Associations Between Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Variants and Risk of Coronavirus Disease 2019 (COVID-19) Hospitalization Among Confirmed Cases in Washington State: A Retrospective Cohort Study.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic is dominated by variant viruses; the resulting impact on disease severity remains unclear. Using a retrospective cohort study, we assessed the hospitalization risk following infection with 7 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants. METHODS: Our study includes individuals with positive SARS-CoV-2 reverse transcription polymerase chain reaction (RT-PCR) in the Washington Disease Reporting System with available viral genome data, from 1 December 2020 to 14 January 2022. The analysis was restricted to cases with specimens collected through sentinel surveillance. Using a Cox proportional hazards model with mixed effects, we estimated hazard ratios (HR) for hospitalization risk following infection with a variant, adjusting for age, sex, calendar week, and vaccination. RESULTS: In total, 58 848 cases were sequenced through sentinel surveillance, of which 1705 (2.9%) were hospitalized due to COVID-19. Higher hospitalization risk was found for infections with Gamma (HR 3.20, 95% confidence interval [CI] 2.40-4.26), Beta (HR 2.85, 95% CI 1.56-5.23), Delta (HR 2.28 95% CI 1.56-3.34), or Alpha (HR 1.64, 95% CI 1.29-2.07) compared to infections with ancestral lineages; Omicron (HR 0.92, 95% CI .56-1.52) showed no significant difference in risk. Following Alpha, Gamma, or Delta infection, unvaccinated patients show higher hospitalization risk, while vaccinated patients show no significant difference in risk, both compared to unvaccinated, ancestral lineage cases. Hospitalization risk following Omicron infection is lower with vaccination. CONCLUSIONS: Infection with Alpha, Gamma, or Delta results in a higher hospitalization risk, with vaccination attenuating that risk. Our findings support hospital preparedness, vaccination, and genomic surveillance.

Chiral Diol-Based Organocatalysts in Enantioselective Reactions.

Organocatalysis has emerged as a powerful synthetic tool in organic chemistry in the last few decades. Among various classes of organocatalysis, chiral diol-based scaffolds, such as BINOLs, VANOLs, and tartaric acid derivatives, have been widely used to induce enantioselectivity due to the ability of the hydroxyls to coordinate with the Lewis acidic sites of reagents or substrates and create a chiral environment for the transformation. In this review, we will discuss the applications of these diol-based catalysts in different types of reactions, including the scopes of reactions and the modes of catalyst activation. In general, the axially chiral aryl diol BINOL and VANOL derivatives serve as the most competent catalyst for most examples, but examples of exclusive success using other scaffolds, herein, suggests that they should not be overlooked. Lastly, the examples, to date, are mainly from tartrate and biaryl diol catalysts, suggesting that innovation may be available from new diol scaffolds.

Quaternary and Tertiary Carbon Centers Synthesized via Gallium-Catalyzed Direct Substitution of Unfunctionalized Propargylic Alcohols with Boronic Acids.

(IPr)GaCl3/AgSbF6, AgSbF6, and GaCl3 catalyzed substitution of the hydroxyl of secondary and tertiary propargylic alcohols with organoboronic acids via C-C bond formation, and GaCl3 effectively synthesized all-carbon quaternary propargylic centers. These catalysts performed the substitution at carbons bearing alkyl substituents, which has been problematic for other systems. Highly hindered carbon stereocenters were thus produced, including quaternary centers bearing doubly ortho-substituted aryl rings, that are difficult to access with traditional methods.

Associations between SARS-CoV-2 variants and risk of COVID-19 hospitalization among confirmed cases in Washington State: a retrospective cohort study.

BACKGROUND: The COVID-19 pandemic is dominated by variant viruses; the resulting impact on disease severity remains unclear. Using a retrospective cohort study, we assessed the hospitalization risk following infection with seven SARS-CoV-2 variants. METHODS: Our study includes individuals with positive SARS-CoV-2 RT-PCR in the Washington Disease Reporting System with available viral genome data, from December 1, 2020 to January 14, 2022. The analysis was restricted to cases with specimens collected through sentinel surveillance. Using a Cox proportional hazards model with mixed effects, we estimated hazard ratios (HR) for hospitalization risk following infection with a variant, adjusting for age, sex, calendar week, and vaccination. FINDINGS: 58,848 cases were sequenced through sentinel surveillance, of which 1705 (2.9%) were hospitalized due to COVID-19. Higher hospitalization risk was found for infections with Gamma (HR 3.20, 95%CI 2.40-4.26), Beta (HR 2.85, 95%CI 1.56-5.23), Delta (HR 2.28 95%CI 1.56-3.34) or Alpha (HR 1.64, 95%CI 1.29-2.07) compared to infections with ancestral lineages; Omicron (HR 0.92, 95%CI 0.56-1.52) showed no significant difference in risk. Following Alpha, Gamma, or Delta infection, unvaccinated patients show higher hospitalization risk, while vaccinated patients show no significant difference in risk, both compared to unvaccinated, ancestral lineage cases. Hospitalization risk following Omicron infection is lower with vaccination. CONCLUSION: Infection with Alpha, Gamma, or Delta results in a higher hospitalization risk, with vaccination attenuating that risk. Our findings support hospital preparedness, vaccination, and genomic surveillance. SUMMARY: Hospitalization risk following infection with SARS-CoV-2 variant remains unclear. We find a higher hospitalization risk in cases infected with Alpha, Beta, Gamma, and Delta, but not Omicron, with vaccination lowering risk. Our findings support hospital preparedness, vaccination, and genomic surveillance.

