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.
•SARS-CoV-2 reinfection incidence was 2.7% versus 21.6% for Delta versus Omicron variants.•COVID-19 vaccination reduced the reinfection risk with the Delta and Omicron variants.•A high ...antinucleocapsid level during the first illness markedly reduced the Omicron reinfection risk.•Previous antispike antibodies against the Wuhan and Alpha strains reduced the Omicron risk.•The neutralizing antibodies against the Wuhan and Alpha strains reduced the Omicron risk.
The predictors of SARS-CoV-2 reinfection are unclear. We examined predictors of reinfection with pre-Omicron and Omicron variants among COVID-19-recovered individuals.
Randomly selected COVID-19-recovered patients (N = 1004) who donated convalescent plasma during 2020 were interviewed between August 2021 and March 2022 regarding COVID-19 vaccination and laboratory-proven reinfection. The sera from 224 (22.3%) participants were tested for antispike (anti-S) immunoglobulin G and neutralizing antibodies.
The participants’ median age was 31.1 years (78.6% males). The overall reinfection incidence rate was 12.8%; 2.7% versus 21.6% for the pre-Omicron (mostly Delta) versus Omicron variants. Negative associations were found between fever during the first illness and pre-Omicron reinfection: relative risk 0.29 (95% confidence interval 0.09-0.94), high anti-N level at first illness and Omicron reinfection: 0.53 (0.33-0.85), and overall reinfection: 0.56 (0.37-0.84), as well as between subsequent COVID-19 vaccination with the BNT162b2 vaccine and pre-Omicron 0.15 (0.07-0.32), Omicron 0.48 (0.25-0.45), and overall reinfections 0.38 (0.25-0.58). These variables significantly correlated with immunoglobulin G anti-S follow-up levels. High pre-existing anti-S binding and neutralizing antibody levels against the SARS-CoV-2 Wuhan and Alpha strains predicted protection against Omicron reinfections.
Strong immune responses after the first COVID-19 infection and subsequent vaccination with the BNT162b2 vaccine provided cross-protection against reinfections with the Delta and Omicron variants.
We assessed outcome of patients with moderate and severe COVID-19 following treatment with convalescent plasma (CP) and the association with IgG levels in transfused CP.
A prospective cohort study. ...Primary outcome was improvement at day 14 defined as alive, not on mechanical ventilation, and moderate, mild, or recovered from COVID-19. Antibody levels in CP units were unknown at the time of treatment. IgG against the spike protein S1 was subsequently measured by ELISA. Neutralizing antibodies titers were determined in a subset. Outcome was assessed in relation to the mean antibody level transfused to the patients (≤4.0 versus >4.0).
Of 49 patients, 11 (22.4%) had moderate, 38 (77.6%) had severe disease, 28 were ventilated. At day 14, 24 (49.0%) patients improved, 9 (18.4%) died, and 13 (26.5%) were ventilated. In 14/98 (14.3%) CP units IgG was < 1.1 (cutoff calibration) and in 60 (61.2%) ≤4.0. IgG level and neutralizing antibody titer were correlated (0.85 p < 0.001). In patients receiving ≤4.0 antibody levels, 11/30 improved (36.7%) versus 13/19 (68.4%) in patients receiving >4.0 odds ratio (OR) 0.267 95% confidence interval (CI) 0.079–0.905, P = 0.030. In patients diagnosed >10 days prior to treatment, 4/14 (22.4%) improved in the ≤4.0 antibody group, versus 6/7 (85.7%) in the >4.0 antibody group, OR 0.048 (95% CI, 0.004–0.520), P = 0.007. No serious adverse events were reported.
Treatment with CP with higher levels of IgG against S1 may benefit patients with moderate and severe COVID-19. IgG against S1 level in CP predicts neutralization antibodies titers.
