Covid-19 and Kidney Transplantation Akalin, Enver; Azzi, Yorg; Bartash, Rachel ...
The New England journal of medicine,
06/2020, Letnik:
382, Številka:
25
Journal Article
Recenzirano
Odprti dostop
A cohort of 36 consecutive kidney-transplant recipients had less fever, lower CD3, CD4, and CD8 cell counts, more rapid clinical deterioration, and a higher mortality than the general population of ...patients with Covid-19.
As COVID-19 adversely affects patients with cancer, prophylactic strategies are critically needed. Using a validated antibody assay against SARS-CoV-2 spike protein, we determined a high ...seroconversion rate (94%) in 200 patients with cancer in New York City that had received full dosing with one of the FDA-approved COVID-19 vaccines. On comparison with solid tumors (98%), a significantly lower rate of seroconversion was observed in patients with hematologic malignancies (85%), particularly recipients following highly immunosuppressive therapies such as anti-CD20 therapies (70%) and stem cell transplantation (73%). Patients receiving immune checkpoint inhibitor therapy (97%) or hormonal therapies (100%) demonstrated high seroconversion post vaccination. Patients with prior COVID-19 infection demonstrated higher anti-spike IgG titers post vaccination. Relatively lower IgG titers were observed following vaccination with the adenoviral than with mRNA-based vaccines. These data demonstrate generally high immunogenicity of COVID-19 vaccination in oncology patients and identify immunosuppressed cohorts that need novel vaccination or passive immunization strategies.
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•COVID-19 vaccines lead to high rates of seroconversion among patients with cancer•Patients with hematologic malignancies show lower immunogenicity post vaccination•Prior immunosuppressive therapies lead to lower responsiveness to COVID-19 vaccines•Prior COVID infection leads to more robust antibody responses to COVID-19 vaccines
Evaluating the IgG levels against SARS-CoV-2 spike protein, Thakkar et al. demonstrate high rates of seroconversion in a diverse cohort of patients with cancer, while identifying lower immunogenicity in patients with hematologic malignancies and in patients having received immunosuppressive therapies.
Background:
Surveillance of SARS-CoV-2 across the globe has enabled detection of new variants and informed the public health response. With highly sensitive methods like qPCR widely adopted for ...diagnosis, the ability to sequence and characterize specimens with low titers needs to keep pace.
Methods:
Nucleic acids extracted from nasopharyngeal swabs collected from four sites in the United States in early 2020 were converted to NGS libraries to sequence SARS-CoV-2 genomes using metagenomic and xGen target enrichment approaches. Single nucleotide polymorphism (SNP) analysis and phylogeny were used to determine clade assignments and geographic origins of strains.
Results:
SARS-CoV-2-specific xGen enrichment enabled full genome coverage for 87 specimens with C
t
values <29, corresponding to viral loads of >10,000 cp/ml. For samples with viral loads between 10
3
and 10
6
cp/ml, the median genome coverage for xGen was 99.1%, sequence depth was 605X, and the “on-target” rate was 57 ± 21%, compared to 13%, 2X and 0.001 ± 0.016%, respectively, for metagenomic sequencing alone. Phylogenetic analysis revealed the presence of most clades that existed at the time of the study, though clade GH dominated in the Midwest.
Conclusions:
Even as vaccines are being widely distributed, a high case load of SARS-CoV-2 infection persists around the world. Viral genetic surveillance has succeeded in warning the public of new variants in circulation and ensured that diagnostic tools remain resilient to a steadily increasing number of mutations. Target capture offers a means of characterizing low viral load samples which would normally pose a challenge for metagenomic sequencing.
The addition of high-risk HPV (hrHPV) testing to cytologic sampling has unquestionably ushered in a new age of cervical cancer screening with their combined clinical sensitivity being superior to ...either Pap or hrHPV testing alone.2-7 Recently, there have been major changes to guidelines presented by various organizations in their suggested use of hrHPV testing as part of an overhaul of cervical cancer screening and management in the United States.8-10 These organizations are to be applauded for their efforts and their comprehensive evaluations. Risk-based approach to screening In 2019, the American Society for Colposcopy and Cervical Pathology (ASCCP) updated its management guidelines to provide greater focus on treating patients based on their risk of disease progression instead of an algorithm based solely on individual test results.8 To this end, any patient whose current test results and testing history places her risk of having a CIN3+ lesion on a biopsy at 4% or greater should be referred for colposcopic evaluation. The ASCCP risk calculations were developed based on a mathematical model formed from over ten years of data collected from Kaiser Permanente Northern California (KPNC).11 The population in this integrated healthcare system is generally more closely screened, resulting in lower cervical cancer rates than the broader U.S.12 Additionally, the patient demographic and socioeconomic breakdowns at KPNC are not wholly representative of the entire country.13 The new ASCCP guidelines recognize the importance of differentiating risk based on whether patients have known or unknown screening histories. Disparities in data selection It is not surprising, therefore, that when the KPNC risk estimations were validated for general applicability using three external data sets - namely the Centers for Disease Control and Prevention's (CDC) National Breast and Cervical Cancer Early Detection Program (NBCCEDP), the Roche ATHENA trial and the BD Onclarity trial - it was found that all three external datasets demonstrated significantly higher immediate CIN3+ rates than KPNC.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK, VSZLJ
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