CT chest differences reveal less severe infection with omicron compared to delta

29th June 2022

CT chest changes are less severe with the omicron COVID-19 variant compared to delta and help explain the better patient outcomes with delta

Computed tomography (CT) chest scan changes after infection with the omicron COVID-19 variant are less severe than those seen with the delta variant and lead to better patient outcomes. This was the conclusion of an analysis of CT chest scans by researchers from Oxford University, UK.

The COVID-19 omicron variant of concern was first identified in South Africa in November 2021 and an analysis in January 2022 suggested a significantly reduced chance of being hospitalised for individuals infected with the omicron variant compared to previous variants of concern. In fact, the authors suggested that this reduction in severity was most likely due due to a degree of protection from prior immunity.

While there is evidence to show that among those who experience a breakthrough COVID-19 infection, examination of CT chest scans indicate a lower level of pneumonia, the study did not provide any information on the infective variants involved. Moreover, a CT chest has become a valuable tool for the detection of both alternative diagnoses and complications of COVID-19, but to date, there is a lack of information on the CT changes induced after infection with different COVID-19 variants.

For the present study, the Oxford team compared the radiological patterns, imaging characteristics and disease severity on initial CT chest angiograms of patients infected with the omicron and delta variants of concern.

They retrospectively collected data on patients hospitalised and with a PCR confirmed positive COVID-19 test, using the S gene target failure as a surrogate for omicron infections. For the CT chest scans, a severity score (CT-SS) was calculated (ranging from 0 to 25, with higher scores reflecting greater severity) and CT imaging features such as bronchial wall thickening were also assessed.

Additional data collected included demographics, co-morbidities, laboratory findings, in-hospital treatments and clinical outcomes. Logistic regression models were created and adjusted for potential confounding variables to identify any differences in outcomes for the two variants.

CT chest changes induced by omicron and delta variants

A total of 106 adult patients with a mean age of 58 years (55% male) were included in the final analysis, of whom, 66 were infected with the delta variant.

Based on the CT chest findings, a higher proportion of scans were categorised as normal in patients with omicron compared to delta (37% vs 15%, omicron vs delta, p = 0.016). Interestingly, only 40% of those infected with omicron compared to 83% of those with delta, displayed the typical signs of pneumonia.

Patients infected with omicron had a lower median CT-SS score compared to those with delta (3.5 vs 11.8). Furthermore, bronchial wall thickening was more common in those with omicron (odds ratio, OR = 2.4, 95% CI 1.01 – 5.92, p = 0.04).

Infection with the delta variant was also associated with a higher odds of more severe infection (OR = 4.6, 95% CI 1.2 – 26, p = 0.01) and critical care admission (OR = 7).

The authors concluded that infection with the omicron variant is associated with fewer and less severe changes on a CT chest compared to the delta variant and led to better patient outcomes.

Citation
Tsakok MT et al. Chest CT and Hospital Outcomes in Patients with Omicron Compared with Delta Variant SARS-CoV-2 Infection Radiology 2022

Study shows that BNT162b vaccination reduces risk of Omicron-associated hospitalisation by two-thirds in children aged 5-11 years

22nd April 2022

A study by researchers in the US has concluded that BNT162b vaccination given to children aged 5 to 11 years reduced the risk of Omicron-associated hospitalisation by more than two-thirds but was less effective against hospitalisation among adolescents.

BNT162b2 vaccination in 12 to 15-year-old recipients has been shown to have a favourable safety profile, produce a greater immune response than in young adults and be highly effective against COVID-19. Nevertheless, data on vaccine effectiveness have only been assessed up to 3 months post-vaccination and the available data preceded circulation of the Omicron COVID-19 variant. Furthermore, there are limited data on the effectiveness of vaccines in younger children, although one study has indicated that vaccination against laboratory-confirmed COVID-19-associated hospitalisation among children aged 5-11 years was 74%, and between 14 and 67 days after a second dose, although this estimate had wide confidence interval (–35% to 95%) that included zero.

