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

13th April 2022

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

Vital sign cut-off levels for risk stratification in ED patients questioned

1st February 2022

Absolute vital sign cut off levels used in risk stratification and prognosis in emergency department patients has been called into question

Relevant vital sign cut off values used for the risk stratification and hence prognosis for patients attending an emergency department do not exist for some signs which has important implications for their use and interpretation. This was the conclusion of a large study by a team from the Emergency Department, Maxima Medical Centre, Veldhoven, The Netherlands.

An emergency department encounters a large number of sick patients who require quick evaluation to detect those who have serious medical problems and which might require hospital admission. This has led to the introduction of various triage tools such as the modified early warning score (MEWS) which serves as a rapid, simple triage method to identify medical patients in need of hospital admission and those at increased risk of in-hospital death. Other tools commonly used such as the quick sequential organ failure assessment (qSOFA) rely on the use of vital sign measurements and specify a cut-off for each vital sign to discriminate between a better or worse prognosis. However, the use of disease severity assessment tools may not be appropriate, particularly for elderly patients as revealed in one study of sepsis, which concluded that ‘prognostic and discriminative performance of the five most commonly used disease severity scores was poor and less useful for risk stratification of older ED sepsis patients.’

For the present study, the Dutch team looked to assess the association between vital signs and relevant clinical outcomes such as mortality and admission to an intensive care unit. In addition, they wanted to determine whether a single cut-off or threshold existed for each vital sign and the extent to which these were influenced by advancing age. They undertook an observational study at three EDs in the Netherlands and examined consecutive adult patients (18 years and older) where one or more of the following vital signs were measured: respiratory rate (RR), peripheral oxygen saturation (SpO2), systolic (SBP) and diastolic (DBP) blood pressure, mean arterial blood pressure (MAP), heart rate (HR) and temperature. Patients were stratified by age into three categories; 18 – 65, 66 – 80 and > 80 years and the primary outcome was whether there was a vital sign category that could be used as a cut-off to predict the outcome of in-hospital mortality or ICU admission.

Findings

A total of 101,416 patients with a mean age of 59.6 years (49.6% female) were included in their analysis. In many cases the vital sign values were outside of the usual range. For example, 23.4%, 79.1% and 14.2% of the total cohort had a RR, SBP and SP02 respectively, outside of the normal range. This proportion was also higher in older patients as seen for example with SBP for which 83.3% of patients aged > 80 had a reading outside of the normal range compared to 76.3% of those aged 18 to 65 years.

Among the cohort, a total of 2374 (2.3%) patients died. The adjusted odds ratios (aOR) for predicted mortality increased gradually with worsening values of SBP and SpO2 although there was no clear cut-off point for SBP, DBP, Sp02 and HR and mortality. In addition, for all vital signs, older adults had a larger increase in absolute mortality. For ICU admission, SBP had a relevant cut-off at 70mmHg and for MAP there was a threshold of < 60 mmHg.

In summarising their findings, the authors noted how in-hospital mortality increased gradually with decreasing SBP and SpO2 and there was no evidence of a specific cut-off for either vital sign. For DPB, MAP and HR, there was a quasi-U-shaped association with in-hospital mortality and while there was a single cut-off for MAP, RR and temperature, the authors argued that using a single cut-off value would ignore further increase of risk with more extreme values for these vital signs.

They concluded that the use of a single cut-off for each vital sign in acute care deserves scrutiny and that age-adjusted numerical scores would improve risk stratification since older patients have a larger increase in mortality with changing vital signs even after adjustment for confounds.

Citation

Candel BGJ et al. The association between vital signs and clinical outcomes in emergency department patients of different age categories Emerg Med J 2022