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Author

Kai Kupferschmidt

Bio: Kai Kupferschmidt is an academic researcher from Geneva College. The author has contributed to research in topics: Medicine & Coronavirus. The author has an hindex of 25, co-authored 211 publications receiving 2830 citations.
Topics: Medicine, Coronavirus, Outbreak, Pandemic, Population


Papers
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Journal ArticleDOI
20 Mar 2020-Science
TL;DR: The hastily introduced measures vary widely between countries and even within countries, and reflect different phases of the epidemic, as well as differences in resources, cultures, governments, and laws.
Abstract: After 2 months of mostly waiting and seeing, many countries have suddenly implemented strict measures to slow the spread of coronavirus disease 2019. They had little choice, given the rapid rise in the number of cases and deaths in Europe and the United States. "This is war," President Emmanuel Macron told the French people. But how to fight that war is still under discussion. The hastily introduced measures vary widely between countries and even within countries. That reflects different phases of the epidemic, as well as differences in resources, cultures, governments, and laws. And there9s also confusion about what works best, and how to balance what is necessary with what is reasonable.

360 citations

Journal ArticleDOI
27 Mar 2020-Science
TL;DR: The study will examine an experimental antiviral compound called remdesivir; the malaria medication chloroquine (or its chemical cousin hydroxychloroquine); a combination of the HIV drugs lopinavir and ritonavir; and that combination plus interferon-beta, an immune system messenger that can help cripple viruses.
Abstract: As the race to find treatments for coronavirus disease 2019 (COVID-19) accelerates, the World Health Organization (WHO) last week announced a major study to compare treatment strategies in a streamlined clinical trial design that doctors around the world can join. SOLIDARITY—an unprecedented, coordinated push to collect robust scientific data rapidly during a pandemic—could include many thousands of patients in dozens of countries and has emphasized simplicity so that even hospitals overwhelmed by an onslaught of COVID-19 patients can participate. The study will examine an experimental antiviral compound called remdesivir; the malaria medication chloroquine (or its chemical cousin hydroxychloroquine); a combination of the HIV drugs lopinavir and ritonavir; and that combination plus interferon-beta, an immune system messenger that can help cripple viruses. WHO hopes to start to enroll patients as early as this week.

315 citations

Journal ArticleDOI
06 Mar 2020-Science
TL;DR: A key feature was the lockdown in many cities in Hubei, which restricted much of the transmission to households, where the virus eventually burned out and prevented potentially hundreds of thousands of cases in other provinces.
Abstract: A new report confirms drops in the spread of COVID-19 in China and contends that the effective response there could inform other countries. But critics say the report failed to acknowledge the human rights costs of the most severe measures imposed by China9s authoritarian government: massive lockdowns and electronic surveillance of millions of people. The report was jointly written by an international team of scientists, organized by the World Health Organization, who toured five cities in China with colleagues from that country to better understand the COVID-19 epidemic there. Using the country9s massive data set about cases, the report offers many insights about the severity of the disease and how it affects different age groups and people with underlying health problems. It concludes that efforts to contain the virus in Hubei province prevented potentially hundreds of thousands of cases in other provinces. A key feature was the lockdown in many cities in Hubei, which restricted much of the transmission to households, where the virus eventually burned out. Many public health and legal experts questioned whether these stringent strategies would work elsewhere and noted the downsides to mandatory quarantines and the intensive surveillance done by governments.

209 citations

Journal ArticleDOI
25 Jun 2021-Science
TL;DR: A SARS-CoV-2 variant called Delta is slowly taking over the pandemic, and the surge has set off a frenzy of research to understand why the variant appears to spread so much faster than the three other variants of concern.
Abstract: A SARS-CoV-2 variant called Delta is slowly taking over the pandemic. Denoted a "variant of concern" by the World Health Organization, Delta appears to be more transmissible than previous variants and better able to infect people that have only had one vaccine dose. The surge has set off a frenzy of research to understand why the variant appears to spread so much faster than the three other variants of concern, whether it is more dangerous in other ways, and how its unique pattern of mutations, which cause subtle changes in its proteins, can wreak havoc. Delta9s arrival has also brought fresh attention to the potential of SARS-CoV-2 to evolve and adapt in the months and years ahead.

128 citations


Cited by
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Journal ArticleDOI
12 May 2020-JAMA
TL;DR: The COVID-19 pandemic represents the greatest global public health crisis of this generation and, potentially, since the pandemic influenza outbreak of 1918 and both the need and capability to produce high-quality evidence even in the middle of a pandemic.
Abstract: Importance The pandemic of coronavirus disease 2019 (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presents an unprecedented challenge to identify effective drugs for prevention and treatment. Given the rapid pace of scientific discovery and clinical data generated by the large number of people rapidly infected by SARS-CoV-2, clinicians need accurate evidence regarding effective medical treatments for this infection. Observations No proven effective therapies for this virus currently exist. The rapidly expanding knowledge regarding SARS-CoV-2 virology provides a significant number of potential drug targets. The most promising therapy is remdesivir. Remdesivir has potent in vitro activity against SARS-CoV-2, but it is not US Food and Drug Administration approved and currently is being tested in ongoing randomized trials. Oseltamivir has not been shown to have efficacy, and corticosteroids are currently not recommended. Current clinical evidence does not support stopping angiotensin-converting enzyme inhibitors or angiotensin receptor blockers in patients with COVID-19. Conclusions and Relevance The COVID-19 pandemic represents the greatest global public health crisis of this generation and, potentially, since the pandemic influenza outbreak of 1918. The speed and volume of clinical trials launched to investigate potential therapies for COVID-19 highlight both the need and capability to produce high-quality evidence even in the middle of a pandemic. No therapies have been shown effective to date.