Megakaryocytes assemble and release platelets through the extension of proplatelet processes, which are cytoplasmic extensions that extrude from the megakaryocyte and form platelets at their tips. ...Proplatelet formation and platelet release are complex processes that require a combination of structural rearrangements. While the signals that trigger the initiation of proplatelet formation process are not completely understood, it has been shown that inhibition of cytoskeletal signaling in mature megakaryocytes induces proplatelet formation. Megakaryocyte apoptosis may also be involved in initiation of proplatelet extension, although this is controversial. This study inquires whether the proplatelet production induced by cytoskeletal signaling inhibition is dependent on activation of apoptosis.
Megakaryocytes derived from human umbilical cord blood CD34+ cells were treated with the actin polymerization inhibitor latrunculin and their ploidy and proplatelet formation were quantitated. Apoptosis activation was analyzed by flow cytometry and luminescence assays. Caspase activity was inhibited by two compounds, ZVAD and QVD. Expression levels of pro-survival and pro-apoptosis genes were measured by quantitative RT-PCR. Protein levels of Bcl-XL, Bax and Bak were measured by western blot. Cell ultrastructure was analyzed by electron microscopy.
Actin inhibition resulted in increased ploidy and increased proplatelet formation in cultured umbilical cord blood-derived megakaryocytes. Actin inhibition activated apoptosis in the cultured cells. The effects of actin inhibition on proplatelet formation were blocked by caspase inhibition. Increased expression of both pro-apoptotic and pro-survival genes was observed. Pro-survival protein (Bcl-xL) levels were increased compared to levels of pro-apoptotic proteins Bak and Bax. Despite apoptosis being activated, the megakaryocytes underwent minimal ultrastructural changes during actin inhibition.
We report a correlation between increased proplatelet formation and activation of apoptosis, and that the increase in proplatelet formation in response to actin inhibition is caspase dependent. These findings support a role for apoptosis in proplatelet formation in this model.
The emergence of rapidly spreading variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a major challenge to the ability of vaccines and therapeutic antibodies to provide ...immunity. These variants contain mutations of specific amino acids that might impede vaccine efficacy. BriLife
(rVSV-ΔG-spike) is a newly developed SARS-CoV-2 vaccine candidate currently in phase II clinical trials. It is based on a replication-competent vesicular stomatitis virus (VSV) platform. The rVSV-ΔG-spike contains several spontaneously acquired spike mutations that correspond to SARS-CoV-2 variants' mutations. We show that human sera from BriLife
vaccinees preserve comparable neutralization titers towards alpha, gamma, and delta variants and show less than a three-fold reduction in the neutralization capacity of beta and omicron compared to the original virus. Taken together, we show that human sera from BriLife
vaccinees overall maintain a neutralizing antibody response against all tested variants. We suggest that BriLife
-acquired mutations may prove advantageous against future SARS-CoV-2 VOCs.
Currently approved anti-COVID-19 vaccines have been found to be safe and effective and almost 60% of Israeli residents are already vaccinated with BNT162b2 vaccine.This observational study was ...designed to evaluate the adverse events of vaccine reported by 61 healthcare workers at least 7 days after the 2nd vaccination, and to investigate the correlation of adverse events and anti-SARS-CoV-2 IgG antibody levels.The median participant's age was 51.25 years, 16 men and 45 women; 77% (44% of male and 84.5% of female participants) reported adverse events. Injection site pain, fatigue and fever were the most common symptoms, and significantly higher antibody levels (average 19,387 AU/mL) were found in participants who had fever compared to those who did not experience fever (average antibody levels of 9,977 AU/mL, p < 0.001). This finding corresponds to previous observations of higher anti-SARS-CoV-2 IgG antibody levels in COVID-19 patients presented with fever.
Currently approved anti-COVID-19 vaccines have been found to be safe and effective and almost 60% of Israeli residents are already vaccinated with BNT162b2 vaccine.
This observational study was ...designed to evaluate the adverse events of vaccine reported by 61 healthcare workers at least 7 days after the 2nd vaccination, and to investigate the correlation of adverse events and anti-SARS-CoV-2 IgG antibody levels.
