Two Years into the COVID-19 Pandemic: Lessons Learned

ACS Infectious Diseases, Год журнала: 2022, Номер 8(9), С. 1758 - 1814

Опубликована: Авг. 8, 2022

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly transmissible and virulent human-infecting that emerged in late December 2019 Wuhan, China, causing disease called (COVID-19), which has massively impacted global public health caused widespread disruption to daily life. The crisis by COVID-19 mobilized scientists authorities across the world rapidly improve our knowledge about this devastating disease, shedding light on its management control, spawned development of new countermeasures. Here we provide an overview state art gained last years virus COVID-19, including origin natural reservoir hosts, viral etiology, epidemiology, modes transmission, clinical manifestations, pathophysiology, diagnosis, treatment, prevention, emerging variants, vaccines, highlighting important differences from previously known pathogenic coronaviruses. We also discuss selected key discoveries each topic underline gaps for future investigations.

Язык: Английский

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Enhanced metanephric specification to functional proximal tubule enables toxicity screening and infectious disease modelling in kidney organoids

Nature Communications, Год журнала: 2022, Номер 13(1)

Опубликована: Окт. 8, 2022

While pluripotent stem cell-derived kidney organoids are now being used to model renal disease, the proximal nephron remains immature with limited evidence for key functional solute channels. This may reflect early mispatterning of nephrogenic mesenchyme and/or insufficient maturation. Here we show that enhanced specification metanephric progenitors results in elongated and radially aligned proximalised nephrons distinct S1 - S3 tubule cell types. Such PT-enhanced possess improved albumin organic cation uptake, appropriate KIM-1 upregulation response cisplatin, expression SARS-CoV-2 entry factors resulting increased viral replication. The striking proximo-distal orientation resulted from localized WNT antagonism originating organoid stromal core. represent an study inherited acquired tubular disease as well drug responses.

Язык: Английский

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An ultrathin membrane mediates tissue-specific morphogenesis and barrier function in a human kidney chip

Science Advances, Год журнала: 2024, Номер 10(23)

Опубликована: Июнь 5, 2024

Organ-on-chip (OOC) systems are revolutionizing tissue engineering by providing dynamic models of structure, organ-level function, and disease phenotypes using human cells. However, nonbiological components OOC devices often limit the recapitulation in vivo–like tissue-tissue cross-talk morphogenesis. Here, we engineered a kidney glomerulus-on-a-chip that recapitulates glomerular morphogenesis barrier function biomimetic ultrathin membrane human-induced pluripotent stem The resulting chip comprised proximate epithelial-endothelial interface, which reconstituted selective molecular filtration healthy diseased kidneys. In addition, fenestrated endothelium was successfully induced from cells an device, through paracrine signaling across membrane. Thus, this device provides platform for modeling kidney–specific enabling mechanistic studies cell differentiation, organ physiology, pathophysiology.

Язык: Английский

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Can COVID-19 Vaccines Induce Premature Non-Communicable Diseases: Where Are We Heading to?

Vaccines, Год журнала: 2023, Номер 11(2), С. 208 - 208

Опубликована: Янв. 17, 2023

According to the WHO, as of January 2023, more than 850 million cases and over 6.6 deaths from COVID-19 have been reported worldwide. Currently, death rate has reduced due decreased pathogenicity new SARS-CoV-2 variants, but major factor in rates is administration 12.8 billion vaccine doses globally. While vaccines are saving lives, serious side effects after vaccinations for several premature non-communicable diseases (NCDs). However, adverse events low number. The scientific community must investigate entire spectrum COVID-19-vaccine-induced complications so that necessary safety measures can be taken, current re-engineered avoid or minimize their effects. We describe depth severe metabolic, mental, neurological disorders; cardiovascular, renal, autoimmune diseases, reproductive health issues detected whether these causal incidental. In any case, it become clear benefits outweigh risks by a large margin. pre-existing conditions vaccinated individuals need taken into account prevention treatment events.

