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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

Subclinical axillary lymphadenopathy due to COVID-19 vaccine seen on mammograms

10th December 2021

Subclinical axillary lymphadenopathy seen on mammography suggests scans are done before or several weeks after COVID-19 vaccination

The presence of subclinical axillary lymphadenopathy (sLAD) on mammography was significantly more likely among women who had received a COVID-19 vaccination, indicating that they should either delay screening or schedule visits before vaccination. This was the finding of a retrospective study by a team from the Baylor University Medical Center, Dallas, USA.

The term lymphadenopathy refers to lymph nodes that are abnormal in size and axillary lymphadenopathy, describes changes in the size and consistency of lymph nodes in the armpit. There are several potential causes of unilateral axillary lymphadenopathy including breast cancer and which therefore warrants further diagnostic investigations if these changes are observed during screening. Although the presence of sLAD has been observed in women who have received a COVID-19 vaccination, what remains uncertain, is the proportion of vaccinated women that will develop these lesions after either the Pfizer or Moderna vaccines.

Based on case reports of sLAD in vaccinated women, for the present study, the authors investigated the prevalence of the condition in all women who had attended a breast screening programme since December 2020 until April 2021. Data from medical records included the woman’s vaccination status, the vaccine received and the presence or absence of sLAD on mammography. The researchers cross-referenced prior imaging for all women to ensure that there was no baseline evidence of an axillary lymphadenopathy and excluded women who had presented for diagnostic mammography for a palpable axillary lump or pain and those with a history of breast cancer.

Findings

In total, 1027 women with a mean age range of 56.4 to 63.7 years were included in the analysis. There were 158 who received the Moderna vaccine, 144 (Pfizer) and 725 who had not been vaccinated. From these 1027 women, 43 (4.2%) had an sLAD; 3.3% of those who had been vaccinated compared to 0.9% who were unvaccinated and this difference was statistically significant (p < 0.01).

When comparing the two vaccines, the incidence of unilateral axillary lymphadenopathy was higher among those who received the Pfizer vaccination (13.2% vs 9.5%, Pfizer vs Moderna). Among the 43 women with sLAD and who were recalled after screening, vaccine induced sLAD was more likely to have resolved when re-scanned an average of 46.5 days since their COVID-19 vaccination.

The authors concluded that women who have received a COVID-19 vaccination within 8 weeks of their screening mammogram, were significantly more likely to present with a subclinical axillary lymphadenopathy and that this could result in unnecessary further diagnostic workload. They suggested that providers should either delay screening mammograms by 8 weeks in patients who have been vaccinated or that screening should be undertaken before vaccination to avoid unnecessary follow-up.

Citation

Raj S et al. COVID-19 vaccine-associated subclinical axillary lymphadenopathy on screening mammogram Acad Radiol 2021


mRNA-1273 vaccine associated with lower risk of COVID-19 outcomes than BNT162b

8th December 2021

mRNA-1273 appears to be associated with a lower risk of COVID-19-related outcomes such as infection, hospitalisation and death compared to BNT162b. This was the finding of the first head-to-head vaccine effectiveness analysis undertaken by a group of researchers from the Brigham and Women’s Hospital, Harvard Medical School, Boston, US.

Randomised controlled trials have already demonstrated the effectiveness of the currently available COVID-19 vaccines. For instance, the mRNA-1273 vaccine (Moderna) has an efficacy of 94.1% at preventing COVID-19 illness and that a similar efficacy (95%) has been observed for BNT162b (Pfizer-BioNTech).

However, despite this near identical level of efficacy, other work has suggested that there might be differences between these two vaccines, even though they have the same mode of action. One study, for example, indicated that the mRNA-1273 vaccine produced a higher humoral immunogenicity than BNT162b, while other data show that the Moderna vaccine it is associated with a two-fold reduced risk of breakthrough infections compared to BNT162b and also results in a lower incidence of COVID-19-related hospitalisations.

For the present study, the US team turned to data from the national healthcare databases of the Department of Veterans Affairs, which is the largest US integrated healthcare system. The researchers sought to compare the relative effectiveness of the Moderna and Pfizer-BioNTech vaccines with respect to documented COVID-19 infections, symptomatic COVID-19, hospitalisation, admission to an intensive care unit (ICU) and death. In addition, the team examined the effectiveness of the two vaccines against the delta COVID-19 variant and examined these outcomes after 24 weeks.

