This website is intended for healthcare professionals only.
Take a look at a selection of our recent media coverage:
15th May 2023
A study of almost three million women found no evidence of an increased risk of menstrual changes after Covid vaccination.
Researchers suggested there was a weak association between the vaccine and menstrual disturbance or premenstrual bleeding, in a paper published in the BMJ.
The findings do not provide ‘any substantial support’ for a causal association between the Covid vaccination and healthcare contacts related to menstrual or bleeding disorders, the authors said.
Many women self-report changes to their periods after a Covid vaccine – including excessive, frequent, absent or irregular menstruation – and a link between the vaccine and menstrual disturbance has also been discussed on social media, causing global concern.
The researchers in Sweden drew on high-quality health registry data to evaluate the risks of menstrual disturbance and bleeding after the Covid vaccination in 2,946,448 women aged 12-74 from December 2020 to February 2022.
The authors, led by Rickard Ljung, professor at the Swedish Medical Products Agency, said: ‘We observed weak and inconsistent associations between SARS-CoV-2 vaccination and healthcare contacts for postmenopausal bleeding, and even less consistent for menstrual disturbance, and premenstrual bleeding.’
The healthcare contacts in the study included primary care visits, specialist outpatient visits, and days of hospital stay related to menstrual disturbance or bleeding before or after menopause.
Pfizer-BioNTech, Moderna, and Oxford-AstraZeneca vaccines were all assessed along with the dose number, whether that be unvaccinated, first, second, and third dose.
This was measured over a control period of one to seven days, followed by a second time window of eight to 90 days.
More than 88% of women received at least one Covid vaccination and over 64% of vaccinated women received three doses during the study period.
The highest risks for bleeding in post-menopausal women were seen after the third dose in the one-to-seven-day risk window (28%) and in the eight-to-90-day risk window (25%).
The analysis also suggested a 23-33% increased risk of post-menopausal bleeding after eight to 90 days, with Pfizer-BioNTech and Moderna after the third dose, but a less clear association with Oxford-AstraZeneca.
However, the study concluded that after adjusting for socioeconomic factors, previous healthcare use and specific medical conditions, this almost completely removed weak associations, suggesting a casual effect was unlikely.
A version of this story was originally published by our sister publication Pulse.
28th February 2023
Researchers from Washington university in the US, performed a systematic review and meta-analysis finding that the protection afforded by a prior COVID-19 infection was high against re-infection from most pre-omicron variants and remained high against severe disease for all variants and was comparable to the protection from a two-dose vaccination with mRNA vaccines.
To date, several studies have suggested that a previous infection with COVID-19 offers some degree of protection against re-infection. However, studies have included different time periods as well as COVID-19 variants yet there are no analyses that have provided an overview of how the level of protection against re-infection varies over time and in relation to the different variants.
In the current analysis, the US researchers extracted data from studies through to September 2022 that examined the reduction in risk of developing COVID-19 in those with a prior COVID-19 infection compared to those without a previous infection. The data were then analysed to show the effectiveness of a prior infection against several outcomes including the risk of re-infection, symptomatic disease and severe disease based on the variant and time since infection.
Prior COVID-19 infection and re-infection outcomes
A total of 65 studies were included in the analysis from 19 different countries.
The pooled protection against re-infection varied depending on the variant ranging from 82% against delta to 90% against alpha. In contrast, the pooled protection against re-infection with omicron BA.1 was 45.3%. The protection against symptomatic disease was broadly similar, e.g. 85% for delta and 87.2% against alpha and only 44% against omicron BA.1.
The protection against severe infection (i.e., hospitalisation or death) was high for delta (97.2%), slightly lower against alpha (79.6%) but actually also high against omicron BA.1 (81.9%).
The pooled protection against ancestral, alpha and delta variants was initially high at 85.2% after 4 weeks but reduced to 78.6% at 40 weeks. In contrast, protection against re-infection from omicron BA.1 rapidly declined to 36.1% at 40 weeks.
The authors concluded that protection against re-infection was high against most variants pre omicron BA.1 adding that this level of protection was at least equivalent, if not greater than that provided by two-dose mRNA vaccines, which has also been observed in a previous study.
