Differences in incidence and fatality of COVID-19 by SARS-CoV-2 Omicron variant versus Delta variant in relation to vaccine coverage: A world-wide review

We aim to evaluate the evolution differences in the incidence and case fatality rate (CFR) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta and Omicron variants. The average incidence and CFRs were described between different countries. A gamma generalized linear mixed model (GLMM) was used to compare the CFRs of Delta and Omicron variants based on vaccination coverage. Totally, 50 countries were included for analyses. The incidence of coronavirus disease 2019 (COVID-19) ranged from 0.16/100,000 to 82.95/100,000 during the Delta period and 0.03/100,000 to 440.88/100,000 during the Omicron period. The median CFRs were 8.56 (interquartile range [IQR]: 4.76–18.39) during the Delta period and 3.04 (IQR: 1.87–7.48) during the Omicron period, respectively. A total of 47 out of 50 countries showed decreased CFRs of the Omicron variant with the rate ratio ranging from 0.02 (95% confidence interval [CI]: 0.01–0.03) (in Cambodia) to 0.97 (95% CI: 0.87–1.08) (in Ireland). Gamma GLMM analysis showed that the decreased CFR was largely a result of the decreased pathogenicity of Omicron besides the increased vaccination coverage. The Omicron variant shows a higher incidence but a lower CFR around the world as a whole, which is mainly a result of the decreased pathogenicity by SARS-CoV-2's mutation, while the vaccination against SARS-CoV-2 still acts as a valuable measure in preventing people from death.     

Lopinavir/ritonavir and interferon combination therapy may help shorten the duration of viral shedding in patients with COVID-19: A retrospective study in two designated hospitals in Anhui,China

Prolonged viral shedding may pose a threat to the control of coronavirus disease-2019 (COVID-19), and data on the duration of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) shedding are still limited, with the associated factors being unknown. All adult patients with laboratory-confirmed COVID-19 were included in this retrospective cross-sectional study in two designated hospitals during 21 January 2020 to 16 March 2020 in Anhui, China. In all patients, data on the duration of SARS-CoV-2 RNA shedding were analyzed by reviewing all RNA detection results during hospitalization. In addition, demographic, clinical, treatment, laboratory, and outcome data were also collected from electronic medical records. Factors associated with prolonged viral shedding were analyzed with the Cox proportional hazards model. Among 181 patients, the mean age was 44.3 ± 13.2 years, and 55.2% were male. The median duration of viral shedding from illness onset was 18.0 days (interquartile range [IQR], 15.0-24.0). Prolonged viral shedding was associated with longer hospital stays (P < .001) and higher medical costs (P < .001). The severity of COVID-19 had nothing to do with prolonged shedding. Moreover, the median time from onset to antiviral treatment initiation was 5.0 days (IQR, 3.0-7.0). Delayed antiviral treatment (hazard ratio [HR], 0.976; 95% confidence interval [CI], 0.962-0.990]) and lopinavir/ritonavir + interferon-α (IFN-α) combination therapy as the initial antiviral treatment (HR 1.649; 95% CI, 1.162-2.339) were independent factors associated with prolonged SARS-CoV-2 RNA shedding. SARS-CoV-2 showed prolonged viral shedding, causing increased hospital stays and medical costs. Early initiation of lopinavir/ritonavir + IFN-α combination therapy may help shorten the duration of SARS-CoV-2 shedding.     

Evidence of co-infections during Delta and Omicron SARS-CoV-2 variants co-circulation through prospective screening and sequencing

ObjectivesTo describe Delta/Omicron SARS-CoV-2 variants co-infection detection and confirmation during the fifth wave of COVID-19 pandemics in France in 7 immunocompetent and epidemiologically unrelated patients.MethodsSince December 2021, the surveillance of Delta/Omicron SARS-CoV-2 variants of concern (VOC) circulation was performed through prospective screening of positive-samples using single nucleotide polymorphism (SNP) PCR assays targeting SARS-CoV-2 S-gene mutations K417N (Omicron specific) and L452R (Delta specific). Samples showing unexpected mutational profiles were further submitted to whole genome sequencing (WGS) using three different primer sets.ResultsBetween weeks 49-2021 and 02-2022, SARS-CoV-2 genome was detected in 3831 respiratory samples, of which 3237 (84.5%) were screened for VOC specific SNPs. Unexpected mutation profiles suggesting a dual Delta/Omicron population were observed in 7 nasopharyngeal samples (0.2%). These co-infections were confirmed by WGS. For 2 patients, the sequence analyses of longitudinal samples collected 7 to 11 days apart showed that Delta or Omicron can outcompete the other variant during dual infection. Additionally, for one of these samples, a recombination event between Delta and Omicron was detected.ConclusionsThis work demonstrates that SARS-CoV-2 Delta/Omicron co-infections are not rare in high virus co-circulation periods. Moreover, co-infections can further lead to genetic recombination which may generate new chimeric variants with unpredictable epidemic or pathogenic properties that could represent a serious health threat.     

