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2.
Int J Environ Res Public Health ; 19(11)2022 05 24.
Article in English | MEDLINE | ID: covidwho-1903381

ABSTRACT

The COVID-19 pandemic raises awareness of how the fatal spreading of infectious disease impacts economic, political, and cultural sectors, which causes social implications. Across the world, strategies aimed at quickly recognizing risk factors have also helped shape public health guidelines and direct resources; however, they are challenging to analyze and predict since those events still happen. This paper intends to invesitgate the association between air pollutants and COVID-19 confirmed cases using Deep Learning. We used Delhi, India, for daily confirmed cases and air pollutant data for the dataset. We used LSTM deep learning for training the combination of COVID-19 Confirmed Case and AQI parameters over the four different lag times of 1, 3, 7, and 14 days. The finding indicates that CO is the most excellent model compared with the others, having on average, 13 RMSE values. This was followed by pressure at 15, PM2.5 at 20, NO2 at 20, and O3 at 22 error rates.


Subject(s)
Air Pollutants , Air Pollution , COVID-19 , Deep Learning , Air Pollutants/analysis , Air Pollution/analysis , COVID-19/epidemiology , Humans , Pandemics , Particulate Matter/analysis
4.
J Virol Methods ; 307: 114564, 2022 Sep.
Article in English | MEDLINE | ID: covidwho-1878302

ABSTRACT

The COVID-19 pandemic caused by SARS-CoV-2 infections has led to excess deaths worldwide. Neutralizing antibodies (nAbs) against viral spike protein acquired from natural infections or vaccinations contribute to protection against new- and re-infections. Besides neutralization, antibody-mediated cellular cytotoxicity (ADCC) and phagocytosis (ADCP) are also important for viral clearance. However, due to the lack of convenient methods, the ADCC and ADCP responses elicited by viral infections or vaccinations remain to be explored. Here, we developed cell-based assays using target cells stably expressing SARS-CoV-2 spikes and Jurkat-NFAT-CD16a/CD32a effector cells for ADCC/ADCP measurements of monoclonal antibodies and human convalescent COVID-19 plasmas (HCPs). In control samples (n = 190), the specificity was 99.5% (95%CI: 98.4-100%) and 97.4% (95%CI: 95.1-99.6%) for the ADCC and ADCP assays, respectively. Among 87 COVID-19 HCPs, 83 (sensitivity: 95.4%, 95%CI: 91.0-99.8%) and 81 (sensitivity: 93.1%, 95%CI: 87.8-98.4%) showed detectable ADCC (titer range: 7.4-1721.6) and ADCP activities (titer range: 4-523.2). Notably, both ADCC and ADCP antibody titers positively correlated with the nAb titers in HCPs. In summary, we developed new tools for quantitative ADCC and ADCP analysis against SARS-CoV-2, which may facilitate further evaluations of Fc-mediated effector functions in preventing and treating against SARS-CoV-2.


Subject(s)
Antibody-Dependent Cell Cytotoxicity , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Antibodies, Neutralizing , Antibodies, Viral , COVID-19 , Humans , Immunoassay/methods , Pandemics , Phagocytosis , SARS-CoV-2/chemistry , SARS-CoV-2/metabolism , Spike Glycoprotein, Coronavirus/metabolism
5.
International Journal of Environmental Research and Public Health ; 19(11):6373, 2022.
Article in English | MDPI | ID: covidwho-1857816

ABSTRACT

The COVID-19 pandemic raises awareness of how the fatal spreading of infectious disease impacts economic, political, and cultural sectors, which causes social implications. Across the world, strategies aimed at quickly recognizing risk factors have also helped shape public health guidelines and direct resources;however, they are challenging to analyze and predict since those events still happen. This paper intends to invesitgate the association between air pollutants and COVID-19 confirmed cases using Deep Learning. We used Delhi, India, for daily confirmed cases and air pollutant data for the dataset. We used LSTM deep learning for training the combination of COVID-19 Confirmed Case and AQI parameters over the four different lag times of 1, 3, 7, and 14 days. The finding indicates that CO is the most excellent model compared with the others, having on average, 13 RMSE values. This was followed by pressure at 15, PM2.5 at 20, NO2 at 20, and O3 at 22 error rates.

