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24th June 2022
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.
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
7th June 2022
The use of hormone replacement therapy (HRT) by women within 6 months of developing an infection with COVID-19 has been found to be linked with a significantly reduced risk of subsequent death, according to a retrospective analysis by a group of UK researchers.
Deaths from COVID-19 have shown a male bias with one estimate suggesting that men are 1.7-times more likely to die than women. However, this observation is not new and similar findings were observed with severe acute respiratory syndrome, where the mortality rate was 21.9% for men but only 13.2% for women. The reasons behind these apparent sex-related differences are unclear but attention has focused on a potentially protective effect of oestrogens. Data from the COVID symptom study found that women using the combined oral contraceptive pill had a lower rate of predicted infection with COVID-19 although the relationship with the use of hormone replacement therapy was less clear. To date, only one retrospective analysis of women using hormone replacement therapy has been undertaken and suggested that the fatality risk for women over 50 years of age and in receipt of oestradiol therapy was reduced by more than 50%.
In an effort to better understand the relationship between HRT use and mortality after infection with COVID-19, the UK team retrospectively examined information held in the Oxford-Royal College of General Practitioners Research and Surveillance Central database. They identified a cohort of women with a PCR confirmed COVID-19 infection and who had been prescribed HRT within 6 months of their date of infection. The researchers set the study’s primary outcome as all-cause mortality during the follow-up period (January 2020 to June 2020) and also extracted included age, ethnicity and co-morbidities which were adjusted for in their regression analysis.
HRT use and all-cause mortality
A total of 5451 women with a mean age of 59 years were included and followed for a mean of 164.9 days and of whom 4.3% were prescribed HRT.
As in other studies, the risk of death was higher among women who were older, underweight and with co-morbidities such as hypertension and the use of immunosuppressants.
During the follow-up period, a total of 664 women (12.2%) died and the risk of all-cause mortality was significantly less likely in those using HRT (odds ratio, OR = 0.22, 95% 0.05 – 0.94, p = 0.041). Interestingly, women prescribed HRT and asthma, had a much lower risk of mortality (OR = 0.58, 95% CI 0.42 – 0.81, p = 0.001) and the authors suggested that since these women were also likely to be prescribed steroids, this could have produced an added protective effect.
The authors concluded that women should be reassured that there was no reason to stop using HRT because of the pandemic and called for future studies to examine the effect of different doses and formulations and how these might impact on COVID-19 outcomes.
Dambha-Miller H et al. Mortality in COVID-19 among women on hormone replacement therapy: a retrospective cohort study Fam Pract 2022
1st June 2022
Vasopressor use in COVID-19 patients who become critically ill is linked to an increased risk of death compared to those not given such drugs according to the results of a meta-analysis by a team of Greek and US researchers.
Patients who are critically ill with not only COVID-19 but any illness, require haemodynamic support. In 2020, the Surviving Sepsis Campaign COVID-19 panel issued a number of statements regarding the management of COVID-19. In relation to COVID-19 and shock, the panel advocated that for adults who experience shock, use of norepinephrine should be used as the first-line vasoactive agent. Vasopressor use is designed to increase vascular tone and is necessary in critically ill patients with profound haemodynamic impairment such that tissue blood flow is not sufficient to meet metabolic requirements. Vasopressors are commonly used, in fact, one survey of critical care staff managing patients with COVID-19 found that overall, 56% reported (combined very frequent/frequent use) vasopressor use in COVID-19 patients. Despite the impact on haemodynamic stability, vasopressors are known to have several adverse cardiovascular effects. For example, in one study, new-onset tachyarrhythmias, prolonged elevation of heart rate and myocardial cell damage were frequently observed and that overall, adverse cardiac events occurred in 48.2 % of all intensive care patients. Although current guidelines recommend the use of catecholamines for their haemodynamic effects, these drugs have numerous other biological effects in shock states including aggravation of hyper-metabolism by promoting hyperglycaemia, which further increase oxygen demands and can contribute to further organ damage. It is possible therefore that vasopressor use in critically ill COVID-19 patients could have a deleterious effect although this has not been fully examined.