COVID-19 Forecasting team. Past SARS-CoV-2 infection protection against re-infection: a systematic review and meta-analysis. Lancet 2023
15th February 2023
According to the findings of a systematic review in the Lancet, COVID-19 vaccine effectiveness wanes over time, even following booster doses, indicating that in the longer-term, it may be necessary to continue with preventative measures such as face-mask wearing and physical distancing to help manage the pandemic.
While the introduction of COVID-19 vaccines had an enormous impact on hospitalisations and mortality due to infection with the virus, it has been recognised that induced antibody levels reduce over time. A previous systematic review in 2022 observed that while vaccine efficacy against severe disease only dropped by 10% from one to six months, it reduced by approximately 21% against infection after 6 months and by nearly 25% against symptomatic illness. However, the analysis did not consider the impact of COVID-19 booster doses. As a result, in the current study, researchers examined the effectiveness of vaccination against infection, hospitalisation and death among those who had received a booster dose.
The team examined studies that provided data on vaccine effectiveness for at least 112 days after the primary series of vaccinations or at least 84 days after receipt of a booster dose. They set the primary outcomes of interest as effectiveness against COVID-19 infection, hospitalisation and mortality.
Vaccine effectiveness against COVID-19 outcomes
A total of 68 studies were included in the final analysis.
Overall effectiveness against any strain of COVID-19 reduced from 83% after a primary series of vaccinations to 62% by 112 to 139 days. Similarly, baseline effectiveness against hospitalisation was initially high at 92% but dropped to 79% after 168 – 195 days, as did effectiveness against mortality (91% to 86%) over the same period of time.
Among those who had received booster doses and for which most studies included the omicron variant, vaccine effectiveness against infection was initially 70% but reduced to 43% after 112 days. Similarly, boosted doses against hospitalisation reduced from a baseline of 89% to 71% over the same period of time. The authors reported that there was insufficient data to assess the impact on mortality.
Commenting on their findings, the authors suggested that maintaining COVID-19 prevention behaviours including the wearing of face-masks and physical distancing as well as vaccination may be necessary to reduce transmission of the virus, given how immunity wanes over time. They called for future studies to investigate the effectiveness of simultaneously using multiple approaches such as vaccination and face-masks as transmission preventative strategies.
Wu N et al. Long-term effectiveness of COVID-19 vaccines against infections, hospitalisations, and mortality in adults: findings from a rapid living systematic evidence synthesis and meta-analysis up to December, 2022. Lancet Respir Med 2023
5th January 2023
Receiving a COVID-19 vaccination has been found to reduce the risk of subsequently developing post-COVID-19 condition (or long covid) although the vaccine effectiveness is low according to the findings of a meta-analysis by US researchers.
Vaccine effectiveness is a measure of how well vaccination protects individuals against a condition but differs from the efficacy measured in a trial, because efficacy cannot predict exactly just how effective a vaccine might be in a larger and more variable population. Nevertheless, real-world evidence suggests that some vaccines, such as BNT162b2, have an effectiveness comparable to that reported in phase III clinical trials. Although in practice, many patients make a full recovery after an acute COVID-19 infection, for a minority, there is the continuation or development of other symptoms. The World Health Organisation has described this as ‘Post COVID-19 condition’ and which occurs in individuals with a history of probable or confirmed COVID-19 infection, usually 3 months from the onset of COVID-19 with symptoms that last for at least 2 months and cannot be explained by an alternative diagnosis.
While the effectiveness of vaccination against COVID-19 is widely accepted, what is uncertain, is whether vaccination reduces the risk of post–COVID-19 condition. This was the subject of the current study by the US researchers who reviewed the literature on the effectiveness of COVID-19 vaccines for post–COVID-19 condition and pooled the results of published studies to allow for a more precise estimate of effectiveness. The team looked for studies that: involved vaccinated and unvaccinated individuals and evaluated the long-term effectiveness of the COVID-19 vaccine. Post–COVID-19 conditions were defined as a wide range of health symptoms that were present 3 or more weeks after having COVID-19. Any studies without a comparison between vaccinated and unvaccinated individuals (or other vaccinated control group) were excluded. The team calculated the pooled diagnostic odds ratio (DORs) for post–COVID-19 conditions between vaccinated (i.e., those who received at least 1 dose of a COVID-19 vaccine) and unvaccinated individuals.