For the present study, the US team set out to determine the duration of protection from BNT162b vaccination in adolescents during different periods of time in which the Delta and Omicron were the dominant circulating strains. They also examined the protection of the vaccine against hospitalisation in children aged 5 to 18 years of age infected with the Omicron variant.

The team used a case-control, test-negative design to assess BNT162b effectiveness against COVID-19-related hospitalisation and against critical illness. The researchers also included a group of control patients who were in the same age categories and defined as hospitalised individuals who tested negative for COVID-19 and with no recognised symptoms of the virus. The effectiveness of BNT162b vaccination was assessed after 2 to 22 weeks and after longer than 22 weeks.

BNT162b vaccination and COVID-19

Among those hospitalised aged 12 – 18, there were 918 case patients with a median age of 16 years (50% female), of whom 78% had at least one underlying health condition. In addition, there were 267 case patients with a median age of 8 years (43% female) and of whom 82% had at least one underlying health condition.

Overall among the 1185 cases (i.e., 267 and 918), 25% had critical COVID-19, 14 of whom died. In the 12 to 18 group (918 cases), 27% had critical COVID-19 and 13 died. In the 5 – 11 group (267 cases), 16% had critical COVID-19, one of whom died.

The effectiveness of BNT162b vaccination against COVID-19-associated hospitalisation among adolescents was 92% during the Delta period, 2 to 22 weeks after vaccination and 92% between 23 and 44 weeks post-vaccination. However, during the omicron period, vaccine effectiveness was only 40% against COVID-19-associated hospitalisation, 2 to 22 weeks after vaccination and dropped slightly to 38% between 23 and 44 weeks post-vaccination. Nevertheless, during the Omicron period, vaccine effectiveness was 79% against critical COVID-19 but only 20% against non-critical illness.

Among those aged 5 – 11 years of age, vaccine effectiveness against COVID-19-associated hospitalisation was 68% during the Omicron period, a median of 34 days after vaccination.

The authors concluded that vaccination in children aged 5 to 11 years reduced the risk of COVID-19-associated hospitalisation by two-thirds during the Omicron period adding that while vaccination was less effective in adolescents during the omicron period, it was still able to prevent critical illness.

Citation
Price AM et al. BNT162b2 Protection against the Omicron Variant in Children and Adolescents N Engl J Med 2022

Large study confirms less severe outcomes after infection with Omicron compared with Delta variant

29th March 2022

A large UK comparative analysis has found that infection with the Omicron COVID-19 variant leads to less severe outcomes than with Delta

Individuals who become infected with the Omicron COVID-19 variant experience less severe outcomes such as hospitalisation and death compared to those with the Delta variant according to the results of a large study by a multi-disciplinary group of UK researchers.

The Omicron COVID-19 variant has produced a surge of infections and been found to be associated with high transmission among household contacts, particularly among those who lived with index patients who were not vaccinated or who did not take measures to reduce the risk of transmission to household contacts.

Nevertheless, despite a higher level of transmissibility, studies have also suggested that the Omicron variant is associated with substantial severity of illness in comparison to the Delta variant.

With an increasing number of individuals now fully vaccinated against COVID-19, the purpose of the present study was to offer a more detailed understanding of the overall impact of both less severe outcomes and greater immunity on rates of hospitalisation and mortality during the Omicron wave.

The UK team obtained individual-level data on confirmed cases of COVID-19 infection in England between November 2021 and 9 January 2022 and linked these to vaccination status, hospital attendance and admission as well as deaths.

During the period of study genomic sequencing was performed for some of the infections which enabled the team to distinguish between the two variants. For the study, a hospital admission was defined as a stay of at least one or more days. The analysis was stratified by age, vaccination status and adjusted for sex, deprivation index and evidence of prior infection.

Omicron caused less severe outcomes

During the period of study there were 4,135,347 confirmed cases of COVID-19, of which 1,526,702 (37%) had information on the infecting variant and consisted of 448,843 Delta and 1,067,859 Omicron cases.

The adjusted hazard ratio (HR) for attendance at hospital, but not necessarily admission, was lower for Omicron than Delta (HR = 0.56, 95% CI 0.54 – 0.58). In addition, compared to Delta, the risk of hospital admission among those infected with Omicron was 59% lower (HR = 0.41, 95% CI 0.39 – 0.43) and the risk of death within 28 days was 69% lower (HR = 0.31, 95% CI 0.26 – 0.37).

