Early Treatment with Monoclonal Antibodies or Convalescent Plasma Reduces Mortality in Non-Vaccinated COVID-19 High-Risk Patients.

Vulnerable patients such as immunosuppressed or elderly patients are at high risk for a severe course of COVID-19 upon SARS-CoV-2 infection. Immunotherapy with SARS-CoV-2 specific monoclonal antibodies (mAb) or convalescent plasma represents a considerable treatment option to protect these patients from a severe or lethal course of infection. However, monoclonal antibodies are not always available or less effective against emerging SARS-CoV-2 variants. Convalescent plasma is more commonly available and may represent a good treatment alternative in low-income countries. We retrospectively evaluated outcomes in individuals treated with mAbs or convalescent plasma and compared the 30-day overall survival with a patient cohort that received supportive care due to a lack of SARS-CoV-2 specific therapies between March 2020 and April 2021. Our data demonstrate that mAb treatment is highly effective in preventing severe courses of SARS-CoV-2 infection. All patients treated with mAb survived. Treatment with convalescent plasma improved overall survival to 82% compared with 61% in patients without SARS-CoV-2 targeted therapy. Our data indicate that early convalescent plasma treatment may be an option to improve the overall survival of high-risk COVID-19 patients. This is especially true when other antiviral drugs are not available or their efficacy is significantly reduced, which may be the case with emerging SARS-CoV-2 variants.

Convalescent Plasma Therapy in Late-State, Severe COVID-19 Infection.

OBJECTIVES: Current evidence favors plasma to be effective against coronavirus disease 2019 (COVID-19) in critically ill patients in the early stages of infection. We investigated the safety and efficacy of convalescent plasma in specifically late-stage (designated as after 2 weeks of hospital admission) severe COVID-19 infection. We also conducted a literature review on the late-stage use of plasma in COVID-19. METHODS: This case series examined eight COVID-19 patients admitted to the intensive care unit (ICU) who met criteria for severe or life-threatening complications. Each patient received one dose (200 mL) of plasma. Clinical information was gathered in intervals of 1 day pretransfusion and 1 hour, 3 days, and 7 days posttransfusion. The primary outcome was effectiveness of plasma transfusion, measured by clinical improvement, laboratory parameters, and all-cause mortality. RESULTS: Eight ICU patients received plasma late in the course of COVID-19 infection, on average at 16.13 days postadmission. On the day before transfusion, the averaged initial Sequential Organ Failure Assessment (SOFA) score, PaO2:FiO2 ratio, Glasgow Coma Scale (GCS), and lymphocyte count were 6.5, 228.03, 8.63, and 1.19, respectively. Three days after plasma treatment, the group averages for the SOFA score (4.86), PaO2:FiO2 ratio (302.73), GCS (9.29), and lymphocyte count (1.75) improved. Although the mean GCS improved to 10.14 by posttransfusion day 7, the other means marginally worsened with an SOFA score of 5.43, a PaO2:FiO2 ratio of 280.44, and a lymphocyte count of 1.71. Clinical improvement was noted in six patients who were discharged from the ICU. CONCLUSIONS: This case series provides evidence that convalescent plasma may be safe and effective in late-stage, severe COVID-19 infection. Results showed clinical improvement posttransfusion as well as decreased all-cause mortality in comparison to pretransfusion predicted mortality. Randomized controlled trials are needed to conclusively determine benefits, dosage, and timing of treatment.

Convalescent plasma transfusion in severe COVID-19 patients: Clinical and laboratory outcomes.

