Protective prototype-Beta and Delta-Omicron chimeric RBD-dimer vaccines against SARS-CoV-2.

Breakthrough infections by SARS-CoV-2 variants become the global challenge for pandemic control. Previously, we developed the protein subunit vaccine ZF2001 based on the dimeric receptor-binding domain (RBD) of prototype SARS-CoV-2. Here, we developed a chimeric RBD-dimer vaccine approach to adapt SARS-CoV-2 variants. A prototype-Beta chimeric RBD-dimer was first designed to adapt the resistant Beta variant. Compared with its homotypic forms, the chimeric vaccine elicited broader sera neutralization of variants and conferred better protection in mice. The protection of the chimeric vaccine was further verified in macaques. This approach was generalized to develop Delta-Omicron chimeric RBD-dimer to adapt the currently prevalent variants. Again, the chimeric vaccine elicited broader sera neutralization of SARS-CoV-2 variants and conferred better protection against challenge by either Delta or Omicron SARS-CoV-2 in mice. The chimeric approach is applicable for rapid updating of immunogens, and our data supported the use of variant-adapted multivalent vaccine against circulating and emerging variants.

Neutralizing immunity in vaccine breakthrough infections from the SARS-CoV-2 Omicron and Delta variants.

Virus-like particle (VLP) and live virus assays were used to investigate neutralizing immunity against Delta and Omicron SARS-CoV-2 variants in 259 samples from 128 vaccinated individuals. Following Delta breakthrough infection, titers against WT rose 57-fold and 3.1-fold compared with uninfected boosted and unboosted individuals, respectively, versus only a 5.8-fold increase and 3.1-fold decrease for Omicron breakthrough infection. Among immunocompetent, unboosted patients, Delta breakthrough infections induced 10.8-fold higher titers against WT compared with Omicron (p = 0.037). Decreased antibody responses in Omicron breakthrough infections relative to Delta were potentially related to a higher proportion of asymptomatic or mild breakthrough infections (55.0% versus 28.6%, respectively), which exhibited 12.3-fold lower titers against WT compared with moderate to severe infections (p = 0.020). Following either Delta or Omicron breakthrough infection, limited variant-specific cross-neutralizing immunity was observed. These results suggest that Omicron breakthrough infections are less immunogenic than Delta, thus providing reduced protection against reinfection or infection from future variants.

Inferring the differences in incubation-period and generation-interval distributions of the Delta and Omicron variants of SARS-CoV-2.

Estimating the differences in the incubation-period, serial-interval, and generation-interval distributions of SARS-CoV-2 variants is critical to understanding their transmission. However, the impact of epidemic dynamics is often neglected in estimating the timing of infection-for example, when an epidemic is growing exponentially, a cohort of infected individuals who developed symptoms at the same time are more likely to have been infected recently. Here, we reanalyze incubation-period and serial-interval data describing transmissions of the Delta and Omicron variants from the Netherlands at the end of December 2021. Previous analysis of the same dataset reported shorter mean observed incubation period (3.2 d vs. 4.4 d) and serial interval (3.5 d vs. 4.1 d) for the Omicron variant, but the number of infections caused by the Delta variant decreased during this period as the number of Omicron infections increased. When we account for growth-rate differences of two variants during the study period, we estimate similar mean incubation periods (3.8 to 4.5 d) for both variants but a shorter mean generation interval for the Omicron variant (3.0 d; 95% CI: 2.7 to 3.2 d) than for the Delta variant (3.8 d; 95% CI: 3.7 to 4.0 d). The differences in estimated generation intervals may be driven by the "network effect"-higher effective transmissibility of the Omicron variant can cause faster susceptible depletion among contact networks, which in turn prevents late transmission (therefore shortening realized generation intervals). Using up-to-date generation-interval distributions is critical to accurately estimating the reproduction advantage of the Omicron variant.

Prototype and BA.5 protein nanoparticle vaccines protect against Omicron BA.5 variant in Syrian hamsters.

