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1.
International Journal of Environmental Research and Public Health ; 19(9):5269, 2022.
Article in English | ProQuest Central | ID: covidwho-1837388

ABSTRACT

Mental health literacy (MHL) plays an important role in public health. Improving MHL can promote mental health at the individual and public levels. To date, no published studies have assessed the effectiveness of MHL curriculum interventions among undergraduate public health students. The participants in this study were undergraduate public health students (n = 48) who were enrolled in an 18-week MHL curriculum for 100 min per week. MHL was assessed using the Mental Health Literacy Scale for Healthcare Students. A paired sample t-test was performed to examine the immediate and delayed effects of the MHL curriculum. The total MHL score significantly improved, and a moderate effect size was found directly after the intervention and six weeks later. There were significant differences in the recognition of mental illness (p < 0.01), help-seeking efficacy (p < 0.05), and help-seeking attitude (p < 0.05) in the five components of MHL between pre- and post-test. Furthermore, significant improvements were obtained for the maintenance of positive mental health (p < 0.05) and reduction of mental illness stigma (p < 0.001) between the pre-test and follow-up. Our findings provide evidence for the development and implementation of an MHL curriculum for public health education.

2.
International journal of biological sciences ; 18(7):3066-3081, 2022.
Article in English | EuropePMC | ID: covidwho-1823884

ABSTRACT

During the development of COVID-19 caused by SARS-CoV-2 infection from mild disease to severe disease, it can trigger a series of complications and stimulate a strong cellular and humoral immune response. However, the precise identification of blood immune cell response dynamics and the relevance to disease progression in COVID-19 patients remains unclear. We propose for the first time to use changes in cell numbers to establish new subgroups, which were divided into four groups: first from high to low cell number (H_L_Group), first from low to high (L_H_Group), continuously high (H_Group), and continuously low (L_Group). It was found that in the course of disease development. In the T cell subgroup, the immune response is mainly concentrated in the H_L_Group cell type, and the complications are mainly in the L_H_Group cell type. In the NK cell subgroup, the moderate patients are mainly related to cellular immunity, and the severe patients are mainly caused by the disease, while severe patients are mainly related to complications caused by diseases. Our study provides a dynamic response of immune cells in human blood during SARS-CoV-2 infection and the first subgroup analysis using dynamic changes in cell numbers, providing a new reference for clinical treatment of COVID-19.

3.
Cell Insight ; : 100029, 2022.
Article in English | ScienceDirect | ID: covidwho-1814234

ABSTRACT

The emergence of the SARS-CoV-2 Omicron variant poses a striking threat to human society. More than 30 mutations in the Spike protein of the Omicron variant severely compromised the protective immunity elicited by either vaccination or prior infection. The persistent viral evolutionary trajectory generates Omicron-associated lineages, such as BA.1 and BA.2. Moreover, the virus recombination upon Delta and Omicron co-infections has been reported lately, although the impact remains to be assessed. This minireview summarizes the characteristics, evolution and mutation control, and immune evasion mechanisms of SARS-CoV-2 variants, which will be helpful for the in-depth understanding of the SARS-CoV-2 variants and policy-making related to COVID-19 pandemic control.

4.
Journal of Education Research ; - (334):144-157, 2022.
Article in Chinese | ProQuest Central | ID: covidwho-1812216

ABSTRACT

The operation of education and sports facilities in the England was affected during COVID-19 pandemic due to the lockdowns regulation. Before the pandemic happened, the physical education (PE) in the schools was implanted according to the National curriculum in England: PE programmes of study. Sport and PE related organisation such as Association for PE also provided PE teachers and instructors resource and support to deliver PE lessons. Such organisations also provided information and online resource that help remotely deliver PE lessons during the pandemic. Most the online resource aimed to motivate students to participate physical activity and maintain physical fitness during the remote learning period. When the schools reopened, PE teachers and instructors could deliver PE lessons following the PE curriculum, but the group activities and sports were still limited. The supports that provided to schools in England by sport and PE related organisation during the pandemic including the detailed guidance on how to implemented PE, and the online resource to assist remote learning are useful for Taiwan when facing the disruption caused by COVID-19. It is also important to recognise that the inevitable effects on how the PE lessons are delivered during the pandemic, although all the supporting resource are provided.

