The assessment of parameters of convalescent plasma and their impact on COVID-19 symptoms
Agnieszka Kuś
Orcid profile, Szymon Wieczorek
Orcid profile, Jarosław Dybko
Orcid profile, Małgorzata Szymczyk-Nużka
Orcid profile, Aleksandra Butrym
Orcid profile, Krzysztof Dudek
Orcid profile, Grzegorz Mazur
Orcid profile and Siddarth Agrawal
Orcid profile 
Article Category: Original Study
Published Online: Apr 17, 2025
Page range: 35 - 49
Received: Jul 29, 2024
Accepted: Feb 19, 2025
DOI: https://doi.org/10.2478/ahem-2025-0006
Keywords
© 2025 Agnieszka Kuś et al., published by Sciendo
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
Since late 2020, when the COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) started, no one expected such an incredibly negative impact on healthcare systems, the effects of which are evident until today. To date, the virus has infected approximately 660 million people worldwide and led to over 6 million deaths [1]. Due to other underlying comorbidities, including cardiovascular or respiratory disease, diabetes, and hypertension, older people are at the highest risk of infection [2].
To date, the United States Food and Drug Administration (FDA) has authorized certain antiviral medications, monoclonal antibodies, and molecular drugs to treat COVID-19, including paxlovid, remdesivir, bebtelovimab, molnupiravir, etc. [3]. Furthermore, more than 300 drugs are being investigated under clinical trials worldwide [4,5,6]. Due to the historical success of similar to SARS-CoV-2 infectious diseases[7] and its overall safety, convalescent plasma (CP) has been employed as a promising strategy for COVID-19 treatment. The active ingredient of CP is neutralizing antibodies (nAb) against SARS-CoV-2, which consists of serum collected from previously infected individuals. Neutralizing antibodies neutralize the virus, avoiding further infection and improving clinical outcomes. Furthermore, it provides passive immunomodulatory properties that optimize the exaggerated inflammatory cascade [4]. This strategy is significantly critical for life-threatening patients who require a fast and robust response to lesser symptoms of COVID-19 infection [5].
Several analytical parameters must be determined to establish the basic efficacy of CP therapy. Since comprehensive assessment of clinical and laboratory parameters is not feasible in large-scale Atrials, smaller investigational studies are needed to define suitable outcomes and parameter measures [8]. Our study aimed to evaluate the efficacy of CP among COVID-19-infected patients and determine possible factors associated with its efficacy. These effects were analyzed by assessing 1) the probability of overall survival, 2) the duration of hospitalization, and 3) the changes in the distribution of laboratory test results in the subsequent visits after CP administration. This study is beneficial for better understanding the potential of CP as a therapeutic tool against severe COVID-19 infection.
Three hundred patients who recovered from COVID-19 infection were offered to participate in this open-label, multi-center, phase IV, single-arm trial (ClinicalTri-als.gov number NCT04642014). The recovery criteria included body temperature normalization for more than three days, resolution of respiratory tract symptoms, and two consecutively negative results of the SARS-CoV-2 RT-PCR assay test. Forty-four donor patients (5 non-pregnant women and 39 men) aged between 21 and 59 years old (Me=42 years old) met the inclusion criteria; their blood was collected after four weeks post-onset of illness. The donor patients reported typical symptoms of COVID-19 infection, excluding two who had an asymptomatic disease. The duration of symptoms was 2 to 33 days (Me = 14 days). Eight donors smoked cigarettes, and the mean body mass index (BMI) was 29.4 kg/m2. Most donors had blood group A Rh + (13/44, 29.5%), followed by 0 Rh + (11/44, 25.0%), B Rh + (8/44; 18.2%) and AB Rh + (7/44; 15.9%). The donor’s blood was collected four weeks post-onset of illness. 600 ml ABO-compatible plasma sample was harvested during apheresis from each donor, and each sample was divided and stored at 200 mL aliquots without any detergent or heat treatment. The plasma-neutralizing titers ranged from 700 to 2000 (Me = 2000). Further details can be found in the clinical trial database (NCT04642014).
