Comparison of biomarkers of COVID-19 patients with the alpha variant (B.1.1.7), the delta variant (B.1.617), and no mutation detected

Objectives: We aimed to compare biomarkers of COVID-19 patients with the Alpha variant (B.1.1.7), the Delta variant (B.1.617), and no mutation detected in our study. Method(s): A total of 600 patients with positive COVID PCR test and Alpha, Delta variant and no mutation detected with Covid PCR mutation test were included in the study. Troponin I, creatinine, Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Lactate Dehydrogenase (LDH), fibrinogen, D-dimer, ferritin, number of lymphocytes, lymphocytes (%), platelet (PLT), mean platelet volume (MPV), platelet distribution width (PDW), trombosite ratio in the blood (PCT), C-reactive protein (CRP) values were analyzed retrospectively. The age, gender, and hospitalization of the patients were evaluated concurrently. Result(s): Age, troponin, creatinine, LDH, PLT, MPV, and D-dimer were laboratory parameters that vary significantly with COVID-19 virus mutation. Age, troponin, LDH, and MPV values were lower in patients with Delta variant according to patients with the Alpha variant. Lymphocytes (N) and lymphocytes (%) values were lower in hospitalized patients relative to outpatients while age, troponin, LDH, CRP, and D-dimer values were higher in hospitalized patients than outpatients irrespective of mutation. Creatinine values were higher only in hospitalized patients with no mutation detected while ferritin and fibrinogen values were higher in hospitalized patients with Delta variant and no mutation detected. Conclusion(s): Age, troponin, creatinine, LDH, PLT, MPV, D-dimer, fibrinogen, ferritin, CRP, lymphocytes (N), and lymphocytes (%) values can guide to evaluate the diagnosis and hospitalization of patients with future different mutations.Copyright © 2023 by Prusa Medical Publishing.

Detection of SARS-CoV-2 Variants via Different Diagnostics Assays Based on Single-Nucleotide Polymorphism Analysis.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is characterized by fast evolution with the appearance of several variants. Next-Generation Sequencing (NGS) technology is considered the gold standard for monitoring known and new SARS-CoV-2 variants. However, the complexity of this technology renders this approach impracticable in laboratories located in areas with limited resources. We analyzed the capability of the ThermoFisher TaqPath COVID-19 RT-PCR (TaqPath) and the Seegene Novaplex SARS-CoV-2 Variant assay (Novaplex) to detect Omicron variants; the Allplex VariantII (Allplex) was also evaluated for Delta variants. Sanger sequencing (SaS) was the reference method. The results obtained with n = 355 nasopharyngeal samples were: negative with TaqPath, although positive with other qualitative molecular assays (n = 35); undetermined (n = 40) with both the assays; negative for the ∆69/70 mutation and confirmed as the Delta variant via SaS (n = 100); positive for ∆69/70 and confirmed as Omicron BA.1 via SaS (n = 80); negative for ∆69/70 and typed as Omicron BA.2 via SaS (n = 80). Novaplex typed 27.5% of samples as undetermined with TaqPath, 11.4% of samples as negative with TaqPath, and confirmed 100% of samples were Omicron subtypes. In total, 99/100 samples were confirmed as the Delta variant with Allplex with a positive per cent agreement (PPA) of 98% compared to SaS. As undermined samples with Novaplex showed RdRp median Ct values (Ct = 35.4) statistically higher than those of typed samples (median Ct value = 22.0; p < 0.0001, Mann-Whitney test), the inability to establish SARS-CoV-2 variants was probably linked to the low viral load. No amplification was obtained with SaS among all 35 negative TaqPath samples. Overall, 20% of samples which were typed as negative or undetermined with TaqPath, and among them, twelve were not typed even by SaS, but they were instead correctly identified with Novaplex. Although full-genome sequencing remains the elected method to characterize new strains, our data show the high ability of a SNP-based assay to identify VOCs, also resolving samples typed as undetermined with TaqPath.

Effects of SARS-CoV-2 Alpha, Beta, and Delta variants, age, vaccination, and prior infection on infectiousness of SARS-CoV-2 infections.

