The persistence of SARS-CoV-2 in tissues and its association with long COVID symptoms: a cross-sectional cohort study in China

The Lancet Infectious Diseases, Journal Year: 2024, Volume and Issue: 24(8), P. 845 - 855

Published: April 22, 2024

Growing evidence suggests that symptoms associated with post-COVID-19 condition (also known as long COVID) can affect multiple organs and systems in the human body, but their association viral persistence is not clear. The aim of this study was to investigate SARS-CoV-2 diverse tissues at three timepoints following recovery from mild COVID-19, well its COVID symptoms.

Language: Английский

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Nirmatrelvir Resistance—de Novo E166V/L50V Mutations in an Immunocompromised Patient Treated With Prolonged Nirmatrelvir/Ritonavir Monotherapy Leading to Clinical and Virological Treatment Failure—a Case Report

Clinical Infectious Diseases, Journal Year: 2023, Volume and Issue: 78(2), P. 352 - 355

Published: Aug. 19, 2023

Abstract Resistance of SARS-CoV-2 to antivirals was shown develop in immunocompromised individuals receiving remdesivir. We describe an patient who treated with repeated and prolonged courses nirmatrelvir developed de-novo E166V/L50F mutations the Mpro region. These were associated clinical virological treatment failure.

Language: Английский

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The Burden of COVID-19 in the Immunocompromised Patient: Implications for Vaccination and Needs for the Future

The Journal of Infectious Diseases, Journal Year: 2023, Volume and Issue: 228(Supplement_1), P. S4 - S12

Published: May 25, 2023

Approximately 3% of US adults are immunocompromised and less capable fighting infections such as SARS-CoV-2 (the causative agent COVID-19). Individuals may be for reasons related to an underlying medical condition or immunomodulatory therapies that alter the immune response. In general, vaccination with mRNA-based vaccines is effective at reducing COVID-19-associated hospitalization death among populations, particularly after 3 more doses. However, population heterogeneous, COVID-19 vaccine-elicited responses risk severe existing on a continuum. Therefore, understanding impact complexity across heterogeneous individuals essential guiding regimens including additional (booster) this article, we provide overview burden disease attributable COVID-19, while discussing key opportunities challenges vaccinating individuals.

Language: Английский

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Conversion of monoclonal IgG to dimeric and secretory IgA restores neutralizing ability and prevents infection of Omicron lineages

Proceedings of the National Academy of Sciences, Journal Year: 2024, Volume and Issue: 121(3)

Published: Jan. 9, 2024

The emergence of Omicron lineages and descendent subvariants continues to present a severe threat the effectiveness vaccines therapeutic antibodies. We have previously suggested that an insufficient mucosal immunoglobulin A (IgA) response induced by mRNA is associated with surge in breakthrough infections. Here, we further show intramuscular and/or inactivated cannot sufficiently boost secretory IgA uninfected individuals, particularly against variant. thus engineered characterized recombinant monomeric, dimeric, IgA1 antibodies derived from four neutralizing IgG monoclonal (mAbs 01A05, rmAb23, DXP-604, XG014) targeting receptor-binding domain spike protein. Compared their parental antibodies, dimeric showed higher activity different variants concern (VOCs), part due increased avidity. Importantly, or form DXP-604 antibody significantly outperformed its antibody, neutralized BA.1, BA.2, BA.4/5 25- 75-fold increase potency. In human angiotensin converting enzyme 2 (ACE2) transgenic mice, single intranasal dose conferred prophylactic protection BA.5. Thus, delivered nasal administration may potentially be exploited for treatment prevention infection, thereby providing alternative tool combating immune evasion current circulating and, potentially, future VOCs.

Language: Английский

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Characteristics and risk factors of prolonged viable virus shedding in immunocompromised patients with COVID-19: a prospective cohort study

Journal of Infection, Journal Year: 2023, Volume and Issue: 86(4), P. 412 - 414

Published: Jan. 20, 2023

Language: Английский

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Comparative effectiveness of mRNA-1273 and BNT162b2 COVID-19 vaccines in immunocompromised individuals: a systematic review and meta-analysis using the GRADE framework

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: Sept. 12, 2023

Despite representing only 3% of the US population, immunocompromised (IC) individuals account for nearly half COVID-19 breakthrough hospitalizations. IC generate a lower immune response after vaccination in general, and CDC recommended third dose either mRNA-1273 or BNT162b2 vaccines as part their primary series. Influenza vaccine trials have shown that increasing dosage could improve effectiveness populations. The objective this systematic literature review pairwise meta-analysis was to evaluate clinical (50 100 mcg/dose) vs (30 populations using GRADE framework.

