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2.
Ther Drug Monit ; 42(3): 360-368, 2020 06.
Article in English | MEDLINE | ID: covidwho-2152206

ABSTRACT

BACKGROUND: COVID-19 is a novel infectious disease caused by the severe acute respiratory distress (SARS)-coronavirus-2 (SARS-CoV-2). Several therapeutic options are currently emerging but none with universal consensus or proven efficacy. Solid organ transplant recipients are perceived to be at increased risk of severe COVID-19 because of their immunosuppressed conditions due to chronic use of immunosuppressive drugs (ISDs). It is therefore likely that solid organ transplant recipients will be treated with these experimental antivirals. METHODS: This article is not intended to provide a systematic literature review on investigational treatments tested against COVID-19; rather, the authors aim to provide recommendations for therapeutic drug monitoring of ISDs in transplant recipients infected with SARS-CoV-2 based on a review of existing data in the literature. RESULTS: Management of drug-drug interactions between investigational anti-SARS-CoV-2 drugs and immunosuppressants is a complex task for the clinician. Adequate immunosuppression is necessary to prevent graft rejection while, if critically ill, the patient may benefit from pharmacotherapeutic interventions directed at limiting SARS-CoV-2 viral replication. Maintaining ISD concentrations within the desired therapeutic range requires a highly individualized approach that is complicated by the pandemic context and lack of hindsight. CONCLUSIONS: With this article, the authors inform the clinician about the potential interactions of experimental COVID-19 treatments with ISDs used in transplantation. Recommendations regarding therapeutic drug monitoring and dose adjustments in the context of COVID-19 are provided.


Subject(s)
Antiviral Agents/adverse effects , Coronavirus Infections/drug therapy , Drug Monitoring , Immunosuppressive Agents/adverse effects , Pneumonia, Viral/drug therapy , Transplant Recipients , Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , Antibodies, Monoclonal, Humanized , Antiviral Agents/therapeutic use , Betacoronavirus , COVID-19 , Drug Interactions , Glucocorticoids , Humans , Hydroxychloroquine , Immunosuppressive Agents/therapeutic use , Pandemics , Protease Inhibitors , SARS-CoV-2
3.
Int J Environ Res Public Health ; 19(22)2022 Nov 15.
Article in English | MEDLINE | ID: covidwho-2116144

ABSTRACT

Due to the global COVID-19 pandemic, a concomitant increase in awareness for end-of-life decisions (EOLDs) and advance care planning has been noted. Whether the dynamic pandemic situation impacted EOLD-processes on the intensive care unit (ICU) and patient-sided advance care planning in Germany is unknown. This is a retrospective analysis of all deceased patients of surgical ICUs of a university medical center from March 2020 to July 2021. All included ICUs had established standardized protocols and documentation for EOLD-related aspects of ICU therapy. The frequency of EOLDs and advance directives and the process of EOLDs were analyzed (No. of ethical approval EA2/308/20). A total number of 319 (85.5%) of all deceased patients received an EOLD. Advance directives were possessed by 83 (22.3%) of the patients and a precautionary power of attorney by 92 (24.7%) of the patients. There was no difference in the frequency of EOLDs and patient-sided advance care planning between patients with COVID-19 and non-COVID-19 patients. In addition, no differences in frequencies of do-not-resuscitate orders, withholding or withdrawing of intensive care medicine therapeutic approaches, timing of EOLDs, and participation of senior ICU attendings in EOLDs were noted between patients with COVID-19 and non-COVID-19 patients. Documentation of family conferences occurred more often in deceased patients with COVID-19 compared to non-COVID-19 patients (COVID-19: 80.0% vs. non-COVID-19: 56.8, p = 0.001). Frequency of EOLDs and completion rates of advance directives remained unchanged during the pandemic compared to pre-pandemic years. The EOLD process did not differ between patients with COVID-19 and non-COVID-19 patients. Institutional standard procedures might contribute to support the robustness of EOLD-making processes during unprecedented medical emergencies, such as new pandemic diseases.


Subject(s)
COVID-19 , Terminal Care , Humans , Pandemics , Retrospective Studies , Decision Making , COVID-19/epidemiology , Intensive Care Units
4.
Pathogens ; 11(10)2022 Sep 20.
Article in English | MEDLINE | ID: covidwho-2099690

ABSTRACT

Despite extensive vaccination and booster programs, SARS-CoV-2 outbreaks in long-term care facilities (LTCF) continue to occur. We retrospectively describe a SARS-CoV-2 outbreak amongst a partially vaccinated LTCF population in The Netherlands which occurred in March 2021. The facility comprised three floors functioning as separate wards. Nasopharyngeal swabs for SARS-CoV-2 qRT-PCR were obtained from residents and staff presenting with COVID-19-like symptoms and from all residents and staff during two point prevalence screenings (PPS). Samples meeting technical criteria were included for phylogenetic analysis. Positive SARS-CoV-2 qRT-PCR were obtained from 11 (18%) of 61 residents and 8 (7%) of 110 staff members between March 8 and March 25. Seven (37%) cases and five (63%) vaccinated cases were diagnosed through PPS. Cases were found on all wards. Phylogenetic analysis (n = 11) showed a maximum difference of four nucleotides between sequences on the outer branches of the tree, but identified two identical sequences on the root differing maximum two nucleotides from all other sequences, suggesting all did belong to the same cluster. Our results imply that PPS is useful in containing SARS-CoV-2 outbreaks amongst (vaccinated) LTCF populations, as an entire LTCF might behave as a single epidemiological unit and it is preferable to maximize the number of samples included for phylogenetic analysis.

