Effectiveness of COVID-19 Convalescent Plasma (CCP) During the Pandemic Era: A Literature Review.

Worldwide pandemic with coronavirus disease-2019 (COVID-19) was caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). As November 2, 2022, World Health Organization (WHO) received 628,035,553 reported incidents on COVID-19, with 6,572,800 mortalities and, with a total 12,850,970,971 vaccine doses have been delivered as of October 31, 2022. The infection can cause mild or self-limiting symptoms of pulmonary and severe infections or death may be caused by SARS-CoV-2 infection. Simultaneously, antivirals, corticosteroids, immunological treatments, antibiotics, and anticoagulants have been proposed as potential medicines to cure COVID-19 affected patients. Among these initial treatments, COVID-19 convalescent plasma (CCP), which was retrieved from COVID-19 recovered patients to be used as passive immune therapy, in which antibodies from cured patients were given to infected patients to prevent illness. Such treatment has yielded the best results in earlier with preventative or early stages of illness. Convalescent plasma (CP) is the first treatment available when infectious disease initially appears, although few randomized controlled trials (RCTs) were conducted to evaluate its effectiveness. The historical record suggests with potential benefit for other respiratory infections, as coronaviruses like Severe Acute Respiratory Syndrome-CoV-I (SARS-CoV-I) and Middle Eastern Respiratory Syndrome (MERS), though the analysis of such research is constrained by some non-randomized experiments (NREs). Rigorous studies on CP are made more demanding by the following with the immediacy of the epidemics, CP use may restrict the ability to utilize it for clinical testing, non-homogenous nature of product, highly decentralized manufacturing process; constraints with capacity to measure biologic function, ultimate availability of substitute therapies, as antivirals, purified immune globulins, or monoclonal antibodies. Though, it is still not clear how effectively CCP works among hospitalized COVID-19 patients. The current review tries to focus on its efficiency and usage in clinical scenarios and identifying existing benefits of implementation during pandemic or how it may assist with future pandemic preventions.

COVID-19 and China's Global Image

With the outbreak of the novel coronavirus, the PRC experienced one of its worst internal and international crises, in economic terms but above all in terms of image and prestige. The COVID-19 pandemic, in fact, came at a critical juncture in both China's internal and international relations, given that in recent years the communist Government has become a target of criticism on various internal and international issues. At the same time, it represented a crucial challenge for the CCP, while preparing the celebrations for its 100th anniversary and the achievement of its first «centenary goal». Beyond the undeniable effects on the country's economy, undoubtedly the most relevant effects were recorded in terms of image and reputation, as has emerged in different global opinion polls. Despite the Chinese authorities' highly effective management of the health emergency crisis after a first period of inaction, Beijing's authoritarian rule has again been an object of consistent criticism from liberal Western democracies, both on the intrusive methods adopted to cope with the crisis and its aggressiveness in imposing its official narrative regarding events. After analysing the effects of COVID-19 on China's global image, the paper focuses on the importance of «image» for China and its quest for prestige and image-building throughout history, with special reference to the communist experience. In the last part, it reflects on the opportunity that vaccine diplomacy may represent for China to recover its reputation.

China 2021: Coping with the resilience dilemma of the Chinese model

In 2021 Chinese internal politics were dominated by the domestic economy and the COVID-19 pandemic. The celebration of the 100th anniversary of the Chinese Communist Party (CCP) worked well to project the numerous successes of Chinese politics through history. Yet, Beijing's insistence on the need to rethink the developmental path of China's economic model also demonstrates the extent to which the important engines that have driven China's growth in the past four decades must now be diverted to an internal dimension. This is the case of the dual circulation strategy and the common prosperity policy, whose guidelines are envisioned by Chinese leaders and political elites to transform the country's existing growth model through a fully fledged internal rebalancing, and which spared not even the once unscrutinized, cross-border flow of data coming out of China.

The Economic Consequences of Xi Jinping

In the aftermath of the 20th National Congress of the Chinese Communist Party, Xi Jinping’s principal focus will be on state and national security, while an entirely new economic- and financial-policy team, with little experience, will take charge of China’s troubled economy. Its members will have to manage several systemic problems – a debt mountain, a property bust, a rapidly ageing population, zero-COVID policies – and develop a viable new economic-development model. This would be a demanding agenda anywhere, but Xi’s China has to tackle it guided by an ever more devoutly Leninist approach to economic management, industrial policy and governance, at a time when China faces the most hostile external environment it has known since Mao Zedong, as exemplified by foreign decoupling. Although Xi’s China is capable of important accomplishments in science and technology, and of flexing its diplomatic and military muscles in defence of its interests, China’s politics may be much less capable of fixing the country’s systemic economic and financial weaknesses. The consequences of Xi Jinping’s economic programme, including an emphasis on self-reliance, promise to extend beyond China’s borders to foreign actors and countries that once benefited from its economic rise.

