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Higher convalescent plasma antibody titre levels associated with lower risk of death in COVID-19

18th January 2021

Passive antibody transfer (convalescent plasma therapy) has been widely used to treat COVID-19; however, little is known about the effect on mortality of different antibody titre levels.

The use of convalescent plasma (CP) to treat respiratory infections has a long history having been used for over a century. During the current pandemic, interest in this therapeutic modality has picked up although the efficacy signals from this approach are still preliminary and require further study. As a result, a team led by researchers from the Department of Anaesthesiology and Peri-operative Medicine, Rochester, Minnesota, in the US, retrospectively studied the results obtained from an expanded-access programme to CP across a range of hospitals. Eligible patients were 18 years and over, hospitalised with a laboratory confirmed positive COVID-19 test and deemed at high risk for progression to severe or life-threatening COVID-19.

Treatment consisted of CP given intravenously although the corresponding IgG COVID-19 antibody levels within these samples were unknown. The researchers therefore collected and quantitively analysed, remnant aliquots of serum retained from the donation process for IgG antibody levels. These which were divided into low (<4.62), medium (4.62 to 18.45) and high (>18.45) titre levels. The primary outcome for the study was mortality at 30 days after transfusion of CP.

Findings
The patient cohort consisted of 3082 individuals of whom, 61% were male and 69% were younger than 70 years of age. In total, two-thirds received CP prior to mechanical ventilation. Death within 30 days after CP occurred in a 26.9% of all patients. Furthermore, the outcome occurred in 29.6%, 27.4% and 22.3% of those in the low, medium and high, IgG titre ranges respectively. The risk of death among those with higher antibody titre levels was reduced by 46% compared to the lowest antibody titre (relative risk, RR = 0.66, 95% CI 0.48-0.91) in patients who were not mechanically ventilated. However, there was no effect of antibody titre levels on death rates among patients who required mechanical ventilation.

The authors concluded that their data support the notion that the benefits of CP are largely dependent on the levels of antibody present within samples.

Citation
Joyner MJ et al. Convalescent plasma antibody levels and the risk of death from COVID-19. N Engl J Med 2021

Plasma therapy ineffective for COVID-19

23rd October 2020

Given the current limited treatments available for COVID-19, one area of interest has been convalescent or plasma therapy, which represents a form of passive immunity and has been successfully used to treat other viral infections.

To date only two clinical trials have examined the value of convalescent plasma therapy (CP) in patients with COVID-19 though both were stopped early and did not appear to show any significant benefit. For this new study, researchers from the Indian Council of Medical Research have undertaken a randomised trial in over 400 patients but the results also suggest that CP is of limited value. The study recruited 464 adult patients (aged 18 and over) with a median age of 52 years (75% male) from 39 public and private hospitals across India who were admitted to hospital with confirmed moderate COVID-19, based on a positive PCR test. Included patients had a partial pressure of oxygen in arterial blood/fraction of inspired oxygen (Pa02/FiO2) ratio between 200mmHg and 300mmHg, or a respiratory rate of more than 24/minute and an oxygen saturation < 93%. Eligible CP donors were required to have had a PCT positive test for COVID-19 and symptom resolution for 28 consecutive days before donation or a 14-day period which included two negative PCR tests collected 24 hours apart.

Patients were randomised to either CP and best standard of care (intervention group) or care lone (the control group) and intervention patients received two doses of 200ml CP transfused 24 hours apart. The primary outcome as a composite of progression to severe disease Pa02/FiO2 ratio < 100mmHg, anytime within 28 days of enrolment or mortality at 28 days.

Findings
Progression to severe disease occurred in 19% vs 18% (intervention vs control) and 28 day mortality occurred in 15% vs 14% (intervention vs control) of patients. There was a statistically significant higher proportion of patients receiving CP with a resolution of shortness of breath after 7 days (76% vs 66%) and fatigue (73% vs 60%), there was no difference for fever or cough. In addition, significantly more patients (68% vs 55%) had a negative PCR test at day 7. The authors concluded that as a treatment for COVID-19, CP appeared to be of limited value.

Reference
Agarwal A et al. Convalescent plasma in the management of moderate covid-19 in adults in India: open label phase II multicentre randomised controlled trial (PLACID Trial). BMJ 2020;371:m3939.