Immunological considerations for COVID-19 vaccine strategies

Nature reviews. Immunology, Journal Year: 2020, Volume and Issue: 20(10), P. 615 - 632

Published: Sept. 4, 2020

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome 2 (SARS-CoV-2) is the most formidable challenge to humanity in a century. It widely believed that prepandemic normalcy will never return until safe and effective vaccine strategy becomes available global vaccination programme implemented successfully. Here, we discuss immunological principles need be taken into consideration development of COVID-19 strategies. On basis these principles, examine current candidates, their strengths potential shortfalls, make inferences about chances success. Finally, scientific practical challenges faced process developing successful ways which strategies may evolve over next few years. This Review outlines guiding for design analyses landscape ahead.

Language: Английский

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mRNA vaccines for infectious diseases: principles, delivery and clinical translation

Nature Reviews Drug Discovery, Journal Year: 2021, Volume and Issue: 20(11), P. 817 - 838

Published: Aug. 25, 2021

Language: Английский

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Aging in COVID-19: Vulnerability, immunity and intervention

Ageing Research Reviews, Journal Year: 2020, Volume and Issue: 65, P. 101205 - 101205

Published: Oct. 31, 2020

Language: Английский

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Structural basis for translational shutdown and immune evasion by the Nsp1 protein of SARS-CoV-2

Science, Journal Year: 2020, Volume and Issue: 369(6508), P. 1249 - 1255

Published: July 17, 2020

A viral block on host protein synthesis As the coronavirus disease 2019 (COVID-19) pandemic continues to cause devastation, scientists race increase their understanding of disease-causing severe acute respiratory syndrome 2. Once inside cells, not only does virus hijack cells' translational machinery make proteins, but virulence factor nonstructural 1 (Nsp1) also shuts down translation messenger RNA. Thoms et al. determined a 2.6-angstrom resolution cryo–electron microscopy structure reconstituted complex Nsp1 bound human 40 S ribosomal subunit and showed that blocks RNA entry tunnel. structural inventory native Nsp1-ribosome complexes from cells confirms this mechanism. Cellular studies show shutdown almost completely inhibits innate immune response. The binding pocket ribosome may be target for drugs treat COVID-19. Science , issue p. 1249

Language: Английский

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Incidence, co-occurrence, and evolution of long-COVID features: A 6-month retrospective cohort study of 273,618 survivors of COVID-19

PLoS Medicine, Journal Year: 2021, Volume and Issue: 18(9), P. e1003773 - e1003773

Published: Sept. 28, 2021

Background Long-COVID refers to a variety of symptoms affecting different organs reported by people following Coronavirus Disease 2019 (COVID-19) infection. To date, there have been no robust estimates the incidence and co-occurrence long-COVID features, their relationship age, sex, or severity infection, extent which they are specific COVID-19. The aim this study is address these issues. Methods findings We conducted retrospective cohort based on linked electronic health records (EHRs) data from 81 million patients including 273,618 COVID-19 survivors. within 6 months in 3 after diagnosis were calculated for 9 core features (breathing difficulties/breathlessness, fatigue/malaise, chest/throat pain, headache, abdominal symptoms, myalgia, other cognitive anxiety/depression). Their network was also analyzed. Comparison with propensity score–matched diagnosed influenza during same time period achieved using Kaplan–Meier analysis Cox proportional hazard model. atopic dermatitis used as negative control. Among survivors (mean [SD] age: 46.3 [19.8], 55.6% female), 57.00% had one more feature recorded whole 6-month (i.e., acute phase), 36.55% between months. each was: abnormal breathing (18.71% 1- 180-day period; 7.94% 90- to180-day period), fatigue/malaise (12.82%; 5.87%), pain (12.60%; 5.71%), headache (8.67%; 4.63%), (11.60%; 7.19%), (15.58%; 8.29%), myalgia (3.24%; 1.54%), (7.88%; 3.95%), anxiety/depression (22.82%; 15.49%). All frequently than (with an overall excess 16.60% ratios 1.44 2.04, all p < 0.001), co-occurred commonly, formed interconnected network. Significant differences associated illness severity. Besides limitations inherent EHR data, include that (i) do not generalize who but diagnosed, nor seek receive medical attention when experiencing long-COVID; (ii) say nothing about persistence clinical features; (iii) difference cohorts might be affected seeking receiving symptoms. Conclusions occurred showed some specificity COVID-19, though observed influenza. Different profiles demographics

