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

Intermittent fasting reduces hospitalisation and death from COVID-19

19th July 2022

Intermittent fasting is associated with a significantly reduced risk of both hospitalisation and death among patients infected with COVID-19

Individuals who practice intermittent fasting long-term have a significantly lower risk of hospitalisation or death from COVID-19 but not of becoming infected with the virus. These were the key findings of a study by US researchers.

Intermittent fasting (IF) is a practice that involves restricting eating and there are several different approaches. For example, with the 16/8, food is only consumed over 8 hours or the 5:2 approach, that involves eating regularly five days a week and limiting daily calorie intake the other two days, to 500 –600 calories. There is now good evidence that IF may benefit cardiometabolic health by decreasing blood pressure, insulin resistance, and oxidative stress. One metabolic change of IF is increased linoleic acid-enriched triacylglycerol species in the liver and serum during fasting. Furthermore, recent in vivo data have revealed how the COVID-19 spike protein tightly binds linoleic acid in three composite pockets, resulting in reduced angiotensin-converting enzyme 2 interaction. Another advantage to IF is increased levels of galectin-3 and this protein has been shown to directly bind to pathogens and to have various effects on the functions of innate immune system cells.

Taken together, the available evidence would suggest, at least in theory, that IF could reduce disease severity in COVID-19. Consequently, the researchers undertook a prospective, observational study and turned to data held in the INtermountain Healthcare Biological Samples Collection Project and Investigational REgistry (INSPIRE) which collects biological samples, clinical information and laboratory data from patients. For the purposes of the study, the team included registry patients who had undergone COVID-19 testing but also included demographic and clinical data from these patients. For the study, the primary endpoint was a composite of all-cause mortality and hospitalisation for COVID-19. The main secondary outcome was a positive test for COVID-19.

Intermittent fasting and adverse COVID-19 outcomes

A total of 205 individuals with a mean age of 63.5 years (37.1% female) were included, of whom 73 practiced IF and had done so for a mean of 40.4 years before their COVID-19 diagnosis.

From the whole cohort, 11% of IF individuals and 28.8% of non-fasters experienced the primary endpoint and this difference was significant (hazard ratio, HR = 0.61, 95% CI 0.42 – 0.90, p = 0.013). In fully adjusted models, this difference remained significant (HR = 0.63, 95% CI 0.42 – 0.93, p = 0.021). Predictors of hospitalisation and mortality included age, coronary artery disease, hypertension, smoking and hyperlipidaemia.

Interestingly, for the secondary outcome, testing positive for COVID-19, there were no significant differences, with 14.3% of those practising IF and 13% of non-fasters becoming infected (p = 0.51).

The authors concluded that IF appeared to reduce the severity of COVID-19. In addition, they suggested that further work should examine the complementary role of IF with vaccination to reduce COVID-19 severity and how it might impact on long COVID.

Citation
Horne BD et al. Association of periodic fasting with lower severity of COVID-19 outcomes in the SARS-CoV-2 prevaccine era: an observational cohort from the INSPIRE registry BMJ nutr. prev. health 2022

Statin use linked to reduced hospitalisation and mortality risk from COVID-19

6th July 2022

Prior statin use resulted in a significantly lower risk of both hospitalisation and mortality among patients infected with COVID-19

Statin use as primary prevention against cardiovascular disease is associated with a significant reduction in the risk of hospitalisation and mortality among patients who become infected with COVID-19. This was the conclusion of a large, propensity-matched analysis of the French National Healthcare database by a team from the French National Agency for Medicines and Health Products Safety, Paris, France.

While the introduction of COVID-19 vaccines has significantly reduced both hospitalisation and mortality from COVID-19, prior to this drug repurposing was examined as a potential means for reducing the severity of infection and one class of drugs examined were the statins. There were good reasons to consider statins as potentially anti-viral agents because previous work had shown that in patients hospitalised with laboratory-confirmed seasonal influenza, statin treatment is associated with a 41% reduction in 30-day mortality. Moreover, other work found that cells treated with statins produced Ebola virus particles devoid of the surface glycoproteins required for virus infectivity.

