Convalescent plasma therapy for managing infectious diseases: A narrative review

The coronavirus disease 2019 (COVID-19) pandemic in 2020 is one of the worst catastrophic events in human history. A number of therapeutic modalities have been utilized in order to fight the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), although the majority of them failed to demonstrate a beneficial clinical effect. Among the anti-COVID-19 agents being investigated, the convalescent plasma collected from recovered donors has gained a growing interest. Convalescent plasma has been employed for over a hundred years to treat severe acute viral infections when a vaccine or a specific antiviral treatment was not yet available. In this narrative review, we summarize the literature data on the use of convalescent plasma during previous viral outbreaks and pandemics, including influenza viruses, coronaviruses other than SARS-CoV-2 and Ebola virus. A literature search, using the Medline and PubMed electronic database, was performed to retrieve publications on the use of convalescent plasma in previous viral epidemics. In conclusion, the available literature data suggest the safety profile of convalescent plasma and its potential benefit in treating emerging viral infectious diseases. In addition, these data retrieved from previous viral epidemics provide a solid rationale for the employment of plasma from convalescent donors also in COVID-19 patients.Copyright © 2021 AME Publishing Company. All rights reserved.

COVID-19 and pregnancy: A narrative review on the use of convalescent plasma

The emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic is a global concern, considering both the severity of the disease, with a high mortality rate compared to that of other influenza-like viral illnesses, and the lack of a specific, effective treatment. Pregnant women with coronavirus disease 2019 (COVID-19) represent a further challenge for clinicians. Indeed, although the majority of them are asymptomatic or their SARS-CoV-2 disease has a mild to moderate course, in some cases this viral infection is accompanied by severe respiratory symptoms. In such a critical clinical setting, the already limited therapeutic armamentarium available for COVID-19 patients is further restricted in pregnant women because of the risk of fetal toxicity especially during the first trimester of gestation. Among the treatment options, the use of convalescent plasma has gained increasing interest from investigators in pregnant women, given the initial positive reports on safety and efficacy aspects of this treatment in critically ill COVID-19 patients. However, the literature data are scanty and almost limited to single case reports, considering that pregnant women are usually excluded from trials on convalescent plasma. In this narrative review, we will critically discuss the current literature evidence on the use of hyperimmune plasma during pregnancies complicated by COVID-19.Copyright © 2021 AME Publishing Company.

Investigating a Signal of Acquired Haemophilia Associated with COVID-19 Vaccination: A Systematic Case Review

Introduction: Acquired haemophilia A (AHA) is a rare, haematological disorder characterized by the development of autoantibodies to Anti-Factor VIII (FVIII), which can cause spontaneous hemorrhage 1. During 2021, some authors reported an unusual and unexpected number of AHA diagnoses that were temporally related to COVID-19 vaccination2,3 Objective: To explore a possible signal of risk of AHA associated with COVID-19 immunization. Method(s): We performed a disproportionality analysis on the World Health Organization (WHO) database (VigiBase-) to investigate the presence of a signal of risk for AHA associated with COVID-19 vaccines. We calculated the information component (IC) for all the COVID-19 vaccines and for single COVID-19 vaccine product using the entire database as reference. Reports of AHA have been systematically reviewed all the selected cases to check for clinical plausibility Results: In Vigibase, we identified 150 cases of suspected AHA associated with COVID-19 vaccines (146 included the PT ''acquired haemophilia''). Only three vaccine products have been reported as suspected causative agents for AHA. The disproportionality analysis showed a significant IC for the Preferred term ''Acquired haemophilia'' associated with all COVID-19 vaccines (IC: 1.3;IC025: 1.1) and with the vaccine product BNT162b2 (IC: 1.9;IC025: 1.6). After the integration with data available on VAERS and on the medical literature, and after the elimination of duplicates, 96 unique cases of AHA following COVID-19 vaccines (mostly mRNA vaccines) have been reviewed. Overall, about 22% of cases occurred in patients B 65 and no case associated with pregnancy was reported. Patients with at least one pre-existing condition that can be considered a risk factor for AHA (history of AHA, cancer, autoimmune disorder) were 20 (21%). A pre-existing condition predisposing to AHA was excluded in 57 (59%) of cases and not reported in 19 (20%) cases. The outcome was death in 10 (11%) patients and complete resolution or recovering in 39 (41%) patients with a single resolution without specific AHA treatment. Median time from last vaccine dose to diagnosis was 18 days and 40% of cases documented the occurrence after the second dose. Conclusion(s): Our disproportionality analysis confirmed a reporting risk for AHA associated with COVID-19 vaccines. The case review analysis identified several good-quality reports of AHA for which no alternative causes other than COVID-19 immunization can be considered. Although detection bias should be considered to explain the unexpected frequency of AHA in the population, the signal identified is robust and deserves further investigation.