Language: Английский

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Endothelial dysfunction and immunothrombosis as key pathogenic mechanisms in COVID-19

Nature reviews. Immunology, Journal Year: 2021, Volume and Issue: 21(5), P. 319 - 329

Published: April 6, 2021

Language: Английский

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Elevated Glucose Levels Favor SARS-CoV-2 Infection and Monocyte Response through a HIF-1α/Glycolysis-Dependent Axis

Cell Metabolism, Journal Year: 2020, Volume and Issue: 32(3), P. 437 - 446.e5

Published: July 17, 2020

Language: Английский

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Long COVID: An overview

Diabetes & Metabolic Syndrome Clinical Research & Reviews, Journal Year: 2021, Volume and Issue: 15(3), P. 869 - 875

Published: April 20, 2021

Language: Английский

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Presence of Genetic Variants Among Young Men With Severe COVID-19

JAMA, Journal Year: 2020, Volume and Issue: 324(7), P. 663 - 663

Published: July 24, 2020

Severe coronavirus disease 2019 (COVID-19) can occur in younger, predominantly male, patients without preexisting medical conditions. Some individuals may have primary immunodeficiencies that predispose to severe infections caused by acute respiratory syndrome 2 (SARS-CoV-2).To explore the presence of genetic variants associated with among young COVID-19.Case series pairs brothers history meeting selection criteria (age <35 years) brother admitted intensive care unit (ICU) due COVID-19. Four men from unrelated families were ICUs 4 hospitals Netherlands between March 23 and April 12, 2020. The final date follow-up was May 16, Available family members included for variant segregation analysis as controls functional experiments.Severe COVID-19.Results rapid clinical whole-exome sequencing, performed identify a potential monogenic cause. Subsequently, basic immunological tests immune cells isolated characterize any defects.The male had mean age 26 years (range, 21-32), no major chronic disease. They previously well before developing insufficiency COVID-19, requiring mechanical ventilation ICU. duration ventilatory support 10 days 9-11); ICU stay 13 10-16). One patient died. Rapid sequencing available identified loss-of-function X-chromosomal TLR7. In 1, maternally inherited 4-nucleotide deletion (c.2129_2132del; p.[Gln710Argfs*18]); affected carried missense (c.2383G>T; p.[Val795Phe]). peripheral blood mononuclear patients, downstream type I interferon (IFN) signaling transcriptionally downregulated, measured significantly decreased mRNA expression IRF7, IFNB1, ISG15 on stimulation TLR7 agonist imiquimod compared controls. production IFN-γ, II IFN, response imiquimod.In this case rare putative impaired IFN responses. These preliminary findings provide insights into pathogenesis

Language: Английский

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Immune Response, Inflammation, and the Clinical Spectrum of COVID-19

Frontiers in Immunology, Journal Year: 2020, Volume and Issue: 11

Published: June 16, 2020

The current COVID-19 pandemic began in December 2019 Wuhan (China) and rapidly extended to become a global sanitary economic emergency. Its etiological agent is the coronavirus SARS-CoV-2. presents wide spectrum of clinical manifestations, which ranges from an asymptomatic infection severe pneumonia accompanied by multisystemic failure that can lead patient's death. immune response SARS-CoV-2 known involve all components system together appear responsible for viral elimination recovery infection. Nonetheless, such responses are implicated disease's progression more lethal process. This review describes general aspects both its SARS-CoV-2, stressing similarities with other infections, as SARS MERS, but importantly, pointing toward evidence supporting hypothesis consequence corresponding variable virus. critical point where disease ensues appears center on loss regulation between protective altered due exacerbation inflammatory components. Finally, it possible delineate certain major challenges deserving exhaustive investigation further understand immunopathogenesis, thus helping design effective diagnostic, therapeutic, prophylactic strategies.

Language: Английский

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