Safety and efficacy of COVID-19 hyperimmune globulin (HIG) solution in the treatment of active COVID-19 infection- Findings from a Prospective, Randomized, Controlled, Multi-Centric Trial

Parikh, Devang; Chaturvedi, Alok; Shah, Naman K.; Patel, Piyush M.; Patel, Ronak; Ray, Suma

doi:10.1101/2021.07.26.21261119

Cited by 14 publications

(20 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For patients who fail to seroconvert, the ongoing management is likely to remain a challenge and they will almost certainly rely on passive immunity. In some settings, hyperimmune COVID‐19 immunoglobulin 40 is available but supply is likely to remain limited. Immunoglobulin replacement therapies may soon have anti‐S antibodies detectable; however, the level of antibody and whether it confers any protective activity will be difficult to establish.…”

Section: Discussionmentioning

confidence: 99%

COVID‐19 vaccine failure in chronic lymphocytic leukaemia and monoclonal B‐lymphocytosis; humoural and cellular immunity

Shen

Freeman

Holland³

et al. 2022

Br J Haematol

View full text Add to dashboard Cite

Summary Chronic lymphocytic leukaemia (CLL) is associated with immunocompromise and high risk of severe COVID‐19 disease and mortality. Monoclonal B‐cell lymphocytosis (MBL) patients also have immune impairment. We evaluated humoural and cellular immune responses in 181 patients with CLL (160) and MBL (21) to correlate failed seroconversion [<50 AU/ml SARS‐CoV‐2 II IgG assay, antibody to spike protein; Abbott Diagnostics)] following each of two vaccine doses with clinical and laboratory parameters. Following first and second doses, 79.2% then 45% of CLL, and 50% then 9.5% of MBL patients respectively remained seronegative. There was significant association between post dose two antibody level with pre‐vaccination reduced IgM (p < 0.0001), IgG2 (p < 0.035), and IgG3 (p < 0.046), and CLL therapy within 12 months (p < 0.001) in univariate analysis. By multivariate analysis, reduced IgM (p < 0.0002) and active therapy (p < 0.0002) retained significance. Anti‐spike protein levels varied widely and were lower in CLL than MBL patients, and both lower than in normal donors. Neutralisation activity showed anti‐spike levels <1000 AU/ml were usually negative for both an early viral clade and the contemporary Delta variant and 72.9% of CLL and 53.3% of MBL failed to reach levels ≥1000 AU/ml. In a representative sample, ~80% had normal T‐cell responses. Failed seroconversion occurred in 36.6% of treatment‐naïve patients, in 78.1% on therapy, and in 85.7% on ibrutinib.

show abstract

Section: Discussionmentioning

confidence: 99%

COVID‐19 vaccine failure in chronic lymphocytic leukaemia and monoclonal B‐lymphocytosis; humoural and cellular immunity

Shen

Freeman

Holland³

et al. 2022

Br J Haematol

View full text Add to dashboard Cite

show abstract

“…PRISMA flow diagram can be seen on Figure 1 . A total of 6 studies were excluded for not reporting on an adequate control group, 21 , 22 , 23 , 24 , 25 , 26 while 3 studies reported on convalescent plasma or hyperimmune anti‐SARS‐CoV‐2 serum 27 , 28 , 29 and some assessed studies were reviews, commentaries or publications that did not report any new data.…”

Section: Resultsmentioning

confidence: 99%

Intravenous immunoglobulin (IVIg) therapy in hospitalised adult COVID‐19 patients: A systematic review and meta‐analysis

Marčec

Dodig

Radanovic

et al. 2022

Reviews in Medical Virology

View full text Add to dashboard Cite

Intravenous immunoglobulin (IVIg) therapy has been suggested as a potential treatment option for hospitalised COVID‐19 patients. The aim of this systematic review and meta‐analysis was to investigate the potential impact of IVIg on mortality and length of hospitalisation in adult COVID‐19 patients. PubMed, Scopus, Web of Science and medRxiv were searched in the week of 20.12.2021 for English language, prospective trials, and retrospective studies with control groups, reporting on the use of intravenous immunoglobulin therapy in adult hospitalised COVID‐19 patients. Exclusion criteria were: studies evaluating the use of IVIg in paediatric COVID‐19 cases, trials using convalescent anti‐SARS‐CoV‐2 plasma or immunoglobulins derived from convalescent anti‐SARS‐CoV‐2 plasma. A random effects meta‐analysis with subgroup analyses regarding study design and patient disease severity according to WHO criteria was also performed. A total of 13 studies were included, of which 6 were prospective, on a total of 2313 (IVIg = 1104, control = 1209) patient outcomes. Meta‐analysis results indicated that IVIg therapy had no statistically significant effect on mortality (RR 0.91 [0.59; 1.39], p = 0.65, I 2 = 69% [46%; 83%]) or length of hospital stay (MD 0.51 [−2.80; 3.81], p = 0.76, I 2 = 96% [94%; 98%]). Subgroup analyses indicated no statistically significant impact on either outcome, but prospective studies' results suggested that IVIg may increase the length of hospitalisation in the severe COVID‐19 patient group (MD 2.66 [1.43; 3.90], p < 0.01, I 2 = 0% [0%; >90%]). The results of this meta‐analysis do not support use of IVIg in hospitalised adult COVID‐19 patients.