In 2021, Qatar experienced considerable incidence of SARS-CoV-2 infection that was dominated sequentially by the Alpha, Beta, and Delta variants. Using the cycle threshold (Ct) value of an RT-qPCR-positive test to proxy the inverse of infectiousness, we investigated infectiousness of SARS-CoV-2 infections by variant, age, sex, vaccination status, prior infection status, and reason for testing in a random sample of 18,355 RT-qPCR-genotyped infections. Regression analyses were conducted to estimate associations with the Ct value of RT-qPCR-positive tests. Compared to Beta infections, Alpha and Delta infections demonstrated 2.56 higher Ct cycles (95% CI: 2.35-2.78), and 4.92 fewer cycles (95% CI: 4.67- 5.16), respectively. The Ct value declined gradually with age and was especially high for children <10 years of age, signifying lower infectiousness in small children. Children <10 years of age had 2.18 higher Ct cycles (95% CI: 1.88-2.48) than those 10-19 years of age. Compared to unvaccinated individuals, the Ct value was higher among individuals who had received one or two vaccine doses, but the Ct value decreased gradually with time since the second-dose vaccination. Ct value was 2.07 cycles higher (95% CI: 1.42-2.72) for those with a prior infection than those without prior infection. The Ct value was lowest among individuals tested because of symptoms and was highest among individuals tested as a travel requirement. Delta was substantially more infectious than Beta. Prior immunity, whether due to vaccination or prior infection, is associated with lower infectiousness of breakthrough infections, but infectiousness increases gradually with time since the second-dose vaccination.

Factors associated with negative conversion of viral RNA in hospitalized children infected with SARS-CoV-2 Omicron variant in Shanghai, China: a retrospective analysis.

OBJECTIVES: This study aimed to identify the related risk factors and potential predictors of SARS-CoV-2 RNA negative conversion by describing the dynamics of viral shedding in infected children admitted to two hospitals from Shanghai during the Omicron variant outbreak. METHODS: This retrospective cohort included laboratory-confirmed cases of SARS-CoV-2 infection from Shanghai between March 28 and May 31, 2022. Clinical characteristics, personal vaccination, and household vaccination rates were collected through electronic health records and telephone interviews. RESULTS: A total of 603 paediatric patients confirmed to have COVID-19 were included in this study. Both univariate and multivariate analyses were performed to filter independent factors for the duration to viral RNA negative conversion. Data on the redetection of SARS-CoV-2 in the patients after they showed negative results on the RT‒PCR test (intermittent negative status) were also analysed. The median duration of virus shedding was 12 (interquartile range, IQR: 10-14) days. The severity of clinical outcome, personal vaccination-2doses, household vaccination rates, and abnormal defecation were factors indecently affecting negative conversion of SARS-CoV-2 RNA, suggesting that patients who had abnormal defecation or with more severe conditions would have delayed virological clearance, while patients who previously had 2 doses of vaccination or had higher household vaccination rates would have accelerated virological clearance. Loss of appetite (odds ratio (OR): 5.343; 95% CI: 3.307-8.632) and abnormal defecation (OR: 2.840; 95% CI: 1.736-4.645) were significantly associated with intermittent negative status. CONCLUSION: These findings could provide clues for the early identification of paediatric patients with prolonged viral shedding and could enrich the evidence for the development of prevention and control strategies, especially vaccination policies for children and adolescents.

Whole Genome Sequence Analysis to Identify SARS-CoV-2 Variant in Nepal

Background The spread of SARS-CoV-2 has become a global public health crisis. Nepal is facing the second wave of COVID-19 pandemic but, there is still a limited data on the genomic sequence of SARS-CoV-2 variants circulating in Nepal. Objective The objective of this study is to sequence the whole genome of SARS-CoV-2 in Nepal to detect possible mutation profiles and phylogenetic lineages of circulating SARS-CoV-2 variants. Method In this study, swab samples tested positive for SARS-CoV-2 were investigated. After RNA extraction, the investigation was performed through real-time PCR followed by whole genome sequencing. The consensus genome sequences were, then, analyzed with appropriate bioinformatics tools. Result Sequence analysis of two SARS-CoV-2 genomes from patient without travel history (Patient A1 and A2) were found to be of lineage B.1.1. Similarly, among other four samples from subjects returning from the United Kingdom, genomes of two samples were of lineage B.1.36, and the other two were of lineage B.1.1.7 (Alpha Variant). The mutations in the consensus genomes contained the defining mutations of the respective lineages of SARS-CoV-2. Conclusion We confirmed two genomic sequences of variant of concern VOC-202012/01 in Nepal. Our study provides the concise genomic evidence for spread of different lineages of SARS-CoV-2 - B.1.1, B.1.36 and B.1.1.7 of SARS-CoV-2 in Nepal.Copyright © 2021, Kathmandu University. All rights reserved.