Clinical characteristics of 1139 mild cases of the SARS-CoV-2 Omicron variant infected patients in Shanghai

In March 2022, the Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) surged during the Coronavirus Disease 2019 (COVID-19) pandemic in Shanghai, but over 90% of patients were mild. This study included 1139 COVID-19 patients mildly infected with the Omicron variant of SARS-CoV-2 in Shanghai from May 1 to 10, 2022, aiming to clarify the demographic characteristics and clinical symptoms of patients with mild Omicron infection. The clinical phenotypes of Omicron infection were identified by model-based cluster analysis to explore the features of different clusters. The median age of the patients was 41.0 years [IQR: 31.0–52.0 years] and 73.0% were male. The top three clinical manifestations are cough (57.5%), expectoration (48.3%), and nasal congestion and runny nose (43.4%). The prevalence of nasal congestion and runny nose varied significantly across the doses of vaccinations, with 23.1% in the unvaccinated population and 30%, 45.9%, and 44.3% in the 1-dose, 2-dose and 3-dose vaccinated populations, respectively. In addition, there were significant differences for fever (23.1%, 26.0%, 28.6%, 18.4%), head and body heaviness (15.4%, 14.0%, 26.7%, 22.4%), and loss of appetite (25.6%, 30.0%, 33.6%, 27.7%). The unvaccinated population had a lower incidence of symptoms than the vaccinated population. Cluster analysis revealed that all four clusters had multisystemic symptoms and were dominated by both general and respiratory symptoms. The more severe the degree of the symptoms was, the higher the prevalence of multisystemic symptoms will be. The Omicron variant produced a lower incidence of symptoms in mildly infected patients than previous SARS-CoV-2 variants, but the clinical symptoms caused by the Omicron variant are more complex, so that it needs to be differentiated from influenza.     

SARS-CoV-2 infection in children evaluated in an ambulatory setting during Delta and Omicron time periods

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants and re-emergence of other respiratory viruses highlight the need to understand the presentation of and factors associated with SARS-CoV-2 in pediatric populations over time. The objective of this study was to evaluate the sociodemographic characteristics, symptoms, and epidemiological risk factors associated with ambulatory SARS-CoV-2 infection in children and determine if factors differ by variant type. We conducted a retrospective cohort study of outpatient children undergoing SARS-CoV-2 polymerase chain reaction testing between November 2020 and January 2022. Test-positive were compared with test-negative children to evaluate symptoms, exposure risk, demographics, and comparisons between Omicron, Delta, and pre-Delta time periods. Among 2264 encounters, 361 (15.9%) were positive for SARS-CoV-2. The cohort was predominantly Hispanic (51%), 5–11 years (44%), and 53% male; 5% had received two coronavirus disease 2019 (COVID-19) vaccine doses. Factors associated with a positive test include loss of taste/smell (adjusted odds ratio [aOR]: 6.71, [95% confidence interval, CI: 2.99–15.08]), new cough (aOR: 2.38, [95% CI: 1.69–3.36]), headache (aOR: 1.90, [95% CI: 1.28–2.81), fever (aOR: 1.83, [95% CI: 1.29–2.60]), contact with a positive case (aOR: 5.12, [95% CI: 3.75–6.97]), or household contact (aOR: 2.66, [95% CI: 1.96–3.62]). Among positive children, loss of taste/smell was more predominant during the Delta versus Omicron and pre-Delta periods (12% vs. 2% and 3%, respectively, p = 0.0017), cough predominated during Delta/Omicron periods more than the pre-Delta period (69% and 65% vs. 41%, p = 0.0002), and there were more asymptomatic children in the pre-Delta period (30% vs. 18% and 10%, p = 0.0023). These findings demonstrate that the presentation of COVID-19 in children and most susceptible age groups has changed over time.     