Vaccination and effectiveness against post-COVID-19 condition
A total of 10 studies with 1,600,830 individuals evaluated the effect of vaccination on post–COVID-19 conditions and of which 6, were included in the meta-analysis. The pooled prevalence of post–COVID-19 conditions was 39.1% among those who were unvaccinated and 37.6% among those who received at least 1 dose.
The pooled DOR for post–COVID-19 conditions among individuals who received at least 1 dose was 0.708 (95% CI 0.69 – 0.73), giving an estimated vaccine effectiveness of 29.2% (95% CI, 27.5%–30.8%).
However, vaccine effectiveness varied depending on whether an individual received the vaccine before or after being infected with COVID-19. For example, effectiveness was 35.3% (95% CI 32.3% – 38.1%) among those who received the COVID-19 vaccine before having COVID-19 but 27.4% (95% CI 25.4% – 29.3%) among those who received it after being infected.
The authors concluded that COVID-19 vaccination before and after having COVID-19 provided a low but statistically significant decrease in post–COVID-19 conditions for the variants circulating during the study period. They added that a more standardised definition of post–COVID-19 conditions was also needed both for research and clinical purposes.
Marra AR et al. The effectiveness of coronavirus disease 2019 (COVID-19) vaccine in the prevention of post–COVID-19 conditions: A systematic literature review and meta-analysis. Antimicrob Steward Health Epidemiol 2022
31st October 2022
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.
Wang Q et al. Antibody responses to Omicron BA.4/BA.5 bivalent mRNA vaccine booster shot. BioRxiv 2022
29th August 2022
A triple dose vaccination against COVID-19 is associated with a significantly reduced risk of developing long covid among individuals who experience a breakthrough infection but who do not require hospitalisation according to the results of a study by a team of Italian researchers based in Milan.
Following an acute infection with COVID-19, it has become widely recognised that some patients can develop post-acute sequelae, i.e., long covid, 6 months after their initial infection. Potential risk factors linked to the development of long covid include female gender, respiratory symptoms at the onset and the severity of the initial illness. With the widespread introduction of vaccination against COVID-19, there remains some uncertainty over whether vaccination and in particular, triple dose vaccination, protects against the development of long covid. To date, only one study has examined the relationship between vaccination, breakthrough infections and long covid. In that study, the authors suggested that among individuals who experience a breakthrough infection, there was a 15% lower risk of post-acute sequelae. However, a limitation of the study was that the authors only considered the risk reduction after two doses of a COVID-19 vaccine, whereas current recommendations are for individuals to receive a triple dose.
For the present study, the Italian team set out to examine the impact of a triple dose vaccination on the development of long covid. They turned to healthcare professionals who had received three doses of the BNT162b2 vaccine and did not require hospitalisation if they developed a breakthrough infection. The researchers also defined long covid as the presence of at least one COVID-19 related symptom which continued for more than 4 weeks. They also considered the three COVID-19 waves and used multi-variable logistic regression to assess the relationship between the development of long covid and patient demographics, co-morbidities and vaccination status.
Triple dose vaccination and long covid
A total of 739 individuals with a mean age of 42.8 years (25.4% male) were included, of whom, 31% developed long covid and 16% of these individuals had received a triple dose of BNT162b.
The incidence of long covid varied depending on the pandemic wave. During the first wave (February – September 2020), 48.1% were affected, reducing to 35.9% in wave 2 (October 2020 – July 2021) and 16.5% in wave 3 (August 2021 – March 2022).
The number of vaccine doses was also associated with the development of long covid which ranged from 41.8% among unvaccinated individuals, to 30% in those with a single dose, 17.4% after two doses and 16% in those after a triple dose of vaccine.
Using unvaccinated women in wave 1 without allergies or co-morbidities as the reference point, having 2 vaccine doses significantly reduced the risk of long covid (odds ratio, OR = 0.25, 95% CI 0.07 – 0.87, p = 0.03) but this was reduced further still among those with three doses of the vaccine (OR = 0.16, 95% CI 0.03 -0.84, p = 0.03).
The authors concluded that among those receiving a triple dose vaccination against COVID-19, who develop a breakthrough infection which does not lead to hospitalisation, there was a significantly lower risk of developing long covid.
