Omicron BQ.1.1 and XBB.1 unprecedentedly escape broadly neutralizing antibodies elicited by prototype vaccination.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron subvariants have seriously attacked the antibody barrier established by natural infection and/or vaccination, especially the recently emerged BQ.1.1 and XBB.1. However, crucial mechanisms underlying the virus escape and the broad neutralization remain elusive. Here, we present a panoramic analysis of broadly neutralizing activity and binding epitopes of 75 monoclonal antibodies isolated from prototype inactivated vaccinees. Nearly all neutralizing antibodies (nAbs) partly or totally lose their neutralization against BQ.1.1 and XBB.1. We report a broad nAb, VacBB-551, that effectively neutralizes all tested subvariants including BA.2.75, BQ.1.1, and XBB.1. We determine the cryoelectron microscopy (cryo-EM) structure of VacBB-551 complexed with the BA.2 spike and perform detailed functional verification to reveal the molecular basis of N460K and F486V/S mutations mediating the partial escape of BA.2.75, BQ.1.1, and XBB.1 from the neutralization of VacBB-551. Overall, BQ.1.1 and XBB.1 raised the alarm over SARS-CoV-2 evolution with unprecedented antibody evasion from broad nAbs elicited by prototype vaccination.

Design and Application of Vague Set Theory and Adaptive Grid Particle Swarm Optimization Algorithm in Resource Scheduling Optimization.

The purpose of resource scheduling is to deal with all kinds of unexpected events that may occur in life, such as fire, traffic jam, earthquake and other emergencies, and the scheduling algorithm is one of the key factors affecting the intelligent scheduling system. In the traditional resource scheduling system, because of the slow decision-making, it is difficult to meet the needs of the actual situation, especially in the face of emergencies, the traditional resource scheduling methods have great disadvantages. In order to solve the above problems, this paper takes emergency resource scheduling, a prominent scheduling problem, as an example. Based on Vague set theory and adaptive grid particle swarm optimization algorithm, a multi-objective emergency resource scheduling model is constructed under different conditions. This model can not only integrate the advantages of Vague set theory in dealing with uncertain problems, but also retain the advantages of adaptive grid particle swarm optimization that can solve multi-objective optimization problems and can quickly converge. The research results show that compared with the traditional resource scheduling optimization algorithm, the emergency resource scheduling model has higher resolution accuracy, more reasonable resource allocation, higher efficiency and faster speed in dealing with emergency events than the traditional resource scheduling model. Compared with the conventional fuzzy theory emergency resource scheduling model, its handling speed has increased by more than 3.82 times.

Household curricula during the COVID‐19 pandemic: A collective biography

Households with school‐aged children worldwide were affected by school closures caused by COVID‐19. Using a sociomaterial orientation and collective biography methodology, this study examined the household curricula of diverse families in Ontario, Canada with children in pre‐school through Grade 12. It found two distinct curricular phases to the pandemic, each with its own networked constituents, movements, and effects. Phase I involved learning at home during the lockdown in Spring and Summer 2020;Phase II involved online and face‐to‐face learning in the Fall of 2020. The constituents involved in curriculum making in Phase I were expansive and unexpected. Multiple timescales, modes, languages, and knowledge disciplines assembled to (re)configure households as learning spaces that produced novel opportunities for children's knowing, doing, and being. The makeup and movements of the Phase II assemblages were more of a return to the normalized boundaries of implemented school curricula that demarcated subject areas, languages, learning/play, learning/assessment, and body/mind. Concerned with questions of equity in/through curriculum, this study suggests a curriculum paradigm that foregrounds learners' and teachers' engagement with sociomaterial lifeworlds and their ethical relationship building with the more‐than‐human and the world. [ FROM AUTHOR] Copyright of Curriculum Journal is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Three Experimental Common High-Risk Procedures: Emission Characteristics Identification and Source Intensity Estimation in Biosafety Laboratory

