Administration Of Convalescent Plasma Research Articles

Gravity-driven crossflow membrane filtration and mechanical centrifugation yield plasma with equivalent total and COVID-19-specific immunoglobulin content

While the administration of convalescent plasma is a promising therapy for coronavirus disease 2019 (COVID-19), upfront costs and technological barriers of conventional plasmapheresis have limited the collection and processing of COVID-19 convalescent plasma (CCP) in Low- and Middle-Income Countries (LMICs). We previously reported that bedside plasma separation using gravity-driven microfiltration has made CCP therapy accessible as a treatment option in Suriname. However, the question remains whether the gravity-driven microfiltration method yields similar amounts of immunoglobulins as compared to conventional plasmapheresis. Here, we compared the gravity-driven microfiltration method with conventional plasma centrifugation for the total and COVID-19-specific immunoglobulin content of the obtained CCP. Blood donations from 10 donors recovered from PCR-confirmed COVID-19 were processed using both methods. Samples were collected pre- and post-processing for analysis to allow direct comparison of both methods. There were no differences in COVID-19-specific IgG levels between convalescent plasma obtained by microfiltration and centrifugation for 4 of the 5 assays used. Anti-RBD-Omicron IgG levels were slightly higher in the plasma obtained after filtration (median 274, range 69 to 1258) than after centrifugation (median 249, range 67 to 1175), Wilcoxon P = 0.0488. No significant differences were detected between the two methods for levels of total albumin, total cholesterol, total IgA, IgM and IgG levels. These results indicate that gravity-driven microfiltration and conventional centrifugation yield CCP with equivalent amounts of total and COVID-19-specific antibodies. This makes the gravity-driven microfiltration method a viable option for the collection and treatment with CCP in the LMICs setting.

Effect of convalescent plasma in the treatment of severe acute respiratory distress syndrome caused by covid-19 infection

Introduction/Objective. Convalescent plasma (CP) has been used in the past to treat several infectious diseases. It was hypothesized that CP could have a positive impact on severely ill patients with Covid-19 infection. The aim of the study was to present the results of CP application in patients with severe acute respiratory distress syndrome (ARDS) caused by Covid-19 infection. Methods. An observational study of critically ill patients who received CP according to the National Protocol for the treatment of Covid-19 infection at the Clinical Center of Vojvodina in Novi Sad, Serbia, in 2020. Clinical outcomes were monitored before and after CP administration. Results. A total of 14 patients with severe life-threatening Covid-19 infection were included in the study. The patients age ranged from 53 to 79 years. Most of them had two or more comorbidities, and more than half of them had blood type A Rh positive. Prior to CP administration, all patients received antibiotic therapy for severe pneumonia, corticosteroids, and anticoagulant therapy. Twelve out of 14 patients (85.7%) required endotracheal intubation and mechanical ventilation of the lungs, while two patients were on non-invasive mechanical ventilation. CP was administered 2 to 13 days after the confirmed diagnosis of Covid-19. The PaO2/FiO2 ratio before CP administration ranged from 49.5 to 78.6. Twelve patients (85.7%) died during the course of the study. Conclusion. The use of CP in cases of severe ARDS caused by Covid-19 infection does not impact survival or lead to other forms of clinical improvement.

Convalescent Plasma Treatment for Moderate to Critical Ill COVID-19 Patients – A Safe but Futile Treatment: A Non-Randomized Comparative Study

Background: In a number of cases of viral infection, convalescent plasma therapy has been effective. Reportedly, the use of convalescent plasma as a therapy for COVID-19 patients with severe and life-threatening disorders is beneficial at this time. This study aims to assess the effectiveness and safety of convalescent plasma transfusions in hospitalized COVID-19 patients. Subjects and Method: This was a clinical trial employing a non-randomized comparative study. A historical control group (21 samples) and convalescent plasma transfusions (21 samples) was selected consecutively from hospitalized COVID-19 patients between May 6th, 2020, and May 6th, 2021 at Dr. Moewardi General Hospital. We assessed and quantified viral clearance in the laboratory. Statistical analysis is performed in SPSS version 20.0. Results: Plasma was taken from fifteen convalescent donors. In the plasma convalescent treatment group, there was a statistically significant difference between outcome and severity degree (p = 0.005). In addition, there was a substantial discrepancy between the result group and the control group (p 0.005). Significant differences in post-treatment NLR between the control and treatment groups (p 0.005). In addition, there were statistically significant differences between the control and treatment groups in post-treatment hsCRP levels (p 0.005). In addition, there were statistically significant differences (p 0.005) between all groups' inflammatory markers and outcomes. Conclusion: Using convalescent plasma to treat patients with COVID-19 is a rather safe practice. Our analysis demonstrated that the administration of convalescent plasma did not enhance survival or clinical outcomes for COVID-19 patients with moderate to severe disease. Keywords: COVID-19, convalescent therapy, critical ill

