3- Wednesday Research News – 22th September 

 1 – Mycophenolate Mofetil for First-Line Treatment of Immune Thrombocytopenia

• Immune thrombocytopenia is a rare autoimmune disorder with associated bleeding risk and fatigue. Recommended first-line treatment for immune thrombocytopenia is high-dose glucocorticoids, but side effects, variable responses, and high relapse rates are serious drawbacks.
• In this multicenter, open-label, randomized, controlled trial conducted in the United Kingdom, we assigned adult patients with immune thrombocytopenia, in a 1:1 ratio, to first-line treatment with a glucocorticoid only (standard care) or combined glucocorticoid and mycophenolate mofetil.
• The addition of mycophenolate mofetil to a glucocorticoid for first-line treatment of immune thrombocytopenia resulted in greater response and a lower risk of refractory or relapsed immune thrombocytopenia, but with somewhat decreased quality of life.

Source: NEJM

2- Comparison of SARS-CoV-2 Antibody Response by Age Among Recipients of the BNT162b2 vs the mRNA-1273 Vaccine

• Two COVID-19 mRNA vaccines, BNT162b2 (ie, Pfizer/BioNTech) and mRNA-1273 (ie, Moderna), were approved via the US Food and Drug Administration Emergency Use Authorization (FDA-EUA) for adults in December 2020.
• Both incorporate mRNA that encodes for the prefusion stabilized spike glycoprotein, use a prime-boost strategy, and have shown strong immunogenicity in preclinical and clinical studies.
• In this cohort study, they used a quantitative assay for IgG to SARS-CoV-2 spike-receptor binding protein to compare antibody responses in an employee cohort in which both BNT162b2 and mRNA-1273 were administered.
• They hypothesized that there could be differences in antibody levels elicited by the 2 vaccines and explored the effect of age on immunogenicity.

Source: JAMA Network

3- Effectiveness of the mRNA BNT162b2 vaccine six months after vaccination: findings from a large Israeli HMO

• Israel is currently experiencing a new wave of CoVid-19 infection, six months after implementing a national vaccination campaign.
• They carried out three discrete analyses using data from a large Israeli HMO to determine whether IgG levels of those fully vaccinated drop over time, the relationship between IgG titer and subsequent PCR-confirmed infection, and compare PCR-confirmed infection rates by period of vaccination.
• They found that mean IgG antibody levels steadily decreased over the six-month period in the total tested population, and in all age groups.
• The BNT162b2 vaccine was found to be less effective in protecting against Covid-19 infection after six months, and vaccination with a third dose is indicated.

Source: MedRxiv

4- Severe COVID-19 is associated with sustained biochemical disturbances and prolonged symptomatology; A retrospective single-centre cohort study

• Coronavirus disease 2019 (COVID-19) is associated with significant acute clinical manifestations, and reports indicate that some patients experience prolonged symptomatology and morbidity. These late clinical manifestations have been termed Post-Acute Sequelae of COVID-19 (PASC) and hypothesised to be associated with clinical severity in the acute infection phase and biochemical abnormalities.
• This study aims to evaluate the incidence of PASC in previously hospitalised COVID-19 patients and compare the admission and follow-up levels of biochemical parameters stratified according to baseline clinical severity.
• Previously hospitalised severe COVID-19 patients are more likely to experience Post-Acute Sequelae of COVID-19 and prolonged biochemical disturbances, evident by abnormal values of D-dimers and Ferritin.

Source: MedRxiv

5- Potentially effective drugs for the treatment of COVID-19 or MIS-C in children: a systematic review

• The purpose of this systematic review is to evaluate the efficacy and safety of using potential drugs: remdesivir and glucocorticoid in treating children and adolescents with COVID-19 and intravenous immunoglobulin (IVIG) in treating MIS-C.
• They searched seven databases, three preprint platform, ClinicalTrials.gov, and Google from December 1, 2019, to August 5, 2021, to collect evidence of remdesivir, glucocorticoid, and IVIG which were used in children and adolescents with COVID-19 or MIS-C.
• Overall, the current evidence in the included studies is insignificant and of low quality. It is recommended to conduct high-quality randomized controlled trials of remdesivir, glucocorticoids, and IVIG in children and adolescents with COVID-19 or MIS-C to provide substantial evidence for the development of guidelines.

Source: MedRxiv

6- Immunogenicity of Pfizer mRNA COVID-19 vaccination followed by J&J adenovirus COVID-19 vaccination in two CLL patients

• Individuals with Chronic Lymphocytic Leukemia have significant immune disfunction, often further disrupted by treatment.
• While currently available COVID-19 vaccinations are highly effective in immunocompetent individuals, they are often poorly immunogenic in CLL patients.
• It is important to understand the role heterologous boost would have in patients who did not respond to the recommended two-dose mRNA vaccine series with a SARS-CoV-2 specific immune response
• This study aims to characterize the immune response of two CLL patients who failed to seroconvert after initial mRNA vaccine series following a third, heterologous, COVID-19 vaccination with Ad26.COV2.
• Of the two subjects who received Ad26.COV2.S doses, Subject 1 seroconverted, had RBD-specific memory B-cells as well as spike-specific CD4 T-cells while Subject 2 did not.
• Both subjects had a spike-specific CD8 T-cell response after original mRNA vaccination series that was further boosted after third dose (Subject 1), or remained stable (Subject 2).

Source: MedRxiv

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