Übersicht

Fünf neue Studien zu SARS-CoV-2

Wie verläuft die Krankheit bei Kindern? Was sind die Faktoren für eine ungünstige Prognose? Ist das Virus via Oberflächen übertragbar? Gibt es eine Wirkstoff-Therapie? Das Coronavirus wird fieberhaft erforscht. Eine Übersicht der relevantesten Studien.

Die Studien werten die Daten der Virus-Erkrankten auf Krankheitsverlauf, Ansteckung und mögliche Heilung aus. Adobe Stock_metamorworks

  1. Unter welchen Einflussfaktoren und Voraussetzungen die Erkrankung mit dem Coronavirus ein erhöhtes Sterblichkeitsrisiko darstellt, untersuchten chinesische Forscher unter anderem von der Chinese Academy of Medical Science in Wuhan.
  2. Wie sich die Krankheit bei Kindern verläuft, wurde mit Daten aus China von internationalen Wissenschaftlern ausgewertet.
  3. Eine chinesischen Krankenhaus-Studie belegt die Übertragbarkeit via Oberflächen. Das Lungenvirus ist demnach nicht nur von Mensch zu Mensch oder Tier zu Mensch übertragbar.
  4. Eine US-Studie zeigt, wie lange Sars-CoV-2 auf Oberflächen und in Aerosolen überdauert: bis zu drei Stunden in Partikeln in der Luft, bis zu vier Stunden auf Kupfer, bis zu 24 Stunden auf Karton und zwei bis drei Tage auf Plastik und rostfreiem Stahl.
  5. Die ersten Anhaltspunkte für eine Wirkstoff-Therapie liefern Auswertungen zu Remdesivir von US-amerikanischen Forschern, ein Virustatikum, das bereits bei Ebola-Infizierten getestet wurde. Dort aber keinen Erfolg hatte.


Die wichtigsten internationalen Studien zum Coronavirus

Summary

Background:
Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described.

Methods:
In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death.

Findings:
191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03-1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61-12·23; p<0·0001), and d-dimer greater than 1 μg/L (18·42, 2·64-128·55; p=0·0033) on admission. Median duration of viral shedding was 20·0 days (IQR 17·0-24·0) in survivors, but SARS-CoV-2 was detectable until death in non-survivors. The longest observed duration of viral shedding in survivors was 37 days.

Interpretation:
The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/L could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future.

Copyright© 2020 Elsevier Ltd. All rights reserved

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Abstract:

Air, Surface Environmental, and Personal Protective Equipment Contamination by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) from a Symptomatic Patient: Coronaviruses have been implicated in nosocomial outbreaks with environmental contamination as a route of transmission. Similarly, nosocomial transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been reported. However, the mode of transmission and extent of environmental contamination are unknown.

 

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Abstract:

32 HCoV-19 (SARS-2) has caused >88,000 reported illnesses with a current case-fatality ratio of ~2%. Here, 33 we investigate the stability of viable HCoV-19 on surfaces and in aerosols in comparison with SARS-34 CoV-1. Overall, stability is very similar between HCoV-19 and SARS-CoV-1. We found that viable virus 35 could be detected in aerosols up to 3 hours post aerosolization, up to 4 hours on copper, up to 24 hours on 36 cardboard and up to 2-3 days on plastic and stainless steel. HCoV-19 and SARS-CoV-1 exhibited similar 37 half-lives in aerosols, with median estimates around 2.7 hours. Both viruses show relatively long viability 38 on stainless steel and polypropylene compared to copper or cardboard: the median half-life estimate for 39 HCoV-19 is around 13 hours on steel and around 16 hours on polypropylene. Our results indicate that 40 aerosol and fomite transmission of HCoV-19 is plausible, as the virus can remain viable in aerosols for 41 multiple hours and on surfaces up to days.

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Abstract:

Abstract Background Rapid spread of SARS-CoV-2 in Wuhan prompted heightened surveillance in Shenzhen and elsewhere in China. The resulting data provide a rare opportunity to measure key metrics of disease course, transmission, and the impact of control. Methods The Shenzhen CDC identified 391 SARS-CoV-2 cases from January 14 to February 12, 2020 and 1286 close contacts. We compare cases identified through symptomatic surveillance and contact tracing, and estimate the time from symptom onset to confirmation, isolation, and hospitalization. We estimate metrics of disease transmission and analyze factors influencing transmission risk. Findings Cases were older than the general population (mean age 45) and balanced between males (187) and females (204). Ninety-one percent had mild or moderate clinical severity at initial assessment. Three have died, 225 have recovered (median time to recovery is 32 days). Cases were isolated on average 4.6 days after developing symptoms; contact tracing reduced this by 1.9 days. Household contacts and those travelling with a case where at higher risk of infection (ORs 6 and 7) than other close contacts. The household secondary attack rate was 15%, and children were as likely to be infected as adults. The observed reproductive number was 0.4, with a mean serial interval of 6.3 days. Interpretation Our data on cases as well as their infected and uninfected close contacts provide key insights into SARS-CoV-2 epidemiology. This work shows that heightened surveillance and isolation, particularly contact tracing, reduces the time cases are infectious in the community, thereby reducing R. Its overall impact, however, is uncertain and highly dependent on the number of asymptomatic cases. We further show that children are at similar risk of infection as the general population, though less likely to have severe symptoms; hence should be considered in analyses of transmission and control.

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Abstract

Antiviral drugs for managing infections with human coronaviruses are not yet approved, posing a serious challenge to current global efforts aimed at containing the outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Remdesivir (RDV) is an investigational compound with a broad spectrum of antiviral activities against RNA viruses, including SARS-CoV and Middle East respiratory syndrome (MERS-CoV). RDV is a nucleotide analog inhibitor of RNA-dependent RNA polymerases (RdRps). Here, we co-expressed the MERS-CoV nonstructural proteins nsp5, nsp7, nsp8, and nsp12 (RdRp) in insect cells as a part a polyprotein to study the mechanism of inhibition of MERS-CoV RdRp by RDV. We initially demonstrated that nsp8 and nsp12 form an active complex. The triphosphate form of the inhibitor (RDV-TP) competes with its natural counterpart ATP. Of note, the selectivity value for RDV-TP obtained here with a steady-state approach suggests that it is more efficiently incorporated than ATP and two other nucleotide analogues. Once incorporated at position i, the inhibitor caused RNA synthesis arrest at position i+3. Hence, the likely mechanism of action is delayed RNA chain termination. The additional three nucleotides may protect the inhibitor from excision by the viral 3’–5’ exonuclease activity. Together, these results help to explain the high potency of RDV against RNA viruses in cell-based assays.

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Das neu identifizierte Coronavirus SARS-CoV-2 verursacht die "Corona virus disease 2019" (Covid-19) und ist Auslöser der COVID-19-Pandemie.

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