COVID-19 outcome is not affected by anti-CD20 or high-titer convalescent plasma in immunosuppressed patients

The role of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) convalescent plasma in the treatment of Coronavirus Disease 2019 (COVID-19) in immunosuppressed individuals remains controversial. We describe the course of COVID-19 in patients who had received anti-CD20 therapy within the 3 years prior to infection. We compared outcomes between those treated with and those not treated with high titer SARS-CoV2 convalescent plasma. We identified 144 adults treated at Mayo clinic sites who had received anti-CD20 therapies within a median of 5.9 months prior to the COVID-19 index date. About one-third (34.7%) were hospitalized within 14 days and nearly half (47.9%) within 90 days. COVID-19 directed therapy included anti-spike monoclonal antibodies (n = 30, 20.8%), and, among those hospitalized within 14 days (n = 50), remdesivir (n = 45, 90.0%), glucocorticoids (n = 36, 72.0%) and convalescent plasma (n = 24, 48.0%). The duration from receipt of last dose of anti-CD20 therapy did not correlate with outcomes. The overall 90-day mortality rate was 14.7%. Administration of convalescent plasma within 14 days of the COVID-19 diagnosis was not significantly associated with any study outcome. Further study of COVID-19 in CD20-depleted individuals is needed focusing on the early administration of new and potentially combination antiviral agents, associated or not with vaccine-boosted convalescent plasma.

Factors associated with mortality among hospitalized patients with COVID-19 disease treated with convalescent plasma.

The use of convalescent plasma (CP) for hospitalized patients with SARS-CoV-2 infection might be a useful option in certain settings. Soon after the outbreak of COVID-19, the National Ministry of Health of Argentina recommended the use of CP transfusion for hospitalized patients with COVID-19 disease. Between 1 June and 3 October 2020, 480 patients, excluding those on invasive mechanical ventilation (IMV), received at least one CP infusion in the province of Santa Fe. We aimed to find factors associated with mortality among this cohort of patients. The median age was 60 years (interquartile range: 49-69 years) and 320 (66.7%) were males. Most of these patients (93.75%) received a single CP infusion, 82.1% and 95.6% before day 4 and day 7 of hospitalization, respectively. Anti-SARS-CoV-2 titers were determined in the CP units administered using Elecsys Anti-SARS-CoV-2 S assay. At 28 days of follow-up, 250 patients were discharged (52.1%), 131 (27.3%) remained hospitalized without and 16 (3.3%) with oxygen requirement, 27 (5.6%) were on IMV, and 56 (11.7%) had died. In the multivariate logistic regression analysis, the factors significantly associated with 28-day mortality were (i) requirement of IMV, (ii) the administration of CP after the third day of hospitalization, (iii) age, and (iv) number of comorbidities. The qualitative and quantitative analyses of antibodies against SARS-CoV-2 in the infused CP were not associated with mortality. Our findings may imply a seemingly favorable effect of CP administration among patients with severe COVID-19 disease when infused sooner after hospitalization.IMPORTANCEThe use of convalescent plasma (CP) could be an option for patients with severe COVID-19, especially in poor-resource countries where direct antiviral drugs are not commercially available. Currently, the U.S. Food and Drug Administration limits the CP administration for outpatients and inpatients with COVID-19 who are immunocompromised and only if high levels of anti-SARS-CoV-2 antibodies are confirmed in the CP unit. Although most of the randomized clinical trials failed to show a clear-cut benefit of CP in hospitalized patients with severe COVID-19, other studies have shown that if given early in the course of the disease, it might be a useful therapeutic option. In this retrospective study, we demonstrated that early treatment (within 3 days of hospitalization) was significantly associated with reduced 28-day mortality compared with those patients treated beyond day 3. The results from our study add up to the scientific evidence on the use of CP as a relatively safe, cheap, and possibly effective therapy in certain patients suffering from severe SARS-CoV-2 infection.

