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Background: COVID-19 is a respiratory disease caused by a novel coronavirus (SARS-CoV-2) and causes substantial morbidity and mortality. At the time this clinical trial was planned, there were no available vaccine or therapeutic agents with proven efficacy, but the severity of the condition prompted the use of several pharmacological and non-pharmacological interventions. It has long been hypothesized that the use of convalescent plasma (CP) from infected patients who have developed an effective immune response is likely to be an option for the treatment of patients with a variety of severe acute respiratory infections (SARI) of viral etiology. The aim of this study is to assess the efficacy and safety of convalescent plasma in adult patients with severe COVID-19 pneumonia., Methods/design: The ConPlas-19 study is a multicenter, randomized, open-label controlled trial. The study has been planned to include 278 adult patients hospitalized with severe COVID-19 infection not requiring mechanical ventilation (invasive or non-invasive). Subjects are randomly assigned in a 1:1 ratio (139 per treatment arm), stratified by center, to receive intravenously administered CP (single infusion) plus SOC or SOC alone, and are to be followed for 30 days. The primary endpoint of the study is the proportion of patients that progress to category 5, 6, or 7 (on the 7-point ordinal scale proposed by the WHO) at day 15. Interim analyses for efficacy and/or futility will be conducted once 20%, 40%, and 60% of the planned sample size are enrolled and complete D15 assessment., Discussion: This clinical trial is designed to evaluate the efficacy and safety of passive immunotherapy with convalescent plasma for the treatment of adult patients hospitalized with COVID-19. The results of this study are expected to contribute to establishing the potential place of CP in the therapeutics for a new viral disease., Trial Registration: ClinicalTrials.gov NCT04345523 . Registered on 30 March, 2020. First posted date: April 14, 2020.

Background and Aim: The COVID‐19 pandemic has plagued our lives for more than 2 years, and the preference for convalescent plasma (CP) as a life‐saving treatment since CP has proven as a potential therapeutic option for acute COVID‐19 patients who were suffering from severe disease. It is important to identify which factors are associated with plasma donation. Therefore, this study aimed to assess the associated factors for CP donation to COVID‐19 patients. Methods: A cross‐sectional study was conducted online from December 21, 2021 to February 15, 2022 to identify different socio‐demographic factors and knowledge related to CP donation. People who recovered from the COVID‐19 infections and those who are willing to participate were included in the study. A total of 60 participants were included in the study. The data were analyzed using descriptive statistics, correlation matrix, and factor analysis. Results: The analysis results confirm that 41.67% (n = 25) of the participants aged 26–30 years; among the recovered patients, only about 23% (n = 14) of the participants donated plasma. Though 97% (n = 58) of the participants agreed to donate plasma when it will be needed, however, when someone asked to donate plasma then 76.67% (n = 46) of the patients declined it. Findings depict that gender had a weak positive relationship with ever decline in plasma donation at 5% level of significance and the age of the participants inversely related to plasma donation. Conclusion: Almost all the recovered participants were willing to donate plasma, however, due to a lack of knowledge and misconception, relatively few people actually did. This study reemphasizes the importance of health education to overcome the misconception about plasma donation, which is crucial for the treatment of COVID‐19 infection. [ABSTRACT FROM AUTHOR]

Abstract Background and Aim The COVID‐19 pandemic has plagued our lives for more than 2 years, and the preference for convalescent plasma (CP) as a life‐saving treatment since CP has proven as a potential therapeutic option for acute COVID‐19 patients who were suffering from severe disease. It is important to identify which factors are associated with plasma donation. Therefore, this study aimed to assess the associated factors for CP donation to COVID‐19 patients. Methods A cross‐sectional study was conducted online from December 21, 2021 to February 15, 2022 to identify different socio‐demographic factors and knowledge related to CP donation. People who recovered from the COVID‐19 infections and those who are willing to participate were included in the study. A total of 60 participants were included in the study. The data were analyzed using descriptive statistics, correlation matrix, and factor analysis. Results The analysis results confirm that 41.67% (n = 25) of the participants aged 26–30 years; among the recovered patients, only about 23% (n = 14) of the participants donated plasma. Though 97% (n = 58) of the participants agreed to donate plasma when it will be needed, however, when someone asked to donate plasma then 76.67% (n = 46) of the patients declined it. Findings depict that gender had a weak positive relationship with ever decline in plasma donation at 5% level of significance and the age of the participants inversely related to plasma donation. Conclusion Almost all the recovered participants were willing to donate plasma, however, due to a lack of knowledge and misconception, relatively few people actually did. This study reemphasizes the importance of health education to overcome the misconception about plasma donation, which is crucial for the treatment of COVID‐19 infection.