We analyzed the results of 108 patients (34 women and 74 men) with COVID-19 who received convalescent plasma (CP) between December 15, 2020, and February 28, 2022. The median age of patients treated with CP was 54,9 years old (range 23–88); 25% of patients were older than 66. According to the WHO Interim Guidance, the plasma recipients were diagnosed with COVID-19 with real-time RT-PCR assay confirmation. The inclusion criteria to receive CP involved at least one of the following: respiratory distress with tachypnea ≥ 30 breaths per minute, oxygen level less than 94% in resting state, partial pressure of oxygen (pO2) ≤ 80 mm Hg. Patients who met the criteria received one dose (200ml) of ABO-compatible inactivated CP with a confirmed neutralization activity.
Each CP dose delivered to one recipient came from an individual donor. The efficacy of COVID-19 treatment, defined as the desired change in clinical parameters after CP administration, was measured by (1) the time from CP transfusion to death for any reason, (2) duration of the hospitalization, and (3) the results of laboratory tests performed in four subsequent visits (V0 – results directly prior the CP administration; V1 – after three days; V2 – after seven days; V3 – after 28 days of CP administration). Clinical parameters included in our study were as follows: the level of hematocrit, monocytes, leukocytes, erythrocytes, hemoglobin, platelets, neutrophils, eosinophils, C-reactive protein (CRP), procalcitonin, ferritin, mean corpuscular hemoglobin (MCH), D-dimer, lactate dehydrogenase (LDH), pH, pO2, pCO2, HCO3, Arterial Blood Gas (BE), O2, sodium, and potassium, as well as mean platelet volume (MPV), mean corpuscular volume (MCV), mean corpuscular hemoglobin concentration (MCHC), and red blood cell distribution width (RDW). Furthermore, CP recipients were tested with regard to the level of IgA anti-SARS-CoV-2, IgM anti-SARS-CoV-2, and IgG anti-SARS-CoV-2 antibodies after CP transplantation.
The studied variables were (1) the time from the onset of COVID-19 symptoms to CP administration, (2) plasma donor antibody titers, (3) age, and (4) body mass index (BMI). The cut-off values of these risk factors of death were determined based on the ROC curve analysis and summarized in Table 1.
The results of the ROC curves analysis of variables for the assessment of the likelihood of death caused by COVID-19 infection
| Duration from the first COVID-19 symptom to CP administration (days) | <9 | 0.510 | 0.500 | 0.598 (0.388–0.807) | p = 0.797 |
| Plasma titers | <2000 | 0.625 | 0.400 | 0.536 (0.342–0.730) | p = 0.670 |
| Age (years old) | ≥68 | 0.750 | 0.840 | 0.842 (0.706–0.978) | p < 0.001 |
| BMI (kg/m2) | ≥30 | 0.500 | 0.760 | 0.577 (0.372–0.781) | p = 0.136 |
The impact of the risk factors studied was analyzed using correlation and regression coefficients to evaluate the relationships between the number of days since CP transfusion and laboratory test results. Kaplan-Meier survival analysis was conducted to identify factors influencing overall survival probability following CP administration. The normality of data distribution was tested using the Shapiro-Wilk test. Continuous variables were described using medians and interquartile ranges, and comparisons were performed using the Mann-Whitney U test or Friedman test for non-parametric data. Pearson’s chi-squared test was used for categorical variables. Post-hoc analyses were performed to further investigate significant differences identified by the Friedman test. The Wilcoxon signed-rank test with Bonferroni correction was used. Statistical analyses were performed to evaluate relationships between variables, including Spearman’s and Pearson’s correlation coefficients. ROC curve analysis was used to assess predictive accuracy for key parameters. All analyses were performed using the statistical software package Statistica (v13.0). Results are presented as point estimates and 95% confidence intervals (±95% CI), and a p-value of < 0.05 was considered statistically significant.