Effect of SARS-CoV-2 infection on anti-HLA antibodies and de novo donor specific antibodies incidence in lung transplant recipients

PurposeThere are no clear guidelines on how to handle immunosuppression in lung transplant recipients (LTRs) infected by SARS-CoV-2. Antimetabolite reduction with corticosteroid escalation is the most frequent strategy. The aim of this study was to determine the effect of this therapeutic approach on the incidence of de novo donor specific-antibodies (dnDSA). MethodsWe retrospectively analysed a cohort of 27 LTRs diagnosed with SARS-CoV-2 infection between September 2020 and April 2021 with available anti-HLA antibodies screening before and after infection. Managed as per the centre's SARS-CoV-2 protocol, the treatment modalities included specific virostatic treatment, convalescent plasma administration, reduction or discontinuation of mycophenolate and transient corticosteroid escalation initiated in the second week post-infection. ResultsAll 27 patients received virostatics: 15 (55.6%) remdesivir and 12 (44.4%) favipiravir. In addition, 18 patients (66.7%) underwent convalescent plasma therapy. Of the 27 patients, 25 (92.6%) received mycophenolate as a part of their maintenance immunosuppressive regimen, which was temporarily reduced in 10 (37%) and discontinued in 15 LTRs (55.6%), the median resumption times for mycophenolate daily doses of at least 1000 mg being 13 days (IQR 11.0–63.5) and 59 days (IQR 26.0–130.0), respectively. Corticosteroids were escalated in 25 patients (92.6%), of whom 9 (33.3%) received IV methylprednisolone (median 80 mg/day; IQR 80–187.5) and 16 (59.3%) had oral prednisone adjusted (median 20 mg/day; IQR 16.3–38.8). The median time to revert to the corticosteroid dosage of ≤20 mg/day was 42 days (IQR 36.0–87.0). Notably, no dnDSA were detected in any LTR between 1 and 9 months from the onset of the SARS-CoV-2 infection. ConclusionOur findings suggest that antimetabolite cessation with a transient corticosteroid escalation is a safe therapeutic strategy regarding anti-HLA dynamics in SARS-CoV-2 infected LTRs.

Re-Infection of COVID-19 at Dr. Moewardi General Hospital, Surakarta, from March 2020 to June 2021

Background: COVID-19 reinfection has been identified and is being studied. Several risk factors, including being a health worker and having A blood type, are linked to reinfection, and comorbidities such as hypertension, obesity, diabetes, and asthma influence the disease's severity. To identify mutational variations associated with viral virulence and spread, genetic studies are required. The purpose of this study is to determine the prevalence of SARS-CoV-2 reinfection, as well as patient characteristics and risk factors related to SARS-CoV-2 reinfection. Subjects and Method: This is a retrospective cohort study using data from the medical records of patients with COVID-19 reinfection treated at the Dr. Moewardi General Hospital (RSDM) Surakarta from March 2020 to June 2021. A sample was collected from 19 men and 20 women. The degree of COVID-19 infection is the dependent variable. Gender, occupation, comorbidities, and immunization history were the independent variables. The entire sampling method was employed in this investiga¬tion (consecutive sampling). Data is handled in Microsoft Excel 2010, and statistical analysis is performed in SPSS version 20.0. Results: COVID-19 re-infection is equally likely in men and women. The average patient age was 42 years, with patients ranging in age from 25 to 73 years. Patients in the study were classified as either health workers or non-health workers, with 29 (76.3%) and 9 (23.7%) respectively. Due of restricted resources, the average period of COVID-19 re-infection is 197.6 +/- 97 days without genomic sequence investigation. Comorbidities were discovered in 11 of 38 COVID-19 reinfection patients (29%) Only 6 individuals (15.8%) with COVID-19 reinfection had a history of vaccination. Conclusion: Using convalescent plasma to treat patients with COVID-19 is a rather safe practice. Our analysis demonstrated that the administration of convalescent plasma did not enhance survival or clinical outcomes for COVID-19 patients with moderate to severe disease. Keywords: COVID-19, COVID-19 reinfection, health workers, comorbidity Correspondence: Jatu Aphridasari. Department of Pulmonology and Respiratory Medicine, Dr. Moewardi General Hospital, Surakarta – Indonesia. jatuparu@staff.uns.ac.id. Mobile: +6281289991329.

