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1.
Indian J Med Microbiol ; 44: 100371, 2023.
Article in English | MEDLINE | ID: covidwho-2314779

ABSTRACT

PURPOSE: Infection due to SARS-CoV-2 shows wide spectrum of disease from asymptomatic to severe disease and death. Coinfection of SARS-CoV-2 with other respiratory pathogens may affect the severity of disease and its outcome. Identification of other respiratory pathogens may help to initiate proper management and avoid unnecessary complications. MATERIALS AND METHODS: Total 250 SARS-COV-2 positive patients admitted in S.M.S hospitalwere included in study. Throat and nasopharyngeal swabs samples were collected in Viral Transport Medium (VTM) and nucleic acid extraction was done by automated EasyMag extractor and tested for 20 respiratory viruses and two bacteria by real time PCR. RESULTS: Out of 250 SARS CoV2 positive samples, 176 (70%) were positive for other respiratory pathogens also. The highest co-infection was due to HCoVOC43 (32.8%) virus followed by bacterial co-infection with S. pneumoniae (14.8%). Six (2.4%) patients with co-infection were on ventilator with age >65yr and three (1.2%) died during treatment. All three cases were found to have other co-morbid diseases like; asthma, Parkinson's and hypertension. CONCLUSION: High number of patients were found to have coinfection with other viruses and bacteria, timely identification and providing specific treatment to these patients can help improve outcome.


Subject(s)
Bacterial Infections , COVID-19 , Coinfection , Viruses , Humans , SARS-CoV-2 , COVID-19/epidemiology , Coinfection/epidemiology , India/epidemiology , Streptococcus pneumoniae , Bacteria
2.
Br J Neurosurg ; : 1-6, 2021 Sep 21.
Article in English | MEDLINE | ID: covidwho-2254161

ABSTRACT

BACKGROUND: The COVID-19 pandemic has compelled a global shift in healthcare service delivery towards virtualisation, including in Neurosurgery. Our study aims to elucidate the patient and neurosurgeon perceptions of virtual neurosurgery consultations (VNCs) and formulate a guidance algorithm based on our experience. METHODS: Between June 2020 and December 2020, we prospectively surveyed patients and neurosurgeons following their VNCs using a 10-item survey (four qualitative and six five-point Likert scale questions). Non-parametric hypothesis testing and grounded coding with inter-coder agreement was used to analyse quantitative and qualitative data, respectively. RESULTS: 106 patients and 10 neurosurgeons completed the survey. Wilcoxon rank-sum test revealed a statistically significant difference between the neurosurgeon and patient responses (p < 0.001). Patients perceived VNCs benefits to be enhanced efficiency (n = 142) and communication (28); and VNCs drawbacks as safety (46), technological (32), and administration (15) issues. Neurosurgeons perceived VNCs benefits to be enhanced efficiency (13), reduced COVID-19 exposure (2); and VNCs drawbacks as examination practicality (14), technological (6), and concerns for patients (6). Neurosurgeons perceived the relative indications for VNCs as postoperative follow-up clinics, and scan result discussions; and relative contraindications as neuro-oncology, new patients, and patients with worsening neurological symptoms. CONCLUSIONS: Our mirror-survey study provides preliminary evidence that VNCs render increased efficiency, communication, and safety in the current COVID-19 era. Going forward, we believe that further improvements in technology and administration are necessary, greater neurosurgeon appreciation of the patient-perceived benefits of VNCs is required, and neurosurgeons are to exercise clinical discernment on when to use VNCs.Key PointsWhat are the perceptions of patient and consultant neurosurgeons towards virtual neurosurgery consultations (VNCs)?Patient-perceived benefits of VNCs: enhanced efficiency/communication; VNC drawbacks: safety, technological, and administration issues. Neurosurgeon-perceived VNCs benefits of VNCs: enhanced efficiency, reduced COVID-19 exposure; VNC drawbacks: examination practicality, technological, and concerns for patients.Post-operative reviews and scan result discussions are perceived relative indications for VNCs; whereas new patient consultations, neuro-oncology and patients with new-onset neurological deficits are perceived relative contraindications for VNCs.Improvement in technology and administration is necessary; greater neurosurgeon appreciation of patient-perceived VNCs benefits is required, and neurosurgeons are to exercise clinical discernment on when to use VNCs.

