Interpreting the Omicron drama

Omicron variant of SARS-CoV-2 emerged in southern Africa in November 2021, showing more mutations on the spike protein gene than other variants, high efficiency in transmission, immune evasion, causing a mild disease, mostly upper respiratory and low mortality. Its proximate parent is unknown. We argue that its evolutionary pathway was reverse zoonosis in rodents, acquiring rodent adaptation mutations and subsequently infecting humans as zoonosis - conceptually a 'deviant' with antigenic shift rather than variant with antigenic drift;its pathogenesis is modified by its cell entry pathway resulting in the absence of syncytia, low virus load, sparing lungs of pneumonia and hypoxia. [ FROM AUTHOR] Copyright of Current Science (00113891) is the property of Indian Academy of Sciences 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.)

Acute cerebellar ataxia during acute COVID-19: A case series and review of the literature.

Acute coronavirus disease 2019 (COVID-19)-associated cerebellar ataxia without multisystem inflammatory syndrome in children (MIS-C) or encephalopathy in children has been rarely reported. We reviewed medical records of hospitalized children who had developed cerebellar ataxia during the acute phase of COVID-19 infection, without MIS-C or encephalopathy, in our center. We also conducted a literature review and summarized the clinical characteristics, treatment, and outcomes. We found three cases in our center and additional three cases in the literature. All patients were male and five were preschool children. The cerebellar symptoms started between day 2 and day 10 during the acute phase of the COVID-19 infection. Two cases were complicated by mutism. One patient received therapy for acute cerebellar ataxia with corticosteroids, and others did not receive any specific therapy for acute cerebellar ataxia. The symptoms improved completely in all patients, with the recovery interval ranging from one week to two months. Further studies are warranted to elucidate the pathogenesis of acute cerebellar ataxia during acute COVID-19 in children.

Vaccine effectiveness against transmission of alpha, delta and omicron SARS-COV-2-infection, Belgian contact tracing, 2021-2022.

OBJECTIVES: Vaccine effectiveness against transmission (VET) of SARS-CoV-2-infection can be estimated from secondary attack rates observed during contact tracing. We estimated VET, the vaccine-effect on infectiousness of the index case and susceptibility of the high-risk exposure contact (HREC). METHODS: We fitted RT-PCR-test results from HREC to immunity status (vaccine schedule, prior infection, time since last immunity-conferring event), age, sex, calendar week of sampling, household, background positivity rate and dominant VOC using a multilevel Bayesian regression-model. We included Belgian data collected between January 2021 and January 2022. RESULTS: For primary BNT162b2-vaccination we estimated initial VET at 96% (95%CI 95-97) against Alpha, 87% (95%CI 84-88) against Delta and 31% (95%CI 25-37) against Omicron. Initial VET of booster-vaccination (mRNA primary and booster-vaccination) was 87% (95%CI 86-89) against Delta and 68% (95%CI 65-70) against Omicron. The VET-estimate against Delta and Omicron decreased to 71% (95%CI 64-78) and 55% (95%CI 46-62) respectively, 150-200 days after booster-vaccination. Hybrid immunity, defined as vaccination and documented prior infection, was associated with durable and higher or comparable (by number of antigen exposures) protection against transmission. CONCLUSIONS: While we observed VOC-specific immune-escape, especially by Omicron, and waning over time since immunization, vaccination remained associated with a reduced risk of SARS-CoV-2-transmission.

SARS-CoV-2 Omicron variant shedding during respiratory activities.