Efficacy and safety of convalescent plasma administration in patients with COVID-19

IntroductionDuring the COVID-19 pandemic, several strategies were suggested for the management of the disease, including pharmacological and non-pharmacological treatments such as convalescent plasma (CP). The use of CP was suggested due to the beneficial results shown in treating other viral diseases. ObjectiveTo determine the efficacy and safety of CP obtained from whole blood in patients with COVID-19. MethodsPilot clinical trial in patients with COVID-19 from a general hospital. The subjects were separated into three groups that received the transfusion of 400 ml of CP (n = 23) or 400 ml of standard plasma (SP) (n = 19) and a non-transfused group (NT) (n = 37). Patients also received the standard available medical treatment for COVID 19. Subjects were followed up daily from admission to day 21. ResultsCP did not improve the survival curve in moderate and severe variants of COVID-19, nor did it reduce the degree of severity of the disease evaluated with the COVID-19 WHO and SOFA clinical progression scale. No patient had a severe post-transfusion reaction to CP. ConclusionsTreatment with CP does not reduce the mortality of patients even when its administration has a high degree of safety.

Association of substance use with outcomes in mildly ill COVID-19 outpatients

BackgroundSmoking, alcohol use, and non-prescription drug use are associated with worsened COVID-19 outcomes in hospitalized patients. Whether there is an association between substance use and outcomes in patients with COVID-19 who visited the Emergency Department (ED) but did not require hospitalization has not been well established. We investigated whether smoking, alcohol, and non-prescription drug use were associated with worsened COVID-19 outcomes among such patients presenting to the ED. MethodsWe conducted a secondary analysis of a clinical trial which sought to determine the effect of early convalescent plasma administration in patients presenting to the ED within 7 days of onset of mild COVID-19 symptoms. The study recruited 511 participants who were aged 50 years or older or had one or more risk factors for severe COVID-19. The primary outcome was disease progression within 15 days after randomization, which was defined as a composite of hospital admission for any reason, seeking emergency or urgent care, or death without hospitalization. Secondary outcomes included: no hospitalization within 30 days post-randomization, symptom worsening on the 5-category COVID-19 outpatient ordinal scale within 15 days post-randomization, and all-cause mortality. Substance use was categorized into either use or never use based on participant self-report. Logistic regression models were used to determine the association between substance use and outcomes. ResultsThe mean age of the 511 patients enrolled was 52 years and the majority were females (274, 54%). Approximately 213 (42%) were non-Hispanic Whites, 156 (30%) Hispanics, 100 (20%) non-Hispanic Blacks, 18 (4%) non-Hispanic Asian, 8 (1%) American Indian Alaskan, and 16 (3%) unknown race.Tobacco 152 (30%) was the most common substance use reported. Alcohol use 36 (7%) and non-prescription drug use 33 (6%) were less common. Tobacco use and non-prescription drug use were associated with an increased risk for meeting the primary outcome ((tobacco: adjusted odds ratio [aOR] =2.08; 95% confidence interval [CI]: 1.37–3.15) and (drug: aOR =2.41; 95%CI: 1.17–5.00)) and increased risk for symptom worsening on the 5-category COVID-19 outpatient scale ((tobacco: aOR = 1.62; 95%CI: 1.09–2.42) and (drug: aOR = 2.32 95% CI: 1.10–4.87)) compared to non-use after adjusting for age, sex, plasma administration, and comorbidity. ConclusionTobacco and non-prescription drug use but not alcohol use were associated with worsened COVID-19 outcomes in patients who did not require hospitalization on their initial presentation. Future studies should determine the quantity, duration, and type of drug/tobacco use that may worsen COVID-19.

Intranasal administration of convalescent plasma protects against SARS-CoV-2 infection in hamsters.