Biosafety laboratory is an important place to study high-risk microbes. In biosafety laboratories, with the outbreak of infectious diseases such as COVID-19, experimental activities have become increasingly frequent, and the risk of exposure to bioaerosols has increased. To explore the exposure risk of biosafety laboratories, the intensity and emission characteristics of laboratory risk factors were investigated. In this study, high-risk microbe samples were substituted with Serratia marcescens as the model bacteria. The resulting concentration and particle size segregation of the bioaerosol produced by three experimental procedures (spill, injection, and sample drop) were monitored, and the emission sources' intensity were quantitatively analyzed. The results showed that the aerosol concentration produced by injection and sample drop was

Additional mutations based on Omicron BA.2.75 mediate its further evasion from broadly neutralizing antibodies

SARS-CoV-2 Omicron BA.2.75 subvariant has evolved to a series of progeny variants carrying several additional mutations in the receptor-binding domain (RBD). Here, we investigated whether and how these single mutations based on BA.2.75 affect the neutralization of currently available anti-RBD monoclonal antibodies (mAbs) with well-defined structural information. Approximately 34% of mAbs maintained effective neutralizing activities against BA.2.75, consistent with that against BA.2, BA.4/5, and BA.2.12.1. Single additional R346T, K356T, L452R, or F486S mutations further facilitated BA.2.75-related progeny variants to escape from broadly neutralizing antibodies (bnAbs) at different degree. Only LY-CoV1404 (bebtelovimab) displayed a first-class neutralization potency and breadth against all tested Omicron subvariants. Overall, these data make a clear connection between virus escape and antibody recognizing antigenic epitopes, which facilitate to develop next-generation universal bnAbs against emerging SARS-CoV-2 variants. Graphical

Family Literacies During the COVID-19 Lockdown: Semiotic Assemblages and Meaning Making at Home

When home became the primary place for children's learning during the COVID-19 lockdown, a dominant rhetoric emerged about a literacy-skills crisis, especially involving learners from low-income and culturally and linguistically diverse families. By documenting the literacies practiced and the literacy-learning opportunities created in and among households during the lockdown in the spring and summer of 2020, this study turns this deficit-oriented rhetoric on its head. Conducted by parents with their children (aged 2-15), this collective biography found that during the lockdown households were forced into spaces that were physically constrained yet replete with a wide range of semiotic resources. Parents and children used these resources, which included multiple modes, media, and languages, to produce expansive literacies and literacy-learning opportunities. The present study offers suggestions about how to recognize and build on learners' linguistic, cultural, and semiotic repertoires in the creation of literacy curricula.

Mental health conditions of Chinese international students and associated predictors amidst the pandemic.

The current study aims to examine the mental health conditions and the associated predictors among Chinese international students. A sample of 256 Chinese international students aged 16 or above living primarily in Canada were asked to complete an online survey. Mental health conditions were assessed with the Depression, Anxiety, and Stress Scale-21 and the Physical and Mental Health Summary Scales. 15.3%, 20.4%, and 10.5% of respondents reported severe to extremely severe depression, anxiety, and stress levels, respectively. Univariate analysis of variance models and multiple linear regression models identified education and financial status as significant sociodemographic predictors while controlling for the effect of physical health status. Higher financial status and lower level of education were associated with better mental health conditions. These findings shed light on our understanding of mental health conditions and the risk factors among Chinese international students during the COVID-19 pandemic.

Additional mutations based on Omicron BA.2.75 mediate its further evasion from broadly neutralizing antibodies.

SARS-CoV-2 Omicron BA.2.75 subvariant has evolved to a series of progeny variants carrying several additional mutations in the receptor-binding domain (RBD). Here, we investigated whether and how these single mutations based on BA.2.75 affect the neutralization of currently available anti-RBD monoclonal antibodies (mAbs) with well-defined structural information. Approximately 34% of mAbs maintained effective neutralizing activities against BA.2.75, consistent with those against BA.2, BA.4/5, and BA.2.12.1. Single additional R346T, K356T, L452R, or F486S mutations further facilitated BA.2.75-related progeny variants to escape from broadly neutralizing antibodies (bnAbs) at different degree. Only LY-CoV1404 (bebtelovimab) displayed a first-class neutralization potency and breadth against all tested Omicron subvariants. Overall, these data make a clear connection between virus escape and antibody recognizing antigenic epitopes, which facilitate to develop next-generation universal bnAbs against emerging SARS-CoV-2 variants.