Findings

During the period of study, there were 367,113 recipients of the BN162b and 397,690 of the mRNA-1273 vaccines. Over a 24-week period, 2016 COVID-19 infections were documented, of which 559 were detected as symptomatic, 411 which led to hospitalisation, 125 ICU admissions and 81 deaths.

The absolute risk of infection was low in both vaccine groups; 5.75 events per 1000 persons with the Pfizer-BioNTech and 4.52 with the Moderna vaccine. The 24 week risk ratio for infections for BNT162b compared to mRAN-1273 was 1.27 (95% CI 1.15 – 1.42), 1.39 for symptomatic infection, 1.70 for hospitalisation, 1.38 for ICU admission and 1.11 for death. Each of these risks was statistically significant apart from the risk of death. The overall risk difference expressed as events over 24 weeks per 1,000 persons was 1.23 for a documented infection.

Using these data, the authors calculated the number needed to vaccinate with mRNA-1273 instead of BN162b to prevent one case of documented infection was 813.

Analysis during the time period characterised by dominance of the delta COVID-19 variant, there was a 58% higher risk of infection in those vaccinated with BNT162b although this difference was non-significant (risk ratio = 1.58, 95% CI 0.85 – 2.33).

Commenting on these findings, the authors highlighted how their study had shown that recipients of the BNT162b vaccine had a 27% higher risk of a documented COVID-19 infection and a 70% increased risk of hospitalisation compared to the Moderna vaccine.

They concluded that the data provided evidence of a lower 24-week risk of COVID-19-related outcomes among those receiving the m-RNA-1273 vaccine compared to BNT162b.

Citation

Dickerman BA et al. Comparative Effectiveness of BNT162b2 and mRNA-1273 Vaccines in U.S. Veterans. New Eng J Med 2021

Comirnaty COVID-19 booster shows greater than 90% effectiveness in over 50s

6th December 2021

A Comirnaty booster dose given to those aged 50 years and over provides >90% vaccine effectiveness against COVID-19 infection

A Comirnaty booster dose in those over the age of 50 provides a greater than 90% vaccine effectiveness, irrespective of whether individuals had been previously fully vaccinated with ChAdOx1-S (AstraZeneca) or Comirnaty (BNT162b). This was the finding of a study by a team from the UK Health Security Agency, UK, which is available online but not published in a peer-reviewed journal.

With evidence that the efficacy of COVID-19 vaccines wanes 20 weeks after vaccination, the Joint Committee on Vaccination and Immunisation (JCVI) in the UK issued a statement highlighting the need for a booster dose of COVID-19 vaccines in an effort to combat the virus during the winter months. Moreover, after a review of the available data on booster responses, the JCVI advised a preference for the Comirnaty vaccine as the booster dose irrespective of which product was used to provide the initial full vaccination.

In the present study, the UK team sought to estimate the real-world effectiveness of a single Comirnaty booster dose in those aged 50 years and older. The researchers compared vaccination status in this patient cohort, who were symptomatic for COVID-19 and with a positive PCR test result. Data was obtained from the National Immunisation Management System (NIMS) and a booster dose was defined as one given 140 days or more after a second vaccination dose. Vaccine effectiveness was adjusted in regression models for age, deprivation, ethnicity, care home residence status and co-morbidities. The analysis was also stratified by the primary vaccination received, i.e., either ChAdOx1-S (AstraZeneca) or Comirnaty and vaccine effectiveness assessed at several time points e.g., 2 to 6 days post booster dose and 14 or more days later.

For the primary analysis, the team compared vaccine effectiveness in those who received a booster with those who had been fully vaccinated but without a booster dose. In a secondary analysis, they determined the absolute vaccine effectiveness which was the difference in rates of infection between those who had two doses (at least 140 days apart) and a booster with those who were unvaccinated.

Findings

There were 271,747 eligible tests in people 50 years and older, of which 13,568 (5%) were unvaccinated with the remainder being fully vaccinated with either ChAdOx1-S or comirnaty (BNT162b)

The vaccine effectiveness from a BNT162b booster in those who were fully vaccinated with ChAdOx1-S was 87.4% (95% CI 84.9 – 89.4) and 84.4% (95% CI 82.8 – 85.8%) in those fully vaccinated with BNT162b.

In the secondary analysis, compared with unvaccinated individuals, those fully vaccinated with a primary course of ChAdOx1-S had an absolute vaccine effectiveness of 93.1% (95% CI 91.7 – 94.3%) and 94% (95% CI 93.4 – 94.6%) in those fully vaccinated with BNT162b.

