Detection of asymptomatic or subclinical novel human coronavirus SARS-CoV-2 infection is critical for understanding the overall prevalence and infection potential of COVID-19. To estimate the cumulative prevalence of SARS-CoV-2 infection in China, we evaluated the host serologic response, measured by the levels of immunoglobulins M and G in 17,368 individuals, in the city of Wuhan, the epicenter of the COVID-19 pandemic in China, and geographic regions in the country, during the period from 9 March 2020 to 10 April 2020. In our cohorts, the seropositivity in Wuhan varied between 3.2% and 3.8% in different subcohorts. Seroposivity progressively decreased in other cities as the distance to the epicenter increased. Patients who visited a hospital for maintenance hemodialysis and healthcare workers also had a higher seroprevalence of 3.3% (51 of 1,542, 2.5-4.3%, 95% confidence interval (CI)) and 1.8% (81 of 4,384, 1.5-2.3%, 95% CI), respectively. More studies are needed to determine whether these results are generalizable to other populations and geographic locations, as well as to determine at what rate seroprevalence is increasing with the progress of the COVID-19 pandemic. Serologic surveillance has the potential to provide a more faithful cumulative viral attack rate for the first season of this novel SARS-CoV-2 infection.The novel human coronavirus SARS-CoV-2 is a highly contagious virus, and its disease, COVID-19, can lead to significant morbidity and mortality in a proportion of patients 1-3 . On 12 March 2020, the World Health Organization declared it a global pandemic 4 . As of 12 May 2020, there were more than 4.2 million confirmed infections globally in more than 180 countries with over 290,000 deaths (https://www.arcgis.com/apps/opsdashboard/index.html#/ bda7594740fd40299423467b48e9ecf6).Detection of SARS-CoV-2 in asymptomatic individuals 5,6 suggests that subclinical active infection might be an important contributor to this outbreak. Currently, reported cases of COVID-19 are mainly limited to symptomatic individuals, those having close

Alzheimer's disease (AD) is an age-related disorder that threatens to become an epidemic as the world population ages. Neurotoxic oligomers of A␤42 are believed to be the main cause of AD; therefore, disruption of A␤ oligomerization is a promising approach for developing therapeutics for AD. Formation of A␤42 oligomers is mediated by intermolecular interactions in which the C terminus plays a central role. We hypothesized that peptides derived from the C terminus of A␤42 may get incorporated into oligomers of A␤42, disrupt their structure, and thereby inhibit their toxicity. We tested this hypothesis using A␤ fragments with the general formula A␤(x؊42) (x ‫؍‬ 28 -39). A cell viability screen identified A␤(31-42) as the most potent inhibitor. In addition, the shortest peptide, A␤(39 -42), also had high activity. Both A␤(31-42) and A␤(39 -42) inhibited A␤-induced cell death and rescued disruption of synaptic activity by A␤42 oligomers at micromolar concentrations. Biophysical characterization indicated that the action of these peptides likely involved stabilization of A␤42 in nontoxic oligomers. Computer simulations suggested a mechanism by which the fragments coassembled with A␤42 to form heterooligomers. Thus, A␤(31-42) and A␤(39 -42) are leads for obtaining mechanism-based drugs for treatment of AD using a systematic structure-activity approach.Alzheimer's disease ͉ amyloid ␤-protein ͉ inhibitor design A lzheimer's disease (AD) is the predominant cause of dementia and one of the leading causes of death among elderly people. It is estimated that there are currently Ϸ27 million people suffering from AD worldwide (1). Because the world population is aging rapidly, if no cure is found in the near future AD will become an epidemic (2).The amyloid cascade hypothesis proposed that amyloid ␤-protein (A␤) fibrils-an aggregated form of A␤ found in amyloid plaques in the brains of patients with AD-were the neurotoxic agents causing AD (3). However, in recent years, multiple lines of evidence have led to a revision of this view, and today the primary toxins causing AD are believed to be early-forming A␤ oligomers rather than A␤ fibrils (4, 5). This paradigm shift suggests that efforts toward development of therapeutic agents targeting A␤ assembly should be directed at A␤ oligomers rather than fibrils. In particular, genetic, physiologic, and biochemical data indicate that oligomers of the 42-aa form of A␤, A␤42, are most strongly linked to the etiology of AD (6-9) and therefore are a particularly attractive target for inhibitor design.Several groups have reported small-molecule inhibitors of A␤ oligomerization (10-13). The importance of understanding the mechanism of inhibition recently has been highlighted (14) after findings that many small-molecule inhibitors of fibrillogenesis may act nonspecifically, likely making them unsuitable for treating amyloid-related disorders (15). In addition, inhibition of fibril formation may actually lead to stabilization of toxic oligomers (16). Interestingly, when oligomers are stabiliz...

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