INTRODUCTION: The objective of this study was to investigate the effect of convalescent plasma (CP) transfusion on clinical and serial laboratory parameters in severe COVID-19 patients. The Coronavirus Disease 2019 (COVID-19) pandemic presents a challenge to the healthcare system worldwide due to the limited treatment options available. The body of evidence reported that CP containing anti- COVID-19 antibodies could be effective against the infection. MATERIALS AND METHODS: This was a cross-sectional study that involved retrospective data collection of severe COVID-19 adult patients who received CP transfusion along with the best-of-care (CP group, n: 53) and best-of-care only (control group, n: 53). An age, gender, and comorbidity were manually matched approximately at a 1:1 ratio. RESULTS: The prevalence of adverse transfusion reactions was 5.7%. A shorter duration of oxygen support (median: 12 days vs 14 days, P=0.030) and a shorter duration of mechanical ventilation (median: 6 days vs 10 days, P=0.048) were found in the CP group. The laboratory parameters were also improved. However, there was no significant difference in the mechanical ventilation rate, length of hospital stay, length of intensive care unit (ICU) stay, and mortality rate across both groups (P = 0.492, 0.614, 0.793, 0.374). CONCLUSION: CP transfusion is safe and effective in the treatment of severe COVID-19 patients. However, a revision of our approaches such as early CP transfusion and use of a high-titre anti-COVID-19 neutralising antibody (nAb) unit is necessary to unlock the full potential benefits of CP transfusion among COVID-19 patients.

Convalescent Plasma Treatment of Patients Previously Treated with B-Cell-Depleting Monoclonal Antibodies Suffering COVID-19 Is Associated with Reduced Re-Admission Rates.

Patients receiving treatment with B-cell-depleting monoclonal antibodies, such as anti-CD20 monoclonal antibodies, such as rituximab and obinutuzumab, either for hematological disease or another diagnosis, such as a rheumatological disease, are at an increased risk for medical complications and mortality from COVID-19. Since inconsistencies persist regarding the use of convalescent plasma (CP), especially in the vulnerable patient population that has received previous treatment with B-cell-depleting monoclonal antibodies, further studies should be performed in thisdirection. The aim of the present study was to describe the characteristics of patients with previous use of B-cell-depleting monoclonal antibodies and describe the potential beneficial effects of CP use in terms of mortality, ICU admission and disease relapse. In this retrospective cohort study, 39 patients with previous use of B-cell-depleting monoclonal antibodies hospitalized in the COVID-19 department of a tertiary hospital in Greece were recorded and evaluated. The mean age was 66.3 years and 51.3% were male. Regarding treatment for COVID-19, remdesivir was used in 89.7%, corticosteroids in 94.9% and CP in 53.8%. In-hospital mortality was 15.4%. Patients who died were more likely to need ICU admission and also had a trend towards a longer hospital stay, even though the last did not reach statistical significance. Patients treated with CP had a lower re-admission rate for COVID-19 after discharge. Further studies should be performed to identify the role of CP in patients with treatment with B-cell-depleting monoclonal antibodies suffering from COVID-19.

The safety of plasma apheresis from donors recovering from COVID-19 infection in Japan.

PURPOSE: Since 2020, the novel coronavirus infection (COVID-19) has spread globally. A few studies have investigated the safety of COVID-19 convalescent plasma (CCP) apheresis from COVID-19. This study was the first retrospective observational study of CCP in Japan. METHODS: We recruit donors from April 2020 to November 2021 and plasmapheresis in our center (NCGM: national center for global health and medicine). We set the primary endpoint as the Donors Adverse Event (DAE) occurrence at the time of the CCP collection. Variable selection was used to explore the determinants of DAE. RESULTS: Mean and SD age was 50.5 (10.6) years old. Seventy-three (42.2 %) were female, and 87 (33.3 %) were multiple-times donors. Twelve (6.97 % by donors and 4.6 % in total collections) adverse events occurred. The DAEs were VVR (Vaso Vagal Reaction), paresthesia, hypotension, agitation, dizziness, malaise, and hearing impairment/paresthesia. Half of them were VVR during apheresis. DAE occurred only in first-time donors and more in severe illnesses such as using ventilation and ECMO. From the donor characteristics and variable selection, the risk factors are as follows: younger age, female, the severity of disease at the time of the disease, and lower SBP before initiation. Our DAE incidence did not differ from previous studies. DAEs were more likely to occur in CCP apheresis than in healthy donors. CONCLUSION: We confirm the safety of CCP apheresis in this study, although DAEs were more than healthy donors. More caution should be exercised in the plasma collection for future outbreaks of emerging infectious diseases.

