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

Multi-inflammatory index predicts mortality in critically ill COVID-19 patients

25th May 2022

The multi-inflammatory index has been shown to an effective biomarker for the prediction of mortality in critically ill COVID-19 patients

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.

Citation
Gozdas HT et al. Multi-inflammatory Index as a Novel Mortality Predictor in Critically Ill COVID-19 Patients J Intensive Care Med 2022

Scent dogs have comparable accuracy to PCR for detecting COVID-19 infected individuals

24th May 2022

Screening individuals for COVID-19 with scent dogs at an airport has been shown to have similar accuracy to PCR testing

Pre-screening airport arriving passengers for COVID-19 with scent dogs has been found to be as accurate as PCR tests for the identification of infected individuals according to the results of a study by a team of Finnish researchers.

Currently, the identification of COVID-19 relies upon either a polymerase chain reaction (PCR) or the results of lateral flow tests. The PCR tests are very accurate, such that when someone has a positive result, there is a 98% probability that they have COVID-19. Although less accurate, antigen tests have a pooled sensitivity of 79% but a pooled specificity of 100%. Another potential yet rapid means of testing for COVID-19, involves using scent dogs. In fact, a 2016 study found that such dogs were able to differentiate between infected and non-infected cultured cells with bovine viral diarrhoea virus. The value of using dogs for the rapid detection of a virus is that the animals have an extremely sensitive olfactory system with a lower limit of detection of one part per trillion.

During the pandemic, a number of small scale studies demonstrated how scent dogs can detect COVID-19 in different body fluids and while these results have been encouraging, real-world data are needed to confirm the value of scent dogs, particularly in situations where rapid detection is needed; for example, the screening of people arriving at an airport.

For the present study, the team compared the accuracy of scent dogs to detect COVID-19 in airport arrivals with standard PCR tests. The dogs were initially trained to identify the COVID-19 scent and this process was subsequently validated by randomly presenting each of the dogs with both positive and negative samples over a period of a few days. In the final and real-world part of the study, the scent dogs screened skin swab samples from incoming passengers at an airport and for whom PCR tests were also performed. The main outcomes of interest were diagnostic accuracy (based on sensitivity, specificity and positive predictive value) and which were compared against the PCR test result.

Scent dogs and detection of COVID-19

A total of 4 dogs were used in the study and, during the validation part, the dogs had an overall accuracy of 92% with a sensitivity of 92% and a specificity of 91% compared to PCR test results.

For the real-world aspect of the study, the results for scent dogs and PCR tests were correctly matched for 97.7% of samples. However, there were few individuals actually infected with COVID-19; hence there was a very low (0.47%) positivity rate. As a result, the researchers included an additional 155 positive samples, of which the dogs accurately identified 98.7% of these as positive.

The authors concluded that while the validation part of the study was successful, the lack of positive samples in the real-world part made it difficult to confirm the sensitivity for detection although use of additional samples did offer evidence of convincing accuracy.

Citation
Kantele A et al. Scent dogs in detection of COVID-19: triple-blinded randomised trial and operational real-life screening in airport setting BMJ Glob Health 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

Androgen suppression with degarelix fails to improve outcomes in men hospitalised with COVID-19

2nd May 2022

Treatment with degarelix, which suppresses androgen levels, in men hospitalised with COVID-19 failed to improve any measured clinical outcomes compared with placebo

The androgen suppressant degarelix, used in the treatment for adult men with advanced hormone-dependent prostate cancer, did not reduce either mortality, the ongoing need for hospitalisation or a requirement for mechanical ventilation, in men hospitalised with COVID-19 compared with placebo. This was the conclusion of a randomised controlled trial by researchers from the Division of Hematology-Oncology, Department of Medicine, VA Greater Los Angeles Healthcare System, Los Angeles, USA.

The COVID-19 virus utilises both a cell surface ACE2 receptor and a serine protease, transmembrane serine proteases 2 (TMPRSS2) for S protein priming, to gain entry into cells. This complex process requires the concerted action of binding to the ACE2 receptor and TMPRSS2 proteolytic processing of the S protein on the virus, to facilitate virus-cell fusion. It has been found that androgens regulate the expression of ACE2, TMPRSS2 as well as the androgen receptor (AR) in subsets of lung epithelial cells. Moreover, AR levels are markedly elevated in males compared to females and in men older than 70 years of age, who also smoked, researchers observed elevated levels of AR and ACE2 in lung epithelial cells. As TMPRSS2 levels are controlled by androgens, the US team speculated that using specific androgen deprivation therapy (ADT) which would reduce TMPRSS2 expression, thereby limiting cellular entry of COVID-19 and reducing the severity of infection. In fact, using both a human and mouse cell model, researchers identified that camostat-a TMPRSS2 inhibitor, blocked the cleavage of a pseudo-type COVID-19 surface spike protein thus providing evidence for a direct role of TMPRSS2 in viral fusion to the host cell.

