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Hausarztpraxis Sonnenhof
Dr. med. Fabian Treusch
Facharzt für Innere Medizin, Kardiologe
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Aktuelle SARS-CoV-2-Preprints
medRxiv
Quelle: medRxiv-Server-Feed
(Filter: "SARS-CoV-2" oder "COVID-19" im Titel oder in der Beschreibung)

Generalizable Long COVID Subtypes: Findings from the NIH N3C and RECOVER Programs
Accurate stratification of patients with Post-acute sequelae of SARS-CoV-2 infection (PASC, or long COVID) would allow precision clinical management strategies and could enable more focussed investigation of the molecular pathogenetic mechanisms of this disease. However, the natural history of long COVID is incompletely understood and characterized by an extremely wide range of manifestations that are difficult to analyze computationally. In addition, the generalizability of machine learning classification of COVID-19 clinical outcomes has rarely been tested. We present a method for computationally modeling long COVID phenotype data based on electronic healthcare records (EHRs) and for assessing pairwise phenotypic similarity between patients using semantic similarity. Using unsupervised machine learning (k-means clustering), we found six distinct clusters of long COVID patients, each with distinct profiles of phenotypic abnormalities with enrichments in pulmonary, cardiovascular, neuropsychiatric, and constitutional symptoms such as fatigue and fever. There was a highly significant association of cluster membership with a range of pre-existing conditions and with measures of severity during acute COVID-19. We show that the clusters we identified in one hospital system were generalizable across different hospital systems. Semantic phenotypic clustering can provide a foundation for assigning patients to stratified subgroups for natural history or therapy studies on long COVID. [Veröffentlicht: 25.05.2022]
Reese, J., Blau, H., Bergquist, T., Loomba, J. J., Callahan, T., Laraway, B., Antonescu, C., Casiraghi, E., Coleman, B., Gargano, M., Wilkins, K., Cappelletti, L., Fontana, T., Ammar, N., Antony, B., Murali, T. M., Karlebach, G., McMurry, J. A., Williams, A., Moffitt, R., Banerjee, J., Solomonides, A. E., Davis, H., Kostka, K., Valentini, G., Sahner, D., Chute, C. G., Madlock-Brown, C., Haendel, M. A., Robinson, P. N.

Clearing the Fog: A Systematic Review on Cognitive Dysfunction in COVID-19
Objective: The systematic review aims to examine the association between COVID-19 and cognitive dysfunction, including the link between the severity of COVID-19 and the occurrence of cognitive impairment and the potential pathophysiological mechanisms related to brain fog among COVID-19 patients. Methods: PubMed, Oxford University Press, ProQuest Health and Medical Complete, ScienceDirect, Ovid, HERDIN, Google Scholar, and Cochrane Library databases were accessed to retrieve literature using the PRISMA guidelines. Results: After critical appraisal, thirteen full journal articles were included in the study. The studies showed the most frequent cognitive impairment are attention, memory, and executive function in COVID-19 patients. Compared with healthy controls (HC) in 3 out of 4 studies, cognitive impairment was only evident in COVID-19 patients. Furthermore, two studies showed no correlation between brain fog and depression, and five studies showed a link between the severity of COVID-19 infection and cognitive impairment. Cases ranging from mild to severe illness presented manifestations of brain fog. However, a disparity in the evidence of the pathophysiology of COVID-19 and cognitive dysfunction exists, prompting the need to investigate further. Additionally, recent studies provide insufficient evidence for direct central nervous system invasion, and there are emerging studies that contrast the presumed pathogenesis of neurological complications from neuroinflammation. Conclusion: There is an association between COVID-19 and cognitive dysfunction. Manifestation of cognitive dysfunction is present regardless of illness severity. Moreover, there are existing pathophysiological mechanisms of the Coronavirus that lead to cognitive dysfunction in COVID-19 patients; however, additional studies are required to substantiate such mechanisms further. [Veröffentlicht: 25.05.2022]
Butardo, N. D., Coronel, M. F. D., Dino, A. M. O., Mendoza, T. R. F., Sto. Domingo, O. K. D., Regencia, Z. J. G., Dominguez, J. C., Baja, E. S., Ligsay, A. D.