OBJECTIVES: As the world transitions to COVID-19 endemicity, studies focusing on aerosol shedding of highly transmissible SARS-CoV-2 variants of concern (VOCs) are vital for the calibration of infection control measures against VOCs that are likely to circulate seasonally. This follow-up Gesundheit-II aerosol sampling study aims to compare the aerosol shedding patterns of Omicron VOC samples with pre-Omicron variants analyzed in our previous study. DESIGN: Coarse and fine aerosol samples from 47 patients infected with SARS-CoV-2 were collected during various respiratory activities (passive breathing, talking, and singing) and analyzed using reverse transcription-quantitative polymerase chain reaction and virus culture. RESULTS: Compared with patients infected with pre-Omicron variants, comparable SARS-CoV-2 RNA copy numbers were detectable in aerosol samples of patients infected with Omicron despite being fully vaccinated. Patients infected with Omicron also showed a slight increase in viral aerosol shedding during breathing activities and were more likely to have persistent aerosol shedding beyond 7 days after disease onset. CONCLUSION: This follow-up study reaffirms the aerosol shedding properties of Omicron and should guide continued layering of public health interventions even in highly vaccinated populations.

Overlapping Delta and Omicron Outbreaks During the COVID-19 Pandemic: Dynamic Panel Data Estimates.

BACKGROUND: The Omicron variant of SARS-CoV-2 is more transmissible than prior variants of concern (VOCs). It has caused the largest outbreaks in the pandemic, with increases in mortality and hospitalizations. Early data on the spread of Omicron were captured in countries with relatively low case counts, so it was unclear how the arrival of Omicron would impact the trajectory of the pandemic in countries already experiencing high levels of community transmission of Delta. OBJECTIVE: The objective of this study is to quantify and explain the impact of Omicron on pandemic trajectories and how they differ between countries that were or were not in a Delta outbreak at the time Omicron occurred. METHODS: We used SARS-CoV-2 surveillance and genetic sequence data to classify countries into 2 groups: those that were in a Delta outbreak (defined by at least 10 novel daily transmissions per 100,000 population) when Omicron was first sequenced in the country and those that were not. We used trend analysis, survival curves, and dynamic panel regression models to compare outbreaks in the 2 groups over the period from November 1, 2021, to February 11, 2022. We summarized the outbreaks in terms of their peak rate of SARS-CoV-2 infections and the duration of time the outbreaks took to reach the peak rate. RESULTS: Countries that were already in an outbreak with predominantly Delta lineages when Omicron arrived took longer to reach their peak rate and saw greater than a twofold increase (2.04) in the average apex of the Omicron outbreak compared to countries that were not yet in an outbreak. CONCLUSIONS: These results suggest that high community transmission of Delta at the time of the first detection of Omicron was not protective, but rather preluded larger outbreaks in those countries. Outbreak status may reflect a generally susceptible population, due to overlapping factors, including climate, policy, and individual behavior. In the absence of strong mitigation measures, arrival of a new, more transmissible variant in these countries is therefore more likely to lead to larger outbreaks. Alternately, countries with enhanced surveillance programs and incentives may be more likely to both exist in an outbreak status and detect more cases during an outbreak, resulting in a spurious relationship. Either way, these data argue against herd immunity mitigating future outbreaks with variants that have undergone significant antigenic shifts.

CNN-LSTM deep learning based forecasting model for COVID-19 infection cases in Nigeria, South Africa and Botswana.

Background: COVID-19 pandemic has indeed plunged the global community especially African countries into an alarming difficult situation culminating into a great deal amounts of catastrophes such as economic recession, political instability and loss of jobs. The pandemic spreads exponentially and causes loss of lives. Following the outbreak of the omicron new variant of concern, forecasting and identification of the COVID-19 infection cases is very vital for government at various levels. Hence, having knowledge of the spread at a particular point in time, swift actions can be taken by government at various levels with a view to accordingly formulate new policies and modalities towards minimizing the trajectory of the consequences of COVID-19 pandemic to both public health and economic sectors. Methods: Here, a potent combination of Convolutional Neural Network (CNN) learning algorithm along with Long Short Term Memory (LSTM) learning algorithm has been proposed in this work in order to produce a hybrid of a deep learning algorithm Convolutional Neural Network - Long Short Term Memory (CNN-LSTM) for forecasting COVID-19 infection cases particularly in Nigeria, South Africa and Botswana. Forecasting models for COVID-19 infection cases in Nigeria, South Africa and Botswana, were developed for 10 days using deep learning-based approaches namely CNN, LSTM and CNN-LSTM deep learning algorithm respectively. Results: The models were evaluated on the basis of four standard performance evaluation metrics which include accuracy, MSE, MAE and RMSE respectively. However, the CNN-LSTM deep learning-based forecasting model achieved the best accuracy of 98.30%, 97.60%, and 97.74% for Nigeria, South Africa and Botswana respectively; and in the same manner, achieved lesser MSE, MAE and RMSE values compared to models developed with CNN and LSTM respectively. Conclusions: Taken together, the CNN-LSTM deep learning-based forecasting model for COVID-19 infection cases in Nigeria, South Africa and Botswana dramatically surpasses the two other DL based forecasting models (CNN and LSTM) for COVID-19 infection cases in Nigeria, South Africa and Botswana in terms of not only the best accuracy of with 98.30%, 97.60%, and 97.74% but also in terms of lesser MSE, MAE and RMSE.

