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1.
Euro Surveillance: Bulletin Europeen sur les Maladies Transmissibles = European Communicable Disease Bulletin ; 27(18), 2022.
Article in English | MEDLINE | ID: covidwho-1834267

ABSTRACT

We compared vaccine effectiveness against severe COVID-19 between December 2021 and March 2022 when Omicron BA.1 and BA.2 were the dominating SARS-CoV-2 variants in Scania county, Sweden. Effectiveness remained above 80% after the transition from BA.1 to BA.2 among people with at least three vaccine doses but the point estimate decreased markedly to 54% among those with only two doses. Protection from prior infection was also lower after the transition to BA.2. Booster vaccination seems necessary to maintain sufficient protection.

2.
Euro Surveillance: Bulletin Europeen sur les Maladies Transmissibles = European Communicable Disease Bulletin ; 27(18), 2022.
Article in English | MEDLINE | ID: covidwho-1834266

ABSTRACT

BackgroundOmicron subvariant BA.2 circulation is rapidly increasing globally.AimWe evaluated the neutralising antibody response from vaccination or prior SARS-CoV-2 infection against symptomatic infection by BA.2 or other variants. Methods Using 50% plaque reduction neutralisation tests (PRNT50), we assessed neutralising antibody titres to BA.2, wild type (WT) SARS-CoV-2 and other variants in Comirnaty or CoronaVac vaccinees, with or without prior WT-SARS-CoV-2 infection. Titres were also measured for non-vaccinees convalescing from a WT-SARS-CoV-2 infection. Neutralising antibodies in BA.2 and BA.1 breakthrough infections and in BA.2 infections affecting non-vaccinees were additionally studied. Results In vaccinees or prior WT-SARS-CoV-2-infected people, BA.2 and BA.1 PRNT50 titres were comparable but significantly (p < 10 - 5) lower than WT. In each group of 20 vaccinees with (i) three-doses of Comirnaty, (ii) two CoronaVac followed by one Comirnaty dose, or (iii) one dose of either vaccine after a WT-SARS-CoV-2 infection, >= 19 individuals developed detectable (PRNT50 titre >= 10) antibodies to BA.2, while only 15 of 20 vaccinated with three doses of CoronaVac did. Comirnaty vaccination elicited higher titres to BA.2 than CoronaVac. In people convalescing from a WT-SARS-CoV-2 infection, a single vaccine dose induced higher BA.2 titres than three Comirnaty (p = 0.02) or CoronaVac (p = 0.00001) doses in infection-naive individuals. BA.2 infections in previously uninfected and unvaccinated individuals elicited low (PRNT50 titre <= 80) responses with little cross-neutralisation of other variants. However, vaccinees with BA.1 or BA.2 breakthrough infections had broad cross-neutralising antibodies to WT viruses, and BA.1, BA.2, Beta and Delta variants. Conclusions Existing vaccines can be of help against the BA.2 subvariant.

3.
JMIR Public Health and Surveillance ; 29:29, 2022.
Article in English | MEDLINE | ID: covidwho-1834201

ABSTRACT

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 hospital 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 who 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 two groups: those that were in a Delta outbreak (defined by at least ten 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 two 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 two-fold increase (2.04) in the average apex of the Omicron outbreak compared to countries that were not yet in 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 precluded 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. CLINICALTRIAL: Not applicable.