Duration of infectious shedding of SARS-CoV-2 Omicron variant and its relation with symptoms

ObjectivesSARS-CoV-2 infections with Omicron variants have a high capability of human-to-human transmission. Nevertheless, the duration of isolation for mild cases was shortened to 5 to 7 days. We aimed to detect the duration of viral shedding among healthcare workers (HCWs) with Omicron by using viral culture.MethodsWe prospectively included newly diagnosed nonsevere, symptomatic SARS-CoV-2 positive HCWs. Nasopharyngeal swab samples were obtained consecutively on days 5, 7,10, and 14 of onset of symptoms. The samples were examined by nucleic acid amplification test and viral culture.ResultsIn total, 55 non-severe patients with SARS-CoV-2 Omicron variant were included. The mean age of the population was 34 years (range, 23 to 54) and 78% (43/55) were female. The PCR positivity rate on days 5, 7, 10, and 14 was 96.4% (53/55), 87.3% (48/55), 74.545% (41/55), and 41.8% (23/55) consecutively, whereas the viral culture positivity rates were 83% (44/53), 52% (26/50), 13.5% (7/52), and 8% (4/50). Among the patients who became symptom-free, the viral culture positivity rates were 100% (4/4), 58% (7/12), 11% (3/27), and 5% (2/41).DiscussionWe showed that among the SARS-CoV-2 Omicron variant infected patients, viral shedding continues for ≥10 days in 13.5% of all cases and 11% in symptom-free cases. The decision for cessation of isolation according to the presence of symptoms could be reconsidered until further studies disapprove of our results. Meanwhile, the infected HCWs who give care to high-risk patients for severe COVID-19 might extend their isolations ≤10 days after the onset of symptoms, regardless of their symptoms.     

Molecular evolution of SARS-CoV-2 from December 2019 to August 2022

Severe acute respiratorysyndrome coronavirus-2 (SARS-CoV-2) pandemic spread rapidly and this scenario is concerning worldwide, presenting more than 590 million coronavirus disease 2019 cases and 6.4 million deaths. The emergence of novel lineages carrying several mutations in the spike protein has raised additional public health concerns worldwide during the pandemic. The present study review and summarizes the temporal spreading and molecular evolution of SARS-CoV-2 clades and variants worldwide. The evaluation of these data is important for understanding the evolutionary histories of SARSCoV-2 lineages, allowing us to identify the origins of each lineage of this virus responsible for one of the biggest pandemics in history. A total of 2897 SARS-CoV-2 whole-genome sequences with available information from the country and sampling date (December 2019 to August 2022), were obtained and were evaluated by Bayesian approach. The results demonstrated that the SARS-CoV-2 the time to the most recent common ancestor (tMRCA) in Asia was 2019-12-26 (highest posterior density 95% [HPD95%]: 2019-12-18; 2019-12-29), in Oceania 2020-01-24 (HPD95%: 2020-01-15; 2020-01-30), in Africa 2020-02-27 (HPD95%: 2020-02-21; 2020-03-04), in Europe 2020-02-27 (HPD95%: 2020-02-20; 2020-03-06), in North America 2020-03-12 (HPD95%: 2020-03-05; 2020-03-18), and in South America 2020-03-15 (HPD95%: 2020-03-09; 2020-03-28). Between December 2019 and June 2020, 11 clades were detected (20I [Alpha] and 19A, 19B, 20B, 20C, 20A, 20D, 20E [EU1], 20F, 20H [Beta]). From July to December 2020, 4 clades were identified (20J [Gamma, V3], 21 C [Epsilon], 21D [Eta], and 21G [Lambda]). Between January and June 2021, 3 clades of the Delta variant were detected (21A, 21I, and 21J). Between July and December 2021, two variants were detected, Delta (21A, 21I, and 21J) and Omicron (21K, 21L, 22B, and 22C). Between January and June 2022, the Delta (21I and 21J) and Omicron (21K, 21L, and 22A) variants were detected. Finally, between July and August 2022, 3 clades of Omicron were detected (22B, 22C, and 22D). Clade 19A was first detected in the SARS-CoV-2 pandemic (Wuhan strain) with origin in 2019-12-16 (HPD95%: 2019-12-15; 2019-12-25); 20I (Alpha) in 2020-11-24 (HPD95%: 2020-11-15; 2021-12-02); 20H (Beta) in 2020-11-25 (HPD95%: 2020-11-13; 2020-11-29); 20J (Gamma) was 2020-12-21 (HPD95%: 2020-11-05; 2021-01-15); 21A (Delta) in 2020-09-20 (HPD95%: 2020-05-17; 2021-02-03); 21J (Delta) in 2021-02-26 (2020-11-02; 2021-04-24); 21M (Omicron) in 2021-01-25 (HPD95%: 2020-09-16; 2021-08-08); 21K (Omicron) in 2021-07-30 (HPD95%: 2021-05-30; 2021-10-19); 21L (Omicron) in 2021-10-03 (HPD95%: 2021-04-16; 2021-12-23); 22B (Omicron) in 2022-01-25 (HPD95%: 2022-01-10; 2022-02-05); 21L in 2021-12-20 (HPD95%: 2021-05-16; 2021-12-31). Currently, the Omicron variant predominates worldwide, with the 21L clade branching into 3 (22A, 22B, and 22C). Phylogeographic data showed that Alpha variant originated in the United Kingdom, Beta in South Africa, Gamma in Brazil, Delta in India, Omicron in South Africa, Mu in Colombia, Epsilon in the United States of America, and Lambda in Peru. The COVID-19 pandemic has had a significant impact on global health worldwide and the present study provides an overview of the molecular evolution of SARS-CoV-2 lineage clades (from the Wuhan strain to the currently circulating lineages of the Omicron).     