5.
BMC Med ; 20(1): 406, 2022 10 24.
Article in English | MEDLINE | ID: covidwho-2089197

ABSTRACT

BACKGROUND: The diagnostic accuracy of unsupervised self-testing with rapid antigen diagnostic tests (Ag-RDTs) is mostly unknown. We studied the diagnostic accuracy of a self-performed SARS-CoV-2 saliva and nasal Ag-RDT in the general population. METHODS: This large cross-sectional study consecutively included unselected individuals aged ≥ 16 years presenting for SARS-CoV-2 testing at three public health service test sites. Participants underwent molecular test sampling and received two self-tests (the Hangzhou AllTest Biotech saliva self-test and the SD Biosensor nasal self-test by Roche Diagnostics) to perform themselves at home. Diagnostic accuracy of both self-tests was assessed with molecular testing as reference. RESULTS: Out of 2819 participants, 6.5% had a positive molecular test. Overall sensitivities were 46.7% (39.3-54.2%) for the saliva Ag-RDT and 68.9% (61.6-75.6%) for the nasal Ag-RDT. With a viral load cut-off (≥ 5.2 log10 SARS-CoV-2 E-gene copies/mL) as a proxy of infectiousness, these sensitivities increased to 54.9% (46.4-63.3%) and 83.9% (76.9-89.5%), respectively. For the nasal Ag-RDT, sensitivities were 78.5% (71.1-84.8%) and 22.6% (9.6-41.1%) in those symptomatic and asymptomatic at the time of sampling, which increased to 90.4% (83.8-94.9%) and 38.9% (17.3-64.3%) after applying the viral load cut-off. In those with and without prior SARS-CoV-2 infection, sensitivities were 36.8% (16.3-61.6%) and 72.7% (65.1-79.4%). Specificities were > 99% and > 99%, positive predictive values > 70% and > 90%, and negative predictive values > 95% and > 95%, for the saliva and nasal Ag-RDT, respectively, in most analyses. Most participants considered the self-performing and result interpretation (very) easy for both self-tests. CONCLUSIONS: The Hangzhou AllTest Biotech saliva self Ag-RDT is not reliable for SARS-CoV-2 detection, overall, and in all studied subgroups. The SD Biosensor nasal self Ag-RDT had high sensitivity in individuals with symptoms and in those without prior SARS-CoV-2 infection but low sensitivity in asymptomatic individuals and those with a prior SARS-CoV-2 infection which warrants further investigation.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , COVID-19/diagnosis , Cross-Sectional Studies , COVID-19 Testing , Saliva , Sensitivity and Specificity , Antigens, Viral
6.
Proceedings of Emerging Trends and Technologies on Intelligent Systems (Ettis 2021) ; 1371:243-249, 2022.
Article in English | Web of Science | ID: covidwho-2085280

ABSTRACT

Due to the advancement in technology, the exchange of information via a network has been taking such a great peak that each and every person is highly dependent on the Internet, like in the current Covid-19 pandemic situation. But sharing information/secret medical data by means of the Internet has created a risk to the information loss. Thus, data exchange should be done in such a way that its presence cannot be perceived by the third party with bad intentions and should not be able to modify or alter the important message. For the safety of important data, many algorithms like cryptography, steganography, watermarking, etc. have been used by researchers to safeguard data sharing via an insecure Internet. Cryptography and steganography together can provide better security to the data as one encrypts the data and the other hides its presence in multimedia, like image, audio, video, etc. In this paper, data encryption and image steganography have been presented to provide security to the message that is being transferred through the Internet. The experimental outcomes show that the proposed technique is able to transfer important data securely without coming into the eyes of a hacker. The PSNR value for the proposed system is about 51.14 with 1 bit per pixel (bpp) capacity. As per the security view, the presented method has a 7.99 entropy value, which means the system is secure against attacks.

