Clinical course and management of COVID-19 in the era of widespread population immunity

Nature Reviews Microbiology, Год журнала: 2023, Номер 22(2), С. 75 - 88

Опубликована: Дек. 19, 2023

Язык: Английский

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Treatments for COVID-19

Annual Review of Medicine, Год журнала: 2023, Номер 75(1), С. 145 - 157

Опубликована: Сен. 19, 2023

The treatment for COVID-19 has evolved rapidly since the start of pandemic and now consists mainly antiviral immunomodulatory agents. Antivirals, such as remdesivir nirmatrelvir-ritonavir, have proved to be most useful earlier in illness (e.g., outpatient therapy) less severe disease. Immunomodulatory therapies, dexamethasone interleukin-6 or Janus kinase inhibitors, are disease critical illness. role anti-SARS-CoV-2 monoclonal antibodies diminished because emergence viral variants that not anticipated susceptible these treatments, there still is a consensus on use convalescent plasma. been associated with increased rates venous thromboembolism, but antithrombotic therapy limited. Multiple investigational agents continue studied, which will alter current paradigms new data released.

Язык: Английский

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SARS-CoV-2 Related Antibody-Dependent Enhancement Phenomena In Vitro and In Vivo

Microorganisms, Год журнала: 2023, Номер 11(4), С. 1015 - 1015

Опубликована: Апрель 13, 2023

Antibody-dependent enhancement (ADE) is a phenomenon in which antibodies produced the body after infection or vaccination may enhance subsequent viral infections vitro and vivo. Although rare, symptoms of diseases are also enhanced by ADE following This thought to be due production with low neutralizing activity that bind virus facilitate entry, antigen-antibody complexes cause airway inflammation, predominance T-helper 2 cells among immune system leads excessive eosinophilic tissue infiltration. Notably, disease different phenomena overlap. In this article, we will describe three types ADE: (1) Fc receptor (FcR)-dependent macrophages, (2) FcR-independent other cells, (3) FcR-dependent cytokine macrophages. We their relationship natural infection, discuss possible involvement COVID-19 pathogenesis.

Язык: Английский

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The role of SARS-CoV-2 N protein in diagnosis and vaccination in the context of emerging variants: present status and prospects

Frontiers in Microbiology, Год журнала: 2023, Номер 14

Опубликована: Авг. 14, 2023

Despite many countries rapidly revising their strategies to prevent contagions, the number of people infected with Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues surge. The emergent variants that can evade immune response significantly affect effectiveness mainstream vaccines and diagnostic products based on original spike protein. Therefore, it is essential focus highly conserved nature nucleocapsid protein as a potential target in field diagnostics. In this regard, our review initially discusses structure, function, mechanism action N Based discussion, we summarize relevant research in-depth development application methods protein, such serology nucleic acid detection. Such valuable information aid designing more efficient vaccine tools could help end SARS-CoV-2 pandemic.

Язык: Английский

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Autoimmunity and Immunodeficiency in Severe SARS-CoV-2 Infection and Prolonged COVID-19

Current Issues in Molecular Biology, Год журнала: 2022, Номер 45(1), С. 33 - 50

Опубликована: Дек. 21, 2022

SARS-CoV-2 causes the complex and heterogeneous illness known as COVID-19. The disease primarily affects respiratory system but can quickly become systemic, harming multiple organs leading to long-lasting sequelae in some patients. Most infected individuals are asymptomatic or present mild symptoms. Antibodies, complement, immune cells efficiently eliminate virus. However, 20% of develop severe organ failure. Virus replication has been described several patients who died from COVID-19, suggesting a compromised response. Immunodeficiency autoimmunity responsible for this impairment facilitate viral escape. Mutations IFN signal transduction T cell activation inadequate response young individuals. Autoantibodies accountable secondary immunodeficiency with infection prolonged Antibodies against cytokines (interferons α, γ ω, IL1β, IL6, IL10, IL-17, IL21), chemokines, nuclear proteins DNA, anticardiolipin, extracellular have reported. type titer autoantibodies depend on age gender. Organ-specific Their role is under study. Autoimmunity should be screened risk factors

Язык: Английский

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Viral and Host Factors Are Associated With Mortality in Hospitalized Patients With COVID-19