5.
PLoS One ; 17(4), 2022.
Article in English | ProQuest Central | ID: covidwho-1808557

ABSTRACT

TLR7 and TLR8 are key members of the Toll-like receptor family, playing crucial roles in the signaling pathways of innate immunity, and thus become attractive therapeutic targets of many diseases including infections and cancer. Although TLR7 and TLR8 show a high degree of sequence homology, their biological response to small molecule binding is very different. Aiming to understand the mechanism of selective profiles of small molecule modulators against TLR7 and TLR8, we carried out molecular dynamic simulations on three imidazoquinoline derivatives bound to the receptors separately. They are Resiquimod (R), Hybrid-2 (H), and Gardiquimod (G), selective agonists of TLR7 and TLR8. Our MD trajectories indicated that in the complex of TLR7-R and TLR7-G, the two chains forming the TLR7 dimer tended to remain “open” conformation, while the rest systems maintained in the closed format. The agonists R, H, and G developed conformational deviation mainly on the aliphatic tail. Furthermore, we attempted to quantify the selectivity between TLR7 and TLR8 by binding free energies via MM-GBSA method. It showed that the three selected modulators were more favorable for TLR7 than TLR8, and the ranking from the strongest to the weakest was H, R and G, aligning well with experimental data. In the TLR7, the flexible and hydrophobic aliphatic side chain of H has stronger van der Waals interactions with V381 and F351 but only pick up interaction with one amino acid residue i.e. Y353 of TLR8. Unsurprisingly, the positively charged side chain of G has less favorable interaction with I585 of TLR7 and V573 of TLR8 explaining G is weak agonist of both TLR7 and TLR8. All three imidazoquinoline derivatives can form stable hydrogen bonds with D555 of TLR7 and the corresponding D543 of TLR8. In brief, the set of total 400ns MD studies sheds light on the potential selectivity mechanisms of agonists towards TLR7 and TLR8, indicating the van der Waals interaction as the driving force for the agonists binding, thus provides us insights for designing more potent and selective modulators to cooperate with the hydrophobic nature of the binding pocket.

6.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-334378

ABSTRACT

Background: This study investigated the effects of nutritional status at the time of admission on clinical outcomes in patients with Coronavirus disease 2019 (COVID-19). Methods A retrospective analysis was performed on 54 patients diagnosed with COVID-19. Clinical data of admitted patients, albumin and pre-serum albumin levels, gastrointestinal intolerance, and general information were collected and analyzed. The primary clinical outcomes were length of hospital stay and hospitalization costs. Results The results showed that albumin and pre-serum albumin levels of patients at admission were negatively associated with the length of hospital stay and hospitalization costs (P < 0.001). Patients with poor appetite had longer hospital stays (P < 0.001) and higher hospital costs (P = 0.022). Conclusion These results indicated that the nutritional status at admission can directly influence the clinical outcomes of COVID-19.

