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Take a look at a selection of our recent media coverage:

Myocarditis rate higher in younger people following mRNA vaccination

5th December 2022

Although the myocarditis rate after mRNA vaccination is low these rates appear to higher in those aged 18 – 30 compared to older adults

The overall myocarditis rate following a mRNA vaccination for COVID-19 is generally low but is higher than expected among those aged 12 to 29 years of age according to the findings of a post-marketing observational study by Canadian researchers.

Although there has been a huge uptake of COVID-19 vaccines, hesitancy remains a significant challenge with acceptance rates ranging from 53.6 to 84.4%. In fact, a US survey of 5,088,772 individuals identified that almost half (49.2%) of vaccine hesitant respondents reported fear of side effects. One such adverse effect following vaccination and which was not identified during the clinical trials was myocarditis with one US surveillance study concluding that the risk of myocarditis after receiving mRNA-based COVID-19 vaccines was increased across multiple age and sex strata and highest after the second vaccination dose in adolescent males and young men. However, little is known about the incidence of the condition following a third vaccination dose and this was the subject of the current study in which the Canadian team compared the myocarditis rate after a first, second and third dose compared to the background or expected rate.

The team used an integrated COVID-19 surveillance platform which contained all COVID-19-related data including infections and hospital or intensive care admissions. They focused on individuals aged 12 years and older and set the primary outcome as hospital admission or an emergency department visit for myocarditis.

Myocarditis rate and mRNA vaccination

During the study period (December 2020 to March 2022), a total of 1,025,385 doses of an mRNA vaccine (mRNA-1273 and BNT162b) were administered.

A total of 99 incident cases of myocarditis were identified within 7 days of vaccination, giving a rate per 100,000 of 0.97 (95% CI 0.78 – 1.17). The expected rate was 0.13 (95% CI 0.06 – 0.28) so that the observed:expected (OE) ratio was 14.81. The observed rate was higher in males than females (1.64 vs 0.35) and occurred in younger men (median age males = 28 vs median age females = 45).

Within 21 days following vaccination, there were 141 cases of myocarditis with an OE ratio of 7.03 (95% CI 5.92 – 8.29). As with the 7-day risk period, the 21-day incidence rate was higher in men than women (2.15 vs 0.67). In fact, when researchers looked at the incidence rate across different ages, the rates were much higher among those aged 12 – 29. For example, the incidence rate was 2.95 (ages 12 – 17) and 2.97 (ages 18 – 29) compared to 0.77 (ages 50 – 59) and 0.71 (ages 60 – 69).

Interestingly, the incidence myocarditis in both the 7 and 21-day post-vaccination periods reduced after the second dose. For example, the incidence rate during the first 7 days after the first vaccination was 0.18, 1.90 after the second dose but 0.76 after the third dose.

When comparing vaccines, there was a much higher rate of myocarditis following mRNA-1273 compared to BNT162b (1.44 vs 0.74). In addition, the incidence rate was highest among males aged 18 – 29 after the second dose (22.97 vs 5.84, mRNA vs BNT162b).

The authors concluded that although absolute rates of myocarditis were low, their findings support the preferential use of the BNT162b2 vaccine over the mRNA-1273 vaccine for people aged 18-29 years.

Citation
Naveed Z et al. Observed versus expected rates of myocarditis after SARS-CoV-2 vaccination: a population-based cohort study. CMAJ 2022

Telmisartan fails to improve disease severity among patients hospitalised with COVID-19

An RCT has found that the use of telmisartan failed to improve disease severity among patients hospitalised with COVID-19 compared to placebo

Telmisartan given to patients hospitalised due to COVID-19 but not requiring oxygen, provided no benefit (in terms of improvement in disease severity score) compared to placebo according to the findings of randomised, double-blind, placebo-controlled trial by Australian and Indian researchers.