Infection with wild-type SARS-CoV-2 elicits broadly neutralizing and protective antibodies against omicron subvariants.

The omicron variants of SARS-CoV-2 have substantial ability to escape infection- and vaccine-elicited antibody immunity. Here, we investigated the extent of such escape in nine convalescent patients infected with the wild-type SARS-CoV-2 during the first wave of the pandemic. Among the total of 476 monoclonal antibodies (mAbs) isolated from peripheral memory B cells, we identified seven mAbs with broad neutralizing activity to all variants tested, including various omicron subvariants. Biochemical and structural analysis indicated the majority of these mAbs bound to the receptor-binding domain, mimicked the receptor ACE2 and were able to accommodate or inadvertently improve recognition of omicron substitutions. Passive delivery of representative antibodies protected K18-hACE2 mice from infection with omicron and beta SARS-CoV-2. A deeper understanding of how the memory B cells that produce these antibodies could be selectively boosted or recalled can augment antibody immunity against SARS-CoV-2 variants.

Characterizing the cellular and molecular variabilities of peripheral immune cells in healthy recipients of BBIBP-CorV inactivated SARS-CoV-2 vaccine by single-cell RNA sequencing.

Over 3 billion doses of inactivated vaccines for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been administered globally. However, our understanding of the immune cell functional transcription and T cell receptor (TCR)/B cell receptor (BCR) repertoire dynamics following inactivated SARS-CoV-2 vaccination remains poorly understood. Here, we performed single-cell RNA and TCR/BCR sequencing on peripheral blood mononuclear cells at four time points after immunization with the inactivated SARS-CoV-2 vaccine BBIBP-CorV. Our analysis revealed an enrichment of monocytes, central memory CD4+ T cells, type 2 helper T cells and memory B cells following vaccination. Single-cell TCR-seq and RNA-seq comminating analysis identified a clonal expansion of CD4+ T cells (but not CD8+ T cells) following a booster vaccination that corresponded to a decrease in the TCR diversity of central memory CD4+ T cells and type 2 helper T cells. Importantly, these TCR repertoire changes and CD4+ T cell differentiation were correlated with the biased VJ gene usage of BCR and the antibody-producing function of B cells post-vaccination. Finally, we compared the functional transcription and repertoire dynamics in immune cells elicited by vaccination and SARS-CoV-2 infection to explore the immune responses under different stimuli. Our data provide novel molecular and cellular evidence for the CD4+ T cell-dependent antibody response induced by inactivated vaccine BBIBP-CorV. This information is urgently needed to develop new prevention and control strategies for SARS-CoV-2 infection. (ClinicalTrials.gov Identifier: NCT04871932).

Obesity Is Associated with Attenuated Tissue Immunity in COVID-19.

RATIONALE: Obesity affects 40% of US adults, is associated with a pro-inflammatory state, and presents a significant risk factor for the development of severe COVID-19. To date, there is limited information on how obesity might affect immune cell responses in SARS-CoV-2 infection. OBJECTIVES: To determine the impact of obesity on respiratory tract immunity in COVID-19 across human lifespan. METHODS: We analysed single cell transcriptomes from bronchiolar lavage in three ventilated adult cohorts with (n=24) or without COVID-19 (n=9), from nasal immune cells in children with (n=14) or without COVID-19 (n=19), and from peripheral blood mononuclear cells in an independent adult COVID-19 cohort (n=42), comparing obese (Ob) and non-obese subjects (N-Ob). MEASUREMENTS AND MAIN RESULTS: Surprisingly, we found that adult Ob subjects had attenuated lung immune/inflammatory responses in SARS-CoV-2 infection, with decreased expression of interferon (IFN)α, IFNγ and tumour necrosis factor (TNF) alpha response gene signatures in almost all lung epithelial and immune cell subsets, and lower expression of IFNG and TNF in specific lung immune cells. Peripheral blood immune cells in an independent adult cohort showed a similar, but less marked, reduction in type I IFN and IFNγ response genes, as well as decreased serum IFNα in Ob patients with SARS-CoV-2. Nasal immune cells from Ob children with COVID-19 also showed reduced enrichment of IFNα and IFNγ response genes. CONCLUSIONS: These findings show blunted tissue immune responses in Ob COVID-19 patients, with implications for treatment stratification, supporting the specific application of inhaled recombinant type I IFNs in this vulnerable subset. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Three Experimental Common High-Risk Procedures: Emission Characteristics Identification and Source Intensity Estimation in Biosafety Laboratory.