Receiving of SARS-CoV-2/COVID-19 convalescent plasma in 2020–2021 in context of activity of Regional Center of Blood Donation and Blood Treatment in Bydgoszcz, Poland

Introduction: We analyzed SARS-CoV-2/COVID-19 convalescent plasma (CCP) production in the process of qualifying donors-convalescents, plasma collection and dispensing from the Regional Center of Blood Donation and Blood Treatment (RCKiK, Regionalne Centrum Krwiodawstwa i Krwiolecznictwa) in Bydgoszcz in the light of Polish national data. Material and methods: This retrospective analysis based on the RCKiK documentation covers the first year of convalescent plasma production and use, i.e. from 1 May 2020 to 30 April 2021. Evaluations of the qualifying process for convalescent donors, plasma collection, and dispensing to hospitals were carried out. The data was analyzed in relation to data from all over Poland provided by the National Blood Center. Results: In the 12 months ending on 30 April, 2021, 121,896.2 CCP units were acquired in total in 21 Regional Blood Donation and Treatment Centers. Of these, 14,683 units (12%) were acquired in Bydgoszcz, which places RCKiK Bydgoszcz in first place in Poland. The majority of donors were men, and most men were multiple donors, but most women were first-time donors. Most donors donated blood once, but 28.8% of donors donated at least twice. Most donations took place between December 2020 and March 2021, i.e. after the peak of the second and during the third wave of the pandemic. Nearly all the CCP preparations were dispensed to 29 hospitals in the Kuyavian-Pomeranian Voivodeship, and about 0.4% to other voivodeships. Conclusions: In the period from 1 May 2020 to 30 April 2021, the RCKiK in Bydgoszcz was the most active center in Poland for obtaining, producing and distributing plasma from people who were convalescing. In the plasma collection process, a very high level of commitment among of RBC personnel and donors was found, expressed in an increased number of donations. A relatively high proportion of donors were first-time and repeat multiple donors, although most donors gave only one donation. The mean anti-SARS-CoV-2 antibodies titer remained at a comparable level up to 150 days after disease. Copyright © 2022 The Polish Society of Haematologists and Transfusiologists, Insitute of Haematology and Transfusion Medicine. All rights reserved.

COVID-19 AND CHINA’S GLOBAL IMAGE

With the outbreak of the novel coronavirus, the PRC experienced one of its worst internal and international crises, in economic terms but above all in terms of image and prestige. The COVID-19 pandemic, in fact, came at a critical juncture in both China’s internal and international relations, given that in recent years the communist Government has become a target of criticism on various internal and international issues. At the same time, it represented a crucial challenge for the CCP, while preparing the celebrations for its 100th anniversary and the achievement of its first «centenary goal». Beyond the undeniable effects on the country’s economy, undoubtedly the most rele-vant effects were recorded in terms of image and reputation, as has emerged in different global opinion polls. Despite the Chinese authorities’ highly effective management of the health emergency crisis after a first period of inaction, Beijing’s authoritarian rule has again been an object of consistent criticism from liberal Western democracies, both on the intrusive methods adopted to cope with the crisis and its aggressiveness in imposing its official narrative regarding events. After analysing the effects of COV-ID-19 on China’s global image, the paper focuses on the importance of «image» for China and its quest for prestige and image-building throughout history, with special reference to the communist experience. In the last part, it reflects on the opportunity that vaccine diplomacy may represent for China to recover its reputation. © Viella s.r.l. & Associazione Asia Maior.

CHINA 2021: COPING WITH THE RESILIENCE DILEMMA OF THE CHINESE MODEL

In 2021 Chinese internal politics were dominated by the domestic economy and the COVID-19 pandemic. The celebration of the 100th anniversary of the Chinese Communist Party (CCP) worked well to project the numerous successes of Chinese politics through history. Yet, Beijing’s insistence on the need to rethink the developmental path of China’s economic model also demonstrates the extent to which the important engines that have driven China’s growth in the past four decades must now be diverted to an internal dimension. This is the case of the dual circulation strategy and the common prosperity policy, whose guidelines are envisioned by Chinese leaders and political elites to transform the country’s existing growth model through a fully fledged internal rebalancing, and which spared not even the once unscrutinized, cross-border flow of data coming out of China. © Viella s.r.l. & Associazione Asia Maior.