7.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-334361

ABSTRACT

During the COVID-19 pandemic, most of the endoscopic services were electively postponed or suspended. We aimed to assess the safety of a triage policy in patients receiving esophageal variceal ligation during the COVID-19 pandemic. Triage policy of endoscopic variceal ligation (EVL) was implemented in our hospital during the lockdown period from 15th May 2021 to 26th July 2021. We compared the clinical characteristics and outcomes with those receiving endoscopy due to esophageal varices from 17th May 2020 to 28th July 2020. Of the 124 patients receiving EVL, a higher percentage of esophageal variceal bleeding (EVB) was noted (9/32, 28.1% vs. 8/92, 8.7%, p = 0.006) during the lockdown period, with a higher percentage of EVB in the referrals (7/9, 77.8% vs. 2/14, 14.2%, p = 0.007). Twenty-three patients whose endoscopies were postponed by triage policy due to low-risk or eradicated varices did not experience EVB during the lockdown period. Child-Pughs class C was independent factor predictive of EVB (relative risk 7.674, P = 0.004), entering the program of prophylactic EVL was the protective factor of EVB (relative risk 0.158, P = 0.004). Entrance into the prophylaxis program does not only decrease risk of EVB but also fosters comprehensive triage to postpone endoscopy during the lockdown period.

8.
Journal of Microbiology, Immunology and Infection ; 2022.
Article in English | ScienceDirect | ID: covidwho-1796470

ABSTRACT

Background In Taiwan, there were only 799 confirmed COVID-19 cases in 2020. The unique backdrop amidst a pandemic and promotion of nonpharmaceutical interventions generated some distinct changes in the epidemiology of common respiratory pathogens. In this study, we aimed to investigate the dynamic changes in respiratory pathogens in children during 2020. Methods We performed a retrospective cohort study at a tertiary hospital in southern Taiwan during 2020. Patients aged 0 to 18 years who visited the pediatric emergency department were enrolled. Children who presented with clinical symptoms (fever or respiratory illness) and received nasopharyngeal swabs for multiplex polymerase chain reaction (PCR) were included in our analysis. We also compared respiratory syncytial virus (RSV) trends from previous years by PCR and lateral flow immunochromatographic assays from 2017 to 2020. Results A total of 120 children were tested. The overall detection rate was 55%. With strengthened restrictions, the detection rate dropped from 70% to 30%. However, non-enveloped viruses (rhinovirus/enterovirus and adenovirus) were in constant circulation. Upon easing prevention measures, the detection rate remained above 60%, and an outbreak of an enveloped virus (RSV and parainfluenza virus) was noted. Compared with 2017 to 2019, the cyclical RSV epidemic was delayed, with a large surge in late 2020. Conclusions We observed a constant circulation of non-enveloped viruses when strict nonpharmaceutical interventions were employed and a delayed surge of enveloped viruses during the easing of restrictions. Continuous surveillance and monitoring of the evolutionary dynamics of respiratory viruses is important, while easing restrictions requires balanced judgment.

9.
Front Public Health ; 10: 850191, 2022.
Article in English | MEDLINE | ID: covidwho-1785450

ABSTRACT

Objective: To investigate whether first-trimester fasting plasma glucose (FPG), blood coagulation function and lipid metabolism could predict gestational diabetes mellitus (GDM) risk. Methods: From October 2020 to May 2021, a total of 584 pregnant women who took prenatal care in Shanghai Jiaotong University Affiliated Sixth People's Hospital were chosen as the observation subjects. The clinical information and serum samples of all pregnant women were collected at 10-13 weeks of gestation and the blood coagulation function, fasting blood glucose and lipid profiles of the pregnant women were detected. A 75 g oral glucose tolerance test was performed up to 24-28 weeks of gestation. One hundred forty-two pregnant women with GDM and 442 pregnant women without GDM were detected. Data were expressed by x ± s or median (interquartile range) and were analyzed using student's t-test, Wilcoxon rank sum test and Logistic regression analysis. The area under the curve (AUC) was calculated by receiver operating characteristic curve (ROC) to analyze the predictive values. Results: Compared with non-GDM group, age, pre-pregnancy BMI, FPG, FIB, D-Dimer, FDP, FPG, TC, TG, LDL-C, sdLDL-C, APOB and APOE in GDM group were significantly higher than those in non-GDM group, while PT, INR, APTT and TT were significantly lower than those in non-GDM group. Univariate logistic regression analysis was used to explore the risk factors of GDM. Gestational age, pre-pregnancy BMI, FPG, PT, INR, APTT, FIB, TT, D-Dimer, TC, TG, LDL-C, sdLDL-C, APOB and APOE were all independent predictors of GDM. Multivariatelogistic regression showed that pre-pregnancy BMI, FPG, APTT, TT, TG, LDL-C, sdLDL-C and APOB were risk factors for GDM. The AUC of the established GDM risk prediction model was 0.892 (0.858-0.927), and the sensitivity and specificity were 80.71 and 86.85%, respectively; which were greater than that of pre-pregnancy BMI, FPG, APTT, TT,TG, LDL-C, sdLDL-C, APOB alone, and the difffference was statistically signifificant (P < 0.05). Conclusions: FPG, APTT, TT, TG, LDL-C, sdLDL-C, APOB and pre-pregnancy BMI in early pregnancy has important clinical value for the prediction of GDM, We combined these laboratory indicators and established a GDM risk prediction model, which is conducive to the early identification, intervention and treatment of GDM, so as to reduce the morbidity of maternal and infant complications.