Given these early findings, the US examined whether using androgen suppression with degarelix, would improve the clinical outcomes of men hospitalised with COVID-19. The team undertook the Hormonal Intervention for the Treatment in Veterans with COVID-19 Requiring Hospitalisation (HITCH) trial, which was a multi-centre, Phase II randomised trial of standard care either with or without degarelix in male patients hospitalised with COVID-19. Participants were given a single, 240mg subcutaneous dose of degarelix which was administered within 24 hours of being randomised, 2:1 (degarelix:placebo). The primary endpoint of the trial was a composite of mortality, the need for ongoing hospitalisation or the requirement for mechanical ventilation, 15 days after randomisation.

Degarelix and COVID-19 outcomes

A total of 96 men with a mean age of 68.5 years (with 70.8% > 65 years of age) were included in the trial. Overall, baseline co-morbidities included COPD (15.6%), hypertension (78.1%) and cardiovascular disease (28.1%).

On day 15, 30.6% of those assigned to degarelix and 26.5% of those given placebo achieved the primary composite endpoint (adjusted odds ratio, OR = 1.19, 95% CI 0.46 – 3.06. p = 0.67). Similarly, after 30 days, there was still no significant difference between the two groups in the primary endpoint (24.2% vs 20.6%, p = 0.69, degarelix vs placebo). In fact, the trial was stopped for futility.

The authors concluded that androgen suppression did not improve the clinical outcome of men hospitalised with COVID-19 and suggested that further studies using this type of intervention were not warranted.

Citation
Nickols NG et al. Effect of Androgen Suppression on Clinical Outcomes in Hospitalized Men With COVID-19: The HITCH Randomized Clinical Trial JAMA Netw Open 2022

Fourth COVID-19 vaccination superior to third against adverse COVID-19-related outcomes

29th April 2022

A fourth COVID-19 vaccination offers greater protection against adverse COVID-19 outcomes compared to individuals having had only three doses

Having a fourth COVID-19 vaccination at least four months after the third dose, offers better short-term protection against COVID-19-related adverse outcomes compared to only three doses of the vaccine. This was the main finding of a study by Israeli researchers from the Clalit Research Institute, Innovation Division, Tel-Aviv, Isreal.

Whilst millions of individuals have now received at least three doses of a COVID-19 vaccine, there is evidence that with the emergence of variants such as Omicron, vaccine effectiveness wanes over time. This was observed, for example, in one US study, during the Omicron period. The authors found that vaccine effectiveness against emergency department visits was 87% during the first 2 months after a third dose but decreased to 66% among those vaccinated 4-5 months earlier. In fact, it is already apparent, albeit from a single study, that the rates of confirmed COVID-19 infection and severe illness were lower after a fourth dose of BNT162b2 vaccine compared to after only three doses. Whilst this is an important finding, to date, the effectiveness of a fourth COVID-19 vaccination against other outcomes of interest such as hospitalisation and deaths remains uncertain.

For the present study the Israeli team examined the relative effectiveness of four compared to three doses of vaccine among those aged 60 years and older who had received a third dose at least 4 months earlier.

Using data contained within the Clalit Health Services, which is the largest payer-provide organisation in Israel, the team included patients deemed eligible for a fourth dose and who had no previously recorded infection with COVID-19. There were a total of 5 outcomes of interest: COVID-19 infection; symptomatic COVID-19, COVID-19-related hospitalisation, severe COVID-19 and COVID-19-related death. All of these outcomes were assessed 7 to 30 days after the fourth COVID-19 vaccination and 14 to 30 days after vaccination. Those who received a fourth vaccine dose were matched with individuals who had only received three doses and with similar co-morbidities.

Fourth COVID-19 vaccination and adverse COVID-19-related outcomes

A total of 182,122 individuals who received a fourth vaccination dose and a median age of 72 years (53% female) were matched with a group of control patients (three vaccine doses).

During days 7 to 30, the estimated relative effectiveness of the fourth COVID-19 vaccination compared to three doses was 45% against a PCR confirmed COVID-19 infection, 55% against symptomatic COVID-19, 68% against COVID-19 hospitalisation and 74% against COVID-19-related mortality. Moreover, these effectiveness values were broadly similar when assessed 14 to 30 days after the fourth dose.

The authors discussed how use of a fourth dose appeared to be effective against the Omicron variant which was the main circulating variant at the time of the study (January 3 to February 18, 2022). They concluded that a fourth COVID-19 vaccination dose provided additional protection compared to only three doses in those older than 60 years of age.