The “vaccine” hubbub: Viral load comparisons of SARS-CoV-2 Delta and Omicron variants against different vaccine–booster vaccine combinations

There is a significant body of evidence showing that efficient vaccination schemes against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is helping control the coronavirus disease 2019 (COVID-19) pandemic. However, this goal cannot be achieved without real world data highlighting the impact of vaccines against viral spread. In this study, we have aimed at differentially investigating the impact of COVID-19 vaccines (CoronaVac, Pfizer/BioNTech, Astra/Zeneca Oxford, Janssen) used in North Cyprus in limiting the viral load of Delta and Omicron variants of SARS-COV-2. We have utilized real-time quantitative polymerase chain reaction cycle threshold values (Ct values) as a proxy of viral load of the two SARS-CoV-2 variants. Our results indicate that the administration of at least two doses of the messenger RNA-based Pfizer/BioNTech vaccine leads to the lowest viral load (highest Ct values) obtained for both Omicron and Delta variants. Interestingly, regardless of the vaccine type used, our study revealed that Delta variant produced significantly higher viral loads (lower Ct values) compared with the Omicron variant, where the latter was more commonly associated with younger patients. Viral spread is a crucial factor that can help determine the future of the pandemic. Thus, prioritizing vaccines that will play a role in not only preventing severe disease but also in limiting viral load and spread may contribute to infection control strategies.     

Viable SARS-CoV-2 in various specimens from COVID-19 patients

ObjectivesThe aim was to determine whether various clinical specimens obtained from COVID-19 patients contain the infectious virus.MethodsTo demonstrate whether various clinical specimens contain the viable virus, we collected naso/oropharyngeal swabs and saliva, urine and stool samples from five COVID-19 patients and performed a quantitative polymerase chain reaction (qPCR) to assess viral load. Specimens positive with qPCR were subjected to virus isolation in Vero cells. We also used urine and stool samples to intranasally inoculate ferrets and evaluated the virus titres in nasal washes on 2, 4, 6 and 8 days post infection.ResultsSARS-CoV-2 RNA was detected in all naso/oropharyngeal swabs and saliva, urine and stool samples collected between days 8 and 30 of the clinical course. Notably, viral loads in urine, saliva and stool samples were almost equal to or higher than those in naso/oropharyngeal swabs (urine 1.08 ± 0.16–2.09 ± 0.85 log₁₀ copies/mL, saliva 1.07 ± 0.34–1.65 ± 0.46 log₁₀ copies/mL, stool 1.17 ± 0.32 log₁₀ copies/mL, naso/oropharyngeal swabs 1.18 ± 0.12–1.34 ± 0.30 log₁₀ copies/mL). Further, viable SARS-CoV-2 was isolated from naso/oropharyngeal swabs and saliva of COVID-19 patients, as well as nasal washes of ferrets inoculated with patient urine or stool.DiscussionViable SARS-CoV-2 was demonstrated in saliva, urine and stool samples from COVID-19 patients up to days 11–15 of the clinical course. This result suggests that viable SARS-CoV-2 can be secreted in various clinical samples and respiratory specimens.     

