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Anti-CD20 therapy increases complication risk in COVID-19 for blood cancer patients

16th January 2023

Anti-CD20 therapy for haematological cancer patients is linked to an increased risk of adverse outcomes despite triple vaccination

Anti-CD20 therapy use in patients with haematological cancers, despite triple vaccination, still poses an increased risk for adverse outcomes following a breakthrough COVID-19 infection, according to the findings of a retrospective population-based cohort study by Canadian researchers.

Although patients with cancer were excluded from the initial clinical trials of COVID-19 vaccines, emerging evidence suggested that adult patients with haematological malignancies, infected with the virus, especially those who were hospitalised and over 60 years of age, were at an increased risk of death. Moreover, once vaccinated, it became clear that patients with haematological cancers displayed an impaired humoral response and the recognition that breakthrough infections were possible and that these infections were correlated with the level of neutralising antibody titers during the peri-infection period, researchers hypothesised that haematological malignancy patients and even those with other types of cancer, might experience a more severe outcomes if infected with COVID-19.

In the present study, the Canadian team set out to examine the relative risk of COVID-19 breakthrough infections and COVID-19-related outcomes in vaccinated patients with cancer (including haematological and solid tumours) compared to matched non-cancer controls. In addition, they considered whether current treatment of cancer, with for example, anti-CD20 therapy, impacted on the risk of COVID-related outcomes. Using a retrospective design, researchers matched patients with haematologic cancer to non-cancer controls (1:4), based on age, sex, type of vaccine, date of vaccine. The primary outcome was COVID-19 breakthrough infection, whereas secondary outcomes were emergency department visits, hospitalisation and death within 4 weeks of infection and the outcomes adjusted for gender, age socioeconomic status and vital status.

Anti-CD20 therapy and COVID-19 outcomes

A total of 289,400 vaccinated cancer patients with a mean age of 66.05 years (65.4% female) were matched with 1,157,600 non-cancer controls. During the period of the study, there were 3118 and 12 150 breakthrough infections in the cancer and non-cancer groups, respectively.

Overall, the risk of a COVID-19 breakthrough infection was significantly higher among cancer patients compared to non-cancer controls (adjusted Hazard ratio, aHR = 1.05, 95% CI, 1.01 – 1.09, p = 0.02). However, the risk was significantly greater among patients with haematologic cancers (aHR = 1.33, 95% CI 1.20 – 1.46, p < 0.01) compared to controls. There were also significantly elevated risks for haematological cancer patients (compared to controls) for emergency department visits, hospitalisation and death. However, when researchers looked at patients who had received a third COVID-19 vaccine dose, this was associated with lower risk of breakthrough infection for blood cancer patients (aHR = 0.61, 95% CI 0.54. – 0.69, p < 0.01). 

Among haematological cancer patients in receipt of anti-CD20 therapy, there remained an elevated risk of breakthrough infection (aHR = 1.88, 95% CI 1.27 – 2.78, p =0.02) as well as for emergency department visits, hospitalisation and death. Although a third vaccine dose was associated with a lower risk of infection and COVID-19 complications for all cancer patients, this did not significantly reduce the risk among haematological cancer patients receiving anti-CD20 therapy. For example, the adjusted hazard ratio for death was 0.49 (p = 0.24) and 1.19 (p = 0.46) for severe outcomes.

The authors concluded that patients with haematological cancer had the highest risk for breakthrough infections and adverse COVID-19 outcomes, particularly for those who received anti-CD20 therapy.

Citation
Gong IY et al. Association of COVID-19 Vaccination With Breakthrough Infections and Complications in Patients With Cancer. JAMA Oncol 2022.

CT chest scans reveal fewer cases of pneumonia in breakthrough COVID-19 infections

30th May 2022

CT chest scans in patients with breakthrough COVID-19 infections show lower levels of pneumonia compared to scans of unvaccinated patients

A significantly higher proportion of CT chest scans in fully vaccinated patients who experience a breakthrough infection showed no signs of pneumonia during their stay in hospital, according to a study by Korean researchers.

COVID-19 vaccination across the globe has led to a protection against both symptomatic and asymptomatic COVID-19 as well as severe disease, hospitalisation and death. Although a CT chest scan has been described as an indispensable diagnostic tool in COVID-19, no studies have reported on using this imaging modality to examine the features associated with breakthrough infections that are generally less severe.

In the present study, the Korean team compared the imaging features of fully, partially and unvaccinated patients, who were hospitalised because of a COVID-19 infection. The team focused only on patients with a PCR-confirmed positive COVID-19 test result and who underwent at least one CT chest scan during their period of hospitalisation.

Partially vaccinated individuals were defined as those for which the infection occurred less than 14 days after their first COVID-19 vaccine. In contrast, fully vaccinated individuals were those who became infected 14 days after their second vaccine dose.