Assessment of the Biological Impact of SARS-CoV-2 Genetic Variation Using an Authentic Virus Neutralisation Assay with Convalescent Plasma, Vaccinee Sera, and Standard Reagents.

In the summer of 2020, it became clear that the genetic composition of SARS-CoV-2 was changing rapidly. This was highlighted by the rapid emergence of the D614G mutation at that time. In the autumn of 2020, the project entitled "Agility" was initiated with funding from the Coalition for Epidemic Preparedness Innovations (CEPI) to assess new variants of SARS-CoV-2. The project was designed to reach out and intercept swabs containing live variant viruses in order to generate highly characterised master and working stocks, and to assess the biological consequences of the rapid genetic changes using both in vitro and in vivo approaches. Since November 2020, a total of 21 variants have been acquired and tested against either a panel of convalescent sera from early in the pandemic, and/or a panel of plasma from triple-vaccinated participants. A pattern of continuous evolution of SARS-CoV-2 has been revealed. Sequential characterisation of the most globally significant variants available to us, generated in real-time, indicated that the most recent Omicron variants appear to have evolved in a manner that avoids immunological recognition by convalescent plasma from the era of the ancestral virus when analysed in an authentic virus neutralisation assay.

Both simulation and sequencing data reveal coinfections with multiple SARS-CoV-2 variants in the COVID-19 pandemic.

SARS-CoV-2 is a single-stranded RNA betacoronavirus with a high mutation rate. The rapidly emerging SARS-CoV-2 variants could increase transmissibility and diminish vaccine protection. However, whether coinfection with multiple SARS-CoV-2 variants exists remains controversial. This study collected 12,986 and 4,113 SARS-CoV-2 genomes from the GISAID database on May 11, 2020 (GISAID20May11), and Apr 1, 2021 (GISAID21Apr1), respectively. With single-nucleotide variant (SNV) and network clique analyses, we constructed single-nucleotide polymorphism (SNP) coexistence networks and discovered maximal SNP cliques of sizes 16 and 34 in the GISAID20May11 and GISAID21Apr1 datasets, respectively. Simulating the transmission routes and SNV accumulations, we discovered a linear relationship between the size of the maximal clique and the number of coinfected variants. We deduced that the COVID-19 cases in GISAID20May11 and GISAID21Apr1 were coinfections with 3.20 and 3.42 variants on average, respectively. Additionally, we performed Nanopore sequencing on 42 COVID-19 patients and discovered recurrent heterozygous SNPs in twenty of the patients, including loci 8,782 and 28,144, which were crucial for SARS-CoV-2 lineage divergence. In conclusion, our findings reported SARS-CoV-2 variants coinfection in COVID-19 patients and demonstrated the increasing number of coinfected variants.

Reduced neutralization against Delta, Gamma, Mu, and Omicron BA.1 variants of SARS-CoV-2 from previous non-Omicron infection.

The understanding of the host immune response to SARS-CoV-2 variants of concern is critical for improving diagnostics, therapy development, and vaccines. Here, we analyzed the level of neutralizing antibodies against SARS-CoV-2 D614G, Delta, Gamma, Mu, and Omicron variants in D614G infected healthcare workers during a follow-up up to 6 months after recovery. We followed up 76 patients: 60.5% were women and 39.5% men. The 96.1% and 3.9% were symptomatic and asymptomatic, respectively. The most frequent symptoms were headache, myalgia, and cough. The 65.8%, 65.8%, and 92.1% of the infected individuals were positive for neutralizing antibodies against D614G variant at 2, 4, and 6 months of follow-up, respectively. The 26.3%, 48.7% and 65.8% of patients neutralized Delta variant, 19.7%, 32.9% and 52.6% of patients neutralized Gamma, 7.9%, 19.7% and 44.7% of patients neutralized Mu, and 4.0%, 9.2% and 15.8% of patients neutralized Omicron. Low neutralization against Gamma and Mu variants was observed during the follow-up, and very low against the Omicron variant was detected during the same period. The median of neutralizing antibody titers against D614G and Delta variants increased significantly during the follow-up. An association was observed between the levels of neutralizing antibodies against D614G and Delta variants and the severity of the disease. Our results suggest an immune escape from neutralizing antibodies with the Omicron variant because of the many mutations localized in the S protein.

Dynamics of SARS-CoV-2 VOC Neutralization and Novel mAb Reveal Protection against Omicron.