For the present study (which is available as a preprint), the researchers systematically reviewed the literature for studies in which adult critically ill patients were given vasopressors. They set the primary outcome of interest as all-cause mortality at days 28 or 30 but if this data was missing, simply referred to the level of all-cause mortality reported. A secondary outcome considered was the level of acute kidney injury.
Vasopressor use and all-cause mortality
A total of 33 observational studies were included in the final analysis although only 30 included a direct comparison of vasopressor use vs no use. The remaining three studies examined either use of angiotensin-II use only (1 study) or angiotensin-II vs vasopressor use.
The primary outcome could be assessed from 21 of the studies with 7,900 patients. The analysis revealed that vasopressor use was associated with a statistically significant increased risk of mortality (relative risk, RR = 4.26, 95% CI 3.15 – 5.76,p < 0.001). In subgroup analysis by department of admission, i.e., intensive care (RR = 3.45) or high dependency unit (RR = 6.25) also revealed a significant increased mortality risk (p < 0.001 in both cases).
For the secondary outcome of acute kidney injury, vasopressor use was also significantly associated with a greater risk of the outcome (RR = 3.17, 95% CI 2.21 – 4.54, p < 0.001).
The authors concluded that vasopressor use was associated with a higher level of mortality in critically ill COVID-19 patients and called for further studies to estimate the correlation of specific vasopressor agents with adverse effects and mortality.
Mermiri M et al. The effect of vasopressors on mortality in critically ill patients with COVID-19: A systematic review and meta-analysis Med Rxiv 2022
25th May 2022
A multi-inflammatory index (MII) biomarker have been shown to have good predictive power for mortality among COVID-19 patients admitted to an intensive care unit (ICU). This was the main finding of a study by a team of Turkish researchers.
It is common among patients with severe COVID-19 to develop acute respiratory distress syndrome (ARDS) which represents a life-threatening form of respiratory failure and after the initial infection, neutrophils, which form part of the innate immune system, rapidly infiltrate the lungs. However, lymphocytes also have an important role in both immune homeostasis and inflammatory responses throughout the body and lymphopenia has been shown to be an effective and reliable indicator of the severity and hospitalisation in COVID-19 patients. Nevertheless, infection with COVID-19 produces several biochemical abnormalities including elevation of C-reactive protein in patients with severe disease, together with hyper-inflammation and a cytokine storm. In fact, alterations in the level of several markers has been shown to be of value in predicting the prognosis of patients infected with the virus.
One particular biomarker, the multi-inflammatory index (MMI), which includes the neutrophil to lymphocyte ratio (NLR) and C-reactive protein (CRP), has been shown to have good prognostic mortality value when originally examined in patients with metastatic colorectal cancer undergoing first-line chemotherapy.
As other research has found that both the neutrophil-lymphocyte ratio and C-reactive protein are significantly higher in patients with COVID-19 and who subsequently die, the Turkish team wondered if the MII – which includes both measures – would have prognostic value for identifying which critically ill patients with COVID-19, were at a higher risk of mortality.
The team retrospectively analysed data on COVID-19 patients admitted to an ICU and compared the prognostic value of MII with a range of inflammatory biomarkers including the urea to albumin ratio, CRP to albumin ratio and the D-dimer to albumin ratio.
Multi-inflammatory index and COVID-19 mortality
A total of 348 patients with a median age of 74 years (59% male) were admitted to ICU due to COVID-19 and included in the analysis.
Overall, 24.7% of patients survived and the remainder died. While co-morbidities such as hypertension, diabetes and COPD were numerically higher among those who died, these differences were not statistically different.
Using multiple logistic regression, among all the inflammatory measures used, only MII was found to be an independent predictor of mortality (odds ratio, OR = 0.99, 95% CI 0.99 – 0.99, p = 0.03). Other significant predictors included age (OR = 1.07), the NLR (OR = 1.07).
Commenting on their results, the authors suggested that the likely reason why the NLR ratio was elevated in COVID-19 patients was because of an increased neutrophil count and a corresponding lymphopenia. They concluded that MII represents a simple and practical biomarker which could help identify COVID-19 patients with a poor prognosis and called for further studies to validate these retrospective findings.