Subject(s)
Diabetes, Gestational , Apolipoproteins B/metabolism , Apolipoproteins E/metabolism , Blood Coagulation , Blood Glucose/analysis , Blood Glucose/metabolism , Body Mass Index , Cholesterol, LDL/metabolism , Diabetes, Gestational/diagnosis , Early Diagnosis , Female , Glycolipids , Humans , Lipid Metabolism , Pregnancy
10.
Aging Dis ; 13(1): 144-156, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1780302

ABSTRACT

Coronavirus disease 2019 (COVID-19) is still an ongoing pandemic worldwide. COVID-19 is an age-related disease with a higher risk of organ dysfunction and mortality in older adults. Coagulation disorders and thrombosis are important pathophysiological changes in COVID-19 infection. Up to 95% of COVID-19 patients have coagulation disorders characterized by an elevated D-dimer, a prolonged prothrombin time, a low platelet count and other laboratory abnormalities. Thrombosis is found in critical cases with an increased risk of death. Endothelial cells are prone to be affected by the novel SARS-CoV-2 and express angiotensin-converting enzyme 2. The evidence, such as the presence of the virus, has been identified, leading to the inflammation and dysfunction. Endothelial cell activation and dysfunction play a pivotal role in the hypercoagulation status in COVID-19 patients. In addition to the direct exposure of subendothelial tissue to blood, Weibel-Palade bodies within the endothelium containing coagulants can be released into the circulation. Endothelial nitric oxide synthase may be impaired, thus facilitating platelet adhesion. Moreover, anti-ß2-glycoprotein I antibodies may also contribute to the coagulopathy in COVID-19 by inducing the upregulation of proinflammatory mediators and adhesion molecules. To conclude, coagulation disorders and thrombosis are vital and predict a poor outcome in COVID-19 patients, especially in severe cases. Endothelial cell activation and dysfunction may play an important role in causing clot formation. More basic and clinical research is warranted to further our understanding of the role of coagulopathy and their possible mechanism in COVID-19 patients.

12.
Front Public Health ; 10: 838661, 2022.
Article in English | MEDLINE | ID: covidwho-1776044

ABSTRACT

Introduction: The aim of this study was to develop and validate a new diabetes distress scale suitable for Chinese and Taiwanese culture. Methods: This study collected the current diabetes distress measurement tools, re-organized current definitions about the domains of diabetes distress, and then developed a new tool. Three hundred and ninety-five participants from four hospitals in northern Taiwan were recruited by cluster randomized sampling for validity test. Results: We found the new diabetes distress scale had appropriate reliability and validity, including an acceptable model fit for the 12-item scale. Conclusions: This new diabetes distress scale might be more directly related to emotional distress issues blood glucose control, improve the clinical conspicuity of diabetes distress, and even benefit the overall care of diabetic patients in Taiwan. Further studies about the validity and reliability of this new tool in a nationwide setting are needed.