Convalescent plasma (CP) transfusion is an early option for treating infections with pandemic potential, often preceding vaccine or antiviral drug rollout. Heterogenous findings from randomized clinical trials on transfusion of COVID-19 CP (CCP) have been reported. However, meta-analysis suggests that transfusion of high titer CCP is associated with a mortality benefit for COVID-19 outpatients or inpatients treated within 5 days after symptom onset, indicating the importance of early administration. We tested if CCP is an effective prophylactic against SARS-CoV-2 infection by the intranasal administration of 25μL CCP/nostril (i.e. 0.01-0.06mg anti-RBD antibodies/kg) in hamsters exposed to infected littermates. In this model, 40% of CCP treated hamsters were fully protected and 40% had significantly reduced viral loads, the remaining 20% was not protected. The effect seems dose-dependent because high-titer CCP from a vaccinated donor was more effective than low-titer CCP from a donation prior to vaccine rollout. Intranasal administration of human CCP resulted in a reactive (immune) response in hamster lungs, however this was not observed upon administration of hamster CCP. We conclude that CCP is an effective prophylactic when used directly at the site of primary infection. This option should be considered in future prepandemic preparedness plans. Flanders Innovation & Entrepreneurship (VLAIO) and the Foundation for Scientific Research of the Belgian Red Cross Flanders.

Efficacy of convalescent plasma therapy for COVID-19 in Japan: An open-label, randomized, controlled trial

BackgroundConvalescent plasma is a potential therapeutic option for patients with coronavirus disease 2019 (COVID-19). Despite its use for treating several viral infections, we lack comprehensive data on its efficacy against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). MethodsWe conducted a multicenter, open-label, randomized controlled trial of convalescent plasma therapy with high neutralizing activity against SARS-CoV-2 in high-risk patients within five days after the onset of COVID-19 symptoms. The primary endpoint was the time-weighted average change in the SARS-CoV-2 viral load in nasopharyngeal swabs from days 0–5. ResultsBetween February 24, 2021, and November 30, 2021, 25 patients were randomly assigned to either convalescent plasma (n = 14) or standard of care (n = 11) groups. Four patients discontinued their allocated convalescent plasma, and 21 were included in the modified intention-to-treat analysis. The median interval between the symptom onset and plasma administration was 4.5 days (interquartile range, 3–5 days). The primary outcome of the time-weighted average change in the SARS-CoV-2 viral load in nasopharyngeal swabs did not significantly differ between days 0–5 (1.2 log10 copies/mL in the convalescent plasma vs. 1.2 log10 copies/mL in the standard of care (effect estimate, 0.0 [95% confidence interval, −0.8–0.7]; P = 0.94)). No deaths were observed in either group. ConclusionsThe early administration of convalescent plasma with high neutralizing activity did not contribute to a decrease in the viral load within five days compared with the standard of care alone.

Mid-titer human convalescent plasma administration results in suboptimal prophylaxis against SARS-CoV-2 infection in rhesus macaques.

ARS-CoV-2 is a respiratory pathogen currently causing a worldwide pandemic, with resulting pathology of differing severity in humans, from mild illness to severe disease and death. The rhesus macaque model of COVID-19 was utilized to evaluate the added benefit of prophylactic administration of human post-SARS-CoV-2 infection convalescent plasma (CP) on disease progression and severity. A pharmacokinetic (PK) study using CP in rhesus monkeys preceded the challenge study and revealed the optimal time of tissue distribution for maximal effect. Thereafter, CP was administered prophylactically three days prior to mucosal SARS-CoV-2 viral challenge. Results show similar viral kinetics in mucosal sites over the course of infection independent of administration of CP or normal plasma, or historic controls with no plasma. No changes were noted upon necropsy via histopathology, although there were differences in levels of vRNA in tissues, with both normal and CP seemingly blunting viral loads. Results indicate that prophylactic administration with mid-titer CP is not effective in reducing disease severity of SARS-CoV-2 infection in the rhesus COVID-19 disease model.

Effect of Convalescent Plasma Therapy on Mortality and Viral Load in Severely Ill Patients with COVID-19.

The use of convalescent plasma (CP) appeared to be a promising, easily available and safe way of treatment of severe COVID-19 at the onset of the pandemic in early 2020. Conducted in 2020 and 2021, our study of 52 severely to critically ill COVID-19 patients who received CP plasma as a treatment and of 97 controls found no difference in 30-day or 90-day mortality rates. A significant viral load drop in most patients (4.7 log10 [p<0.001] copies/ml) was observed following CP administration. Retrospective analysis of selected inflammatory markers and immunoglobulins showed higher C-reactive protein levels among the study group, and their decrease on Day 7.