The COVID-19 virus gains entry into cells via the angiotensin converting enzyme 2 (ACE2) receptor and makes use of the serine protease TMPRSS2 for protein priming. ACE2 is a key regulator of the renin-angiotensin system, responsible for degrading angiotensin II and thereby counteracting its pro-inflammatory effect mediated through the angiotensin II type 1 receptor (ATR1). Consequently, it is possible that blockage of the ATR1) receptor with angiotensin receptor blockers (ARBs) such as telmisartan, may represent a safe, low-cost solution for reducing COVID-19 respiratory outcomes. In fact, a prospective study has already demonstrated that angiotensin converting enzyme inhibitors and ARBs are associated with reduced risks of COVID-19 disease after adjusting for a wide range of variables. However, randomised trials with ARBs to date have been equivocal. For example, one trial using losartan concluded that initiation of the drug to hospitalised COVID-19 patients did not improve the arterial partial pressure of oxygen to fraction of inspired oxygen ratio at 7 days compared to placebo. Furthermore, use of losartan did not reduce hospitalisations among outpatients prescribed the drug. In contrast, a study using telmisartan 80 mg twice daily, among patients hospitalised with COVID-19, showed that the drug reduced C-reactive protein (CRP) plasma levels compared to placebo.

In order to provide more data on the value of ARBs, in the current trial researchers randomised patients hospitalised with COVID-19, 1:1 to either telmisartan 40 mg daily or matching placebo. The primary outcome was COVID-19 disease severity (based on the World Health Organisation (WHO) Clinical Progression Scale) assessed after 14 days. The WHO scale ranges from 1 to 7 with lower scores indicating less severe disease.

Telmisartan and COVID-19 disease severity outcome

A total of 788 participants with a mean age of 49 years (64 % male) were randomised to either telmisartan (393) or placebo. The baseline overall WHO scale score was 3, equating to hospitalised but not requiring oxygen.

At day 14, the WHO score had improved to 1 (i.e., not admitted to hospital and with no activity limitations) in 384 telmisartan patients with 382 assigned to placebo (Odds ratio, OR = 1.51, 95% CI 1.02 – 2.23, p = 0.98). There were also no significant differences when the primary outcome was examined in different subgroups based on gender, co-morbidities or hypertension. In fact, the trial was stopped when a pre-specified futility rule was met.

Based on these findings, the authors concluded that there was no evidence of benefit, based on disease severity score, from the use of telmisartan in hospitalised patients with COVID-19 and who had predominately mild disease.

Citation
Jardine MJ et al. Angiotensin receptor blockers for the treatment of covid-19: pragmatic, adaptive, multicentre, phase 3, randomised controlled trial. BMJ 2022

Post-COVID-19 condition persists for at least 2 years

24th November 2022

Post-COVID-19 condition symptoms are still present in both hospitalised and non-hospitalised patients two years after their acute infection

Research by a Spanish team has revealed how symptoms of post-COVID-19 condition (i.e., long covid) persist in both hospitalised and non-hospitalised patients for at least 2 years following their acute infection with the virus.

It has become increasingly recognised that approximately 10% – 20% of people infected with COVID-19 continue to experience a variety of mid- and long-term effects after they recover from their initial illness. The World Health Organisation uses the term ‘post-COVID-19 condition’ and which refers to the constellation of long-term symptoms that some people experience after they have been infected with COVID-19. A wide range of symptoms have been reported affecting various systems in the body, some of which leading to both cognitive and sensory impairment. In fact, a 2021 scoping review identified more than 100 symptoms and whose prevalence varied significantly and were not explained by data collection approaches, study design or other methodological approaches. To date several reviews have examined post-COVID-19 condition symptoms but have only been able to report on the prevalence up to 1 year following an acute infection. In the present study, the Spanish team set out to explore and compare the presence of symptoms in both hospitalised and non-hospitalised patients after a follow-up period of two years.

Hospitalised and non-hospitalised patient data was collected and a random sample from both cohorts who were infected during the first wave of the pandemic and had not been subsequently re-infected were included. Demographic and clinical data were collected from medical records and invited participants agreed to have a scheduled telephone interview 2 years after their infection and which enquired about the presence of a range of symptoms.