Including all studied variables, age was the only factor influencing the overall survival probability of 28 days with COVID-19 infection (S(t)=28) after CP transfusion. COVID-19-infected recipients younger than 68 were more likely to survive 28 days after CP transfusion (p < 0.001; Fig. 1).
Kaplan-Meier survival curve demonstrating the probability of survival at 28 days post-CP transfusion stratified by age groups (≥ 68 years vs. < 68 years). The log-rank test revealed a significant difference in survival rates (p < 0.001), with younger patients displaying a higher survival probability (97.5% vs. 70.2%)
Furthermore, we compared the overall survival probability rates of COVID-19-infected patients based on different laboratory parameters. Kaplan-Meier survival analysis showed significant differences in survival probability depending on hematocrit (p = 0.002, Fig. 2A), monocyte (p = 0.017, Fig. 2B), and pCO2 (p = 0.042, Fig. 2C) levels. Post-hoc analysis (Table 2) revealed that patients with hematocrit levels above the standard had significantly lower survival probability compared to those with normal levels (p < 0.001), while those below standard had a better survival rate than those above standard (p = 0.019). For monocytes, survival probability was significantly higher in the normal group compared to the below-standard group (p = 0.006). Regarding pCO2, survival probability was lower in the above-standard group than normal (p = 0.039) and below-standard groups (p = 0.021).
Kaplan-Meier curves among COVID-19 patients differ by the assessment of the laboratory test results: A) hematocrit level (p = 0.002), B) monocytes level (
Post-hoc pairwise comparisons of overall survival probability based on hematocrit, monocyte, and pCO2 levels after CP transfusion
| Normal vs Below standard | p = 0.257 | p = 0.006 | p = 0.653 |
| Normal vs Above standard | p < 0.001 | p = 0.283 | p = 0.039 |
| Below vs Above standard | p = 0.019 | p = 0.512 | p = 0.021 |
The duration of hospitalization from CP transfusion to potential recovery or death among 108 COVID-19-infected patients ranged from 2 to 67 days (Me = 10, SD = 8 days). Table S1 presents the results of the median probability of overall survival of COVID-19 infection in the groups with different risk factors of death. Patients admitted to the hospital due to COVID-19-associated dyspnea were likelier to stay there for extended periods (p = 0.047) (Figure S1).
Taking into account four subsequent visits after CP administration, a significant change in the distribution of leukocytes (p<0.001, Fig. 3A) and hemoglobin (p = 0.006, Fig. 3B) levels were observed (Table S2). This ratio is shifting towards an increase in the level of the analyzed clinical parameters. For instance, during CP transfusion, 13 patients had leukocyte levels above standards; after 28 days, this parameter was observed in 36 patients (Fig. 3A). Considering hemoglobin, the number of patients with standard results increased over time. Subsequently, the number of patients with lower standard results decreased (Fig. 3B). These results were also confirmed while assessing the mean daily leukocytes and hemoglobin counts after CP transfusion (from 0 to 12 days) (p<0.001, Fig.3C and p=0.024, Fig. 3D, respectively). There was a more rapid increase in leukocytes than hemoglobin levels.