When stratified by age, there was no difference between the two variants among those 10 years of age and younger (HR = 1.10, 95% CI 0.85 – 1.42). However, there was a significant difference and reduction among those at least 80 years of age (HR = 0.47, 95% CI 0.40 – 0.56).

For both of the variants, prior infection offered protected against death in those who were vaccinated (HR = 0.47) and unvaccinated (HR = 0.18). Interestingly, among those who were vaccinated, prior infection appeared to offer no additional protection against infection (HR = 0.96, 95% CI 0.88 – 1.04), which was in contrast to those who were unvaccinated but had a previous infection (HR = 0.55, 95% CI 0.48 – 0.63).

The authors concluded that the less severe outcomes observed for Omicron were largely driven by a less severe variant and increased immunity due to vaccination.

Citation
Nyberg T et al. Comparative analysis of the risks of hospitalisation and death associated with SARS-CoV-2 omicron (B.1.1.529) and delta (B.1.617.2) variants in England: a cohort study Lancet 2022

Vaccination leads to smaller reduction in transmission of delta compared to alpha COVID-19 variants

13th January 2022

Vaccination against COVID-19 leads to a higher level of transmission for the delta compared to the alpha variant

Vaccination has been found to result in a smaller reduction in the transmission of the Delta compared to the alpha variant according to a study by researchers from Oxford University, UK.

Vaccination against COVID-19 has been shown to reduce symptomatic infection and even onward transmission of the virus among household contacts. Furthermore, some data indicates that this reduced risk of onward transmission is because of a lower viral load among vaccinated individuals although other evidence points to a similar viral load among those who are vaccinated but infected with the Delta variant.

For the present study, the Oxford team used national contact testing data in England for adults (> 18 yeas of age) with both symptomatic and asymptomatic infections. Their analysis included vaccination with either BNT162b2 or ChAdOx1 to investigate differences in transmission from index patients infected with either variant. The analysis included regression models to determine any associations between onward transmission and the vaccination status of the index patient.

Findings

Among 146,243 tested contacts from a total of 108,498 index patients, with a median age of 34 years (51% female), 37% had a positive PCR test.

Using regression modelling, among index patients doubly vaccinated with BNT162b2 and who became infected, there was a significantly reduced risk of onward transmission of the Alpha variant (adjusted rate ratio, aRR = 0.32, 95% CI 0.21 – 0.48) compared unvaccinated individuals. Similarly, those with two vaccinations of ChAdOx1, also had a reduced risk of onward transmission (aRR = 0.48, 95% CI 0.30 – 0.78) compared to the unvaccinated.

In contrast, the extent of onward transmission of the Delta variant was reduced compared to Alpha by both vaccines but was greater among those doubly vaccinated with BNT162b2 (aRR = 0.50, 95% CI 0.39 – 0.65) compared to ChAdOx1 (aRR = 0.76, 95% 0.70 – 0.82). In other words, index patients vaccinated with BNT162b2 were less likely to have contacts with a positive PCR test for Delta compared to those given the ChAdOx1 vaccine.

The Delta variant was also associated with more onward transmission from both symptomatic index patients (aRR = 1.24, 95% CI 1.12 – 1.38) and from asymptomatic individuals (aRR = 1.40, 95% CI 1.22 – 1.59) and this was independent of both index and contact vaccination status.

Interestingly, the risk of infection with the Alpha variant among fully vaccinated contacts, was much lower among those given BNT162b2 (aRR = 0.15, 95% CI 0.11 – 021) compared to those fully vaccinated with ChAdOx1 (aRR = 0.40, 95% CI 0.27 – 0.59) and the magnitude of these reductions were similar for infections with the Delta variant.

Both symptomatic and asymptomatic index patients infected with the Delta variant had lower Ct values (i.e., higher viral loads) compared to those infected with the Alpha variant. When including Ct values in their regression models, the authors reported that lower Ct values were independently associated with increased transmission of either variant.