Limited Correlation between SARS-CoV-2 Serologic Assays for Identification of High-Titer COVID-19 Convalescent Plasma Using FDA Thresholds.

In August 2020, the Food and Drug Administration (FDA) Emergency Use Authorization (EUA) for COVID-19 convalescent plasma (CCP) specified 12 authorized serologic assays and associated assay-specific cutoff values for the selection of high-titer CCP for use in hospitalized patients. The criteria used for establishing these cutoff values remains unclear. Here, we compare the overall agreement and concordance of five serologic assays included in the August 2020 FDA EUA at both the manufacturer-recommended qualitative cutoff thresholds and at the FDA-indicated thresholds for high-titer CCP, using serum samples collected as part of the CCP Expanded Access Program (EAP). The qualitative positive percent agreement (PPA) across assays ranged from 92.3% to 98.8%. However, the high-titer categorization across assays varied significantly, with the PPA ranging from 26.5% to 82.7%. The Roche anti-NC ECLIA provided the lowest agreement compared to all other assays. Efforts to optimize high-titer cutoffs could reduce, although not eliminate, the discordance across assays. The consequences of using nonstandardized assays are apparent in our study, and the high-titer cutoffs chosen for each assay are not directly comparable to each other. The generalized findings in our study will be relevant to any future use of convalescent plasma for either COVID-19 or future pandemics of newly emerged pathogens. IMPORTANCE COVID-19 convalescent plasma (CCP) was one of the first therapeutic options available for the treatment of SARS-CoV-2 infections and continues to be used selectively for immunosuppressed patients. Given the emergence of novel SARS-CoV-2 variants which are resistant to treatment with available monoclonal antibody (MAb) therapy, CCP remains an important therapeutic consideration. The FDA has released several emergency use authorizations (EUA) that have specified which serological assays can be used for qualification of CCP, as well as assay-specific cutoffs that must be used to identify high-titer CCP. In this study, a cohort of donor CCP was assessed across multiple serological assays which received FDA EUA for qualification of CCP. This study indicates a high degree of discordance across the assays used to qualify CCP for clinical use, which may have precluded the optimal use of CCP, including during clinical trials. This study highlights the need for assay standardization early in the development of serological assays for emerging pathogens.

Treatment of COVID-19 Patients with Two Units of Convalescent Plasma in a Resource-Constrained State.

IMPORTANCE: Many therapies are used to treat COVID-19, the disease caused by the virus SARS-CoV-2, including convalescent plasma. The clinical utility of using 2 units of convalescent plasma for COVID-19 hospitalized patients is not fully understood. OBJECTIVE: Many therapies are used to treat COVID-19, the disease caused by the virus SARS-CoV-2, including convalescent plasma. The clinical utility of using 2 units of convalescent plasma for COVID-19 hospitalized patients is not fully understood. Our study aims to determine the safety and efficacy of treating hospitalized COVID-19 patients with 2 units of COVID-19 convalescent plasma (CCP). METHOD: This was a retrospective study of Arkansas patients treated with CCP using the (US) Food and Drug Administration (FDA) emergency Investigational New Drug (eIND) mechanism from April 9, 2020, through August 9, 2020. It was a multicenter, statewide study in a low-resource setting, which are areas that lack funding for health care cost coverage on various levels including individual, family, or social. Adult patients (n = 165, volunteer sample) in Arkansas who were hospitalized with severe or life-threatening acute COVID-19 disease as defined by the FDA criteria were transfused with 2 units of CCP (250 mL/unit) using the FDA eIND mechanism. The primary outcome was 7- and 30-day mortality after the second unit of CCP. RESULTS: Unadjusted mortality was 12.1% at 7 days and 23.0% at 30 days. The unadjusted mortality was reduced to 7.7% if the first CCP unit was transfused on the date of diagnosis, 8.7% if transfused within 3 days of diagnosis, and 32.0% if transfused at or after 4 or more days of diagnosis. The risk of death was higher in patients that received low, negative, or missing titer CCP units in comparison to those that received higher titer units. CONCLUSION: The provision of 2 units of CCP was associated with a reduction in mortality in patients treated with high titer units within 3 days of COVID-19 diagnosis. Given the results, CCP is a viable, low-cost therapy in resource-constrained states and countries.