Longitudinal cellular and humoral immune responses after triple BNT162b2 and fourth full-dose mRNA-1273 vaccination in haemodialysis patients.

Haemodialysis patients respond poorly to vaccination and continue to be at-risk for severe COVID-19. Therefore, dialysis patients were among the first for which a fourth COVID-19 vaccination was recommended. However, targeted information on how to best maintain immune protection after SARS-CoV-2 vaccinations in at-risk groups for severe COVID-19 remains limited. We provide, to the best of our knowledge, for the first time longitudinal vaccination response data in dialysis patients and controls after a triple BNT162b2 vaccination and in the latter after a subsequent fourth full-dose of mRNA-1273. We analysed systemic and mucosal humoral IgG responses against the receptor-binding domain (RBD) and ACE2-binding inhibition towards variants of concern including Omicron and Delta with multiplex-based immunoassays. In addition, we assessed Spike S1-specific T-cell responses by interferon γ release assay. After triple BNT162b2 vaccination, anti-RBD B.1 IgG and ACE2 binding inhibition reached peak levels in dialysis patients, but remained inferior compared to controls. Whilst we detected B.1-specific ACE2 binding inhibition in 84% of dialysis patients after three BNT162b2 doses, binding inhibition towards the Omicron variant was only detectable in 38% of samples and declining to 16% before the fourth vaccination. By using mRNA-1273 as fourth dose, humoral immunity against all SARS-CoV-2 variants tested was strongly augmented with 80% of dialysis patients having Omicron-specific ACE2 binding inhibition. Modest declines in T-cell responses in dialysis patients and controls after the second vaccination were restored by the third BNT162b2 dose and significantly increased by the fourth vaccination. Our data support current advice for a four-dose COVID-19 immunisation scheme for at-risk individuals such as haemodialysis patients. We conclude that administration of a fourth full-dose of mRNA-1273 as part of a mixed mRNA vaccination scheme to boost immunity and to prevent severe COVID-19 could also be beneficial in other immune impaired individuals. Additionally, strategic application of such mixed vaccine regimens may be an immediate response against SARS-CoV-2 variants with increased immune evasion potential.

Reduced B cell antigenicity of Omicron lowers host serologic response.

The SARS-CoV-2 Omicron variant evades most neutralizing vaccine-induced antibodies and is associated with lower antibody titers upon breakthrough infections than previous variants. However, the mechanism remains unclear. Here, we find using a geometric deep-learning model that Omicron's extensively mutated receptor binding site (RBS) features reduced antigenicity compared with previous variants. Mice immunization experiments with different recombinant receptor binding domain (RBD) variants confirm that the serological response to Omicron is drastically attenuated and less potent. Analyses of serum cross-reactivity and competitive ELISA reveal a reduction in antibody response across both variable and conserved RBD epitopes. Computational modeling confirms that the RBS has a potential for further antigenicity reduction while retaining efficient receptor binding. Finally, we find a similar trend of antigenicity reduction over decades for hCoV229E, a common cold coronavirus. Thus, our study explains the reduced antibody titers associated with Omicron infection and reveals a possible trajectory of future viral evolution.