Use of immunoglobulin replacement therapy in patients with secondary antibody deficiency in daily practice: a European expert Q&A-based review.

INTRODUCTION: Secondary antibody deficiencies (SAD) are often a side effect of specific therapies that target B cells directly or affect the antibody response indirectly. Treatment of immunodeficiency by immunoglobulin replacement therapy (IgRT) is well established in primary antibody deficiencies, although the evidence for its use in SAD is less well established. To fill the gap and provide opinion and advice for daily practice, a group of experts met to discuss current issues and share best practical experience. AREAS COVERED: A total of 16 questions were considered that covered use of a tailored approach, definition of severe infections, measurement of IgG levels and specific antibodies, indications for IgRT, dosage, monitoring, discontinuation of IgRT, and Covid-19. EXPERT OPINION: Key points for better management SID should include characterization of the immunological deficiency, determination of the severity and degree of impairment of antibody production, distinguish between primary and secondary deficiency, and design a tailored treatment protocol that should include dose, route, and frequency of Ig replacement. There remains the need to carry out well-designed clinical studies to develop clear guidelines for the use of IgRT in patients with SAD.

Long-term high-dose immunoglobulin successfully treats Long COVID patients with pulmonary, neurologic, and cardiologic symptoms.

Introduction: Long COVID is the overarching name for a wide variety of disorders that may follow the diagnosis of acute SARS-COVID-19 infection and persist for weeks to many months. Nearly every organ system may be affected. Methods: We report nine patients suffering with Long COVID for 101 to 547 days. All exhibited significant perturbations of their immune systems, but only one was known to be immunodeficient prior to the studies directed at evaluating them for possible treatment. Neurological and cardiac symptoms were most common. Based on this data and other evidence suggesting autoimmune reactivity, we planned to treat them for 3 months with long-term high-dose immunoglobulin therapy. If there was evidence of benefit at 3 months, the regimen was continued. Results: The patients' ages ranged from 34 to 79 years-with five male and four female patients, respectively. All nine patients exhibited significant immune perturbations prior to treatment. One patient declined this treatment, and insurance support was not approved for two others. The other six have been treated, and all have had a significant to remarkable clinical benefit. Conclusion: Long-term high-dose immunoglobulin therapy is an effective therapeutic option for treating patients with Long COVID.

Multi-institutional experience with COVID-19 convalescent plasma in children.

BACKGROUND AND OBJECTIVES: Convalescent COVID-19 plasma (CCP) was developed and used worldwide as a treatment option by supplying passive immunity. Adult studies suggest administering high-titer CCP early in the disease course of patients who are expected to be antibody-negative; however, pediatric experience is limited. We created a multi-institutional registry to characterize pediatric patients (<18 years) who received CCP and to assess the safety of this intervention. METHODS: A REDCap survey was distributed. The registry collected de-identified data including demographic information (age, gender, and underlying conditions), COVID-19 disease features and concurrent treatments, CCP transfusion and safety events, and therapy response. RESULTS: Ninety-five children received CCP: 90 inpatients and 5 outpatients, with a median age of 10.2 years (range 0-17.9). They were predominantly Latino/Hispanic and White. The most frequent underlying medical conditions were chronic respiratory disease, immunosuppression, obesity, and genetic syndromes. CCP was primarily given as a treatment (95%) rather than prophylaxis (5%). Median total plasma dose administered and transfusion rates were 5.0 ml/kg and 2.6 ml/kg/h, respectively. The transfusions were well-tolerated, with 3 in 115 transfusions reporting mild reactions. No serious adverse events were reported. Severity scores decreased significantly 7 days after CCP transfusion or at discharge. Eighty-five patients (94.4%) survived to hospital discharge. All five outpatients survived to 60 days. CONCLUSIONS: CCP was found to be safe and well-tolerated in children. CCP was frequently given concurrently with other COVID-19-directed treatments with improvement in clinical severity scores ≥7 days after CCP, but efficacy could not be evaluated in this study.