3.
J Med Virol ; 95(4): e28687, 2023 04.
Article in English | MEDLINE | ID: covidwho-2288701

ABSTRACT

Measles virus (MeV) has been an excellent vector platform for delivering vaccines against many pathogens because of its high safety and efficacy, and induction of long-lived immunity. Early in the COVID-19 pandemic, a recombinant MeV (rMeV) expressing the prefusion full-length spike protein stabilized by two prolines (TMV-083) was developed and tested in phase 1 and 1/2 clinical trials but was discontinued because of insufficient immunogenicity and a low seroconversion rate in adults. Here, we compared the immunogenicity of rMeV expressing a soluble prefusion spike (preS) protein stabilized by two prolines (rMeV-preS-2P) with a rMeV expressing a soluble preS protein stabilized by six prolines (rMeV-preS-6P). We found that rMeV-preS-6P expressed approximately five times more preS than rMeV-preS-2P in cell culture. Importantly, rMeV-preS-6P induced 30-60 and six times more serum immunoglobulin G and neutralizing antibody than rMeV-preS-2P, respectively, in IFNAR-/- mice. IFNAR-/- mice immunized with rMeV-preS-6P were completely protected from challenge with a mouse-adapted SARS-CoV-2, whereas those immunized with rMeV-preS-2P were partially protected. In addition, hamsters immunized with rMeV-preS-6P were completely protected from the challenge with a Delta variant of SARS-CoV-2. Our results demonstrate that rMeV-preS-6P is significantly more efficacious than rMeV-preS-2P, highlighting the value of using preS-6P as the antigen for developing vaccines against SARS-CoV-2.


Subject(s)
COVID-19 , Cricetinae , Animals , Humans , Mice , COVID-19/prevention & control , SARS-CoV-2/genetics , COVID-19 Vaccines , Pandemics , Spike Glycoprotein, Coronavirus/genetics , Antibodies, Neutralizing , Measles virus/genetics , Proline , Antibodies, Viral
4.
Indian J Tuberc ; 69(4): 558-564, 2022 Oct.
Article in English | MEDLINE | ID: covidwho-2281162

ABSTRACT

BACKGROUND: Non-adherence is major factor in failure of any drug regimen. The significance of non-adherence is so much that WHO states that increasing the effectiveness of Adherence Interventions may have far greater impact on health of population than any improvement in specific medical treatments. Incidence of non-adherence to Anti Tubercular Treatment (ATT) usually ranges from 8.4% to 55.8%. This study aims to find out the reasons of Non-adherence to ATT in patients receiving anti-tubercular treatment at DIRECTLY OBSERVED TREATMENT SHORTCOURSE (DOTS) Centre at District Tuberculosis Centre (DTC), Kalibadi, Raipur during COVID-19 pandemic. METHODS: A cross sectional study was conducted at Department of Pharmacology, Pt. JNM Medical College and DTC Kalibadi Raipur. 55 Patients taking ATT fulfilling inclusion and exclusion criteria were interviewed using structured questionnaire. The data obtained was analysed to know causes of non-adherence. RESULTS: Study was carried out between March & April 2020. In our study, 80% subjects were male and 20% were female. The main reasons for Non-adherence were Side-effects of drug in 36% cases, missing medication intentionally in 34% cases, lack of encouragement by family members in 32% cases, patient's unawareness of consequences of skipping medication in 25% cases, unaware of treatment duration in 22%, not feeling any change, forgetting to take medication, and burden of concomitant medication besides ATT, each in 20% cases, 13% cases had difficulty in procuring medication due to lockdown, 5% cases did not go to collect their medicine due to fear of contracting COVID-19 infection. CONCLUSIONS: Our study shows reasons for Non-adherence are multi-factorial with drug side -effects & intentionally skipping medication being major factors.