Vaccine-Induced T-Cell and Antibody Responses at 12 Months after Full Vaccination Differ with Respect to Omicron Recognition.

More than a year after the first vaccines against the novel SARS-CoV-2 were approved, many questions still remain about the long-term protection conferred by each vaccine. How long the effect lasts, how effective it is against variants of concern and whether further vaccinations will confer additional benefits remain part of current and future research. For this purpose, we examined 182 health care employees-some of them with previous SARS-CoV-2 infection-12 months after different primary immunizations. To assess antibody responses, we performed an electrochemiluminescence assay (ECLIA) to determine anti-spike IgGs, followed by a surrogate virus neutralization assay against Wuhan-Hu-1 and B.1.1.529/BA.1 (Omicron). T cell response against wild-type and the Omicron variants of concern were assessed via interferon-gamma ELISpot assays and T-cell surface and intracellular cytokine staining. In summary, our results show that after the third vaccination with an mRNA vaccine, differences in antibody quantity and functionality observed after different primary immunizations were equalized. As for the T cell response, we were able to demonstrate a memory function for CD4+ and CD8+ T cells alike. Importantly, both T and antibody responses against wild-type and omicron differed significantly; however, antibody and T cell responses did not correlate with each other and, thus, may contribute differentially to immunity.

Sub-lineages of the Omicron variant of SARS-CoV-2: characteristic mutations and their relation to epidemiological behavior

By the end of 2021, the Omicron variant of SARS-CoV-2, the coronavirus responsible for COVID-19, emerges, causing immediate concern, due to the explosive increase in cases in South Africa and a large number of mutations. This study describes the characteristic mutations of the Omicron variant in the Spike protein, and the behavior of the successive epidemic waves associated to the sub-lineages throughout the world. The mutations in the Spike protein described are related to the virus ability to evade the protec-tion elicited by current vaccines, as well as with possible reduced susceptibility to host proteases for priming of the fusion process, and how this might be related to changes in tropism, a replication enhanced in nasal epithelial cells, and reduced in pulmonary tissue;traits probably associated with the apparent reduced severity of Omicron compared to other variants. © 2022, Instituto de Investigaciones Clinicas. All rights reserved.

Change in Seizure Incidence in Febrile Children With COVID-19 in the Era of Omicron Variant of Concern.

In this single-center retrospective observational study, we report that the incidence of seizures in febrile children with COVID-19 was significantly higher in the Omicron era than in the pre-Omicron era (14.6% vs 1.7%, P < .001). One-third of the cases in the Omicron era were older than 5 years.

Impact of COVID-19 Vaccination on Healthcare Worker Infection Rate and Outcome during SARS-CoV-2 Omicron Variant Outbreak in Hong Kong.

Immune escape is observed with SARS-CoV-2 Omicron (Pango lineage B.1.1.529), the predominant circulating strain worldwide. A booster dose was shown to restore immunity against Omicron infection; however, real-world data comparing mRNA (BNT162b2; Comirnaty) and inactivated vaccines' (CoronaVac; Sinovac) homologous and heterologous boosting are lacking. A retrospective study was performed to compare the rate and outcome of COVID-19 in healthcare workers (HCWs) with various vaccination regimes during a territory-wide Omicron BA.2.2 outbreak in Hong Kong. During the study period from 1 February to 31 March 2022, 3167 HCWs were recruited, and 871 HCWs reported 746 and 183 episodes of significant household and non-household close contact. A total of 737 HCWs acquired COVID-19, all cases of which were all clinically mild. Time-dependent Cox regression showed that, compared with two-dose vaccination, three-dose vaccination reduced infection risk by 31.7% and 89.3% in household contact and non-household close contact, respectively. Using two-dose BNT162b2 as reference, two-dose CoronaVac recipient had significantly higher risk of being infected (HR 1.69 p < 0.0001). Three-dose BNT162b2 (HR 0.4778 p< 0.0001) and two-dose CoronaVac + BNT162b2 booster (HR 0.4862 p = 0.0157) were associated with a lower risk of infection. Three-dose CoronaVac and two-dose BNT162b2 + CoronaVac booster were not significantly different from two-dose BNT162b2. The mean time to achieve negative RT-PCR or E gene cycle threshold 31 or above was not affected by age, number of vaccine doses taken, vaccine type, and timing of the last dose. In summary, we have demonstrated a lower risk of breakthrough SARS-CoV-2 infection in HCWs given BNT162b2 as a booster after two doses of BNT162b2 or CoronaVac.