Symptom Duration and Resolution With Early Outpatient Treatment of Convalescent Plasma for Coronavirus Disease 2019: A Randomized Trial.

BACKGROUND: Coronavirus disease 2019 (COVID-19) convalescent plasma (CCP) reduces hospitalizations among outpatients treated early after symptom onset. It is unknown whether CCP reduces time to symptom resolution among outpatients. METHODS: We evaluated symptom resolution at day 14 by trial arm using an adjusted subdistribution hazard model, with hospitalization as a competing risk. We also assessed the prevalence of symptom clusters at day 14 between treatments. Clusters were defined based on biologic clustering, impact on ability to work, and an algorithm. RESULTS: Among 1070 outpatients followed up after transfusion, 381 of 538 (70.8%) receiving CCP and 381 of 532 (71.6%) receiving control plasma were still symptomatic (P = .78) at day 14. Associations between CCP and symptom resolution by day 14 did not differ significantly from those in controls after adjustment for baseline characteristics (adjusted subdistribution hazard ratio, 0.99; P = .62). The most common cluster consisted of cough, fatigue, shortness of breath, and headache and was found in 308 (57.2%) and 325 (61.1%) of CCP and control plasma recipients, respectively (P = .16). CONCLUSIONS: In this trial of outpatients with early COVID-19, CCP was not associated with faster resolution of symptoms compared with control. Overall, there were no differences by treatment in the prevalence of each symptom or symptom clusters at day 14. CLINICAL TRIALS REGISTRATION: NCT04373460.

Anti-SARS-CoV-2 antibody-containing plasma improves outcome in patients with hematologic or solid cancer and severe COVID-19: a randomized clinical trial.

Patients with cancer are at high risk of severe coronavirus disease 2019 (COVID-19), with high morbidity and mortality. Furthermore, impaired humoral response renders severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines less effective and treatment options are scarce. Randomized trials using convalescent plasma are missing for high-risk patients. Here, we performed a randomized, open-label, multicenter trial ( https://www.clinicaltrialsregister.eu/ctr-search/trial/2020-001632-10/DE ) in hospitalized patients with severe COVID-19 (n = 134) within four risk groups ((1) cancer (n = 56); (2) immunosuppression (n = 16); (3) laboratory-based risk factors (n = 36); and (4) advanced age (n = 26)) randomized to standard of care (control arm) or standard of care plus convalescent/vaccinated anti-SARS-CoV-2 plasma (plasma arm). No serious adverse events were observed related to the plasma treatment. Clinical improvement as the primary outcome was assessed using a seven-point ordinal scale. Secondary outcomes were time to discharge and overall survival. For the four groups combined, those receiving plasma did not improve clinically compared with those in the control arm (hazard ratio (HR) = 1.29; P = 0.205). However, patients with cancer experienced a shortened median time to improvement (HR = 2.50; P = 0.003) and superior survival with plasma treatment versus the control arm (HR = 0.28; P = 0.042). Neutralizing antibody activity increased in the plasma cohort but not in the control cohort of patients with cancer (P = 0.001). Taken together, convalescent/vaccinated plasma may improve COVID-19 outcomes in patients with cancer who are unable to intrinsically generate an adequate immune response.

The efficiency of convalescent plasma in COVID-19 patients: A systematic review and meta-analysis of randomized controlled clinical trials.