New variants of SARS-CoV-2 continue to emerge and evade immunity. We isolated SARS-CoV-2 temporally across the pandemic starting with the first emergence of the virus in the western hemisphere and evaluated the immune escape among variants. A clinic-to-lab viral isolation and characterization pipeline was established to rapidly isolate, sequence, and characterize SARS-CoV-2 variants. A virus neutralization assay was applied to quantitate humoral immunity from infection and/or vaccination. A panel of novel monoclonal antibodies was evaluated for antiviral efficacy. We directly compared all variants, showing that convalescence greater than 5 months post-symptom onset from ancestral virus provides little protection against SARS-CoV-2 variants. Vaccination enhances immunity against viral variants, except for Omicron BA.1, while a three-dose vaccine regimen provides over 50-fold enhanced protection against Omicron BA.1 compared to a two-dose. A novel Mab neutralizes Omicron BA.1 and BA.2 variants better than the clinically approved Mabs, although neither can neutralize Omicron BA.4 or BA.5. Thus, the need remains for continued vaccination-booster efforts, with innovation for vaccine and Mab improvement for broadly neutralizing activity. The usefulness of specific Mab applications links with the window of clinical opportunity when a cognate viral variant is present in the infected population.

Viable SARS-CoV-2 detected in the air of hospital rooms of patients with COVID-19 with an early infection.

OBJECTIVES: This study assessed the concentration of SARS-CoV-2 in the air of hospital rooms occupied by patients with COVID-19 who had viable SARS-CoV-2 in nasopharyngeal (NP) samples in early infection. METHODS: Between July and October 2021, NP swabs were collected from 20 patients with early SARS-CoV-2 infection admitted to a tertiary hospital in Japan. Air samples were collected from their rooms, tested for SARS-CoV-2 RNA, and cultured to determine potential infectivity. RESULTS: The NP swab samples of 18 patients were positive for viable SARS-CoV-2 (median concentration: 4.0 × 105 tissue culture infectious dose 50/ml). In the air samples, viral RNA (median concentration: 1.1 × 105 copies/m3) was detected in 12/18 (67%) patients, and viable virus (median concentration: 8.9 × 102 tissue culture infectious dose 50/m3) was detected in 5/18 (28%) patients. The median time between illness onset and sampling was 3 days. The RNA concentration was significantly higher in samples wherein viable SARS-CoV-2 was detected than in samples in which viable virus was not detected (P-value = 0.027). CONCLUSION: Viable SARS-CoV-2 can be detected in the air surrounding patients with early SARS-CoV-2 infection. Health care workers should pay attention to infection control when caring for patients with early SARS-CoV-2 infection.

The application of a novel 5-in-1 multiplex RT-PCR assay for rapid detection of SARS-CoV-2 and differentiation between variants of concern.

OBJECTIVES: To rapid detect for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and immediately distinguish whether positive samples represent variants of concern (VOCs), we established a novel 5-in-1 VOC assay. METHODS: This assay could distinguish among five VOCs: Alpha, Beta, Gamma, Delta, and Omicron, in a single reaction tube. The five variants exhibit different single nucleotide polymorphisms (SNPs) in their viral genome, which can be exploited to distinguish them. We selected target SNPs in the spike gene, including N501Y, P681R, K417N, and deletion H69/V70 for the assay. RESULTS: The limit of detection of each gene locus was 80 copies per PCR reaction. We observed a high consistency among the results when comparing the performance of our 5-in-1 VOC assay, whole gene sequencing, and the Roche VirSNiP SARS-CoV-2 test in retrospectively analyzing 150 clinical SARS-CoV-2 variant positive samples. The 5-in-1 VOC assay offers an alternative and rapid high-throughput test for most diagnostic laboratories in a flexible sample-to-result platform. CONCLUSION: The assay can also be applied in a commercial platform with completion of the SARS-CoV-2 confirmation test and identification of its variant within 2.5 hours.

Infection by SARS-CoV-2 with alternate frequencies of mRNA vaccine boosting.

One of the most consequential unknowns of the COVID-19 pandemic is the frequency at which vaccine boosting provides sufficient protection from infection. We quantified the statistical likelihood of breakthrough infections over time following different boosting schedules with messenger RNA (mRNA)-1273 (Moderna) and BNT162b2 (Pfizer-BioNTech). We integrated anti-Spike IgG antibody optical densities with profiles of the waning of antibodies and corresponding probabilities of infection associated with coronavirus endemic transmission. Projecting antibody levels over time given boosting every 6 months, 1, 1.5, 2, or 3 years yielded respective probabilities of fending off infection over a 6-year span of >93%, 75%, 55%, 40%, and 24% (mRNA-1273) and >89%, 69%, 49%, 36%, and 23% (BNT162b2). Delaying the administration of updated boosters has bleak repercussions. It increases the probability of individual infection by SARS-CoV-2, and correspondingly, ongoing disease spread, prevalence, morbidity, hospitalization, and mortality. Instituting regular, population-wide booster vaccination updated to predominant variants has the potential to substantially forestall-and with global, widespread uptake, eliminate-COVID-19.