The distribution of patients differed in leukocyte levels (A) across four visits (pre-CP and three post-CP follow-ups). A significant leukocyte increase is observed (Friedman ANOVA, χ2 = 145.1,
Furthermore, our study revealed a statistically significant relationship between the distribution of the number of patients differing in assessing the level of serological parameters on consecutive days of visits. Analyzed biochemical tests included the hematocrit (p=0.009, Fig. S2A), lymphocytes (p<0.001, Fig. S2B), neutrophils (p=0.032, Fig. S2C), and eosinocytes (p<0.001, Fig. S2D) levels (Table S2). The distribution of patients in these laboratory tests is related to their normalization in each visit; due to the decrease in the number of patients with results below standards over time, more of them had normal biochemical parameters. For instance, during CP administration, 27 patients (27/108; 25.0%) and 79 patients (79/108; 73.1%) had hematocrit levels below standards and normal, respectively. After 28 days, the number of patients with lower standards was decreased to 14 patients (14/108; 13.9%), and the number of patients having normal hematocrit levels was enhanced to 85 patients (84.2%) (Fig. S2A). Furthermore, as shown in Table S2, a statistical correlation between the distribution of the number of patients was also found while analyzing mean corpuscular hemoglobin (MCH) (p=0.005, Fig. S2E), platelets (p<0.001, Fig. S2F), and monocytes (p=0.004, Fig. S2G) levels over time. Although there was no increase in the number of patients with normal results, the increase in the level of each biochemical parameter may be determined by evaluating the ratio between the number of patients having results below and above standards. For instance, over time, after 28 post-CP administrations, the number of patients with blood platelet levels above standards increased from 4 (4/108; 3.7%) to 38 (38/101; 37.6%), while the number of patients with blood platelet levels below standards decreased from 16 (16/108; 14.8%) to 1 (1/101; 1.0%, Table S2). These data show the increased level of different biochemical parameters after CP administration. It is worth considering the sizes in the following groups: normal, below standards, and above standards of each biochemical parameter. Although statistical significance is observed, several groups are too limited to report any correlations, which may result in false positive results.
Considering the inflammation indicators, since the CP plasma administration, there was a decrease in the CRP (p <0.001, Fig. 4A, and Fig. 4B, Table S3) and procalcitonin (p <0.001, Fig. 4C and Fig. 4D, Table S3) levels in each visit. For instance, 105 patients had CRP levels above standards prior CP administration (105/109; 96.3%); after 28 days, this number was decreased to 57 patients (57/100; 57.0%, Fig. 4A). Consistently, the number of patients with procalcitonin levels above standards has decreased from 55 (55/103; 52.9%) to 14 (14/97; 14.4%, Fig. 4C). Post hoc analysis using the Wilcoxon signed-rank test with Bonferroni correction confirmed significant decreases in CRP and procalcitonin levels between baseline (V0) and all subsequent visits (V1, V2, and V3). Therefore, CP plasma decreased the inflammation indicators levels, as shown by CRP and procalcitonin results.
Patients’ structure differs in assessing the level of inflammation indicators on consecutive days. Panels A and B illustrate CRP levels, with significant declines from baseline to post-CP follow-ups (Friedman ANOVA, χ2 = 145.1,
In addition, as shown in Fig. 5 and Table S3, the significant role of CP administration on COVID-19 treatment was also observed by the increase of the IgA anti-SARS-CoV-2 (p < 0.001, Fig. 5A), IgM anti-SARS-CoV-2 (p < 0.001, Fig. 5B), and IgG anti-SARS-CoV-2 levels (p < 0.001, Fig. 5C). Prior CP administration, 73 patients had positive results of IgA anti-SARS-CoV-2 and IgG anti-SARS-CoV-2 (73/108; 66.4%) and 58 patients had positive results of IgM anti-SARS-CoV-2 (58/108; 52.7%). After 28 days of CP plasma administration, the number of patients with positive results of IgA, IgM, and IgG anti-SARS-CoV-2 was increased significantly (95/96; 99.0% for IgA anti-SARS-CoV-2 and IgG anti-SARS-CoV-2, p<0.001 and 82/96; 85.4% for IgM an-ti-SARS-CoV-2, p<0.001, respectively). Post hoc analysis confirmed significant increases in all antibody levels between baseline (V0) and 28 days post-CP administration (V3), highlighting the sustained production of high-titer antibodies.