Biosafety laboratory is an important place to study high-risk microbes. In biosafety laboratories, with the outbreak of infectious diseases such as COVID-19, experimental activities have become increasingly frequent, and the risk of exposure to bioaerosols has increased. To explore the exposure risk of biosafety laboratories, the intensity and emission characteristics of laboratory risk factors were investigated. In this study, high-risk microbe samples were substituted with Serratia marcescens as the model bacteria. The resulting concentration and particle size segregation of the bioaerosol produced by three experimental procedures (spill, injection, and sample drop) were monitored, and the emission sources' intensity were quantitatively analyzed. The results showed that the aerosol concentration produced by injection and sample drop was 103 CFU/m3, and that by sample spill was 102 CFU/m3. The particle size of bioaerosol is mainly segregated in the range of 3.3-4.7 µm. There are significant differences in the influence of risk factors on source intensity. The intensity of sample spill, injection, and sample drop source is 3.6 CFU/s, 78.2 CFU/s, and 664 CFU/s. This study could provide suggestions for risk assessment of experimental operation procedures and experimental personnel protection.

Omicron variants escape the persistent SARS-CoV-2-specific antibody response in 2-year COVID-19 convalescents regardless of vaccination.

With the ongoing COVID-19 pandemic and the emergence of various SARS-CoV-2 variants, a comprehensive evaluation of long-term efficacy of antibody response in convalescent individuals is urgently needed. Several longitudinal studies had reported the antibody dynamics after SARS-CoV-2 acute infection, but the follow-up was mostly limited to 1 year or 18 months at the maximum. In this study, we investigated the durability, potency, and susceptibility to immune evasion of SARS-CoV-2-specific antibody in COVID-19 convalescents for 2 years after discharge. These results showed the persistent antibody-dependent immunity could protect against the WT and Delta variant to some extent. However, the Omicron variants (BA.1, BA.2, and BA.4/5) largely escaped this preexisting immunity in recovered individuals. Furthermore, we revealed that inactivated vaccines (BBIBP-CorV, CoronaVac, or KCONVAC) could improve the plasma neutralization and help to maintain the broadly neutralizing antibodies at a certain level. Notably, with the time-dependent decline of antibody, 1-dose or 2-dose vaccination strategy seemed not to be enough to provide immune protection against the emerging variants. Overall, these results facilitated our understanding of SARS-CoV-2-induced antibody memory, contributing to the development of immunization strategy against SARS-CoV-2 variants for such a large number of COVID-19 survivors.

CRISPR‐Cas13d effectively targets SARS‐CoV‐2 variants, including Delta and Omicron, and inhibits viral infection

The recent pandemic of variants of concern (VOC) of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) highlights the need for innovative anti‐SARS‐CoV‐2 approaches in addition to vaccines and antiviral therapeutics. Here, we demonstrate that a CRISPR‐Cas13‐based strategy against SARS‐CoV‐2 can effectively degrade viral RNA. First, we conducted a cytological infection experiment, screened CRISPR‐associated RNAs (crRNAs) targeting conserved regions of viruses, and used an in vitro system to validate functional crRNAs. Reprogrammed Cas13d effectors targeting NSP13, NSP14, and nucleocapsid transcripts achieved >99% silencing efficiency in human cells which are infected with coronavirus 2, including the emerging variants in the last 2 years, B.1, B.1.1.7 (Alpha), D614G B.1.351 (Beta), and B.1.617 (Delta). Furthermore, we conducted bioinformatics data analysis. We collected the sequence information of COVID‐19 and its variants from China, and phylogenetic analysis revealed that these crRNA oligos could target almost 100% of the SARS‐CoV family, including the emerging new variant, Omicron. The reprogrammed Cas13d exhibited high specificity, efficiency, and rapid deployment properties;therefore, it is promising for antiviral drug development. This system could possibly be used to protect against unexpected SARS‐CoV‐2 variants carrying multiple mutations. Cas13d‐crRNAs inhibit both ancestral and mutated SARS‐CoV‐2 replication. Cas13d‐crRNAs inhibit both ancestral and mutated SARS‐CoV‐2 replication including Delta. Cas13d‐crRNAs could inhibit Omicron and other SARS family strains and are a potential pan‐SARS inhibition strategy.

