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1.
British Journal of Haematology ; : 1, 2022.
Article in English | Academic Search Complete | ID: covidwho-2019153

ABSTRACT

Summary We investigated antibody and coronavirus disease 2019 (COVID‐19)‐specific T‐cell mediated responses via ultra‐deep immunosequencing of the T‐cell receptor (TCR) repertoire in patients with plasma cell dyscrasias (PCD). We identified 364 patients with PCD who underwent spike antibody testing using commercially available spike‐receptor binding domain immunoglobulin G antibodies ≥2 weeks after completion of the initial two doses of mRNA vaccines or one dose of JNJ‐78436735. A total of 56 patients underwent TCR immunosequencing after vaccination. Overall, 86% tested within 6 months of vaccination had detectable spike antibodies. Increasing age, use of anti‐CD38 or anti‐B‐cell maturation antigen therapy, and receipt of BNT162b2 (vs. mRNA‐1273) were associated with lower antibody titres. We observed an increased proportion of TCRs associated with surface glycoprotein regions of the COVID‐19 genome after vaccination, consistent with spike‐specific T‐cell responses. The median spike‐specific T‐cell breadth was 3.11 × 10−5, comparable to those in healthy populations after vaccination. Although spike‐specific T‐cell breadth correlated with antibody titres, patients without antibody responses also demonstrated spike‐specific T‐cell responses. Patients receiving mRNA‐1273 had higher median spike‐specific T‐cell breadth than those receiving BNT162b2 (p = 0.01). Although patients with PCD are often immunocompromised due to underlying disease and treatments, COVID‐19 vaccination can still elicit humoral and T‐cell responses and remain an important intervention in this patient population. [ FROM AUTHOR] Copyright of British Journal of Haematology is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

2.
EBioMedicine ; 80: 104025, 2022 Jun.
Article in English | MEDLINE | ID: covidwho-1821211

ABSTRACT

BACKGROUND: Evolutionary pressure has led to the emergence of SARS-CoV-2 variants, with the most recent Omicron variant containing an unparalleled 30 mutations in the spike protein. Many of these mutations are expected to increase immune evasion, thus making breakthrough cases and re-infection more common. METHODS: From June 2020 to December 2021 serial blood samples (initial post recovery, 6 months, 12 months) were collected from a COVID-19 convalescent cohort in Boston, MA. Plasma was isolated for use in Mesoscale Discovery based antibody binding assays. Unvaccinated donors or those vaccinated prior to the primary blood draw were excluded from this analysis, as were those who did not have at least two blood draws. Wilcoxon signed rank tests were used to compare pre- and post-vaccination titers and antibody response against different variants, while McNemar tests were used to compare the proportions of achieving ≥ 4 fold increases against different variants. FINDINGS: Forty-eight COVID convalescent donors with post-infection vaccination (hybrid immunity) were studied to evaluate the levels of cross-reactive antibodies pre- and post- vaccination against various SARS-CoV-2 Spike and receptor binding domain (RBD) proteins. Vaccination with BNT162b2, mRNA-1273 or Ad26.COV2.S led to a 6·3 to 7·8 fold increase in anti-Spike antibody titers and a 7·0 to 7·4 fold increase in anti-WT, Alpha and Delta RBD antibody. However, a lower response was observed for Beta and Omicron RBDs with only 7/48 (15%) and 15/48 (31%) donors having a ≥4 fold increase in post-vaccination titers against Beta and Omicron RBDs. Structural analysis of the Beta and Omicron RBDs reveal a shared immune escape strategy involving residues K417-E484-N501 that is exploited by these variants of concern. INTERPRETATION: Through mutations of the K417-E484-N501 triad, SARS-CoV-2 has evolved to evade neutralization by the class I/II anti-RBD antibody fraction of hybrid immunity plasma as the polyclonal antibody response post-vaccination shows limitations in the ability to solve the structural requirements to bind the mutant RBDs. FUNDING: Massachusetts Consortium on Pathogen Readiness (280870.5116709.0016) and the National Institute of Allergy and Infectious Diseases (1R01AI161152-01A1).


Subject(s)
COVID-19 , Viral Vaccines , Ad26COVS1 , Antibodies, Neutralizing , Antibodies, Viral , BNT162 Vaccine , Humans , Neutralization Tests , SARS-CoV-2 , Spike Glycoprotein, Coronavirus
3.
Transplant Direct ; 8(1): e1268, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1583924

ABSTRACT

BACKGROUND: Few reports have focused on newer coronavirus disease 2019 (COVID-19) therapies (remdesivir, dexamethasone, and convalescent plasma) in solid organ transplant recipients; concerns had been raised regarding possible adverse impact on allograft function or secondary infections. METHODS: We studied 77 solid organ transplant inpatients with COVID-19 during 2 therapeutic eras (Era 1: March-May 2020, 21 patients; and Era 2: June-November 2020, 56 patients) and 52 solid organ transplant outpatients. RESULTS: In Era 1, no patients received remdesivir or dexamethasone, and 4 of 21 (19.4%) received convalescent plasma, whereas in Era 2, remdesivir (24/56, 42.9%), dexamethasone (24/56, 42.9%), and convalescent plasma (40/56, 71.4%) were commonly used. Mortality was low across both eras, 4 of 77 (5.6%), and rejection occurred in only 2 of 77 (2.8%) inpatients; infections were similar in hypoxemic patients with or without dexamethasone. Preexisting graft dysfunction was associated with greater need for hospitalization, higher severity score, and lower survival. Acute kidney injury was present in 37.3% of inpatients; renal function improved more rapidly in patients who received remdesivir and convalescent plasma. Post-COVID-19 renal and liver function were comparable between eras, out to 90 d. CONCLUSIONS: Newer COVID-19 therapies did not appear to have a deleterious effect on allograft function, and infectious complications were comparable.

4.
Health Inf Sci Syst ; 8(1): 28, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-805373

ABSTRACT

The novel coronavirus (COVID-19) is continuing its spread across the world, claiming more than 160,000 lives and sickening more than 2,400,000 people as of April 21, 2020. Early research has reported a basic reproduction number (R0) between 2.2 to 3.6, implying that the majority of the population is at risk of infection if no intervention measures were undertaken. The true size of the COVID-19 epidemic remains unknown, as a significant proportion of infected individuals only exhibit mild symptoms or are even asymptomatic. A timely assessment of the evolving epidemic size is crucial for resource allocation and triage decisions. In this article, we modify the back-calculation algorithm to obtain a lower bound estimate of the number of COVID-19 infected persons in China in and outside the Hubei province. We estimate the infection density among infected and show that the drastic control measures enforced throughout China following the lockdown of Wuhan City effectively slowed down the spread of the disease in two weeks. We also investigate the COVID-19 epidemic size in South Korea and find a similar effect of its "test, trace, isolate, and treat" strategy. Our findings are expected to provide guidelines and enlightenment for surveillance and control activities of COVID-19 in other countries around the world.

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