The authors concluded that vaccination was associated with a smaller reduction in transmission of the Delta compared to the Alpha variant.

Citation

Eyre DW wt al. Effect of Covid-19 Vaccination on Transmission of Alpha and Delta Variants. N Eng J Med 2022.

Janssen vaccine effective against COVID-19 delta variant

5th July 2021

The COVID-19 Delta variant is spreading around the world and preliminary data suggests the Janssen vaccine could protect against this variant.

With a number of COVID-19 vaccines in clinical testing, the Janssen vaccine, Ad26.COV2. S, has received emergency use authorisation in over 50 countries. The vaccine is designed to be given as a prime dose without the need for a boost and studies have shown a vaccine efficacy of 66.9%, 14 days after administration.

Nevertheless, while all of the available vaccines appear to be effective, with the emergence of an increasing number variants, it is important to evaluate the efficacy against these evolving mutants, especially those, such as the Delta variant, which appear to have a greater degree of transmissibility.

While data from a small number of patients vaccinated with Ad26.COV2. S have indicated a reduction in antibody binding titre against some variants including the B.1.351 (South Africa), the alpha variant (B.1.1.7, UK), functional non-neutralising antibody and T cell responses were largely preserved after vaccination although the significance of these findings are uncertain.

As there are currently no data on whether the Ad26.COV2. S is effective against the Delta COVID-19 variant, a team from Janssen Vaccines & Prevention, Leiden, The Netherlands, have examined the in vitro binding and neutralising titres detected in sera of adults from the phase 3 EMSEMBLE trial against several variants of concern, including the delta variant.

Participants in the EMSEMBLE trial were immunised with a single dose of the Ad26.COV2. S vaccine and sera collected 71 days and tested against a range of COVID-19 variants, including the original Wuhan strain and a number of variants, e.g., B.1, alpha (B.1.1.7), Beta (B.1.251), Zeta (P.2), Gamma (B.1.617) and Delta (B.1.617.2).

Findings

Sera from a total of eight patients, ranging in age from 47 to 91 years, were assessed for the ability to bind to B.1. Spike protein and neutralising capacity against the COVID-19 variants using a pseudo-virus neutralisation assay.

The neutralisation against B.1.1.7 and B.1 were similar but for the other variants, binding was reduced. For example, it was reduced 1.5-fold against B.1.617 but the greatest reductions occurred against B.1.351 (3.6-fold) and B.1.617 (3.4-fold). However, for the delta variant (B. 1.167.2), there was only a 1.6-fold reduction in neutralising sensitivity.

In their discussion, the authors noted that in the absence of real-world data, the efficacy of Ad26.COV2. S against the delta variant remains unknown but confirmation of its efficacy may arise from the ongoing Phase III trials.

Nevertheless, using UK data showing how both the Pfizer-BioNTech vaccines appear to be effective against the Delta variant, the authors suggest it is likely that this will also be true for Ad26.COV2. S.

They concluded that while in vitro neutralising antibody titres against the delta variant were found to be lower, levels are still sufficient to protect individuals and that the enhanced non-neutralising antibody response may also prove to be a relevant factor.

Citation
Jongeneelen M et al. Ad26.COV2. S elicited neutralising activity against Delta and other SARSCoV2.S variants of concern. 2021 BioRxiv preprint.

Scottish data suggest COVID-19 vaccines protect against Delta variant of concern

28th June 2021

Early findings from a Scottish study indicate that, in fully vaccinated individuals, COVID-19 vaccines are protective against the Delta variant.

With the emergence of COVID-19 variants, there is a race to ensure that the whole adult population is vaccinated to reduce the risk of severe illness and hospitalisation. But what is the real-world effectiveness against the predominant COVID-19 variants?

This was a question posed in a preliminary analysis of data from EAVE II, a Scotland-wide surveillance programme which contains data on 5.4 million people (around 99% of the Scottish population), by researchers from Public Health Scotland.

In a letter to the Lancet, the researchers used this database to profile COVID-19 patients and explore the risk of hospitalisation for the virus and to estimate the effectiveness of vaccines at preventing hospital admissions.