Post-COVID-19 condition symptoms after 2 years

A total of 360 hospitalised patients with a mean age of 60.7 years (45% female) and 308 non-hospitalised patients (mean age = 56.7, 59.4% female) were included in the study. The hospitalised and non-hospitalised groups were assessed after a mean of 23.8 and 23.4 months respectively.

Overall, 59.7% of hospitalised and 67.5% of non-hospitalised patients reported having at least 1 post-COVID-19 condition symptom at their follow-up interview. Dyspnoea was more prevalent at the onset of illness among hospitalised compared to non-hospitalised patients (31.1% vs 11.7%, p < 0.001). In contrast, anosmia was more common among non-hospitalised individuals (21.4% vs 10.0%, p = .003).

Th most frequent condition in both cohorts was fatigue (44.7% vs 47.7%, hospitalised vs non-hospitalised), with a similar level of pain symptoms including headaches (35.8% vs 29.9%), memory loss (20% vs 15.9%) and dyspnoea at rest (3.9% both groups).

In multivariate regression analysis, among hospitalised patients, the number of pre-existing co-morbidities was significantly associated with fatigue (odds ratio, OR = 1.93, 95% CI 1.09 – 3.42, p = 0.02) and dyspnoea (OR = 1.91, 95% CI 1.04 – 3.48, p = 0.03). Among non-hospitalised patients, the number of pre-existing co-morbidities (OR = 3.75) and the number of symptoms at infection onset (OR = 3.84) were both associated with the presence of fatigue.

The authors concluded that their cross-sectional study suggested the presence of at least 1 post-COVID-19 symptom in a large proportion of infected patients and which appeared to be irrespective of disease severity.

Citation
Fernández-de-las-Peñas C et al. Post-COVID-19 Symptoms 2 Years After SARS-CoV-2 Infection Among Hospitalized vs Nonhospitalized Patients. JAMA New Open 2022

Review suggests serum vitamin D levels might protect against developing COVID-19

21st November 2022

Serum vitamin D levels may protect against the development of COVID-19 but appears to have little impact on other outcomes such as mortality

Serum vitamin D levels might offer some protection against infection from COVID-19 but there is a lack of positive evidence for other outcomes such as reducing disease severity or mortality, according to the conclusion of a systematic review (available as a preprint) by researchers from the Philadelphia College of Osteopathic Medicine, US.

Much has been made of the potential protective role of higher serum vitamin D levels and COVID-19. This arises from studies showing how vitamin D affects multiple immune system mechanisms including a dampening of the entry and replication of the virus, reducing concentrations of pro-inflammatory cytokines, raising levels of anti-inflammatory cytokines, enhances the production of natural antimicrobial peptide and activation of defensive cells such as macrophages. Much of the hope for the vitamin comes from a 2017 systematic review in which the vitamin was given as a supplement, concluding that it protected against acute respiratory tract infections and how those who had a deficiency of vitamin D or who did not receive bolus doses, experienced the most benefit. Moreover, throughout the COVID-19 pandemic, emerging data has demonstrated an association between deficiency of vitamin D and the severity of infection and subsequent post-infection mortality.

In the present review, the US researchers looked at studies assessing vitamin D levels and how this impacted on the level of infection, levels of inflammatory markers, disease severity and mortality. The team compared the effects of sufficient vitamin D (serum 25(OH) D levels > 30 ng/ml, insufficient (21 – 29 ng/ml) and deficient levels (< 20 ng/ml).

Serum vitamin D levels and COVID-19 outcomes

A total of 19 studies were included. Among those who tested positive for COVID-19, the median vitamin D levels were 27.08 nmol/L and 48.67 nmol/L in those who were negative. The authors termed this difference to be ‘near significant’ (p = 0.059).

In some of the included studies, elevated levels of C-Reactive Protein (which is a marker for inflammation) and therefore disease severity, were found to be significantly associated with low levels of vitamin D. In one such study, inpatients with a median serum vitamin D levels < 12 ng/ml had more severe disease compared to those with median values > 12 ng/ml (p = 0.004). However, this was not a consistent finding.