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with greater transmissibility or immune evasion properties has jeopardized the existing vaccine and antibody-based countermeasures. Here, we evaluated the efficacy of boosting pre-immune hamsters with protein nanoparticle vaccines (Novavax, Inc.) containing recombinant Prototype (Wuhan-1) or BA.5 S proteins against a challenge with the Omicron BA.5 variant of SARS-CoV-2. Serum antibody binding and neutralization titers were quantified before challenge, and viral loads were measured 3 days after challenge. Boosting with Prototype or BA.5 vaccine induced similar antibody binding responses against ancestral Wuhan-1 or BA.5 S proteins, and neutralizing activity of Omicron BA.1 and BA.5 variants. One and three months after vaccine boosting, hamsters were challenged with the Omicron BA.5 variant. Prototype and BA.5 vaccine-boosted hamsters had reduced viral infection in the nasal washes, nasal turbinates, and lungs compared to unvaccinated animals. Although no significant differences in virus load were detected between the Prototype and BA.5 vaccine-boosted animals, fewer breakthrough infections were detected in the BA.5-vaccinated hamsters. Thus, immunity induced by Prototype or BA.5 S protein nanoparticle vaccine boosting can protect against the Omicron BA.5 variant in the Syrian hamster model. IMPORTANCE: As SARS-CoV-2 continues to evolve, there may be a need to update the vaccines to match the newly emerging variants. Here, we compared the protective efficacy of the updated BA.5 and the original Wuhan-1 COVID-19 vaccine against a challenge with the BA.5 Omicron variant of SARS-CoV-2 in hamsters. Both vaccines induced similar levels of neutralizing antibodies against multiple variants of SARS-CoV-2. One and three months after the final immunization, hamsters were challenged with BA.5. No differences in protection against the BA.5 variant virus were observed between the two vaccines, although fewer breakthrough infections were detected in the BA.5-vaccinated hamsters. Together, our data show that both protein nanoparticle vaccines are effective against the BA.5 variant of SARS-CoV-2 but given the increased number of breakthrough infections and continued evolution, it is important to update the COVID-19 vaccine for long-term protection.

Innate immune signatures in the nasopharynx after SARS-CoV-2 infection and links with the clinical outcome of COVID-19 in Omicron-dominant period.

While severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is characterized by impaired induction of interferons (IFNs) and IFN-stimulated genes (ISGs), the IFNs and ISGs in upper airway is essential to restrict the spread of respiratory virus. Here, we identified the prominent IFN and ISG upregulation in the nasopharynx (NP) of mild and even severe coronavirus disease 2019 (COVID-19) patients (CoV2+) in Omicron era and to compare their clinical outcome depending on the level of IFNs and ISGs. Whereas the induction of IFNB was minimal, transcription of IFNA, IFNG, and IFNLs was significantly increased in the NP of CoV2 + patients. IFNs and ISGs may be more upregulated in the NP of CoV2 + patients at early phases of infection according to viral RNA levels and this is observed even in severe cases. IFN-related innate immune response might be characteristic in macrophages and monocytes at the NP and the CoV2 + patients with higher transcription of IFNs and ISGs in the NP showed a correlation with good prognosis of COVID-19. This study presents that IFNs and ISGs may be upregulated in the NP, even in severe CoV2 + patients depending on viral replication during Omicron-dominant period and the unique IFN-responsiveness in the NP links with COVID-19 clinical outcomes.

Structural basis for mouse receptor recognition by SARS-CoV-2 omicron variant.

The sudden emergence and rapid spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) omicron variant has raised questions about its animal reservoir. Here, we investigated receptor recognition of the omicron's receptor-binding domain (RBD), focusing on four of its mutations (Q493R, Q498R, N501Y, and Y505H) surrounding two mutational hotspots. These mutations have variable effects on the RBD's affinity for human angiotensin-converting enzyme 2 (ACE2), but they all enhance the RBD's affinity for mouse ACE2. We further determined the crystal structure of omicron RBD complexed with mouse ACE2. The structure showed that all four mutations are viral adaptations to mouse ACE2: three of them (Q493R, Q498R, and Y505H) are uniquely adapted to mouse ACE2, whereas the other one (N501Y) is adapted to both human ACE2 and mouse ACE2. These data reveal that the omicron RBD was well adapted to mouse ACE2 before omicron started to infect humans, providing insight into the potential evolutionary origin of the omicron variant.

Inferring Incidence of Unreported SARS-CoV-2 Infections Using Seroprevalence of Open Reading Frame 8 Antigen, Hong Kong.