The results of Friedman tests representing the level of antibodies against: A) IgA – anti - SARS-CoV-2, B) IgM – anti-SARS-CoV-2, and C) IgG – anti-SARS-CoV-2 in the following days of visits (Friedman ANOVA,
For over a century, convalescent plasma (CP) therapy has been applied to prevent and treat many infectious diseases. This strategy was successfully used in the treatment of SARS, Middle East respiratory syndrome (MERS), and 2009 influenza A (H1N1), leading to increased efficacy, safety, and disease progression [9,10,11,12]. In a meta-analysis of 32 studies of SARS coronavirus infection and severe influenzas, Mair-Jenkins et al. determined a significant reduction of mortality of recipients after CP administration, especially in those receiving CP early after the first symptom onset [7]. However, no association between CP therapy and increased survival was observed in 84 Ebola virus-infected patients. It is possible due to the absence of data on neutralizing antibody titration for stratified analysis [13]. Therefore, due to the virological and clinical similarity among SARS, MERS, and SARS-CoV-2, it is reasonable to work on determining the role of CP therapy in COVID-19 treatment.
CP obtained from recovered COVID-19 patients consists of many neutralizing antibodies leading to eradicating the SARS-CoV-2 virus from blood circulation and pulmonary tissues [14]. In the early stages of the COVID-19 pandemic, reports from open-label trials and case series provided the safety and effectiveness of CP transfusion to patients with COVID-19 infection[15]. Therefore, the World Health Organization (WHO) has provided guidelines for the usage of CP plasma and standardized donor selection, which was further supported by an Emergency Use Authorization (EUA) from the United States Food and Drug Administration (FDA) [16]. However, this initial enthusiasm has been extinguished after publishing many randomized clinical trials, large platform trials, and systematic reviews showing no or only modest efficacy of CP plasma in COVID-19-infected patients. Therefore, on the day of publishing this article, WHO and FDA are consistent in their statement; they do not recommend using CP in patients with severe and non-severe COVID-19 [7]. Nevertheless, due to conflicting results, CP therapy still needs further consideration. This investigational medicinal product is an object of more than 140 registered clinical trials worldwide [17]. Our study adds to the growing body of evidence supporting the efficacy of CP among COVID-19-infected patients.
Due to the large-scale study group (108 patients were considered), the results obtained are reliable and convincing. For instance, leukocyte counts tended to increase and remain high until 28 days after CP transfusion (p < 0.001, Fig. 3A). In contrast, inflammation indicators such as C-reactive protein (CRP) or procalcitonin tended to decrease after CP transfusion (CRP - p <0.001, Fig. 4A, and Fig. 4B, and procalcitonin - p <0.001, Fig. 4C and Fig. 4D). This phenomenon is thought to result from the immunomodulatory effect of CP such as providing passive immunity by blocking inflammatory cytokines, autoantibodies, and complement pathways [18].
Results from our study are in accord with another study conducted in Pakistan by Khan et al., who observed decreased CRP levels over 72 hours after CP administration among patients with moderately severe (p < 0.030) and severe (p < 0.014) COVID-19 infection[19]. In a separate study of ten patients with severe COVID-19, seven of them showed increased lymphocyte counts (0.65×109/L vs. 0.76×109/L) and decreased CRP levels (55.98 mg/L vs. 18.13 mg/L) over 12 days after CP transfusion [20]. Furthermore, from 136 patients, Alsharidah et al. reported an improvement in lymphocyte counts from seven days after CP transfusion in patients with moderate COVID-19 infection and eleven days in patients with severe disease. Simultaneously, CRP levels declined throughout the first 14 days after CP transfusion [21]. The clinical improvement observed by the rapid decline of CRP levels was also assessed among 30 COVID-19-infected patients nine days after CP transfusion. Studied patients also had increased fibrinogen and D-dimer levels after four days of CP therapy, suggesting the emergence of coagulopathy [8]. This disease has been frequently observed in patients with COVID-19 and is associated with subsequent thromboembolic events and severe outcomes. This result is inconsistent with our findings; there is no statistical significance in the D-dimer and fibrinogen levels after CP administration. Therefore, according to our study, there is no increased risk of coagulopathy while receiving CP. Furthermore, in Italy, Franchini et al., showed improvement in clinical, functional, radiologic, and laboratory parameters among nineteen elderly patients over 65 years old with COVID-19 infection 14 days after CP transfusion. There was a significant decrease in CRP values at all the time points analyzed (from a median baseline level of 7.40 mg/L to a median level of 0.73 mg/L at day 14 after CP infusion) [22]. These results, as seen by CRP levels, suggest the anti-inflammatory properties of CP. Thus, CP therapy could improve clinical outcomes by enhancing laboratory parameters among patients with COVID-19 infection, which is mostly seen by decreased CRP levels and increased leukocyte counts.