SARS-CoV-2 Omicron and its current known unknowns: A narrative review

The emergence of the SARS-CoV-2 Omicron variant (B.1.1.529) has created great global distress. This variant of concern shows multiple sublineages, importantly B.1.1.529.1 (BA.1), BA.1 + R346K (BA.1.1), and B.1.1.529.2 (BA.2), each with unique properties. However, little is known about this new variant, specifically its sub-variants. A narrative review was conducted to summarise the latest findings on transmissibility, clinical manifestations, diagnosis, and efficacy of current vaccines and treatments. Omicron has shown two times higher transmission rates than Delta and above ten times more infectious than other variants over a similar period. With more than 30 mutations in the spike protein's receptor-binding domain, there is reduced detection by conventional RT-PCR and rapid antigen tests. Moreover, the two-dose vaccine effectiveness against Delta and Omicron variants was found to be approximately 21%, suggesting an urgent need for a booster dose to prevent the possibility of breakthrough infections. However, the current vaccines remain highly efficacious against severe disease, hospitalisation, and mortality. Japanese preliminary lab data elucidated that the Omicron sublineage BA.2 shows a higher illness severity than BA.1. To date, the clinical management of Omicron remains unchanged, except for monoclonal antibodies. Thus far, only Bebtelovimab could sufficiently treat all three sub-variants of Omicron. Further studies are warranted to understand the complexity of Omicron and its sub-variants. Such research is necessary to improve the management and prevention of Omicron infection.     

Omicron-specific mRNA vaccine induced cross-protective immunity against ancestral SARS-CoV-2 infection with low neutralizing antibodies

The major challenge in COVID-19 vaccine effectiveness is immune escape by SARS-CoV-2 variants. To overcome this, an Omicron-specific messenger RNA (mRNA) vaccine was designed. The extracellular domain of the spike of the Omicron variant was fused with a modified GCN4 trimerization domain with low immunogenicity (TSomi). After immunization with TSomi mRNA in hamsters, animals were challenged with SARS-CoV-2 virus. The raised nonneutralizing antibodies or cytokine secretion responses can recognize both Wuhan S and Omicron S. However, the raised antibodies neutralized SARS-CoV-2 Omicron virus infection but failed to generate Wuhan virus neutralizing antibodies. Surprisingly, TSomi mRNA immunization protected animals from Wuhan virus challenge. These data indicated that non-neutralizing antibodies or cellular immunity may play a more important role in vaccine-induced protection than previously believed. Next-generation COVID-19 vaccines using the Omicron S antigen may provide sufficient protection against ancestral or current SARS-CoV-2 variants.     

Humoral and cellular immunity of two-dose inactivated COVID-19 vaccination in Chinese children: A prospective cohort study

Children are the high-risk group for COVID-19, and in need of vaccination. However, humoral and cellular immune responses of COVID-19 vaccine remain unclear in vaccinated children. To establish the rational immunization strategy of inactivated COVID-19 vaccine for children, the immunogenicity of either one dose or two doses of the vaccine in children was evaluated. A prospective cohort study of 322 children receiving inactivated COVID-19 vaccine was established in China. The baseline was conducted after 28 days of the first dose, and the follow-up was conducted after 28 days of the second dose. The median titers of receptor binding domain (RBD)-IgG, and neutralizing antibody (NAb) against prototype strain and Omicron variant after the second dose increased significantly compared to those after the first dose (first dose: 70.0, [interquartile range, 30.0–151.0] vs. second dose: 1261.0 [636.0–2060.0] for RBD-IgG; 2.5 [2.5–18.6] vs. 252.0 [138.6–462.1] for NAb against prototype strain; 2.5 [2.5–2.5] vs. 15.0 [7.8–26.5] for NAb against Omicron variant, all p < 0.05). The flow cytometry results showed that the first dose elicited SARS-CoV-2 specific cellular immunity, while the second dose strengthened SARS-CoV-2 specific IL-2⁺ or TNF-α⁺ monofunctional, IFN-γ⁺TNF-α⁺ bifunctional, and IFN-γ⁻IL-2⁺TNF-α⁺ multifunctional CD4⁺ T cell responses (p < 0.05). Moreover, SARS-CoV-2 specific memory T cells were generated after the first vaccination, including the central memory T cells and effector memory T cells. The present findings provide scientific evidence for the vaccination strategy of the inactive vaccines among children against COVID-19 pandemic.     

Impact of prior statin use on clinical outcomes in COVID-19 patients: data from tertiary referral hospitals during COVID-19 pandemic in Italy