We tested seroprevalence of open reading frame 8 antigens to infer the number of unrecognized SARS-CoV-2 Omicron infections in Hong Kong during 2022. We estimate 33.6% of the population was infected, 72.1% asymptomatically. Surveillance and control activities during large-scale outbreaks should account for potentially substantial undercounts.

Efficacy of ensitrelvir for cough due to COVID-19 Omicron variant in medical healthcare workers.

We evaluated the efficacy of ensitrelvir for the treatment of cough due to coronavirus disease 2019 Omicron variant in medical healthcare workers. A total of 633 patients were registered in this study: 206 patients chose ensitrelvir and 427 patients chose symptomatic treatment. Difference in score changes using the Leicester Cough Questionnaire between groups was 3.17 on day 4, 3.24 on day 7, and 2.46 on day 14. The analysis demonstrated a significant difference at all time points.

Deciphering the omicron variant: integrated omics analysis reveals critical biomarkers and pathophysiological pathways.

BACKGROUND: The rapid emergence and global dissemination of the Omicron variant of SARS-CoV-2 have posed formidable challenges in public health. This scenario underscores the urgent need for an enhanced understanding of Omicron's pathophysiological mechanisms to guide clinical management and shape public health strategies. Our study is aimed at deciphering the intricate molecular mechanisms underlying Omicron infections, particularly focusing on the identification of specific biomarkers. METHODS: This investigation employed a robust and systematic approach, initially encompassing 15 Omicron-infected patients and an equal number of healthy controls, followed by a validation cohort of 20 individuals per group. The study's methodological framework included a comprehensive multi-omics analysis that integrated proteomics and metabolomics, augmented by extensive bioinformatics. Proteomic exploration was conducted via an advanced Ultra-High-Performance Liquid Chromatography (UHPLC) system linked with mass spectrometry. Concurrently, metabolomic profiling was executed using an Ultra-Performance Liquid Chromatography (UPLC) system. The bioinformatics component, fundamental to this research, entailed an exhaustive analysis of protein-protein interactions, pathway enrichment, and metabolic network dynamics, utilizing state-of-the-art tools such as the STRING database and Cytoscape software, ensuring a holistic interpretation of the data. RESULTS: Our proteomic inquiry identified eight notably dysregulated proteins (THBS1, ACTN1, ACTC1, POTEF, ACTB, TPM4, VCL, ICAM1) in individuals infected with the Omicron variant. These proteins play critical roles in essential physiological processes, especially within the coagulation cascade and hemostatic mechanisms, suggesting their significant involvement in the pathogenesis of Omicron infection. Complementing these proteomic insights, metabolomic analysis discerned 146 differentially expressed metabolites, intricately associated with pivotal metabolic pathways such as tryptophan metabolism, retinol metabolism, and steroid hormone biosynthesis. This comprehensive metabolic profiling sheds light on the systemic implications of Omicron infection, underscoring profound alterations in metabolic equilibrium. CONCLUSIONS: This study substantially enriches our comprehension of the physiological ramifications induced by the Omicron variant, with a particular emphasis on the pivotal roles of coagulation and platelet pathways in disease pathogenesis. The discovery of these specific biomarkers illuminates their potential as critical targets for diagnostic and therapeutic strategies, providing invaluable insights for the development of tailored treatments and enhancing patient care in the dynamic context of the ongoing pandemic.

Clinical characteristics and immunogenicity after Omicron breakthrough infection in patients with chronic hepatitis B infection: A longitudinal observational study.

The clinical and immunological features after breakthrough infection (BTI) during Omicron wave in patients with chronic hepatitis B virus infection (CHB) are still unclear. A total of 101 patients with CHB from our previous coronavirus disease 2019 (COVID-19) vaccination cohort (NCT05007665), were continued to be followed up at the Second Affiliated Hospital of Chongqing Medical University after BTI, while an additional 39 healthcare workers after BTI were recruited as healthy controls (HCs). Clinical data were collected using questionnaire survey and electronic medical record. Blood samples were used to determine the antibody responses, as well as B and T cell responses. After BTI, the clinical symptoms of COVID-19 were mild to moderate in patients with CHB, with a median duration of 5 days. Compared with HCs, patients with CHB were more susceptible to develop moderate COVID-19. The liver function was not significantly damaged, and HBV-DNA was not activated in patients with CHB after BTI. Patients with CHB could elicit robust antibody responses after BTI (NAbs 13.0-fold, BA.5 IgG: 24.2-fold, respectively), which was also significantly higher than that in every period after vaccination (all p < 0.001), and compared to that in HCs after BTI. The CD4+, cTfh, and CD8+ T cell responses were also augmented in patients with CHB after BTI, while exhibiting comparability to those observed in HCs. In patients with CHB after BTI, the immune imprint was observed in B cell responses, rather than in T cell responses. In conclusion, Omicron breakthrough infection induced mild to moderate COVID-19 symptoms in patients with CHB, without exacerbating the progress of liver diseases. Meanwhile, BTI demonstrated the ability to induce robust antibody and T cell responses in patients with CHB, which was comparable to those observed in HCs.