Notably, it is beneficial to monitor laboratory tests, especially for patients at high risk of developing chronic diseases, such as hypertension or diabetes, and for elderly adults over 67 years old, who, according to our results, are less likely to survive 28 days after CP transfusion than their younger counterparts (p < 0.001; Fig. 1). Therefore, older than 67 years old adults are predicted to live shorter than 28 days after CP transfusion compared to younger counterparts, potentially despite the improvement of clinical parameters. In contrast, in a study composed of extremely old (median age, 87 years) patients with COVID-19 infection, Franchini et al. determined that CP reduced the mortality risk by 65% compared with a control population after 14 days of CP transfusion [22]. Nevertheless, due to the gap in the knowledge of SARS-CoV-2 pathogenesis and strategies for its treatment, it is worth considering other factors potentially affecting the efficacy of CP transfusion, including administered antiviral agents. For instance, the combination therapy with CP transfusion and hydroxychloride was already determined by Xu et al., but their results did not show optimal improvement, and specific treatment needs further analysis [23].
Antibodies increase the affinity and neutralization capacity of CP plasma over time. Even if low-titered, they may be highly effective [8]. Our study revealed a significant increase of IgA, IgM, and IgG anti-SARS-CoV-2 antibodies that persisted after 28 days of CP transfusion (p<0.001). Therefore, the question appears whether this increase contributes to reducing viral load. Although the answer will be described in further perspective of the study, according to the literature, we assume these correlations may be observed. In a group of 35 322 CP transfused COVID-19-infected patients, Joyner et al. found that for patients receiving high IgG plasma (>18.45 S/Co), the mortality rate after seven days of CP transfusion was 8.9%. For recipients with medium IgG plasma (4.62 to 18.45 S/Co), the mortality rate was 11.6%. However, for recipients with low IgG plasma (<4.62 S/Co), the mortality was 13.7% (p=0.048). Thus, the higher the anti-SARS-CoV-2 IgG concentration level, the lower the mortality rate due to COVID-19 infection [24]. This study did not provide the role of time from CP transfusion to the mortality rate, which could affect the final anti-SARS-CoV-2 IgG concentration. Consistent with our findings, Arreita et al. determined that following CP therapy, anti-SARS-CoV-2 IgG increased significantly at 24 hours, and high levels were sustained at 7- and 21-day [25]. Furthermore, Franchini et al. showed an increase in anti-SARS-CoV-2 IgG levels three days after CP transfusion, reaching a plateau on day 7 and then increasing again by day 14 [22]. These studies lead to the conclusion that the persistence of anti-SARS-CoV-2 IgG antibodies over time (even 28 days – as shown in our study – Fig. 5C) after CP transfusion may reduce viral load and hence reduce mortality rate (as indicated by Joyner et al. [24]) due to COVID-19 infection.
Furthermore, according to our study, there is an increased level of an-ti-SARS-CoV-2 IgA antibodies that persisted even for 28 days after CP transfusion (Fig. 5A). Consistently, our recently published data revealed that patients who received plasma with IgA > 1.15 AU / ml displayed an eight-fold increase in survival compared to patients who received CP with IgA <1.15 AU / ml (OR = 7.92 95% CI 1.20–52.3). Moreover, we found IgA affects the level of IgG antibodies in donor plasma; a decrease in the levels of IgG accompanied by increases in IgA levels [26]. Nevertheless, the question still requiring further consideration is whether increased levels of IgA during CP transplantation impact the overall survival of COVID-19-infected patients or if it is due to the direct correlation with other antibodies. However, considering that studies evaluating the efficacy of CP therapy concentrate predominantly on examining total Ig or IgG-specific anti-SARS-CoV-2 antibody levels [27]. Our findings, taken together, may shed new light on the potential mechanisms of action of CP through the activity of IgA.