7.
Acta Orthop ; 93: 808-818, 2022 Oct 14.
Article in English | MEDLINE | ID: covidwho-2080026

ABSTRACT

BACKGROUND AND PURPOSE: During the first COVID-19 lockdown elective surgery was greatly reduced. Prioritization of patients with greater need and expected benefit in terms of quality of life was advised. The lockdown also potentially affected follow-up outcomes. Therefore, our study compared patient-reported outcome measures (PROMs) retrieved during the lockdown of Dutch primary total hip and knee arthroplasty (THA, TKA) patients with previous years. PATIENTS AND METHODS: We performed cross-sectional analyses using national data from the Dutch Orthopaedic Registry (LROI). All primary elective THA and TKA patients with preoperative or postoperative PROMs (EQ-5D-3L index, OHS/OKS) during the first COVID-19 lockdown between March and July 15, 2020 were included. Patients with PROMs during the same months in 2018 plus 2019 were used as control. Finally, 33,453 THA and 27,335 TKA patients were included. Patient characteristics were compared during versus before the lockdown. Subsequently, the lockdown effect on PROMs scores was analyzed with multivariable linear regression. RESULTS: During the COVID-19 lockdown, THA and TKA patients had a lower age and BMI preoperatively, and more often had surgery in private clinics. Both preoperative PROMs in THA patients, but not in TKA patients, were worse (EQ-5D: Adjusted mean difference (AMD) -0.021, p < 0.001) during the lockdown compared with prior years. Both postoperative PROMs in THA and TKA patients were better during the lockdown (12-month EQ-5D in THA: AMD 0.010, p = 0.003; and in TKA: AMD 0.013, p < 0.001). INTERPRETATION: During the COVID-19 lockdown, THA patients had slightly worse preoperative PROMs, suggesting selection of patients with greater urgency. Postoperative PROMs in both THA and TKA patients differed minimally. Overall, the observed differences were likely not clinically relevant.


Subject(s)
Arthroplasty, Replacement, Hip , Arthroplasty, Replacement, Knee , COVID-19 , COVID-19/epidemiology , Communicable Disease Control , Cross-Sectional Studies , Humans , Patient Reported Outcome Measures , Quality of Life
8.
BMJ ; 378: e071215, 2022 09 14.
Article in English | MEDLINE | ID: covidwho-2029495

ABSTRACT

OBJECTIVE: To assess the performance of rapid antigen tests with unsupervised nasal and combined oropharyngeal and nasal self-sampling during the omicron period. DESIGN: Prospective cross sectional diagnostic test accuracy study. SETTING: Three public health service covid-19 test sites in the Netherlands, 21 December 2021 to 10 February 2022. PARTICIPANTS: 6497 people with covid-19 symptoms aged ≥16 years presenting for testing. INTERVENTIONS: Participants had a swab sample taken for reverse transcription polymerase chain reaction (RT-PCR, reference test) and received one rapid antigen test to perform unsupervised using either nasal self-sampling (during the emergence of omicron, and when omicron accounted for >90% of infections, phase 1) or with combined oropharyngeal and nasal self-sampling in a subsequent (phase 2; when omicron accounted for >99% of infections). The evaluated tests were Flowflex (Acon Laboratories; phase 1 only), MPBio (MP Biomedicals), and Clinitest (Siemens-Healthineers). MAIN OUTCOME MEASURES: The main outcomes were sensitivity, specificity, and positive and negative predictive values of each self-test, with RT-PCR testing as the reference standard. RESULTS: During phase 1, 45.0% (n=279) of participants in the Flowflex group, 29.1% (n=239) in the MPBio group, and 35.4% ((n=257) in the Clinitest group were confirmatory testers (previously tested positive by a self-test at own initiative). Overall sensitivities with nasal self-sampling were 79.0% (95% confidence interval 74.7% to 82.8%) for Flowflex, 69.9% (65.1% to 74.4%) for MPBio, and 70.2% (65.6% to 74.5%) for Clinitest. Sensitivities were substantially higher in confirmatory testers (93.6%, 83.6%, and 85.7%, respectively) than in those who tested for other reasons (52.4%, 51.5%, and 49.5%, respectively). Sensitivities decreased from 87.0% to 80.9% (P=0.16 by χ2 test), 80.0% to 73.0% (P=0.60), and 83.1% to 70.3% (P=0.03), respectively, when transitioning from omicron accounting for 29% of infections to >95% of infections. During phase 2, 53.0% (n=288) of participants in the MPBio group and 44.4% (n=290) in the Clinitest group were confirmatory testers. Overall sensitivities with combined oropharyngeal and nasal self-sampling were 83.0% (78.8% to 86.7%) for MPBio and 77.3% (72.9% to 81.2%) for Clinitest. When combined oropharyngeal and nasal self-sampling was compared with nasal self-sampling, sensitivities were found to be slightly higher in confirmatory testers (87.4% and 86.1%, respectively) and substantially higher in those testing for other reasons (69.3% and 59.9%, respectively). CONCLUSIONS: Sensitivities of three rapid antigen tests with nasal self-sampling decreased during the emergence of omicron but was only statistically significant for Clinitest. Sensitivities appeared to be substantially influenced by the proportion of confirmatory testers. Sensitivities of MPBio and Clinitest improved after the addition of oropharyngeal to nasal self-sampling. A positive self-test result justifies prompt self-isolation without the need for confirmatory testing. Individuals with a negative self-test result should adhere to general preventive measures because a false negative result cannot be ruled out. Manufacturers of MPBio and Clinitest may consider extending their instructions for use to include combined oropharyngeal and nasal self-sampling, and other manufacturers of rapid antigen tests should consider evaluating this as well.