Citation
Magen O et al. Fourth Dose of BNT162b2 mRNA Covid-19 Vaccine in a Nationwide Setting New Eng J Med 2022

Study shows that BNT162b vaccination reduces risk of Omicron-associated hospitalisation by two-thirds in children aged 5-11 years

22nd April 2022

A study by researchers in the US has concluded that BNT162b vaccination given to children aged 5 to 11 years reduced the risk of Omicron-associated hospitalisation by more than two-thirds but was less effective against hospitalisation among adolescents.

BNT162b2 vaccination in 12 to 15-year-old recipients has been shown to have a favourable safety profile, produce a greater immune response than in young adults and be highly effective against COVID-19. Nevertheless, data on vaccine effectiveness have only been assessed up to 3 months post-vaccination and the available data preceded circulation of the Omicron COVID-19 variant. Furthermore, there are limited data on the effectiveness of vaccines in younger children, although one study has indicated that vaccination against laboratory-confirmed COVID-19-associated hospitalisation among children aged 5-11 years was 74%, and between 14 and 67 days after a second dose, although this estimate had wide confidence interval (–35% to 95%) that included zero.

For the present study, the US team set out to determine the duration of protection from BNT162b vaccination in adolescents during different periods of time in which the Delta and Omicron were the dominant circulating strains. They also examined the protection of the vaccine against hospitalisation in children aged 5 to 18 years of age infected with the Omicron variant.

The team used a case-control, test-negative design to assess BNT162b effectiveness against COVID-19-related hospitalisation and against critical illness. The researchers also included a group of control patients who were in the same age categories and defined as hospitalised individuals who tested negative for COVID-19 and with no recognised symptoms of the virus. The effectiveness of BNT162b vaccination was assessed after 2 to 22 weeks and after longer than 22 weeks.

BNT162b vaccination and COVID-19

Among those hospitalised aged 12 – 18, there were 918 case patients with a median age of 16 years (50% female), of whom 78% had at least one underlying health condition. In addition, there were 267 case patients with a median age of 8 years (43% female) and of whom 82% had at least one underlying health condition.

Overall among the 1185 cases (i.e., 267 and 918), 25% had critical COVID-19, 14 of whom died. In the 12 to 18 group (918 cases), 27% had critical COVID-19 and 13 died. In the 5 – 11 group (267 cases), 16% had critical COVID-19, one of whom died.

The effectiveness of BNT162b vaccination against COVID-19-associated hospitalisation among adolescents was 92% during the Delta period, 2 to 22 weeks after vaccination and 92% between 23 and 44 weeks post-vaccination. However, during the omicron period, vaccine effectiveness was only 40% against COVID-19-associated hospitalisation, 2 to 22 weeks after vaccination and dropped slightly to 38% between 23 and 44 weeks post-vaccination. Nevertheless, during the Omicron period, vaccine effectiveness was 79% against critical COVID-19 but only 20% against non-critical illness.

Among those aged 5 – 11 years of age, vaccine effectiveness against COVID-19-associated hospitalisation was 68% during the Omicron period, a median of 34 days after vaccination.

The authors concluded that vaccination in children aged 5 to 11 years reduced the risk of COVID-19-associated hospitalisation by two-thirds during the Omicron period adding that while vaccination was less effective in adolescents during the omicron period, it was still able to prevent critical illness.

Citation
Price AM et al. BNT162b2 Protection against the Omicron Variant in Children and Adolescents N Engl J Med 2022

Pre-existing hypertension not independently associated with in-hospital COVID-19 mortality

21st April 2022

Pre-existing hypertension does not appear to be an independent risk factor for in-hospital mortality in patients with COVID-19

Pre-existing hypertension does not appear to be an independent risk factor for in-hospital mortality in patients with COVID-19. This was the conclusion of an analysis of a COVID-19 patient registry by researchers from University College London, UK and University Medical Center Utrecht, Utrecht University, the Netherlands.

Early in the course of the COVID-19 pandemic, Chinese researchers reported that after adjustment for confounders, patients with hypertension had a two-fold increased risk of mortality compared to those without the disease. In contrast, other Chinese work suggested that neither hypertension nor elevated blood pressure were independent risk factors for death or acute respiratory distress syndrome (ARDS)/respiratory failure, but that hypertension marginally increased the risk of severe COVID-19 infection. Following these early reports, a 2020 systematic review analysing the effect of co-morbidities in COVID-19, concluded that underlying diseases, including hypertension, respiratory system disease and cardiovascular disease, may be risk factors for severe COVID-19 infection. Additionally, although some studies have concluded that hypertension may be an independent risk factor for all-cause mortality in patients with COVID-19, a US study of over 2,000 patients identified several clinical and hospital-level risk factors that may be associated with death in critically ill patients with COVID-19, but this list excluded hypertension.