2,143 citations

Journal ArticleDOI
17 Mar 2016-Nature
TL;DR: These results show the first substantive post-exposure protection by a small-molecule antiviral compound against EBOV in nonhuman primates, and the broad-spectrum antiviral activity of GS-5734 in vitro against other pathogenic RNA viruses, including filoviruses, arenavirus, and coronavirus suggests the potential for wider medical use.
Abstract: The most recent Ebola virus outbreak in West Africa, which was unprecedented in the number of cases and fatalities, geographic distribution, and number of nations affected, highlights the need for safe, effective, and readily available antiviral agents for treatment and prevention of acute Ebola virus (EBOV) disease (EVD) or sequelae. No antiviral therapeutics have yet received regulatory approval or demonstrated clinical efficacy. Here we report the discovery of a novel small molecule GS-5734, a monophosphoramidate prodrug of an adenosine analogue, with antiviral activity against EBOV. GS-5734 exhibits antiviral activity against multiple variants of EBOV and other filoviruses in cell-based assays. The pharmacologically active nucleoside triphosphate (NTP) is efficiently formed in multiple human cell types incubated with GS-5734 in vitro, and the NTP acts as an alternative substrate and RNA-chain terminator in primer-extension assays using a surrogate respiratory syncytial virus RNA polymerase. Intravenous administration of GS-5734 to nonhuman primates resulted in persistent NTP levels in peripheral blood mononuclear cells (half-life, 14 h) and distribution to sanctuary sites for viral replication including testes, eyes, and brain. In a rhesus monkey model of EVD, once-daily intravenous administration of 10 mg kg(-1) GS-5734 for 12 days resulted in profound suppression of EBOV replication and protected 100% of EBOV-infected animals against lethal disease, ameliorating clinical disease signs and pathophysiological markers, even when treatments were initiated three days after virus exposure when systemic viral RNA was detected in two out of six treated animals. These results show the first substantive post-exposure protection by a small-molecule antiviral compound against EBOV in nonhuman primates. The broad-spectrum antiviral activity of GS-5734 in vitro against other pathogenic RNA viruses, including filoviruses, arenaviruses, and coronaviruses, suggests the potential for wider medical use. GS-5734 is amenable to large-scale manufacturing, and clinical studies investigating the drug safety and pharmacokinetics are ongoing.

1,216 citations

Journal ArticleDOI
TL;DR: The structure of the liganded VDR/RXR complex was recently characterized using cryoelectron microscopy, X-ray scattering, and hydrogen deuterium exchange, which will result in a more complete understanding of VDR coactivator interactions, thus facilitating cell and gene specific clinical applications.
Abstract: 1,25-Dihydroxvitamin D3 [1,25(OH)2D3] is the hormonally active form of vitamin D. The genomic mechanism of 1,25(OH)2D3 action involves the direct binding of the 1,25(OH)2D3 activated vitamin D receptor/retinoic X receptor (VDR/RXR) heterodimeric complex to specific DNA sequences. Numerous VDR co-regulatory proteins have been identified, and genome-wide studies have shown that the actions of 1,25(OH)2D3 involve regulation of gene activity at a range of locations many kilobases from the transcription start site. The structure of the liganded VDR/RXR complex was recently characterized using cryoelectron microscopy, X-ray scattering, and hydrogen deuterium exchange. These recent technological advances will result in a more complete understanding of VDR coactivator interactions, thus facilitating cell and gene specific clinical applications. Although the identification of mechanisms mediating VDR-regulated transcription has been one focus of recent research in the field, other topics of fundamental importance include the identification and functional significance of proteins involved in the metabolism of vitamin D. CYP2R1 has been identified as the most important 25-hydroxylase, and a critical role for CYP24A1 in humans was noted in studies showing that inactivating mutations in CYP24A1 are a probable cause of idiopathic infantile hypercalcemia. In addition, studies using knockout and transgenic mice have provided new insight on the physiological role of vitamin D in classical target tissues as well as evidence of extraskeletal effects of 1,25(OH)2D3 including inhibition of cancer progression, effects on the cardiovascular system, and immunomodulatory effects in certain autoimmune diseases. Some of the mechanistic findings in mouse models have also been observed in humans. The identification of similar pathways in humans could lead to the development of new therapies to prevent and treat disease.

1,135 citations

Journal ArticleDOI
TL;DR: A literature review of publicly available information to summarize knowledge about the pathogen and the current epidemic is presented in this article, where the causative agent, pathogenesis and immune responses, epidemiology, diagnosis, treatment and management of the disease, control and preventions strategies are all reviewed.

1,035 citations

Journal ArticleDOI
TL;DR: Since the outbreak of the novel coronavirus disease COVID-19, caused by the SARS-CoV-2 virus, this disease has spread rapidly around the globe and the potential threat of a pandemic is considered.
Abstract: Since the outbreak of the novel coronavirus disease COVID-19, caused by the SARS-CoV-2 virus, this disease has spread rapidly around the globe. Considering the potential threat of a pandemic, scien...

1,029 citations