Using a retrospective design, the team collected demographic and co-morbidity data for all patients, as well as whether an individual required supplemental oxygen, was admitted to an intensive care unit (ICU) admission or died in hospital. The CT chest scans were obtained either upon admission or within a week of symptom onset and follow-up chest radiographs were obtained every two to three days until discharge.

The extent of pneumonia was scored from 0 to 2 (i.e., 0 = no evidence, 1 = 1 – 25% involvement and 2 = > 25% involvement) and the patterns of pneumonia were categorised as either typical, indeterminate, atypical or negative. The researchers used logistic regression to evaluate any associations between clinical factors such as vaccination status and clinical outcomes.

CT chest scan and clinical outcomes

A total of 761 patients with a mean age of 47 years (51% women) were included, of whom, 77% were unvaccinated, 17% partially vaccinated and 6% fully vaccinated. Relevant co-morbidities for the whole cohort included hypertension (22%), diabetes (13%) and cardiovascular disease (5%).

All 761 patients underwent a CT chest scan at admission and 86% had at least one follow-up scan. During the initial scan, 63% of unvaccinated individuals had negative chest radiographs (i.e., a score of 0) whereas 75% of fully vaccinated patients were negative.

In 412 patients who underwent a CT chest scan during their stay in hospital, there was no evidence of pneumonia in 59% of those who were fully vaccinated compared to 22% of those who were unvaccinated (p < 0.01).

Fully vaccinated patients were also significantly less likely to need supplemental oxygen (Odds ratio, OR = 0.24, 95% CI 0.09 – 0.64, p = 0.05) compared to unvaccinated patients and to be admitted to an ICU (OR = 0.08, 95% CI 0.09 – 0.78, p = 0.02).

The authors concluded that fully vaccinated individuals who experienced a breakthrough COVID-19 infection had a higher proportion of CT chest scans without signs of pneumonia compared with unvaccinated individuals.

Citation
Lee JE et al. Imaging and Clinical Features of COVID-19 Breakthrough Infections: A Multicenter Study Radiology 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

Emergency care rarely needed for breakthrough COVID-19 infections

17th September 2021

A study of breakthrough COVID-19 infections found that less than 1% of all emergency care visits occurred in those fully vaccinated.

The efficacy of currently available COVID-19 vaccines, such as BNT162b, has been clearly demonstrated in clinical trials. Nevertheless, because vaccines are not 100% effective, there are likely to be individuals who experience a breakthrough COVID-19 infection. However, what is less clear is the extent to which these breakthrough infections result in either emergency care (EC) visits or even hospital admission.

In trying to better understand this question, a team from the Department of Emergency Medicine, Beaumont Hospital, Michigan, US, performed an observational cohort analysis comparing the need for EC among those with confirmed COVID-19 infection. The team compared the outcomes for adult patients who were either unvaccinated (UV), partially vaccinated (PV) or fully vaccinated (FV). For the purposes of the study, FV individuals were defined as those who had a positive COVID-19 test result and symptom onset < 14 days after their second vaccination. The team used electronic health records to confirm COVID-19 infection status and collect demographic and clinical data such as co-morbidities. The primary outcome measure was the rate of emergency care/hospitalisation encounters in those testing positive among the three groups. This was defined as the number of newly presenting hospital-based COVID-19 encounters divided by the state population within each respective vaccination group and expressed as a rate per 100,000 visits. The team also calculated weekly rates of COVID-19 EC encounters for each group. Secondary outcomes included severe disease represented as a composite outcome (intensive care admission, mechanical ventilation or in-hospital death), length of hospital stay.

Findings
There was a total of 11,834 EC visits which met the inclusion criteria. Patients had an overall mean age of 53 years (47.2% male) of whom 10,880 (91.9%) were UV, 825 (7%) PV and 129 (1.1%) FV. In terms of the weekly rate of COVID-19 EC encounters, the rate of breakthrough COVID-19 infections among FV individuals was 96% lower compared with the UV group. COVID-19 EC visits peaked at 22.61, 12.88 and 1.29 visits per 100,000 for those who were UV, PV and FV respectively.

The composite secondary outcome of severe disease occurred in 6.8% of the UV, 10.3% of the PV and 12.4% of the FV group. While those who were FV had a lower risk of severe disease compared to the UV group, this difference was not significant (hazard ratio, HR = 0.84, 95% CI 0.52–1.38) and the mean age of those with severe disease was 74.1 years. Among the PV group, the risk was either higher or lower (HR = 1.03, 95% CI 0.78–1.35).

The authors concluded that while breakthrough COVID-19 infections occurred in fully vaccinated individuals, these were rare, accounting for only 1% of all COVID-19-related EC visits. Nevertheless, when admission to hospital was required for those who were fully vaccinated, the risk of severe outcomes was similar to those who were unvaccinated.

Citation
Bahl A et al. Vaccination reduces need for emergency care in breakthrough COVID-19 infections: A multicenter cohort study. The Lancet Regional Health Americas 2021

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