5.
Antimicrobial Agents & Chemotherapy ; : e0022222, 2022.
Article in English | MEDLINE | ID: covidwho-1832332

ABSTRACT

Genetic variation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in the emergence and rapid spread of multiple variants throughout the pandemic, of which Omicron is currently the predominant variant circulating worldwide. SARS-CoV-2 variants of concern/variants of interest (VOC/VOI) have evidence of increased viral transmission, disease severity, or decreased effectiveness of vaccines and neutralizing antibodies. Remdesivir (RDV [VEKLURY]) is a nucleoside analog prodrug and the first FDA-approved antiviral treatment of COVID-19. Here, we present a comprehensive antiviral activity assessment of RDV and its parent nucleoside, GS-441524, against 10 current and former SARS-CoV-2 VOC/VOI clinical isolates by nucleoprotein enzyme-linked immunosorbent assay (ELISA) and plaque reduction assay. Delta and Omicron variants remained susceptible to RDV and GS-441524, with 50% effective concentration (EC50) values 0.30- to 0.62-fold of those observed against the ancestral WA1 isolate. All other tested variants exhibited EC50 values ranging from 0.13- to 2.3-fold of the observed EC50 values against WA1. Analysis of nearly 6 million publicly available variant isolate sequences confirmed that Nsp12, the RNA-dependent RNA polymerase (RdRp) target of RDV and GS-441524, is highly conserved across variants, with only 2 prevalent changes (P323L and G671S). Using recombinant viruses, both RDV and GS-441524 retained potency against all viruses containing frequent variant substitutions or their combination. Taken together, these results highlight the conserved nature of SARS-CoV-2 Nsp12 and provide evidence of sustained SARS-CoV-2 antiviral activity of RDV and GS-441524 across the tested variants. The observed pan-variant activity of RDV supports its continued use for the treatment of COVID-19 regardless of the SARS-CoV-2 variant.

6.
Science immunology ; : eabo3425, 2022.
Article in English | MEDLINE | ID: covidwho-1832328

ABSTRACT

Neutralizing antibodies that recognize the SARS-CoV-2 spike glycoprotein are the principal host defense against viral invasion. Variants of SARS-CoV-2 bear mutations that allow escape from neutralization by many antibodies, especially those belonging to classes widely distributed in the human population. Identifying antibodies that neutralize these variants of concern and determining their prevalence are important goals for understanding immune protection. To determine the Delta- and Omicron BA.1-variant specificity of B cell repertoires established by an initial Wuhan strain infection, we measured neutralization potencies of 73 antibodies from an unbiased survey of the early memory B cell response. Antibodies recognizing each of three, previously defined, epitopic regions on the spike receptor-binding domain (RBD) varied in neutralization potency and variant-escape resistance. The ACE2 binding surface ("RBD-2") harbored the binding sites of the neutralizing antibodies with highest potency but with the greatest sensitivity to viral escape;two other epitopic regions on the RBD ("RBD-1 and "RBD-3") bound antibodies of more modest potency but greater breadth. The structures of several Fab:spike complexes that neutralized all five variants of concern tested, including one Fab each from the RBD-1, -2 and -3 clusters, illustrated the determinants of broad neutralization and showed that B cell repertoires can have specificities that avoid immune escape driven by widely distributed ("public") antibodies. The structure of the RBD-2-binding, broad neutralizer shows why it retains neutralizing activity for Omicron BA.1, unlike most others in the same public class. Our results correlate with real-world data on vaccine efficacy, which indicate mitigation of disease caused by Omicron BA.1.

7.
Journal of the Pediatric Infectious Diseases Societ ; 05:05, 2022.
Article in English | MEDLINE | ID: covidwho-1831236

ABSTRACT

In this retrospective analysis, we describe weekly croup and corresponding viral prevalence patterns in a pediatric quaternary care system in metropolitan Atlanta. We characterize a series of 24 patients with croup associated with SARS-CoV-2 infection and show that this clinical presentation increased substantially in frequency during the period of high Omicron vs Delta transmission.

8.
Journal of Infectious Diseases ; 05:05, 2022.
Article in English | MEDLINE | ID: covidwho-1831182

ABSTRACT

The SARS-CoV-2 variant Omicron is now under investigation. We evaluated cross-neutralizing activity against Omicron in COVID-19 convalescent patients (n = 23) who had received two doses of an mRNA vaccination (BNT162b2 or mRNA-1273). Intriguingly, after the second vaccination, the neutralizing antibody titers of subjects against SARS-CoV-2 variants, including Omicron, all became seropositive, and significant fold-increases (21.1-52.0) were seen regardless of the disease severity of subjects. Our findings thus demonstrate that two doses of mRNA vaccination to SARS-CoV-2 convalescent patients can induce cross-neutralizing activity against Omicron.