Associations Between Symptoms, Donor Characteristics and IgG Antibody Response in 2082 COVID-19 Convalescent Plasma Donors.

Many studies already reported on the association between patient characteristics on the severity of COVID-19 disease outcome, but the relation with SARS-CoV-2 antibody levels is less clear. To investigate this in more detail, we performed a retrospective observational study in which we used the IgG antibody response from 11,118 longitudinal antibody measurements of 2,082 unique COVID convalescent plasma donors. COVID-19 symptoms and donor characteristics were obtained by a questionnaire. Antibody responses were modelled using a linear mixed-effects model. Our study confirms that the SARS-CoV-2 antibody response is associated with patient characteristics like body mass index and age. Antibody decay was faster in male than in female donors (average half-life of 62 versus 72 days). Most interestingly, we also found that three symptoms (headache, anosmia, nasal cold) were associated with lower peak IgG, while six other symptoms (dry cough, fatigue, diarrhoea, fever, dyspnoea, muscle weakness) were associated with higher IgG concentrations.

SARS-CoV-2 antibody changes in patients receiving COVID-19 convalescent plasma from normal and vaccinated donors.

Vaccination has been shown to stimulate remarkably high antibody levels in donors who have recovered from COVID-19. Our objective was to measure patient antibody levels before and after transfusion with COVID-19 Convalescent Plasma (CCP) and compare the antibody levels following transfusion of CCP from vaccinated and nonvaccinated donors. Plasma samples before and after transfusion were obtained from 25 recipients of CCP and COVID-19 antibody levels measured. Factors that effect changes in antibody levels were examined. In the 21 patients who received CCP from nonvaccinated donors, modest increases in antibody levels were observed. Patients who received two units were more likely to seroconvert than those receiving just one unit. The strongest predictor of changes in patient antibody level was the CCP dose, calculated by the unit volume multiplied by the donor antibody level. Using patient plasma volume and donor antibody level, the post-transfusion antibody level could be predicted with reasonable accuracy(R2> 0.90). In contrast, the 4 patients who received CCP from vaccinated donors all had dramatic increases in antibody levels following transfusion of a single unit. In this subset of recipients, antibody levels observed after transfusion of CCP were comparable to those seen in donors who had fully recovered from COVID-19. If available, CCP from vaccinated donors with very high antibody levels should be used. One unit of CCP from vaccinated donors increases patient antibody levels much more than 1 or 2 units of CCP from unvaccinated donors.

Black and White and Red All Over: Chinas Improving Foreign Directed Media

Over the last 15 years, the Chinese Communist Party (CCP) has conducted an ambitious campaign to increase the efficacy of its external propaganda. Drawing from primary Chinese languages sources, this study identifies and traces the origins of the overarching objectives of these efforts. In addition, it outlines the concrete steps that Beijing has taken to date to strengthen Chinese foreign-directed media. Using translated professional journals, the study also analyzes how Chinese subject matter experts in their own words assess Beijings successes and shortcomings in improving the reach and resonance of Chinas external propaganda. This research was conducted on behalf of the US Indo-Pacific Commands China Strategic Focus Group in support of USINDOPACOM requirements.

Homologous and Heterologous Anti-COVID-19 Vaccination Does Not Induce New-Onset Formation of Autoantibodies Typically Accompanying Lupus Erythematodes, Rheumatoid Arthritis, Celiac Disease and Antiphospholipid Syndrome.

The COVID-19 pandemics has caused the death of almost six million people worldwide. In order to establish collective immunity, the first vaccines that were approved in Germany were the vector virus-based vaccine Vaxzevria and the mRNA vaccines Comirnaty and Spikevax, respectively. As it was reported that SARS-CoV-2 can trigger autoimmunity, it is of significant interest to investigate whether COVID-19 vaccines evoke the formation of autoantibodies and subsequent autoimmunity. Here, we analyzed immune responses after different vaccination regimens (mRNA/mRNA, Vector/Vector or Vector/mRNA) with respect to anti-SARS-CoV-2-specific immunity and the development of autoantibodies well known for their appearance in distinct autoimmune diseases. We found that anti-SARS-CoV-2 antibody levels were 90% lower after Vector/Vector vaccination compared to the other vaccinations and that Vector/mRNA vaccination was more effective than mRNA/mRNA vaccination in terms of IgM and IgA responses. However, until 4 months after booster vaccination we only detected increases in autoantibodies in participants with already pre-existing autoantibodies whereas vaccinees showing no autoantibody formation before vaccination did not respond with sustained autoantibody production. Taken together, our study suggests that all used COVID-19 vaccines do not significantly foster the appearance of autoantibodies commonly associated with lupus erythematodes, rheumatoid arthritis, Celiac disease and antiphospholipid-syndrome but provide immunity to SARS-CoV-2.