The Use of Convalescent Plasma Therapy on COVID-19 Filipino Patients: A Tertiary Center Experience

Aim: To know the effect of Convalescent plasma in clinical and laboratory parameters of the recipients, the effect of convalescent plasma in clinical and laboratory parameters of the CPT arm and control arm, to identify the association of early consultation to severity and outcome, early administration of convalescent plasma to severity and outcome and lastly to identify overall effect of convalescent plasma to overall mortality and overallmortality with severity. Methods: Prospective, non-randomized, Cohort Study. Results: 35 patients were assigned as plasma recipients and 35 patient as control arm receiving standard of treatment alone. They were matched based on age, sex, severity. Descriptive statistics shows comparability of both arms. There is noted positive effect of convalescent plasma in the temperature(Mean Pre-CPT Temperature of 37.05±0.61, Mean Post-CPT Temp of 36.54±0.50, p-value of 0.001), and Systolic Blood pressure (Mean Pre-CPT SBP 126.62±17.41, Mean Post-CPT SBP 119.32±14.66, p-value of 0.033). Among the clinical parameters, CBC, significant difference was noted in the eosinophils and MCHC, CRP among the inflammatory markers, SGOT for the liver function test, in the arterial blood gas parameters there was noted significant difference in the level of paO2, pCO2, HCO3 in favor of a positive effect of convalescent plasma except for the eosinophils which may be negative in nature. Among the clinical parameters, there is noted significant difference in favor of CPT in the values of Oxygen saturation, white blood cell, neutrophil count, lymphocytes count, basophils, eosinophil count; there was significantly lower values for inflammatory markers in the CPT arm namely in LDH, CRP, DDMER, Procalcitonin; the same was noted in the liver function test(SGPT, SGOT), arterial blood gas, specifically, in paO2 and Chest-Xray lesion. There is significant difference favoring the control arm in the Rox index, O2 support. There is significant difference favoring those who were discharged in both mean systolic and diastolic pressure, in the hematocrit, white blood cell count, monocytes, Basophils, MCV, MCH, MCHC. All inflammatory markers favors the CPT arm. Same positive effect was seen in the pH and pCO2 and Chest-X Ray lesion. Results showed that there is weak positive correlation between duration of symptoms to consult and disease severity with Spearman's correlation coefficient of 0.1591 but not significant. No sufficient statistical evidence to conclude that duration of symptoms to consult is associated with mortality. Furthermore, in looking at the association of giving CPT early in the disease presentation and severity as well as outcome, results showed that there is weak negative correlation between duration of symptoms to CPT and disease severity. But, not significant. Duration of symptoms to CPT was found to be significantly associated with mortality. There is no sufficient evidence to conclude that CPT is associated with a favorable outcome among COVID-19 patients. Same results were observed after doing sub-analysis according to severity of disease. Conclusion: Convalescent plasma, in general, did not show improvement in clinical and laboratory parameters among recipients. But, CPT recipients show better clinical and laboratory parameters compared to the control arm(non-CPT recipient). Early administration of convalescent plasma may decrease mortality. There are no significant differences observed in over-all cause mortality among CPT recipients and those recipients of the best available treatment alone.

Convalescent plasma treatment for SARS-CoV-2 infected high-risk patients: a matched pair analysis to the LEOSS cohort

Establishing the optimal treatment for COVID-19 patients remains challenging. Specifically, immunocompromised and pre-diseased patients are at high risk for severe disease course and face limited therapeutic options. Convalescent plasma (CP) has been considered as therapeutic approach, but reliable data are lacking, especially for high-risk patients. We performed a retrospective analysis of 55 hospitalized COVID-19 patients from University Hospital Duesseldorf (UKD) at high risk for disease progression, in a substantial proportion due to immunosuppression from cancer, solid organ transplantation, autoimmune disease, dialysis. A matched-pairs analysis (1:4) was performed with 220 patients from the Lean European Open Survey on SARS-CoV-2-infected Patients (LEOSS) who were treated or not treated with CP. Both cohorts had high mortality (UKD 41.8%, LEOSS 34.1%). A matched-pairs analysis showed no significant effect on mortality. CP administration before the formation of pulmonary infiltrates showed the lowest mortality in both cohorts (10%), whereas mortality in the complicated phase was 27.8%. CP administration during the critical phase revealed the highest mortality: UKD 60.9%, LEOSS 48.3%. In our cohort of COVID-19 patients with severe comorbidities CP did not significantly reduce mortality in a retrospective matched-pairs analysis. However, our data supports the concept that a reduction in mortality is achievable by early CP administration.