There is already some evidence that among patients taking statins, there is a statistically significant decrease in the odds of in-hospital mortality in those with COVID-19. Nevertheless, this is not a consistent finding with other data has suggesting that the use of statins (in patients with type 2 diabetes) is associated with increased mortality among those hospitalised with COVID-19. Much of the research to date did not include a control group and for the present study, the French team identified patients aged 40 years and older, prescribed one of several statins (the exposed group) and propensity-matched these individuals based on age, gender, co-morbidities and sociodemographic factors (control group). But the team were also interested in whether there were differences between individual drugs within the class and if the intensity of therapy (e.g., low, moderate or high) impacted on either COVID-related hospitalisation or mortality. The primary outcome of the study was COVID-19-related hospitalisation and using Cox proportion hazard models, adjusted for several covariates e.g., age, gender, co-morbidities, the researchers calculated event rates between those using statins and the matched-control patients.

Statin use and COVID-19 hospitalisation

A total of 2,058249 patients with a mean age 68.7 years (46.6% male) taking statins were matched with the same of number of control patients. The most common co-morbidities were hypertension (41.8%) and diabetes (33.7%). There were a total of 9,396 hospitalisations for COVID-19, 4372 among those in the control group.

In fully adjusted models, patients in the statin group had a 16% lower risk of hospitalisation (hazard ratio, HR = 0.84, 95% CI 0.81 – 0.88, p < 0.0001). This relationship was maintained for the different agents within the class. For example, the risk was reduced by 25% for fluvastatin (HR = 0.75) and simvastatin (HR = 0.79). The relationship was also significant for low (e.g. fluvastatin 20/40 mg), medium (e.g., simvastatin 10 mg), not not for high (e.g., atorvastatin 40 or 80 mg) intensity therapy.

A similar reduction in risk was also evident for mortality among those taking statins (HR = 0.77, 95% CI 0.69 – 0.86). However, both atorvastatin and fluvastatin did not have a significant effect on mortality and as with hospitalisation, there was no significant effect for high intensity therapy on mortality.

The authors concluded that their data suggested a relatively small, but robust reduction in the risk of COVID-19-related hospitalisation and death among those prescribed statins before hospital admission.

Citation
Bouillon K et al. Association of Statins for Primary Prevention of Cardiovascular Diseases With Hospitalization for COVID‐19: A Nationwide Matched Population‐Based Cohort Study J Am Heart Assoc 2022

Single dose of Evusheld reduces progression of COVID-19 and mortality

24th June 2022

A single dose of Evusheld given intramuscularly to unvaccinated, patients with COVID-19 reduced both the need for hospitalisation and death, according to the TACKLE study

A single dose of Evusheld given to non-hospitalised, unvaccinated patients experiencing mild to moderate COVID-19 led to a significant reduction in progression to more severe disease (i.e., hospitalisation) and mortality compared to those given placebo. These were the key findings from the the TACKLE study by a group of UK and US researchers.

Evusheld contains the two monoclonal antibodies, tixagevimab and cilgavimab, which simultaneously bind to distinct, non-overlapping epitopes on the spike protein receptor binding domain and are therefore able to neutralise COVID-19. It is administered as a single intra-muscular dose and in March 2022, the EMA granted a marketing authorisation for Evusheld for the prevention of COVID-19 in adults and adolescents from 12 years of age weighing at least 40kg before potential exposure to the virus.

The combination of monoclonal antibodies has been examined in TACKLE, which is an ongoing, Phase III randomised, double-blind trial conducted in 95 sites across the USA, Latin America, Europe and Japan. Included patients are adults (18 years and over) with a documented, laboratory confirmed PCR or antigen test, COVID-19 infection, at least 3 days before enrolment in the trial. An additional entry requirement is a score of > 1 but less than 4 on the World Health Organization (WHO) Clinical progression Scale.

For the study, all eligible participants were randomised 1:1 to a single dose of Evusheld (600mg, which consists of two consecutive doses of 300mg of each) or saline solution (which served as the placebo) on the first day of the trial. The primary outcome of the study was a composite endpoint of either severe COVID-19, defined by either the presence of pneumonia, hypoxaemia plus a WHO scale score of 5 and higher or all-cause mortality.

Single dose of Evusheld and COVID-19 outcomes

A total of 903 participants with mean age of 46.1 years (50% female) were enrolled and randomised to evusheld (452) or placebo. Just over half (52%) of participants were of Hispanic or Latino ethnicity with 62% being White and 4% Black or African American. A total of 89% of the entire cohort had at least one or more risk factors for severe COVID-19 including a body mass index > 30 (43%), hypertension (28%), current smokers (40%) and diabetes (12%).