Interestingly, when compared with those who were fully vaccinated but had not received a booster dose, the vaccine effectiveness after 20 or more weeks was 44.1% for the ChAdOx1-S vaccine and 62.5% for BNT162b.

In their conclusion, the authors wrote ‘our study provides real world evidence of significant increased protection from the booster dose against symptomatic disease in those aged over 50 years of age irrespective of which primary course was received.’

Citation

Andrews N et al. Effectiveness of BNT162b2 (Comirnaty, PfizerBioNTech) COVID-19 booster vaccine against
COVID-19 related symptoms in England: test negative case-control study
.

Comirnaty COVID-19 vaccine approved by EMA for children aged 5 – 11

30th November 2021

Comirnaty has now been granted a license extension and approved by the EMA for COVID-19 vaccination in children aged 5 to 11 years of age

Comirnaty is the COVID-19 vaccine made by Pfizer-BioNTech and has now been approved by the EMA for use in children aged between 5 and 11 years of age given as two doses, three weeks apart. The vaccine was previously approved for use in adults and children from the age of 12.

Although a study published in Nature Medicine in November 2021, reported that the majority of children and young people infected with COVID-19 survive, the analysis was based on the wild-type and alpha variant only. However, more recent data from the US, shows that once the delta variant became the dominant COVID-19 strain in circulation, weekly COVID-19–associated hospitalisation rates among children and adolescents rose nearly five-fold during late June–mid-August 2021.

Based on these findings, the Centers for Disease Control in the US considered that ‘preventive measures to reduce transmission and severe outcomes in children and adolescents are critical, including vaccination, universal masking in schools, and masking by persons aged ≥2 years in other indoor public spaces and child care centers.’

Clinical efficacy in younger children

The EMA approval of comirnaty in children from the age of 5 was based on a single study of the vaccine in those aged 5 to 11 years. The study itself was undertaken in two stages; an initial phase 1 dosing-finding trial, in which a total of 48 children 5 to 11 years of age, received two 10-μg doses of BNT162b2 administered 21 days apart (which was a third of the dose given for 12 to 15 year olds), after which, the participants were randomised in a 2:1 ratio and given two 10 μg doses BNT162b2 or saline placebo.

The study examined the immunogenicity of the 10-μg dose but also the vaccine efficacy against confirmed COVID-19 infection which had an onset at least 7 days after the second dose. For the phase 2 arm of the study, 2268 children with a mean age of 8.2 years (52.1% male) were randomised to BNT162b2 or placebo. The immunogenicity showed a similar geometric mean ratio to that achieved from a 30-μg dose given to older children.

In terms of vaccine efficacy, there were three cases of COVID-19, with an onset 7 or more days after the second vaccination dose in the BNT162b2 group and 16 among placebo recipients, giving a vaccine efficacy of 90.7% (95% CI, 67.7 to 98.3). 

While the EMA has approved comirnaty in younger children, this has not occurred in the UK, with the MHRA only approving vaccination for those aged 12 – 15 years.

Source. EMA News 25th November 2021

Haematological cancer patients at increased risk of severe breakthrough COVID-19 infections

22nd November 2021

Haematological cancer patients have been found to be at an increased risk of severe breakthrough COVID-19 infections

Haematological cancer patients are still at an increased risk of severe COVID-19 infections despite receiving two vaccination doses. This is according to a preliminary analysis of a disease register by researchers from Fondazione Policlinico Universitario Agostino Gemelli, Rome, Italy.

In April 2020, the European Haematological Association – infectious Diseases Working Party, established an open, web-based registry, EPICOVIDEHA. This was designed with a view to collecting information on the epidemiology, risk factors and mortality rates among patients with haematological cancer, who became infected with COVID-19. This was considered necessary given how patients with these malignancies and therefore a dysfunctional immune system are at an increased risk of complications if infected with COVID-19. Published data from the registry on 3801 patients has already shown a mortality rate of 31.2%, of whom, 58% died due to COVID-19 and 13.1% due to a combination of their malignancy and COVID-19.