show abstract

“…One phase I/II trial randomised 50 hospitalised COVID-19 patients to COVIG or standard of care and demonstrated a lower mortality in the COVIG arm (25% in COVIG arm versus 60% in control group), however, this benefit could not be confirmed in two phase III trials. [17][18][19] Highly potent virus neutralizing monoclonal or combined monoclonal antibodies yield supraphysiological levels of neutralizing antibodies unachievable with plasma-derived products. The landmark trial by the UK RECOVERY group evaluating treatment with a combination of casirivimab and imdevimab in hospitalised patients showed reduced mortality, but only in the predefined subgroup of seronegative patients.…”

Section: Introductionmentioning

confidence: 99%

SARS-CoV-2 hyperimmune globulin for severely immunocompromised patients with COVID-19: a randomised, controlled, double-blind, phase 3 trial

Huygens

Hofsink

Nijhof

et al. 2022

Preprint

View full text Add to dashboard Cite

SummaryBackgroundSeverely immunocompromised patients are at risk for severe COVID-19. Benefit from convalescent plasma in these patients is suggested but data from randomised trials are lacking. The aim of this study is to determine efficacy of SARS-CoV-2 hyperimmune globulin (“COVIG”) in treatment of severely immunocompromised, hospitalised COVID-19 patients.MethodsIn this randomised, controlled, double-blind, multicentre, phase 3 trial, severely immunocompromised patients who were hospitalised with symptomatic COVID-19 were randomly assigned (1:1) to receive 15 grams of COVIG or 15 grams of intravenous immunoglobulin without SARS-CoV-2 antibodies (IVIG, control). Patients included were solid organ transplant patients with three drugs from different immunosuppressive classes or patient with disease or treatment severely affecting B-cell function. Patients that required mechanical ventilation or high flow nasal oxygen were excluded. All investigators, research staff, and participants were masked to group allocation. The primary endpoint was occurrence of severe COVID-19 evaluated up until day 28 after treatment, defined as the need for mechanical ventilation, high-flow nasal oxygen, readmission for COVID-19 after hospital discharge or lack of clinical improvement on day seven or later. This trial is registered with Netherlands Trial Register (NL9436).FindingsFrom April, 2021, to July, 2021, 18 participants were enrolled at three sites in the Netherlands; 18 patients were analysed. Recruitment was halted prematurely when casirivimab/imdevimab became the recommended therapy in the Dutch COVID-19 treatment guideline for seronegative, hospitalised COVID-19 patients. Median age was 58 years and all but two were negative for SARS-CoV-2 spike IgG at baseline. Severe COVID-19 was observed in two out of ten (20%) patients treated with COVIG compared to seven of eight (88%) in the IVIG control group (p = 0·015, Fisher’s exact test).InterpretationCOVIG reduced the incidence of severe COVID-19 in severely immunocompromised patients, hospitalised with COVID-19. COVIG may be a valuable treatment in this patient group and can be used when no monoclonal antibody therapies are available.FundingThe Netherlands Organisation for Health Research and Development, Sanquin Blood Supply Foundation.

show abstract

Safety and efficacy of COVID-19 hyperimmune globulin (HIG) solution in the treatment of active COVID-19 infection- Findings from a Prospective, Randomized, Controlled, Multi-Centric Trial

Cited by 14 publications

References 21 publications

COVID‐19 vaccine failure in chronic lymphocytic leukaemia and monoclonal B‐lymphocytosis; humoural and cellular immunity

COVID‐19 vaccine failure in chronic lymphocytic leukaemia and monoclonal B‐lymphocytosis; humoural and cellular immunity

Intravenous immunoglobulin (IVIg) therapy in hospitalised adult COVID‐19 patients: A systematic review and meta‐analysis

SARS-CoV-2 hyperimmune globulin for severely immunocompromised patients with COVID-19: a randomised, controlled, double-blind, phase 3 trial

Contact Info

Product

Resources

About