The primary endpoint (severe COVID-19 or death) occurred in 4% of those receiving a single dose of Evusheld and in 9% of those given a placebo and this difference was significant (absolute risk reduction = 4.5%, 95% CI 1.1 – 8.0, p < 0.0001).

In terms of safety, adverse effects occurred in 29% of those given Evusheld and 36% of those using placebo and most were deemed to be of mild or moderate severity.

The authors concluded that a single dose of Evusheld was associated with a statistical and clinically meaningful reduction in both progression to more severe COVID-19 and death compared with placebo among unvaccinated adult patients.

Citation
Montgomery H et al. Efficacy and safety of intramuscular administration of tixagevimab–cilgavimab for early outpatient treatment of COVID-19 (TACKLE): a phase 3, randomised, double-blind, placebo-controlled trial Lancet Respir Med 2022

Head injuries in children requiring hospitalisation two-fold higher during COVID-19

23rd May 2022

Head injuries leading to hospitalisation in children significantly increased during the COVID-19 period compared with pre-pandemic levels

Head injuries in children, and which resulted in hospitalisation, were more than two-fold higher during the COVID-19 pandemic compared with pre-pandemic levels, although the use of CT head scans was not appreciably different. This was the conclusion of a retrospective study by researchers from John Hopkin’s University, Baltimore, Maryland, USA.

Head injuries in children are a common cause for hospitalisation with a report by the US Centers for Disease Control and Prevention citing that in the US in 2016, 8.3% of boys and 5.6% of girls aged 3 –17 years had ever had a significant head injury in their lifetime. Head injuries are damage to the scalp, skull, or brain caused by trauma and in cases where this affects the brain, it is referred to as a traumatic brain injury. The most common causes of such head injuries are falls although other causes in older children are related to sports injuries or even motor vehicle accidents. Little is known about how the pandemic has impacted upon the incidence of head injuries in during during the pandemic although some work based on neuro-trauma admissions observed that while there was a decline in the number of head injury admissions during the pandemic, the severity of the injuries actually increased. However, no studies have compared the level of presentation during COVID-19 with the years prior to the pandemic.

For the present analysis, the US team retrospectively examined the proportion of emergency department visits for head injury in children and the severity of those injuries between March 2020 to June 2020. These data were then compared with data from between March 2019 – June 2019, i.e., pre-pandemic levels. For the analysis, researchers included anyone aged 0 to 21 and set the primary outcomes of interest as the presence of a medically attended head injury, hospital admission for the injury and the need for CT head scanning.

Head injuries in children and hospitalisations

There were a total of 8616 patients with a mean age of 7.4 years (51.4% male) seen with a head injury at the emergency department during the COVID-19 pandemic. This compared with 19,083 visits in the same period during 2019. Overall, there was a significant increase in the proportion of visits during COVID-19 (6.4% vs 5.5%, p = 0.004), for a head injury in children, giving an odds ratio (OR) of 1.2 (95% CI 1.1 – 1.4), even though the absolute number of visits was lower (1058 vs 553, pre-covid vs covid).

In addition, the proportion of visits requiring hospitalisation was more than two-fold higher (OR = 2.3, 95% CI 1.3 – 4.3), which was more likely in male patients (OR = 1.58). However, the need for a CT head scan was not significantly different (OR = 1.04, 955 CI 0.70 – 1.60). Interestingly, there was a lower level of hospital admissions associated with children aged < 2 years (OR = 0.3, 95% CI 0.2 – 0.6) which suggested that head injuries in this age group were less severe.

The authors concluded by suggesting that the higher level of head injuries in children observed during the pandemic period were potentially due to changes in certain factors including supervision and risk exposure in the home.

Citation
Satoskar S et al. Impact of the COVID-19 pandemic on pediatric emergency department utilization for head injuries J Investig Med 2022

Study finds cancer patients with COVID-19 at greater risk of hospitalisation and death

12th May 2022

Cancer patients with COVID-19 have a greater risk of both hospitalisation and death following infection compared with those without the disease

Cancer patients with COVID-19 have been found to be at a greater risk of hospitalisation and 30-day all-cause mortality compared to those without the disease according to the results of a study by a US team from Texas.