6.
Nat Microbiol ; 7(5): 716-725, 2022 05.
Article in English | MEDLINE | ID: covidwho-1852420

ABSTRACT

Emerging SARS-CoV-2 variants continue to cause waves of new infections globally. Developing effective antivirals against SARS-CoV-2 and its variants is an urgent task. The main protease (Mpro) of SARS-CoV-2 is an attractive drug target because of its central role in viral replication and its conservation among variants. We herein report a series of potent α-ketoamide-containing Mpro inhibitors obtained using the Ugi four-component reaction. The prioritized compound, Y180, showed an IC50 of 8.1 nM against SARS-CoV-2 Mpro and had oral bioavailability of 92.9%, 31.9% and 85.7% in mice, rats and dogs, respectively. Y180 protected against wild-type SARS-CoV-2, B.1.1.7 (Alpha), B.1.617.1 (Kappa) and P.3 (Theta), with EC50 of 11.4, 20.3, 34.4 and 23.7 nM, respectively. Oral treatment with Y180 displayed a remarkable antiviral potency and substantially ameliorated the virus-induced tissue damage in both nasal turbinate and lung of B.1.1.7-infected K18-human ACE2 (K18-hACE2) transgenic mice. Therapeutic treatment with Y180 improved the survival of mice from 0 to 44.4% (P = 0.0086) upon B.1.617.1 infection in the lethal infection model. Importantly, Y180 was also highly effective against the B.1.1.529 (Omicron) variant both in vitro and in vivo. Overall, our study provides a promising lead compound for oral drug development against SARS-CoV-2.


Subject(s)
COVID-19 , SARS-CoV-2 , Angiotensin-Converting Enzyme 2 , Animals , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , COVID-19/drug therapy , Disease Models, Animal , Dogs , Humans , Mice , Rats
8.
Journal of Shandong University ; 58(3):58-61, 2020.
Article in Chinese | GIM | ID: covidwho-1813108

ABSTRACT

Objective To describe the diagnosis and treatment of a patient with severe novel coronavirus pneumonia, and to improve the understanding and management of clinicians on novel coronavirus pneumonia. Methods The onset, development, treatment and outcome of a patient with severe 2019 novel coronavirus pneumonia were retrospectively analyzed and relevant literatures were reviewed. Results At the beginning of the disease, the patient presented fever and dry cough, and later the disease progressed to dyspnea. Chest CT showed bilateral exudation of the lung. Lopinavir/ritonavir, IFN-a and immunoglobulin were given to the patient according to the expert group's opinion. The pneumonia was cured and the patient was discharged two weeks later. Conclusion Appropriate management strategies are effective on diagnosis and treatment of new coronavirus pneumonia.

9.
Cell Rep ; 38(12): 110558, 2022 03 22.
Article in English | MEDLINE | ID: covidwho-1797096

ABSTRACT

Mutations in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike receptor-binding domain (RBD) may alter viral host tropism and affect the activities of neutralizing antibodies. Here, we investigated 153 RBD mutants and 11 globally circulating variants of concern (VOCs) and variants of interest (VOIs) (including Omicron) for their antigenic changes and cross-species tropism in cells expressing 18 ACE2 orthologs. Several RBD mutations strengthened viral infectivity in cells expressing ACE2 orthologs of non-human animals, particularly those less susceptible to the ancestral strain. The mutations surrounding amino acids (aas) 439-448 and aa 484 are more likely to cause neutralization resistance. Strikingly, enhanced cross-species infection potential in the mouse and ferret, instead of the neutralization-escape scores of the mutations, account for the positive correlation with the cumulative prevalence of mutations in humans. These findings present insights for potential drivers of circulating SARS-CoV-2 variants and provide informative parameters for tracking and forecasting spreading mutations.


Subject(s)
COVID-19 , SARS-CoV-2 , Animals , Ferrets , Humans , Membrane Glycoproteins/metabolism , Mice , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus , Tropism , Viral Envelope Proteins
11.
Protein Cell ; 13(12): 920-939, 2022 12.
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.


Subject(s)
COVID-19 , SARS-CoV-2 , Animals , COVID-19/genetics , Macaca mulatta , SARS-CoV-2/genetics , Transcriptome
12.
Cell reports ; 2022.
Article in English | EuropePMC | ID: covidwho-1728589

ABSTRACT

Zhang et al. show in vitro cross-species infectivity and neutralization-escape characteristics of 153 SARS-CoV-2 RBD mutants and 11 globally circulating VOC/VOI variants. They reveal an association between enhanced cross-species infection potential and the current cumulative prevalence of mutations, which can inform surveillance and forecasting of SARS-CoV-2 spike mutations.