Investigating a Signal of Acquired Haemophilia Associated with COVID-19 Vaccination: A Systematic Case Review: An International Journal of Medical Toxicology and Drug Experience

Introduction: Acquired haemophilia A (AHA) is a rare, haematological disorder characterized by the development of autoantibodies to Anti-Factor VIII (FVIII), which can cause spontaneous hemorrhage 1. During 2021, some authors reported an unusual and unexpected number of AHA diagnoses that were temporally related to COVID-19 vaccination2,3 Objective: To explore a possible signal of risk of AHA associated with COVID-19 immunization. Methods: We performed a disproportionality analysis on the World Health Organization (WHO) database (VigiBase) to investigate the presence of a signal of risk for AHA associated with COVID-19 vaccines. We calculated the information component (IC) for all the COVID-19 vaccines and for single COVID-19 vaccine product using the entire database as reference. Reports of AHA have been systematically reviewed all the selected cases to check for clinical plausibility Results: In Vigibase, we identified 150 cases of suspected AHA associated with COVID-19 vaccines (146 included the PT "acquired haemophilia"). Only three vaccine products have been reported as suspected causative agents for AHA. The disproportionality analysis showed a significant IC for the Preferred term "Acquired haemophilia" associated with all COVID-19 vaccines (IC: 1.3;IC025: 1.1) and with the vaccine product BNT162b2 (IC: 1.9;IC025: 1.6). After the integration with data available on VAERS and on the medical literature, and after the elimination of duplicates, 96 unique cases of AHA following COVID-19 vaccines (mostly mRNA vaccines) have been reviewed. Overall, about 22% of cases occurred in patients B 65 and no case associated with pregnancy was reported. Patients with at least one pre-existing condition that can be considered a risk factor for AHA (history of AHA, cancer, autoimmune disorder) were 20 (21%). A pre-existing condition predisposing to AHA was excluded in 57 (59%) of cases and not reported in 19 (20%) cases. The outcome was death in 10 (11%) patients and complete resolution or recovering in 39 (41%) patients with a single resolution without specific AHA treatment. Median time from last vaccine dose to diagnosis was 18 days and 40% of cases documented the occurrence after the second dose. Conclusion: Our disproportionality analysis confirmed a reporting risk for AHA associated with COVID-19 vaccines. The case review analysis identified several good-quality reports of AHA for which no alternative causes other than COVID-19 immunization can be considered. Although detection bias should be considered to explain the unexpected frequency of AHA in the population, the signal identified is robust and deserves further investigation.

Higher testosterone is associated with increased inflammatory markers in women with SARS-CoV-2 pneumonia: preliminary results from an observational study.

PURPOSE: Objective of this study was to assess the association between testosterone (T) levels and biochemical markers in a cohort of female patients admitted for SARS-CoV-2 infection in a respiratory intensive care unit (RICU). METHODS: A consecutive series of 17 women affected by SARSCoV-2 pneumonia and recovered in the RICU of the Hospital of Mantua were analyzed. Biochemical inflammatory markers as well as total testosterone (TT), calculated free T (cFT), sex hormone-binding globulin (SHBG), and luteinizing hormone (LH) were determined. RESULTS: TT and cFT were significantly and positively associated with PCT, CRP, and fibrinogen as well as with a worse hospital course. We did not observe any significant association between TT and cFT with LH; conversely, both TT and cFT showed a positive correlation with cortisol. By LOWESS analysis, a linear relationship could be assumed for CRP and fibrinogen, while a threshold effect was apparent in the relationship between TT and procalcitonin, LDH and ferritin. When the TT threshold value of 1 nmol/L was used, significant associations between TT and PCT, LDH or ferritin were observed for values above this value. For LDH and ferritin, this was confirmed also in an age-adjusted model. Similar results were found for the association of cFT with the inflammatory markers with a threshold effect towards LDH and ferritin with increased LDH and ferritin levels for values above cFT 5 pmol/L. Cortisol is associated with serum inflammatory markers with similar trends observed for TT; conversely, the relationship between LH and inflammatory markers had different trends. CONCLUSION: Opposite to men, in women with SARS-CoV-2 pneumonia, higher TT and cFT are associated with a stronger inflammatory status, probably related to adrenal cortex hyperactivity.

