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There are limited data comparing the transmission rates and kinetics of viable virus shedding of the Omicron variant to those of the Delta variant. We compared these rates in hospitalized patients infected with Delta and Omicron variants. We prospectively enrolled adult patients with COVID-19 admitted to a tertiary care hospital in South Korea between September 2021 and May 2022. Secondary attack rates were calculated by epidemiologic investigation, and daily saliva samples were collected to evaluate viral shedding kinetics. Genomic and subgenomic SARS-CoV-2 RNA was measured by PCR, and virus culture was performed from daily saliva samples. A total of 88 patients with COVID-19 who agreed to daily sampling and were interviewed, were included. Of the 88 patients, 48 (59%) were infected with Delta, and 34 (41%) with Omicron; a further 5 patients gave undetectable or inconclusive RNA PCR results and 1 was suspected of being coinfected with both variants. Omicron group had a higher secondary attack rate (31% [38/124] vs. 7% [34/456], p < 0.001). Survival analysis revealed that shorter viable virus shedding period was observed in Omicron variant compared with Delta variant (median 4, IQR [1-7], vs. 8.5 days, IQR [5-12 days], p < 0.001). Multivariable analysis revealed that moderate-to-critical disease severity (HR: 1.96), and immunocompromised status (HR: 2.17) were independent predictors of prolonged viral shedding, whereas completion of initial vaccine series or first booster-vaccinated status (HR: 0.49), and Omicron infection (HR: 0.44) were independently associated with shorter viable virus shedding. Patients with Omicron infections had higher transmission rates but shorter periods of transmissible virus shedding than those with Delta infections., (© 2022 Wiley Periodicals LLC.)

Background: Data on the clinical and virological characteristics of the Delta variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are limited. This prospective cohort study compared the characteristics of the Delta variant to other variants., Methods: Adult patients with mild coronavirus disease 2019 (COVID-19) who agreed to daily saliva sampling at a community isolation facility in South Korea between July and August 2021 were enrolled. Scores of 28 COVID-19-related symptoms were recorded daily. The genomic RNA and subgenomic RNA from saliva samples were measured by real-time reverse-transcription polymerase chain reaction (PCR). Cell cultures were performed on saliva samples with positive genomic RNA results., Results: A total of 141 patients (Delta group, n = 108 [77%]; non-Delta group, n = 33 [23%]) were enrolled. Myalgia was more common in the Delta group than in the non-Delta group (52% vs 27%, P = .03). Total symptom scores were significantly higher in the Delta group between days 3 and 10 after symptom onset. Initial genomic RNA titers were similar between the 2 groups; however, during the late course of disease, genomic RNA titers were higher in the Delta group. Negative conversion of subgenomic RNA was slower in the Delta group (median 9 vs 5 days; P < .001). The duration of viral shedding in terms of positive viral culture was also longer in the Delta group (median 5 vs 3 days; P = .002)., Conclusions: COVID-19 patients infected with the Delta variant exhibited prolonged viable viral shedding with more severe symptoms than those infected with non-Delta variants., (© The Author(s) 2022. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Since the coronavirus disease outbreak in 2019, several antibody therapeutics have been developed to treat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. Antibody therapeutics are effective in neutralizing the virus and reducing hospitalization in patients with mild and moderate infections. These therapeutics target the spike protein of SARS-CoV-2; however, emerging mutations in this protein reduce their efficiency. In this study, we developed a universal SARS-CoV-2 neutralizing antibody. We generated a humanized monoclonal antibody, MG1141A, against the receptor-binding domain of the spike protein through traditional mouse immunization. We confirmed that MG1141A could effectively neutralize live viruses, with an EC 50 of 92 pM, and that it exhibited effective Fc-mediated functions. Additionally, it retained its neutralizing activity against the alpha (UK), beta (South Africa), and gamma (Brazil) variants of SARS-CoV-2. Taken together, our study contributes to the development of a novel antibody therapeutic approach, which can effectively combat emerging SARS-CoV-2 mutations., Competing Interests: SL, SJ, JKa, SP, YH, HN, MK, JL, KC, MO, JR, JL, and D-SK submitted a patent application on neutralizing antibodies against SARS-CoV-2. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Lee, Jang, Kang, Park, Han, Nam, Kim, Lee, Cho, Kim, Oh, Ryu, Seok, Kim, Lee, Park, Kim, Park and Kim.)

COVID-19 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which infected >200 million people resulting in >4 million deaths. However, temporal landscape of the SARS-CoV-2 translatome and its impact on the human genome remain unexplored. Here, we report a high-resolution atlas of the translatome and transcriptome of SARS-CoV-2 for various time points after infecting human cells. Intriguingly, substantial amount of SARS-CoV-2 translation initiates at a novel translation initiation site (TIS) located in the leader sequence, termed TIS-L. Since TIS-L is included in all the genomic and subgenomic RNAs, the SARS-CoV-2 translatome may be regulated by a sophisticated interplay between TIS-L and downstream TISs. TIS-L functions as a strong translation enhancer for ORF S, and as translation suppressors for most of the other ORFs. Our global temporal atlas provides compelling insight into unique regulation of the SARS-CoV-2 translatome and helps comprehensively evaluate its impact on the human genome., (© 2021. The Author(s).)

