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1.
Germs ; 12(4):538-547, 2022.
Article in English | EMBASE | ID: covidwho-20239510

ABSTRACT

Risk and predisposing factors for viral zoonoses abound in the sub-Saharan Africa (SSA) region with significant public health implications. For several decades, there have been several reports on the emergence and re-emergence of arbovirus infections. The lifetime burden of arboviral diseases in developing countries is still poorly understood. Studies indicate significant healthcare disruptions and economic losses attributed to the viruses in resource-poor communities marked by impairment in the performance of daily activities. Arboviruses have reportedly evolved survival strategies to aid their proliferation in favorable niches, further magnifying their public health relevance. However, there is poor knowledge about the viruses in the region. Thus, this review presents a survey of zoonotic arboviruses in SSA, the burden associated with their diseases, management of diseases as well as their prevention and control, mobility and determinants of infections, their vectors, and co-infection with various microorganisms. Lessons learned from the ongoing coronavirus disease 2019 (COVID-19) pandemic coupled with routine surveillance of zoonotic hosts for these viruses will improve our understanding of their evolution, their potential to cause a pandemic, control and prevention measures, and vaccine development.Copyright © GERMS 2022.

2.
Front Microbiol ; 14: 1192832, 2023.
Article in English | MEDLINE | ID: covidwho-20239068

ABSTRACT

Introduction: Pulmonary and extrapulmonary manifestations have been described after infection with SARS-CoV-2, the causative agent of coronavirus disease 2019 (COVID-19). The virus is known to persist in multiple organs due to its tropism for several tissues. However, previous reports were unable to provide definitive information about whether the virus is viable and transmissible. It has been hypothesized that the persisting reservoirs of SARS-CoV-2 in tissues could be one of the multiple potentially overlapping causes of long COVID. Methods: In the present study, we investigated autopsy materials obtained from 21 cadaveric donors with documented first infection or reinfection at the time of death. The cases studied included recipients of different formulations of COVID-19 vaccines. The aim was to find the presence of SARS-CoV-2 in the lungs, heart, liver, kidneys, and intestines. We used two technical approaches: the detection and quantification of viral genomic RNA using RT-qPCR, and virus infectivity using permissive in vitro Vero E6 culture. Results: All tissues analyzed showed the presence of SARS-CoV-2 genomic RNA but at dissimilar levels ranging from 1.01 × 102 copies/mL to 1.14 × 108 copies/mL, even among those cases who had been COVID-19 vaccinated. Importantly, different amounts of replication-competent virus were detected in the culture media from the studied tissues. The highest viral load were measured in the lung (≈1.4 × 106 copies/mL) and heart (≈1.9 × 106 copies/mL) samples. Additionally, based on partial Spike gene sequences, SARS-CoV-2 characterization revealed the presence of multiple Omicron sub-variants exhibiting a high level of nucleotide and amino acid identity among them. Discussion: These findings highlight that SARS-CoV-2 can spread to multiple tissue locations such as the lungs, heart, liver, kidneys, and intestines, both after primary infection and after reinfections with the Omicron variant, contributing to extending knowledge about the pathogenesis of acute infection and understanding the sequelae of clinical manifestations that are observed during post-acute COVID-19.

3.
Revista Chilena de Infectologia ; 39(5):614-622, 2022.
Article in English | EMBASE | ID: covidwho-2323002

ABSTRACT

Given the actual risk of poliomyelitis outbreaks in the region due to poliovirus derived from the Sabin vaccine or the importation of wild poliovirus, the Latin American Society of Pediatric Infectious Diseases commissioned an ad hoc group of experts from the institution's Vaccines and Biologicals Committee, to draft an official position paper on the urgent need to increase immunization levels against the disease in the region and incorporate inactivated polio vaccine exclusive schedules in all national immunization programs. This publication discusses the main conclusions and recommendations generated as a result of such activity.Copyright © 2022, Sociedad Chilena de Infectologia. All rights reserved.