9.
Clinical Infectious Diseases ; 03:03, 2022.
Article in English | MEDLINE | ID: covidwho-1831058

ABSTRACT

BACKGROUND: Returning universities to full on-campus operations while the COVID-19 pandemic is ongoing has been a controversial discussion in many countries. The risk of large outbreaks in dense course settings is contrasted by the benefits of in-person teaching. Transmission risk depends on a range of parameters, such as vaccination coverage and efficacy, number of contacts and adoption of non-pharmaceutical intervention measures (NPIs). Due to the generalised academic freedom in Europe, many universities are asked to autonomously decide on and implement intervention measures and regulate on-campus operations. In the context of rapidly changing vaccination coverage and parameters of the virus, universities often lack sufficient scientific insight to base these decisions on. METHODS: To address this problem, we analyse a calibrated, data-driven agent-based simulation of transmission dynamics of 13,284 students and 1,482 faculty members in a medium-sized European university. We use a co-location network reconstructed from student enrollment data and calibrate transmission risk based on outbreak size distributions in education institutions. We focus on actionable interventions that are part of the already existing decision-making process of universities to provide guidance for concrete policy decisions. RESULTS: Here we show that, with the Omicron variant of the SARS-CoV-2 virus, even a reduction to 25% occupancy and universal mask mandates are not enough to prevent large outbreaks given the vaccination coverage of about 85% recently reported for students in Austria. CONCLUSIONS: Our results show that controlling the spread of the virus with available vaccines in combination with NPIs is not feasible in the university setting if presence of students and faculty on campus is required.

10.
Clinical Infectious Diseases ; 03:03, 2022.
Article in English | MEDLINE | ID: covidwho-1831057

ABSTRACT

BACKGROUND: The current SARS-CoV-2 vaccines may be less effective against the Omicron variant. With recent resurgence of SARS-CoV-2 cases, the role of booster doses of the vaccine needs to be highlighted. METHODS: Using a retrospective cohort study design emulating a target trial, we determined the relative effectiveness of a homologous booster dose of a SARS-CoV-2 mRNA vaccine compared with primary series alone in preventing infection, hospitalization, and intensive care unit (ICU) admission, and death in the Department of Veterans Affairs healthcare system in the US. Among infection-free survivors who received two doses of an mRNA vaccine prior to April 30, 2021, we identified those who received a booster between September 22 and December 25, 2021 and 1:1 matched individuals who did not receive a booster. RESULTS: Among 2,384,272 previously uninfected persons with two doses of an mRNA vaccine by April 30, 2021, we identified 462,950 booster recipients between September 22 and December 25, 2021 who were matched 1:1 with non-booster recipients. RVE (95% CI) was 19% (17-22%) for confirmed infection, 52% (46-57%) for hospitalization, and 83% (65-92%) for ICU admission or death. Recipients of the mRNA-1273 vaccine had a lower cumulative incidence of infections and hospitalizations compared with BNT-162b2 vaccine (log-rank p-value <0.001 for both comparisons). CONCLUSION: While the RVE of SARS-CoV-2 mRNA booster vaccine dose in preventing infection against the Omicron variant is low, the RVE is substantial in preventing hospitalization and high in preventing the most severe/critical disease.

11.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-335531

ABSTRACT

Background: The Omicron (lineage B.1.1.529) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported in Wales, UK on 3rd December 2021. The aim of the study was to describe the first 1000 cases of the Omicron variant by demographic, vaccination status, travel and severe outcome status and compare this to contemporaneous cases of the Delta variant. Methods: Testing, typing and contact tracing data were collected by Public Health Wales and analysis undertaken by the Communicable Disease Surveillance Centre (CDSC). Prevalence ratios for demographic factors and symptoms were calculated comparing Omicron cases to Delta cases identified over the same time period. Results: By 14th December 2021, 1000 cases of the Omicron variant had been identified in Wales. Of the first 1000, just 3% of cases had a prior history of travel revealing rapid community transmission. Most cases (82%) were double vaccinated (65.9%) or boosted (16.1%) and overall, 0.5% were hospitalised. Conclusion: Key findings include a lower prevalence of anosmia and a reduced risk of hospitalisation in the first 1000 Omicron cases compared to co-circulating Delta cases. We also identify that existing measures for travel restrictions to control importations of new variants identified outside the UK did not prevent the rapid ingress of Omicron within Wales.