Subject(s)
COVID-19 , COVID-19/diagnosis , COVID-19 Testing , Citric Acid , Copper Sulfate , Cross-Sectional Studies , Humans , Prospective Studies , Sodium Bicarbonate , Specimen Handling , United States
9.
Neurol Neuroimmunol Neuroinflamm ; 9(6)2022 11.
Article in English | MEDLINE | ID: covidwho-2021402

ABSTRACT

BACKGROUND AND OBJECTIVES: Certain demographic and clinical characteristics, including the use of some disease-modifying therapies (DMTs), are associated with severe acute respiratory syndrome coronavirus 2 infection severity in people with multiple sclerosis (MS). Comprehensive exploration of these relationships in large international samples is needed. METHODS: Clinician-reported demographic/clinical data from 27 countries were aggregated into a data set of 5,648 patients with suspected/confirmed coronavirus disease 2019 (COVID-19). COVID-19 severity outcomes (hospitalization, admission to intensive care unit [ICU], requiring artificial ventilation, and death) were assessed using multilevel mixed-effects ordered probit and logistic regression, adjusted for age, sex, disability, and MS phenotype. DMTs were individually compared with glatiramer acetate, and anti-CD20 DMTs with pooled other DMTs and with natalizumab. RESULTS: Of 5,648 patients, 922 (16.6%) with suspected and 4,646 (83.4%) with confirmed COVID-19 were included. Male sex, older age, progressive MS, and higher disability were associated with more severe COVID-19. Compared with glatiramer acetate, ocrelizumab and rituximab were associated with higher probabilities of hospitalization (4% [95% CI 1-7] and 7% [95% CI 4-11]), ICU/artificial ventilation (2% [95% CI 0-4] and 4% [95% CI 2-6]), and death (1% [95% CI 0-2] and 2% [95% CI 1-4]) (predicted marginal effects). Untreated patients had 5% (95% CI 2-8), 3% (95% CI 1-5), and 1% (95% CI 0-3) higher probabilities of the 3 respective levels of COVID-19 severity than glatiramer acetate. Compared with pooled other DMTs and with natalizumab, the associations of ocrelizumab and rituximab with COVID-19 severity were also more pronounced. All associations persisted/enhanced on restriction to confirmed COVID-19. DISCUSSION: Analyzing the largest international real-world data set of people with MS with suspected/confirmed COVID-19 confirms that the use of anti-CD20 medication (both ocrelizumab and rituximab), as well as male sex, older age, progressive MS, and higher disability are associated with more severe course of COVID-19.


Subject(s)
COVID-19 , Multiple Sclerosis, Chronic Progressive , Multiple Sclerosis , Antigens, CD20 , Glatiramer Acetate/therapeutic use , Humans , Immunosuppressive Agents/therapeutic use , Information Dissemination , Male , Multiple Sclerosis/drug therapy , Multiple Sclerosis/epidemiology , Multiple Sclerosis, Chronic Progressive/drug therapy , Natalizumab/therapeutic use , Risk Factors , Rituximab/therapeutic use
10.
Ann Work Expo Health ; 2022 Sep 07.
Article in English | MEDLINE | ID: covidwho-2017721

ABSTRACT

There is an ongoing debate on airborne transmission of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) as a risk factor for infection. In this study, the level of SARS-CoV-2 in air and on surfaces of SARS-CoV-2 infected nursing home residents was assessed to gain insight in potential transmission routes. During outbreaks, air samples were collected using three different active and one passive air sampling technique in rooms of infected patients. Oropharyngeal swabs (OPS) of the residents and dry surface swabs were collected. Additionally, longitudinal passive air samples were collected during a period of 4 months in common areas of the wards. Presence of SARS-CoV-2 RNA was determined using RT-qPCR, targeting the RdRp- and E-genes. OPS, samples of two active air samplers and surface swabs with Ct-value ≤35 were tested for the presence of infectious virus by cell culture. In total, 360 air and 319 surface samples from patient rooms and common areas were collected. In rooms of 10 residents with detected SARS-CoV-2 RNA in OPS, SARS-CoV-2 RNA was detected in 93 of 184 collected environmental samples (50.5%) (lowest Ct 29.5), substantially more than in the rooms of residents with negative OPS on the day of environmental sampling (n = 2) (3.6%). SARS-CoV-2 RNA was most frequently present in the larger particle size fractions [>4 µm 60% (6/10); 1-4 µm 50% (5/10); <1 µm 20% (2/10)] (Fischer exact test P = 0.076). The highest proportion of RNA-positive air samples on room level was found with a filtration-based sampler 80% (8/10) and the cyclone-based sampler 70% (7/10), and impingement-based sampler 50% (5/10). SARS-CoV-2 RNA was detected in 10 out of 12 (83%) passive air samples in patient rooms. Both high-touch and low-touch surfaces contained SARS-CoV-2 genome in rooms of residents with positive OPS [high 38% (21/55); low 50% (22/44)]. In one active air sample, infectious virus in vitro was detected. In conclusion, SARS-CoV-2 is frequently detected in air and on surfaces in the immediate surroundings of room-isolated COVID-19 patients, providing evidence of environmental contamination. The environmental contamination of SARS-CoV-2 and infectious aerosols confirm the potential for transmission via air up to several meters.