Language: Английский

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Dual combined antiviral treatment with remdesivir and nirmatrelvir/ritonavir in patients with impaired humoral immunity and persistent SARS‐CoV‐2 infection

Hematological Oncology, Journal Year: 2023, Volume and Issue: 41(5), P. 904 - 911

Published: July 15, 2023

Despite global vaccination efforts, immunocompromized patients remain at high risk for COVID-19-associated morbidity. In particular, with impaired humoral immunity have shown a of persistent infection. We report case series adult B cell malignancies and/or undergoing targeting therapies persisting SARS-CoV-2 infection and treated combination antiviral therapy remdesivir nirmatrelvir/ritonavir, in three Italian tertiary academic hospitals. A total 14 adaptive prolonged were the dual therapy. The median age was 60 (IQR 56-68) years, 11 male. Twelve had lymphoma, one patient chronic lymphocytic leukemia multiple sclerosis. Thirteen out received prior cell-targeting therapies, consisting anti-CD20 monoclonal antibodies patients, chimeric antigen receptor T 2 patients. time between diagnosis start 42.0 35-46) days. Seven mild, 6 moderate severe disease. Nine signs interstitial pneumonitis on chest computed tomography scans before treatment. duration nirmatrelvir/ritonavir 10 All showed resolution COVID-19-related symptoms after 4-11) days viral clearance 9 5-11) Combination is promising treatment option COVID-19 impairment, worthy prospective comparative trials.

Language: Английский

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Persistent COVID-19 in immunocompromised patients—Israeli society of infectious diseases consensus statement on diagnosis and management

Clinical Microbiology and Infection, Journal Year: 2024, Volume and Issue: 30(8), P. 1012 - 1017

Published: April 18, 2024

Language: Английский

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B-cell-depleted patients with persistent SARS-CoV-2 infection: combination therapy or monotherapy? A real-world experience

Frontiers in Medicine, Journal Year: 2024, Volume and Issue: 11

Published: Feb. 29, 2024

Objectives The aim of the study was to describe a cohort B-cell-depleted immunocompromised (IC) patients with prolonged or relapsing COVID-19 treated monotherapy combination therapy. Methods This is multicenter observational retrospective conducted on IC consecutively hospitalized SARS-CoV-2 infection from November 2020 January 2023. subjects were stratified according anti-SARS-CoV-2 therapy received. Results Eighty-eight enrolled, 19 under and 69 population had history immunosuppression (median 2 B-cells/mm 3 , IQR 1–24 cells), residual hypogammaglobulinemia observed in 55 patients. A reduced length hospitalization time negative molecular nasopharyngeal swab (NPS) versus group observed. In univariable multivariable analyses, percentage change rate days NPS negativity showed significant reduction receiving compared those monotherapy. Conclusion persistent patients, it essential explore new therapeutic strategies such as multi-target (antiviral double antiviral plus antibody-based therapies) avoid viral shedding and/or severe infection.

Language: Английский

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SARS-CoV-2 resistance to monoclonal antibodies and small-molecule drugs

Cell chemical biology, Journal Year: 2024, Volume and Issue: 31(4), P. 632 - 657

Published: April 1, 2024

Over four years have passed since the beginning of COVID-19 pandemic. The scientific response has been rapid and effective, with many therapeutic monoclonal antibodies small molecules developed for clinical use. However, given ability viruses to become resistant antivirals, it is perhaps no surprise that field identified resistance nearly all these compounds. Here, we provide a comprehensive review profile each therapeutics. We hope this resource provides an atlas mutations be aware agent, particularly as springboard considerations next generation antivirals. Finally, discuss outlook thoughts moving forward in how continue manage this, next,

Language: Английский

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