The presence of cancer has become a recognised factor that is associated with a higher risk for severe outcomes in those infected with COVID-19 and which is largely due to the presence of a compromised immune system. During the early course of the pandemic, studies observed that a higher proportion of cancer patients infected with COVID-19 were both hospitalised and subsequently died, compared to those without the disease. In contrast, however, other studies have suggested that cancer and non-cancer patients have comparable COVID-19 outcomes after adjusting for age, sex, and comorbidity. Furthermore, the impact of factors such as cancer treatments, different cancer types on COVID-19 related outcomes has been less well studied. For the present study, the US researchers examined the association between cancer-specific characteristics and COVID-19 outcomes. They turned to the Optum de-identified COVID-19 electronic health record, which is derived from over 700 hospitals and 7000 clinics across the USA. Using these data, the researchers examined the outcome of those with a laboratory confirmed COVID-19 and a recorded cancer diagnosis. The primary objective was to determine the effect of cancer on COVID-19 outcomes including 30-day all-cause mortality, hospitalisation, intensive care unit (ICU) admission and ventilator use. These outcomes were also analysed by the nature and type of cancer in comparison to patients without cancer. The authors the explored if there were any other specific factors in those with cancer which impacted on COVID-19 outcomes.

Cancer patient with COVID-19 and related outcomes

A total of 271,639 patients with confirmed COVID-19 of whom 18,460, with a mean age of 66 years (45.3% male) had a cancer diagnosis were analysed. Among those with cancer, 8034 patients had a history of cancer for longer than 12 months and 10,426 had a more recent diagnosis, i.e., within 1 year before COVID-19.

30-day all-cause mortality was more than three times higher among those with cancer (6.8% vs 1.9%) compared to non-cancer patients. After adjustment for age, sex, ethnicity and risk factors, the presence of cancer was associated with a 7% higher risk of death (relative risk, RR = 1.07, 95% CI 1.01 – 1.14, p = 0.028) compared to those without the disease. Similarly, there was a 4% higher risk of hospitalisation (RR = 1.04, 95% CI 1.01 – 1.07, p = 0.006). When comparing the duration of cancer, those with a recent diagnosis had both a significant (p < 0.001) increased risk of mortality (RR = 1.17) and hospitalisation (RR = 1.10) although this risk was non-significant for those who had cancer for much longer.

There was also an increased mortality risk for those with recent metastatic (RR = 2.09), solid tumour (RR = 1.12) and haematological (RR = 1.48) cancers compared with those without the disease. Individual cancers with a significantly elevated risk were leukaemia (RR = 1.58), liver (RR = 2.46), lung (RR = 1.85) and pancreatic (RR = 1.94).

When exploring the factors related to COVID-19 mortality in those with recent cancer, both chemotherapy (RR = 1.37) and radiotherapy (RR = 1.83) within 3-months before COVID-19, were significantly associated with a higher risk of death as was increasing age (i.e., > 75 years) (RR = 6.69). In addition, the only significant co-morbidities were cardiovascular disease (RR = 1.72), diabetes (RR = 1.39) and renal disease (RR = 1.51).

Citation
Kim Y et al. Characterizing cancer and COVID-19 outcomes using electronic health records PLoS One 2022

COVID-19 vaccinated cancer patients at increased risk of breakthrough infections

13th April 2022

COVID-19 vaccinated cancer patients have a greater risk of breakthrough infections leading to higher rates of hospitalisation and mortality

COVID-19 vaccinated cancer patients have been found to be at a higher risk of breakthrough infections and which are associated with a substantial risk of hospitalisation and mortality. This was the conclusion of a retrospective cohort study of electronic health records by a team from the Center for Artificial Intelligence in Drug Discovery, Case Western Reserve University, Ohio, US.

Patients with cancer have been found to be at a significantly increased risk for COVID-19 infection and worse outcomes though fortunately, COVID-19 vaccination has been shown to be associated with lower infection rates in cancer patients. However, despite vaccination, the occurrence of breakthrough infections has also been reported and this appears to be correlated with neutralising antibody titers during the peri-infection period. While COVID-19 vaccinated cancer patients are also potentially likely to experience breakthrough infections, there is a lack of data on the extent to which such breakthrough infections occur among those with cancer and how, or if, this might be influenced by the different cancer sites.

For the present study, the US team turned to the TriNetX database which contains de-identified information on 90 million patients in the US. The team looked for vaccinated patients with one of 12 different cancers including pancreatic, liver, lung, colorectal, skin and thyroid and compared the level of breakthrough infections with a group of vaccinated, patients without any of the specified cancers. Data on age, sex, race and co-morbidities were collected for all patients and adjusted for in the analysis. The researchers examined the monthly incidence of breakthrough infections between December 2020 and November 2021 as well as the risk of hospitalisation and death among those infected.