Gozdas HT et al. Multi-inflammatory Index as a Novel Mortality Predictor in Critically Ill COVID-19 Patients J Intensive Care Med 2022
21st February 2022
Use of oestrogen supplementation in the form of hormone replacement therapy (HRT) in postmenopausal women is associated with a reduced risk of death from COVID-19. This is according to research by a team from the Department of Surgical and Peri-operative Sciences, Umeå University Faculty of Medicine, Umeå, Sweden.
Previous studies have suggested that the prevalence of symptomatic COVID-19 is higher in men than in women. Moreover, a similar pattern has been observed with severe acute respiratory syndrome, with one analysis finding that males appear to be more severely affected by the disease than females. Such data clearly highlight an important biological difference in susceptibility to infection with both viruses although the precise nature of this difference is uncertain.
One potentially important factor is the hormone oestrogen. In an effort to better understand the effect of this hormone on COVID-19-related mortality, the Swedish team examined the mortality outcomes for women either with augmented or reduced levels of oestrogen. They used a retrospective design to explore data held in a national register and included postmenopausal women aged 50 to 80 years of age. These individuals were then stratified into three groups: group 1 (decreased oestrogen, e.g., prescribed tamoxifen, fulvestrant or an aromatase inhibitor); group 2 (oestrogen supplementation with HRT) and finally a native oestrogen group which served as a control, with women who did not have breast cancer diagnosis and were not prescribed HRT or anti-oestrogen treatment. The primary outcome of interest was COVID-19 mortality and the result was adjusted for several covariates including a co-morbidities index, income and education levels.
Oestrogen supplementation and COVID-19 mortality
A total of 14,685 women with a mean age of 62.1 years, of whom 227 received oestrogen reducing treatment and 2,535 received HRT were included in the analysis. Women receiving oestrogen reducing therapy were slightly older (mean age 64.4 years) had a higher mean co-morbidity index.
Reducing oestrogen levels was associated with an increased mortality risk from COVID-19 (odds ratio, OR = 2.25, 95% CI 1.51 – 3.65). However, after adjustment, this effect was no longer significant (OR = 1.21, 95% CI 0.74 – 1.98). In contrast, oestrogen supplementation was associated with a decreased odds of COVID-19 mortality, even after adjustment (OR = 0.47, 95% CI 0.34 – 0.63). Overall, the absolute risk of dying from COVID-19 was 4.6% in the control group, 10.1% in the oestrogen reducing group and 2.1% in those using HRT.
In addition and as might be expected, mortality was also related to age and the co-comorbidity index. The authors calculated that for each year increase in age, the odds of dying were increased (OR = 1.15, 95% CI 1.14 – 1.17) and a similar trend was seen for increases in the co-morbidity index (OR = 1.13).
The authors concluded that their study identified how the use of oestrogen supplementation may have a therapeutic role in COVID-19 mortality and which should be explored in future studies.
Sund M et al. Association between pharmaceutical modulation of oestrogen in postmenopausal women in Sweden and death due to COVID-19: a cohort study BMJ Open 2022
13th January 2022
Atorvastatin given to patients infected with COVID-19 and admitted to an intensive care unit (ICU) is not associated with a significant reduction in adverse outcomes according to research by a team from the Rajaie Cardiovascular Medical and Research Centre, Tehran, Iran.
Hydroxymethylglutaryl coenzyme A reductase inhibitors (or statins), are known to exert a direct antithrombotic effect in models of arterial and venous thrombosis via a mechanism unrelated to the cholesterol-lowering activity, as well as having anti-inflammatory properties. Furthermore, a 2021 systematic review also identified additional pleiotropic effects including antiviral and immunomodulatory that might help treat COVID-19.
Given this potential beneficial role for statins, the Iranian team sought to examine the impact of atorvastatin on thromboembolic events or death, in patients with the COVID-19, admitted to ICU. Their study was part of the INSPIRATION trial which had two arms: one that explored the effect of prophylactic anticoagulation and the other focusing on the use of atorvastatin.