Why Have Chinese Diplomats Become So Aggressive?

This article explores why Chinese diplomats have become so aggressive, discarding the professionalism and courtesy that have facilitated China's engagement with the world for more than four decades. Some argue that Chinese diplomats want to distract foreign audiences from Beijing's handling of the COVID-19 pandemic. Others suggest that they are trying to demonstrate their strength abroad in response to popular nationalism at home. Still others argue that their bluster is intended to show their loyalty to President and Chinese Communist Party General Secretary Xi Jinping. All of these explanations appear to be valid to some extent.

COVID-19 convalescent plasma experience in the US

Convalescent whole blood, plasma, and serum have been used as passive immune therapy of infectious diseases since the late 1800s. Following favorable reports of safety and clinical improvement after limited use of convalescent plasma (CP) to treat SARS-CoV-2 disease (COVID-19), the United States Food and Drug Administration (FDA) invited investigational use of this product. Single-patient emergency Investigational New Drug Applications (eINDs) were soon followed by an expanded access program (EAP). Data from the EAP led to FDA’s emergency use authorization of COVID-19 CP (CCP). The elements of a CCP program are donor recruitment, prevention of disease transmission at the collection site, donor screening at the collection site, plasma collection, testing plasma for potency, and the use of postdonation information from the donor. These elements are based on practices already used for allogeneic donation generally. Data supporting current CCP potency criteria, which are related to the titer of antibody against SARS-CoV-2, are limited. A report of rates of adverse donor outcomes and product loss exceeding those for non-CCP donations needs further study. Initially high demand for CCP appears to have declined. Regulatory restrictions on eligible recipients may further decrease demand. The effects of vaccination on donor and recipient availability are to be determined. © Annals of Blood. All rights reserved.

A novel competition ELISA for the rapid quantification of SARS-CoV-2 neutralizing antibodies in convalescent plasma.

BACKGROUND: COVID-19 convalescent plasma (CCP) ideally contains high titers of (neutralizing) anti-SARS-CoV-2 antibodies. Several scalable immunoassays for CCP selection have been developed. We designed an enzyme-linked immunosorbent assay (ELISA) that measures neutralizing antibodies (of all isotypes) in plasma by determining the level of competition between CCP and a mouse neutralizing antibody for binding to the receptor binding domain (RBD) of SARS-CoV-2. METHODS: Plasma was collected from 72 convalescent individuals and inhibition of viral infection was determined by plaque reduction neutralization (PRNT50). The level of neutralizing antibodies was measured in the novel competition ELISA and in a commercially available ELISA that measures inhibition of recombinant ACE2 binding to immobilized RBD. These results were compared with a high throughput chemiluminescent microparticle immunoassay (CMIA). RESULTS: The results from both ELISAs were correlating, in particular for high titer CCP (PRNT50 ≥ 1:160) (Spearman r = .73, p < .001). Moderate correlation was found between the competition ELISA and CMIA (r = .57 for high titer and r = .62 for low titer CCP, p < .001). Receiver operator characteristic analysis showed that the competition ELISA selected CCP with a sensitivity and specificity of 61% and 100%, respectively. However, discrimination between low and high titer CCP had a lower resolution (sensitivity: 34% and specificity: 89%). CONCLUSION: The competition ELISA screens for neutralizing antibodies in CCP by competition for just a single epitope. It exerts a sensitivity of 61% with no false identifications. These ELISA designs can be used for epitope mapping or for selection of CCP.

The safety of COVID-19 convalescent plasma donation: A multi-institutional donor hemovigilance study.

