Effects of oral of administration of monoglycide laurate on virus load and inflammation in PEDV infected porcine.

To investigate the effect of monoglyceryl laurate (GML) against PEDV in vivo, the clinical signs, pathological changes, tissue viral load and cytokine levels of piglets were compared in different GML treatment groups and PEDV infected group. The diets of experimental groups were supplemented with different doses of GML (5g for A1, 10g for A2, 20g for A3) on day 1, 2, and 3 after PEDV challenge, and the virus challenge group (group C) and blank group (group B) were set as control. The results showed that compared with group C, groups As could reduce the mortality rate of piglets, among which the protection rates of groups A2 and A3 could reach 100%. The trend of weight loss of piglets was effectively slowed down and growth performance recovered in GML treated groups. GML reduced the pathological damage of intestinal tract and the viral load in intestine and mesenteric lymph nodes. The levels of IL-8 and TNF-α in the blood of group As were inhibited by GML in a dose-dependent manner when compared with group C. Our study suggests that GML has potential anti-PEDV effects in vivo.

Characterization and Evaluation of the Pathogenicity of a Natural Gene-Deleted Transmissible Gastroenteritis Virus in China

Porcine transmissible gastroenteritis virus is the major pathogen that causes fatal diarrhea in newborn piglets. In this study, a TGEV strain was isolated from the small intestine of diarrhea piglets in Sichuan Province, China, and designated SC2021. The complete genomic sequence of TGEV SC2021 was 28561 bp, revealing a new natural deletion TGEV strain. Based on phylogenetic analyses, TGEV SC2021 belonged to the Miller cluster and was closely related to CN strains. The newborn piglets orally challenged with TGEV SC2021 showed typical watery diarrhea. In addition, macro and micropathological changes in the lungs and intestines were observed. In conclusion, we isolated a new natural deletion virus strain and confirmed that the virus strain has high pathogenicity in newborn piglets. Moreover, macroscopic and microscopic lesions were observed in the lungs and intestines of all TGEV SC2021-infected piglets. In summary, we isolated a new natural deletion TGEV strain and demonstrated that the natural deletion strain showed high pathogenicity in newborn piglets. These data enrich the diversity of TGEV strains and help us to understand the genetic evolution and molecular pathogenesis of TGEV.

Establishment and application of SYBR Green I fluorescence quantitative RT-PCR method for detection of Porcine epidemic diarrhea virus

To develop a real-time fluorescent quantitative PCR method for rapid, accurate, sensitive and quantitative detection of porcine epidemic diarrhea virus (PEDV), according to the highly conserved nucleotide sequence of S gene reported by GenBank, a pair of PEDV S gene specific primers were designed, and a fluorescent quantitative RT-PCR detection method using SYBR Green I as the dye was established. The clinical samples suspected of PEDV infection were tested and compared with the results of ordinary RT-PCR. The results showed that the established standard curve of the SYBR Green I fluorescence quantitative RT-PCR method had a good linear relationship. The linear correlation coefficient R2=1, its amplification efficiency E=2.03, and the melting curve was a sharp single peak. The amplification of transmissible gastroenteritis virus, porcine parvovirus, classical swine fever virus, porcine reproductive and respiratory syndrome virus, porcine deltacoronavirus and porcine rotavirus was negative and had strong specificity. The lowest detection concentration of 1 x 101 copies/L was 100 times more sensitive than that of the ordinary RT-PCR method. The coefficient of variation of intra- and inter-assay repeatability test were both less than 2%, with good repeatability and stability. Comparing the test results of 36 clinical samples, the total coincidence rate with ordinary RT-PCR was 88.89%. The results show that the established real-time fluorescent quantitative RT-PCR detection method has strong specificity, good reproducibility, and high sensitivity, which is of great significance for the rapid and quantitative detection of PEDV.

Prone positioning improves ventilation-perfusion matching assessed by electrical impedance tomography in patients with ARDS: a prospective physiological study.