The team recruited adult patients (> 18 years of age) with a PCR confirmed COVID-19 infection, admitted to ICU and in whom there was no baseline therapeutic need for a statin. Enrolled patients were then randomised 1:1 to atorvastatin 20 mg daily or matching placebo and followed for 30 days after randomisation. For patients requiring mechanical ventilation, the drug was delivered via a nasogastric or orogastric tube. The primary outcome of interest was a composite of venous or arterial thrombosis, treatment with extracorporeal membrane oxygenation or all-cause mortality within 30 days of randomisation.
A total of 587 patients with a median age of 57 years (44% female) were randomised to atorvastatin or placebo and treatment was used for a median of 21 days and slightly less, at 19 days for placebo. The median length of stay within ICU was 5 days in both groups.
After 30 days, the primary outcome had occurred in 95 (33%) of patients assigned to atorvastatin and 108 (36%) of those given placebo (odds ratio, OR = 0.84, 95% CI 0.58 – 1.21, p = 0.35). The results for the primary outcome were largely driven by mortality, with 31% and 35% of deaths in the atorvastatin and placebo groups respectively although no patients required extracorporeal membrane oxygenation.
The use of imaging tests such as computed tomography pulmonary angiograms and doppler, revealed a similar level of venous thromboembolism diagnoses in the two groups (20% vs 20%, p = 0.64). There was also no difference in the incidence of arterial thrombosis. In subgroup analysis, there were no sex-related differences, among patients older/younger than 65 years, smokers or in those with/without obesity or diabetes.
In trying to account for their findings, the authors speculated that atorvastatin may have had a small protective effect which was undetectable or that statins were only of benefit in the early stages of COVID-19 infection prior to the inflammatory response which led to irreversible damage.
INSPIRATION-S investigators. Atorvastatin versus placebo in patients with covid-19 in intensive care: randomized controlled trial. BMJ 2022
11th January 2022
Immunosuppressive biologics are not associated with an increased risk of either infection with COVID-19 or a higher incidence of death according to the findings from a team from the Department of Dermatology, Massachusetts General Hospital, Boston, US.
Whether immunosuppressive biologics would heighten the risk of infection with COVID-19 seems, at least from some evidence, to be unfounded. Despite this, other work has revealed an increased risk of mortality among patients with rheumatic diseases prescribed non-biologic immunosuppressants such as azathioprine, cyclophosphamide, ciclosporin, mycophenolate or tacrolimus.
With a potential risk for viral reactivation of an underlying chronic viral infection during immunosuppressive therapy, some have questioned whether patients with psoriasis, for example, should be started on immunosuppressive biologics.
In the present analysis, the US team focused on adult patients (18 years and over) and given at least one prescription for a biologic between July 2019 and February 2020 at their hospital. They undertook a retrospective, matched cohort study and set the primary outcome as the risk of COVID-19 infection and the secondary outcome as subsequent mortality. Using multivariable logistic regression, they calculated the odds ratio (OR) for a COVID-19 diagnosis between those prescribed immunosuppressant biologics and the control group and examined other potential factors associated with either infection or mortality.
A total of 7361 patients receiving immunosuppressant biologics were matched with 74,910 controls. The most common biologic agents were tumour necrosis factor inhibitors including adalimumab (28.4%), infliximab (15.6%) and etanercept (11.9%), CD20-directed antibodies including rituximab (15.6%) and interleukin-4A inhibitors such as dupilumab (8.6%).
Among the 7361 patients, the primary indication for the immunosuppressive biologics were mainly dermatological diseases such as psoriasis (27.3%) and atopic dermatitis (27.5%), although patients also received these drugs for rheumatoid arthritis (27.5%) and asthma (19.4%).
After adjustment for demographics and co-morbidities, overall, biologics were not associated with COVID-19 (OR = 0.88, 95% CI 0.71-1.09, p = 0.25). Patients prescribed tumour necrosis factor inhibitors were less likely to be diagnosed with COVID-19 compared to matched controls (OR = 0.69, 95% CI 0.48 – 0.98, p = 0.05). Similarly, those treated with dupilumab also had lower risk of being diagnosed, but this difference was non-significant (OR = 0.38, 95% CI 0.12 – 1.18, p = 0.10).