While analyzing the therapeutic role of CP among COVID-19-infected patients, we wondered if donor sex is the factor affecting the efficacy of CP. In our study, CP plasma came from 5 non-pregnant women and 39 men. To the best of our knowledge, most studies show no statistical correlation between the sex of donors and the efficacy of CP plasma [28]. However, articles dominating males [29,30] or female [31] donors are also observed. In a study by Schmidt et al., female CP donors had higher mean initial anti-SARS-CoV-2 antibody levels than males. However, the rate of decline was more rapid in females, perhaps suggesting that lower initial titers in males might be offset by a slower rate of decline [31]. In contrast, Jain et al. demonstrated that higher levels of anti-nucleocapsid IgG S/C ratios were associated with males, older age, Hispanic ethnicity, and fewer days between symptom onset and first donation [32]. Mehew J. consistently found that higher neutralizing antibody levels were observed in males, older donors, and previously hospitalized donors [33]. The discrepancies in the association of CP donor sex with antibody response could result from several factors. One of them is a methodological workflow of the study; some studies evaluated neutralizing antibody levels, others anti-NC IgG levels using the Abbott assay [31]. Furthermore, females tend to have more robust immune responses to infection, which is thought to be caused by genetic and hormonal influences on the immune system [34]. Additionally, testosterone has been found to suppress immune function [35]. Therefore, differences in antibody levels can result from biological factors. Nevertheless, further studies are required to determine sex discrepancies in the neutralizing SARS-CoV-2 antibody.
Due to the emergence of new COVID-19 variants and the decreasing efficacy of existing vaccines, finding alternative strategies for SARS-CoV-2 treatment is a critical point in disease progression [36]. While plasma products (e.g., hyperimmune globulin, monoclonal antibodies) and/or vaccination are successful therapeutic options, human CP is the only medicinal product that is immediately available for use to prevent and treat COVID-19, especially in low- and middle-income countries, where it is challenging to get more expensive drugs [37]. The other significant advantage of CP is versatility, with the potential to respond to new emerging variants [38]. Therefore, our results provide the basis for investigating the effects of CP plasma on the elimination of novel SARS-CoV-2 variants from COVID-19-infected patients.
The presented study has some limitations. First, the median time from the onset of COVID-19-related symptoms to CP transfusion was 16 days. To answer the question of whether changes in the values of clinical outcomes come from the therapeutic effects of CP or are a result of the natural kinetics of viremia, further studies are needed. Secondly, the randomization represented by the control group was not included in this study; this study group is needed to determine the benefits or disadvantages of CP transfusion in COVID-19 patients. Third, at the time of analysis, some patients were still hospitalized (the duration of hospitalization ranged from 2 to 67 days (median
In conclusion, this open-label, multi-center, single-arm study shows a potential therapeutic effect of CP transfusion among COVID-19-infected patients. One dose of CP with antibodies with neutralizing activity can rapidly improve clinical outcomes by increasing leukocyte counts and decreasing inflammation biomarkers, including C-reactive protein and procalcitonin. Prompt CP administration within the initial 9 days post-symptom onset correlated with accelerated improvements in blood leukocyte and platelet levels. Decreases in inflammation indicators (CRP and procalcitonin) and robust increases in anti-SARS-CoV-2 antibodies post-CP administration underscore the therapeutic potential of this intervention. These findings contribute valuable insights into factors influencing CP efficacy. Consideration of specific laboratory markers and timely administration is crucial for optimizing the benefits of CP therapy in severe COVID-19 cases. However, the optimal dose, treatment time point, and detailed changes of each diagnostic value need to be further investigated.