12.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-335494

ABSTRACT

Recent emergence of SARS-CoV-2 Omicron sublineages BA.2.12.1, BA.2.13, BA.4 and BA.5 all contain L452 mutations and show potential higher transmissibility over BA.2. The new variants’ receptor binding and immune evasion capability require immediate investigation, especially on the role of L452 substitutions. Herein, coupled with structural comparisons, we showed that BA.2 sublineages, including BA.2.12.1 and BA.2.13, exhibit increased ACE2-binding affinities compared to BA.1;while BA.4/BA.5 shows the weakest receptor-binding activity due to F486V and R493Q reversion. Importantly, compared to BA.2, BA.2.12.1 and BA.4/BA.5 exhibit stronger neutralization escape from the plasma of 3-dose vaccinees and, most strikingly, from vaccinated BA.1 convalescents. To delineate the underlying evasion mechanism, we determined the escaping mutation profiles, epitope distribution and Omicron sub-lineage neutralization efficacy of 1640 RBD-directed neutralizing antibodies (NAbs), including 614 isolated from BA.1 convalescents. Interestingly, post-vaccination BA.1 infection mainly recalls wildtype-induced humoral memory and elicits antibodies that neutralize both wild-type and BA.1. These cross-reactive NAbs are significantly enriched on non-ACE2-competing epitopes;and surprisingly, the majority are undermined by R346 and L452 substitutions, namely R346K (BA.1.1), L452M (BA.2.13), L452Q (BA.2.12.1) and L452R (BA.4/BA.5), suggesting that R346K and L452 mutations appeared under the immune pressure of Omicron convalescents. Nevertheless, BA.1 infection can also induce new clones of BA.1-specific antibodies that potently neutralize BA.1 but do not respond to wild-type SARS-CoV-2, due to the high susceptibility to N501, N440, K417 and E484. However, these NAbs are largely escaped by BA.2 sublineages and BA.4/BA.5 due to D405N and F486V, exhibiting poor neutralization breadths. As for therapeutic NAbs, LY-CoV1404 (Bamlanivimab) and COV2-2130 (Cilgavimab) can still effectively neutralize BA.2.12.1 and BA.4/BA.5, while the S371F, D405N and R408S mutations carried by BA.2/BA.4/BA.5 sublineages would undermine most broad sarbecovirus NAbs. Together, our results indicate that Omicron can evolve mutations to specifically evade humoral immunity elicited by BA.1 infection. The continuous evolution of Omicron poses great challenges to SARS-CoV-2 herd immunity and suggests that BA.1-derived vaccine boosters may not be ideal for achieving broad-spectrum protection.

13.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-335487

ABSTRACT

Compared to previous variants, the SARS-CoV-2 B.1.1.529 (Omicron) variant has relatively high infection rates, including among children. Even though severe COVID-19 in children is rare, this group is susceptible to the multisystem inflammatory syndrome in Children (MIS-C), long-COVID and downstream effects of COVID-19, including social isolation and education disruption. There is evidence that vaccination with an mRNA vaccine offers protection against infection and severe forms of COVID-19 for children. However, data on the effectiveness of inactivated virus vaccine, the most used platform worldwide, is scarce during the Omicron period. In Brazil, children between 6 to 11 years are eligible to receive the CoronaVac vaccine. Using a national linked database from January 21, 2022, up to April 19, 2022, during the Omicron dominant period in Brazil, we conducted a test-negative design with 194,258 tests to assess CoronaVac effectiveness against infection and severe (hospitalisation or death) outcomes among children aged 6 to 11 years. The estimated VE for symptomatic infection was 35.0% (95% CI 27.7–41.5) at 0–13 days and 41.5% (95% CI: 34.4–47.7) at ≥ 14 days post-second dose. For severe outcomes (hospitalisation or death) VE was 69.2% (95% CI: 11.7–93.6) at 0–13 days and 63.5% (95% CI: 5.8–90.0). Two doses of CoronaVac in children during the Omicron period showed low levels of protection against symptomatic infection, and modest levels against severe illness.

14.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-335477

ABSTRACT

The B.1.1.529 (Omicron) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has previously been reported as more transmissible, but less severe than other SARS-CoV-2 variants. To test this assumption, we linked state-level vaccination data with quality-controlled electronic health records from a large healthcare system, including 13 hospitals, in Massachusetts, USA. We then performed a weighted case-control study to compare risks of hospital admission and mortality across the SARS-CoV-2 waves in over 130,000 COVID patients. Although the unadjusted rates of hospital admission and mortality appeared to be higher in previous waves compared to the Omicron period, after adjusting for confounders including various demographics, Charlson comorbidity index scores, and vaccination status (and holding the healthcare utilization constant), we found that the risks of hospitalization and mortality were nearly identical between periods. Our analysis suggests that the intrinsic severity of the Omicron variant may be as severe as previous variants.