BACKGROUND: The physiological effects of prone ventilation in ARDS patients have been discussed for a long time but have not been fully elucidated. Electrical impedance tomography (EIT) has emerged as a tool for bedside monitoring of pulmonary ventilation and perfusion, allowing the opportunity to obtain data. This study aimed to investigate the effect of prone positioning (PP) on ventilation-perfusion matching by contrast-enhanced EIT in patients with ARDS. DESIGN: Monocenter prospective physiologic study. SETTING: University medical ICU. PATIENTS: Ten mechanically ventilated ARDS patients who underwent PP. INTERVENTIONS: We performed EIT evaluation at the initiation of PP, 3 h after PP initiation and the end of PP during the first PP session. MEASUREMENTS AND MAIN RESULTS: The regional distribution of ventilation and perfusion was analyzed based on EIT images and compared to the clinical variables regarding respiratory and hemodynamic status. Prolonged prone ventilation improved oxygenation in the ARDS patients. Based on EIT measurements, the distribution of ventilation was homogenized and dorsal lung ventilation was significantly improved by PP administration, while the effect of PP on lung perfusion was relatively mild, with increased dorsal lung perfusion observed. The ventilation-perfusion matched region was found to increase and correlate with the increased PaO2/FiO2 by PP, which was attributed mainly to reduced shunt in the lung. CONCLUSIONS: Prolonged prone ventilation increased dorsal ventilation and perfusion, which resulted in improved ventilation-perfusion matching and oxygenation. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04725227. Registered on 25 January 2021.

Potential of vibrational spectroscopy coupled with machine learning as a non-invasive diagnostic method for COVID-19.

BACKGROUND AND OBJECTIVE: Efforts to alleviate the ongoing coronavirus disease 2019 (COVID-19) crisis showed that rapid, sensitive, and large-scale screening is critical for controlling the current infection and that of ongoing pandemics. METHODS: Here, we explored the potential of vibrational spectroscopy coupled with machine learning to screen COVID-19 patients in its initial stage. Herein presented is a hybrid classification model called grey wolf optimized support vector machine (GWO-SVM). The proposed model was tested and comprehensively compared with other machine learning models via vibrational spectroscopic fingerprinting including saliva FTIR spectra dataset and serum Raman scattering spectra dataset. RESULTS: For the unknown vibrational spectra, the presented GWO-SVM model provided an accuracy, specificity and F1_score value of 0.9825, 0.9714 and 0.9778 for saliva FTIR spectra dataset, respectively, while an overall accuracy, specificity and F1_score value of 0.9085, 0.9552 and 0.9036 for serum Raman scattering spectra dataset, respectively, which showed superiority than those of state-of-the-art models, thereby suggesting the suitability of the GWO-SVM model to be adopted in a clinical setting for initial screening of COVID-19 patients. CONCLUSIONS: Prospectively, the presented vibrational spectroscopy based GWO-SVM model can facilitate in screening of COVID-19 patients and alleviate the medical service burden. Therefore, herein proof-of-concept results showed the chance of vibrational spectroscopy coupled with GWO-SVM model to help COVID-19 diagnosis and have the potential be further used for early screening of other infectious diseases.

Childhood trauma and suicide risk in schizophrenia inpatients: the sequential mediating roles of COVID-19 related psychological impact, sleep quality, and emotional distress (preprint)

Purpose The stressful global situation due to the COVID-19 pandemic has had a tremendous impact on mental health in hospitalized patients with schizophrenia. The mediating roles of psychological impacts related to COVID-19 sleep quality and emotional distress were investigated in the association between childhood trauma and suicide risk in inpatients with schizophrenia. Methods A total of 270 participants, including 125 in-patients with schizophrenia and 145 healthy controls (HCs) were enrolled. Childhood trauma, psychological impact related to COVID-19, global sleep quality, and psychological distress were measured using the Childhood Trauma Questionnaires (CTQ), Impact of Event Scale-Revised (IES-R), Pittsburgh Sleep Quality Index (PSQI), and Depression, Anxiety and Stress Scale (DASS-21), respectively. Results The total score and subtype scores of CTQ and the mean scores of the IES-R, PSQI, and DASS-21 in patients with schizophrenia were higher than those in HCs (all p < 0.001). Hierarchical linear regression analyses showed that a history of childhood trauma or schizophrenia was a good predictor of psychological impact, global sleep quality, and emotional distress (all p < 0.01). Moreover, the chain mediation model showed that the effect of childhood trauma on suicide risk in hospitalized patients with schizophrenia was totally sequentially mediated by thepsychological impact of COVID-19, sleep quality, and emotional distress. Conclusions It is important for clinicians to recognize the increased suicide risk associated with COVID-19-related psychological distress in patients with schizophrenia with a history of childhood trauma.