Subject(s)
COVID-19 Drug Treatment , Drug-Related Side Effects and Adverse Reactions , Humans , Female , Male , Cross-Sectional Studies , Pandemics , Communicable Disease Control , Duration of Therapy
5.
QJM ; 2022 Feb 16.
Article in English | MEDLINE | ID: covidwho-2280900
6.
Front Med (Lausanne) ; 9: 888408, 2022.
Article in English | MEDLINE | ID: covidwho-2065554

ABSTRACT

Background: Omicron, a new variant of Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV-2), was first detected in November 2021. This was believed to be highly transmissible and was reported to evade immunity. As a result, an urgent need was felt to screen all positive samples so as to rapidly identify Omicron cases and isolate them to prevent the spread of infection. Genomic surveillance of SARS-CoV-2 was planned to correlate disease severity with the genomic profile. Methods: All the SARS-CoV-2 positive cases detected in the state of Rajasthan were sent to our Lab. Samples received from 24 November 2021 to 4 January 2022 were selected for Next-Generation Sequencing (NGS). Processing was done as per protocol on the Ion Torrent S5 System for 1,210 samples and bioinformatics analysis was done. Results: Among the 1,210 samples tested, 762 (62.9%) were Delta/Delta-like and other lineages, 291 (24%) were Omicron, and 157 (12.9%) were invalid or repeat samples. Within a month, the proportion of Delta and other variants was reversed, 6% Omicron became 81%, and Delta and other variants became 19%, initially all Omicron cases were seen in international travelers and their contacts but soon community transmission was seen. The majority of patients with Omicron were asymptomatic (56.7%) or had mild disease (33%), 9.2% had moderate symptoms, and two (0.7%) had severe disease requiring hospitalization, of which one (0.3%) died and the rest were (99.7%) recovered. History of vaccination was seen in 81.1%, of the previous infection in 43.2% of cases. Among the Omicron cases, BA.1 (62.8%) was the predominant lineage followed by BA.2 (23.7%) and B.1.529 (13.4%), rising trends were seen initially for BA.1 and later for BA.2 also. Although 8.9% of patients with Delta lineage during that period were hospitalized, 7.2% required oxygen, and 0.9% died. To conclude, the community spread of Omicron occurred in a short time and became the predominant circulating variant; BA.1 was the predominant lineage detected. Most of the cases with Omicron were asymptomatic or had mild disease, and the mortality rate was very low as compared to Delta and other lineages.

7.
Proc Natl Acad Sci U S A ; 119(35): e2110105119, 2022 08 30.
Article in English | MEDLINE | ID: covidwho-2000999

ABSTRACT

The spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the main target for neutralizing antibodies (NAbs). The S protein trimer is anchored in the virion membrane in its prefusion (preS) but metastable form. The preS protein has been stabilized by introducing two or six proline substitutions, to generate stabilized, soluble 2P or HexaPro (6P) preS proteins. Currently, it is not known which form is the most immunogenic. Here, we generated recombinant vesicular stomatitis virus (rVSV) expressing preS-2P, preS-HexaPro, and native full-length S, and compared their immunogenicity in mice and hamsters. The rVSV-preS-HexaPro produced and secreted significantly more preS protein compared to rVSV-preS-2P. Importantly, rVSV-preS-HexaPro triggered significantly more preS-specific serum IgG antibody than rVSV-preS-2P in both mice and hamsters. Antibodies induced by preS-HexaPro neutralized the B.1.1.7, B.1.351, P.1, B.1.427, and B.1.617.2 variants approximately two to four times better than those induced by preS-2P. Furthermore, preS-HexaPro induced a more robust Th1-biased cellular immune response than preS-2P. A single dose (104 pfu) immunization with rVSV-preS-HexaPro and rVSV-preS-2P provided complete protection against challenge with mouse-adapted SARS-CoV-2 and B.1.617.2 variant, whereas rVSV-S only conferred partial protection. When the immunization dose was lowered to 103 pfu, rVSV-preS-HexaPro induced two- to sixfold higher antibody responses than rVSV-preS-2P in hamsters. In addition, rVSV-preS-HexaPro conferred 70% protection against lung infection whereas only 30% protection was observed in the rVSV-preS-2P. Collectively, our data demonstrate that both preS-2P and preS-HexaPro are highly efficacious but preS-HexaPro is more immunogenic and protective, highlighting the advantages of using preS-HexaPro in the next generation of SARS-CoV-2 vaccines.