CRISPR-Cas13d effectively targets SARS-CoV-2 variants, including Delta and Omicron, and inhibits viral infection.

The recent pandemic of variants of concern (VOC) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) highlights the need for innovative anti-SARS-CoV-2 approaches in addition to vaccines and antiviral therapeutics. Here, we demonstrate that a CRISPR-Cas13-based strategy against SARS-CoV-2 can effectively degrade viral RNA. First, we conducted a cytological infection experiment, screened CRISPR-associated RNAs (crRNAs) targeting conserved regions of viruses, and used an in vitro system to validate functional crRNAs. Reprogrammed Cas13d effectors targeting NSP13, NSP14, and nucleocapsid transcripts achieved >99% silencing efficiency in human cells which are infected with coronavirus 2, including the emerging variants in the last 2 years, B.1, B.1.1.7 (Alpha), D614G B.1.351 (Beta), and B.1.617 (Delta). Furthermore, we conducted bioinformatics data analysis. We collected the sequence information of COVID-19 and its variants from China, and phylogenetic analysis revealed that these crRNA oligos could target almost 100% of the SARS-CoV family, including the emerging new variant, Omicron. The reprogrammed Cas13d exhibited high specificity, efficiency, and rapid deployment properties; therefore, it is promising for antiviral drug development. This system could possibly be used to protect against unexpected SARS-CoV-2 variants carrying multiple mutations.

Self-paced Multi-view Learning for CT-based severity assessment of COVID-19.

Prior studies for the task of severity assessment of COVID-19 (SA-COVID) usually suffer from domain-specific cognitive deficits. They mainly focus on visual cues based on single cognitive functions but fail to reconcile the valuable information from other alternative views. Inspired by the cognitive process of radiologists, this paper shifts naturally from single-symptom measurements to a multi-view analysis, and proposes a novel Self-paced Multi-view Learning (SPML) framework for automated SA-COVID. Specifically, the proposed SPML framework first comprehensively aggregates multi-view contexts in lung infection with different measure paradigms, i.e., Global Feature Branch, Texture Feature Branch, and Volume Feature Branch. In this way, multiple-perspective clues are taken into account to reflect the most essential pathological manifestation on CT images. To alleviate small-sample learning problems, we also introduce an optimization with self-paced learning strategy to cognitively increase the characterization capabilities of training samples by learning from simple to complex. In contrast to traditional batch-wise learning, a pure self-paced way can further guarantee the efficiency and accuracy of SPML when dealing with small and biased samples. Furthermore, we construct a well-established SA-COVID dataset that contains 300 CT images with fine annotations. Extensive experiments on this dataset demonstrate that SPML consistently outperforms the state-of-the-art baselines. The SA-COVID dataset is publicly released at https://github.com/YishuLiu/SA-COVID.

Immunological and metabolic characteristics of the Omicron variants infection.

The Omicron variants of SARS-CoV-2, primarily authenticated in November 2021 in South Africa, has initiated the 5th wave of global pandemics. Here, we systemically examined immunological and metabolic characteristics of Omicron variants infection. We found Omicron resisted to neutralizing antibody targeting receptor binding domain (RBD) of wildtype SARS-CoV-2. Omicron could hardly be neutralized by sera of Corona Virus Disease 2019 (COVID-19) convalescents infected with the Delta variant. Through mass spectrometry on MHC-bound peptidomes, we found that the spike protein of the Omicron variants could generate additional CD8 + T cell epitopes, compared with Delta. These epitopes could induce robust CD8 + T cell responses. Moreover, we found booster vaccination increased the cross-memory CD8 + T cell responses against Omicron. Metabolic regulome analysis of Omicron-specific T cell showed a metabolic profile that promoted the response of memory T cells. Consistently, a greater fraction of memory CD8 + T cells existed in Omicron stimulated peripheral blood mononuclear cells (PBMCs). In addition, CD147 was also a receptor for the Omicron variants, and CD147 antibody inhibited infection of Omicron. CD147-mediated Omicron infection in a human CD147 transgenic mouse model induced exudative alveolar pneumonia. Taken together, our data suggested that vaccination booster and receptor blocking antibody are two effective strategies against Omicron.