11.
J Gen Intern Med ; 37(Suppl 3): 778-785, 2022 09.
Article in English | MEDLINE | ID: covidwho-2007240

ABSTRACT

BACKGROUND: Increasingly, women are serving in the military and seeking care at the Veterans Health Administration (VHA). Women veterans face unique challenges and barriers in seeking mental health (MH) care within VHA. VA Video Connect (VVC), which facilitates video-based teleconferencing between patients and providers, can reduce barriers while maintaining clinical effectiveness. OBJECTIVE: Primary aims were to examine gender differences in VVC use, describe changes in VVC use over time (including pre-COVID and 6 months following the beginning of COVID), and determine whether changes over time differed by gender. DESIGN: A retrospective cohort investigation of video-to-home telehealth for MH care utilization among veterans having at least 1 MH visit from October 2019 to September 2020. PARTICIPANTS: Veterans (236,268 women; 1,318,024 men). INTERVENTIONS (IF APPLICABLE): VVC involves face-to-face, synchronous, video-based teleconferencing between patients and providers, enabling care at home or another private location. MAIN MEASURES: Percentage of MH encounters delivered via VA Video Connect. KEY RESULTS: Women veterans were more likely than men to have at least 1 VVC encounter and had a greater percentage of MH care delivered via VVC in FY20. There was an increase in the percentage of MH encounters that were VVC over FY20, and this increase was greater for women than men. Women veterans who were younger than 55 (compared to those 55 and older), lived in urban areas (compared to those in rural areas), or were Asian (compared to other races) had a greater percentage of MH encounters that were VVC since the start of the pandemic, controlling for the mean percentage of VVC MH encounters in the 6 months pre-pandemic. CONCLUSIONS: VVC use for MH care is greater in women veterans compared to male veterans and may reduce gender-specific access barriers. Future research and VVC implementation efforts should emphasize maximizing patient choice and satisfaction.


Subject(s)
COVID-19 , Telemedicine , Veterans , COVID-19/epidemiology , Female , Humans , Male , Patient Acceptance of Health Care , Retrospective Studies , United States/epidemiology , United States Department of Veterans Affairs , Veterans/psychology , Veterans Health
12.
Lancet Digit Health ; 4(10): e727-e737, 2022 10.
Article in English | MEDLINE | ID: covidwho-2004682

ABSTRACT

BACKGROUND: The SARS-CoV-2 pandemic is a worldwide challenge. The CRIT-CoV-U pilot study generated a urinary proteomic biomarker consisting of 50 peptides (COV50), which predicted death and disease progression from SARS-CoV-2. After the interim analysis presented for the German Government, here, we aimed to analyse the full dataset to consolidate the findings and propose potential clinical applications of this biomarker. METHODS: CRIT-CoV-U was a prospective multicentre cohort study. In eight European countries (Austria, France, Germany, Greece, North Macedonia, Poland, Spain, and Sweden), 1012 adults with PCR-confirmed COVID-19 were followed up for death and progression along the 8-point WHO scale. Capillary electrophoresis coupled with mass spectrometry was used for urinary proteomic profiling. Statistical methods included logistic regression and receiver operating characteristic curve analysis with a comparison of the area under curve (AUC) between nested models. Hospitalisation costs were derived from the care facility corresponding with the Markov chain probability of reaching WHO scores ranging from 3 to 8 and flat-rate hospitalisation costs adjusted for the gross per capita domestic product of each country. FINDINGS: From June 30 to Nov 19, 2020, 228 participants were recruited, and from April 30, 2020, to April 14, 2021, 784 participants were recruited, resulting in a total of 1012 participants. The entry WHO scores were 1-3 in 445 (44%) participants, 4-5 in 529 (52%) participants, and 6 in 38 (4%) participants; and of all participants, 119 died and 271 had disease progression. The odds ratio (OR) associated with COV50 in all 1012 participants for death was 2·44 (95% CI 2·05-2·92) unadjusted and 1·67 (1·34-2·07) when adjusted for sex, age, BMI, comorbidities, and baseline WHO score; and for disease progression, the OR was 1·79 (1·60-2·01) when unadjusted and 1·63 (1·41-1·91) when adjusted (p<0·0001 for all). The predictive accuracy of the optimised COV50 thresholds was 74·4% (71·6-77·1%) for mortality (threshold 0·47) and 67·4% (64·4-70·3%) for disease progression (threshold 0·04). When adjusted for covariables and the baseline WHO score, these thresholds improved AUCs from 0·835 to 0·853 (p=0·033) for death and from 0·697 to 0·730 (p=0·0008) for progression. Of 196 participants who received ambulatory care, 194 (99%) did not reach the 0·04 threshold. The cost reductions associated with 1 day less hospitalisation per 1000 participants were million Euro (M€) 0·887 (5-95% percentile interval 0·730-1·039) in participants at a low risk (COV50 <0·04) and M€2·098 (1·839-2·365) in participants at a high risk (COV50 ≥0·04). INTERPRETATION: The urinary proteomic COV50 marker might be predictive of adverse COVID-19 outcomes. Even in people with mild-to-moderate PCR-confirmed infections (WHO scores 1-4), the 0·04 COV50 threshold justifies earlier drug treatment, thereby potentially reducing the number of days in hospital and associated costs. FUNDING: German Federal Ministry of Health.