Morbidity and mortality of COVID-19 is increased in patients with inborn errors of immunity (IEI). Age and comorbidities and also impaired type I interferon immunity were identified as relevant risk factors. In patients with primary antibody deficiency (PAD) and lack of specific humoral immune response to SARS-CoV-2, clinical disease outcome is very heterogeneous. Despite extensive clinical reports, underlying immunological mechanisms are poorly characterized and levels of T cellular and innate immunity in severe cases remain to be determined. In the present study, we report clinical and immunological findings of 5 PAD patients with severe and fatal COVID-19 and undetectable specific humoral immune response to SARS-CoV-2. Reactive T cells to SARS-CoV-2 spike (S) and nucleocapsid (NCAP) peptide pools were analyzed comparatively by flow cytometry in PAD patients, convalescents and naïve healthy individuals. All examined PAD patients developed a robust T cell response. The presence of polyfunctional cytokine producing activated CD4+ T cells indicates a memory-like phenotype. An analysis of innate immune response revealed elevated CD169 (SIGLEC1) expression on monocytes, a surrogate marker for type I interferon response, and presence of type I interferon autoantibodies was excluded. SARS-CoV-2 RNA was detectable in peripheral blood in three severe COVID-19 patients with PAD. Viral clearance in blood was observed after treatment with COVID-19 convalescent plasma/monoclonal antibody administration. However, prolonged mucosal viral shedding was observed in all patients (median 67 days) with maximum duration of 127 days. PAD patients without specific humoral SARS-CoV-2 immunity may suffer from severe or fatal COVID-19 despite robust T cell and normal innate immune response. Intensified monitoring for long persistence of SARS-CoV-2 viral shedding and (prophylactic) convalescent plasma/specific IgG as beneficial treatment option in severe cases with RNAemia should be considered in seronegative PAD patients. [ABSTRACT FROM AUTHOR]

Coronavirus disease-2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently the most concerning health problem worldwide. SARS-CoV-2 infects cells by binding to angiotensin-converting enzyme 2 (ACE2). It is believed that the differential response to SARS-CoV-2 is correlated with the differential expression of ACE2. Several reports proposed the use of ACE2 pharmacological inhibitors and ACE2 antibodies to block viral entry. However, ACE2 inhibition is associated with lung and cardiovascular pathology and would probably increase the pathogenesis of COVID-19. Therefore, utilizing ACE2 soluble analogs to block viral entry while rescuing ACE2 activity has been proposed. Despite their protective effects, such analogs can form a circulating reservoir of the virus, thus accelerating its spread in the body. Levels of ACE2 are reduced following viral infection, possibly due to increased viral entry and lysis of ACE2 positive cells. Downregulation of ACE2/Ang (1-7) axis is associated with Ang II upregulation. Of note, while Ang (1-7) exerts protective effects on the lung and cardiovasculature, Ang II elicits pro-inflammatory and pro-fibrotic detrimental effects by binding to the angiotensin type 1 receptor (AT1R). Indeed, AT1R blockers (ARBs) can alleviate the harmful effects associated with Ang II upregulation while increasing ACE2 expression and thus the risk of viral infection. Therefore, Ang (1-7) agonists seem to be a better treatment option. Another approach is the transfusion of convalescent plasma from recovered patients with deteriorated symptoms. Indeed, this appears to be promising due to the neutralizing capacity of anti-COVID-19 antibodies. In light of these considerations, we encourage the adoption of Ang (1-7) agonists and convalescent plasma conjugated therapy for the treatment of COVID-19 patients. This therapeutic regimen is expected to be a safer choice since it possesses the proven ability to neutralize the virus while ensuring lung and cardiovascular protection through modulation of the inflammatory response.