COVID-19 vaccinated cancer patients and breakthrough infections

A total of 45,253 vaccinated cancer patients with a mean age of 68.7 years (53.5% female) were included in the analysis and matched with 591,212 vaccinated, non-cancer patients.

The cumulative risk of a breakthrough infection during the period of study among vaccinated COVID-19 cancer patients, was 13.6% which was higher than vaccinated, non-cancer patients, (Hazard ratio, HR = 1.24, 95% CI 1.19 – 1.29). Among the different cancer sites, the highest risk was for patients with pancreatic cancer (24.7%), followed by liver (22.8%), lung (20.4%) and colorectal (17.5%). The only cancer not associated with a significant increased risk for a breakthrough infection was thyroid (HR = 1.07, 95% CI 0.88 – 1.30) although the increased risk among patients with skin cancer was of borderline significance (HR = 1.17, 95% CI 0.99 – 1.38).

The risk of hospitalisation among cancer patients with breakthrough infections was much higher than matched, non-cancer patients (31.6% vs 3.9%, HR = 13.48). In addition, mortality risks were also significantly elevated (HR = 6.76, 95% CI 4.97 – 9.20).

The authors concluded that their results emphasised the need for those with cancer to maintain mitigation practices, especially given the emergence of COVID-19 variants for which vaccination might not provide full protection.

Citation
Wang W et al. Breakthrough SARS-CoV-2 Infections, Hospitalizations, and Mortality in Vaccinated Patients With Cancer in the US Between December 2020 and November 2021 JAMA Oncol 2022

Large RCT shows early ivermectin use fails to prevent progression of COVID-19

4th April 2022

Ivermectin use among symptomatic COVID-19 patients does not halt hospitalisation or ED visits for disease worsening compared to placebo

The results of a large RCT have shown that early ivermectin use in patients who are symptomatic with COVID-19 does not reduce either hospitalisation or emergency department (ED) visits due to a worsening of the disease compared to placebo. The TOGETHER trial was designed to examine the potential value of several repurposed drugs for the management of COVID-19 including fluvoxamine, metformin and ivermectin and conducted by researchers from Brazil although the present study only describes the use of ivermectin.

In 2020 an in vitro study reported that the anti-parasitic, drug ivermectin, was able to inhibit COVID-19 leading to an approximate 5000-fold reduction in viral RNA after 48 hours. As a result, several clinical studies were initiated and a review of the emerging evidence in 2021 concluded that meta-analyses based on 18 randomised trials of ivermectin in COVID-19 have found large, statistically significant reductions in mortality, time to clinical recovery, and time to viral clearance. Furthermore, the authors added how results from numerous controlled prophylaxis trials report significantly reduced risks of contracting COVID-19 with the regular use of ivermectin. However, a later meta-analysis virtually reversed the earlier conclusions, finding that ivermectin did not show a statistically significant effect on survival or hospitalisations and no significant effect of ivermectin on time to clinical recovery. Interestingly, the authors later retracted their analysis and in February 2022, they described how in their original analysis, many of the included studies were at a high risk of bias and that others were later identified to be potentially fraudulent. In their 2022 article, they concluded that ‘failure to recognise the potentially fraudulent studies, which led to multiple meta-analyses suggesting significant benefits of ivermectin for COVID-19, indicates that the tools currently used to evaluate the quality of clinical trials are insufficient.’

In order to provide more definitive evidence, the Brazilian team randomised adult patients with symptoms suggestive of COVID-19 (for no longer than seven days), on a 1:1 basis, to ivermectin use (400 microgram/kg body weight) once daily for three days or matching placebo. In addition, all participants had at least one risk factor for disease progression. The primary outcome was a composite of hospitalisation due to COVID-19 within 28 days of randomisation or an emergency department visit because of worsening symptoms (defined as remaining under observation for > 6 hours) also within 28 days of randomisation. Secondary outcomes included COVID-19 viral clearance at days 3 and 7, time to hospitalisation and time to clinical recovery.

Ivermectin use and COVID-19 outcomes

A total of 1358 patients with a median age of 49 years (58.2% women) were randomised to either ivermectin (679) or placebo. Risk factors for disease progression included cardiovascular disease, uncontrolled hypertension, COPD, asthma, type 1 diabetes and chronic kidney disease.