BackgroundEpidemiological evidence suggests that anti-inflammatory and immunomodulatory properties of statins may reduce the risk of infections and infection-related complications.ObjectiveWe aimed to assess the impact of prior statin use on coronavirus disease (COVID-19) severity and mortality.MethodsIn this observational multicenter study, consecutive patients hospitalized for COVID-19 were enrolled. In-hospital mortality and severity of COVID-19 assessed with National Early Warning Score (NEWS) were deemed primary and secondary outcomes, respectively. Propensity score (PS) matching was used to obtain balanced cohorts.ResultsAmong 842 patients enrolled, 179 (21%) were treated with statins before admission. Statin patients showed more comorbidities and more severe COVID-19 (NEWS 4 [IQR 2–6] vs 3 [IQR 2–5], p < 0.001). Despite having similar rates of intensive care unit admission, noninvasive ventilation, and mechanical ventilation, statin users appeared to show higher mortality rates. After balancing pre-existing relevant clinical conditions that could affect COVID-19 prognosis with PS matching, statin therapy confirmed its association with a more severe disease (NEWS ≥5 61% vs. 48%, p = 0.025) but not with in-hospital mortality (26% vs. 28%, p = 0.185). At univariate logistic regression analysis, statin use was confirmed not to be associated with mortality (OR 0.901; 95% CI: 0.537 to 1.51; p = 0.692) and to be associated with a more severe disease (NEWS≥5 OR 1.7; 95% CI 1.067–2.71; p = 0.026).ConclusionsOur results did not confirm the supposed favorable effects of statin therapy on COVID-19 outcomes. Conversely, they suggest that statin use should be considered as a proxy of underlying comorbidities, which indeed expose to increased risks of more severe COVID-19.     

Varicella zoster virus reactivation following COVID-19 vaccination in patients with autoimmune inflammatory rheumatic diseases: A cross-sectional Chinese study of 318 cases

Recently, varicella-zoster virus (VZV) reactivation has been observed after the administration of coronavirus disease 2019 (COVID-19) vaccines. Autoimmune inflammatory rheumatic diseases (AIIRDs) patients are at a higher risk for VZV reactivation for immunocompromised status. The study aimed to investigate the adverse events (AEs), especially VZV reactivation, following vaccination against  severe acute respiratory syndrome coronavirus-2 in a Chinese cohort of AIIRD patients. A cross-sectional survey using an online questionnaire was conducted among AIIRD patients and healthy controls (HCs). Multivariate logistic regression was used to identify potential factors associated with VZV reactivation. 318 AIIRD patients and 318 age and sex-matched HCs who got COVID-19 inactivated vaccines were recruited. The main AIIRDs are rheumatoid arthritis (31.8%) and systemic lupus erythematous (23.9%). Most of patients (85.5%) had stable disease and 13.2% of them had aggravation after vaccination. Compared to HCs, patients had higher rates of rash (p = 0.001), arthralgia (p < 0.001) and insomnia (p = 0.007). In addition, there were 6 (1.9%) AIIRD patients and 5 (1.6%) HCs reported VZV reactivation after the COVID-19 vaccination (p = 0.761). Multivariate logistic regression analysis illustrated that diabetes mellitus (odd ratio [OR], 20.69; 95% confidence interval [CI], 1.08−396.79; p = 0.044), chronic hepatitis B virus infection (OR, 24.34; 95% CI, 1.27−466.74; p = 0.034), and mycophenolate mofetil (OR, 40.61; 95% CI, 3.33−496.15; p = 0.004) independently identified patients with VZV reactivation. Our findings showed that the inactivated COVID-19 vaccination was safe for AIIRD patients though some patients could suffer from VZV reactivation.     

Current immunoassays and detection of antibodies elicited by Omicron SARS-CoV-2 infection

The present study aimed to determine whether current commercial immunoassays are adequate for detecting anti-Omicron antibodies. We analyzed the anti-SARS-CoV-2 antibody response of 23 unvaccinated individuals 1–2 months after an Omicron infection. All blood samples were tested with a live virus neutralization assay using a clinical Omicron BA.1 strain and four commercial SARS-CoV-2 immunoassays. We assessed three anti-Spike immunoassays (SARS-CoV-2 IgG II Quant [Abbott S], Wantaï anti-SARS-CoV-2 antibody ELISA [Wantaï], Elecsys Anti-SARS-CoV-2 S assay [Roche]) and one anti-Nucleocapsid immunoassay (Abbott SARS-CoV-2 IgG assay [Abbott N]). Omicron neutralizing antibodies were detected in all samples with the live virus neutralization assay. The detection rate of the Abbott S, Wantai, Roche, and Abbott N immunoassays were 65.2%, 69.6%, 86.9%, and 91.3%, respectively. The sensitivities of Abbott S and Wantai immunoassays were significantly lower than that of the live virus neutralization assay (p = 0.004, p = 0.009; Fisher's exact test). Antibody concentrations obtained with anti-S immunoassays were correlated with Omicron neutralizing antibody concentrations. These data provide clinical evidence of the loss of performance of some commercial immunoassays to detect antibodies elicited by Omicron infections. It highlights the need to optimize these assays by adapting antigens to the circulating SARS-CoV-2 strains.     