In relation to length of hospital stay (used as a measure of disease severity), studies were mixed, with some highlighting a significant association and others no difference. In fact, median vitamin D levels were 45.02 nmol/L in those categorised as having moderate severity disease and 38.08 nmol/L in those with severe disease and this difference was not significant (p = 0.22). Finally, the differences in serum levels between those who survived and died of COVID-19 were also not significantly different.

The authors concluded that there seemed to be a correlation between vitamin D deficiency and the likelihood of developing severe illness from COVID-19 when observing studies individually but that when comparing studies on a larger scale, the significant difference seemed to fade.

Citation
Kersh L et al. What is the Impact of Vitamin D Levels on COVID-19 Severity?: A Systematic Review. Research Square 2022

Review finds tixagevimab/cilgavimab effective for immunocompromised patients

17th November 2022

A systematic review of real-world evidence suggests that the combination tixagevimab/cilgavimab is effective for immunocompromised patients

A systematic review by UK researchers, which is currently available as a preprint, has concluded that the monoclonal antibody combination tixagevimab/cilgavimab is effective against COVID-19 breakthrough infections, hospitalisation, intensive care unit (ITU) admission and both all-cause and COVID-19 specific mortality.

Tixagevimab/cilgavimab (Evusheld) is licensed as a pre-exposure prophylaxis of COVID-19 in adults who are not currently infected with COVID-19, without a known recent exposure to an infected individual infected as well as those who are unlikely to mount an adequate immune response to the vaccination against the virus and finally in those where vaccination is not recommended. Both monoclonal antibodies simultaneously bind to distinct, non-overlapping epitopes of the COVID-19 spike-protein receptor-binding domain to potently neutralise the virus. Trial data in those who were at an increased risk of an inadequate response to vaccination showed that COVID-19 occurred in only 0.2% of those given tixagevimab/cilgavimab compared to 1% of patients receiving placebo.  Furthermore, combination treatment has also been found to be effective in protection against progression to severe COVID-19 or death compared to placebo in unvaccinated individuals with mild to moderate disease.

Despite these positive findings, there is limited evidence from a real-world setting and against COVID-19 variants such as Omicron. Moreover, while Evusheld has been approved for use in many countries, the UK government recently took the decision that there is insufficient evidence available to support procurement and deployment of Evusheld through emergency procedures. In an attempt to provide more data on the effectiveness of tixagevimab/cilgavimab in those who are immunocompromised, in the present study the UK researchers sought to assess the efficacy against breakthrough infections, hospitalisation, ITU admission and mortality.

They searched for randomised, controlled trials, observational or cohort studies where the combination was used as prophylaxis and in studies where breakthrough infections were reported. Secondary outcomes reported upon were hospitalisations, ITU admissions and death.

Tixagevimab/cilgavimab outcomes among immunocompromised patients

A total of 17 studies with 24,773 immunocompromised participants of whom, 10,775 had received the combination therapy were included in the analysis.

Overall, the clinical effectiveness of the combination against breakthrough infections compared to control patients was 40.47% (95% CI 29.82 – 49.67, p < 0.0001). The combination was also significantly more effective than control against hospital admissions (69.23%, 95% CI 50.78 – 81.64, p < 0.00001). Moreover, the effectiveness against ITU admission was also very high at 87.89% (95% CI 47.12 – 98.66, p = 0.0008).

In relation to both all-cause and COVID-19-related mortality, tixagevimab/cilgavimab was also very effective with overall values of 81.29% (p < 0.0001) and 86.36% (p = 0.035) respectively.

The authors concluded that their study, based on real-world evidence showed that tixagevimab/cilgavimab proved to be highly effective, particularly during the Omicron wave and called for future trials to evaluate the on-going certain of this benefit.

Citation
Suribhatla R et al. Systematic review of the clinical effectiveness of Tixagevimab/Cilgavimab for prophylaxis of COVID-19 in immunocompromised patients. MedRxiv 2022.

