Case Report: Serial Cases: Prolongation of High Immunoglobulin G Level in Repetitive COVID-19 Convalescence Plasma Donor in Saiful Anwar Hospital Malang, Indonesia.

Background: Convalescent plasma therapy is expected to be a promising alternative to supportive therapy during the SARS-CoV-2 pandemic outbreak. Altered immune response in repetitive convalescent plasma donors has not been widely studied. This case series was reported to analyze the patterns of immune responses and the factors that might influence them in repetitive convalescent plasma donors and increase awareness of COVID-19 survivors to donate their convalescent plasma. Cases Illustration: There were five repetitive donors who were eligible as convalescent plasma donor requirements. It was found two donors who showed increment of anti-SARS-CoV-2 IgG level after donation and two others who showed persistent anti-SARS-CoV-2 IgG level more than two months after recovered. Discussion: There was a difference in immune response in survivors who have the probability of being exposed to same antigens with survivors who did not, where the group of survivors who are at risk of exposure to antigens after recovery could trigger anamnestic immune response that can increase antiSARS-CoV-2 IgG levels. The other factor that influence the prolongation of anti-SARS-CoV-2 IgG levels are the possibility of neutralizing antibodies in plasma upregulation. Conclusion: Immunological phenomenon in SARS-CoV-2, both in survivors and convalescent plasma donors, have not been widely observed and studied. From the case series discussed above, it can be concluded that convalescent plasma donation does not yet have strong evidence of decreasing levels of specific antibodies against SARS-CoV-2 and plasmapheresis procedure is safe to be done without reducing the protective effect of donor antibody post-plasma donation.

Association between convalescent plasma and the risk of mortality among patients with COVID-19: a meta-analysis.

Background: Convalescent plasma (CCP) has been used for treating some infectious diseases; however, the efficacy of CCP in coronavirus disease 2019 (COVID-19) remains controversial. The aim of this research was to assess the efficacy of CCP as an adjunctive treatment in COVID-19 patients. Methods: Four bibliographic databases and a preprint database were searched for potentially relevant articles. Mortality rates between patients treated with standard treatment and standard treatment with CCP were compared using a Z test. Results: A total of 1,937 patients treated with CCP and 3,405 patients without CCP retrieved from 12 studies were included. The risk of mortality was 1.92-fold higher in patients without CCP compared to patients treated with CCP (OR: 1.92; 95%CI: 1.33, 2.77; p=0.0005). In severe COVID-19 sub-group analysis, we found that patients without the CCP had a 1.32 times higher risk of mortality than those treated with the CCP (OR: 1.32; 95%CI: 1.09, 1.60; p=0.0040). Conclusions: CCP, as adjunctive therapy, reduces the mortality rate among COVID-19 patients.

The predictors of high titer of anti-SARS-CoV-2 antibody of convalescent plasma donors.

BACKGROUND: Recent evidence suggested that the higher titers of anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody from convalescent plasma donors contributed to the clinical improvement in coronavirus disease 2019 (COVID-19) patients. However, the titers of anti-SARS-CoV-2 antibodies varied in each individual, and the precise factors that might govern such variation have not been elucidated. OBJECTIVES: To assess the factors associated with high titers of anti-SARS-CoV-2 antibody among COVID-19 convalescent plasma (CCP) donors. METHODS: A cross-sectional study was conducted in Saiful Anwar General Hospital, Malang, Indonesia. Information of interest including demographic characteristics, clinical symptoms, comorbidities, laboratory findings, and the titers of anti-SARS-CoV-2 antibody among COVID-19 CCP donors were collected. The correlation was assessed using multiple logistic regression. RESULTS: A total of 50 COVID-19 CCP donors with the titers of anti-SARS-CoV-2 antibody of more than 1:320 and 33 donors with the titers of less than 1:320 were analyzed. Our analysis revealed that CCP donors with history of cough, fever, dyspnea, and pneumonia significantly had higher titers of anti-SARS-CoV-2 antibody compared to asymptomatic donors. Moreover, CCP donors with elevated levels of eosinophils and immature granulocytes and low levels of albumins had higher levels of anti-SARS-CoV-2 antibody. The titer of antibody was not affected by comorbidities of donors. CONCLUSIONS: CPP donors who had experience of symptomatic COVID-19 with high eosinophils level, high immature granulocytes and low albumin level have higher titers of anti-SARS-COV-2 antibody than those who experienced asymptomatic COVID-19. Our current findings may be used as the additional baseline criteria for selecting the donors of CCP for the management of COVID-19.