However, since the introduction of COVID-19 vaccines, it is likely that the mortality rate would have been substantially lower. As a result, the Italian team prospectively collected registry data on adults who were either partially or fully vaccinated and who developed breakthrough COVID-19 infections, to assess the efficacy of the vaccines among those with haematological cancer. The register was used to capture data on the underlying condition of the patients before infection with COVID-19, their malignancy and vaccination status and details of their infection, e.g., disease severity, hospitalisation and mortality. They deemed fully vaccinated individuals as those form whom the second vaccine dose was administered 14 days before COVID-19 symptom onset or a positive PCR test result.

Findings

The researchers identified 113 patients with COVID-19 episodes and which occurred among both partially and fully vaccinated individuals with a haematological cancer. The median age of the patients was 66 years (61.1% male) and the most common malignancies were chronic lymphoid leukaemia (24.8%) and non-Hodgkin lymphoma (31.9%) and slightly more patients had active (53.1%) compared to controlled disease (45.1%) before infection with COVID-19. In addition, 87 (77%) of patients were fully vaccinated. From a subset of 40 of these fully vaccinated patients, only 13 (32.5%) had mounted an antibody response to vaccination with the remaining patients (67.5%) deemed non-responders.

Overall, 79 (60.4%) of haematological cancer patients had a severe COVID-19 infection, with 66.4% hospitalised and 21.3% admitted to an intensive care unit. Thirty days post-COVID-19 infection, the overall mortality rate was 12.4% (14 patients) and 10 of the 14 died due to their underlying malignancy. Interestingly, there were no differences in mortality between partially or fully vaccinated individuals (15.4% vs 11.5%, partial vs full vaccination, p = 0.73) or in terms of whether patients were considered as responders or non-responders to vaccination.

While the authors recognised that this was preliminary data, they are continuing to recruit haematological caner patients and will draw further conclusions once more data becomes available.

Citation

Pagano L et al. COVID-19 in vaccinated adult patients with hematological malignancies. Preliminary results from EPICOVIDEHA. Blood 2021.

Breast milk found to contain neutralising COVID-19 antibodies

17th November 2021

Breast milk from both vaccinated and previously infected women has been found to produce antibodies to live COVID-19 virus.

Samples of breast milk obtained from women who had been either vaccinated or previously infected with COVID-19 contained antibodies capable to mounting a robust response to live virus. This was the conclusion of a study by researchers from the Division of Allergy and Immunology, University of Rochester, New York, US. Previous studies have shown that breast milk does not contain COVID-19 although while other work has suggested that the virus can be detected, it is present at very low levels and does not represent a risk for infection. Whether human milk contains COVID-19 antibodies is uncertain since, to date, only one study has addressed the immunogenic response in lactating women but this was against a pseudovirus rather than a live virus.

For the present study, researchers recruited two groups of women 18 years of age and older; an infected and vaccinated cohort. Eligible patients for the infection group were required to have had a PCR positive test result within the previous 14 days, whereas among the vaccination group, a previous COVID-19 diagnosis was an exclusion criteria. For this latter group, all women had received two vaccinations and were breast-feeding. Samples of breast milk were collected from the infected cohort on days 0, 3, 7, 10, 28 and 90 whereas for the vaccinated women, samples were obtained 18 days after the first and second vaccination doses and 90 days after the second dose. All samples from both cohorts were analysed for both Ig A and Ig G as well as for COVID-19 virus.

Findings

A total of 77 women, 47 of whom were in the infected group and 30 in the vaccinated group were included in the analysis. The mean age of the infection group was slightly lower than the vaccinated group (29.9 vs 33, infected vs vaccinated, p = 0.002). Samples from neither of the two groups contained COVID-19 although both cohorts demonstrated neutralising activity against COVID-19 which was slightly higher in the infected cohort.

Among the infected cohort, breast milk samples showed a robust and fast Ig A response that was stable at 90 days but a more variable Ig G response. In contrast, among the vaccinated cohort, levels of Ig A rose after the first vaccination but then decreased after the second dose and while Ig G levels were uniformly larger in response to vaccination but levels had declined by day 90.

Commenting on their results, the authors suggested that collectively, Ig A is the first antibody up-regulated in human breast milk in response to infection with COVID-19. In contrast, among vaccinated women, there is a larger Ig G response which increases after the first and second doses but which declines over time.

They concluded that both Ig A and Ig G contribute towards COVID-19 neutralising capacity and that this implies a clinical benefit to infants receiving breast milk from either previously infected or vaccinated mothers.