In total, 14.7% of those assigned to ivermectin use met the primary outcome compared to 16.3% in the placebo arm (relative risk, RR = 0.90, 95% CI 0.70 – 1.16). There were a total of 211 primary outcome events, of which 81% were hospital admissions. Moreover, there were no significant differences for any of the secondary outcomes.

Based on these findings, the authors concluded that ivermectin use had no significant impact on preventing disease progression or prolonged emergency department observations.

Citation
Reis G et al. Effect of Early Treatment with Ivermectin among Patients with Covid-19 N Engl J Med 2022

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

29th March 2022

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

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

The Omicron COVID-19 variant has produced a surge of infections and been found to be associated with high transmission among household contacts, particularly among those who lived with index patients who were not vaccinated or who did not take measures to reduce the risk of transmission to household contacts. Nevertheless, despite a higher level of transmissibility, studies have also suggested that the Omicron variant is associated with substantial severity of illness in comparison to the Delta variant.

With an increasing number of individuals now fully vaccinated against COVID-19, the purpose of the present study was to offer a more detailed understanding of the overall impact of both less severe outcomes and greater immunity on rates of hospitalisation and mortality during the Omicron wave. The UK team obtained individual-level data on confirmed cases of COVID-19 infection in England between November 2021 and 9 January 2022 and linked these to vaccination status, hospital attendance and admission as well as deaths. During the period of study genomic sequencing was performed for some of the infections which enabled the team to distinguish between the two variants. For the study, a hospital admission was defined as a stay of at least one or more days. The analysis was stratified by age, vaccination status and adjusted for sex, deprivation index and evidence of prior infection.

Omicron caused less severe outcomes

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

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

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

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

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

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

Vitamin D-deficient patients 14-times more likely to get severe COVID-19

7th February 2022

Vitamin D-deficient patients are more likely to get severe COVID-19 and die compared with those with sufficient levels of the vitamin

Vitamin D-deficient individuals have been shown to be much more likely to experience severe COVID-19 and die in comparison to those with normal or sufficient levels of the vitamin. This was an important finding by researchers from the Department of Otolaryngology, Head and Neck Surgery, Galilee Medical Center, Israel.

Previous research has shown how vitamin D has a protective effect against respiratory tract infections when taken as a once daily dosage. Moreover, a 2021 systematic review which included 46 randomised controlled trials with 48,488 individuals, re-affirmed the benefits of daily supplementation with 400 –1000 IU of vitamin D for reducing the risk of acute respiratory tract infections compared with placebo. Several studies undertaken during the COVID-19 pandemic have suggested that a vitamin D deficient status was associated with increased COVID-19 risk. Furthermore, other data has shown how the vitamin D level is markedly low in severe COVID-19 patients although this was measured once in hospital. However, what is less clear, is the extent to which pre-infection or baseline vitamin D levels, impact on the clinical outcomes once patients become infected with COVID-19.

For the present study, the Israeli team set out to determine whether COVID-19 disease severity correlated with patient’s most recent vitamin D levels as documented in their medical records. They undertook a retrospective study of hospitalised, adult patients with a PCR-confirmed COVID-19 infection. The team defined COVID-19 disease severity at the point of highest severity. For instance, if a patient was admitted with mild disease and which subsequently deteriorated, this would be categorised as a critical illness. They used the most recent medical record for vitamin D status and then categorised patients as vitamin D deficient (< 20 ng/ml), insufficient (20 – 29.9 ng/ml), adequate (30 – 39.9 ng/ml) and high-normal (40 ng/ml). They used multivariable analysis to examine the relationship between vitamin D status and COVID-19 disease severity.

Vitamin D deficient status and COVID-19 severity

A total of 253 individuals with a mean age of 63.3 years (56.9% female) were included in the analysis. Among the cohort, 52.5% were vitamin D-deficient, 14.2% had levels between 20 and 30ng/ml and 15.8% had a level of 40ng/ml or above.