Signals of Significantly Increased Vaccine Breakthrough,Decreased Hospitalization Rates,and Less Severe Disease in Patients with Coronavirus Disease 2019 Caused by the Omicron Variant of Severe Acute Respiratory Syndrome Coronavirus 2 in Houston, Texas

Genetic variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continue to dramatically alter the landscape of the coronavirus disease 2019 (COVID-19) pandemic. The recently described variant of concern designated Omicron (B.1.1.529) has rapidly spread worldwide and is now responsible for the majority of COVID-19 cases in many countries. Because Omicron was recognized recently, many knowledge gaps exist about its epidemiology, clinical severity, and disease course. A genome sequencing study of SARS-CoV-2 in the Houston Methodist health care system identified 4468 symptomatic patients with infections caused by Omicron from late November 2021 through January 5, 2022. Omicron rapidly increased in only 3 weeks to cause 90% of all new COVID-19 cases, and at the end of the study period caused 98% of new cases. Compared with patients infected with either Alpha or Delta variants in our health care system, Omicron patients were significantly younger, had significantly increased vaccine breakthrough rates, and were significantly less likely to be hospitalized. Omicron patients required less intense respiratory support and had a shorter length of hospital stay, consistent with on average decreased disease severity. Two patients with Omicron stealth sublineage BA.2 also were identified. The data document the unusually rapid spread and increased occurrence of COVID-19 caused by the Omicron variant in metropolitan Houston, Texas, and address the lack of information about disease character among US patients.

Over the past 14 months, the Alpha and Delta variants of concern (VOCs) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have caused two distinct coronavirus disease 2019 (COVID-19) surges in the United States, Southeast Asia, Europe, and elsewhere (https://www.cdc.gov/coronavirus/2019-ncov/cases-updates/variant-surveillance/variant-info.html, last accessed December 30, 2021; https://www.gov.uk/government/collections/new-sars-cov-2-variant, last accessed December 30, 2021), and remodeled the landscape of human behavior and many societies. Delta replaced the Alpha variant as the cause of virtually all COVID-19 in many countries (https://www.who.int/publications/m/item/weekly-epidemiological-update-on-covid-19---13-july-2021, last accessed August 18, 2021; https://www.ons.gov.uk/peoplepopulationandcommunity/healthandsocialcare/conditionsanddiseases/bulletins/coronaviruscovid19infectionsurveypilot/9july2021, last accessed August 18, 2021).At the start of the pandemic almost 2 years ago, the Houston Methodist health care system instituted a comprehensive and integrated population genomics project designed to sequence all SARS-CoV-2 samples causing COVID-19 in patients cared for at our facilities, which include eight hospitals located throughout the metroplex. The project was implemented when the initial Houston Methodist COVID-19 case was diagnosed at the end of February 2020, and has continued unabated.1, 2, 3, 4, 5, 6, 7 This project was facilitated by the existence of a single large diagnostic laboratory that serves the entire system and is seamlessly integrated with a research institute with extensive genomics expertise and capacity. A key goal was to comprehensively map the population genomics, trajectory, and other features of the pandemic in metropolitan Houston, Texas, with a population size of approximately 7.2 million. Houston is the fourth largest city in the United States, is the most ethnically diverse metropolitan area in the country, and is a major port of entry. To date, SARS-CoV-2 genomes have been sequenced from >70,000 patient samples. Many features of four distinct SARS-CoV-2 waves in Houston have been described.2, 3, 4, 5, 6The successes of rapid SARS-CoV-2 vaccine development and documented efficacy, coupled with the significant downturn of the disease wave caused by Delta in Houston and elsewhere in fall 2021,⁶ suggested that the pandemic was abating. However, the identification of a new VOC designated B.1.1.529 and known as Omicron that has spread rapidly in South Africa and the United Kingdom has tempered this optimism.8, 9, 10 Inasmuch as Omicron was recognized recently, and much is not known about its epidemiology and clinical characteristics and course, we used our integrated infrastructure in an effort to address the lack of information available for US Omicron patients. Genome sequencing identified 4468 COVID-19 patients with symptomatic disease caused by Omicron in the Houston Methodist health care system beginning in late November 2021 and ending January 5, 2022. In 3 weeks, Omicron spread throughout the Houston metropolitan region to become the cause of 90% of new COVID-19 cases, and at the end of the study period caused 98% of all new cases. Compared with patients infected with either Alpha or Delta variant and cared for in our system, significantly fewer Omicron patients were hospitalized, and those who were hospitalized required significantly less intense respiratory support and had a shorter length of stay. Our findings are consistent with decreased disease severity among Houston Methodist Omicron patients. Many factors undoubtedly have contributed, including but not limited to increased vaccination uptake, population immunity, and patient demographics, such as younger age. The extent to which our findings translate to other cities and other patient populations, including children, is unknown. These data expand on our initial Omicron work⁷ and address the lack of information about disease character among US patients with COVID-19 caused by this VOC.     