Csp3-H Trifluoromethylation of Unactivated Aliphatic Systems.

A straightforward method for the undirected trifluoromethylation of unactivated methylene units was developed. The reaction proceeds in aqueous acetonitrile with Grushin's reagent, bpyCu(CF3)3, under broad-spectrum white-light irradiation. The trifluoromethylation tolerates a wide range of functional groups including ketones, esters, nitriles, amides, alcohols, and carboxylic acids. The C-H cleavage step is performed via intermolecular H atom abstraction, and the selectivities across a range of methylene units are reported. Mechanistic studies offer a general reaction coordinate for the overall transformation.

Cryptic transmission of SARS-CoV-2 in Washington state.

After its emergence in Wuhan, China, in late November or early December 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus rapidly spread globally. Genome sequencing of SARS-CoV-2 allows the reconstruction of its transmission history, although this is contingent on sampling. We analyzed 453 SARS-CoV-2 genomes collected between 20 February and 15 March 2020 from infected patients in Washington state in the United States. We find that most SARS-CoV-2 infections sampled during this time derive from a single introduction in late January or early February 2020, which subsequently spread locally before active community surveillance was implemented.

Cryptic transmission of SARS-CoV-2 in Washington State.

Following its emergence in Wuhan, China, in late November or early December 2019, the SARS-CoV-2 virus has rapidly spread throughout the world. On March 11, 2020, the World Health Organization declared Coronavirus Disease 2019 (COVID-19) a pandemic. Genome sequencing of SARS-CoV-2 strains allows for the reconstruction of transmission history connecting these infections. Here, we analyze 346 SARS-CoV-2 genomes from samples collected between 20 February and 15 March 2020 from infected patients in Washington State, USA. We found that the large majority of SARS-CoV-2 infections sampled during this time frame appeared to have derived from a single introduction event into the state in late January or early February 2020 and subsequent local spread, strongly suggesting cryptic spread of COVID-19 during the months of January and February 2020, before active community surveillance was implemented. We estimate a common ancestor of this outbreak clade as occurring between 18 January and 9 February 2020. From genomic data, we estimate an exponential doubling between 2.4 and 5.1 days. These results highlight the need for large-scale community surveillance for SARS-CoV-2 introductions and spread and the power of pathogen genomics to inform epidemiological understanding.

Oxyallyl Cation Capture via Electrophilic Deborylation of Organoboronates: Access to α,α'-Substituted Cyclic Ketones.

An umpolung strategy to synthesize α,α'-substituted cyclic ketones through the nucleophilic addition of organoboronates to α-hydroxyl silyl enol ethers is described. The reaction proceeds via the trapping of in situ generated oxyallyl cations via the electrophilic deborylation of C(sp2) and C(sp) borates. This efficient and straightforward method provides direct access to α-substituted silyl enol ethers in high yield with complete regioselectivity. Desilylation in a one-pot procedure provides the corresponding α,α'-disubstituted ketones with high diastereoselectivity.

Branched Amine Synthesis via Aziridine or Azetidine Opening with Organotrifluoroborates by Cooperative Brønsted/Lewis Acid Catalysis: An Acid-Dependent Divergent Mechanism.

A practical catalytic method to synthesize ß,ß- and γ,γ-substituted amines by opening aziridines and azetidines, respectively, using alkenyl, alkynyl, or aryl/heteroaryl trifluoroborate salts is described. This reaction features simple open-flask reaction conditions, the use of transition-metal-free catalysis, complete regioselectivity, and high diastereoselectivity. Preliminary mechanistic studies suggest that carbocation formation is disfavored. Stereoretentive addition is favored with Brønsted acid present, while stereoinversion is favored in its absence, indicating divergent mechanisms.

Tertiary and Quaternary Carbon Formation via Gallium-Catalyzed Nucleophilic Addition of Organoboronates to Cyclopropanes.

GaCl3 and (IPr)GaCl3/AgSbF6 formed γ-tertiary and γ-quaternary carbons via homoconjugate addition of organoboron nucleophiles to diester- and ketone-functionalized cyclopropanes. Electron donor group cyclopropane substituents were not needed, allowing electron-deficient aryl, alkenyl, alkyl, and hydrogen-substituted cyclopropanes to be used. The catalytic conditions were compatible with alkenyl, alkynyl, and aryl nucleophiles, including ortho-substituted aromatics, to synthesize highly hindered quaternary carbons. Alkynyl nucleophiles formed substituted cyclopentenes. A control experiment supports an intermediate carbocation in quaternary carbon center formation.

Brønsted Acid Catalyzed Homoconjugate Addition of Organotrifluoroborates to Arylated Cyclopropyl Ketones.

A novel and practical homoconjugate addition of alkenyl, alkynyl, heteroaryl, and aryl trifluoroborates to arylated cyclopropyl ketones to synthesize γ,γ-disubstituted ketones is reported. A preliminary mechanistic proposal involving ketone protonation, an intermediary carbocation, and intermolecular nucleophile addition has been made based on control studies.