4.
Infectious Diseases: News, Opinions, Training ; 10(3):23-32, 2021.
Article in Russian | EMBASE | ID: covidwho-2327473

ABSTRACT

Patients with end-stage chronic kidney disease treated with hemodialysis are at risk of infection and severe course of the new coronavirus infection. This opinion was based on the data obtained as a result of PCR testing during the active phase of the disease with detailed clinical symptoms. However, this diagnostic method does not allow one to fully assess the prevalence of infection in the population. The aim - studying of the frequency of SARS-CoV-2 infection in patients receiving hemodialysis treatment and the spectrum of antiviral antibodies, depending on the nature of the course of COVID-19. Material and methods. 100 patients with chronic kidney disease (stage 5D) treated at the outpatient Dialysis Center (MCVTP) were included in the study by a simple random sample. The assessment of SARS-CoV-2 infection was carried out by analyzing the material of smears obtained from the naso-oropharynx by PCR and blood serum samples by ELISA. The study excluded 14 patients with dubious results for the determination of serological markers SARS-CoV-2 and 1 patient with active infection, who was isolated from the RNA of the virus. Results. IgM and IgG antibodies were detected in 49 (57.6%) of the 85 examined patients. 24 of them (group 1) were diagnosed with COVID-19 infection with typical clinical symptoms 3-9 months ago, and 25 (group 2) had no clinical manifestations of the acute respiratory infection at the appropriate time suggesting an asymptomatic course of the disease. IgM class antibodies were detected with equal frequency in group 1 and in group 2 (33.3 vs 24.0%, respectively, p<0.6). IgG antibodies exclusively to the nucleocapsid N-protein (IgGn) were detected only in the latent form of the disease (32%), while antibodies against the S-protein (spike protein) of the virus (IgGs and IgGn+s) were detected more often in the manifest form compared to the asymptomatic one (100 vs 60%, respectively, p<0.05). Conclusion. In a random cohort of patient receiving hemodialysis treatment, more than half were asymptomatic.Despite a wide range of prevention measures, SARS-CoV-2 infection among patients treated with hemodialysis is more than 2 times higher than in the general population.Copyright © 2021 Geotar Media Publishing Group. All rights reserved.

5.
Russian Journal of Infection and Immunity ; 13(1):37-45, 2023.
Article in Russian | EMBASE | ID: covidwho-2320798

ABSTRACT

Introduction. The rapid spread of a new coronavirus infection among populations in many countries worldwide has contributed to the genetic evolution of the virus, resulting in the emergence of multiple genetic variants of the SARSCoV-2 coronavirus. Mutations in the viral genome can affect the ability of the virus to bypass the immune system and complicate development of diagnostic and prophylactic drugs. Data on the neutralizing activity of the sera obtained against previously circulating genetic variants of the virus in relation to current SARS-CoV-2 strains may serve as a scientific basis for the selection of the antigens in vaccine development. The aim of this work was to study cross-reactivity of SARSCoV-2 coronavirus strains belonging to different genetic variants, which were isolated in the territory of the Russian Federation during 2020-2022 in the neutralization reaction using mouse hyperimmune sera. Materials and methods. Ten strains of SARS-CoV-2 coronavirus belonging to different genetic variants were used (three non-VOC strains, alpha, beta, gamma, delta, delta+AY, omicron 1 and omicron 2). The hCoV-19/Australia/VIC01/2020 strain (Wuhan) was included in the study as a prototypical variant. BALBc mice were immunized with inactivated concentrated antigen mixed with a 1:1 adjuvant, which was a virus-like immunostimulatory complex based on Quillaja saponaria (Quillaja saponaria). The antibody titer was determined in the neutralization reaction. Results. Essential decrease of neutralizing ability of antibodies specific to non-vOC genetic variants of SARS-CoV-2 coronavirus was revealed against beta VOC and to a lesser degree against alpha and gamma VOC variants. The differences in the neutralizing activity level of antibodies for alpha and beta VOC variants are not significant among themselves, and with gamma VOC variants - there are no significant differences. Neutralizing ability of antibodies specific to delta VOC against alpha and beta VOC variants decreased 4-fold. Neutralizing activity of sera obtained to omicron 1 and 2 variants in relation to the prototype coronavirus variant was reduced 18-fold, to the gamma variant - 12-fold, to delta variants - more than 30-fold;for other variants it was even lower. Conclusions. The results obtained testify to the presence of cross-reactivity between strains of coronavirus belonging to genetic lines Wuhan, alpha, beta, gamma;it is weaker for delta variants. Mutations in the genome of VOC omicron variants led to a significant decrease in antigenic cross-links with earlier genetic variants of the coronavirus. These findings explain the low efficacy of vaccines based on the Wuhan strain, synthetic immunogens, and recombinant proteins based on it against omicron VOC variants, which have caused a rise in morbidity since early 2022, as well as cases of re-infection of humans with new genetic variants of the coronavirus.Copyright © 2023 Saint Petersburg Pasteur Institute. All rights reserved.