They focused on two COVID-19 variants of concern (VOC); the alpha VOC (S gene negative) and the Delta VOC (S gene positive). The analysis was based on all individuals who had a PCR test and compared the proportion of cases which were positive among individuals who had been vaccinated with those who were unvaccinated.

The team defined a COVID-19 hospital admission as being within 14 days of testing positive for virus or individuals who tested positive within 2 days of hospitalisation. The period of analysis was 1 April to 6 June 2021.

Findings

Prior to the period of analysis, 44.7% of the population in Scotland had received at least one dose of a COVID-19 vaccine and 7.6% had been fully vaccinated. By the end of the study period (6 June), the proportion of adults who had received at least one vaccine dose rose to 59.4% and 39.4% had been fully vaccinated.

There were 19,543 confirmed positive COVID-19 infections during the period of study, of whom 377 were admitted to hospital. In addition, 7723 (39.5%) of infections and 124 (35.5%) of hospital admissions were for the Delta VOC and 70% of infections occurred in those without any vaccination.

Using regression analysis, the researchers calculated that delta VOC cases were associated with an increased risk of hospitalisation (hazard ratio, HR = 1.85, 95% CI 1.39 – 2.47) compared with the Alpha VOC. Moreover, the risk of hospitalisation increased with the number of COVID-19 relevant co-morbidities.

Among those infected with the alpha VOC, the risk of hospitalisation was significantly reduced (HR = 0.28) for vaccinated compared to unvaccinated individuals. Similarly, the risk was reduced among those infected with the delta VOC (HR = 0.38).

In terms of vaccine effectiveness in the whole cohort, 14 days after being fully vaccinated with the BNT162b vaccine, there was a good level of protection against the alpha VOC although this was reduced for the delta VOC (92% vs 79%, Alpha VOC vs Delta VOC). In contrast, protection with the ChAdOx1 was lower (73% vs 60%, alpha VOC vs delta VOC).

In summarising their findings, the authors noted that the risk of hospitalisation was nearly double with the Delta VOC compared with the Alpha VOC. Moreover, while the results suggested that the BNT162b vaccine appeared to be more effective against the Delta VOC, the small number of cases meant that these results should be interpreted with caution.

Citation
Shiekh A et al. SARS-CoV-2 Delta VOC in Scotland: Demographics, Risk of Hospital Admission, and Vaccine Effectiveness. Lancet 2021.

Latest REACT-1 findings indicate a surge in infections

21st June 2021

Despite the national rollout of the COVID-19 vaccine, the latest results from latest (round 12) REACT-1 study reveal that since the end of May 2021, cases of COVID-19 in England have been increasing.

The results are based on random testing of approximately 110,000 people using a throat and nose swab between 20 May and 7 June 2021. Each time the results are available, the REACT-1 team compare the results with those obtained in the penultimate survey (in this case, 15 April to 3 May 2021).

For round 12, the researchers identified 135 positive samples from 108,911 valid swabs which gives a weighted prevalence of 0.15% (95% CI 0.12-0.18%). In round 11, the weighted prevalence was 0.10% (95% CI 0.08 – 0.13%) and, with the latest figures, the team has estimated that the reproduction or R rate for England is 1.44, an increase from 1.07 in the previous round.

National variation

As with earlier rounds, the REACT-1 team have observed considerable regional variability. For instance, the weighted prevalence is highest in the North West (0.26%) and lowest in the South West (0.05%).

The prevalence is also very different across age ranges. Among those aged five to 12 years and 18-24, there is a much higher prevalence (0.35% and 0.36% respectively) compared to those aged 65 years and over (0.07%).

It is also still higher among those of Asian ethnicity (0.28%) compared with people of white ethnicity (0.13%) and varies considerably with the household size. For instance, the prevalence ranges from 0.07% among those living alone to 0.34% where there are six or more household members.

In line with other data, the results from round 12 show that around 90% of swab samples subjected to genomic analysis were for the Delta variant. As this latest variant is known to be more transmissible, the REACT-1 authors have estimated a doubling time of infections of 11 days.