Understanding adaptive immunity to SARS-CoV-2 is important for vaccine development, interpreting coronavirus disease 2019 (COVID-19) pathogenesis, and calibration of pandemic control measures. Using HLA class I and II predicted peptide “megapools,” circulating SARS-CoV-2-specific CD8+ and CD4+ T cells were identified in ∼70% and 100% of COVID-19 convalescent patients, respectively. CD4+ T cell responses to spike, the main target of most vaccine efforts, were robust and correlated with the magnitude of the anti-SARS-CoV-2 IgG and IgA titers. The M, spike, and N proteins each accounted for 11%-27% of the total CD4+ response, with additional responses commonly targeting nsp3, nsp4, ORF3a, and ORF8, among others. For CD8+ T cells, spike and M were recognized, with at least eight SARS-CoV-2 ORFs targeted. Importantly, we detected SARS-CoV-2-reactive CD4+ T cells in ∼40%-60% of unexposed individuals, suggesting cross-reactive T cell recognition between circulating “common cold” coronaviruses and SARS-CoV-2.
From January 21 through February 23, 2020, public health agencies detected 14 U.S. cases of coronavirus disease 2019 (COVID-19), all related to travel from China (1,2). The first nontravel-related U.S. case was confirmed on February 26 in a California resident who had become ill on February 13 (3). Two days later, on February 28, a second nontravel-related case was confirmed in the state of Washington (4,5). Examination of four lines of evidence provides insight into the timing of introduction and early transmission of SARS-CoV-2, the virus that causes COVID-19, into the United States before the detection of these two cases. First, syndromic surveillance based on emergency department records from counties affected early by the pandemic did not show an increase in visits for COVID-19-like illness before February 28. Second, retrospective SARS-CoV-2 testing of approximately 11,000 respiratory specimens from several U.S. locations beginning January 1 identified no positive results before February 20. Third, analysis of viral RNA sequences from early cases suggested that a single lineage of virus imported directly or indirectly from China began circulating in the United States between January 18 and February 9, followed by several SARS-CoV-2 importations from Europe. Finally, the occurrence of three cases, one in a California resident who died on February 6, a second in another resident of the same county who died February 17, and a third in an unidentified passenger or crew member aboard a Pacific cruise ship that left San Francisco on February 11, confirms cryptic circulation of the virus by early February. These data indicate that sustained, community transmission had begun before detection of the first two nontravel-related U.S. cases, likely resulting from the importation of a single lineage of virus from China in late January or early February, followed by several importations from Europe. The widespread emergence of COVID-19 throughout the United States after February highlights the importance of robust public health systems to respond rapidly to emerging infectious threats.
- Proceedings of the National Academy of Sciences of the United States of America
- Published 4 days ago
The ongoing sixth mass species extinction is the result of the destruction of component populations leading to eventual extirpation of entire species. Populations and species extinctions have severe implications for society through the degradation of ecosystem services. Here we assess the extinction crisis from a different perspective. We examine 29,400 species of terrestrial vertebrates, and determine which are on the brink of extinction because they have fewer than 1,000 individuals. There are 515 species on the brink (1.7% of the evaluated vertebrates). Around 94% of the populations of 77 mammal and bird species on the brink have been lost in the last century. Assuming all species on the brink have similar trends, more than 237,000 populations of those species have vanished since 1900. We conclude the human-caused sixth mass extinction is likely accelerating for several reasons. First, many of the species that have been driven to the brink will likely become extinct soon. Second, the distribution of those species highly coincides with hundreds of other endangered species, surviving in regions with high human impacts, suggesting ongoing regional biodiversity collapses. Third, close ecological interactions of species on the brink tend to move other species toward annihilation when they disappear-extinction breeds extinctions. Finally, human pressures on the biosphere are growing rapidly, and a recent example is the current coronavirus disease 2019 (Covid-19) pandemic, linked to wildlife trade. Our results reemphasize the extreme urgency of taking much-expanded worldwide actions to save wild species and humanity’s crucial life-support systems from this existential threat.
The environmental severity of large impacts on Earth is influenced by their impact trajectory. Impact direction and angle to the target plane affect the volume and depth of origin of vaporized target, as well as the trajectories of ejected material. The asteroid impact that formed the 66 Ma Chicxulub crater had a profound and catastrophic effect on Earth’s environment, but the impact trajectory is debated. Here we show that impact angle and direction can be diagnosed by asymmetries in the subsurface structure of the Chicxulub crater. Comparison of 3D numerical simulations of Chicxulub-scale impacts with geophysical observations suggests that the Chicxulub crater was formed by a steeply-inclined (45-60° to horizontal) impact from the northeast; several lines of evidence rule out a low angle (<30°) impact. A steeply-inclined impact produces a nearly symmetric distribution of ejected rock and releases more climate-changing gases per impactor mass than either a very shallow or near-vertical impact.
To describe detection of severe acute respiratory syndrome (SARS)-coronavirus 2 (CoV-2) in seminal fluid of patients recovering from coronavirus disease 2019 (COVID-19) and to describe the expression profile of angiotensin-converting enzyme 2 (ACE2) and Transmembrane Serine Protease 2 (TMPRSS2) within the testicle.
More than 1.6 million Americans have been infected with SARS-CoV-2 and >10 times that number carry antibodies to it. High-risk patients presenting with progressing symptomatic disease have only hospitalization treatment with its high mortality. An outpatient treatment that prevents hospitalization is desperately needed. Two candidate medications have been widely discussed: remdesivir, and hydroxychloroquine+azithromycin. Remdesivir has shown mild effectiveness in hospitalized inpatients, but no trials have been registered in outpatients. Hydroxychloroquine+azithromycin has been widely misrepresented in both clinical reports and public media, and outpatient trials results are not expected until September. Early outpatient illness is very different than later hospitalized florid disease and the treatments differ. Evidence about use of hydroxychloroquine alone, or of hydroxychloroquine+azithromycin in inpatients, is irrelevant concerning efficacy of the pair in early high-risk outpatient disease. Five studies, including two controlled clinical trials, have demonstrated significant major outpatient treatment efficacy. Hydroxychloroquine+azithromycin has been used as standard-of-care in more than 300,000 older adults with multicomorbidities, with estimated proportion diagnosed with cardiac arrhythmias attributable to the medications 47/100,000 users, of which estimated mortality is <20%, 9/100,000 users, compared to the 10,000 Americans now dying each week. These medications need to be widely available and promoted immediately for physicians to prescribe.
Coronavirus disease 2019 (Covid-19) occurs after exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). For persons who are exposed, the standard of care is observation and quarantine. Whether hydroxychloroquine can prevent symptomatic infection after SARS-CoV-2 exposure is unknown.
Many reports on coronavirus disease 2019 (Covid-19) have highlighted age- and sex-related differences in health outcomes. More information is needed about racial and ethnic differences in outcomes from Covid-19.
To investigate the nature and extent of financial relationships between leaders of influential professional medical associations in the United States and pharmaceutical and device companies.