Knowledge of the factors affecting the difference in kinetics and longevity of the neutralizing antibody (nAb) response to SARS-CoV-2 is necessary to properly prioritize vaccination. In the present study, from March to December 2020, of the 143 patients who recovered from COVID-19, 87 underwent study visits scheduled every 3 months. Patient demographics and blood samples were collected followed by a plaque reduction neutralization test to analyze nAb titers. A linear mixed model was used to compare the effects of sex, age, and disease severity over time. Results demonstrated a gradual reduction in nAb titers over time with a significant decrease from 6 to 9 months post-COVID-19 infection (p < 0.001). In time-to-sex, age, and disease severity comparisons, reduction in nAb titers over time was unaffected by sex (p = 0.167), age (p = 0.188), or disease severity (p = 0.081). Additionally, the nAb titer was 1.46 times significantly higher in those aged ≥ 50 years than in those aged < 50 years (p = 0.036) irrespective of time Moreover, the nAb titer was 2.41 times higher in the moderate or above than that in the below moderate disease severity group (p < 0.001). However, no significant differences were observed in terms of sex (p = 0.300). Given the reduction in nAbs over time, maintaining protective neutralizing antibodies regardless of sex, age, or disease severity is needed. [ABSTRACT FROM AUTHOR]

As an enveloped virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) delivers its viral genome into host cells via fusion of the viral and cell membranes. Here, we show that ANO6/TMEM16F-mediated cell surface exposure of phosphatidylserine is critical for SARS-CoV-2 entry and that ANO6-selective inhibitors are effective against SARS-CoV-2 infections. Application of the SARS-CoV-2 Spike pseudotyped virus (SARS2-PsV) evokes a cytosolic Ca2+ elevation and ANO6-dependent phosphatidylserine externalization in ACE2/TMPRSS2-positive mammalian cells. A high-throughput screening of drug-like chemical libraries identifies three different structural classes of chemicals showing ANO6 inhibitory effects. Among them, A6-001 displays the highest potency and ANO6 selectivity and it inhibits the single-round infection of SARS2-PsV in ACE2/TMPRSS2-positive HEK 293T cells. More importantly, A6-001 strongly inhibits authentic SARS-CoV-2-induced phosphatidylserine scrambling and SARS-CoV-2 viral replications in Vero, Calu-3, and primarily cultured human nasal epithelial cells. These results provide mechanistic insights into the viral entry process and offer a potential target for pharmacological intervention to protect against coronavirus disease 2019 (COVID-19). [Display omitted] • A high-throughput screening of chemical libraries identifies several ANO6 inhibitors • SARS-CoV-2 Spike evokes ANO6-mediated phosphatidylserine scrambling in host cells • Phosphatidylserine scrambling promotes fusion of the viral and cell membranes • The identified ANO6 inhibitors inhibit SARS-CoV-2 viral replications Sim et al. show that ANO6/TMEM16F-mediated phosphatidylserine scrambling participates in the SARS-CoV-2 entry into host cells and ANO6 inhibitors are effective against SARS-CoV-2 infection. These findings provide mechanistic insights into the viral entry process as well as a potential target for the development of drugs to treat COVID-19. [ABSTRACT FROM AUTHOR]

Rapid and accurate measurement of SARS-CoV-2 neutralizing antibodies (nAbs) can aid in understanding the development of immunity against COVID-19. This study evaluated the diagnostic performance of a rapid SARS-CoV-2 nAb detection test called the BZ COVID-19 nAb test BZ-nAb (BZ-nAb; BioZentech). Using the 90% plaque-reduction neutralization test (PRNT-90) as a reference, 104 serum specimens collected from COVID-19-positive and -negative patients were grouped into 40 PRNT-90-positive and 64 PRNT-90-negative specimens. The performance of the BZ-nAb was compared with that of the cPass surrogate virus neutralization test (cPass sVNT; Genscript). The BZ-nAb showed a sensitivity ranging from 92.5%–95.0% and specificity ranging from 96.9%–100%, whereas cPass sVNT showed a sensitivity of 100% (95% confidence interval (CI) 90.5%–100%) and specificity of 98.4% (95% CI, 91.6%–100%). The dilution factor obtained with PRNT-90 showed a stronger correlation with the percent inhibition of cPass sVNT (r = 0.8660, p < 0.001) compared with the test and control line ratio (T/C ratio) of the BZ-nAb (r = −0.7089, p < 0.001). An almost perfect agreement was seen between the BZ-nAb and cPass sVNT results, with a strong negative correlation between the BZ-nAb T/C ratio and cPass sVNT percent inhibition (r = −0.8022, p < 0.001). In conclusion, the diagnostic performance of the BZ-nAb was comparable to that of the cPass sVNT, although the BZ-nAb had a slightly lower sensitivity. [ABSTRACT FROM AUTHOR]