6.
Egyptian Journal of Otolaryngology ; 38(1) (no pagination), 2022.
Article in English | EMBASE | ID: covidwho-2316938

ABSTRACT

Background: Post-viral anosmia is responsible for more than 40% of cases of anosmia. Anosmia has been a neglected symptom in the primary healthcare setting until the emergence of the SARS-CoV-2 pandemic. The spread of SARS-CoV-2 infection highlighted new atypical symptoms of the disease, including anosmia, which has become one of the diagnostic symptoms of the disease, and epidemiological concern. We aimed to detect the incidence of SARS-CoV-2 infection within patients presented with anosmia and to test for other respiratory viruses in the negative COVID-19 patients. We also detected the recovery of anosmia and IgM/IgG against COVID-19. We prospectively included 60 outpatients with the major complaint of anosmia. Nasopharyngeal swabs were done for SARS-CoV-2 real-time PCR, and if negative, PCR to other respiratory pathogens was tested. After one month, we inquired about the recovery of smell loss together with testing for antibodies against SARS-CoV-2. Result(s): Sixty patients were enrolled in the study. Forty-six patients (76.7%) were SARS-CoV-2 PCR positive and 14 (23.3%) were negative. Rhinovirus was the commonest isolated pathogen in the negative cases (5/14). Complete recovery of anosmia occurred in 34 patients (56.7%), while partial recovery in 24 (40.0%), and no recovery in 2 patients (3.3%). The median time to complete recovery was 10 days. 28.3% (13/46) of the patients showed negative antibody response for both IgG and IgM. Conclusion(s): Sudden-onset anosmia is a symptom that is highly predictive of being COVID-19-infected. While recovery is expected within 2 weeks, some patients have no antibodies against SARS-CoV-2.Copyright © 2022, The Author(s).

7.
Vet Clin North Am Food Anim Pract ; 39(1): 129-140, 2023 Mar.
Article in English | MEDLINE | ID: covidwho-2320302

ABSTRACT

Laboratory testing is one part of clinical diagnosis, and quick and reliable testing results provide important data to support treatment decision and develop control strategies. Clinical viral testing has been shifting from traditional virus isolation and electron microscopy to molecular polymerase chain reaction and point-of-care antigen tests. This shift in diagnostic methodology also means change from looking for infectious virions or viral particles to hunting viral antigens and genomes. With technological development, it is predicted that metagenomic sequencing will be commonly used in veterinary clinical diagnosis for unveiling the whole picture of microbes involved in diseases in the future.


Subject(s)
Laboratories , Animals , Polymerase Chain Reaction/veterinary
8.
Emerg Infect Dis ; 28(12): 2500-2503, 2022 Dec.
Article in English | MEDLINE | ID: covidwho-2310054

ABSTRACT

Surveillance of bat betacoronaviruses is crucial for understanding their spillover potential. We isolated bat sarbecoviruses from Rhinolophus cornutus bats in multiple locations in Japan. These viruses grew efficiently in cells expressing R. cornutus angiotensin converting enzyme-2, but not in cells expressing human angiotensin converting enzyme-2, suggesting a narrow host range.