Azzolini E et al. Association Between BNT162b2 Vaccination and Long COVID After Infections Not Requiring Hospitalization in Health Care Workers JAMA 2022
17th August 2022
Patients with hypertension even after receipt of three COVID-19 vaccination doses, remain at an elevated risk of severe breakthrough infections with the Omicron variant according to researchers from the Department of Cardiology, Cedars-Sinai Medical Center, Los Angeles, US.
Although full vaccination against COVID-19 initially required individuals to have two doses, the fact that immunity appears to wane over time has led to a recommendation for a third dose. In fact, a third dose appears to provide greater protection with data showing how a third dose of the BNT162b2 vaccine administered a median of 10.8 months after the second dose provided 95.3% efficacy against COVID-19 compared with two doses. As more information emerged during the pandemic, it became clear that there were several important risk factors associated with the development of more severe illness and hypertensive patients were found to be more vulnerable to the development of serious complications. However, several unanswered questions remained. For example, do the same risk factors apply with COVID-19 variants and does full vaccination mitigate these risk factors? These were the questions raised in the present, retrospective analysis by the US team.
The researchers examined a cohort of adults with at least three doses of the COVID-19 vaccine but who subsequently developed a breakthrough infection with the Omicron variant (confirmed by nasopharyngeal swabs and PCR testing) and were hospitalised at their centre. The team collected demographic and co-morbidity data and used multivariable logistic regression analysis to assess the association between various factors such as age, comorbid conditions and the risk of hospitalisation and these covariates were adjusted for in the final analysis.
Hypertension and risk of severe illness
The researchers identified a total of 912 patients with a mean age of 56 years (41% male) of whom 15.9% were subsequently hospitalised with a breakthrough Omicron infection. Among the overall cohort, 27% were obese, 21% had diabetes and 54% were hypertensive and there was a mean of 72 days between vaccination and infection.
In regression analysis, the presence of hypertension was associated with a more than two-fold higher odds of being hospitalised, after adjustment for covariates (odds ratio, OR = 2.29, 95% CI 1.24 – 4.32). Other related elevated risk factors included the presence of a previous myocardial infarction (OR = 2.21, 95% CI 1.29 – 3.77).
Because hypertension is common in patients with a prior myocardial infarction, heart failure and chronic kidney disease, in a further analysis, the authors excluded patients with these three comorbidities. However, the elevated risk of hospitalisation in those with hypertension remained significant (OR = 2.54, 95% CI 1.32 – 5.37).
The authors concluded that the presence of hypertension remains an important risk factor for breakthrough COVID-19 infections even after full vaccination and that further research is required to understand the relationship between this risk factor to enable the development of mitigation strategies.
Ebinger J et al. Hypertension and Excess Risk for Severe COVID-19 Illness Despite Booster Vaccination Hypertension 2022
9th August 2022
COVID-19 vaccination provides individuals with a reduced risk of experiencing an acute myocardial infarction or ischaemic stroke after becoming infected with the virus according to the findings of a study by Korean researchers.
It has now become recognised that following an acute infection with COVID-19, beyond the first 30 days, individuals with COVID-19 have an increased risk of cardiovascular disease and which includes cerebrovascular disorders, dysrhythmias, ischaemic and non-ischaemic heart disease, pericarditis, myocarditis, heart failure and thromboembolic disease. While it is clear that a COVID-19 vaccination is safe and offers protection against severe COVID-19, hospitalisation and death against all current variants of concern, what is less clear is whether vaccination is able to reduce the post-infection cardiovascular sequelae. As a result, for the present study, the Korean researchers undertook a retrospective cohort study and compared the incidence of acute myocardial infarction and ischaemic stroke in those with and without full COVID-19 vaccination. They linked data from the Korean nationwide COVID-19 registry and the National Health Insurance database and included all adults who were diagnosed with COVID-19 between July 2020 and December 2021. However, the team excluded several patient groups including: individuals whose data showed that they had a cardiovascular event three months before a COVID-19 infection, cases of re-infection with the virus and patients who were vaccinated but hospitalised with the virus for longer than 30 days. They set the primary outcome of interest as a composite of all hospitalisations for an acute myocardial infarction and ischaemic stroke and which had occurred 31 to 120 days after an individual’s COVID-19 diagnosis. They decided to exclude cardiovascular events within the first 30 days of infection because of the inherent difficulty of differentiating whether the event was related to infection of treatment.
