Abstract
INTRODUCTION: Passive immunization therapy with convalescent plasma has been successfully used in prior viral pandemics. For these reasons, from the beginning of the COVID-19 outbreak in March 2020, our hospital has been actively involved in the collection of COVID-19 convalescent plasma (CCP) and its administration to hospitalized COVID-19 patients. We set up a registry to collect prospectively clinical and laboratory data, and blood samples, from CCP donors and CCP recipients (IMMUNOCOVID registry, clinicaltrials.gov identifier #04614012, approved by the local Ethics Committee). In the present study, in a cohort of COVID-19 plasma recipients, we prospectively assessed the effect of CCP treatment on different clinical and laboratory parameters, including anti-SARS-CoV2 IgG antibody (Ab) levels, inflammatory and coagulation biomarkers.
METHODS: Hospitalized COVID-19 patients were treated with maximum 3 CCP units (200 ml/unit), each given every other day, and followed-up clinically for 30 days after first CCP infusion. Venous blood samples were collected on days 0 (D0), 3 (D3), and 5 (D5) before each CCP administration, and on day 7 (D7) after the first administration. The following laboratory measurements were performed: IgG anti-SARS-CoV2 Nucleocapsid protein (anti-N) and IgG anti-Spike protein (anti-S) Ab (quantitative assay); fibrinogen, D-dimer, C reactive protein (CRP), procalcitonin, LDH, Hb, blood cell counts, AST, ALT, creatinine, and GFR. Results are expressed as median and 5th-95th percentile range.
RESULTS: From May 2020 to April 2022, 334 (103F/231M) hospitalized COVID-19 patients received CCP treatment. The median age of the cohort was 67 (41-86) years; 89 were admitted to the intensive care unit (ICU) and 245 were in the medical general ward (non-ICU patients). Among this cohort, 255 patients received 3 CCP units, 47 patients 2 CCP units, and 32 only 1 CCP unit. The median time from hospital admission to CCP infusion was 2 days (0 - 70) and a total of 890 CCP units were infused with a median value of 153 AU/ml (100-400) anti-S IgG Ab. Treatment with CCP led to a significant (p<0.001) 7.1-fold increase in anti-S and 1.7-fold increase in anti-N Ab at day 7. By multivariate analysis, the percentage increase in anti-S Ab [i.e., delta = (D7-D0/D0)] was significantly (p<0.05) associated with younger age (beta=-0.181) and male gender (beta=-0.195), but not with disease severity (ICU vs non-ICU), with the highest increment occurring in males <60 years (9.8-fold). Regarding inflammatory and coagulation biomarkers, at enrollment, CRP, neutrophil count, LDH, procalcitonin, fibrinogen and D-dimer levels were all significantly elevated, while lymphocytes and Hb were significantly lower than the normal range. Compared to non-ICU patients, the ICU group, at D0, had higher levels (p<0.05) of inflammatory biomarkers and D-dimer, and significantly lower (p<0.05) lymphocyte count, Hb, and fibrinogen level.
In the subgroup of 255 patients who received 3 CCP infusions, in parallel to anti-SARS-CoV2 IgG increment, a significant (p<0.001) reduction in CRP, LDH, ferritin, procalcitonin, and fibrinogen levels occurred. This was particularly apparent in the non-ICU subgroup. Among the whole cohort of 334 patients, 66 had cancer (28 hematological tumors, 33 solid tumors, and 5 both hematological and solid tumors). The median age of this subgroup was 70 years (49-88), with 16 of them admitted to ICU. In this category of patients, a significant increase (p<0.01) of both anti-S (4.7-fold) and anti-N (1.3-fold) IgG occurred, not differently from the rest of patients.
Four out of 890 CCP infusions were associated with a mild adverse event with a resolution in 24 hours. Regarding overall mortality, 48 patients (14%) died after 30 days follow-up [15F/33M, median age 64 years (40-81)], 16 of them were in ICU.
CONCLUSIONS: In our study, CCP treatment leads to an increase in antibody levels in the recipients, particularly in males <60 years. This occurs also in subjects with cancer and those with severe COVID-19. Notably, the increase of humoral immune response is associated with a decrease in inflammatory parameters and fibrinogen levels. The low incidence of adverse events observed supports the safety of CCP administration.
Disclosures
No relevant conflicts of interest to declare.
Author notes
Asterisk with author names denotes non-ASH members.