Mortality from COVID-19.

Abstract: The differences of the epidemiology (incidence, case-to-death rate, mortality, etc) of COVID-19 between USA and Italy are analyzed taking into account the social, economic and sanitary characteristics of the two countries, both severely hit be the pandemic; and the causes of the so many different behaviors of the disease in each of them are discussed and explained.

Impact of pathogen-reduction technologies on COVID-19 convalescent plasma potency.

Pathogen reduction technologies (PRT) have been recommended by many regulatory authorities to minimize the residual risk of transfusion-transmitted infections associated with COVID19 convalescent plasma. While its impact on safety and its cost-effectiveness are nowadays well proven, there is theoretical concern that PRT could impact efficacy of convalescent plasma by altering concentration and/or function of the neutralizing antibodies (nAb). We review here the evidence supporting a lack of significant detrimental effect from PRTs on nAbs.

SARS-CoV-2 infection among cancer patients receiving antitumor treatment in Italy: A nationwide observational study (CIPOMO ONCO COVID-19)

Background: Cancer patients are more susceptible to infections and potentially at higher risk to develop COVID-19. Tumor type and antitumor treatment may also affect both the susceptibility to and the severity of SARS COV-2. Methods: To analyze the distribution of patients who developed COVID-19 during active antineoplastic therapy and the related clinical course by tumor type, stage and class of oncologic treatment (chemo, immune, biologic, other) a multicenter, retro-prospective, observational study was proposed to the Hospital Medical Oncologic Units of the National Health Service in Italy (168 centers of the Collegio Italiano dei Primari Oncologi Medici Ospedalieri -CIPOMO). Data were collected on demographics, tumor characteristics, treatment setting, type of ongoing anti-cancer therapy and COVID-19 clinical course (phenotype, hospitalization, therapy, duration and outcome). Eligibility required a positive COVID-19 molecular test before May 4th, 2020 and at least 1 course of antitumor therapy delivered after January 15th. Results: At the present analysis data are available for 116 of 168 centers (7 declined, 28 pending, 17 data awaited). 64 of 116 centers (55%) had COVID-19 positive cases (cases /center: median 3, range 1-40). At these 64 centers, 283 positive cases (males 158, 55.9% - females 125, 44.1%;median age 67 years, range 28-89) were observed among a total population of 40894 patients receiving active treatment between January 15 and May 4 2020. 65 of 283 (23%) had cardiovascular comorbidities and 7 (2%) pre-existent pulmonary disease. 239/283 patients (84.4%) were receiving treatment for metastatic disease and 44 (15.6%) in the adjuvant setting. Breast, lung, colon and prostate cancer were the main tumor types accounting for 61 % of cases. Conclusions: The occurrence of COVID-19 among cancer patients receiving active antitumor treatment appears to reflect tumor epidemiology. Full analysis of the distribution of COVID-19 occurrence and clinical course by tumor type, stage and oncologic treatment will be presented. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.

Patient blood management during the COVID-19 pandemic: a narrative review.

As COVID-19 disease escalates globally, optimising patient outcome during this catastrophic healthcare crisis is the number one priority. The principles of patient blood management are fundamental strategies to improve patient outcomes and should be given high priority in this crisis situation. The aim of this expert review is to provide clinicians and healthcare authorities with information regarding how to apply established principles of patient blood management during the COVID-19 pandemic. In particular, this review considers the impact of the COVID-19 pandemic on blood supply and specifies important aspects of donor management. We discuss how preventative and control measures implemented during the COVID-19 crisis could affect the prevalence of anaemia, and highlight issues regarding the diagnosis and treatment of anaemia in patients requiring elective or emergency surgery. In addition, we review aspects related to patient blood management of critically ill patients with known or suspected COVID-19, and discuss important alterations of the coagulation system in patients hospitalised due to COVID-19. Finally, we address special considerations pertaining to supply-demand and cost-benefit issues of patient blood management during the COVID-19 pandemic.