Subject(s)
COVID-19 , Adult , Biomarkers , COVID-19/diagnosis , Cohort Studies , Disease Progression , Humans , Pilot Projects , Prospective Studies , Proteomics , SARS-CoV-2
13.
Ther Drug Monit ; 2022 Aug 09.
Article in English | MEDLINE | ID: covidwho-1985145

ABSTRACT

ABSTRACT: Nirmatrelvir/ritonavir (Paxlovid®) consists of a peptidomimetic inhibitor (Nirmatrelvir) of the SARS-CoV-2 main protease and a pharmacokinetic enhancer (Ritonavir). It is approved for the treatment of mild-to-moderate COVID-19. This combination of nirmatrelvir and ritonavir can mediate significant and complex drug-drug interactions (DDIs), primarily due to the ritonavir component. Indeed, ritonavir inhibits the metabolism of nirmatrelvir through cytochrome P450 3A (CYP3A) leading to higher plasma concentrations and a longer half-life of nirmatrelvir. Co-administration of nirmatrelvir/ritonavir with immunosuppressant drugs (ISDs) is particularly challenging given the major involvement of CYP3A in the metabolism of most of these drugs and their narrow therapeutic ranges. Exposure of ISDs will be drastically increased through the potent ritonavir-mediated inhibition of CYP3A, resulting in an increased risk of adverse drug reactions. While a decrease in the dosage of ISDs can prevent toxicity, an inappropriate dosage regimen may also result in insufficient exposure and a risk of rejection. Here we provide some general recommendations for therapeutic drug monitoring (TDM) of ISDs and dosing recommendations when co-administered with nirmatrelvir/ritonavir. Particularly, tacrolimus should be discontinued, or patients should be given a microdose on day-1, while cyclosporine dosage should be reduced to 20% of the initial dosage during the antiviral treatment. Dosages of mammalian target of rapamycin inhibitors (m-TORis) should also be adjusted while dosages of mycophenolic acid and corticosteroids are expected to be less impacted.

14.
Clin Exp Rheumatol ; 40(8): 1504-1509, 2022 Sep.
Article in English | MEDLINE | ID: covidwho-1935083

ABSTRACT

OBJECTIVES: The aim of this study is to investigate the cumulative incidence and the severity of COVID-19 infections in patients with Behçet's disease. METHODS: A retrospective cohort study of patients with Behçet's disease was conducted. We obtained the data systematically from electronic patient files and through telephone interviews between February 2020 and May 1, 2021. Main outcomes were COVID-19 infection, disease duration, hospitalisation, intensive care admission and mortality. Secondary outcome was adherence to quarantine measures as recommended by the government. RESULTS: 185 Behçet's disease patients were included (mean age 42.2 years, 54% female); 58% of the patients were receiving colchicine, 30% anti-TNFα, 16% azathioprine and 8% systemic steroids. 30 patients (16.2%) were positive for COVID-19. Within our cohort, the cumulative incidence of COVID-19 was therefore 16.2% (95% CI 11.2-22.3%), which is significantly increased when compared to the general Dutch population (8.7% (95% CI 8.72-8.73%)) (p < 0.001). Four out of 30 (13%) patients were admitted to the hospital. There was no COVID-19 related mortality observed. Patients adhered to government measures; except in the period between the 1st of June and the 28th of September, this cohort received more visitors than in period 1 and 3. CONCLUSIONS: In this cohort, Behçet's disease patients have a higher risk for COVID-19 infection, without an increase of virus-related mortality. The course of COVID-19 disease in this cohort is relatively mild, with a lower admission rate than expected of patients using immunosuppressive medication.


Subject(s)
Behcet Syndrome , COVID-19 , Adult , Azathioprine/therapeutic use , Behcet Syndrome/diagnosis , Behcet Syndrome/drug therapy , Behcet Syndrome/epidemiology , COVID-19/epidemiology , Female , Humans , Male , Netherlands/epidemiology , Retrospective Studies
15.
Transpl Int ; 35: 10369, 2022.
Article in English | MEDLINE | ID: covidwho-1933952