The objective of this study was to assess whether convalescent plasma therapy could offer survival advantages for patients with novel coronavirus disease 2019 (COVID-19). An electronic search of Pubmed, Web of Science, Embase, Cochrane library and MedRxiv was performed from January 1st, 2020 to April 1st, 2022. We included studies containing patients with COVID-19 and treated with CCP. Data were independently extracted by two reviewers and synthesized with a random-effect analysis model. The primary outcome was 28-d mortality. Secondary outcomes included length of hospital stay, ventilation-free days, 14-d mortality, improvements of symptoms, progression of diseases and requirements of mechanical ventilation. Safety outcomes included the incidence of all adverse events (AEs) and serious adverse events (SAEs). The Cochrane risk-of-bias assessment tool 2.0 was used to assess the potential risk of bias in eligible studies. The heterogeneity of results was assessed by I^2 test and Q statistic test. The possibility of publication bias was assessed by conducting Begg and Egger test. GRADE (Grading of Recommendations Assessment, Development and Evaluation) method were used for quality of evidence. This study had been registered on PROSPERO, CRD42021273608. 32 RCTs comprising 21478 patients with Covid-19 were included. Compared to the control group, COVID-19 patients receiving CCP were not associated with significantly reduced 28-d mortality (CCP 20.0% vs control 20.8%; risk ratio 0.94; 95% CI 0.87-1.02; p = 0.16; I² = 8%). For all secondary outcomes, there were no significant differences between CCP group and control group. The incidence of AEs (26.9% vs 19.4%,; risk ratio 1.14; 95% CI 0.99-01.31; p = 0.06; I² = 38%) and SAEs (16.3% vs 13.5%; risk ratio 1.03; 95% CI 0.87-1.20; p = 0.76; I² = 42%) tended to be higher in the CCP group compared to the control group, while the differences did not reach statistical significance. In all, CCP therapy was not related to significantly improved 28-d mortality or symptoms recovery, and should not be viewed as a routine treatment for COVID-19 patients. Trial registration number: CRD42021273608. Registration on February 28, 2022. Systematic review registration: https://www.crd.york.ac.uk/prospero/, Identifier CRD42022313265.

Treatment of COVID-19 with convalescent plasma in patients with humoral immunodeficiency - Three consecutive cases and review of the literature.

Patients lacking humoral response have been suggested to develop a less severe COVID-19, but there are some reports with a prolonged, relapsing or deadly course. From April 2020, there is growing evidence on the benefits of COVID-19 convalescent plasma (CCP) for patients with humoral immunodeficiency. Most of them had a congenital primary immunodeficiency or were on treatment with anti CD20 antibodies. We report on three patients treated in our hospital and review thirty-one more cases described in the literature. All patients but three resolved clinical picture with CCP. A dose from 200 to 800ml was enough in most cases. Antibody levels after transfusion were negative or low, suggesting consumption of them in SARS-CoV-2 neutralization. These patients have a protracted clinical course shortened after CCP. CCP could be helpful for patients with humoral immunodeficiency. It avoid relapses and chronification. CCP should be transfused as early as possible in patients with COVID-19 and humoral immunodeficiency.

Antibodies from convalescent plasma promote SARS-CoV-2 clearance in individuals with and without endogenous antibody response.