SARS-CoV-2 Breakthrough Infection after mRNA-1273 Booster among CoronaVac-Vaccinated Healthcare Workers.

It remains unknown whether the Indonesian healthcare workers (HCWs) who had received two doses of CoronaVac vaccine and one dose of mRNA-1273 booster could be protected during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron wave. In total, 125 infection-naïve and 10 previously infected HCWs were recruited. The mRNA-1273 booster substantially increased titer of anti-SARS-CoV-2 spike protein receptor-binding domain antibodies. However, the monitoring revealed that 34 out of 125 infection-naïve (27.2%) and 3 out of 10 previously infected HCWs (30.0%) were infected during the Omicron wave. All infected HCWs were either asymptomatic or having mild coronavirus disease 2019 (COVID-19) and subsequently fully recovered, supporting the heterologous prime-boost strategy against COVID-19.

Humoral Immune Response Profile of COVID-19 Reveals Severity and Variant-Specific Epitopes: Lessons from SARS-CoV-2 Peptide Microarray.

The amaranthine scale of the COVID-19 pandemic and unpredictable disease severity is of grave concern. Serological diagnostic aids are an excellent choice for clinicians for rapid and easy prognosis of the disease. To this end, we studied the humoral immune response to SARS-CoV-2 infection to map immunogenic regions in the SARS-CoV-2 proteome at amino acid resolution using a high-density SARS-CoV-2 proteome peptide microarray. The microarray has 4932 overlapping peptides printed in duplicates spanning the entire SARS-CoV-2 proteome. We found 204 and 676 immunogenic peptides against IgA and IgG, corresponding to 137 and 412 IgA and IgG epitopes, respectively. Of these, 6 and 307 epitopes could discriminate between disease severity. The emergence of variants has added to the complexity of the disease. Using the mutation panel available, we could detect 5 and 10 immunogenic peptides against IgA and IgG with mutations belonging to SAR-CoV-2 variants. The study revealed severity-based epitopes that could be presented as potential prognostic serological markers. Further, the mutant epitope immunogenicity could indicate the putative use of these markers for diagnosing variants responsible for the infection.

Mathematical analysis of new variant Omicron model driven by Lévy noise and with variable-order fractional derivatives

In this paper, we study a variable-order fractional mathematical model driven by Lévy noise describing the new variant of COVID-19 (Omicron virus). Based on our analysis and discussion under a new set of sufficient conditions, we prove the existence and uniqueness of the related solution. Moreover, we discuss the stability analysis of the corresponding Omicron virus model by employing Ulam–Hyers and Ulam–Hyers–Rassias stabilities in Banach spaces. Finally, we present some numerical results and comparative studies to show clearly the importance of our results and its effects on behaviors of the new variant model.

A Review on Herbal Secondary Metabolites Against COVID-19 Focusing on the Genetic Variants of SARS-CoV-2

Context: An outbreak of the new coronavirus disease 2019 (COVID-19) was reported in Wuhan, China, in December 2019, subse-quently affecting countries worldwide and causing a pandemic. Although several vaccines, such as mRNA vaccines, inactivated vaccines, and adenovirus vaccines, have been licensed in several countries, the danger of severe acute respiratory syndrome coron-avirus 2 (SARS-CoV-2) variants persists. To date, Alpha (B.1.1.7), Beta (B.1.351, B.1.351.2, B.1.351.3), Delta (B.1.617.2, AY.1, AY.2, AY. 3), Gamma (P.1, P.1.1, P.1.2), and Iota (B.1 .526) circulating in the United States, Kappa (B.1.617.1) in India, Lambda (C.37) in Peru and Mu (B.1.621) in Colombia are considered the variants of concern and interest. Evidence Acquisition: Data were collected through the end of August 2021 by searching PubMed, Scopus, and Google Scholar databases. There were findings from in silico, in vitro cell-based, and non-cell-based investigations. Result(s): The potential and safety profile of herbal medicines need clarification to scientifically support future recommendations regarding the benefits and risks of their use. Conclusion(s): Current research results on natural products against SARS-CoV-2 and variants are discussed, and their specific molecular targets and possible mechanisms of action are summarized. Copyright © 2022, Brieflands All rights reserved.