A performance comparison of two (electro) chemiluminescence immunoassays for detection and quantitation of serum anti-spike antibodies according to SARS-CoV-2 vaccination and infections status

The information provided by SARS-CoV-2 spike (S)-targeting immunoassays can be instrumental in clinical-decision making. We compared the performance of the Elecsys® Anti-SARS-CoV-2 S assay (Roche Diagnostics) and the LIAISON® SARS-CoV-2 TrimericS IgG assay (DiaSorin) using a total of 1176 sera from 797 individuals, of which 286 were from vaccinated-SARS-CoV-2/experienced (Vac-Ex), 581 from vaccinated/naïve (Vac-N), 147 from unvaccinated/experienced (Unvac-Ex), and 162 from unvaccinated/naïve (Unvac-N) individuals. The Roche assay returned a higher number of positive results (907 vs. 790; p = 0.45; overall sensitivity: 89.3% vs. 77.6%). The concordance between results provided by the two immunoassays was higher for sera from Vac-N (ϰ: 0.58; interquartile ranges [IQR]: 0.50−0.65) than for sera from Vac-Ex (ϰ: 0.19; IQR: −0.14 to 0.52) or Unvac-Ex (ϰ: 0.18; IQR: 0.06−0.30). Discordant results occurred more frequently among sera from Unvac-Ex (34.7%) followed by Vac-N (14.6%) and Vac-Ex (2.7%). Antibody levels quantified by both immunoassays were not significantly different when <250 (p = 0.87) or <1000 BAU/ml (p = 0.13); in contrast, for sera ≥1000 BAU/ml, the Roche assay returned significantly higher values than the DiaSorin assay (p < 0.008). Neutralizing antibody titers (NtAb) were measured in 127 sera from Vac-Ex or Vac-N using a S-pseudotyped virus neutralization assay of Wuhan-Hu-1, Omicron BA.1, and Omicron BA.2. The correlation between antibody levels and NtAb titers was higher for sera from Vac-N than those from Vac-Ex, irrespective of the (sub)variant considered. In conclusion, neither qualitative nor quantitative results returned by both immunoassays are interchangeable. The performance of both assays was found to be greatly influenced by the vaccination and SARS-CoV-2 infection status of individuals.     

A new SARS-CoV-2 variant with high lethality poorly detected by RT-PCR on nasopharyngeal samples: an observational study

ObjectivesIn early January 2021 an outbreak of nosocomial cases of coronavirus disease 2019 (COVID-19) emerged in Western France; RT-PCR tests were repeatedly negative on nasopharyngeal samples but positive on lower respiratory tract samples. Whole-genome sequencing (WGS) revealed a new variant, currently defining a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lineage B.1.616. In March, the WHO classified this as a ‘variant under investigation’ (VUI). We analysed the characteristics and outcomes of COVID-19 cases related to this new variant.MethodsClinical, virological, and radiological data were retrospectively collected from medical charts in the two hospitals involved. We enrolled those inpatients with: (a) positive SARS-CoV-2 RT-PCR on a respiratory sample, (b) seroconversion with anti-SARS-CoV-2 IgG/IgM, or (c) suggestive symptoms and typical features of COVID-19 on a chest CT scan. Cases were categorized as B.1.616, a variant of concern (VOC), or unknown.ResultsFrom 1st January to 24th March 2021, 114 patients fulfilled the inclusion criteria: B.1.616 (n = 39), VOC (n = 32), and unknown (n = 43). B.1.616-related cases were older than VOC-related cases (81 years, interquartile range (IQR) 73–88 versus 73 years, IQR 67–82, p < 0.05) and their first RT-PCR tests were rarely positive (6/39, 15% versus 31/32, 97%, p < 0.05). The B.1.616 variant was independently associated with severe disease (multivariable Cox model HR 4.0, 95%CI 1.5–10.9) and increased lethality (28-day mortality 18/39 (46%) for B.1.616 versus 5/32 (16%) for VOC, p = 0.006).ConclusionWe report a nosocomial outbreak of COVID-19 cases related to a new variant, B.1.616, which is poorly detected by RT-PCR on nasopharyngeal samples and is associated with high lethality.