Subject(s)
Chiroptera , Animals , Humans , Peptidyl-Dipeptidase A , Japan/epidemiology , Betacoronavirus , Host Specificity
9.
Infectious Microbes and Diseases ; 5(1):3-12, 2023.
Article in English | EMBASE | ID: covidwho-2291361
10.
Kuwait Medical Journal ; 2023(1):28-38, 2023.
Article in English | EMBASE | ID: covidwho-2291077

ABSTRACT

Objectives: This article reports medical interns' knowledge, attitude and practice (KAP) toward COVID-19 prevention measures in the Kingdom of Saudi Arabia (KSA). Design(s): We conducted a cross-sectional online survey. The questionnaire included 10 questions each to assess knowledge and attitudes, and seven questions to assess practice. We did descriptive analyses to report KAP and performed t-test or ANOVA, and multi-variable logistic regression analyses to investigate socio-demographic determinants of KAP. Setting(s): All regions in the KSA Subjects: Medical interns from all medical colleges in the KSA were invited to participate Intervention: Not applicable Main Outcome Measure(s): Attitude about COVID-19 was assessed as positive (>=90% correct responses), moderate (80-90% correct) or poor (< 80% correct);whereas knowledge and practice were assessed as excellent, good or poor respectively for >=90%, 75%-90%, and <75% correct responses. Result(s): Our results suggest that 24% of medical interns rely on social media, television, or friends as primary source of COVID-19 information. The prevalence of positive attitude, excellent knowledge and excellent/good practices are 55.2%, 38% and 24%, respectively. Graduating from government universities are associated with higher odds of excellent knowledge [Odds Ratio (OR): 3.87;95% Confidence Interval (CI): 1.05-14.22] and positive attitude [OR: 4.84 (1.28-18.23)]. Interns from the west [OR: 2.35 (1.05-5.23)] and north [OR: 3.2 (1.32-7.75)] regions have higher odds of excellent/good practice compared to the central region. Conclusion(s): Our findings reveal gaps in KAP among medical interns. Medical interns in the KSA are not deployed as front-line health workers to combat COVID-19. However, community transmission of COVID-19 makes it critical to improve KAP of medical interns toward COVID-19 prevention measures.Copyright © 2023, Kuwait Medical Association. All rights reserved.

11.
Journal of Experimental & Theoretical Artificial Intelligence ; 35(4):489-505, 2023.
Article in English | Academic Search Complete | ID: covidwho-2305033

ABSTRACT

Coronaviridae family consists of many virulent viruses with zoonotic properties that can be transmitted from animals to humans. Different strains of these viruses have caused pandemic in the past such as Severe Respiratory Syndrome Coronavirus (SARS-CoV) in 2002, Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012 and recently Severe Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) also known as COVID-19 in December 2019. Scientists utilised different approaches for the detection and characterisation of CoVs using samples such as serum, throat swabs, nose swabs, nasopharyngeal aspirates and bronchoalveolar lavages. The two common approaches include antigen-based approach and molecular diagnostic approach, which are hindered by limitations such as low sensitivity and requirement for high level of biosafety during isolation of the virus from cell culture. Thus, there is a need for developing a more rapid, sensitive, simple and cheap diagnostic kit for diagnosis of different strains of coronavirus. In this article, we overview 2019 novel coronavirus, pandemic, prior epidemics, diagnosis, treatments, identification of drugs detection based on classification and prediction using artificial intelligence-driven tools. We also overview in-lab molecular testing and on-site testing using CRISPR-based biosensing tools. We also outline limitations of laboratory techniques and open-research issues in the current state of CRISPR-based biosensing applications and artificial intelligence for treatment of Coronaviruses. [ FROM AUTHOR] Copyright of Journal of Experimental & Theoretical Artificial Intelligence is the property of Taylor & Francis Ltd and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

12.
Int J Infect Dis ; 129: 103-109, 2023 Apr.
Article in English | MEDLINE | ID: covidwho-2302951

ABSTRACT

OBJECTIVES: The prolonged presence of infectious SARS-CoV-2 in deceased patients with COVID-19 has been reported. However, infectious virus titers have not been determined. Such information is important for public health, death investigation, and handling corpses. The aim of this study was to assess the level of SARS-CoV-2 infectivity in the corpses of patients with COVID-19. METHODS: We collected 11 nasopharyngeal swabs and 19 lung tissue specimens from 11 autopsy cases with COVID-19 in 2021. We then investigated the viral genomic copy number by real-time reverse transcription-polymerase chain reaction and infectious titers by cell culture and virus isolation. RESULTS: Infectious virus was present in six of 11 (55%) cases, four of 11 (36%) nasopharyngeal swabs, and nine of 19 (47%) lung specimens. The virus titers ranged from 6.00E + 01 plaque-forming units/ml to 2.09E + 06 plaque-forming units/g. In all cases in which an infectious virus was found, the time from death to discovery was within 1 day and the longest postmortem interval was 13 days. CONCLUSION: The corpses of patients with COVID-19 may have high titers of infectious virus after a long postmortem interval (up to 13 days). Therefore, appropriate infection control measures must be taken when handling corpses.


