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1.
Infect Control Hosp Epidemiol ; 42(11): 1327-1332, 2021 11.
Article in English | MEDLINE | ID: covidwho-1575207

ABSTRACT

BACKGROUND: Understanding the extent of aerosol-based transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is important for tailoring interventions for control of the coronavirus disease 2019 (COVID-19) pandemic. Multiple studies have reported the detection of SARS-CoV-2 nucleic acid in air samples, but only one study has successfully recovered viable virus, although it is limited by its small sample size. OBJECTIVE: We aimed to determine the extent of shedding of viable SARS-CoV-2 in respiratory aerosols from COVID-19 patients. METHODS: In this observational air sampling study, air samples from airborne-infection isolation rooms (AIIRs) and a community isolation facility (CIF) housing COVID-19 patients were collected using a water vapor condensation method into liquid collection media. Samples were tested for presence of SARS-CoV-2 nucleic acid using quantitative real-time polymerase chain reaction (qRT-PCR), and qRT-PCR-positive samples were tested for viability using viral culture. RESULTS: Samples from 6 (50%) of the 12 sampling cycles in hospital rooms were positive for SARS-CoV-2 RNA, including aerosols ranging from <1 µm to >4 µm in diameter. Of 9 samples from the CIF, 1 was positive via qRT-PCR. Viral RNA concentrations ranged from 179 to 2,738 ORF1ab gene copies per cubic meter of air. Virus cultures were negative after 4 blind passages. CONCLUSION: Although SARS-CoV-2 is readily captured in aerosols, virus culture remains challenging despite optimized sampling methodologies to preserve virus viability. Further studies on aerosol-based transmission and control of SARS-CoV-2 are needed.


Subject(s)
COVID-19 , RNA, Viral , Hospitals , Humans , Polymerase Chain Reaction , RNA, Viral/genetics , SARS-CoV-2
2.
Zhonghua Nei Ke Za Zhi ; 59(8): 605-609, 2020 Aug 01.
Article in Chinese | MEDLINE | ID: covidwho-1556260

ABSTRACT

Objective: To evaluate the efficacy and safety of lopinavir/ritonavir (LPV/r) and arbidol in treating patients with coronavirus disease 2019 (COVID-19) in the real world. Methods: The clinical data of 178 patients diagnosed with COVID-19 admitted to Guangzhou Eighth People's Hospital from January 20 to February 10, 2020 were retrospectively analyzed. According to patient's antiviral treatment regimens, 178 patients were divided into 4 groups including LPV/r group (59 patients), arbidol group (36 patients), LPV/r plus arbidol combination group (25 patients) and the supportive care group without any antiviral treatment (58 patients). The primary end point was the negative conversion time of nucleic acid of 2019 novel coronavirus (2019-nCoV) by pharyngeal swab. Results: The baseline parameters of 4 groups before treatment was comparable. The negative conversion time of viral nucleic acid was (10.20±3.49), (10.11±4.68), (10.86±4.74), (8.44±3.51) days in LPV/r group, arbidol group, combination group, and supportive care group respectively (F=2.556, P=0.058). There was also no significant difference in negative conversion rate of 2019-nCoV nucleic acid, the improvement of clinical symptoms, and the improvement of pulmonary infections by CT scan (P>0.05). However, a statistically significant difference was found in the changing rates from mild/moderate to severe/critical type at day 7 (χ(2)=9.311, P=0.017), which were 24%(6/25) in combination group, 16.7%(6/36) in arbidol group, 5.4%(3/56) in LPV/r group and 5.2%(3/58) in supportive care group. Moreover, the incidence of adverse reactions in three antiviral groups was significantly higher than that in supportive care group (χ(2)=14.875, P=0.002). Conclusions: Antiviral treatment including LPV/r or arbidol or combination does not shorten the negative conversion time of 2019-nCoV nucleic acid nor improve clinical symptoms. Moreover, these antiviral drugs cause more adverse reactions which should be paid careful attention during the treatment.


Subject(s)
COVID-19 , HIV Infections , COVID-19/drug therapy , HIV Infections/drug therapy , Humans , Indoles , Lopinavir/adverse effects , Retrospective Studies , Ritonavir/adverse effects , SARS-CoV-2
3.
Zhonghua Nei Ke Za Zhi ; 59(8): 610-617, 2020 Aug 01.
Article in Chinese | MEDLINE | ID: covidwho-1555470

ABSTRACT

Objective: To explore the feasibility of direct renin inhibitor aliskiren for the treatment of severe or critical coronavirus disease 2019 (COVID-19) patients with hypertension. Methods: The antihypertensive effects and safety of aliskiren was retrospectively analyzed in three severe and one critical COVID-19 patients with hypertension. Results: Four patients, two males and two females, with an average age of 78 years (66-87 years), were referred to hospital mainly because of respiratory symptoms. Three were diagnosed by positive novel coronavirus 2019 (2019-nCoV) nucleic acid or antibody, and the critical patient with cardiac insufficiency was clinically determined. Two patients were treated with calcium channel antagonist (CCB), one with angiotensin converting enzyme inhibitor (ACEI), and one with angiotensin Ⅱ receptor antagonist (ARB). After admission, ACEI and ARB were discontinued, one patient with heart failure was treated by aliskiren combined with diuretic.Three patients were treated with aliskiren combined with CCB among whom two withdrew CCB due to low blood pressure after 1 to 2 weeks. Based on comprehensive treatment including antiviral and oxygenation treatment, blood pressure was satisfactorily controlled by aliskiren after three to four weeks without serious adverse events. All patients were finally discharged. Conclusion: Our preliminary clinical data shows that antihypertensive effect of aliskiren is satisfactory and safe for severe COVID-19 patients complicated with hypertension.