COVID-19 pandemic unmasking cardiovascular risk factors and non-communicable diseases among migrant workers: a cross-sectional study in Singapore.

OBJECTIVES: This study aims to report the prevalence of cardiovascular risk factors (CVRFs) and other non-communicable diseases among migrant workers in Singapore admitted for COVID-19 infection, to highlight disease burden and the need for changes in health screening and healthcare delivery in this unique population. SETTING: The study was conducted in the largest tertiary hospital in Singapore. DESIGN: Retrospective cross-sectional study. PARTICIPANTS: 883 migrant workers who had mild or asymptomatic COVID-19 infection admitted to three isolation wards between 6 April 2020 and 31 May 2020 were included in this study. OUTCOME MEASURES: The outcome measures were the prevalence of pre-existing and newly diagnosed comorbid conditions and the prevalence of CVRFs-diabetes mellitus, hypertension and hyperlipidaemia-and non-communicable diseases at the time of discharge. The OR of having specific CVRFs depending on country of origin was generated via multivariate logistic regression analysis. RESULTS: The median age of our study population was 45 years. 17.0% had pre-existing conditions and 25.9% received new diagnoses. Of the new diagnoses, 15.7% were acute medical conditions and 84.3% chronic medical conditions. The prevalence of CVRFs was higher in Southeast Asian and South Asian migrant workers compared with Chinese. The prevalence of non-communicable diseases on discharge was highest among Southeast Asians (49.4%). CONCLUSIONS: The COVID-19 outbreak in a large number of migrant workers in Singapore unmasked a significant disease burden among them, increasing stakeholders' interests in their welfare. Moving forward, system-level changes are necessary to deliver healthcare sustainably and effect improvements in migrant workers' health.

Inactivated Vaccines Against SARS-CoV-2: Neutralizing Antibody Titers in Vaccine Recipients.

Background: Although effective vaccines have been developed against coronavirus disease 2019 (COVID-19), the level of neutralizing antibodies (NAbs) induced after vaccination in the real world is still unknown. The aim of this work was to evaluate the level and persistence of NAbs induced by two inactivated COVID-19 vaccines in China. Methods: Serum samples were collected from 1,335 people aged 18 years and over who were vaccinated with an inactivated COVID-19 vaccine at Peking University People's Hospital from January 19 to June 23, 2021, for the detection of anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies. Results: The positive rate for NAbs against SARS-CoV-2 was 79-91% from the first month to the second month after the second vaccine dose. The gradual decline in positivity rate for NAb response was observed from 78% at 3 months post-vaccination to 0% at 12 months post-vaccination. When there was a 21-day interval between the two doses of vaccine, the NAb positivity rate was 0% 6 months after the second dose. NAb levels were significantly higher when the interval between two doses were 3-8 weeks than when it was 0-3 weeks (χ2 = 14.04, p < 0.001). There was a linear correlation between NAbs and IgG antibodies in 1,335 vaccinated patients. NAb levels decreased in 31 patients (81.6%) and increased in 7 patients (18.4%) over time in the series of 38 patients after the second vaccination. The NAb positivity rate was significantly higher in 18- to 40-year-old subjects than in 41- to 60-year-old subjects (t = -1.959, p < 0.01; t = 0.839, p < 0.01). Conclusion: The NAb positivity rate was the highest at the first and second month after the second dose of vaccine, and gradually decreased over time. With a 21-day interval between two doses of vaccine, neutralizing antibody levels persisted for only 6 months after the second dose of vaccine. Therefore, a third vaccine dose is recommended. Our results suggest that in cases in which NAbs cannot be detected, IgM/IgG antibodies can be detected instead. The level of NAbs produced after vaccination was affected by age but not by sex. Our results suggest that an interval of 21 to 56 days between shots is suitable for vaccination.

The Triangle Relationship Between Long Noncoding RNA, RIG-I-like Receptor Signaling Pathway, and Glycolysis.