13.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-329405

ABSTRACT

Antibody therapeutics for the treatment of COVID-19 has been highly successful while faces a challenge of the recent emergence of the Omicron variant which escapes the majority of existing SARS-CoV-2 neutralizing antibodies (nAbs). Here, we successfully generated a panel of SARS-CoV-2/SARS-CoV cross-neutralizing antibodies by sequential immunization of the two pseudoviruses. Of which, nAbs X01, X10 and X17 showed broadly neutralizing breadths against most variants of concern (VOCs) and X17 was further identified as a Class 5 nAb with undiminished neutralization against the Omicron variant. Cryo-EM structures of three-antibody in complex with the spike proteins of prototyped SARS-CoV-2, Delta, Omicron and SARS-CoV defined three non-overlapping conserved epitopes on the receptor-binding domain (RBD). The triple antibody cocktail exhibited enhanced resistance to viral escape and effective protection against the infection of Beta variant in hamsters. Our finding will aid the development of both antibody therapeutics and broad vaccines against SARS-CoV-2 and emerging variants.

14.
Cell Discov ; 8(1): 17, 2022 Feb 15.
Article in English | MEDLINE | ID: covidwho-1692628

ABSTRACT

The continuous emergence of SARS-CoV-2 variants highlights the need of developing vaccines with broad protection. Here, according to the immune-escape capability and evolutionary convergence, the representative SARS-CoV-2 strains carrying the hotspot mutations were selected. Then, guided by structural and computational analyses, we present a mutation-integrated trimeric form of spike receptor-binding domain (mutI-tri-RBD) as a broadly protective vaccine candidate, which combined heterologous RBDs from different representative strains into a hybrid immunogen and integrated immune-escape hotspots into a single antigen. When compared with a homo-tri-RBD vaccine candidate in the stage of phase II trial, of which all three RBDs are derived from the SARS-CoV-2 prototype strain, mutI-tri-RBD induced significantly higher neutralizing antibody titers against the Delta and Beta variants, and maintained a similar immune response against the prototype strain. Pseudo-virus neutralization assay demonstrated that mutI-tri-RBD also induced broadly strong neutralizing activities against all tested 23 SARS-CoV-2 variants. The in vivo protective capability of mutI-tri-RBD was further validated in hACE2-transgenic mice challenged by the live virus, and the results showed that mutI-tri-RBD provided potent protection not only against the SARS-CoV-2 prototype strain but also against the Delta and Beta variants.

15.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-325173

ABSTRACT

Background: COVID-19 continues to spread globally and results in additional challenges for perioperative management in parturients. The purpose of this study was to determine the incidence and identify associated factors for neuraxial anaesthesia-related hypotension in COVDI-19 parturients during caesarean delivery. Methods: : We performed a multicenter case-control study at 3 medical institutions in Hubei province, China form 1th January to 30th May 2020. All ASA Physical Status II full termed pregnant women who received caesarean delivery under neuraxial anaesthesia were eligible for inclusion. The univariate analysis and binary logistic regression analysis were used to identified the independent predictors of neuraxial anaesthesia-related hypotension. Results: : Present study included 102 COVID-19 parturients. The incidence of neuraxial anaesthesia-related hypotension was 58%. Maternal abnormal lymphocyte count (OR = 3.41, p = 0.03), full stomach (OR = 3.22, p = 0.04), baseline heart rate (OR = 1.04, p = 0.03), experience of anaesthetist (OR = 0.86, p = 0.02) and surgeon (OR = 0.76, p = 0.03), and combined spinal-epidural anaesthesia technique (OR = 3.27, p = 0.02) were associated with neuraxial anaesthesia-related hypotension. The area under the receiver operating characteristic curve achieved 0.83 which was significantly higher than 0.5 (p < 0.001). And the sensitivity, specificity and percentage correct were 75%, 79% and 75%, respectively. The Hosmer-Lemeshow test showed a good calibration of the model (H = 2.01, DF = 8, p = 0.98). Conclusions: : Maternal abnormal lymphocyte count, full stomach, baseline heart rate, experience of anaesthetist and surgeon, and combined spinal-epidural anaesthesia technique were identified as the independent predictors of neuraxial anaesthesia-related hypotension.