Clinical characteristics of SARS-CoV-2 Omicron variant infection in children with acute leukemia.

Hematologic diseases and various therapeutic stages can impact the presentation of SARS-CoV-2 Omicron variant infection. This study retrospectively analyzed data on Omicron infection in children with acute leukemia treated at our hospital between January 16, 2023, and February 25, 2023, using questionnaires. The prevalence of Omicron infection in children undergoing consolidation chemotherapy, maintenance chemotherapy, drug withdrawal, and healthy children was 81.8%, 75.2%, 55.2%, and 61.9%, respectively. The observed differences were statistically significant (P < 0.05). During the course of infection, children with leukemia undergoing chemotherapy, including both the consolidation and maintenance chemotherapy groups, exhibited a prolonged time to achieve SARS-CoV-2 negativity compared to the drug withdrawal and healthy groups. However, there was no significant increase in the incidence of symptoms across all body systems, and no children experienced serious sequelae or death. Furthermore, our observations indicated that all manifestations of Omicron infection in children with leukemia after drug withdrawal were not significantly different from those in healthy children. This suggested, to a certain extent, that the immune function of children with leukemia recovers effectively after the cessation of drug treatment. These findings are crucial for guiding clinical management and alleviating concerns about infection for both children with leukemia and their parents.

Clinical characteristics and outcomes of allogeneic hematopoietic stem cell transplantation recipients with coronavirus disease 2019 caused by the Omicron variant: a prospective, observational cohort study.

We aimed to describe the clinical characteristics, particularly the occurrence and risk factors of severe/critical illness, in allogeneic hematopoietic stem cell (allo-HSCT) recipients infected with coronavirus disease 2019 (COVID-19) caused by Omicron variant in an observational prospective study (n = 311). The median time from allo-HSCT to COVID-19 diagnosis was 8.5 months (range 0.8-106.1) months. Four patients (1.3%) were reported to be asymptomatic during Omicron variant infection, and 135 (43.4%) patients showed lower respiratory tract disease. Thirty-four (10.9%) patients were categorized into serious infection (severe illness n = 25; critical illness n = 9) and the median duration from COVID-19 diagnosis to serious infections was 6 days (range, 0-29) days. Thirteen (4.2%) and 6 (1.9%) patients required intensive care unit care and invasive mechanical ventilation, respectively. Receiving more than 1 type of immunosuppressive therapies at COVID-19 diagnosis was associated with severity and persistence of infection. Six patients (1.9%) died after diagnosis of COVID-19 infection. The 4-week probability of overall survival after COVID-19 diagnosis was 98.7%, which was 100% and 88.2% for non-serious and serious infection group (P < 0.001), respectively. Thus, we observed a relatively low serious infection and mortality rate in allo-HSCT recipients infected with COVID-19 caused by Omicron variant.

Real-world clinical outcomes of tixagevimab/cilgavimab in the Omicron outbreak in China: baseline characteristics and interim analysis of the CLEAR study.