Mortality from COVID-19 occurred in 2.3% of those with adequate vitamin D levels and 25.6% of individuals who were vitamin D deficient (p < 0.001). When stratifying COVID-19 disease severity with vitamin D status, among those with the lowest vitamin D levels, a higher proportion (87.4%) developed severe or critical COVID-19 compared to mild to moderate disease, 34.3% (p < 0.001). In regression analysis, patients with vitamin D deficiency compared to those with high-normal levels (40 ng/ml) were 14 times more likely to develop severe or critical illness (odds ratio, OR = 14, 95% CI 4 – 51, p < 0.001). Overall, when comparing pre-hospital vitamin D levels with COVID-19 disease severity, there was a clear inverse relationship such that as vitamin D levels reduced, COVID-19 disease severity increased.

Further analysis revealed that age was an independent risk factor for more severe disease and the strongest correlation between vitamin D status and COVID-19 severity occurred in those aged 50 years and over (r = – 0.74, p < 0.001). However, this correlation was still significant among those under 50 years of age (r = -0.66, p < 0.001).

The authors described how early on in the current pandemic, there was much debate on the role of vitamin D in protecting against COVID-19. They suggested that their study provided further evidence of how vitamin D deficient patients were at a much higher risk of more severe COVID-19 infection and called for further studies to investigate if and when vitamin D supplementing in those who are deficient, impacts on COVID-19-related outcomes.

Citation
Dror AA et al. Pre-infection 25-hydroxyvitamin D3 levels and association with severity of COVID-19 illness PloS One 2022

Omicron infection causes fewer hospitalisations and severe disease compared with Delta variant

24th December 2021

Omicron infection appears to be associated with a lower risk of hospitalisation and less severe disease than the Delta COVID-19 variant, according to a recent study

According to a preprint study by researchers from the Centre for Respiratory Diseases and Meningitis, Johannesburg, South Africa, Omicron infections appear to be associated with reduced risk of hospitalisation and after admission, less severe disease than the Delta variant.

While the Omicron COVID-19 variant was only identified in November 2021, there has been a flurry of research activity directed at trying to understand its transmissibility, the level of disease severity and effect on healthcare services. While initial laboratory studies have indicated that the variant can escape neutralisation by antibodies generated in fully vaccinated and boosted sera samples, these studies cannot foretell the clinical impact of the variant.

The South African researchers undertook a data linkage study of COVID-19 infections, case data and genomic information to establish whether an Omicron infection was associated with higher rates of hospitalisation and more severe disease among those who were hospitalised in comparison to the Delta COVID-19 variant. Although whole genome sequencing was not used, they utilised the presence of a S Gene Target Failure (SGTF), which serves as a proxy for Omicron and samples were examined between 1st October 2021 and 6th December 2021. Positive infections were therefore classified as either an SGTF or non-SGTF. The severity of an Omicron infection was assessed by comparison of SGTF and non-SGTF infections and to infections known to be caused by the Delta variant and regression models created and adjusted for several factors known to be associated with hospitalisation (e.g., age, sex, co-morbidities).

Findings

During the period of study there were 161,328 COVID-19 cases recorded and the proportion of SGTFs increased from 3% (early October 2021) to 98% (early December).

A total of 11,495 hospital admissions occurred with 2.5% due to an SGTF compared to 12.8% with a non-SGTF (p < 0.001). Multivariate analysis revealed that individuals with a SGTF had a lower odds of hospitalisation (adjusted odds ratio, aOR = 0.2, 95% CI 0.1 – 0.3, p < 0.001). In addition, once hospitalised, the odds of having severe disease were also reduced in those with SGTF although there was uncertainty over this estimate given the wide confidence intervals (aOR = 0.70, 95% CI 0.30 – 1.40).

Finally, the researchers found that compared to infection with the Delta variant, those with an SGTF had a significantly lower risk of severe disease (aOR = 0.30, 95% CI 0.20 – 0.50, p < 0.001).

The authors suggested that these data suggested that an Omicron infection was probably less severe than other variants such as Delta but recognised that this reduced severity might be accounted for by the higher levels of population immunity due to either natural infection and/or vaccination.

These results are broadly similar to those of a second recently published preprint from Scotland which found a nearly 70% reduced risk of hospitalisation (expected ratio = 0.32, 95% CI 0.19 – 0.52) for those with an Omicron infection. The study also found that giving a third or booster dose was associated with a 57% reduced risk of symptomatic infection.

Although both studies are preliminary, they do suggest the possibility that infection with the new variant is potentially less severe than other forms.

Citation

Wolter N et al. Early assessment of the clinical severity of the SARS-CoV-2 Omicron variant in South Africa. MedRxiv 2021