Study finds COVID-19 vaccine confidence declined since pandemic

14th November 2022

Vaccine confidence appears to be declining since the start of the COVID-19 pandemic according to the finding of a repeated patient survey

Vaccine confidence has reduced compared to pre-pandemic levels, according to the findings of a recent, repeated public survey by researchers from the School of Biological Sciences, University of Portsmouth, UK.

The World Health Organisation describes immunisation as a global health and development success story. In 2020, the development of a vaccine against COVID-19 occurred very rapidly yet previously, the fastest vaccine development from viral sampling to approval had been four years, for mumps in the 1960s. Patient’s reluctance to receive vaccination, i.e., vaccine hesitancy is influenced by several factors, with a 2021 narrative review finding that COVID-19 vaccine acceptance ranged from 77.6% in the general population to 86.1% among students. A further factor affecting vaccine hesitancy is what might be termed ‘vaccine confidence’ and which has been largely driven by the rapidity of vaccine development and subsequent uncertainties over safety.

In November/December 2019 when the first cases of infection were being reported in China, the UK researchers undertook a patient survey and which was repeated in January/February 2022. In light of the pandemic, the most recent iteration of the survey was modified to include two questions: one on the number of vaccines individuals had received and the second, enquiring about an individual’s confidence in vaccines (whether it had increased/stayed the same/decreased) since the pandemic. For the survey, the researched calculated a vaccine confidence score (VCS) which was compared between the two surveys.

Vaccine confidence score change over time

The original 2019 survey included 739 participants (19.6% male) and of whom, 45.5% were aged 18 – 24 and only 4.2% aged 60 years and over. For the 2022 survey, a total of 270 respondents (27.8% male) were included but this time, the majority (68.8%) were in the 18 to 24 age range and only 3.4% were aged 60 years and older.

The median VCS in 2019 was 22 and significantly reduced to 20 in the follow-up survey (p = 0.001) with lower values seen across all age groups, between the sexes and based on graduate status.

In contrast however, the 2022 survey observed a significant association between the number of COVID-19 vaccines received and vaccine confidence score, which became higher as the number of doses received increased.

Finally, in the 2022 survey, 23.8% of respondents stated that their confidence in vaccines had decreased compared to 21.6% who stated that confidence had increased, whereas it remained unchanged at 54.6%.

The authors concluded that despite the success of the COVID-19 vaccination program, vaccine confidence had significantly declined since the onset of the pandemic.

Citation
Siani A et al. Is vaccine confidence an unexpected victim of the COVID-19 pandemic? Vaccine 2022

mRNA-1273 vaccine response non-inferior to young adults in children from 6 months

10th November 2022

The mRNA-1273 vaccine has been shown to generate an antibody response in children from 6 months that is non-inferior to young adults

The mRNA-1273 vaccine directed against COVID-19 has been shown to produce an antibody response in children aged from 6 months to 5 years that was comparable to the response elicited by young adults, aged 18 to 25 according to the findings of a study by US researchers.

It has become recognised that the efficient transmission of COVID-19 from school-age children and adolescents to household members can occur and lead to the hospitalisation of adults with secondary cases of the virus. While both COVID-19 infections and deaths are less frequent in children compared to adults it has been estimated that of 4.1 million COVID-19 deaths, 0.4% (16,100) occurred in those under 20 years of age and of which, 47% were in those age 0 to 9 years. Vaccination against COVID-19 is known to be effective at reducing hospitalisation and death in adults and the mRNA-1273 vaccine is also known to be safe and effective at inducing an immune response and preventing COVID-19 in children 6 to 11 years of age. However, whether the vaccine remains safe and able to elicit a satisfactory antibody response in children from 6 months of age is uncertain and was the purpose of the present study.