Subject(s)
Proline , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Vaccine Development , Vesicular Stomatitis , Viral Vaccines , Animals , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/genetics , COVID-19/immunology , COVID-19/prevention & control , COVID-19/virology , COVID-19 Vaccines/immunology , Cricetinae , Humans , Mice , Proline/immunology , SARS-CoV-2/genetics , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/immunology , Vesicular Stomatitis/immunology , Vesicular Stomatitis/prevention & control , Vesicular Stomatitis/virology , Vesiculovirus/immunology , Viral Proteins/immunology , Viral Vaccines/immunology
8.
J Photochem Photobiol B ; 234: 112545, 2022 Sep.
Article in English | MEDLINE | ID: covidwho-1996389

ABSTRACT

Clinical diagnostics for SARS-CoV-2 infection usually comprises the sampling of throat or nasopharyngeal swabs that are invasive and create patient discomfort. Hence, saliva is attempted as a sample of choice for the management of COVID-19 outbreaks that cripples the global healthcare system. Although limited by the risk of eliciting false-negative and positive results, tedious test procedures, requirement of specialized laboratories, and expensive reagents, nucleic acid-based tests remain the gold standard for COVID-19 diagnostics. However, genetic diversity of the virus due to rapid mutations limits the efficiency of nucleic acid-based tests. Herein, we have demonstrated the simplest screening modality based on label-free surface enhanced Raman scattering (LF-SERS) for scrutinizing the SARS-CoV-2-mediated molecular-level changes of the saliva samples among healthy, COVID-19 infected and COVID-19 recovered subjects. Moreover, our LF-SERS technique enabled to differentiate the three classes of corona virus spike protein derived from SARS-CoV-2, SARS-CoV and MERS-CoV. Raman spectral data was further decoded, segregated and effectively managed with the aid of machine learning algorithms. The classification models built upon biochemical signature-based discrimination method of the COVID-19 condition from the patient saliva ensured high accuracy, specificity, and sensitivity. The trained support vector machine (SVM) classifier achieved a prediction accuracy of 95% and F1-score of 94.73%, and 95.28% for healthy and COVID-19 infected patients respectively. The current approach not only differentiate SARS-CoV-2 infection with healthy controls but also predicted a distinct fingerprint for different stages of patient recovery. Employing portable hand-held Raman spectrophotometer as the instrument and saliva as the sample of choice will guarantee a rapid and non-invasive diagnostic strategy to warrant or assure patient comfort and large-scale population screening for SARS-CoV-2 infection and monitoring the recovery process.


Subject(s)
COVID-19 , Nucleic Acids , Artificial Intelligence , COVID-19/diagnosis , COVID-19 Testing , Delivery of Health Care , Humans , SARS-CoV-2 , Saliva
9.
Proc Natl Acad Sci U S A ; 119(33): e2201616119, 2022 08 16.
Article in English | MEDLINE | ID: covidwho-1960617