Clinical characteristics of pediatric patients with COVID-19 between Omicron era vs. pre-Omicron era.

INTRODUCTION: Detailed data on clinical characteristics in children with the omicron strain of SARS-COV-2 are limited. METHODS: We conducted a retrospective observational study of children with COVID-19 at the National Center for Child Health and Development to evaluate the clinical manifestations during and before the emergence of the omicron variant. Only symptomatic patients without underlying diseases were included. Participants were divided into two temporal groups: the "omicron era" (1/2022-2/2022) and the "pre-omicron era," where the delta variant predominated (7/2021-11/2021). The patients were subclassified into an older vaccine-eligible group (aged 12-17 years), a younger vaccine-eligible group (aged 5-11 years), and a vaccine-ineligible group (aged 0-4 years). RESULTS: We compared 113 patients in the omicron era with 106 in the pre-omicron era. Most patients in both eras had non-severe disease, and no patients required mechanical ventilation or died. Among patients aged 0-4 years, sore throat and hoarseness were more common during the omicron era than the pre-omicron era (11.1% vs. 0.0% and 11.1% vs. 1.5%, respectively). Croup syndrome was diagnosed in all patients with hoarseness. Among patients aged 5-11 years, vomiting was more frequent during the omicron era (47.2%) than during the pre-omicron era (21.7%). Cough and rhinorrhea were less common during the omicron era in patients aged 0-4 and 5-11 years, respectively, than during the pre-omicron era. CONCLUSIONS: In children with COVID-19, clinical manifestations differed between the omicron and pre-omicron eras. In the Omicron era, croup syndrome was more frequent in vaccine-ineligible children.

Detection of the Omicron variant of SARS-CoV-2 by restriction analysis targeting the mutations K417N and N440K of the spike protein

By the end of 2021, the Omicron variant of concern (VOC) emerges in South Africa. This variant caused immediate concern, due to the explosive increase in cases associated with it and the large number of mutations it exhibits. In this study, the restriction sites that allow detecting the mutations K417N and N440K in the Spike gene are described. This analysis al-lows us to propose a rapid method for the identification of cases infected with the Omicron variant. We show that the proposed methodology can contribute to provide more information on the prevalence and rapid detection of cases of this new VOC. © 2022, Instituto de Investigaciones Clinicas. All rights reserved.

Detection of the Omicron variant of SARS-CoV-2 in international travelers returning to Venezuela.

BACKGROUND: By the end of 2021, the SARS-CoV-2 Variant of Concern (VOC) Delta was predominant in most of the world. At the end of November, the Omicron variant was first detected in South Africa. This variant was immediately classified as VOC, due to the explosive increase of cases in South Africa, and the great number of mutations exhibited by this new lineage. Since then, Omicron VOC displaced Delta one in almost every country. Venezuela implemented in May 2021 molecular testing of all the passengers arriving at Venezuelan airports. METHODS: In this study, we analyzed the presence of variants of SARS-CoV-2 in those positive samples, by sequencing a small fragment of the Spike genomic region. RESULTS: The Omicron variant was found in passengers arriving to Venezuela from the beginning of December. Complete genome analysis confirmed the presence of the Omicron VOC. The detection of this VOC coincided with an unprecedented increase in the frequency of passengers with positive nucleic acid testing. CONCLUSIONS: Genomic surveillance of samples for international travelers returning to Venezuela allowed us to rapidly detect the introduction of the Omicron variant in the country.