Subject(s)
Diabetes Mellitus , Cultural Competency , Humans , Psychological Distress , Psychometrics , Reproducibility of Results , Taiwan
13.
Front Neurol ; 13: 850337, 2022.
Article in English | MEDLINE | ID: covidwho-1775723

ABSTRACT

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a high transmissible infectious disease that primarily impacts the respiratory system and leads to death as it worsens. Ever since the World Health Organization declared the disease as a global pandemic, the pathophysiology, clinical manifestations, and disease prognosis has been discussed in various literature. In addition to impaired respiratory health, the symptoms also indicated the involvement of the cardiovascular and neurological system after SARS-CoV-2 infection. Despite the pulmonary, cardiovascular, and neurological complications, many reports also revealed the prevalence of vestibulocochlear symptoms like dizziness, vertigo, vestibular neuritis, sudden sensorineural hearing loss, and tinnitus. Though many clinical reports and scientific reviews reported the vestibular and cochlear impairments associated with coronavirus disease 2019 (COVID-19) infection, the underlying pathological mechanisms are still unclear and unexplored. In this review, we discussed the published clinical reports, research articles, and literature reviews related to vestibulocochlear manifestations following SARS-CoV-2 infections. We also summarized the current knowledge about the prevalence, epidemiological and clinical features, and potential pathological mechanisms related to vestibular and cochlear manifestations resulting from COVID-19 infections.

14.
Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences ; 49(2):147-157, 2020.
Article in Chinese | EuropePMC | ID: covidwho-1772475

ABSTRACT

当前2019冠状病毒病(COVID-19)疫情仍处于胶着状态。浙江大学医学院附属第一医院是国家感染性疾病临床医学中心,浙江省COVID-19患者救治中心。疫情一线的专家集智攻关,以国家卫生健康委员会和国家中医药管理局发布的COVID-19诊治指南为依据,以抗病毒、抗休克、抗低氧血症、抗继发感染、维持水电解质和酸碱平衡、维持微生态平衡的“四抗二平衡”救治策略为核心,总结完善诊治方案,聚焦临床实践的一些具体问题,为COVID-19患者临床诊治提供借鉴。推荐以多学科协作诊治个性化治疗提高COVID-19患者救治质量。建议病原学检测、炎症指标监测和肺部影像学动态观察指导临床诊治。痰液的病毒核酸检测阳性率最高,约10%的急性期患者血液中检测到病毒核酸,50%的患者粪便中检测到病毒核酸,粪便中可分离出活病毒,须警惕粪便是否具有传染性;开展细胞因子等炎症指标监测有助于发现是否出现细胞因子风暴,判断是否需要人工肝血液净化治疗。通过以“四抗二平衡”为核心的综合治疗提高治愈率、降低病死率;早期抗病毒治疗能减少重症、危重症发生,前期使用阿比多尔联合洛匹那韦/利托那韦抗病毒显示出一定效果。休克和低氧血症多为细胞因子风暴所致,人工肝血液净化治疗能迅速清除炎症介质,阻断细胞因子风暴,对维持水电解质酸碱平衡也有很好的作用,可以提高危重型患者的疗效。重型病例疾病早期可适量、短程应用糖皮质激素。氧疗过程中,患者氧合指数小于200 mmHg时应及时转入重症医学科治疗;采用保守氧疗策略,不推荐常规进行无创通气;机械通气患者应严格执行集束化呼吸机相关性肺炎预防管理策略;氧合指数大于150 mmHg时,及早减、停镇静剂并撤机拔管。不推荐预防性使用抗菌药物,对于病程长,体温反复升高和血降钙素原水平升高的患者可酌情使用抗菌药物;要关注COVID-19患者继发真菌感染的诊治。COVID-19患者有肠道微生态紊乱,肠道乳酸杆菌、双歧杆菌等有益菌减少,推荐对所有患者进行营养和胃肠道功能评估,以营养支持和补充大剂量肠道微生态调节剂,纠正肠道微生态失衡,减少细菌移位和继发感染。COVID-19患者普遍存在焦虑和恐惧心理,应建立动态心理危机干预和处理。提倡中西医结合辨证施治;优化重型患者护理促进康复。严重急性呼吸综合征冠状病毒2(SARS-CoV-2)感染后病毒清除规律仍不明了,出院后仍须居家隔离2周,并定期随访。以上经验和建议在本中心实行,取得较好效果,但COVID-19是一种新的疾病,其诊治方案及策略仍有待进一步探索与完善。