PURPOSE: This study aimed to investigate the real-world use and clinical outcomes of tixagevimab/cilgavimab in China during the Omicron outbreak in late 2022. METHODS: This observational, real-world study included patients who received tixagevimab/cilgavimab from July 9 to December 30, 2022, in Hainan, China. Here, we report the baseline and characteristics and interim analysis results of the clinical outcomes in those receiving at least one dose of tixagevimab/cilgavimab (300 mg) for pre-exposure prophylaxis. RESULTS: Among 248 subjects who received tixagevimab/cilgavimab, 229 subjects were included in this analysis. Until March 28, 2023, the median follow-up was 95 days. The mean age of the subjects was 44.4 ± 15.9 years, 11.8% were ≥ 65 years, and 41.5% were male. Fifty-eight (25.3%) subjects had comorbidities, 16.2% subjects had key immune compromised conditions. Seventy-two (32.6%) patients had laboratory-confirmed SARS-CoV-2 infection and/or received healthcare within three months; 71/72 (98.6%) had mild disease, and one (1.4%) was moderate. No COVID-19-related intensive care unit (ICU) admissions, extracorporeal membrane oxygenation utilizations, or death occurred. Two (0.9%) patients required hospitalization. One (0.4%) serious adverse event occurred, which was considered unrelated to tixagevimab/cilgavimab. CONCLUSION: Among Chinese patients receiving prophylactic tixagevimab/cilgavimab, the incidence of COVID-19-related hospitalization, ICU admission, or death was low during the Omicron surge. Further randomized controlled trials with larger sample sizes are needed to determine the effectiveness of tixagevimab/cilgavimab in preventing severe COVID-19 outcomes. TRIAL REGISTRATION: The study was registered with clinicaltrial.gov (NCT05917951).

Household transmission of Omicron variant of SARS-CoV-2 under conditions of hybrid immunity-a prospective study in Germany.

PURPOSE: We investigated the protection offered by vaccinations and previous infections for the household transmission of Omicron variant of SARS-CoV-2. METHODS: 34,666 participants of the German DigiHero cohort study with two or more household members were invited to a prospective household transmission study between June and December 2022. In case of a positive SARS-CoV-2 test in a household, symptom diaries were completed for at least 14 days. Dry blood spots (DBS) were taken from all household members at the beginning and six to eight weeks later. DBS were analyzed for SARS-CoV-2 antibodies. RESULTS: 1191 individuals from 457 households participated. The risk of acquiring a SARS-CoV-2 infection decreased with higher S-titer levels at the time of exposure (from 80% at titer of 0 binding antibody units (BAU)/ml to 20% at titer of 3000 BAU/ml) and increased linearly with the time since vaccination/previous infection (20% for less than one month to 80% at one year). Transmission probability was also reduced when the symptoms of the primary case were mild and if preventive measures were implemented. CONCLUSION: Vaccinations/previous infections offer a high protection against infection with the Omicron variant for a few months only, supporting the notion of seasonal circulation of the virus.

A fatal course of COVID-19 during the Omicron surge: can you estimate your patients' SARS-CoV-2 immune status?

We present a case of an ultimately fatal course of COVID-19 (coronavirus disease-19) in an 81-year-old female patient during the Omicron surge. The patient did not represent the typical patient at risk for severe COVID-19 with significant causes of immunodeficiency. However, she had been skeptical about the vaccination for severe acute respiratory syndrome virus-2 (SARS-CoV-2) and had refused it. Moreover, there had been no previous COVID-19 episodes. Our case report illustrates that with regard to SARS-CoV-2, immunologically naive patients are still at risk for severe and/or even fatal courses of COVID-19. We call to implement both, recommendations for SARS-CoV-2 vaccinations as well as for antiviral treatment.

Protective role of SARS-CoV-2 anti-S IgG against breakthrough infections among European healthcare workers during pre and post-Omicron surge-ORCHESTRA project.

PURPOSE: Anti SARS-CoV-2 vaccination initially showed high effectiveness in preventing COVID-19. However, after the surge of variants of concern, the effectiveness dropped. Several studies investigated if this was related to the decrease of the humoral response over time; however, this issue is still unclear. The aim of this study was to understand whether SARS-CoV-2 anti-S IgG levels can be used to predict breakthrough infection risk and define the timing for further booster doses administration. METHOD: Within the framework of the ORCHESTRA Project, over 20,000 health workers from 11 European centers were enrolled since December 2020. We performed two Cox proportional hazards survival analyses regarding pre-Omicron (from January to July 2021) and Omicron (December 2021-May 2022) periods. The serological response was classified as high (above the 75th percentile), medium (25th-75th), or low (< 25th). RESULTS: Seventy-four (0.33%) and 2122 (20%) health workers were infected during the first and second periods, respectively. Both Cox analyses showed that having high anti-S titer was linked to a significantly lower risk of infection as compared to having medium serological response [HR of high vs medium anti-S titer = 0.27 (95% CI 0.11-0.66) during the first phase, HR = 0.76 (95% CI 0.62-0.93) during the second phase]. CONCLUSION: Vaccine effectiveness wanes significantly after new variants surge, making anti-S titer unsuitable to predict optimal timing for further booster dose administration. Studies on other immunological indicators, such as cellular immunity, are therefore needed to better understand the mechanisms and duration of protection against breakthrough infection risk.