16.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-325080

ABSTRACT

Background: Compared with Severe Acute Respiratory Syndrome(SARS) and Middle East Respiratory Syndrome(MESR), Corona Virus Disease 2019(COVID-19) spread more rapidly and widely. The population was generally susceptible. However, reports on pregnant women infected with SARS-CoV-2 were very limited. By sharing the clinical characteristics, treatments and outcomes of 18 patients with COVID-19 during late pregnancy, we hoped to provide some references for obstetric treatment and management. Methods: : A total of 18 patients with COVID-19 treated in Renmin Hospital of Wuhan University were collected. The epidemiological characteristics, clinical manifestations, laboratory tests, chest CT and pregnancy outcomes were performed for analysis. Results: : 1 . 18 cases of late pregnancy infected with SARS-CoV-2 pneumonia were delivered at 35 + 5 weeks to 41 weeks. According to the clinical classification of COVID-19, 1 case was mild type, 16 cases were ordinary type, and 1 case was severe type. 2 . According to Imaging examinations: 15 (83%) cases showed unilateral or bilateral pneumonia, 2 (11%) cases had pulmonary infection with pleural effusion, and 1 (6%) case had no abnormal imaging changes. 8 (44%) cases were positive and 10 (56%) cases were negative for nasopharyngeal-swab tests of SARS-CoV-2. 3. Among the 18 newborns, there were 3 (17%) premature infants, 1 (6%) case of mild asphyxia, 5 (28%) cases of bacterial pneumonia, 1 (6%) case of gastrointestinal bleeding, 1 (6%) case of necrotizing enteritis, 2 (11%) cases of hyperbilirubinemia and 1 (6%) case of diarrhea. All the newborns were negative for the first throat swab test of SARS-CoV-2 after birth. 4. Follow-up to Mar 7, 2020, no maternal and neonatal deaths occurred. Conclusions: : The majority of patients in late term pregnancy with COVID-19 were of ordinary type, and they less likely developed into critical pneumonia after early isolation and antiviral treatment. Vertical transmission of SARS-CoV-2 was not detected, but the proportion of neonatal bacterial pneumonia was higher than other neonatal diseases in newborns.

17.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-324533

ABSTRACT

SARS-CoV-2 infection causes complicated clinic 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 tissues/organs examined, 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. Neuronal receptor NRP1 expression showed a significant induction by SARS-CoV-2 in cerebral cortex, which might be responsible for a higher infectivity and consequent inflammatory response. 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.

18.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-323568

ABSTRACT

Background: There is limited information on the difference in epidemiology, clinical characteristics and outcomes of the initial outbreak of the coronavirus disease (COVID-19) in Wuhan (the epicenter) and Sichuan (the peripheral area) in the early phase of the COVID-19 pandemic. This study was conducted to investigate the differences in the epidemiological and clinical characteristics of patients with COVID-19 between the epicenter and peripheral areas of pandemic and thereby generate information that would be potentially helpful in formulating clinical practice recommendations to tackle the COVID-19 pandemic. Methods: The Sichuan & Wuhan Collaboration Research Group for COVID-19 established two retrospective cohorts that separately reflect the epicenter and peripheral area during the early pandemic. The epidemiology, clinical characteristics and outcomes of patients in the two groups were compared. Multivariate regression analyses were used to estimate the adjusted odds ratios (aOR) with regard to the outcomes. Results: The Wuhan (epicenter) cohort included 710 randomly selected patients, and the peripheral (Sichuan) cohort included 474 consecutive patients. A higher proportion of patients from the periphery had upper airway symptoms, whereas a lower proportion of patients in the epicenter had lower airway symptoms and comorbidities. Patients in the epicenter had a higher risk of death (aOR=7.64), intensive care unit (ICU) admission (aOR=1.66), delayed time from illness onset to hospital and ICU admission (aOR=6.29 and aOR=8.03, respectively), and prolonged duration of viral shedding (aOR=1.64). Conclusions: The worse outcomes in the epicenter could be explained by the prolonged time from illness onset to hospital and ICU admission. This could potentially have been associated with elevated systemic inflammation secondary to organ dysfunction and prolonged duration of virus shedding independent of age and comorbidities. Thus, early supportive care could achieve better clinical outcomes.