15.
Protein Cell ; 2022 Apr 04.
Article in English | MEDLINE | ID: covidwho-1773029

ABSTRACT

SARS-CoV-2 infection causes complicated clinical manifestations with variable multi-organ injuries, however, the underlying mechanism, in particular immune responses in different organs, remains elusive. In this study, comprehensive transcriptomic alterations of 14 tissues from rhesus macaque infected with SARS-CoV-2 were analyzed. Compared to normal controls, SARS-CoV-2 infection resulted in dysregulation of genes involving diverse functions in various examined tissues/organs, with drastic transcriptomic changes in cerebral cortex and right ventricle. Intriguingly, cerebral cortex exhibited a hyperinflammatory state evidenced by significant upregulation of inflammation response-related genes. Meanwhile, expressions of coagulation, angiogenesis and fibrosis factors were also up-regulated in cerebral cortex. Based on our findings, neuropilin 1 (NRP1), a receptor of SARS-CoV-2, was significantly elevated in cerebral cortex post infection, accompanied by active immune response releasing inflammatory factors and signal transmission among tissues, which enhanced infection of the central nervous system (CNS) in a positive feedback way, leading to viral encephalitis. Overall, our study depicts a multi-tissue/organ transcriptomic landscapes of rhesus macaque with early infection of SARS-CoV-2, and provides important insights into the mechanistic basis for COVID-19-associated clinical complications.

16.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-331876

ABSTRACT

Middle East Respiratory Syndrome coronavirus (MERS-CoV) and several bat coronaviruses employ Dipeptidyl peptidase-4 (DPP4) as their functional receptors. However, the receptor for NeoCoV, the closest MERS-CoV relative yet discovered in bats, remains enigmatic. In this study, we unexpectedly found that NeoCoV and its close relative, PDF-2180-CoV, can efficiently use some types of bat Angiotensin-converting enzyme 2 (ACE2) and, less favorably, human ACE2 for entry. The two viruses use their spikes' S1 subunit carboxyl-terminal domains (S1-CTD) for high-affinity and species-specific ACE2 binding. Cryo-electron microscopy analysis revealed a novel coronavirus-ACE2 binding interface and a protein-glycan interaction, distinct from other known ACE2-using viruses. We identified a molecular determinant close to the viral binding interface that restricts human ACE2 from supporting NeoCoV infection, especially around residue Asp338. Conversely, NeoCoV efficiently infects human ACE2 expressing cells after a T510F mutation on the receptor-binding motif (RBM). Notably, the infection could not be cross-neutralized by antibodies targeting SARS-CoV-2 or MERS-CoV. Our study demonstrates the first case of ACE2 usage in MERS-related viruses, shedding light on a potential bio-safety threat of the human emergence of an ACE2 using "MERS-CoV-2" with both high fatality and transmission rate.