Sequence analysis of the Spike, RNA-dependent RNA polymerase, and protease genes reveals a distinct evolutionary pattern of SARS-CoV-2 variants circulating in Yogyakarta and Central Java provinces, Indonesia.

During the Covid-19 pandemic, the resurgence of SARS-CoV-2 was due to the development of novel variants of concern (VOC). Thus, genomic surveillance is essential to monitor continuing evolution of SARS-CoV-2 and to track the emergence of novel variants. In this study, we performed phylogenetic, mutation, and selection pressure analyses of the Spike, nsp12, nsp3, and nsp5 genes of SARS-CoV-2 isolates circulating in Yogyakarta and Central Java provinces, Indonesia from May 2021 to February 2022. Various bioinformatics tools were employed to investigate the evolutionary dynamics of distinct SARS-CoV-2 isolates. During the study period, 213 and 139 isolates of Omicron and Delta variants were identified, respectively. Particularly in the Spike gene, mutations were significantly more abundant in Omicron than in Delta variants. Consistently, in all of four genes studied, the substitution rates of Omicron were higher than that of Delta variants, especially in the Spike and nsp12 genes. In addition, selective pressure analysis revealed several sites that were positively selected in particular genes, implying that these sites were functionally essential for virus evolution. In conclusion, our study demonstrated a distinct evolutionary pattern of SARS-CoV-2 variants circulating in Yogyakarta and Central Java provinces, Indonesia.

Analysis of influencing factors on long COVID in COVID-19 patients infected with omicron variant three months after discharge: a cross-sectional study.

BACKGROUND: The purpose of this study is to analyze the influencing factors associated with Long-COVID in patients infected with Omicron variant of COVID-19 in Changchun City, Jilin Province, China three months after discharge in March 2022. METHODS: In this study, we conducted a telephone follow-up based on the real-world data collected from the Affiliated Hospital to Changchun University of Chinese Medicine, Changchun Tongyuan Shelter Hospital and Changchun Infectious Disease Hospital during the COVID-19 epidemic in Changchun in March 2022. We used the Global COVID-19 Clinical Platform Case Report Form for Post COVID condition as a follow-up questionnaire to collect the general information, past medical history, clinical symptoms, COVID-19 vaccine inoculation doses, and other relevant information to analyze the symptom characteristics of COVID-19 patients three months after discharge from the hospital and related factors affecting Long COVID. RESULTS: A total of 1,806 patients with COVID-19 were included in this study, 977 males and 829 females, with a mean age of 38.5 [30.0, 49.4] years, and the number of female patients suffering from Long COVID (50.87%) was greater than male patients (p = 0.023). The binary logistic regression analysis of factors influencing Long COVID showed that smoking history (OR (95%CI) = 0.551(0.425-0.714), p < 0.001, taking never smoking as a reference), allergy history (OR (95%CI) = 1.618 (1.086-2.413), p-value 0.018, taking no allergy as a reference), first symptoms (OR (95%CI) = 0.636 (0.501-0.807), p < 0.001, with no first symptoms as reference) and COVID-19 vaccine inoculation doses (OR (95%CI) = 1.517 (1.190-1.933), p-value 0.001, with ≤ 2 doses of COVID-19 vaccine inoculation doses as reference) constituted its influencing factors. The first symptoms of patients on admission mainly included fever (512 cases, 71.81%), cough (279 cases, 39.13%) and dry or itchy throat (211 cases, 29.59%). The most common symptoms of Long COVID were persistent fatigue (68 cases), amnesia (61 cases), insomnia (50 cases) and excessive sweating (50 cases). CONCLUSION: The first symptoms on admission were predominantly fever, cough and dry or itchy throat. The most common symptoms of Long COVID were persistent fatigue, amnesia, insomnia and excessive sweating, and female patients were at a higher risk of Long COVID.

A cross-sectional study of SARS-CoV-2 antibodies among healthcare workers in a tertiary care hospital in Taiwan: implications for protection against the Omicron variants.