For the secondary outcome of mortality, after adjustment, the difference in rates between the those taking immunosuppressive biologics and controls were non-significant (OR = 1.13, 95% CI 0.57 – 2.76, p = 0.57).
In their regression analysis, the odds of mortality was significantly associated only with age (OR = 1.06, 95% CI 1.04 – 1.09, p < 0.001) with female patients having a much lower odds of mortality (OR = 0.53, 95% CI 0.34 – 0.83, p < 0.01).
They concluded that dermatologists and patients should prioritise the recognised risk factors for infection when making therapy decisions, given how immunosuppressive biologics do not appear to be a risk factor for either infection or mortality.
Pahalyants V et al. Immunosuppressive biologics did not increase the risk of COVID-19 or subsequent mortality: A retrospective matched cohort study from Massachusetts J Am Acad Dermatol 2021
2nd December 2021
Inhibition of the renin-angiotensin-aldosterone system (RAAS inhibition) reduces mortality in those hospitalised with COVID-19 and admitted to an intensive care unit. This was the finding of a retrospective analysis presented at the American Heart Association (AHA) conference 2021.
Inhibition of the RAAS system can be achieved through the use of both angiotensin converting enzyme inhibitors (ACEis) and angiotensin receptor blockers (ARBs). Although it has become widely accepted that the COVID-19 virus gains entry to cells via the angiotensin converting enzyme 2 receptor, whether existing use of drugs affecting the RAAS system affects the outcomes of those with more severe COVID-19 infection remains uncertain.
For the present study, researchers turned to the COVID-19 Critical Care Consortium which represents a global database of de-identified information on treatment outcomes of critically ill COVID-19 patients. The critical care consortium includes data from 354 centres in 54 countries and thus represents an important source of information for researchers as it generates a huge amount of clinical insight about the virus. The stated aim of the study was to examine the role of ACEi / ARB drug exposure (i.e., RAAS inhibition) on outcomes in COVID-19 patients with prior hypertension (HTN) and who had been admitted to intensive care units (ICU) due to the severity of their infection. For the analysis, researchers focused on adult patients (i.e., >18 years of age) and with pre-existing HTN. Outcomes of interest included the length of stay and in-hospital mortality to 90 days post ICU admission.
A total of 663 eligible patients were included in the analysis, of whom, 480 patients, with a median age of 65 years (67% male) had been prescribed an ACEi and / or ARB therapy in the 2 weeks before ICU admission. The average lengths of stays in both ICU and a general ward were longer in those prescribed ACEi / ARB drugs compared to non-users (20.8 days and 6.5 days vs. 15.5 and 6.0 days, respectively). However, RAAS inhibition treatment was associated with a decreased risk of death (Hazard ratio, HR = 0.69, 95% CI 0.54 — 0.88) which persisted after adjusting for propensity scores (HR = 0.67, 95% CI 0.53 — 0.86).
Based on these findings, the authors concluded that the use of ACEi/ARB’s for the management of pre-existing hypertension was associated with a reduced mortality risk in those admitted to an ICU after admission to hospital due to the severity of their COVID-19 infection.
Sato K et al. Abstract 10482: Renin-Angiotensin-Aldosterone System Inhibition is Associated with Reduced In-Hospital Mortality in Critically Ill Covid-19 Patients with Pre-Existing Hypertension. Circulation 2021
19th October 2021
Statin use appears to be associated with a lower mortality in those infected with COVID-19 according to the results of a large, Swedish cohort study. Previous studies in this area have been ambiguous. For example, a Danish observational study concluded that “recent statin exposure in patients with COVID-19 infection was not associated with an increased or decreased risk of all-cause mortality or severe infection.” In contrast, a US study observed a greater than 50% reduction in the risk of developing severe COVID-19 after controlling for co-morbidities and other treatments. Although a meta-analysis of studies on the use of statins and outcomes for COVID-19, concluded that the drug class was not associated with an improvement in a composite of poor outcomes, there was substantial heterogeneity with the included studies. While on-going trials examining the adjunctive value of statins will ultimately provide some much needed clarity of the possible benefit of this class of medicine, a team from the Department of Global Public Health, Karolinska Institute, Stockholm, Sweden, have published data from a large, population-based observational study, examining the relationship between statin use and COVID-19 mortality.