The US researchers undertook a phase 2 – 3 trial to determine the most appropriate dose in younger children. This revealed that a 25-μg dose of the mRNA-1273 vaccine was safe in children from 6 months of age. The team then randomised children aged 6 months to 23 months and between 2 and 5 years in a 3:1 ratio to two 25-μg doses administered 28 days apart or matching placebo. The aim of the study was to assess whether the antibody response was non-inferior to that generated by those aged 18 to 25.

mRNA-1273 vaccine antibody response in children from 6 months

A total of 1761 children with a median age of 16 months (51.7% male) received two doses of the vaccine and of whom, 89.4% tested negative for COVID-19. The median duration of follow-up was 68 days.

When assessed at day 57, the neutralising antibody geometric mean concentration was 1781 (95% CI 1272 – 1563) among those aged 6 – 23 months. This compared to a mean concentration of 1391 in those aged 18 to 25 (who had received 2 x 100 μg doses) and met the pre-defined criteria for non-inferiority. A similar and non-inferior response was also generated in those aged 2 – 5 years. In addition, there were no major safety concerns with adverse events mainly low-grade and transient.

In terms of vaccine effectiveness, within the 6 – 23-month group, infection occurred in 3.4% of the mRNA-1273 vaccine group and 6.6% of the placebo group, giving a vaccine efficacy of 50.6% (95% CI 21.4 – 68.6%). Among those aged 2 to 5, the vaccine efficacy was 36.85 (95% CI 12.5 – 54%) during the period of time when Omicron was the predominately circulating variant.

The authors concluded that two 25-μg doses of the vaccine were found to be safe in children 6 months to 5 years of age and elicited immune responses that were noninferior to those in young adults.

Citation
Anderson EJ et al. Evaluation of mRNA-1273 Vaccine in Children 6 Months to 5 Years of Age. N Eng J Med 2022

Omicron BA.2 sub-variant associated with less severe disease

8th November 2022

A study has suggested that COVID-19 variants may be weakening with Omicron BA.2 giving rise to less severe infections that other variants

With Omicron BA.2 (OBA2) giving rise to less severe infections, it is possible, suggests US researchers, that the COVID-19 virus is mutating to become milder.

In a study covering the period from October to December 2021 in South African, researchers concluded that infection with the Omicron COVID-19 variant led to a significantly reduced odds of hospitalisation. In fact, this was not an isolated finding and a Canadian study with 9,087 cases of Omicron, also found that infection with the variant was less severe. But as the virus mutated, an assessment of the severity of infections with one variant, OBA2, has produced conflicting results. For instance, one study found that all the Omicron variants investigated (including Omicron BA.2) led to a less severe infection compared to the Delta variant. In contrast, a French study showed that patients infected with the OBA2 variant were significantly more likely to be hospitalised and that the BA.2 variant was an independent risk factor for hospitalisation.

This led the US researchers to undertake a large, retrospective analysis of the severity of infection with the Omicron BA.2 lineage. They used data held within both inpatient and outpatient systems in New England and identified individuals infected with the Delta, Omicron B.1.1.529 and the Omicron BA.2 variants. Though genomic sequencing was not performed, infections were categorised as either Delta, Omicron or Omicron sub-variants according to the timing of the onset of disease detection. For example, infections between June and December 2021 were classed as Delta and cases between March and May 2022 as the Omicron BA.2 variant. The researchers included vaccination status, ethnicity and co-morbidities as covariates in their analysis and set the primary outcome as in-hospital death within 30 days of a positive COVID-19 test result. They also considered the need for invasive ventilation and intensive care unit admission as secondary outcomes.

Omicron BA.2 and COVID-19 outcomes

A total of 102,315 confirmed COVID-19 infections in patients with a mean age of 44.2 years (62% female) were included and of whom, 28,940 were classed as OBA2 and 65.9% of these individuals had been fully vaccinated and had a booster, compared to only 2.6% of those infected with the Delta variant.

The mortality rates were 0.7%, 0.4% and 0.3% for the Delta, Omicron and OB2 variants respectively. After adjustment for covariates, the risk of the primary outcome (i.e., mortality) was significantly higher for those infected with the Delta variant compared to OBA2, (Odds ratio, OR = 2.07, 95% CI 1.04 – 4.10) and for the original Omicron strain (OR = 2.20, 95% CI 1.56 – 3.11).