The median participant's age was 51.25 years, 16 men and 45 women; 77% (44% of male and 84.5% of female participants) reported adverse events. Injection site pain, fatigue and fever were the most common symptoms, and significantly higher antibody levels (average 19,387 AU/mL) were found in participants who had fever compared to those who did not experience fever (average antibody levels of 9,977 AU/mL, p < 0.001). This finding corresponds to previous observations of higher anti-SARS-CoV-2 IgG antibody levels in COVID-19 patients presented with fever.
Abstract
Background
It is unknown whether convalescent immunoglobulins (cIgGs) are better than convalescent plasma (CP) for patients with coronavirus 2019 (COVID-19).
Methods
In this randomized ...controlled trial, we assigned high risk COVID-19 patients with ≤10 days of symptoms, to receive cIgGs or CP. The primary endpoint was improvement on day 14 according to the World Health Organization scale. Secondary endpoints were survival on day 14, and improvement, survival, and percent of ventilated patients on day 28, and treatment response in unvaccinated and vaccinated patients.
Results
A total of 319 patients were included: 166 received cIgGs and 153 CP. Median age was 64 to 66 years. A total of 112 patients (67.5%) in the cIgG group and 103 patients (67.3%) in the CP group reached the primary endpoint. Difference between groups was 0.1 (95% confidence interval, −10.1 to 10.4; P = .026), failing to reach noninferiority. More patients receiving cIgG improved by day 28 (136 patients 81.9% and 108 patients 70.6%, respectively; 95% confidence interval, 1.9–20.7; P < .001; for superiority P = .018). Seventeen patients in the cIgG group (10.2%) and 25 patients (16.3%) in the CP group required mechanical ventilation (P = .136). Sixteen (9.6%) and 23 (15%) patients, respectively, died (P = .172). More unvaccinated patients improved by day 28 in the cIgG group (84.1% vs 66.1%; P = .024), and survival was better in the cIgG group (89.9% vs 77.4%; P = .066).
Conclusions
cIgGs failed to reach the primary noninferiority endpoint on day 14 but was superior to CP on day 28. Survival and improvement by day 28 in unvaccinated patients treated with cIgGs were better. In the face of new variants, cIgGs are a viable option for treating COVID-19.
Trial registration number
My Trials MOH_2021-01-14_009667.
Treatment of high-risk patients with coronavirus disease 2019 and convalescent immunoglobulin G compared with convalescent plasma failed to reach noninferiority on day 14 but was superior on day 28. In particular, survival and clinical improvement was better in unvaccinated patients treated with immunoglobulin G.
Thrombocytopenia is one of the most common hematologic disorders, characterized by an abnormally low number of platelets from multiple causes. The normal count of thrombocytes (platelets) is between ...150,000 and 450,000 per microliter. The clinical expression of thrombocytopenia has broad variation from asymptomatic to life-threatening bleeding. Various syndromes and diseases are associated with thrombocytopenia. Thrombocytopenia is sometimes a first sign of hematologic malignancies, infectious diseases, thrombotic microangiopathies, and autoimmune disorders, and is also a common side effect of many medications. There are more than 200 diseases that include low number of platelets among their symptoms. A brief discussion of the most common etiologies and management of them is provided in this review.
Summary
Care of patients with chronic immune thrombocytopenia (ITP) who are refractory to available treatments can be quite challenging. Fostamatinib, an oral Syk inhibitor, is the newest ...FDA‐approved agent for ITP. Phase 3 clinical trials demonstrated an overall response in 43% of patients treated with fostamatinib and use for two years has been reported. Herein, we report two patients with long histories of ITP without lasting responses to numerous first‐, second‐ and third‐line therapies with prolonged responses to ongoing fostamatinib. This shows that patients unresponsive to other agents may respond to fostamatinib and can have sustained benefit.
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