17.
J Formos Med Assoc ; 2022 Apr 01.
Article in English | MEDLINE | ID: covidwho-1768303
18.
Gels ; 8(3)2022 Mar 18.
Article in English | MEDLINE | ID: covidwho-1760484

ABSTRACT

Mesenchymal stem cells (MSCs) possess immunomodulatory properties and capacity for endogenous regeneration. Therefore, MSC therapy is a promising treatment strategy for COVID-19. However, the cells cannot stay in the lung long enough to exert their function. The extracellular matrix from porcine bladders (B-ECM) has been shown not only to regulate cellular activities but also to possess immunoregulatory characteristics. Therefore, it can be hypothesized that B-ECM hydrogel could be an excellent scaffold for MSCs to grow and could anchor MSCs long enough in the lung so that they can exhibit their immunomodulatory functions. In this study, ECM degradation products and a co-culture system of MSCs and macrophages were developed to study the immunomodulatory properties of ECM and MSCs under septic conditions. The results showed that B-ECM degradation products could decrease pro-inflammatory and increase anti-inflammatory cytokines from macrophages. In an in vivo mimicking co-culture system, MSCs cultured on B-ECM hydrogel exhibited immunomodulatory properties at both gene and protein levels. Both B-ECM degradation products and MSC conditioned medium supported the wound healing of alveolar epithelial cells. The results from the study could offer a basis for investigation of immunomodulation by ECM and MSCs before conducting in vivo experiments, which could later be applied in regenerative medicine.

20.
mBio ; : e0366221, 2022 Jan 25.
Article in English | MEDLINE | ID: covidwho-1741579

ABSTRACT

The ongoing coronavirus (CoV) disease 2019 (COVID-19) pandemic caused by infection with severe acute respiratory syndrome CoV 2 (SARS-CoV-2) is associated with substantial morbidity and mortality. Understanding the immunological and pathological processes of coronavirus diseases is crucial for the rational design of effective vaccines and therapies for COVID-19. Previous studies showed that 2'-O-methylation of the viral RNA cap structure is required to prevent the recognition of viral RNAs by intracellular innate sensors. Here, we demonstrate that the guanine N7-methylation of the 5' cap mediated by coronavirus nonstructural protein 14 (nsp14) contributes to viral evasion of the type I interferon (IFN-I)-mediated immune response and pathogenesis in mice. A Y414A substitution in nsp14 of the coronavirus mouse hepatitis virus (MHV) significantly decreased N7-methyltransferase activity and reduced guanine N7-methylation of the 5' cap in vitro. Infection of myeloid cells with recombinant MHV harboring the nsp14-Y414A mutation (rMHVnsp14-Y414A) resulted in upregulated expression of IFN-I and ISG15 mainly via MDA5 signaling and in reduced viral replication compared to that of wild-type rMHV. rMHVnsp14-Y414A replicated to lower titers in livers and brains and exhibited an attenuated phenotype in mice. This attenuated phenotype was IFN-I dependent because the virulence of the rMHVnsp14-Y414A mutant was restored in Ifnar-/- mice. We further found that the comparable mutation (Y420A) in SARS-CoV-2 nsp14 (rSARS-CoV-2nsp14-Y420A) also significantly decreased N7-methyltransferase activity in vitro, and the mutant virus was attenuated in K18-human ACE2 transgenic mice. Moreover, infection with rSARS-CoV-2nsp14-Y420A conferred complete protection against subsequent and otherwise lethal SARS-CoV-2 infection in mice, indicating the vaccine potential of this mutant. IMPORTANCE Coronaviruses (CoVs), including SARS-CoV-2, the cause of COVID-19, use several strategies to evade the host innate immune responses. While the cap structure of RNA, including CoV RNA, is important for translation, previous studies indicate that the cap also contributes to viral evasion from the host immune response. In this study, we demonstrate that the N7-methylated cap structure of CoV RNA is pivotal for virus immunoevasion. Using recombinant MHV and SARS-CoV-2 encoding an inactive N7-methyltransferase, we demonstrate that these mutant viruses are highly attenuated in vivo and that attenuation is apparent at very early times after infection. Virulence is restored in mice lacking interferon signaling. Further, we show that infection with virus defective in N7-methylation protects mice from lethal SARS-CoV-2, suggesting that the N7-methylase might be a useful target in drug and vaccine development.

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