BACKGROUND: Taiwan, deeply impacted by the 2003 SARS outbreak, promptly implemented rigorous infection control and prevention (ICP) measures in January 2020 to combat the global COVID-19 pandemic. This cross-sectional serologic study was conducted among healthcare workers (HCWs) in a tertiary care hospital in Taiwan from August 1, 2022, to February 28, 2023. The study aimed to assess HCWs' antibody responses to COVID-19 vaccination against Omicron subvariants BA.1, BA.4, and BA.5, considering variations in prior infection. Additionally, it evaluated the effectiveness of ICP and vaccination policies within the hospital setting in Taiwan. METHODS: A cross-sectional serology study was conducted in Taiwan to investigate the seroprevalence rates of Omicron subvariants BA.1, BA.4, and BA.5 among HCWs. A total of 777 HCWs participated in this study. A structured questionnaire was collected to obtain the epidemiological characteristics and risk factors for potential exposure. Enzyme-linked immunosorbent assay was used to detect antibody responses. Serum samples were selected for protection against Omicron subvariants BA.1, BA.4, and BA.5 by using a pseudotyped-based neutralization assay. RESULTS: More than 99% of the participants had received SARS-CoV-2 vaccination. Overall, 57.7% had been infected with SARS-CoV-2, with some being asymptomatic. The SARS-CoV-2 Anti-Spike S1 protein IgG (Anti-S) distribution was 40,000 AU/mL for 20.2% (157/777) of participants, with a mean ± standard deviation of 23,442 ± 22,086. The decay curve for Anti-S was less than 20,000 AU/ml after 120 days. The probability curve of 50% neutralization showed an Anti-S of 55,000 AU/ml. The optimum Anti-S was 41,328 AU/mL (equal to 5,869 WHO's standard BAU/mL), with 86.1% sensitivity and 63.5% specificity. CONCLUSIONS: In this significant study, 20.2% of HCWs achieved seroprotection against Omicron subvariants BA.1, BA.4, and BA.5. Their immunity against Omicron subvariants was further reinforced through recommended vaccinations and the development of natural immunity from SARS-CoV-2 exposure, collectively enhancing their protection against Omicron.

Real-world evaluation of early remdesivir in high-risk COVID-19 outpatients during Omicron including BQ.1/BQ.1.1/XBB.1.5.

BACKGROUND: A trial performed among unvaccinated, high-risk outpatients with COVID-19 during the delta period showed remdesivir reduced hospitalization. We used our real-world data platform to determine the effectiveness of remdesivir on reducing 28-day hospitalization among outpatients with mild-moderate COVID-19 during an Omicron period including BQ.1/BQ.1.1/XBB.1.5. METHODS: We did a propensity-matched, retrospective cohort study of non-hospitalized adults with SARS-CoV-2 infection between April 7, 2022, and February 7, 2023. Electronic healthcare record data from a large health system in Colorado were linked to statewide vaccination and mortality data. We included patients with a positive SARS-CoV-2 test or outpatient remdesivir administration. Exclusion criteria were other SARS-CoV-2 treatments or positive SARS-CoV-2 test more than seven days before remdesivir. The primary outcome was all-cause hospitalization up to day 28. Secondary outcomes included 28-day COVID-related hospitalization and 28-day all-cause mortality. RESULTS: Among 29,270 patients with SARS-CoV-2 infection, 1,252 remdesivir-treated patients were matched to 2,499 untreated patients. Remdesivir was associated with lower 28-day all-cause hospitalization (1.3% vs. 3.3%, adjusted hazard ratio (aHR) 0.39 [95% CI 0.23-0.67], p < 0.001) than no treatment. All-cause mortality at 28 days was numerically lower among remdesivir-treated patients (0.1% vs. 0.4%; aOR 0.32 [95% CI 0.03-1.40]). Similar benefit of RDV treatment on 28-day all-cause hospitalization was observed across Omicron periods, aOR (95% CI): BA.2/BA2.12.1 (0.77[0.19-2.41]), BA.4/5 (0.50[95% CI 0.50-1.01]), BQ.1/BQ.1.1/XBB.1.5 (0.21[95% CI 0.08-0.57]. CONCLUSION: Among outpatients with SARS-CoV-2 during recent Omicron surges, remdesivir was associated with lower hospitalization than no treatment, supporting current National Institutes of Health Guidelines.