Population-weighted greenspace exposure tied to lower COVID-19 mortality rates: A nationwide dose-response study
The COVID-19 outbreak has caused enormous deaths and profound social and economic disruption globally. Accumulating evidence suggests exposure to greenspace may reduce the risk of COVID-19 mortality. Greenspace exposure enhances immune functioning, reduces inflammation, and replenishes gut microbiota may protect against the risk of mortality among those with COVID-19. However, previous studies often fail to distinguish the health effect of different types of greenspace, explore the dose-response association and optimal buffer distance, and consider the spatial dynamics of population distribution and geographic locations of greenspace. This study examined the associations among ratio of different types of greenspaces, population-weighted exposure to different types of greenspaces, and COVID-19 mortality rates using a negative binomial generalized linear mixed effects model across 3,025 counties, adjusted for socioeconomic, demographic, pre-existing chronic disease, policy and regulation, behavioral, and environmental factors. The population-weighted measure gave proportionally greater weight to greenspace near areas of higher population density. Exposure to forest and pasture was negatively associated with COVID-19 mortality rates, while developed open space has insignificant or positive associations with mortality rates. Forest outside park has the largest effect size across all buffer distances, followed by forest inside park. The optimal exposure buffer distance is 1km for forest outside park, with 1 unit of increase in exposure associated with a 9.9% decrease in mortality rates (95% confidence interval: 6.9% -12.8%). The optimal exposure buffer distance of forest inside park is 400m, with 1 unit of increase in exposure, associated with a 4.7% decrease in mortality rates (95% confidence interval: 2.4% - 6.9%). Greenspaces, especially nearby forest, may be effective at lowering the mortality risk of COVID-19 patients. Our findings suggest that policymakers and planners should prioritize forestry within walking distance of residential clusters to mitigate mortality rates during current and future respiratory pandemics. [Veröffentlicht: 25.05.2022]
Yang, Y., Lu, Y., Jiang, B.

Health workers Perspective on the Feasibility and Acceptability of the Introduction of AgRDT for COVID-19 in Kisumu County, Western Kenya
COVID-19 pandemic remains a major global public health challenge also in Low- and Middle-Income Countries (LMIC), due to fragile health systems, limited resources and personnel, low testing and counseling capacity, community perceptions, among others. In Kisumu County of Western Kenya, a unique Public Private Partnership (PPP) was rolled-out to increase testing and capacity building by linking private facilities to the ongoing public sector efforts in combating COVID-19. It became increasingly clear that centralized PCR testing for COVID-19 was too labor-intensive, expensive, prone to machine breakdowns and stock-outs of essential reagents, resulting in long turn-around times and sometimes even adaptations of patient selection criteria. A clear need was identified for rapid point-of-care COVID-19 testing (AgRDT). After successful field evaluation, RDT for COVID-19 was offered through the PPP. This paper aimed to understand the health workers perspective on the feasibility and acceptability of the introduction of the AgRDT in Kisumu County. In-Depth Interviews were conducted with selected health workers (n=23) from the participating facilities and analyzed using Nvivo 11 The health workers accepted the use of AgRDT as it enabled the strengthening of the existing health system, increased testing capacity and provided capacity building opportunities. Challenges included poor management of results discrepant with PCR gold standard. The health workers applauded the introduction of AgRDT with the Kisumu County Department of Health as a more realistic and user-friendly approach, leading to fast turn-around times and increased personal safety experience. [Veröffentlicht: 25.05.2022]
Omollo, M. C., Odero, I. A., Barsosio, H. C., Kariuki, S., Kuile, F. T., Okello, S. O., Oyoo, K., K'Oloo, A., Duijn, S. V., Houben, N., Milimo, E., Aroka, R., Odhiambo, A., Onsongo, S. N., Rinke de Wit, T. F.

In the Midst of a Pandemic, Introverts May Have a Mortality Advantage
Extroverts may enjoy lower mortality than introverts under normal circumstances, but the relationship may be different during an airborne pandemic when social contact can be deadly. We used data for midlife Americans surveyed in 1995-96 with mortality follow-up through December 31, 2020 to investigate whether the association between extroversion and mortality changed during the COVID-19 pandemic. We hypothesized that excess mortality during the pandemic will be greater for extroverts than for introverts. Results were based on a Cox model estimating age-specific mortality controlling for sex, race/ethnicity, the period trend in mortality, and an additional indicator for the pandemic period (Mar-Dec 2020). We interacted extroversion with the pandemic indicator to test whether the relationship differed between prepandemic and pandemic periods. Prior to the pandemic, extroversion was associated with somewhat lower mortality (HR=0.93 per SD, 95% CI 0.88-0.97), but the relationship reversed during the pandemic: extroverted individuals appeared to suffer higher mortality than their introverted counterparts, although the effect was not significant (HR=1.20 per SD, 95% CI 0.93-1.54). Extroversion was associated with greater pandemic related excess mortality (HR=1.20/0.93=1.29 per SD, 95% CI 1.00-1.67). Compared with someone who scored at the mean level of extroversion, mortality rates prior to the pandemic were 10% lower for a person who was very extroverted (i.e., top 12% of the sample at Wave 1), while they were 12% higher for someone who was very introverted (i.e., 11th percentile). In contrast, mortality rates during the pandemic appeared to be higher for very extroverted individuals (HR=1.15, 95% CI 0.77-1.71) and lower for those who were very introverted (HR=0.70, 95% CI 0.43-1.14) although the difference was not significant because of limited statistical power. In sum, the slight mortality advantage enjoyed by extroverts prior to the pandemic disappeared during the first 10 months of the COVID-19 pandemic. It remains to be seen whether that pattern continued into 2021-22. We suspect that the mortality benefit of introversion during the pandemic is largely a result of reduced exposure to the risk of infection, but it may also derive in part from the ability of introverts to adapt more easily to reduced social interaction without engaging in self-destructive behavior (e.g., drug and alcohol abuse). Introverts have been training for a pandemic their whole lives. [Veröffentlicht: 25.05.2022]
Glei, D. A., Weinstein, M.