Programmable DNA biocomputing circuits for rapid and intelligent screening of SARS-CoV-2 variants.

The frequent emergence of SARS-CoV-2 variants increased viral transmissibility and reduced protection afforded by vaccines. The rapid, multichannel, and intelligent screening of variants is critical to minimizing community transmissions. DNA molecular logic gates have attracted wide attention in recent years due to the powerful information processing capabilities and molecular data biocomputing functions. In this work, some molecular switches (MSs) were connected with each other to implement arbitrary binary functions by emulating the threshold switching of MOS transistors and the decision tree model. Using specific sequences of different SARS-CoV-2 variants as inputs, the MSs net was used to build several molecular biocomputing circuits, including NOT, AND, OR, INHIBIT, XOR, half adder, half subtractor, full adder, and full subtractor. Four fluorophores (FAM, Cy3, ROX, and Cy5) were employed in the logic systems to realize the multichannel monitoring of the logic operation results. The logic response is fast and can be finished with 10 min, which facilitates the rapid wide-population screening for SARS-CoV-2 variants. Importantly, the logic results can be directly observed by the naked eye under a portable UV lamp, thus providing a simple and intelligent method to enable high-frequency point-of-care diagnostics, particularly in low-resource communities.

Breakthrough infection with SARS-CoV-2 delta variant in old-age homes in a Southern District of Kerala, India.

Background: The incidence of breakthrough infection with the emergence of new variants of concern of SARS-CoV-2 is posing a threat, and it is pertinent to understand the role of vaccines in protecting the elderly and people with comorbidities. Objective: The present study was undertaken to understand the natural history of SARS-CoV-2 infection in a closed cohort of the elderly population in an old-age home who have received two doses of COVID-19 vaccination. The study has also undertaken genomic sequencing to identify SARS-CoV-2 variants of concern from an academic perspective. Materials and Methods: A prospective observational study was conducted from March to August 2021 among residents of 11 old-age homes in Kerala who were vaccinated with 2 doses of the COVID-19 vaccine, from 2 weeks following vaccination. Samples with a threshold cycle value of <25 were subjected to targeted sequencing of the spike protein receptor-binding domain coding region. Results: Among the 479 vaccinated individuals, 86 (17.95%) turned positive during the follow-up period. The mean duration of symptoms was 3-5 days, and no hospitalization was required. A phylogenetic analysis of the nucleotide sequences from the samples indicated B.1.617.2 lineage representing the Delta strain. Conclusion: The evidence supports maximizing the vaccine coverage among vulnerable groups to prevent hospitalization and death rate on the verge of the emergence of new variants of SARS-CoV-2.

Different Neutralization Profiles After Primary SARS-CoV-2 Omicron BA.1 and BA.2 Infections.

Background and Methods: The SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) Omicron (B.1.1.529) variant is the antigenically most distinct variant to date. As the heavily mutated spike protein enables neutralization escape, we studied serum-neutralizing activities of naïve and vaccinated individuals after Omicron BA.1 or BA.2 sub-lineage infections in live virus neutralization tests with Omicron BA.1, Omicron BA.2, wildtype (WT, B1.1), and Delta (B.1.617.2) strains. Serum samples obtained after WT infections and three-dose mRNA vaccinations with and without prior infection were included as controls. Results: Primary BA.1 infections yielded reduced neutralizing antibody levels against WT, Delta, and Omicron BA.2, while samples from BA.2-infected individuals showed almost no cross-neutralization against the other variants. Serum neutralization of Omicron BA.1 and BA.2 variants was detectable after three-dose mRNA vaccinations, but with reduced titers. Vaccination-breakthrough infections with either Omicron BA.1 or BA.2, however, generated equal cross-neutralizing antibody levels against all SARS-CoV-2 variants tested. Conclusions: Our study demonstrates that although Omicron variants are able to enhance cross-neutralizing antibody levels in pre-immune individuals, primary infections with BA.1 or BA.2 induced mostly variant-specific neutralizing antibodies, emphasizing the differently shaped humoral immunity induced by the two Omicron variants. These data thus contribute substantially to the understanding of antibody responses induced by primary Omicron infections or multiple exposures to different SARS-CoV-2 variants and are of particular importance for developing vaccination strategies in the light of future emerging variants.