ABSTRACT

Kidney transplant recipients (KTRs) are at increased risk for a more severe course of COVID-19, due to their pre-existing comorbidity and immunosuppression. Consensus protocols recommend lowering immunosuppression in KTRs with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, but the optimal combination remains unclear. Calcineurin inhibitors (CNIs) are cornerstone immunosuppressants used in KTRs and some have been reported to possess antiviral activity against RNA viruses, including coronaviruses. Here, we evaluated the effect of the CNIs tacrolimus, cyclosporin A, and voclosporin (VCS), as well as other immunosuppressants, on SARS-CoV-2 replication in cell-based assays. Unexpected, loss of compound due to plastic binding and interference of excipients in pharmaceutical formulations (false-positive results) complicated the determination of EC50 values of cyclophilin-dependent CNI's in our antiviral assays. Some issues could be circumvented by using exclusively glass lab ware with pure compounds. In these experiments, VCS reduced viral progeny yields in human Calu-3 cells at low micromolar concentrations and did so more effectively than cyclosporin A, tacrolimus or other immunosuppressants. Although, we cannot recommend a particular immunosuppressive regimen in KTRs with COVID-19, our data suggest a potential benefit of cyclophilin-dependent CNIs, in particular VCS in reducing viral progeny, which warrants further clinical evaluation in SARS-CoV-2-infected KTRs.


Subject(s)
COVID-19 , SARS-CoV-2 , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , COVID-19/drug therapy , Calcineurin Inhibitors/pharmacology , Calcineurin Inhibitors/therapeutic use , Cell Culture Techniques , Cyclophilins , Cyclosporine/pharmacology , Humans , Immunosuppressive Agents/adverse effects , Tacrolimus/pharmacology
16.
American Journal of Respiratory and Critical Care Medicine ; 205(1), 2022.
Article in English | EMBASE | ID: covidwho-1927736

ABSTRACT

Background: The COVID-19 pandemic has led to extremely high levels of emotional distress and burnout amongst frontline healthcare workers. Rapidly deployable and scalable interventions are desperately needed to help combat the burgeoning mental health crisis among frontline healthcare works. Methods: We designed a prospective, randomized, waitlist-controlled pilot study assessing the impact of a mobile mindfulness app (LIFT) among nurses working in COVID-19 units. Participants were randomized in a 2:1 fashion to receive access to mobile mindfulness content (intervention) or to a waitlist to receive access to mobile mindfulness content outside the study period (control). All patients completed a survey that includes the Patient Health Questionairre-9 (PHQ-9), The General Anxiety Disorder-7 (GAD-7), the Perceived Stress Scale-4 (PSS-4), and the Maslach Burnout Index (MBI) at baseline (T1) and at the end of the study period (28 days after enrollment, T2). Primary outcomes are feasibility as assessed by the number of participants completing all 4 weeks of mindfulness therapy as well as the total number of daily mindfulness sessions completed. Secondary outcomes included change in PHQ-9, GAD-7, PSS-4, and MBI scores from T1 to T2. Results: Enrollment began in May of 2021. To date 82 participants have been enrolled and randomized, 56 to intervention and 24 to waitlist, with a target enrollment of 100. Median PHQ-9 scores in each group were 8 (IQR 6-11.25) and 7 (IQR 5-10) indicating moderate amounts of emotional distress in each group. Enrollment and follow-up are ongoing, with enrollment planned to be completed in December 2021. Conclusions: We have successfully enrolled 82 participants in an ongoing randomized, waitlist-controlled trial testing the clinical impact of a mobile mindfulness intervention on emotional distress and burnout in frontline healthcare workers. Final results will be presented at ATS International Meeting.

17.
Intensive Care Med Exp ; 10(1): 28, 2022 Jun 27.
Article in English | MEDLINE | ID: covidwho-1910362

ABSTRACT

Nitric oxide (NO) is a key molecule in the biology of human life. NO is involved in the physiology of organ viability and in the pathophysiology of organ dysfunction, respectively. In this narrative review, we aimed at elucidating the mechanisms behind the role of NO in the respiratory and cardio-cerebrovascular systems, in the presence of a healthy or dysfunctional endothelium. NO is a key player in maintaining multiorgan viability with adequate organ blood perfusion. We report on its physiological endogenous production and effects in the circulation and within the lungs, as well as the pathophysiological implication of its disturbances related to NO depletion and excess. The review covers from preclinical information about endogenous NO produced by nitric oxide synthase (NOS) to the potential therapeutic role of exogenous NO (inhaled nitric oxide, iNO). Moreover, the importance of NO in several clinical conditions in critically ill patients such as hypoxemia, pulmonary hypertension, hemolysis, cerebrovascular events and ischemia-reperfusion syndrome is evaluated in preclinical and clinical settings. Accordingly, the mechanism behind the beneficial iNO treatment in hypoxemia and pulmonary hypertension is investigated. Furthermore, investigating the pathophysiology of brain injury, cardiopulmonary bypass, and red blood cell and artificial hemoglobin transfusion provides a focus on the potential role of NO as a protective molecule in multiorgan dysfunction. Finally, the preclinical toxicology of iNO and the antimicrobial role of NO-including its recent investigation on its role against the Sars-CoV2 infection during the COVID-19 pandemic-are described.