Язык: Английский

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Kidney Disease Modeling with Organoids and Organs-on-Chips

Annual Review of Biomedical Engineering, Год журнала: 2024, Номер 26(1), С. 383 - 414

Опубликована: Март 1, 2024

Kidney disease is a global health crisis affecting more than 850 million people worldwide. In the United States, annual Medicare expenditures for kidney and organ failure exceed $81 billion. Efforts to develop targeted therapeutics are limited by poor understanding of molecular mechanisms underlying human onset progression. Additionally, 90% drug candidates fail in clinical trials, often due toxicity efficacy not accurately predicted animal models. The advent ex vivo models, such as those engineered from induced pluripotent stem (iPS) cells organ-on-a-chip (organ-chip) systems, has garnered considerable interest owing their ability model tissue development patient-specific responses toxicity. This review describes recent advances developing organoids organ-chips harnessing iPS cell biology human-specific functions states. We also discuss challenges that must be overcome realize potential dynamic functional conduits kidney. Achieving these technological could revolutionize personalized medicine applications therapeutic discovery disease.

Язык: Английский

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SARS-CoV-2 ORF3a Protein as a Therapeutic Target against COVID-19 and Long-Term Post-Infection Effects

Pathogens, Год журнала: 2024, Номер 13(1), С. 75 - 75

Опубликована: Янв. 14, 2024

The COVID-19 pandemic caused by SARS-CoV-2 has posed unparalleled challenges due to its rapid transmission, ability mutate, high mortality and morbidity, enduring health complications. Vaccines have exhibited effectiveness, but their efficacy diminishes over time while new variants continue emerge. Antiviral medications offer a viable alternative, success been inconsistent. Therefore, there remains an ongoing need identify innovative antiviral drugs for treating post-infection ORF3a (open reading frame 3a) protein found in SARS-CoV-2, represents promising target treatment multifaceted role viral pathogenesis, cytokine storms, disease severity, mortality. contributes significantly pathogenesis facilitating assembly release, essential processes the life cycle, also suppressing body’s responses, thus aiding replication. implicated triggering excessive inflammation, characterized NF-κB-mediated production, ultimately leading apoptotic cell death tissue damage lungs, kidneys, central nervous system. Additionally, triggers activation of NLRP3 inflammasome, inciting storm, which is major contributor severity subsequent As with spike protein, undergoes mutations, certain mutant correlate heightened COVID-19. These mutations may influence replication host cellular inflammatory responses. While establishing direct link between difficult, involvement promoting inflammation exacerbating likely higher rates severe cases. This review offers comprehensive detailed exploration ORF3a’s potential as drug target. we outline strategies discovering developing inhibitor counteract harmful effects, alleviate damage, reduce lingering

Язык: Английский

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COVID-19 and the brain: understanding the pathogenesis and consequences of neurological damage

Molecular Biology Reports, Год журнала: 2024, Номер 51(1)

Опубликована: Фев. 22, 2024

Язык: Английский

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Models and cellular monolayers to study the effect of SARS-CoV-2 on kidney

Elsevier eBooks, Год журнала: 2025, Номер unknown, С. 533 - 542

Опубликована: Янв. 1, 2025

Язык: Английский

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Repurposing clinically available drugs and therapies for pathogenic targets to combat SARS‐CoV‐2

MedComm, Год журнала: 2023, Номер 4(3)

Опубликована: Май 14, 2023

The coronavirus disease 2019 (COVID-19) pandemic has affected a large portion of the global population, both physically and mentally. Current evidence suggests that rapidly evolving subvariants risk rendering vaccines antibodies ineffective due to their potential evade existing immunity, with enhanced transmission activity higher reinfection rates could lead new outbreaks across globe. goal viral management is disrupt life cycle as well relieve severe symptoms such lung damage, cytokine storm, organ failure. In fight against viruses, combination genome sequencing, elucidation structure proteins, identifying proteins are highly conserved multiple coronaviruses revealed many molecular targets. addition, time- cost-effective repurposing preexisting antiviral drugs or approved/clinical for these targets offers considerable clinical advantages COVID-19 patients. This review provides comprehensive overview various identified pathogenic pathways corresponding repurposed COVID-19. These findings provide insight into discovery novel therapeutic strategies be applied control emanating from SARS-CoV-2 variants.

Язык: Английский

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Acute kidney injury with COVID-19: Mechanisms, management, and long-term outcomes

Elsevier eBooks, Год журнала: 2025, Номер unknown, С. 507 - 532

Опубликована: Янв. 1, 2025

Язык: Английский

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