ABSTRACT

With the rapid increase in SARS-CoV-2 cases in children, a safe and effective vaccine for this population is urgently needed. The MMR (measles/mumps/rubella) vaccine has been one of the safest and most effective human vaccines used in infants and children since the 1960s. Here, we developed live attenuated recombinant mumps virus (rMuV)-based SARS-CoV-2 vaccine candidates using the MuV Jeryl Lynn (JL2) vaccine strain backbone. The soluble prefusion SARS-CoV-2 spike protein (preS) gene, stablized by two prolines (preS-2P) or six prolines (preS-6P), was inserted into the MuV genome at the P-M or F-SH gene junctions in the MuV genome. preS-6P was more efficiently expressed than preS-2P, and preS-6P expression from the P-M gene junction was more efficient than from the F-SH gene junction. In mice, the rMuV-preS-6P vaccine was more immunogenic than the rMuV-preS-2P vaccine, eliciting stronger neutralizing antibodies and mucosal immunity. Sera raised in response to the rMuV-preS-6P vaccine neutralized SARS-CoV-2 variants of concern, including the Delta variant equivalently. Intranasal and/or subcutaneous immunization of IFNAR1-/- mice and golden Syrian hamsters with the rMuV-preS-6P vaccine induced high levels of neutralizing antibodies, mucosal immunoglobulin A antibody, and T cell immune responses, and were completely protected from challenge by both SARS-CoV-2 USA-WA1/2020 and Delta variants. Therefore, rMuV-preS-6P is a highly promising COVID-19 vaccine candidate, warranting further development as a tetravalent MMR vaccine, which may include protection against SARS-CoV-2.


Subject(s)
COVID-19 Vaccines , COVID-19 , Measles-Mumps-Rubella Vaccine , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Vaccine Efficacy , Animals , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , COVID-19/prevention & control , COVID-19 Vaccines/genetics , COVID-19 Vaccines/immunology , Immunogenicity, Vaccine , Measles-Mumps-Rubella Vaccine/genetics , Measles-Mumps-Rubella Vaccine/immunology , Mesocricetus , Mice , Mumps virus/genetics , Mumps virus/immunology , Proline/genetics , SARS-CoV-2/genetics , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/immunology , Vaccines, Attenuated/genetics , Vaccines, Attenuated/immunology
10.
Recent Pat Biotechnol ; 16(2): 82-101, 2022.
Article in English | MEDLINE | ID: covidwho-1902817

ABSTRACT

SARS-CoV-2 belongs to the Coronaviridae family of coronaviruses. This novel virus has predominantly affected a vast world population and was declared a pandemic outbreak. The clinical and scientific communities strive to develop and validate potential treatments and therapeutic measures. The comparative study of existing synthetic drugs, evaluation of safety aspects, and the devel opment of novel vaccines can be efficiently achieved by using suitable animal models of primary infection and validating translational findings in human cell lines and tissues. The current paper explores varied animal and cell/tissue models employed and recapitulate various critical issues of ailment manifestation in humans to develop and evaluate novel therapeutic countermeasures and even include some novel patent developed in this regard.


Subject(s)
COVID-19 , Middle East Respiratory Syndrome Coronavirus , Animals , Models, Theoretical , Patents as Topic , SARS-CoV-2
11.
Disaster Med Public Health Prep ; : 1-7, 2022 Apr 01.
Article in English | MEDLINE | ID: covidwho-1860240

ABSTRACT

In the state of Karnataka, India, the first case of coronavirus disease (COVID-19) was diagnosed on March 9, 2020. As stated by the WHO, around 15% of COVID-19 patients require treatment in the Intensive Care Unit (ICU). Keeping this in mind, along with the increase in COVID-19 patients in Karnataka, it was predicted that the prevailing general wards and ICUs would be overburdened with the added non-COVID-19 diseases and infirmities. Hence, it was decided to set up a separate infrastructure to reduce the chances of transmission among the patients within the hospital. Thus, the board at SDM College of Medical Sciences & Hospital, Dharwad, Karnataka, took the responsibility to establish a fully equipped 100-bedded hospital in its premise as part of the national and state services to combat the outbreak. The aim of the study was to establish an isolated, fully functional hospital, equipped with all necessary diagnostic and critical care facilities to treat patients diagnosed with COVID-19 in North Karnataka, India.

