The detection of SARS-CoV-2-specific antibodies should be used as a serological non-invasive tool for the diagnosis and management of SARS-CoV-2 infection. AIM: To investigate the diagnostic value of SARS-CoV-2 IgM/IgG and nucleic acid detection in COVID-19. METHODS: We retrospectively analyzed 652 suspected COVID-19 patients, and 206 non-COVID-19 patients in Wuhan Integrated TCM and Western Medicine Hospital. Data on SARS-CoV-2 nucleic acid tests and serum antibody tests were collected to investigate the diagnostic value of nucleic acid RT-PCR test kits and immunoglobulin (Ig)M/IgG antibody test kits. The χ2 test was used to compare differences between categorical variables. A 95% confidence interval (CI) was provided by the Wilson score method. All analyses were performed with IBM SPSS Statistics version 22.0 (IBM Corp., Armonk, NY, United States). RESULTS: Of the 652 suspected COVID-19 patients, 237 (36.3%) had positive nucleic acid tests, 311 (47.7%) were positive for IgM, and 592 (90.8%) were positive for IgG. There was a significant difference in the positive detection rate between the IgM and IgG test groups (P < 0.001). Using the RT-PCR results as a reference, the specificity, sensitivity, and accuracy of IgM/IgG combined tests for SARS-CoV-2 infection were 98.5%, 95.8%, and 97.1%, respectively. Of the 415 suspected COVID-19 patients with negative nucleic acid test results, 366 had positive IgM/IgG tests with a positive detection rate of 88.2%. CONCLUSION: Our data indicate that serological IgM/IgG antibody combined test had high sensitivity and specificity for the diagnosis of SARS-CoV-2 infection, and can be used in combination with RT-PCR for the diagnosis of SARS-CoV-2 infection.

19.
Expert Rev Respir Med ; 14(12): 1257-1260, 2020 12.
Article in English | MEDLINE | ID: covidwho-671634

ABSTRACT

BACKGROUND: The aim was to compare the laboratory data of patients with suspected and confirmed new coronavirus pneumonia (COVID-19) and look for diagnostic predictive and early warning indicators, which will help to better manage the disease. METHODS: A total of 36 confirmed COVID-19 patients were divided into the general (n = 17) and critical group (n = 19). The suspected group enrolled 23 suspected COVID-19 patients with the negative nucleic acid test result. We collected all patients' clinical characteristics and some laboratory indicators at the time of admission and conducted Logistic regression analysis after comparing the differences between groups. RESULTS: There were no significant differences in age, gender, disease duration, fever history, and comorbidities between the suspected and general group (P > 0.05); however, fibrinogen was statistically different (P < 0.05). Compared with the general group, the oxygenation index and lymphocytes were significantly reduced and the Neutrophil-to-lymphocyte Ratio (NLR) and total bilirubin were increased in the critical group (P < 0.05). The fibrinogen OR value was 2.52 (95% CI 1.18-5.36, P = 0.017) and the NLR OR value was 2.91 (95% CI 1.36-6.21, P = 0.006). CONCLUSIONS: Fibrinogen is a valuable diagnostic predictor for patients with suspected COVID-19. For confirmed COVID-19 patients, the NLR is a valuable early warning indicator.


Subject(s)
COVID-19/diagnosis , Fibrinogen/analysis , Adult , Bilirubin/analysis , Biomarkers/analysis , Case-Control Studies , Critical Illness , Early Diagnosis , Female , Humans , Lymphocyte Count , Male , Middle Aged , Neutrophils/metabolism , Oxygen/blood , Retrospective Studies , SARS-CoV-2
20.
J Radiol Prot ; 40(3): 877-891, 2020 09.
Article in English | MEDLINE | ID: covidwho-723319

ABSTRACT

OBJECTIVES: The detection of Coronavirus Disease 2019 (COVID-19) by reverse transcription polymerase chain reaction (RT-PCR) has varying sensitivity. Computed tomography (CT) of the chest can verify infection in patients with clinical symptoms and a negative test result, accelerating treatment and actions to prevent further contagion. However, CT employs ionising radiation. The purpose of this study was to evaluate protocol settings, associated radiation exposure, image quality and diagnostic performance of a low-dose CT protocol in a university hospital setting. MATERIALS AND METHODS: Chest CT examinations were performed on a single scanner (Somatom Definition Edge, Siemens Healthineers, Germany) in 105 symptomatic patients (60 male, 45 female). Images were evaluated with regard to protocol parameters, image quality, radiation exposure and diagnostic accuracy. Serial RT-PCR served as the standard of reference. Based on this reference standard sensitivity, specificity, positive and negative predictive values of CT with 95% confidence interval were calculated. RESULTS: The mean effective dose was 1.3 ± 0.4 mSv (0.7-2.9 mSv) for the patient cohort (mean age 66.6 ± 16.7 years (19-94 years), mean body mass index (BMI) 26.6 ± 5.3 kg m-2 (16-46 kg/m2)). A sensitivity of 100 [95% CI: 82-100]%, a specificity of 78 [95% CI: 68-86]%, a positive predictive value of 50 [95% CI: 33-67]% and a negative predictive value of 100 [95% CI: 95-100]% were obtained. No COVID-19 diagnoses were missed by CT. Image noise did not strongly correlate with BMI or patient diameter and was rated as average. CONCLUSIONS: We presented a robust imaging procedure with a chest CT protocol for confident diagnosis of COVID-19. Even for an overweight patient cohort, an associated radiation exposure of only 1.3 ± 0.4 mSv was achieved with sufficient diagnostic quality to exclude COVID-19.


Subject(s)
Coronavirus Infections/diagnostic imaging , Pneumonia, Viral/diagnostic imaging , Radiation Dosage , Radiography, Thoracic/standards , Tomography, X-Ray Computed/standards , Adult , Aged , Aged, 80 and over , Betacoronavirus , COVID-19 , Female , Hospitals, University , Humans , Male , Middle Aged , Pandemics , Predictive Value of Tests , Reverse Transcriptase Polymerase Chain Reaction , SARS-CoV-2 , Sensitivity and Specificity
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