Customization of aptamer to develop CRISPR/Cas12a-derived ultrasensitive biosensor.

The CRISPR/Cas systems have provided wide biosensing applications. Particularly, the aptamer-involved CRISPR/Cas sensor system powerfully expanded to non-nucleic-acid targets. However, tailoring the sequence of the aptamer to explore the relationship between affinity and the activation of CRISPR/Cas12a trans-cleavage activity has not been reported yet. Herein, we developed a series of new aptamers toward the spike protein 1(S1) of SARS-CoV-2. Surface plasmon resonance measurements showed that the affinity of these aptamers to S1 was at the nM level. Subsequently, a "SET" effect (Sequence Essential Trans-cleavage activity) is discovered for the activation of CRISPR/Cas12a trans-cleavage activity. That is, an aptamer, as the activator, sequence needs to be tailored to activate CRISPR/Cas12a efficiently. A balance should be reached between affinity and activation ability. On the one hand, high affinity ensures target recognition performance, and on the other hand, activation can achieve adequate amplification and output of recognition signals. The optimized sequence (with 27 nucleotides, for short 27-nt) not only recognizes the target with a high affinity and specificity but also can trigger the CRISPR/Cas12a trans-cleavage activity efficiently, showing an excellent detection performance in electrochemical biosensors. The detection limit for SARS-CoV-2 S1 can be low at 1.5 pg mL-1. The new CRISPR/Cas12a-derived aptasensor also displays a remarkable ability to detect Beta, Delta, and Omicron variants but is selective toward other kinds of proteins. Above all, it is robust for point-of-care testing (POCT) in complex biological fluids, such as saliva, urine, and serum, and provides a universal and scalable detecting platform. Our results provide new insights into aptamer development and a different strategy for COVID-19 antigen detection and biosensor development.

Randomized, placebo-controlled, single-blind phase 1 studies of the safety, tolerability, and pharmacokinetics of BRII-196 and BRII-198, SARS-CoV-2 spike-targeting monoclonal antibodies with an extended half-life in healthy adults.

Background: BRII-196 and BRII-198 are two anti-SARS-CoV-2 monoclonal neutralizing antibodies as a cocktail therapy for treating COVID-19 with a modified Fc region that extends half-life. Methods: Safety, tolerability, pharmacokinetics, and immunogenicity of BRII-196 and BRII-198 were investigated in first-in-human, placebo-controlled, single ascending dose phase 1 studies in healthy adults. 44 participants received a single intravenous infusion of single BRII-196 or BRII-198 up to 3,000 mg, or BRII-196 and BRII-198 combination up to 1500/1500 mg, or placebo and were followed up for 180 days. Primary endpoints were incidence of adverse events (AEs) and changes from pre-dose baseline in clinical assessments. Secondary endpoints included pharmacokinetics profiles of BRII-196/BRII-198 and detection of anti-drug antibodies (ADAs). Plasma neutralization activities against SARS-CoV-2 Delta live virus in comparison to post-vaccination plasma were evaluated as exploratory endpoints. Results: All infusions were well-tolerated without systemic or local infusion reactions, dose-limiting AEs, serious AEs, or deaths. Most treatment-emergent AEs were isolated asymptomatic laboratory abnormalities of grade 1-2 in severity. BRII-196 and BRII-198 displayed pharmacokinetics characteristic of Fc-engineered human IgG1 with mean terminal half-lives of 44.6-48.6 days and 72.2-83.0 days, respectively, with no evidence of interaction or significant anti-drug antibody development. Neutralizing activities against the live virus of the SARS-CoV-2 Delta variant were maintained in plasma samples taken on day 180 post-infusion. Conclusion: BRII-196 and BRII-198 are safe, well-tolerated, and suitable therapeutic or prophylactic options for SARS-CoV-2 infection. Clinical Trial Registration: ClinicalTrials.gov under identifiers NCT04479631, NCT04479644, and NCT04691180.