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Higher risk was associated with older age, male sex, black ethnicity, lower socioeconomic status, and current/past smoking status. The model can be applied to predict risk of hospitalization and mortality, and could aid decision making when detailed medical history of patients is not easily available.

Emerging evidence suggests that socially vulnerable communities are at higher risk for coronavirus disease 2019 (COVID-19) outbreaks in the United States. However, no prior studies have examined temporal trends and differential effects of social vulnerability on COVID-19 incidence and death rates. The purpose of this study was to examine temporal trends among counties with high and low social vulnerability and to quantify disparities in these trends over time. We hypothesized that highly vulnerable counties would have higher incidence and death rates compared to less vulnerable counties and that this disparity would widen as the pandemic progressed.

We conducted a retrospective longitudinal analysis examining COVID-19 incidence and death rates from March 1 to August 31, 2020 for each county in the US. We obtained daily COVID-19 incident case and death data from USAFacts and the Johns Hopkins Center for Systems Science and Engineering. We classified counties using the Social Vulnerability Index (SVI), a pets indicate that the impact of COVID-19 is not static but can migrate from less vulnerable counties to more vulnerable counties over time. Doramapimod molecular weight This highlights the importance of protecting vulnerable populations as the pandemic unfolds.COVID-19 respiratory infections are associated with copious, adherent respiratory secretions that prolong chronic ventilation and contribute to the morbidity and mortality caused by the disease. We hypothesized that hyaluronan, an extracellular matrix glycosaminoglycan produced at sites of active inflammation that promotes edema in other settings, might be a component of these secretions. To interrogate this, we examined the respiratory secretions collected from eight intubated patients with COVID-19, six control patients with cystic fibrosis (CF), a different respiratory disease also associated with thick adherent secretions, and eight healthy controls. In this sample set we found that hyaluronan content is increased approximately 20-fold in both CF and COVID-19 patients compared to healthy controls. The hyaluronan in COVID-19 samples was comprised of low-molecular weight fragments, the hyaluronan form most strongly linked with pro-inflammatory functions. Hyaluronan is similarly abundant in histologic sections from cadaveric lung tissue from COVID-19 patients. These findings implicate hyaluronan in the thick respiratory secretions characteristic of COVID-19 infection. Therapeutic strategies targeting hyaluronan should be investigated further for potential use in patients with COVID-19.Angiotensin-converting enzyme 2 (ACE2) maintains cardiovascular and renal homeostasis but also serves as the entry receptor for the novel severe acute respiratory syndrome coronavirus (SARS-CoV-2), the causal agent of novel coronavirus disease 2019 (COVID-19). COVID-19 disease severity is typically lower in pediatric patients than adults (particularly the elderly), but higher rates of hospitalizations requiring intensive care are observed in infants than in older children – the reasons for these differences are unknown. ACE2 is expressed in several adult tissues and cells, including alveolar type 2 cells of the distal lung epithelium, but expression at other ages is largely unexplored. Here we show that ACE2 transcripts are expressed in the lung and trachea shortly after birth, downregulated during childhood, and again expressed at high levels in late adulthood. Notably, the repertoire of cells expressing ACE2 protein in the mouse lung and airways shifts during key phases of lung maturation. In particular, podvance our understanding of the regulation of ACE2 and cell death programs in the mammalian lung. Furthermore, our work provides the framework for translation of apoptosis modulating drugs as novel treatments for COVID-19.Although COVID-19 is considered to be primarily a respiratory disease, SARS-CoV-2 affects multiple organ systems including the central nervous system (CNS). Yet, there is no consensus whether the virus can infect the brain, or what the consequences of CNS infection are. Here, we used three independent approaches to probe the capacity of SARS-CoV-2 to infect the brain. First, using human brain organoids, we observed clear evidence of infection with accompanying metabolic changes in the infected and neighboring neurons. However, no evidence for the type I interferon responses was detected. We demonstrate that neuronal infection can be prevented either by blocking ACE2 with antibodies or by administering cerebrospinal fluid from a COVID-19 patient. Second, using mice overexpressing human ACE2, we demonstrate in vivo that SARS-CoV-2 neuroinvasion, but not respiratory infection, is associated with mortality. Finally, in brain autopsy from patients who died of COVID-19, we detect SARS-CoV-2 in the cortical neurons, and note pathologic features associated with infection with minimal immune cell infiltrates. These results provide evidence for the neuroinvasive capacity of SARS-CoV2, and an unexpected consequence of direct infection of neurons by SARS-CoV-2.Antibodies targeting the SARS-CoV-2 spike receptor-binding domain (RBD) are being developed as therapeutics and make a major contribution to the neutralizing antibody response elicited by infection. Here, we describe a deep mutational scanning method to map how all amino-acid mutations in the RBD affect antibody binding, and apply this method to 10 human monoclonal antibodies. The escape mutations cluster on several surfaces of the RBD that broadly correspond to structurally defined antibody epitopes. However, even antibodies targeting the same RBD surface often have distinct escape mutations. The complete escape maps predict which mutations are selected during viral growth in the presence of single antibodies, and enable us to design escape-resistant antibody cocktails-including cocktails of antibodies that compete for binding to the same surface of the RBD but have different escape mutations. Therefore, complete escape-mutation maps enable rational design of antibody therapeutics and assessment of the antigenic consequences of viral evolution.