Long noncoding RNA (LncRNA), a noncoding RNA over 200nt in length, can regulate glycolysis through metabolic pathways, glucose metabolizing enzymes, and epigenetic reprogramming. Upon viral infection, increased aerobic glycolysis providzes material and energy for viral replication. Mitochondrial antiviral signaling protein (MAVS) is the only protein-specified downstream of retinoic acid-inducible gene I (RIG-I) that bridges the gap between antiviral immunity and glycolysis. MAVS binding to RIG-I inhibits MAVS binding to Hexokinase (HK2), thereby impairing glycolysis, while excess lactate production inhibits MAVS and the downstream antiviral immune response, facilitating viral replication. LncRNAs can also regulate antiviral innate immunity by interacting with RIG-I and downstream signaling pathways and by regulating the expression of interferons and interferon-stimulated genes (ISGs). Altogether, we summarize the relationship between glycolysis, antiviral immunity, and lncRNAs and propose that lncRNAs interact with glycolysis and antiviral pathways, providing a new perspective for the future treatment against virus infection, including SARS-CoV-2.

Childhood Trauma and Mental Health Status in General Population: A Series Mediation Examination of Psychological Distress in COVID-19 Pandemic and Global Sleep Quality.

Background: Coronavirus-2019 (COVID-19) has been coexisting with humans for almost 2 years, consistently impacting people's daily life, medical environment, and mental health. This study aimed to test the series mediation model triggered by childhood trauma, in which perceived psychological impact of COVID-19 pandemic and sleep quality mediated the path sequentially and led to adverse mental health outcomes. Methods: A cross-sectional design involving 817 participants were enrolled via WeChat online survey. Participants completed questionnaires, including demographic features, the Childhood Trauma Questionnaire, Impact of Event Scale-Revised (IES-R) questionnaire, Pittsburgh Sleep Quality Index (PSQI) questionnaire, and Depression, Anxiety, and Stress Scale (DASS-21). Pearson correlations and hierarchical multiple linear regression were employed to examine the association of childhood trauma and psychological stress of COVID-19, sleep quality, and mental health status. In addition, a series mediate analysis was carried out to examine sequence mediating effects of psychological impact of COVID-19 and sleep quality between childhood trauma and mental health status. Results: The results showed that childhood trauma is positively and significantly related to psychological distress of COVID-19 pandemic, sleep quality, and mental health status (p < 0.05). Hierarchical multiple linear regression analysis shown that demographic features explained 4.4, 2.1, and 4.0% of the total variance in DASS-21, IES-R, and PSQI total scale scores, respectively. Adding childhood trauma significantly increased the model variance of DASS-21 (ΔR 2 = 0.129, F = 126.092, p = 0.000), IES-R (ΔR 2 = 0.062, F = 54.771, p = 0.000), and PSQI total scale scores (ΔR 2 = 0.055, F = 48.733, p = 0.000), respectively. Moreover, the series mediation model showed that the perceived impact of the COVID-19 pandemic and sleep quality were sequential mediators between childhood trauma and mental health status (proportion explained: 49.17%, p < 0.05). Conclusion: Amid the ravages of COVID-19, childhood trauma predicts poor mental health status, in part because of greater psychological impact related to COVID-19 and poorer global sleep quality. In order to improve mental health, future researchers should pay more attention to individuals with childhood trauma, for its association with greater stress related to life events and poorer sleep quality.

Establishment of a peptide-based enzyme-linked immunosorbent assay for detecting antibodies against PRRSV M protein.

BACKGROUND: Porcine reproductive and respiratory syndrome (PRRS) is one of the most economically devastating diseases affecting the swine industry globally. Evaluation of antibody responses and neutralizing antibody titers is the most effective method for vaccine evaluation. In this study, the B cell line epitopes of PRRSV M protein were predicted, and two peptide ELISA assays were established (M-A110-129 ELISA, M-A148-174 ELISA) to detect antibodies against PRRSV M protein. Field serum samples collected from pig farms were used to validate the peptide ELISA and compare it with an indirect immunofluorescence assay. RESULTS: The sensitivity and specificity of M-A110-129 ELISA and M-A148-174 ELISA were (111/125) 88.80%, (69/70) 98.57% and (122/125) 97.60%, (70/70) 100%, relative to indirect immunofluorescence assay. This peptide ELISA could detect antibodies against different genotypes of PRRSV including type 1 PRRSV, classical PRRSV, HP-PRRSV, and NADC30 like PRRSV, but not antibodies against other common swine viruses. The results of ROC analysis showed that the area under the curve (AUC) of the M-A110-129 ELISA and M-A148-174 ELISA were 0.967 and 0.996, respectively. Compared the concordance of results using two peptide ELISA assays, the IDEXX PRRSV X3 Ab ELISA and a virus neutralization test, were assessed using a series of 147 sera from pigs vaccinated with the NADC30-like PRRSV inactivated vaccine. The M-A148-174 ELISA had the best consistency, with a Cohen's kappa coefficient of 0.8772. The concordance rates of the Hipra PRRSV ELISA kit, M-A110-129 ELISA and M-A148-174 ELISA in the field seropositive detection results were 91.08, 86.32 and 95.35%, relative to indirect immunofluorescence assay. CONCLUSIONS: In summary, compared with M-A110-129 ELISA, the PRRSV M-A148-174 ELISA is of value for detecting antibodies against PRRSV and the evaluation of the NADC30-like PRRSV inactivated vaccine, but the advantage is insufficient in serological early diagnosis.