Alteration of Lung Physiology with the Administration of Convalescent Plasma in ARDS Patients Intubated with COVID-19 Pneumonia

Background: It remains unknown to what degree lung physiology is altered by administration of convalescent plasma in patients intubated with ARDS due to COVID-19 pneumonia. Although no longer clinically used as treatment for COVID-19, convalescent plasma therapy could be deployed again should new virus threats emerge in the future. Aim: To evaluate changes in ventilator physiologic variables in response to convalescent plasma transfusion using a retrospective, observational, case control study of intubated patients with COVID-19 pneumonia. Methods: Patients who were receiving mechanical ventilation due to COVID-19 at the time of administration of convalescent plasma therapy (CPT) were matched to control patients who did not receive convalescent plasma. Ventilatory data such as compliance, positive end-expiratory pressure (PEEP), FiO2 administered, PaO2/FiO2 ratio, and tidal volume were collected pre and post administration. Panel-level random-effects linear regression models were used to assess the mean difference and interactions between CPT and cases vs controls over time. Results: 12 patients received CPT while intubated and were matched to 35 intubated control patients who did not receive CPT. In total, 857 separate measurements of static compliance were obtained over time. No significant difference in static compliance was seen after CPT. In cases, adjusted mean static compliance was 30.8 (95% CI (23.3, 38.4))mL/cm H2O before CPT and 28.2 (95% CI (20.7,35.6)) mL/cm H2O afterwards. Controls adjusted mean static compliance was 33.9 (95% CI (29.5, 38.4)) mL/cm H2O before versus 32.2 (95% CI (27.9, 36.5)) mL/cm H2O afterwards. Variables that had small but statistically significant differences pre vs post CPT among cases and controls were systolic and diastolic blood pressure, FiO2, heart rate, applied PEEP, and respiratory rate. Conclusion: While some statistically significant physiologic effects were seen with CPT in mechanically ventilated patients, these were deemed to be small and clinically insignificant. This is consistent with prior research on less acutely ill COVID-19 patients.

Use of convalescent plasma in patients with COVID-19

Introducton: We wished to evaluate the clinical effectiveness of convalescent plasma (CP) in coronavirus disease 2019 (COVID-19) patients treated in hospitals in the Kuyavian-Pomeranian Voivodeship, including the impact of treatment duration and CP antibody titer on the course of hospitalization and patient survival in relation to other risk factors. Material and methods: This was a retrospective analysis of clinical data of CP use in hospitals in the Kuyavian-Pomeranian Voivodeship. Results: A total of 3,596 patients had available clinical data. In 59% of patients, CP was administered during the initial 24 hours of hospitalization (median: 1 day, range 1–49). In cured patients, hospital length of stay correlated with time of CP administration ( p <0.001), i.e. the sooner the COVID-19 convalescent plasma (CCP) was administered, the shorter the hospitalization. Overall survival in analyzed COVID-19 patients was 78.3%, and it was better when CP was administered during the first day of hospitalization (79.9% vs. 86.8%, p = 0.057), in younger patients (91.0% vs. 76.2% for patients <50 years and older, respectively; p <0.001); in patients not requiring invasive ventilation (78.7% vs. 26.9%, p <0.001), in good performance status patients (92.5% vs. 81.0% and 68.6% in patients in moderate and poor performance status, respectively; p <0.001); and in patients without comorbidities (88.6% vs. 75.9%, p <0.001). In turn, blood group and titers of antibodies against severe acute respiratory syndrome coronavirus 2 in CP had no impact on survival. In multivariate analysis, the following factors increased the risk of death from COVID-19: general clinical status at admission (poor > moderate > good), comorbidities, mechanical ventilation required. Risk of death was decreased in younger patients (continuous variable), while administration of CP within the first day of hospitalization had borderline significance ( p = 0.077). The use of CP was a safe therapeutic approach. Mild reactions were reported after just 5/9,356 (0.05%) transfusions. Conclusions: The early administration of CP had a beneficial effect on the clinical course of treatment in COVID-19 patients.

Efficacy of COVID-19 Convalescent Plasma Based on Antibody Concentration.