Citation

Young BE et al. Association of Human Milk Antibody Induction, Persistence, and Neutralizing Capacity With SARS-CoV-2 Infection vs mRNA Vaccination. JAMA Pediatr 2021

Vaccine efficacy of BNT162b significantly reduced after 5 months

11th October 2021

A large retrospective study has found that while the BNT162b vaccine efficacy is initially high it significantly reduces over 5 months.

In the first clinical trial, the BNT162b COVID-19 vaccine was shown to provide 95% protection against COVID-19 in those 16 years of age and older. In addition, a real-world study has confirmed the efficacy observed in the trial, with two doses of BNT162b2 being highly effective in preventing both symptomatic and asymptomatic infections, COVID-19-related hospitalisations, severe disease and death. However, there have been concerns that approved COVID-19 vaccines might show reduced efficacy over time prompting the need for a booster dose.

In an attempt to provide answers as to whether vaccine efficacy wanes over time, a team from the Department of Research and Evaluation, Kaiser Permanente, California, USA, undertook a retrospective cohort study. The team analysed electronic health records for individuals 12 years and older to assess BNT162b effectiveness against COVID-19 infection and related hospitalisations for up to six months. The study outcomes were COVID-19 infections (based on a positive PCR test) and COVID-19-related hospitalisations over a 6 month period.

Findings

A total of 3,436,957 individuals with a median age of 45 years (52.4% female) were included in the final analysis. There were 184 041 (5·4%) participants infected with COVID-19, of whom, 12130 (6·6%) were admitted to hospital. Among those fully vaccinated, the vaccine efficacy against infection was 73% (95% CI 72 – 74) and against hospital admission 90% (95% CI 89 – 92). Over a period of 5 months however, vaccine efficacy against infection reduced from 88% (in the first month) to 47% after 5 months. Despite this, vaccine efficacy against hospitalisation remained stable over the study period.

The study also examined vaccine efficacy against the COVID-19 delta variant and 4 months after full vaccination, vaccine effectiveness against this variant declined from 93% to 53%.

The authors concluded that their findings underscored the importance of monitoring vaccine efficacy over time and suggested that a booster dose might be needed to restore high levels of protection.

Citation

Tartof SY et al. Effectiveness of mRNA BNT162b2 COVID-19 vaccine up to 6 months in a large integrated health system in the USA: a retrospective cohort study. Lancet 2021

COVID-19 parental vaccine hesitancy greatest among group most severely affected

30th September 2021

Vaccine hesitancy was reported by a third of online study respondents but highest among the group most severely affected by the pandemic.

According to the Centers for Disease Control and Prevention in the US, the risk of infection, hospitalisation and death from COVID-19 among US citizens is higher among ethnic minorities compared their White counterparts. The introduction of COVID-19 vaccines has resulted in a significant reduction in the risk of severe illness, hospitalisation and death. However, not everyone has embraced the need for COVID-19 vaccination with one study finding that among those of Black ethnicity, vaccine hesitancy levels were 5-times higher than their white counterparts. Moreover, vaccine hesitancy is also a recognised problem among parents, with a 2019 study showing that a quarter of parents reported hesitancy over childhood influenza vaccination. With US data indicating that 22% of the population is under the age of 18, there is an urgent need to ensure that children receive a COVID-19 vaccine and therefore increase the levels of community protection against the virus.

But given the existence of vaccine hesitancy, a team from the Division of Advanced General Pediatrics and Primary Care, Ann & Robert H. Lurie Children’s Hospital, Chicago, US, sought to understand, through an online, cross-sectional survey, not only the levels of vaccine hesitancy but how this was influenced by ethnicity and sociodemographic factors. The survey was conducted with parents who had children under 18 years of age and captured information on demographics, race, family income and the type of child insurance (e.g., public or private) as well as sources of information on COVID-19 using a defined list such as friends/word of mouth, internet, social media etc. COVID-19 vaccine hesitancy was measured from the question, “if a new vaccine against COVID-19 became available, how likely would you be to get your child vaccinated?” Responses were dichotomised as vaccine amenable or vaccine hesitancy for those responding “not likely” or “not sure” and this served as the outcome of interest. In their regression analysis, the authors examined the association between hesitancy and ethnicity, adjusting for parental race, household income, child insurance type and sources of information in which parents reported confidence.