Association Between the Concentration and Rangeability of Cystatin C and Mortality of COVID-19 Patients With or Without Type 2 Diabetes Mellitus: A Retrospective Analysis.

Background: We investigated if the concentration and "rangeability" of cystatin C (CysC) influenced the prognosis of coronavirus disease 2019 (COVID-19) in patients suffering from, or not suffering from, type 2 diabetes mellitus (T2DM). Methods: A total of 675 T2DM patients and 572 non-T2DM patients were divided into "low" and "high" CysC groups and low and high CysC-rangeability groups according to serum CysC level and range of change of CysC level, respectively. Demographic characteristics, clinical data, and laboratory results of the four groups were analyzed. Results: COVID-19 patients with a high level and rangeability of CysC had more organ damage and a higher risk of death compared with those with a low level or low rangeability of CysC. Patients with a higher level and rangeability of CysC had more blood lymphocytes and higher levels of C-reactive protein, alanine aminotransferase, and aspartate aminotransferase. After adjustment for possible confounders, multivariate analysis revealed that CysC >0.93 mg/dL was significantly associated with the risk of heart failure (OR = 2.231, 95% CI: 1.125-5.312) and all-cause death (2.694, 1.161-6.252). CysC rangeability >0 was significantly associated with all-cause death (OR = 4.217, 95% CI: 1.953-9.106). These associations were stronger in patients suffering from T2DM than in those not suffering from T2DM. Conclusions: The level and rangeability of CysC may influence the prognosis of COVID-19. Special care and appropriate intervention should be undertaken in COVID-19 patients with an increased CysC level during hospitalization and follow-up, especially for those with T2DM.

Prevalence and Risk Factors of Mental Health Problems Among Healthcare Workers During the COVID-19 Pandemic: A Systematic Review and Meta-Analysis.

Objective: The purpose of this meta-analysis was to summarize the prevalence and risk factors of mental health problems among healthcare workers during the COVID-19 pandemic. Methods: We applied an optimized search strategy across the PubMed, EMBASE, Scopus, PsycINFO, and four Chinese databases, with hand searching supplemented to identify relevant surveys. Studies were eligible for inclusion if they were published in peer-reviewed literature and used a validated method to assess the prevalence and risk factors of mental health problems among healthcare workers during the COVID-19 pandemic. Heterogeneity was quantified using Q statistics and the I 2 statistics. The potential causes of heterogeneity were investigated using subgroup analysis and meta-regression analysis. Sensitivity analysis was performed to examine the robustness of the results. Results: We pooled and analyzed data from 20 studies comprising 10,886 healthcare workers. The prevalence of depression, anxiety, insomnia, post-traumatic stress symptoms, phobia, obsessive-compulsive symptoms, and somatization symptoms was 24.1, 28.6, 44.1, 25.6, 35.0, 16.2, and 10.7%, respectively. Female and nurses had a high prevalence of depression and anxiety. Frontline healthcare workers had a higher prevalence of anxiety and a lower prevalence of depression than the those in the second-line. Furthermore, the proportion of moderate-severe depression and anxiety is higher in the frontline. Additionally, four studies reported on risk factors of mental health problems. Conclusions: In this systematic review, healthcare workers have a relatively high prevalence of depression, anxiety, insomnia, post-traumatic stress symptoms, phobia, obsessive-compulsive symptoms, and somatization symptoms during the COVID-19 pandemic, and focus should be on the healthcare workers at high risk of mental problems. Mental health problems in healthcare workers should be taken seriously, and timely screening and appropriate intervention for the high-risk group are highly recommended. Systematic Review Registration:https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020179189.