BACKGROUNDNeutralizing antibodies are considered a key correlate of protection by current SARS-CoV-2 vaccines. The manner in which human infections respond to therapeutic SARS-CoV-2 antibodies, including convalescent plasma therapy, remains to be fully elucidated.METHODSWe conducted a proof-of-principle study of convalescent plasma therapy based on a phase I trial in 30 hospitalized COVID-19 patients with a median interval between onset of symptoms and first transfusion of 9 days (IQR, 7-11.8 days). Comprehensive longitudinal monitoring of the virological, serological, and disease status of recipients allowed deciphering of parameters on which plasma therapy efficacy depends.RESULTSIn this trial, convalescent plasma therapy was safe as evidenced by the absence of transfusion-related adverse events and low mortality (3.3%). Treatment with highly neutralizing plasma was significantly associated with faster virus clearance, as demonstrated by Kaplan-Meier analysis (P = 0.034) and confirmed in a parametric survival model including viral load and comorbidity (adjusted hazard ratio, 3.0; 95% CI, 1.1-8.1; P = 0.026). The onset of endogenous neutralization affected viral clearance, but even after adjustment for their pretransfusion endogenous neutralization status, recipients benefitted from plasma therapy with high neutralizing antibodies (hazard ratio, 3.5; 95% CI, 1.1-11; P = 0.034).CONCLUSIONOur data demonstrate a clear impact of exogenous antibody therapy on the rapid clearance of viremia before and after onset of the endogenous neutralizing response, and point beyond antibody-based interventions to critical laboratory parameters for improved evaluation of current and future SARS-CoV-2 therapies.TRIAL REGISTRATIONClinicalTrials.gov NCT04869072.FUNDINGThis study was funded via an Innovation Pool project by the University Hospital Zurich; the Swiss Red Cross Glückskette Corona Funding; Pandemiefonds of the UZH Foundation; and the Clinical Research Priority Program "Comprehensive Genomic Pathogen Detection" of the University of Zurich.

Safety and effectiveness of RBD-specific polyclonal equine F(ab´)2 fragments for the treatment of hospitalized patients with severe Covid-19 disease: A retrospective cohort study.

BACKGROUND: Passive immunotherapy has been evaluated as a therapeutic alternative for patients with COVID-19 disease. Equine polyclonal immunotherapy for COVID-19 (EPIC) showed adequate safety and potential efficacy in a clinical trial setting and obtained emergency use authorization in Argentina. We studied its utility in a real world setting with a larger population. METHODS: We conducted a retrospective cohort study at "Hospital de Campaña Escuela-Hogar" (HCEH) in Corrientes, Argentina, to assess safety and effectiveness of EPIC in hospitalized adults with severe COVID-19 pneumonia. Primary endpoints were 28-days all-cause mortality and safety. Mortality and improvement in modified WHO clinical scale at 14 and 21 days were secondary endpoints. Potential confounder adjustment was made by logistic regression weighted by the inverse of the probability of receiving the treatment (IPTW) and doubly robust approach. FINDINGS: Subsequent clinical records of 446 non-exposed (Controls) and 395 exposed (EPIC) patients admitted between November 2020 and April 2021 were analyzed. Median age was 58 years and 56.8% were males. Mortality at 28 days was 15.7% (EPIC) vs. 21.5% (Control). After IPTW adjustment the OR was 0.66 (95% CI: 0.46-0.96) P = 0.03. The effect was more evident in the subgroup who received two EPIC doses (complete treatment, n = 379), OR 0.58 (95% CI 0.39 to 0.85) P = 0.005. Overall and serious adverse events were not significantly different between groups. CONCLUSIONS: In this retrospective cohort study, EPIC showed adequate safety and effectiveness in the treatment of hospitalized patients with severe SARS-CoV-2 disease.

Use of convalescent plasma in pregnant women with early stage COVID-19 infection in a tertiary care hospital in Dubai, February to March 2021: a case series study.