Findings

A total of 1425 usable responses were obtained with 40% self-reporting as non-Hispanic White, 24% non-Hispanic Black and 27% as Hispanic (any race). Overall, 33% of parents reported COVID-19 vaccine hesitancy for their child. This was highest among non-Hispanic Blacks (48%) and lowest among non-Hispanic Whites (26%). The most common source of information on COVID-19 was the internet (67%). The authors calculated that non-Hispanic Black respondents had a significantly higher odds of COVID-19 vaccine hesitancy for their children compared to non-Hispanic White parents (adjusted odds ratio, aOR = 1.75, 95% CI 1.28 – 2.39, p < 0.001). In addition, parents on the lowest income also had a higher odds of hesitancy (aOR = 2.86) as did those having public insurance for their child (aOR = 1.33).

In discussing their findings, the authors commented on how non-Hispanic Black parents, with lower incomes and public health insurance had the highest levels of vaccine hesitancy. They concluded that given how this demographic had been most adversely affected by the pandemic, efforts to improve the dissemination of information about the COVID-19 vaccine should be culturally tailored to reduce disease burden in theis patient group.

Citation

Alfieri NL et al. Parental COVID-19 vaccine hesitancy for children: vulnerability in an urban hotspot. BMC Public Health 2021

COVID-19 risk assessment algorithm predicts hospital admission and mortality after vaccination

28th September 2021

A COVID-19 risk assessment algorithm showed a high level of discrimination for identifying patients at risk of hospitalisation and death.

As the COVID-19 pandemic progressed it became clear that certain factors such as age, male sex and the presence of several co-morbidities increased the risk of worse outcomes after infection with the virus. Incorporation of these factors into a model could therefore be used to identify patients likely to be at a high-risk of worse outcomes from COVID-19. Prior to the introduction of vaccines, a COVID-19 risk assessment tool (QCovid) was developed and performed well, showing high levels of discrimination for COVID-19 deaths in men and women. The introduction of effective COVID-19 vaccines had reduced the number of both hospitalisations and deaths due to the virus. However, because no vaccine is 100 % effective, there remains a small risk of serious outcomes among vaccinated individuals, especially as the vaccination trials excluded individuals for whom the vaccine response might be have been suboptimal, e.g., those prescribed immunosuppressants or in receipt of chemotherapy for cancer.

In an effort to identify those patients who risk is likely to remain elevated even after vaccination, the team who produced the QCovid, have updated their COVID-19 risk assessment model. The model can therefore help prioritise patients who can be targeted for booster vaccination doses. Using data from the second COVID-19 wave, the team who developed QCOVID, created and validated two further COVID-19 risk assessment models: one for those at high risk who were unvaccinated (QCovid2) and a second model (Qcovid3) for at risk patients who have been vaccinated.

The models were created using the QResearch database, which contains personal, clinical and drug data for 12 million people in the UK and was linked with the national immunisation database of COVID-19 vaccinations, to derive an individual’s vaccine status and to the Hospital Episode Statistics dataset for admissions. The team also linked to several other databases including the national data for mortality, COVID-19 infections, systemic anti-cancer treatments, radiotherapy and national cancer registries. For the study, the primary outcome was time to COVID-19 related death or death within 28 days of infection. The secondary outcome was time to hospital admission with COVID-19 and both outcomes were assessed from 14 days or more after the first and second doses of vaccination. The model itself contained a huge number of predictor variables including demographics, deprivation and various co-morbidities.

Findings

The patient cohort included 6,952,440 vaccinated patients with a mean age of 52 years (47.8% female). There were 2031 COVID-19 related deaths and 1929 hospital admissions, of which, 81 deaths and 71 admissions occurred 14 days or more after the second vaccination dose. Using the Qcovid3 model the authors calculated that the of death even after vaccination, was highest for patients with Down’s syndrome (adjusted hazard ratio, aHR = 12.7) and kidney transplant patients (aHR = 8.1). The Qcovid3 model explained 74.1% of the variation in COVID-19 related deaths after two vaccine doses and 71.3% of the variation after a single vaccine dose. Furthermore, the model was slightly less effective in COVID-19 risk assessment for hospital admission at 65.7%. The results of the Qcovid2 model were described as generally similar to the Qcovid3 although no further information was provided in the paper.

Commenting on their results, the authors discussed how their study provided a robust COVID-19 risk assessment model to stratify risk among those already vaccinated against the virus. They concluded that their algorithm was likely to be both updated and extended to younger age groups once more data becomes available.

Further details of the model are available here.

Citation

Hippisley-Cox J et al. Risk prediction of COVID-19 related death and hospital admission in adults after COVID-19 vaccination: national prospective cohort study. BMJ 2021