With some uncertainty over whether pre-existing hypertension is an independent risk factor for mortality in COVID-19, the UK team turned to the CAPACITY-COVID register, which was specifically designed to collate detailed information regarding cardiovascular risk factors and complications from COIVD-19 during hospital admission. Participants in the database were adults and the analysis was based on the presence of confirmed COVID-19 infection and documented pre-existing hypertension. Using regression analysis, the primary outcome focused on the association between pre-existing hypertension and in-hospital mortality and models were adjusted for several factors including age, sex, diabetes and kidney disease.

Pre-existing hypertension and in-hospital mortality

The analysis included 9,197 individuals with a median age of 69 years (60.6% male) of whom, 48.3% had pre-existing hypertension.

In-hospital mortality occurred in 22% of participants with more deaths recorded in those with pre-existing hypertension (26% vs 18.2%, p < 0.001). Moreover, in the unadjusted models, the presence of pre-existing hypertension was associated with an increased odds of mortality (odd ratio, OR = 1.57, 95% CI 1.42 – 1.74). But when the models were fully adjusted for known confounders such as age, this effect was attenuated and became non-significant (aOR = 0.97, 95% CI 0.87 – 1.10).

With respect to anti-hypertensive treatment, in fully adjusted models and when the data were pooled, both angiotensin converting enzyme inhibitor (ACEi) and angiotensin receptor blocker (ARB) drugs, tended to have a protective effect on in-hospital mortality (aOR = 0.88, 95% CI 0.78 – 0.99).

The authors concluded that after appropriate adjustment and in contrast to earlier findings, pre-existing hypertension does not independently confer an increased risk of death among patients hospitalised with COVID-19. They added that despite some early concerns, the use of both ACEi and ARB drugs appeared to offer some degree of protection against in-hospital mortality.

Citation
McFarlane E et al. The impact of pre-existing hypertension and its treatment on outcomes in patients admitted to hospital with COVID-19. Hypertens Res 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

Improved clinical outcomes for haematological malignancy COVID-19 patients after convalescent plasma therapy

Haematological malignancy patients infected with COVID-19 appear to achieve improved clinical outcomes after receiving convalescent plasma therapy

Haematological malignancy patients infected with COVID-19 can expect better clinical outcomes after receipt of convalescent plasma according to the results of a pre-print systematic review by researchers from the Department of Biomedical Science, Qatar University, Doha, Qatar.

Patients with any form of cancer have been deemed particularly vulnerable to infection with COVID‐19 given how immunodeficiency is a secondary consequence of their cancer treatment. Convalescent plasma (CP) therapy is a type of passive immunity whereby plasma enriched with specific antibodies generated by patients who have recovered from a specific infection, is transfused into other patients. The possible value of CP in those with cancers such as a haematological malignancy, the the authors of one study to conclude that convalescent plasma may be a promising therapy in cancer patients with COVID-19. Despite these potentially promising results, the use of convalescent plasma therapy among patients with cancer, especially those with a haematological malignancy has not been systematically reviewed.

For the present study, the Qatarian team focused on haematological malignancies and searched for studies that included patients infected with COVID-19, based on a PCR confirmed result and who were treated with convalescent plasma. Included studies were those reported in English and either randomised trials or prospective and retrospective comparative cohort studies. The authors extracted malignancy data and set several primary outcome measure of clinical improvement including mortality, viral clearance and recovery one month post-treatment. The main secondary outcome was adverse events after use of convalescent therapy.

Haematological malignancy outcomes and convalescent plasma

A total of 17 studies with 1103 patients of whom 258 had one or more haematological malignancies were included in the analysis. Among these studies, 13 were case reports or case series, two were retrospective in nature and two were observational studies. The main haematological malignancies were follicular lymphoma, chronic lymphocytic leukaemia, non-Hodgkin’s lymphoma, diffused large B-cell lymphoma and B-cell lymphoma.

The dose of convalescent plasma ranged from 200 – 300 ml per transfusion and in many cases this therapy was used as the last option.

Mortality was the main clinical outcome reported in 21.7% of patients receiving CP and 25.2% in control patients. The use of CP was associated with an improved overall survival (odds ratio, OR = 1.41, 95% CI 0.99 – 1.99), viral clearance (OR = 2, 95% CI 1.04 – 2.08), detection of COVID-19 antibodies in the recipient’s plasma (OR = 6.33) and recovery one month after the use of CP (OR = 1.74, 95% CI 1.1 – 2.8).

The probability of developing an adverse effect in haematological malignancy patients was significantly reduced in those given CP compared to controls (OR = 0.24, 95% CI 0.14 – 0.40).

The authors concluded that CP was an effective and safe treatment for patients with haematological malignancies infected with COVID-19, adding that there was a need for further studies to provide a better understanding of the value of this intervention in cancer patients.

Citation
Shibeeb S et al. Effectiveness of convalescent plasma therapy in COVID-19 patients with haematological malignancies MedRxiv 2022