BACKGROUND: The use of COVID-19 convalescent plasma (CCP) for the treatment of SARS-CoV-2 infection in pregnancy is intriguing in view of its safety profile in pregnancy and historical precedence of the use of plasma for other viral illnesses. This study aimed to evaluate the use of CCP in pregnant women with early COVID-19 infection. METHODS: This is a retrospective case series study. We have included seven pregnant women admitted with early COVID-19 infection to a tertiary care hospital, Latifa Maternity Hospital in Dubai, United Arab Emirates between 12 February and 04 March 2021 and who consented to receive COVID-19 convalescent plasma as part of their treatment plan. Main outcomes measured were clinical and radiological features, laboratory tests, WHO clinical progression scale pre and post treatment, and maternal, fetal outcomes. COVID-19 clinical severity was classified according to the NIH guidelines for criteria of SARS-CoV-2. For the radiological features, a modified chest X-ray scoring system was used where each lung was divided into 6 zones (3 on each side upper, middle, and lower). Opacities were classified into reticular, ground glass, patchy and dense consolidations patterns. RESULTS: Seven pregnant women with early COVID-19 were enrolled in this study, their mean age was 28 years (SD 3.6). Four had comorbidities: 2 with diabetes, 1 with asthma, and 1 was obese. Five patients were admitted with a WHO clinical progression score of 4 (hospitalized; with no oxygen therapy) and 2 with a score of 5 (hospitalized; oxygen by mask/nasal prongs). Upon follow up on day 10, 6 patients had a WHO score of 1 or 2 (asymptomatic/mild symptoms) indicating clinical recovery. Adverse reactions were reported in 2 patients, one reported a mild skin rash, and another developed transfusion related circulatory overload. All patients were discharged alive. CONCLUSION: CCP seems to be a promising modality of treating COVID-19 infected pregnant women. However, further studies are needed to ascertain the efficacy of CCP in preventing progressive disease in the management of COVID-19 infection in pregnant women.

Comparison of safety and efficacy of convalescent plasma with fresh frozen plasma in severe covid-19 patients.

BACKGROUND: Role of Convalescent plasma (COPLA) to treat severe COVID-19 is under investigation. We compared efficacy and safety of COPLA with fresh frozen plasma (FFP) in severe COVID-19 patients. METHODS: One group received COPLA with standard medical care (n = 14), and another group received random donor FFP, as control with standard medical care (n = 15) in severe COVID-19 disease. RESULTS: The proportion of patients free of ventilation at day seven were 78.5% in COPLA group, and 93.3 % in control group were not significant (p= 0.258). However, improved respiratory rate, O2 saturation, SOFA score, and Ct value were observed in the COPLA group. No serious adverse events were noticed by plasma transfusion in both groups.

A Multicenter, Prospective, Observational, Cohort-Controlled Study of Clinical Outcomes Following Coronavirus Disease 2019 (COVID-19) Convalescent Plasma Therapy in Hospitalized Patients With COVID-19.

BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has caused high inpatient mortality and morbidity throughout the world. COVID-19 convalescent plasma (CCP) has been utilized as a potential therapy for patients hospitalized with coronavirus disease 2019 (COVID-19) pneumonia. This study evaluated the outcomes of hospitalized patients with COVID-19 treated with CCP in a prospective, observational, multicenter trial. METHODS: From April through August 2020, hospitalized patients with COVID-19 at 16 participating hospitals in Colorado were enrolled and treated with CCP and compared with hospitalized patients with COVID-19 who were not treated with convalescent plasma. Plasma antibody levels were determined following the trial, given that antibody tests were not approved at the initiation of the trial. CCP-treated and untreated hospitalized patients with COVID-19 were matched using propensity scores followed by analysis for length of hospitalization and inpatient mortality. RESULTS: A total of 542 hospitalized patients with COVID-19 were enrolled at 16 hospitals across the region. A total of 468 hospitalized patients with COVID-19 were entered into propensity score matching with 188 patients matched for analysis in the CCP-treatment and control arms. Fine-Gray models revealed increased length of hospital stay in CCP-treated patients and no change in inpatient mortality compared with controls. In subgroup analysis of CCP-treated patients within 7 days of admission, there was no difference in length of hospitalization and inpatient mortality. CONCLUSIONS: These data show that treatment of hospitalized patients with COVID-19 treated with CCP did not significantly improve patient hospitalization length of stay or inpatient mortality.

Predictors of mortality in COVID-19 patients treated with convalescent plasma therapy.