12.
Sleep Vigil ; 6(1): 253-254, 2022.
Article in English | MEDLINE | ID: covidwho-1773041
13.
Sci Rep ; 12(1): 810, 2022 01 17.
Article in English | MEDLINE | ID: covidwho-1636259

ABSTRACT

The COVID-19 pandemic has revealed the power of internet disinformation in influencing global health. The deluge of information travels faster than the epidemic itself and is a threat to the health of millions across the globe. Health apps need to leverage machine learning for delivering the right information while constantly learning misinformation trends and deliver these effectively in vernacular languages in order to combat the infodemic at the grassroot levels in the general public. Our application, WashKaro, is a multi-pronged intervention that uses conversational Artificial Intelligence (AI), machine translation, and natural language processing to combat misinformation (NLP). WashKaro uses AI to provide accurate information matched against WHO recommendations and delivered in an understandable format in local languages. The primary aim of this study was to assess the use of neural models for text summarization and machine learning for delivering WHO matched COVID-19 information to mitigate the misinfodemic. The secondary aim of this study was to develop a symptom assessment tool and segmentation insights for improving the delivery of information. A total of 5026 people downloaded the app during the study window; among those, 1545 were actively engaged users. Our study shows that 3.4 times more females engaged with the App in Hindi as compared to males, the relevance of AI-filtered news content doubled within 45 days of continuous machine learning, and the prudence of integrated AI chatbot "Satya" increased thus proving the usefulness of a mHealth platform to mitigate health misinformation. We conclude that a machine learning application delivering bite-sized vernacular audios and conversational AI is a practical approach to mitigate health misinformation.


Subject(s)
COVID-19/epidemiology , Disinformation , Machine Learning , Natural Language Processing , Pandemics , Female , Global Health , Humans , Male
14.
Am J Manag Care ; 27(10): e339-e342, 2021 10 01.
Article in English | MEDLINE | ID: covidwho-1535193

ABSTRACT

OBJECTIVES: Nationwide COVID-19 vaccination was initiated in India on January 16, 2021, in a phased manner with vaccines including Covishield. This vaccine was indigenously prepared by Serum Institute of India in line with the Oxford-AstraZeneca ChAdOx1 vaccine developed at the University of Oxford. This is the first multicenter study to assess the safety of the indigenously prepared Covishield vaccine in India. STUDY DESIGN: Multicenter observational descriptive study. METHODS: This was a multicenter study carried out in northern and eastern India. Individuals who received the first dose of the Covishield vaccine were followed up for 7 days to check for any adverse effects or systemic effects post vaccination. The data were collected by the authors with a participant-administered questionnaire. The primary end point was the incidence of adverse or systemic effects within 7 days post vaccination. RESULTS: No serious adverse or systemic effects were noted in 7 days of follow-up. Nonserious systemic effects were seen in 42.0% of individuals post vaccination. Myalgia and/or fatigue was the most common effect of vaccination in 25.7%, followed by fever in 22.0% of individuals. In most individuals, the systemic effects started 6 to 12 hours post vaccination. There were no reports of fresh onset of systemic effects of any kind beyond 48 hours of vaccination. Women and older adults tolerated the vaccination better. CONCLUSIONS: The absence of serious adverse effects in our study will help allay fears around vaccine acceptance and give a boost to the vaccination campaign worldwide.