19.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-319516

ABSTRACT

Objective: Novel coronavirus (nCoV, SARS-CoV-2) infection becomes a world-wide epidemic which has complicated and diversified symptoms, but no special treatment. In this study, diagnosis and treatment of family clustering nCoV infection were analyzed. Methods: : The Sichuan Suining Central Hospital received 11 patients with confirmed nCoV virus infection from 4 families during January 23 rd , 2020 to February 20 th , 2020. Their clinical symptoms, treatment conditions and changes of disease state were reviewed in the present study. Results: In all 4 families, there were 1-2 members in each family who had contact with epidemic disease. Clinical manifestations were: 3 cases had debilitation only, 1 case had cough only, 1 case had diarrhea (a child patient of four years old), 5 cases had fever and cough, and 1 case had blood-stained sputum. According to image changes, no image change was observed in 1 child patient. Multiple focal ground-glass opacities were detected from 2 patients and multiple patchy shadows were observed from 8 patients, especially in lung periphery. Complications with basic diseases: there were hypertension in 3 cases, diabetes in 2 cases, and hypertension and diabetes in 1 case. Moreover, there’s one patient who had rheumatic heart disease and received mitral and aortic valve replacement 2 years ago. There’s another one who had depression and suicidal tendency. All 11 cases divided into mild type (1 child patient), moderate type (8 patients), severe type (1 patient) and critical type (1 patient). Treatment: the mild child patient (4 years old) was administrated with 2.75ml lopinavir / ritonavir oral liquid (twice per day) and intravenous drip of 0.17g ribavirin injection (1ml: 0.1g*10pcs/box) every 12h for one week. Meanwhile, the child was asked to take azithromycin orally. 7 moderate patients were treated with intravenous drip of 0.5g ribavirin injection (1ml: 0.1g*10pcs/box) every 12h (twice per day) and two pieces of lopinavir/ritonavior (twice per day) for 7-10 days. In the same time, patients were given with reasonable amount of antibiotics by oral or intravenous drip. 1 severe patient and 1 critical patent were treated with 5,000,000 U recombinant human interferon α2b injection (3,000,000 U/pc) and aerosol inhalation of 2ml sterile water for injection (5ml*50 pcs/ box), twice per day. Besides, they took 2 pieces of lopinavir/ritonavior, twice per day. The whole treatment program lasted for 6-12 days, accompanied with appropriate amount of intravenous drip of antibiotics. The critical patient was also provided with mechanical ventilation. During the treatment, severe and critical patients were treated by resochin for 4-5 days for evident respiratory symptoms. One moderate patient was treated with 2 pieces of lopinavir/ritonavior, twice per day. In the same time, it was administrated by intravenous drip of antibiotics. However, resochin treatment was applied for positive novel coronavirus nucleic acid of respiratory sputum specimen after 11 days of treatment. Discharge: After treatment, patients with body temperatures of all patients recovered to normal level, and respiratory symptoms and digestive tract symptoms relieved significantly, significant coefficient of exudative lesion at lung according to chest CT and negative novel coronavirus nucleic acid of continuous two respiratory sputum specimens (sampling interval was at least 1 day) were allowed to be discharged. Adverse reactions: 4 patients had loose stools and abdominal discomfort, and another 2 cases had diarrhea. Conclusions: : SARS-CoV-2 infection have complicated and diversified symptoms, which shall be identified according to epidemic history and novel coronavirus nucleic acid test. In particular, the whole family in which there’s a patient with confirmed SARS-CoV-2 shall be isolated for screening in addition to the patient. The lopinavir/ritonavior administration combined with ribavirin or recombinant Human Interferon (RHI) α2b is effective, accompanied with mild adverse reaction. If lopinavir/ritonavior administration and / or combined with ribavirin and RHI α2b is invalid, adding resochin might be effective.

20.
EuropePMC;
Preprint in English | EuropePMC | ID: ppcovidwho-327136

ABSTRACT

The widespread SARS-CoV-2 in humans results in the continuous emergence of new variants. Recently emerged Omicron variant with multiple spike mutations sharply increases the risk of breakthrough infection or reinfection, highlighting the urgent need for new vaccines with broad-spectrum antigenic coverage. Using inter-lineage chimera and mutation patch strategies, we engineered a recombinant monomeric spike variant (STFK1628x), which showed high immunogenicity and mutually complementary antigenicity to its prototypic form (STFK). In hamsters, a bivalent vaccine comprised of STFK and STFK1628x elicited high titers of broad-spectrum antibodies to neutralize all 14 circulating SARS-CoV-2 variants, including Omicron;and fully protected vaccinees from intranasal SARS-CoV-2 challenges of either the ancestral strain or immune-evasive Beta variant. Strikingly, the vaccination of hamsters with the bivalent vaccine completely blocked the within-cage virus transmission to unvaccinated sentinels, for either the ancestral SARS-CoV-2 or Beta variant. Thus, our study provides new insights and antigen candidates for developing next-generation COVID-19 vaccines.

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