COVID-19 vaccination and cardiovascular outcomes
A total of 231,037 patients were included in the analysis, of whom, 62,727 were unvaccinated and with a median age of 42 years (51.5% female). The median age of the vaccinated group was higher (57 years) and had a greater incidence of co-morbidities including diabetes (11.8% vs 7.1%, vaccinated vs unvaccinated) and hypertension (22.1% vs 10.8%). Furthermore, a higher proportion of unvaccinated individuals had severe COVID-19 (3.1% vs 9.8%). The median period of follow-up was 90 days in the unvaccinated and 84 days in the fully vaccinated group (which was defined as receipt of 2 doses of a vaccine).
The composite outcome occurred in 31 unvaccinated individuals and 74 of those who were fully vaccinated and after adjustment for differences in baseline characteristics, this difference was statistically significant (hazard ratio, HR = 0.42, 95% CI -.29 – 0.62, p < 0.001). This difference was also significant for the individual components of the composite.
The authors concluded that full COVID-19 vaccination was protective against the acute myocardial infarction and an ischaemic stroke that could arise after infection with the virus, compared with individuals who were unvaccinated.
Kim YE et al. Association Between Vaccination and Acute Myocardial Infarction and Ischemic Stroke After COVID-19 Infection JAMA 2022
12th July 2022
Both overweight and obese patients who have been vaccinated against COVID-19 have a similar degree of protection against severe disease and death as those of a healthy weight according to a large, population-based cohort study by researchers from the UK and Spain.
Since the start of the COVID-19 pandemic, considerable evidence has emerged indicating how obesity is a risk factor for more severe disease. For example, in a 2020 systematic review of 24 retrospective cohort studies, the odds ratio for intensive care unit admission for obese patients was 1.21 and higher still, for invasive mechanical ventilation (OR = 2.05). With the widespread introduction of COVID-19 vaccines, it is necessary to understand how overweight and obese patients respond to vaccination. This is especially important in light of evidence showing that despite generating a robust serological response, vaccinated obese adults are twice as likely to develop influenza and influenza-like illness compared with healthy weight adults. Furthermore, another study found that CD4(+) and CD8(+) T cells from overweight and obese individuals expressed lower levels of CD69, CD28, CD40 ligand, and interleukin-12 receptor, compared with healthy weight and which may contribute to the increased morbidity and mortality from H1N1 influenza A virus.
Despite the concern that overweight and obese patients may not produce a satisfactory immune response to vaccination, there are limited data on the association between body mass index (BMI) and COVID-19 vaccine effectiveness and the risk of severe COVID-19 outcomes after vaccination. Using the QResearch database, in the present study, researchers used an anonymised patient data set derived from over 1,700 general practices in England and collated demographic and clinical data. They linked this information with the NHS Digital database of positive COVID-19 tests, hospital episode statistics and death certificates. Included patients were adults and who had a BMI measurement recorded in their medical records and which were then categorised as underweight (BMI < 18.5), healthy weight (BMI 18.5 – 24.9), overweight (BMI 25 – 29.9) and obese (BMI > 30). They examined vaccine effectiveness across the different weight categories and set the main outcomes of interest as hospitalisation and death.
Overweight and obese patients and severe COVID-19 outcomes
A total of 9,171,524 individuals with a mean age of 52 years (47% male) were included in the analysis. During the period of study there were 566,461 positive tests for COVID-19, 32,808 COVID-19-related hospital admissions and 14,389 COVID-related deaths. Across the whole cohort, 19.2% were unvaccinated, 3.1% had at least one dose, 52.6% two doses and 25% three doses. Uptake of two or three vaccine doses was more than 80% among those deemed overweight or obese.