15.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-335446

ABSTRACT

Pathogenic infections cause thymic atrophy, perturb thymic-T cell development and alter immunological response. Previous studies reported dysregulated T cell function and lymphopenia in coronavirus disease-19 (COVID-19) patients. However, immune-pathological changes, in the thymus, post severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection have not been elucidated. Here, we report SARS-CoV-2 infects thymocytes, depletes CD4 + CD8+ (double positive;DP) T cell population associated with an increased apoptosis of thymocytes, which leads to severe thymic atrophy in K18-hACE2-Tg mice. CD44 + CD25- T cells were found to be enriched in infected thymus, indicating an early arrest in the T cell developmental pathway. Further, Interferon gamma (IFN-γ) was crucial for thymic atrophy, as anti-IFN-g antibody neutralization rescued the loss of thymic involution. Therapeutic use of remdesivir (prototype anti-viral drug) was also able to rescue thymic atrophy. While Omicron variant of SARS-CoV2 caused marginal thymic atrophy, delta variant of SARS-CoV-2 exhibited most profound thymic atrophy characterized by severely depleted DP T cells. Recently characterized broadly SARS-CoV-2 neutralizing monoclonal antibody P4A2 was able to rescue thymic atrophy and restore thymic developmental pathway of T cells. Together, we provide the first report of SARS-CoV-2 associated thymic atrophy resulting from impaired T cell developmental pathway and also explains dysregulated T cell function in COVID-19.

16.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-335442

ABSTRACT

The advent of Omicron variant globally hastened the requirement of a booster vaccination dose to confer continuous protection against symptomatic SARS-CoV2 infection. However, different vaccines are available in different countries and individuals who had adverse reactions to certain vaccine types require heterologous vaccine boosters. To understand the efficacy of different vaccination regimens in inducing humoral responses to SARS-CoV2, we examined plasma antibodies and frequencies of Omicron RBD-specific B cells in individuals who had different priming-booster vaccination regimens. We found that individuals with three homologous doses of mRNA vaccines had higher levels of IgG of all subclasses against RBD of Omicron than individuals with three homologous doses of inactivated virus vaccine. More importantly, individuals who received a booster dose of mRNA vaccine, regardless of the types of priming vaccine, had antibodies with higher neutralizing capability against the Omicron variant. Corroborating the antibody results, boosting with the mRNA vaccine increased the frequencies of Omicron RBD-binding B cells. Together, our data demonstrate that an mRNA vaccine (BNT162b2 or mRNA-1273) booster enhances humoral responses against Omicron variant in individuals vaccinated with either two prior doses of mRNA or inactivated virus vaccine (CoronaVac or BBIBP-CorV), potentially providing more effective protection against SARS-CoV-2 infection, particularly by the Omicron variant.

17.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-335355

ABSTRACT

The rapid emergence and worldwide detection of the SARS-CoV-2 omicron variant underscore the importance of robust genomic surveillance systems and prompt information sharing among global public health partners. The Omicron variant has rapidly replaced the delta variant as a dominating SARS-CoV-2 variant because of natural selection, favoring the variant with higher infectivity and more strong vaccine breakthrough ability. Also known as B.1.1.529, Omicron has four sub-variants, BA.1, BA.2, BA.3, and BA.4. Among them, BA.1 is the currently prevailing sub-variant, BA.2 is found to be able to alarmingly re-infect patients initially infected by omicron BA.1. BA.3 sub-variants is a combination of mutations of BA.1 and BA.2, especially in the spike protein. Today emerging is the BA.4, herein described and first detected in Italy, harboring a new mutation, specifically a deletion in the ORF 1 ab gene, corresponding to KSF141_del in non-structural protein 1 (nsp1), a critical virulence factor able to suppress host translation. The bioinformatics comparison analysis with the other three sub-variants pointed out that the deletion was not present previously and was never reported until now. Therefore, we can speculate that omicron BA.4;will become a new dominating “variant of concern”and might also break vaccine protection . On the other hand, we show that other proteins are mutated in the BA.4 in particular, seven mutations are recognized in the nucleocapsid (N) protein, the capability of five different types of rapid antigenic tests to recognize it.