Subject(s)
COVID-19 , Communicable Diseases , Humans , COVID-19/diagnosis , SARS-CoV-2 , Lung , COVID-19 Testing , Cadaver
13.
Coronaviruses ; 3(1):65-72, 2022.
Article in English | EMBASE | ID: covidwho-2272316

ABSTRACT

The Coronavirus Disease 2019 (COVID-19), also known as a novel coronavirus (2019-n-CoV), reportedly originated from Wuhan City, Hubei Province, China. Coronavirus Disease 2019 rapidly spread all over the world within a short period. On January 30, 2020, the World Health Organization (WHO) declared it a global epidemic. COVID-19 is a Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) evolves to respiratory, hepatic, gastrointestinal, and neurological complications, and eventually death. SARS-CoV and the Middle East Respiratory Syndrome coron-avirus (MERS-CoV) genome sequences similar identity with 2019-nCoV or Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2). However, few amino acid sequences of 2019-nCoV differ from SARS-CoV and MERS-CoV. COVID-19 shares about 90% amino acid sequence simi-larity with SARS-CoV. Effective prevention methods should be taken in order to control this pandemic situation. To date, there are no effective treatments available to treat COVID-19. This review provides information regarding COVID-19 history, epidemiology, pathogenesis and molecular diagnosis. Also, we focus on the development of vaccines in the management of this COVID-19 pandemic and limiting the spread of the virus.Copyright © 2022 Bentham Science Publishers.

14.
Coronaviruses ; 3(6):53-56, 2022.
Article in English | EMBASE | ID: covidwho-2257118

ABSTRACT

Background: The Omicron variant B.1.1.529 has led to a new dynamic in the COVID-19 pan-demic, with an increase in cases worldwide. Its rapid propagation favors the emergence of novel sub-lineages, including BA.4 and BA.5. The latter has shown increased transmissibility compared to other Omicron sub-lineages. In Senegal, the emergence of the Omicron variant in December 2021 characterized the triggering of a short and dense epidemiological wave that peaked at the end of February. This wave was followed by a period with a significant drop in the number of COVID-19 cases, but an upsurge in SARS-CoV-2 infection has been noted since mid-June. Objective(s): The purpose of this brief report is to give an update regarding the genomic situation of SARS-CoV-2 in Dakar during this phase of recrudescence of cases. Method(s): We performed amplicon-based SARS-CoV-2 sequencing on nasopharyngeal swab samples from declared COVID-19 patients and outbound travelers that tested positive. Result(s): Ongoing genomic surveillance activities showed that more than half of recent COVID-19 cases were due to the BA.4 and BA.5 sub-lineages that share two critical mutations associated with increased transmissibility and immune response escape. The circulation of recombinants between Omicron sub-lineages was also noted. Conclusion(s): Despite the lack of proven severity of BA.4 and BA.5 sub-lineages, their increased transmis-sibility causes a rapid spread of the virus, hence a surge in the number of cases. This rapid spread consti-tutes a greater risk of exposure for vulnerable patients. To tackle this issue, any increase in the number of cases must be monitored to support public health stakeholders. Therefore, genomic surveillance is an ever-essential element in managing this pandemic.Copyright © 2022 Bentham Science Publishers.

15.
Iranian Journal of Veterinary Medicine ; 13(3):251-259, 2023.
Article in English | EMBASE | ID: covidwho-2250867

ABSTRACT

BACKGROUND: Gammacoronaviruses, which are single-stranded, positive-sense RNA viruses, are responsible for a wide variety of existing and emerging diseases in birds. The Gammacoronaviruses primarily infect avian hosts. OBJECTIVE(S): This study aimed to investigate the genetic diversity of Gammacoronaviruses in quail population in Iran. METHOD(S): In the period from 2016 to 2018, samples from 47 quail flocks with or without enteric signs, were collected from four provinces in Iran. RESULT(S): Gammacoronavirus was detected in samples of 4 flocks by using RT-PCR and characterized by N gene sequencing. The isolates formed a distinct group from other Gamma- coronaviruses groups CONCLUSION(S): The finding suggests the existence of a novel Gammacoronavirus circulating in quail farms. The phylogenetic relationship of the isolates concerning different sequences and geographical regions displayed complexity and diversity. The present study is the first detection of Gammacoronavirus in quail farms in Iran. Further studies are required and should include the isolation and experimental studies of Gammacoronaviruses in Iran.Copyright © 2019.