In subgroup analysis, there were also higher risks of hospitalisation, intensive care admissions and the need for mechanical ventilation, for Delta and original Omicron infections compared to OBA2.

The authors concluded that after having accounted for a variety of confounding factors, it seemed that the Omicron BA.2 sub-variant was intrinsically less severe than other variants.

Citation
Strasser ZH et al. Estimates of SARS-CoV-2 Omicron BA.2 Subvariant Severity in New England JAMA Netw Open 2022

Adverse cardiovascular outcomes higher in patients hospitalised with COVID-19

4th November 2022

The risk of adverse cardiovascular outcomes is significantly higher in patients hospitalised with COVID-19 compared to uninfected controls

There is an elevated risk of several adverse cardiovascular outcomes among patients hospitalised with COVID-19 but the risk of both venous thromboembolism and death is still significant in non-hospitalised cases compared to a group of uninfected, matched controls. These were the key findings from a prospective analysis of participants in the UK Biobank by UK researchers.

Studies have suggested that infection with COVID-19 is a risk factor for acute myocardial infarction and ischaemic stroke. Moreover, a retrospective study has revealed how cardiac arrhythmia is also a clinical sequelae following an acute infection with the virus. Nevertheless, whether these adverse cardiovascular events are restricted to patients with more severe disease, i.e., those who are hospitalised, or whether there is an increased risk among patients with less severe disease remains unclear. In the present study, UK researchers examined if exposure to COVID-19 was associated with incident cardiovascular disease and mortality. The used data from the UK Biobank and identified those infected with COVID-19, linking to Public Health England laboratory information to identify PCR test results. These individuals were then propensity matched to 2 control patients based on a number of factors including age, sex, body mass index, various co-morbidities (e.g., hypertension, diabetes), smoking status and ethnicity. The researchers considered several adverse cardiovascular outcomes including myocardial infarction (MI), venous thromboembolism (VTE), cardiovascular disease (CVD) mortality, stroke, heart failure, atrial fibrillation and pericarditis. In a further analysis, the team assessed if the risk of these adverse cardiovascular outcomes reduced over time.

Adverse cardiovascular outcomes and COVID-19

A total of 471,227 individuals with a median age of 69 years (44.7% male) were included in the analysis which included 17,871 COVID-19 patient cases. Individuals were followed-up for an average of 141 days. Among those with COVID-19, the majority (80%) were not hospitalised and in the hospitalised cohort (3567), 75.7% had primary diagnosis of COVID-19 whereas the remainder had COVID-19 recorded as a secondary diagnosis.

Among non-hospitalised COVID-19 patients (14,304), there was a more than two-fold higher risk of VTE compared to uninfected controls (Hazard ratio, HR = 2.74, 95% CI 1.38 – 5.45, p = 0.004). Additionally, there was a significantly increased risk of death (HR = 10.23, 95% 7.63 – 13.7, p < 0.0001). Interestingly, the risk of incident MI among the non-hospitalised COVID-19 group was significantly lower (HR = 0.19, 95% CI 0.06 – 0.65, p = 0.008).

In contrast to the non-hospitalised group, patients hospitalised with COVID-19 had significantly elevated risks of MI (HR = 9.9), heart failure (HR = 21.6), atrial fibrillation (HR = 14.9), VTE (HR = 27.6) and cardiovascular mortality (HR = 8.76). Furthermore, there were also increased adverse cardiovascular risks in patients for whom COVID-19 was the secondary diagnosis, e.g., MI (HR = 22.2), heart failure (HR = 13.1), atrial fibrillation (HR = 29.3) and cardiovascular mortality (HR = 14.6).

Next researchers examined the interaction with time and considered the risk of events 30 days before and after their acute infection. Although the risks for atrial fibrillation, VTE and heart failure were largely attenuated after 30 days, these risks still remained significant, e.g., for VTE (HR = 3.97) and heart failure (HR = 2.78).