18.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-335346

ABSTRACT

Genomic surveillance represents an important strategy for understanding evolutionary mechanisms, transmission profile, and infectivity of different SARS-CoV-2 variants. We assessed the epidemiological profile of 366 individuals who tested positive for SARS-CoV-2 from 29 municipalities in Rondônia between December 2021 to March 2022. Samples were collected, RNA was ex-tracted and screened using RT-qPCR for Alpha, Beta, Gamma, Delta and Omicron VOCs and viral quantification was performed. Sequences were analyzed for phylogeny, mutations and lineages. Of the samples analyzed, 93.71% were positive for the Omicron variant and 6.28% were positive for the Delta variant. The symptoms observed were cough, sore throat, and fever, with a mean duration of 5 days;no hospitalizations or deaths were reported. We noted that among the positive individuals, 51% had been immunized with two doses, 22% received three doses, 13% received one dose, and 13% were not immunized. Just 242 samples were amenable to analysis for alignment and phylogenetic characterization;corresponding to variants BA.1 and BA.1.1;a total of 120 mutations were identified, 36% of which were found in the S gene. In conclusion, there was a high frequency of mutations in the SARS-CoV-2 genome, but no record of clinical severity, demonstrating the positive effect of vaccination.

19.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-335281

ABSTRACT

The SARS-CoV-2 Omicron variant is increasing in prevalence around the world. Accurate estimation of disease severity associated with Omicron is critical for pandemic planning. We found lower risk of accident and emergency (AE) attendance following SARS-CoV-2 infection with Omicron compared to Delta (HR: 0.39 (95% CI: 0.30 – 0.51;P<.0001). For AE attendances that lead to hospital admission, Omicron was associated with an 85% lower hazard compared with Delta (HR: 0.14 (95% CI: 0.09 – 0.24;P<.0001)). Conflicts of Interests Nothing to declare. Funding statement This work was supported by the Medical Research Council MR/V015737/1. TPP provided technical expertise and infrastructure within their data centre pro bono in the context of a national emergency. Rosalind Eggo is funded by HDR UK (grant: MR/S003975/1), MRC (grant: MC_PC 19065), NIHR (grant: NIHR200908).

20.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-335279

ABSTRACT

We aimed to describe the outcomes of Omicron infection in kidney transplant recipients (KTR), compare the efficacy of the community therapeutic interventions and report the safety profile of molnupiravir. From 142 KTRs diagnosed with COVID-19 infection after Omicron had become the dominant variant in the UK, 116 (78.9%) cases were diagnosed in the community;47 receiving sotrovimab, 21 molnupiravir and 48 no treatment. 10 (20.8%) non-treated patients were hospitalised following infection, which was significantly higher than the sotrovimab group (2.1%), p=0.0048, but not the molnupiravir treated group (14.3%), p=0.47. The only admission following sotrovimab occurred in a patient infected with BA.2. One patient from the molnupiravir and no-treatment groups required ICU support, and both subsequently died, with one other death in the no-treatment group. No patient receiving sotrovimab died. 6/116 (5.2%) patients required dialysis following their diagnosis;2 (9.5%) patients receiving molnupiravir and 4 (8.3%) no-treatment. This requirement was significantly higher in the molnupiravir group compared with the sotrovimab treated patients, in whom no patient required dialysis, p=0.035. Both molnupiravir treated patients requiring dialysis had features of systemic thrombotic microangiopathy. Post-vaccination serostatus was available in 110 patients. Seropositive patients were less likely to require hospital admission compared with seronegative patients, 6 (7.0%) and 6 (25.0%) respectively, p=0.023. Seropositive patients were also less likely to require dialysis therapy, p=0.016. In conclusion, sotrovimab treatment in the community was associated with superior patient and transplant outcomes;it’s clinical efficacy against the BA.2 variant requires a rapid review. The treatment benefit of molnupiravir was not evident, and wider safety reporting in transplant patients is needed.

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