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The novel coronavirus SARS-CoV-2, which emerged in late 2019, has since spread around the world and infected hundreds of millions of people with coronavirus disease 2019 (COVID-19). While this viral species was unknown prior to January 2020, its similarity to other coronaviruses that infect humans has allowed for rapid insight into the mechanisms that it uses to infect human hosts, as well as the ways in which the human immune system can respond. Here, we contextualize SARS-CoV-2 among other coronaviruses and identify what is known and what can be inferred about its behavior once inside a human host. Because the genomic content of coronaviruses, which specifies the virus's structure, is highly conserved, early genomic analysis provided a significant head start in predicting viral pathogenesis and in understanding potential differences among variants. The pathogenesis of the virus offers insights into symptomatology, transmission, and individual susceptibility. Additionally, prior research into interactions between the human immune system and coronaviruses has identified how these viruses can evade the immune system's protective mechanisms. We also explore systems-level research into the regulatory and proteomic effects of SARS-CoV-2 infection and the immune response. Understanding the structure and behavior of the virus serves to contextualize the many facets of the COVID-19 pandemic and can influence efforts to control the virus and treat the disease. IMPORTANCE COVID-19 involves a number of organ systems and can present with a wide range of symptoms. From how the virus infects cells to how it spreads between people, the available research suggests that these patterns are very similar to those seen in the closely related viruses SARS-CoV-1 and possibly Middle East respiratory syndrome-related CoV (MERS-CoV). Understanding the pathogenesis of the SARS-CoV-2 virus also contextualizes how the different biological systems affected by COVID-19 connect. Exploring the structure, phylogeny, and pathogenesis of the virus therefore helps to guide interpretation of the broader impacts of the virus on the human body and on human populations. For this reason, an in-depth exploration of viral mechanisms is critical to a robust understanding of SARS-CoV-2 and, potentially, future emergent human CoVs (HCoVs).Copyright © 2021 Rando et al.
RESUMEN
After emerging in China in late 2019, the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spread worldwide, and as of mid-2021, it remains a significant threat globally. Only a few coronaviruses are known to infect humans, and only two cause infections similar in severity to SARS-CoV-2: Severe acute respiratory syndrome-related coronavirus, a species closely related to SARS-CoV-2 that emerged in 2002, and Middle East respiratory syndrome-related coronavirus, which emerged in 2012. Unlike the current pandemic, previous epidemics were controlled rapidly through public health measures, but the body of research investigating severe acute respiratory syndrome and Middle East respiratory syndrome has proven valuable for identifying approaches to treating and preventing novel coronavirus disease 2019 (COVID-19). Building on this research, the medical and scientific communities have responded rapidly to the COVID-19 crisis and identified many candidate therapeutics. The approaches used to identify candidates fall into four main categories: adaptation of clinical approaches to diseases with related pathologies, adaptation based on virological properties, adaptation based on host response, and data-driven identification (ID) of candidates based on physical properties or on pharmacological compendia. To date, a small number of therapeutics have already been authorized by regulatory agencies such as the Food and Drug Administration (FDA), while most remain under investigation. The scale of the COVID-19 crisis offers a rare opportunity to collect data on the effects of candidate therapeutics. This information provides insight not only into the management of coronavirus diseases but also into the relative success of different approaches to identifying candidate therapeutics against an emerging disease. IMPORTANCE The COVID-19 pandemic is a rapidly evolving crisis. With the worldwide scientific community shifting focus onto the SARS-CoV-2 virus and COVID-19, a large number of possible pharmaceutical approaches for treatment and prevention have been proposed. What was known about each of these potential interventions evolved rapidly throughout 2020 and 2021. This fast-paced area of research provides important insight into how the ongoing pandemic can be managed and also demonstrates the power of interdisciplinary collaboration to rapidly understand a virus and match its characteristics with existing or novel pharmaceuticals. As illustrated by the continued threat of viral epidemics during the current millennium, a rapid and strategic response to emerging viral threats can save lives. In this review, we explore how different modes of identifying candidate therapeutics have borne out during COVID-19.
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Background: Acute kidney injury (AKI) is a common complication of patients hospitalized with coronavirus disease 2019 (COVID-19), however, the epidemiological studies are limited by single or few centers and short duration. How the incidence of COVID-19-associated AKI has changed over the last 18 months since start of the pandemic is not known. Methods: We used the N3C enclave to collect data from 42 centers from all geographical regions of the United States of patients hospitalized with COVID-19 from December 2019 to May 2021. Unique patient visit occurrence ID data across various hospitalizations for each center was harmonized to uniformly collect information on serum creatinine (SCr), acute dialysis, end-stage kidney disease (ESKD) and transplantation. From a total of 127,223 patients hospitalized with COVID-19, 3,662 patients with preexisting ESKD and 20,090 with < 2 measures of SCr were excluded. AKI and AKI stages were defined by KDIGO criteria. Baseline SCr was defined from the outpatient values before hospitalization when available or lowest inpatient value if not available. We analyzed how the incidence of in-hospital AKI changed over time (every 4-month period). Mann-Kendall Test was used to test for monotonic trends of the AKI incidence. Results: Of the 103,471 patients hospitalized with COVID-19, 31,634 (30.6%) were diagnosed with AKI (mean age 63.3 years, 43.7% female, 32.4% non-white, and 19.5% Hispanic). 14,129 (13.7%) patients were diagnosed with AKI-1, 7,996 (7.7%) had AKI-2 and 9,509 (9.2%) patients had AKI-3 (6,285 [6.1%] without dialysis and 3,224 [3.1%] with dialysis). The incidence of 'all AKI' decreased from 38.8% in Dec 2019-March 2020 to 26.2% in March-May 2021 (p-value for trend = 0.086) and the incidence of AKI-3 declined from 15.5% to 6.5% (p = 0.086). Conclusions: This is the largest and most nationally representative cohort of patients hospitalized with COVID-19 with the highest number of cases of AKI and of AKI-3 reported thus far. The incidence of COVID-19-associated AKI has shown a nonstatistically significant decline during the past 18 months of the pandemic.