The authors concluded that while infection with COVID-19 is associated with a higher risk of adverse cardiovascular outcomes, the risks are largely confined to hospitalised patients and highest within the first 30 days following infection.

Citation
Raisi-Estabragh Z et al. Cardiovascular disease and mortality sequelae of COVID-19 in the UK Biobank Heart 2022

Antibody response from Omicron BA.4/BA.5 bivalent booster similar to original vaccine

31st October 2022

The antibody response to an Omicron BA.4/BA.5 bivalent booster appears to be similar to that generated after a fourth monovalent mRNA vaccine

The antibody response generated after receipt of an Omicron BA.4/BA.5 bivalent booster appears no better than the response induced after a fourth dose of monovalent mRNA vaccine dose against COVID-19 variants according to a small pre-print study by a team of US researchers.

The evolving nature of the COVID-19 virus had led to many variants such as Omicron. However, this variant too has further mutated to create the sublineages BA.2.12.1, BA.4 and BA.5 that which can escape neutralisation by current vaccines. As a result, companies have quickly adapted their vaccines and the FDA has given emergency use authorisation to what have been termed ‘bivalent boosters’ produced by both Moderna and Pfizer-BioNTech. Similarly, the European Medicines Agency, has also recommended authorising an adapted bivalent vaccine targeting the Omicron sub-variants BA.4 and BA.5.  The bivalent vaccines contain two messenger RNA components of COVID-19; one directed at the original strain and the other towards the BA.4 and BA.5 lineages of the omicron variant. There is currently limited data on the antibody response generated with these bivalent vaccines. However, one recent study compared the Moderna bivalent vaccine as a second booster to receiving a fourth dose of the original, monovalent vaccine. The results showed that the bivalent vaccine elicited a higher neutralising antibody response against omicron BA.4 and BA.5 than the monovalent vaccine. Moreover, preliminary data on a bivalent vaccine manufactured by Pfizer BioNTech, was reported to show that in sera collected from participants 7 days after administration of a 30-µg booster dose of the Omicron BA.4/BA.5-adapted bivalent COVID-19 vaccine, there was a substantial increase in the Omicron BA.4/BA.5 neutralising antibody response above pre-booster levels.

In the present study, researchers collected sera from individuals who had previously received three doses of a monovalent vaccine, followed by a single dose of a bivalent vaccine. The researchers then compared the neutralising capacity against COVID-19 to panels of sera collected from participants who had received either 3 or 4 monovalent mRNA vaccine doses as well as from individuals who experienced a breakthrough infection with BA.4/BA.5. The sera samples were all tested against the original COVID-19 strain, Omicron sublineages, BA.1, BA.2, BA.4/BA.5, BA.4.6, BA.2.75 and BA.2.75.2.

Antibody response for COVID-19 variants

A total of 74 patients provided samples of whom, 19 with a mean age of 55.3 years (89.5% female) had previously received four doses of a monovalent vaccine although those who were given a bivalent booster were younger (mean age 36.4, 76.2% female). Serum samples were collected a mean of 24 days following the booster dose for the monovalent group and after a similar interval (mean 26.4 days) in the bivalent group.

All the cohorts displayed a high antibody response to the original COVID-19 strain but there were no differences for the other variants. In other words, receiving a booster vaccine which targeted both the original COVID-19 strain and the BA.4/BA.5 variants, did not produce a superior antibody response against all of the variants tested, compared to boosting with a fourth dose of a monovalent vaccine.

The authors suggested that these results may indicate immunological imprinting, i.e., whereby initial exposure to one virus strain effectively primes B cell memory and limits the development of memory B cells and neutralising antibodies against new minor variant strains of the virus. Moreover, they suggested that follow-up studies were needed to determine if the antibody responses change over time.

Citation
Wang Q et al. Antibody responses to Omicron BA.4/BA.5 bivalent mRNA vaccine booster shot. BioRxiv 2022