Toward more realistic social distancing policies via advanced feedback control
A continuously time-varying transmission rate is suggested by many control-theoretic investigations on non-pharmaceutical interventions for mitigating the COVID-19 pandemic. However, such a continuously varying rate is impossible to implement in any human society. Here, we significantly extend a preliminary work (M. Fliess, C. Join, A. d'Onofrio, Feedback control of social distancing for COVID-19 via elementary formulae, MATHMOD, Vienna, 2022), based on the combination of flatness-based and model-free controls of the classic SIR model. Indeed, to take into account severe uncertainties and perturbations, we propose a feedback control where the transmission rate, i.e., the control variable, is piecewise constant. More precisely, the transmission rate remains constant during an appreciable time interval. Strict extended lockdowns may therefore be avoided. The poor knowledge of fundamental quantities such as the rate of infection hinders a precise calibration of the transmission rate. Thus, the results of our approach ought therefore not to be regarded as rules of action to follow accurately but as a guideline for a wise behavior. [Veröffentlicht: 25.05.2022]
Join, C., d'Onofrio, A., Fliess, M.

Atovaquone for Treatment of COVID-19: A Prospective Randomized, Double-Blind, Placebo-Controlled Clinical Trial
Background: An in-silico screen was performed to identify FDA approved drugs that inhibit SARS-CoV-2 main protease (Mpro), followed by in vitro viral replication assays, and in vivo pharmacokinetic studies in mice. These studies identified atovaquone as a promising candidate for inhibiting viral replication. Methods: A 2-center, randomized, double-blind, placebo-controlled trial was performed among patients hospitalized with COVID-19 infection. Enrolled patients were randomized 2:1 to atovaquone 1500 mg BID versus matched placebo. Patients received standard of care treatment including remdesivir, dexamethasone, or convalescent plasma as deemed necessary by the treating team. Saliva was collected at baseline and twice per day for up to 10 days for RNA extraction for SARS-CoV-2 viral load measurement by quantitative reverse-transcriptase PCR. The primary outcome was the between group difference in log-transformed viral load (copies/mL) using a generalized linear mixed-effect models of repeated measures from all samples. Results: Of the 61 patients enrolled; 41 received atovaquone and 19 received placebo. Overall, the population was predominately male (63%) and Hispanic (70%), with a mean age of 51 years, enrolled a mean of 5 days from symptom onset. The log10 viral load was 5.25 copies/mL vs. 4.79 copies/mL at baseline in the atovaquone vs. placebo group. Change in viral load did not differ over time between the atovaquone plus standard of care arm versus the placebo plus standard of care arm. Pharmacokinetic (PK) studies of atovaquone plasma concentration demonstrated a wide variation in atovaquone levels, with an inverse correlation between BMI and atovaquone levels, (Rho -0.45, p=0.02). In post hoc analysis, an inverse correlation was observed between atovaquone levels and viral load (Rho -0.54, p= 0.005). Conclusion: In this prospective, randomized, placebo-controlled trial, atovaquone did not demonstrate evidence of enhanced SARS-CoV-2 viral clearance compared with placebo. However, based on the observed inverse correlation between atovaquone levels and viral load, additional PK-guided studies may be warranted to examine the antiviral effect of atovaquone in COVID-19 patients. clincialtrials.gov (NCT04456153). [Veröffentlicht: 25.05.2022]
Jain, M. K., de Lemos, J., McGuire, D. K., Ayers, C., Eiston, J. L., Sanchez, C. L., Kamel, D., Meisner, J. A., Thomas, E. V., Hegde, A. A., Mocherla, S., Strebe, J. K., Li, X., Williams, N. S., Xing, C., Ahmed, M. S., Wang, P., Sadek, H., Schoggins, J. w.

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