Clinical Infectious Diseases, Год журнала: 2024, Номер 78(6), С. 1490 - 1503

Опубликована: Фев. 20, 2024

Abstract Background Persistent mortality in adults hospitalized due to acute COVID-19 justifies pursuit of disease mechanisms and potential therapies. The aim was evaluate which virus host response factors were associated with risk among participants Therapeutics for Inpatients (TICO/ACTIV-3) trials. Methods A secondary analysis 2625 SARS-CoV-2 infection randomized 1 5 antiviral products or matched placebo 114 centers on 4 continents. Uniform, site-level collection participant baseline clinical variables performed. Research laboratories assayed upper respiratory swabs viral RNA plasma anti–SARS-CoV-2 antibodies, nucleocapsid antigen (viral Ag), interleukin-6 (IL-6). Associations between time by 90 days assessed using univariate multivariable Cox proportional hazards models. Results Viral Ag ≥4500 ng/L (vs <200 ng/L; adjusted hazard ratio [aHR], 2.07; 1.29–3.34), (<35 000 copies/mL [aHR, 2.42; 1.09–5.34], ≥35 2.84; 1.29–6.28], vs below detection), support (<4 L O2 1.84; 1.06–3.22]; ≥4 4.41; 2.63–7.39], noninvasive ventilation/high-flow nasal cannula 11.30; 6.46–19.75] no oxygen), renal impairment (aHR, 1.77; 1.29–2.42), IL-6 >5.8 2.54 [1.74–3.70] ≤5.8 ng/L) significantly final analyses. Ag, RNA, not measured real-time. Conclusions Baseline virus-specific, clinical, biological are strongly within days, revealing pathogen host-response therapeutic targets disease.

Язык: Английский

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Assessment of Immunogenic and Antigenic Properties of Recombinant Nucleocapsid Proteins of Five SARS-CoV-2 Variants in a Mouse Model

Viruses, Год журнала: 2023, Номер 15(1), С. 230 - 230

Опубликована: Янв. 13, 2023

COVID-19 cases caused by new variants of highly mutable SARS-CoV-2 continue to be identified worldwide. Effective control the spread can achieved through targeting conserved viral epitopes. In this regard, nucleocapsid (N) protein, which is much more than evolutionarily influenced spike protein (S), a suitable antigen. The recombinant N considered not only as screening antigen but also basis for development next-generation vaccines, little known about induction antibodies against via different variants. addition, it important understand how produced one variant react with proteins other Here, we used from five strains investigate their immunogenicity and antigenicity in mouse model obtain characterize panel hybridoma-derived monoclonal anti-N antibodies. We analyzed variable epitopes that are potentially involved differential recognition antiviral These results will further deepen our knowledge cross-reactivity humoral immune response COVID-19.

Язык: Английский

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SARS-CoV-2 RNA and Nucleocapsid Antigen Are Blood Biomarkers Associated With Severe Disease Outcomes That Improve in Response to Remdesivir

The Journal of Infectious Diseases, Год журнала: 2024, Номер 230(3), С. 624 - 634

Опубликована: Апрель 24, 2024

Although antivirals remain important for the treatment COVID-19, methods to assess efficacy are lacking. Here, we investigated impact of remdesivir on viral dynamics and their contribution understanding antiviral in multicenter Adaptive COVID-19 Treatment Trial 1, which randomized patients or placebo.

Язык: Английский

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Viral burden and illness severity during acute SARS-CoV-2 infection predict persistent long COVID symptoms

Open Forum Infectious Diseases, Год журнала: 2025, Номер 12(2)

Опубликована: Янв. 30, 2025

Abstract Background Long COVID is a common complication of infection with severe acute respiratory syndrome coronavirus 2, but the prevalence and predictors condition remain poorly characterized. Methods We prospectively studied adults (≥18 years) disease 2019 (COVID-19) presenting to an urban safety net hospital associated clinics between July 2020 December 2022. Logistic regression models were used evaluate association baseline demographic, clinical, laboratory characteristics long status, defined as symptoms persisting at least 9 months after disease. Among unrecovered participants, we describe individual symptoms. Results enrolled 222 162 (73%) whom had known recovery status by months. Median age was 54 years, half (55%) female, majority participants (78%) 1 comorbidity time COVID-19 diagnosis. Based on illness characteristics, adjusted odds ratio for 3.0 (95% confidence interval [CI], 1.1–8.0) among those detectable nucleocapsid antigen 3.6 CI, 1.2–11) who required supplemental oxygen. Of 41% months, central nervous system psychological most commonly reported, 57% reporting functional limitations due their persistent Conclusions The strong initial suggests decreasing illnesses become milder. However, many contemporary patients still experience high viral burden extended replication, even vaccination. Our findings highlight importance properly characterizing evolution shifts presentation.

Язык: Английский

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Overview of Nucleocapsid-Targeting Vaccines against COVID-19

Vaccines, Год журнала: 2023, Номер 11(12), С. 1810 - 1810

Опубликована: Дек. 3, 2023

The new SARS-CoV-2 coronavirus, which emerged in late 2019, is a highly variable causative agent of COVID-19, contagious respiratory disease with potentially severe complications. Vaccination considered the most effective measure to prevent spread and complications this infection. Spike (S) protein-based vaccines were very successful preventing COVID-19 caused by ancestral strain; however, their efficacy was significantly reduced when coronavirus variants antigenically different from original strain circulation. This due high variability major viral antigen escape immunity infection or vaccination spike-targeting vaccines. nucleocapsid protein (N) much more conserved than spike has therefore attracted attention scientists as promising target for broad-spectrum vaccine development. Here, we summarized current data on various N-based that have been tested animal challenge models clinical trials. Despite conservatism N protein, mutations gradually occurring sequence can affect its protective properties. During three years pandemic, at least 12 arisen sequence, affecting 40 known immunogenic T-cell epitopes, so antigenicity recent may be altered. fact should taken into account limitation development cross-reactive based N-protein.

Язык: Английский

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