16.
Clinical Chemistry ; 68(5):739-741, 2022.
Article in English | EMBASE | ID: covidwho-2249692
17.
Methods Mol Biol ; 2610: 129-135, 2023.
Article in English | MEDLINE | ID: covidwho-2241134

ABSTRACT

Certain viral pathogens can be shed into the human breast milk and cause infections in the infant upon breastfeeding. Thus, it is important to clarify whether viral RNA as well as infectious virus can be found in breast milk. The complexity of this body fluid poses several challenges for viral RNA isolation and detection of infectious virus. We here provide a protocol that allowed the identification of SARS-CoV-2 RNA in breast milk and the isolation of infectious virus after the virus has been artificially spiked into milk samples.


Subject(s)
COVID-19 , SARS-CoV-2 , Infant , Female , Humans , Milk, Human , RNA, Viral , Breast Feeding
18.
Front Public Health ; 10: 1011277, 2022.
Article in English | MEDLINE | ID: covidwho-2215442

ABSTRACT

Background: SARS-CoV-2 patients re-experiencing positive nucleic acid test results after recovery is a concerning phenomenon. Current pandemic prevention strategy demands the quarantine of all recurrently positive patients. This study provided evidence on whether quarantine is required in those patients, and predictive algorithms to detect subjects with infectious possibility. Methods: This observational study recruited recurrently positive patients who were admitted to our shelter hospital between May 12 and June 10, 2022. The demographic and epidemiologic data was collected, and nucleic acid tests were performed daily. virus isolation was done in randomly selected cases. The group-based trajectory model was developed based on the cycle threshold (Ct) value variations. Machine learning models were validated for prediction accuracy. Results: Among the 494 subjects, 72.04% were asymptomatic, and 23.08% had a Ct value under 30 at recurrence. Two trajectories were identified with either rapid (92.24%) or delayed (7.76%) recovery of Ct values. The latter had significantly higher incidence of comorbidities; lower Ct value at recurrence; more persistent cough; and more frequently reported close contacts infection compared with those recovered rapidly. However, negative virus isolation was reported in all selected samples. Our predictive model can efficiently discriminate those with delayed Ct value recovery and infectious potentials. Conclusion: Quarantine seems to be unnecessary for the majority of re-positive patients who may have low transmission risks. Our predictive algorithm can screen out the suspiciously infectious individuals for quarantine. These findings may assist the enaction of SARS-CoV-2 pandemic prevention strategies regarding recurrently positive patients in the future.


Subject(s)
COVID-19 , Nucleic Acids , Humans , Quarantine , COVID-19/diagnosis , COVID-19/epidemiology , COVID-19/prevention & control , RNA , SARS-CoV-2 , Machine Learning
19.
Journal of Cell Science ; 135(2) (no pagination), 2022.
Article in English | EMBASE | ID: covidwho-2162487
20.
American Journal of Translational Research ; 14(4):2244-2255, 2022.
Article in English | EMBASE | ID: covidwho-1935224

ABSTRACT

With the COVID-19 epidemic quickly under control in China in the early stage of 2020, global cooperation/ communications may pose great challenges to epidemic control and prevention in the country. Large-scale spread by asymptomatic carriers was a concern. We obtained data on new cluster outbreak regions with COVID-19 caused by asymptomatic carriers from June 2020 to May 2021 in China, and reported the epidemiological characteristics, the possible routes of viral transmission and infection, and different control strategies. These results show the importance of regular screening for high-risk populations and differential management strategies for epidemic control, which provide an objective basis for suppressing the spread of the SARS-CoV-2 virus. These experiences can be used as a reference to minimize the subsequent spread of virus mutants in various places.

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