The association between FOXO3a rs4946936 gene polymorphism and the levels of FOXO3a among chronic granulocytic leukemia patients treated with imatinib mesylate.

Background: The gene  FOXO3a has been elucidated to govern the development of chronic granulocytic leukemia (CGL). Moreover, it has been suggested that the levels of  FOXO3a in circulation are affected by the  FOXO3a rs4946936 gene polymorphism. However, no study has assessed the correlation between the  FOXO3a rs4946936 gene polymorphism and the levels of  FOXO3a. The objective of this study was to assess the association between the  FOXO3a rs4946936 gene polymorphism and the levels of  FOXO3a in CGL patients treated with imatinib mesylate.  Methods: A cross-sectional study was conducted from February 2019 to February 2020. The genotyping of  FOXO3a rs4946936 gene polymorphism was conducted using PCR-RFLP, and the levels of  FOXO3a were assessed using ELISA. The association between the  FOXO3a rs4946936 gene polymorphism and the levels of  FOXO3a were assessed using multiple logistic regression.  Results: A total of 60 CGL patients were assessed in our study. Among them, the CC, CT, and TT genotypes of the  FOXO3a rs4946936 gene polymorphism were 35.0%, 48.3%, and 16.7% respectively. Our calculation revealed that elevated levels of  FOXO3a were found in CGL patients with the CC genotype of the  FOXO3a rs4946936 gene polymorphism. While we failed to clarify the association between either the CT or the TT genotype of  FOXO3a rs4946936 gene polymorphism and the levels of  FOXO3a.  Conclusion: Our study identifies that the CC genotype of the  FOXO3a rs4946936 gene polymorphism affects the elevated levels of  FOXO3a in CGL patients treated with imatinib mesylate.

The association between therapeutic plasma exchange and the risk of mortality among patients critically ill with COVID-19: a meta-analysis.

Background: Cytokine storm has been widely known to contribute to the development of the critical condition in patients with coronavirus disease 2019 (COVID-19), and studies had been conducted to assess the potential aspect of cytokine storm elimination by performing therapeutic plasma exchange (TPE). However, contradictory findings were observed. The objective of this study was to assess the association between TPE and the reduction of mortality of critically ill COVID-19 patients. Methods: A meta-analysis was conducted by collecting data from PubMed, Scopus, and Web of Science. Data on the mortality rate of critically ill COVID-19 patients treated with TPE plus standard of care and that of patients treated with standard of care alone were analyzed using a Z test. Results: We included a total of four papers assessing the association between TPE and the risk of mortality among critically ill COVID-19 patients. Our findings suggested that critically ill COVID-19 patients treated with TPE had lower risk of mortality compared to those without TPE treatment. Conclusion: Our study has identified the potential benefits of TPE in reducing the risk of mortality among critically ill COVID-19 patients.

A 44-Year-Old Man with Waldenstrom Macroglobulinemia and Bilateral Maxillary Sinusitis.

Waldenstrom macroglobulinemia is a chronic, indolent, lymphoproliferative disorder, which is characterized by the presence of a high macroglobulin (IgM) level, elevated serum viscosity, and the presence of a lymphoplasmacytic infiltrate in the bone marrow. Clinical manifestations may be found due to the presence of IgM paraprotein and malignant lymphoplasmacytic cell infiltration of the bone marrow and other tissues. We reported a case of male patient with Waldenstrom macroglobulinemia and bilateral maxillary sinusitis. He had received symptomatic and antibiotic treatment for his sinusitis, FFP and PRC transfusion to improve his general condition and chemotherapy with CHOP regimen as definitive treatment.