BACKGROUND: Although the safety and therapeutic efficacy of COVID-19 convalescent plasma (CCP) has been extensively evaluated, the safety of CCP donation has not been explored in a multi-institutional context. STUDY DESIGN AND METHODS: Nine blood collection organizations (BCOs) participated in a multi-institutional donor hemovigilance effort to assess the safety of CCP donation. Donor adverse events (DAEs) were defined according to the Standard for Surveillance of Complications Related to Blood Donation, and severity was assessed using the severity grading tool. Multivariate analysis was performed to determine attributes associated with DAE severity. RESULTS: The overall DAE rate was 37.7 per 1000 donations. Repeat apheresis and apheresis-naïve donors experienced adverse event rates of 19.9 and 49.8 per 1000 donations, respectively. Female donors contributed 51.9% of CCP donations with a DAE rate of 49.4 per 1000 donations. The DAE rate for male donors was 27.4 per 1000 donations. Vasovagal reactions accounted for over half of all reported DAEs (51.1%). After adjustment, volume of CCP donated was associated with vasovagal reaction severity (odds ratio [OR] 6.5, 95% confidence interval [CI] 2.5-17.1). Donor age and donation history were also associated with DAE severity. Considerable differences in DAE types and rates were observed across the participating BCOs despite the use of standardized hemovigilance definitions. CONCLUSION: The safety of CCP donation appears comparable to that of conventional apheresis plasma donation with similar associated risk factors for DAE types and severity.

The missing link: covalent linkages in structural models.

Covalent linkages between constituent blocks of macromolecules and ligands have been subject to inconsistent treatment during the model-building, refinement and deposition process. This may stem from a number of sources, including difficulties with initially detecting the covalent linkage, identifying the correct chemistry, obtaining an appropriate restraint dictionary and ensuring its correct application. The analysis presented herein assesses the extent of problems involving covalent linkages in the Protein Data Bank (PDB). Not only will this facilitate the remediation of existing models, but also, more importantly, it will inform and thus improve the quality of future linkages. By considering linkages of known type in the CCP4 Monomer Library (CCP4-ML), failure to model a covalent linkage is identified to result in inaccurate (systematically longer) interatomic distances. Scanning the PDB for proximal atom pairs that do not have a corresponding type in the CCP4-ML reveals a large number of commonly occurring types of unannotated potential linkages; in general, these may or may not be covalently linked. Manual consideration of the most commonly occurring cases identifies a number of genuine classes of covalent linkages. The recent expansion of the CCP4-ML is discussed, which has involved the addition of over 16 000 and the replacement of over 11 000 component dictionaries using AceDRG. As part of this effort, the CCP4-ML has also been extended using AceDRG link dictionaries for the aforementioned linkage types identified in this analysis. This will facilitate the identification of such linkage types in future modelling efforts, whilst concurrently easing the process involved in their application. The need for a universal standard for maintaining link records corresponding to covalent linkages, and references to the associated dictionaries used during modelling and refinement, following deposition to the PDB is emphasized. The importance of correctly modelling covalent linkages is demonstrated using a case study, which involves the covalent linkage of an inhibitor to the main protease in various viral species, including SARS-CoV-2. This example demonstrates the importance of properly modelling covalent linkages using a comprehensive restraint dictionary, as opposed to just using a single interatomic distance restraint or failing to model the covalent linkage at all.

NPC1-regulated dynamic of clathrin-coated pits is essential for viral entry.

Viruses utilize cellular lipids and manipulate host lipid metabolism to ensure their replication and spread. Therefore, the identification of lipids and metabolic pathways that are suitable targets for antiviral development is crucial. Using a library of compounds targeting host lipid metabolic factors and testing them for their ability to block pseudorabies virus (PRV) and vesicular stomatitis virus (VSV) infection, we found that U18666A, a specific inhibitor of Niemann-Pick C1 (NPC1), is highly potent in suppressing the entry of diverse viruses including pseudotyped severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). NPC1 deficiency markedly attenuates viral growth by decreasing cholesterol abundance in the plasma membrane, thereby inhibiting the dynamics of clathrin-coated pits (CCPs), which are indispensable for clathrin-mediated endocytosis. Significantly, exogenous cholesterol can complement the dynamics of CCPs, leading to efficient viral entry and infectivity. Administration of U18666A improves the survival and pathology of PRV- and influenza A virus-infected mice. Thus, our studies demonstrate a unique mechanism by which NPC1 inhibition achieves broad antiviral activity, indicating a potential new therapeutic strategy against SARS-CoV-2, as well as other emerging viruses.