Subject(s)
COVID-19 Vaccines , COVID-19 , Aged , Female , Humans , India/epidemiology , SARS-CoV-2 , Vaccination
15.
The American Journal of Managed Care ; 27(10), 2021.
Article in English | ProQuest Central | ID: covidwho-1469249

ABSTRACT

Objectives: Nationwide COVID-19 vaccination was initiated in India on January 16, 2021, in a phased manner with vaccines including Covishield. This vaccine was indigenously prepared by Serum Institute of India in line with the Oxford-AstraZeneca ChAdOx1 vaccine developed at the University of Oxford. This is the first multicenter study to assess the safety of the indigenously prepared Covishield vaccine in India. Study Design: Multicenter observational descriptive study. Methods: This was a multicenter study carried out in northern and eastern India. Individuals who received the first dose of the Covishield vaccine were followed up for 7 days to check for any adverse effects or systemic effects post vaccination. The data were collected by the authors with a participant-administered questionnaire. The primary end point was the incidence of adverse or systemic effects within 7 days post vaccination. Results: No serious adverse or systemic effects were noted in 7 days of follow-up. Nonserious systemic effects were seen in 42.0% of individuals post vaccination. Myalgia and/or fatigue was the most common effect of vaccination in 25.7%, followed by fever in 22.0% of individuals. In most individuals, the systemic effects started 6 to 12 hours post vaccination. There were no reports of fresh onset of systemic effects of any kind beyond 48 hours of vaccination. Women and older adults tolerated the vaccination better. Conclusions: The absence of serious adverse effects in our study will help allay fears around vaccine acceptance and give a boost to the vaccination campaign worldwide.

16.
J Virol ; 95(20): e0059221, 2021 09 27.
Article in English | MEDLINE | ID: covidwho-1440799

ABSTRACT

The current pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to dramatic economic and health burdens. Although the worldwide SARS-CoV-2 vaccination campaign has begun, exploration of other vaccine candidates is needed due to uncertainties with the current approved vaccines, such as durability of protection, cross-protection against variant strains, and costs of long-term production and storage. In this study, we developed a methyltransferase-defective recombinant vesicular stomatitis virus (mtdVSV)-based SARS-CoV-2 vaccine candidate. We generated mtdVSVs expressing SARS-CoV-2 full-length spike (S) protein, S1, or its receptor-binding domain (RBD). All of these recombinant viruses grew to high titers in mammalian cells despite high attenuation in cell culture. The SARS-CoV-2 S protein and its truncations were highly expressed by the mtdVSV vector. These mtdVSV-based vaccine candidates were completely attenuated in both immunocompetent and immunocompromised mice. Among these constructs, mtdVSV-S induced high levels of SARS-CoV-2-specific neutralizing antibodies (NAbs) and Th1-biased T-cell immune responses in mice. In Syrian golden hamsters, the serum levels of SARS-CoV-2-specific NAbs triggered by mtdVSV-S were higher than the levels of NAbs in convalescent plasma from recovered COVID-19 patients. In addition, hamsters immunized with mtdVSV-S were completely protected against SARS-CoV-2 replication in lung and nasal turbinate tissues, cytokine storm, and lung pathology. Collectively, our data demonstrate that mtdVSV expressing SARS-CoV-2 S protein is a safe and highly efficacious vaccine candidate against SARS-CoV-2 infection. IMPORTANCE Viral mRNA cap methyltransferase (MTase) is essential for mRNA stability, protein translation, and innate immune evasion. Thus, viral mRNA cap MTase activity is an excellent target for development of live attenuated or live vectored vaccine candidates. Here, we developed a panel of MTase-defective recombinant vesicular stomatitis virus (mtdVSV)-based SARS-CoV-2 vaccine candidates expressing full-length S, S1, or several versions of the RBD. These mtdVSV-based vaccine candidates grew to high titers in cell culture and were completely attenuated in both immunocompetent and immunocompromised mice. Among these vaccine candidates, mtdVSV-S induces high levels of SARS-CoV-2-specific neutralizing antibodies (Nabs) and Th1-biased immune responses in mice. Syrian golden hamsters immunized with mtdVSV-S triggered SARS-CoV-2-specific NAbs at higher levels than those in convalescent plasma from recovered COVID-19 patients. Furthermore, hamsters immunized with mtdVSV-S were completely protected against SARS-CoV-2 challenge. Thus, mtdVSV is a safe and highly effective vector to deliver SARS-CoV-2 vaccine.