Several options to treat hospitalized severe COVID-19 patients have been suggested. The study aimed to describe survival in patients treated with convalescent COVID plasma (CCP) and to identify in-hospital mortality predictors. This prospective cohort study examined data from 112 severe COVID-19 patients hospitalized in the Corona Departments in an acute care hospital who received two units of CCP (at least one of them high-titer). Demographic and medical data was retrieved from the patients' electronic health records (EHR). Possible predictors for in-hospital mortality were analyzed in a univariate analysis and those found to be clinically significant were further analyzed in a multivariable analysis. Median age was 67 years (IQR 55-74) and 66 (58.9%) of them were males. Of them, 20 (17.9%) died in hospital. On multivariable analysis diabetes mellitus (p = 0.004, OR 91.54), mechanical ventilation (p = 0.001, OR 59.07) and lower albumin levels at treatment (p = 0.027, OR 0.74) were significantly associated with increased in-hospital mortality. In our study, in-hospital mortality in patients receiving CCP is similar to that reported for the general population, however certain variables mentioned above were associated with increased in-hospital mortality. In the literature, these variables were also associated with a worse outcome in patients with COVID-19 who did not receive CCP. As evidence points toward a benefit from CCP treatment in immunocompromised patients, we believe the above risk factors can further define COVID-19 patients at increased risk for mortality, enabling the selection of candidates for early treatment in an outpatient setting if possible.

Convalescent plasma - An insight into a novel treatment of covid-19 ICU patients.

INTRODUCTION: Various therapies have been tried for Covid disease including the use of antivirals, steroids, monoclonal antibodies and convalescent plasma. METHOD: The study was conducted on convalescent plasma transfused ICU patients. Part A of the study involves clinical outcomes based on gender, age, comorbidities, blood group,and the average length of stay. Part B investigates clinical outcomes in patients transfused with convalescent plasma before and after the November 2021 guidelines. Part C of the study includes patients in cytokine storm and the efficacy of tocilizumab in these patients. RESULT: Out of the 326 ICU patients transfused with convalescent plasma the overall mortality was 152 (53.3 %). On comparing blood groups and clinical outcomes, a clinically significant result was found. A clinically significant association was also seen on comparing the clinical outcome of 18-50 years and 61-70 years age group and in female gender patients. The average number of ICU days had a positive impact on the overall patient survival. Out of the patients in 'cytokine storm' (n = 109), on day 20, the survival percentage in the non-Tocilizumab group showed a downward trend throughout. However, in the Tocilizumab group, the survival percentage remained stable throughout till around day 50. CONCLUSION: Amongst the convalescent plasma transfused ICU patients, females, having blood group B, and an average length of stay of fewer than 20 days had a better chance of survival. The patients given tocilizumab and convalescent plasma had a better chance of survival compared to tocilizumab alone.

Effectiveness of Convalescent Plasma Therapy in Moderate to Severely Ill Covid-19 Patients.

Convalescent plasma therapy, a classic adaptive immunotherapy used in the treatment of SARS, MERS, and 2009 H1N1 pandemic with acceptable efficacy and safety in the past. Convalescent plasma therapy was taken into consideration in management of COVID 19 disease during the initial days of pandemic but was withdrawn later due to its doubtful beneficial role. This study aims to explore the beneficial role of convalescent plasma and to determine whether convalescent plasma therapy holds a second chance in treating SARS COV-2. MATERIAL: This cross-sectional observational study includes 82 cases of moderate to severely ill COVID 19 patients who received convalescent plasma therapy and 41 controls who didn't. Regular monitoring of TLC, P/F ratio, N/L ratio inflammatory markers, respiratory rate, oxygen saturation, ABG and radiological imaging was done for comparative analysis. OBSERVATION: In case group 39 patients (47.56%) were on oxygen mask, 17 patients (20.73%) on NIV, 9 Patients on NRM (10.97%), 16 patients (19.51%) on room air, 1(1.21%) on HFNC initially. After 7th day of convalescent plasma therapy 49 patients (59.75%) were on room air which suggests significant improvement in mode of ventilation in case group as compared to control group. Mean respiratory rate in case group was 30.46 CPM initially and 24.7 CPM on day 7th of plasma therapy which is statistically significant. CONCLUSION: Plasma therapy is effective if given in early stage of disease and convalescent plasma donors having adequate antibody titre.