At least 14 days after the second vaccine dose, the likelihood (based on the odds ratio, OR) of a COVID-19-related hospitalisation (compared to those who were unvaccinated) was lowest for those who were either overweight (OR = 0.32, 95% CI 0.30 – 0.34) or obese (OR = 0.32, 95% CI 0.30 – 0.34) which was similar to those with a healthy weight (OR = 0.34). Among those who were underweight, there was a slightly higher risk of hospitalisation (OR = 0.51, 95% CI 0.41 – 0.63). However, the odds of hospitalisation after a third vaccine dose were significantly less and similar for each of the different BMI categories.
In relation to mortality, there was a similar pattern 14 days after the second dose, e.g., underweight individuals (OR = 0.60), healthy weight (OR = 0.30) with overweight and obese individuals having the same odds ratio (OR = 0.26). Mortality was also significantly lower after the third dose though there was more uncertainty given the lower number of cases.
The authors concluded that both overweight and obese patients appear to be equally well protected against severe COVID-19 outcomes as those of a healthy weight although vaccine effectiveness appeared to be less in those classed as underweight.
Piernas C et al. Associations of BMI with COVID-19 vaccine uptake, vaccine effectiveness, and risk of severe COVID-19 outcomes after vaccination in England: a population-based cohort study Lancet Diabetes Endocrinol 2022
4th July 2022
The effectiveness of the anti-viral drug paxlovid in preventing the progression of COVID-19 remains even in those who have been adequately vaccinated against the virus according to the results of a real-world study by Israeli researchers.
Paxlovid consists of nirmatrelivir, a protease inhibitor against COVID-19 and ritonavir, which reduces the in vivo metabolism of nirmatrelivir. The published data for the drug (the EPIC-HR trial) suggested that treatment of symptomatic COVID-19 in patients at risk of progression to severe disease, results in an 89% lower risk compared to placebo. Nevertheless, the study was undertaken before omicron became the main circulating variant and therefore the generalisability of the study’s findings are potentially limited. Consequently, for the present study, the Israeli team decided to undertake a large, retrospective cohort study of high-risk COVID-19 patients, to assess the effectiveness of paxlovid at preventing progression to severe COVID-19 and subsequent death during the time when omicron was the predominant strain.
Using a large, national health service database, the researchers identified all adults (18 years and over) who tested positive for COVID-19 but restricted the search to those who would be suitable candidates for treatment with paxlovid, i.e., those who were older than 60 years, with a body mass index (BMI) greater than 30 and with co-morbidities including diabetes, hypertension and cardiovascular disease. However, unlike in the EPIC-HR trial, where those who had been vaccinated were excluded, for the present analysis, researchers included patients, regardless of their vaccination status. The main outcome of the study was a composite of severe COVID-19 or COVID-19-related mortality. For their analysis, the researchers included demographic and co-morbidity data and which were adjusted for in the analysis.
Paxlovid and progression of COVID-19
A total of 4,737 individuals with a mean age of 68.5 years (42.1% male) were treated with paxlovid and compared with 175,614 individuals who tested positive but who did not receive the drug. In total, 77.8% of those given paxlovid had adequate COVID-19 vaccination compared to 75% of those in the non-paxlovid group.
Overall, the primary outcome occurred in 39 individuals receiving paxlovid compared to 903 in those not given the drug. Paxlovid was therefore associated with a significantly lower risk of severe COVID-19 or mortality (hazard ratio, HR = 0.54, 95% CI 0.39 – 0.75). Moreover, among the whole cohort, having adequate COVID-19 vaccination, was also associated with a significantly lower risk of the primary outcome (HR = 0.20, 95% CI 0.17 – 0.22).
When the analysis was restricted to those diagnosed with COVID-19 when omicron was the main circulating variant, paxlovid was also associated with a greater reduction in the primary endpoint (HR = 0.43, 95% CI 0.64 – 0.85). Interestingly, among those given paxlovid and who were adequately vaccinated, there was still a significant reduction in the primary outcome (HR = 0.62, 95% CI 0.39 – 0.98) as well as among those not vaccinated (HR = 0.52, 95% CI 0.32 – 0.82).
The authors concluded that their study had demonstrated that in a real-world setting and during the period of time when omicron was the dominant variant, paxlovid was associated with a significant reduction in progression of COVID-19 and COVID-19-related mortality.
Najjar-Debbiny R et al. Effectiveness of Paxlovid in Reducing Severe COVID-19 and Mortality in High Risk Patients Clin Infect Dis 2022