Double lock of a potent human therapeutic monoclonal antibody against SARS-CoV-2.

Receptor recognition and subsequent membrane fusion are essential for the establishment of successful infection by SARS-CoV-2. Halting these steps can cure COVID-19. Here we have identified and characterized a potent human monoclonal antibody, HB27, that blocks SARS-CoV-2 attachment to its cellular receptor at sub-nM concentrations. Remarkably, HB27 can also prevent SARS-CoV-2 membrane fusion. Consequently, a single dose of HB27 conferred effective protection against SARS-CoV-2 in two established mouse models. Rhesus macaques showed no obvious adverse events when administrated with 10 times the effective dose of HB27. Cryo-EM studies on complex of SARS-CoV-2 trimeric S with HB27 Fab reveal that three Fab fragments work synergistically to occlude SARS-CoV-2 from binding to the ACE2 receptor. Binding of the antibody also restrains any further conformational changes of the receptor binding domain, possibly interfering with progression from the prefusion to the postfusion stage. These results suggest that HB27 is a promising candidate for immuno-therapies against COVID-19.

Conducting of Web-Based Workshops for Final Year Medical Students Preparing to Enter the Workforce During the COVID-19 Pandemic.

Medical students were temporarily removed from direct patient contact activities during the COVID-19 pandemic, shortening the duration of ward-based attachment programs. Web-based workshops were organized to equip final year medical students with necessary skills to start work in a general medicine setting. Topics included case-based scenarios reviewing patients with new complaints, medical documentation, and inter-professional communication. They were conducted using an online video conference platform and utilized polling platforms, small group discussions, and the "Chat" function to promote interactivity. Web-based learning enables delivery of useful contents without compromising interactivity and clinical applicability during the COVID-19 pandemic.

Comparison of Gray Values of Cone-beam Computed Tomography With Hounsfield Units of Multislice Computed Tomography Using a U-net Based Network (preprint)

Background：Dental departments generally employ cone-beam computed tomography (CBCT) instead of conventional computed tomography (CT), due to its lower price, smaller dosage, and high spatial resolution. During the corona virus disease 2019 (COVID-19) outbreak, CBCT is highly recommended to replace intraoral radiography because it greatly reduces the risk of exposure to salivary droplets. However, CBCT's inability to quantitatively measure tissue attenuation limits its application in differential diagnosis. Methods:We employed a U-Net based network to generate synthetic CT from dental CBCT. The deep neural network can be trained end-to-end to learn the complex mapping between CBCT and CT values. By the U-Net architecture, low-level and high-level features are both utilized to get fine detailed synthetic CT. We applied our method on the collected dataset contains 62 patients. Results:Experimental results on four metrics -- mean absolute error (MAE), root-mean-square error (RMSE), structural similarity index (SSIM), and peak-signal-to-noise ratio (PSNR) -- showed significant improvement of the synthetic CT compared to the original CBCT data. The MAE and RMSE improvement percentages are 64.44% and 66.44%.The MAE level of synthetic CT for most of the tissues are small enough to separate most important tissues,including dentin and cancellous bone, dentin and root canal，implants and cortical bone.Conclusions:CBCT and synthetic CT values can be used to distinguish different high-attenuation structures that are of interest to dentists. The application of CBCT assisted by this U-net based network in medical imaging of other parts of the body is promising.

Development of an inactivated vaccine candidate for SARS-CoV-2.

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in an unprecedented public health crisis. Because of the novelty of the virus, there are currently no SARS-CoV-2-specific treatments or vaccines available. Therefore, rapid development of effective vaccines against SARS-CoV-2 are urgently needed. Here, we developed a pilot-scale production of PiCoVacc, a purified inactivated SARS-CoV-2 virus vaccine candidate, which induced SARS-CoV-2-specific neutralizing antibodies in mice, rats, and nonhuman primates. These antibodies neutralized 10 representative SARS-CoV-2 strains, suggesting a possible broader neutralizing ability against other strains. Three immunizations using two different doses, 3 or 6 micrograms per dose, provided partial or complete protection in macaques against SARS-CoV-2 challenge, respectively, without observable antibody-dependent enhancement of infection. These data support the clinical development and testing of PiCoVacc for use in humans.