18.
Implement Sci Commun ; 3(1): 66, 2022 Jun 20.
Article in English | MEDLINE | ID: covidwho-1896399

ABSTRACT

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic dramatically increased the use of telemental health via videoconferencing (TMH-V). While TMH-V has been found to be effective and satisfactory to both patients and providers, little is known regarding factors that influence site-level uptake. We examined facilitators and barriers to TMH-V uptake at higher and lower adoption sites within the US Department of Veterans Affairs (VA). METHODS: We conducted twenty-four semi-structured qualitative interviews at four northeastern VA medical centers (two with higher TMH-V adoption and two with lower adoption). Six interviews were conducted per site (one member of mental health leadership, one facility telehealth coordinator/technician, and four mental health providers per site). We performed directed content analysis, guided by the Consolidated Framework for Implementation Research (CFIR), followed by a matrix rating process to rank the degree of influence of each of the 19 included CFIR constructs at the four sites. Positive overall influences, negative overall influences, and differentiators were then identified based on patterns in ratings across sites. RESULTS: Five CFIR constructs had positive overall influences across sites: Relative advantage, Patient needs and resources, Relative priority, Knowledge and beliefs, and Self-efficacy. Complexity had a negative overall influence across sites. Four constructs significantly differentiated between higher and lower adoption sites with regards to TMH-V use: Quality, Compatibility, Leadership engagement, and Champions. CONCLUSIONS: Several positive overall influences on TMH-V uptake were identified across sites; respondents acknowledged multiple advantages of TMH-V (e.g., convenience), and providers' attitudes towards TMH-V improved as they gained experience. In contrast, complexity was a negative overall influence; TMH-V platforms and processes must be simple and user friendly to promote use. The emergence of Quality, Leadership engagement, and Champions as differentiators speaks to the importance of educating frontline staff and leadership at lower adoption sites about the evidence base demonstrating that TMH-V is high-quality care. Compatibility also emerged as a differentiator; if TMH-V is not easily integrated into provider workflows, uptake will falter. Future work should draw from these findings to develop implementation strategies aiming to increase TMH-V uptake at lower adoption sites, thereby increasing access to high-quality mental health care.

19.
Psychiatr Serv ; : appips202100363, 2022 Jun 02.
Article in English | MEDLINE | ID: covidwho-1874945

ABSTRACT

OBJECTIVE: The authors examined the use of Veterans Affairs Video Connect (VVC) for mental health care by rural and urban veterans and the impact of the COVID-19 pandemic on patterns of VVC use. METHODS: Data from 557,668 rural and 1,384,093 urban veterans (collected July 2019-October 2020) from the Veterans Health Administration Corporate Data Warehouse were examined with interrupted time-series models to determine rural versus urban VVC use before and during the initial 7 months of the pandemic. RESULTS: Before COVID-19, rates of VVC use as percentages of all mental health care were higher among rural veterans. After implementation of pandemic restrictions, rural veteran VVC use continued to increase, but this increase was surpassed by that of urban veterans. CONCLUSIONS: These findings highlight the need to monitor emerging disparities in telehealth use and to encourage and support use of VVC and access to mental health care for all veterans, particularly those experiencing barriers to care.

20.
Nucl Med Biol ; 112-113: 1-8, 2022.
Article in English | MEDLINE | ID: covidwho-1867632

ABSTRACT

RATIONALE: The aim of this study was to investigate the application of [18F]DPA714 to visualize the inflammation process in the lungs of SARS-CoV-2-infected rhesus monkeys, focusing on the presence of pulmonary lesions, activation of mediastinal lymph nodes and surrounded lung tissue. METHODS: Four experimentally SARS-CoV-2 infected rhesus monkeys were followed for seven weeks post infection (pi) with a weekly PET-CT using [18F]DPA714. Two PET images, 10 min each, of a single field-of-view covering the chest area, were obtained 10 and 30 min after injection. To determine the infection process swabs, blood and bronchoalveolar lavages (BALs) were obtained. RESULTS: All animals were positive for SARS-CoV-2 in both the swabs and BALs on multiple timepoints pi. The initial development of pulmonary lesions was already detected at the first scan, performed 2-days pi. PET revealed an increased tracer uptake in the pulmonary lesions and mediastinal lymph nodes of all animals from the first scan obtained after infection and onwards. However, also an increased uptake was detected in the lung tissue surrounding the lesions, which persisted until day 30 and then subsided by day 37-44 pi. In parallel, a similar pattern of increased expression of activation markers was observed on dendritic cells in blood. PRINCIPAL CONCLUSIONS: This study illustrates that [18F]DPA714 is a valuable radiotracer to visualize SARS-CoV-2-associated pulmonary inflammation, which coincided with activation of dendritic cells in blood. [18F]DPA714 thus has the potential to be of added value as diagnostic tracer for other viral respiratory infections.


Subject(s)
COVID-19 , Pneumonia , Animals , COVID-19/diagnostic imaging , Lung/diagnostic imaging , Lung/pathology , Macaca mulatta , Pneumonia/diagnostic imaging , Pneumonia/pathology , Positron Emission Tomography Computed Tomography/methods , Pyrazoles , Pyrimidines , SARS-CoV-2
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