Using a prescribed drug registry, the team included individuals aged 45 years and older prescribed any type of statin between March 2019 and the end of February 2020. These individuals were followed-up until death from either COVID-19 or any other cause. For their study, the primary outcome of interest was death from COVID-19 and the analysis was presented as adjusted hazard ratios. Adjustments were made for numerous factors including age, gender, income, household crowding and wide range of co-morbidities.
A total of 963,876 individuals were included in the analysis. The cohort comprised, 169, 642 statin users with a median age of 71 years (43.4% female) with hypertension being the most common co-morbidity (74.3%). Overall, 2,545 individuals died from COVID-19 during the period of follow-up; 756 (0.5%) who were statin users, giving an adjusted hazard ratio for mortality of 0.88 (95% CI 0.79 – 0.97, p = 0.01) compared to non-statin users. This association did not differ by gender (p = 0.65), across age groups (p = 0.82) or COVID-19 risk groups (p = 0.72).
Although of course these data do not prove that statin use reduces death in those with COVID-19, it offers some tentative clues that individuals using these drugs appear less likely to die from infection with the virus. The authors concluded that the results provide some support for the continued use of statins during the COVID-19 pandemic.
Bergqvist R et al. HMG-CoA reductase inhibitors and COVID-19 mortality in Stockholm, Sweden: A registry- based cohort study. PLoS Med 2021
29th July 2021
Patients with mental health problems might be at a greater risk of worse outcomes when infected with COVID-19, especially as such patients often have other co-morbidities, some of which have been identified as risk factors. In addition, mental health problems are associated with low socioeconomic status and which has been linked to a greater risk of critical care admission among those infected with COVID-19. In fact, data collected from several countries has already revealed how severe mental illnesses such as schizophrenia, are a risk factor for greater COVID-19 mortality although other work has concluded that a diagnosis of mental illness was not associated with an increased likelihood of testing positive for COVID-19. While a recent meta-analysis has suggested a pre-diagnosis of mental disorders worsens the prognosis of COVID-19, the analysis had methodological issues and did not examine the effect for individual diagnoses. This led a team from the CEReSS-Health Service Research and Quality of Life Centre, Marseille, France, to undertake a systematic review and meta-analysis of the accumulating evidence on mental health disorders and COVID-19. Their primary objective was simple to determine whether patients with mental health disorders were at an increased risk of COVID-19 mortality compared to those without such problems. A secondary objective was to explore if the presence of a mental health disorder increased the risk of intensive care admission and if there were any mental health conditions that specifically increased the risk of COVID-19 mortality. The team searched for articles which included participants with a diagnosis of a mental health disorder and a clinical diagnosis of COVID-19 and where intensive care unit and mortality data were included. Adjustments were made for the presence of other known risk factors for COVID-19, i.e., co-morbidities, age etc.
A total of 16 population-based cohort studies across seven countries with 19,086 patients were included in the meta-analysis. Overall, the present of mental health disorders was associated with an increased risk of COVID-19 mortality (odds ratio, OR = 1.38, 95% CI 1.15–1.65). In studies where only severe mental illness such as schizophrenia or bipolar disorder were included, the mortality risk was higher (OR = 1.67, 95% CI 1.02–2.73). There was no apparent association between any specific mental health disorder and COVID-19 mortality and there was insufficient data to determine whether mental health disorders were associated with intensive care admission.
Commenting on these findings, the authors suggested that individuals with mental health disorders should be targeted as a high-risk population for severe COVID-19, requiring enhanced disease management strategies. They concluded by calling for future studies to examine the risks associated with individual mental health disorders and to confirm their findings of the link between severe mental health and increased COVID-19 mortality.
Fond G et al. Association Between Mental Health Disorders and Mortality Among Patients With COVID-19 in 7 Countries. A Systematic Review and Meta-analysis. JAMA Psychiatry 2021