Subject(s)
COVID-19 Vaccines/immunology , COVID-19/prevention & control , SARS-CoV-2/immunology , Vesicular stomatitis Indiana virus/genetics , Animals , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , Brain/virology , COVID-19/immunology , Cell Line , Cytokine Release Syndrome/prevention & control , DNA-Directed RNA Polymerases/genetics , DNA-Directed RNA Polymerases/metabolism , Humans , Immunogenicity, Vaccine , Lung/immunology , Lung/pathology , Lung/virology , Mesocricetus , Methyltransferases/genetics , Methyltransferases/metabolism , Mice , Protein Domains , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/immunology , Th1 Cells/immunology , Vaccines, Synthetic/immunology , Vesicular stomatitis Indiana virus/enzymology , Vesicular stomatitis Indiana virus/physiology , Viral Proteins/genetics , Viral Proteins/metabolism , Virus Replication
17.
Prim Care Companion CNS Disord ; 23(2)2021 03 25.
Article in English | MEDLINE | ID: covidwho-1231533

ABSTRACT

OBJECTIVE: To examine the various psychosocial factors associated with reverse migration among migrant workers during the coronavirus disease 2019 (COVID-19) lockdown in India. METHODS: A cross-sectional multicenter study was conducted at 4 sites in Northwest India. The migrant workers were recruited from various shelter homes, and information was gathered from reverse migrant workers and controls using various tools including a sociodemographic profile; knowledge, attitudes, and practices questionnaire; and reasons for migration and reverse migration questionnaires. A total of 275 reverse migrant workers and 276 controls participated in the study. RESULTS: There was a considerable difference between reverse migrant workers and controls regarding the question of whether it was safe to travel during lockdown (76.0% vs 26.4%, respectively). The most common route of spread of COVID-19 infection was through touching and sneezing, and symptoms were fever, dry cough, and sore throat in both groups. Reverse migrant workers had low self-esteem and were reluctant to participate in customs of their migration city. A large number of reverse migrant workers reported that they had no money to survive, worried about family back home at their village, felt pressured by family members to come back to the village, and had been terminated from their job. CONCLUSIONS: Reverse migrant workers had the attitude that it was safe to travel during the lockdown. About one-fifth of the reverse migrant workers reported no place to live and fear of getting an infection. The reverse migrant workers also reported feeling low and gloomy, restless, and uncertain about the future and fear of death. Lack of jobs was a major factor driving migrant workers from their native homes.


Subject(s)
COVID-19 , Employment , Family , Health Knowledge, Attitudes, Practice , Transients and Migrants/psychology , Adolescent , Adult , Aged , COVID-19/prevention & control , Communicable Disease Control , Cross-Sectional Studies , Female , Humans , India , Male , Middle Aged , Young Adult
19.
Curr Pharm Biotechnol ; 22(12): 1591-1601, 2021.
Article in English | MEDLINE | ID: covidwho-1052467

ABSTRACT

Coronavirus-19 is a severe acute respiratory disorder in humans which has become a major health problem. It spreads out very rapidly throughout the world since it has been first identified in Wuhan, China (December 2019). The causative virus is known as severe acute respiratory syndrome coronavirus 2. And the World Health Organization has named this respiratory syndrome as a new epidemic disease called COVID-19. The incidence of COVID-19 continued to increase with three million confirmed infected cases and with 244,000 death cases worldwide. Until now there is no specific treatment or vaccine available against COVID- 19. The collective information about the different aspects of COVID-19 viral infection has been gathered from renowned journals, and electronic databases including Science Direct, Web of Science, Scopus and PubMed from 1990 to 2020. This manuscript has highlighted the transmission and symptoms of Covid-19. Therefore, these studies show how the SARS-CoV 2 can facilitate the debut of the virus into targeted host cells.


Subject(s)
COVID-19 , China/epidemiology , Disease Outbreaks , Humans , SARS-CoV-2
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