Background Convalescent plasma obtained from individuals who have recovered from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) contains neutralizing antibodies to the virus and has been frequently used as a treatment in hospitalized patients with severe COVID-19. Methods We conducted a retrospective, observational cohort study involving 96 hospitalized patients with severe COVID-19 who were allocated in a 1 : 1 ratio to having received either high antibody concentration convalescent plasma or low antibody concentration convalescent plasma. Quantitative measurements of IgG to the receptor-binding domain (RBD), the S1 subunit of the spike protein, and the SARS-CoV-2 nucleocapsid (N) protein were determined from donor plasma samples. The primary outcome was all-cause mortality within 30 days following convalescent plasma administration in regard to each of the three antibody domains. Results Within the nucleocapsid antibody domain, death occurred in 22.2% of patients in the low antibody concentration group versus 23.5% in the high antibody concentration group (p=0.88). Within the RBD antibody domain, death occurred in 22.9% of patients in both the low and the high antibody concentration groups (p=1.0). Within the S1 subunit antibody domain, death occurred in 27.1% of patients in the low antibody concentration group versus 18.8% in the high antibody concentration group (p=0.33). Conclusions No significant differences were observed between low and high concentration convalescent plasma in regard to overall mortality at 30 days, hospital length of stay, number of ventilator days, and subsequent receipt of invasive mechanical ventilation in patients who were previously not receiving mechanical ventilation. Trial Registration. This study was not associated with a clinical trial due to the retrospective nature of study design.

Prolonged ICU Stay in Severe and Critically-Ill COVID-19 Patients Who Received Convalescent Plasma Therapy.

Background Convalescent plasma administration in severe and critically-ill COVID-19 patients have been proven to not provide improvement in patients' outcome, yet it is still widely used in countries with limited resources due to its high availability and safety. This study aims to investigate its effects on ICU mortality, ICU length of stay (LoS), and improvement of oxygen support requirements. Methods Data of all severe and critically-ill patients in our COVID-19 ICU was collected retrospectively between May and November 2020. We dichotomized the variables and compared outcome data of 48 patients, who received convalescent plasma to 131 patients, receiving standard of care. Data were analyzed using multiple logistic regression to make prediction models of mortality, length of stay, and oxygen support device requirement. Result Overall mortality rate in our COVID-19 ICU was 55.3%, with a median overall length of stay of 8 (4–11) days. Less patients that received convalescent plasma presented with the need for mechanical ventilation on ICU admission (p < 0.001), but with comparable PaO2 to FiO2 (P/F) ratio (p=0.95). Factors that confounded mortality were obesity (aOR = 14.1; 95% CI (1.25, 166.7); p=0.032), mechanical ventilation (aOR = 333; 95% CI (4.5,1,000); p < 0.001), higher neutrophil-to-lymphocyte ratio (NLR) (aOR = 7.32; 95% CI (1.82, 29.4); p=0.005), and lower P/F ratio (aOR = 7.70; 95% CI (2.04, 29.4); p=0.003). ICU LoS was longer in patients, who had prior history of hypertension (aOR = 2.14; 95% CI (1.05, 4.35); p=0.036) and received convalescent plasma (aOR = 3.88; 95% CI (1.77, 8.05); p < 0.001). Deceased patients, who received convalescent plasma, stayed longer in the ICU with a mean length of stay of 12.87 ± 5.7 days versus 8.13 ± 4.8 days with a significant difference (U = 434; p < 0.000). The chance of improved oxygen support requirements was lower in obese patients (aOR = 9.18; 95%CI (2.0, 42.1); p < 0.004), mechanically ventilated patients (aOR = 13.15; 95% CI (3.75, 46.09); p < 0.001), patients with higher NLR (aOR = 2.5; 95% CI (1.07, 5.85); p=0.034), and lower P/F ratio (aOR = 2.76; 95% CI (1.1, 6.91); p=0.031). Conclusion The length of stay of patients in the convalescent plasma group was significantly longer than the control group. There was no effect of convalescent plasma in ICU mortality and no improvement was observed in terms of oxygen support requirements.

Retrospective study shows that early administration of convalescent plasma in hospitalized COVID-19 patients may have a positive effect on disease progression.

Retrospective study shows that early administration of convalescent plasma in hospitalized COVID-19 patients may have a positive effect on disease progression.