Subject(s)
COVID-19 , Hypertension , Aged , Amides , Angiotensin Receptor Antagonists , Angiotensin-Converting Enzyme Inhibitors , Antihypertensive Agents/therapeutic use , Female , Fumarates , Humans , Hypertension/drug therapy , Male , Renin , Retrospective Studies , SARS-CoV-2
4.
Lancet Infect Dis ; 21(5): 637-646, 2021 05.
Article in English | MEDLINE | ID: covidwho-1510469

ABSTRACT

BACKGROUND: To mitigate the effects of COVID-19, a vaccine is urgently needed. BBV152 is a whole-virion inactivated SARS-CoV-2 vaccine formulated with a toll-like receptor 7/8 agonist molecule adsorbed to alum (Algel-IMDG) or alum (Algel). METHODS: We did a double-blind, multicentre, randomised, controlled phase 1 trial to assess the safety and immunogenicity of BBV152 at 11 hospitals across India. Healthy adults aged 18-55 years who were deemed healthy by the investigator were eligible. Individuals with positive SARS-CoV-2 nucleic acid and/or serology tests were excluded. Participants were randomly assigned to receive either one of three vaccine formulations (3 µg with Algel-IMDG, 6 µg with Algel-IMDG, or 6 µg with Algel) or an Algel only control vaccine group. Block randomisation was done with a web response platform. Participants and investigators were masked to treatment group allocation. Two intramuscular doses of vaccines were administered on day 0 (the day of randomisation) and day 14. Primary outcomes were solicited local and systemic reactogenicity events at 2 h and 7 days after vaccination and throughout the full study duration, including serious adverse events. Secondary outcome was seroconversion (at least four-fold increase from baseline) based on wild-type virus neutralisation. Cell-mediated responses were evaluated by intracellular staining and ELISpot. The trial is registered at ClinicalTrials.gov (NCT04471519). FINDINGS: Between July 13 and 30, 2020, 827 participants were screened, of whom 375 were enrolled. Among the enrolled participants, 100 each were randomly assigned to the three vaccine groups, and 75 were randomly assigned to the control group (Algel only). After both doses, solicited local and systemic adverse reactions were reported by 17 (17%; 95% CI 10·5-26·1) participants in the 3 µg with Algel-IMDG group, 21 (21%; 13·8-30·5) in the 6 µg with Algel-IMDG group, 14 (14%; 8·1-22·7) in the 6 µg with Algel group, and ten (10%; 6·9-23·6) in the Algel-only group. The most common solicited adverse events were injection site pain (17 [5%] of 375 participants), headache (13 [3%]), fatigue (11 [3%]), fever (nine [2%]), and nausea or vomiting (seven [2%]). All solicited adverse events were mild (43 [69%] of 62) or moderate (19 [31%]) and were more frequent after the first dose. One serious adverse event of viral pneumonitis was reported in the 6 µg with Algel group, unrelated to the vaccine. Seroconversion rates (%) were 87·9, 91·9, and 82·8 in the 3 µg with Algel-IMDG, 6 µg with Algel-IMDG, and 6 µg with Algel groups, respectively. CD4+ and CD8+ T-cell responses were detected in a subset of 16 participants from both Algel-IMDG groups. INTERPRETATION: BBV152 led to tolerable safety outcomes and enhanced immune responses. Both Algel-IMDG formulations were selected for phase 2 immunogenicity trials. Further efficacy trials are warranted. FUNDING: Bharat Biotech International.


Subject(s)
COVID-19 Vaccines/immunology , COVID-19/prevention & control , SARS-CoV-2/immunology , Adolescent , Adult , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , COVID-19 Vaccines/adverse effects , Double-Blind Method , Female , Humans , Immunoglobulin G/blood , Male , Middle Aged , Toll-Like Receptor 7/agonists , Toll-Like Receptor 8/agonists , Vaccination , Vaccines, Inactivated/immunology , Young Adult
5.
Clin Infect Dis ; 73(9): e3085-e3094, 2021 11 02.
Article in English | MEDLINE | ID: covidwho-1501024

ABSTRACT

BACKGROUND: Identifying risk factors for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection could help health systems improve testing and screening strategies. The aim of this study was to identify demographic factors, comorbid conditions, and symptoms independently associated with testing positive for SARS-CoV-2. METHODS: This was an observational cross-sectional study at the Veterans Health Administration, including persons tested for SARS-CoV-2 nucleic acid by polymerase chain reaction (PCR) between 28 February and 14 May 2020. Associations between demographic characteristics, diagnosed comorbid conditions, and documented symptoms with testing positive for SARS-CoV-2 were measured. RESULTS: Of 88 747 persons tested, 10 131 (11.4%) were SARS-CoV-2 PCR positive. Positivity was associated with older age (≥80 vs <50 years: adjusted odds ratio [aOR], 2.16 [95% confidence interval {CI}, 1.97-2.37]), male sex (aOR, 1.45 [95% CI, 1.34-1.57]), regional SARS-CoV-2 burden (≥2000 vs <400 cases/million: aOR, 5.43 [95% CI, 4.97-5.93]), urban residence (aOR, 1.78 [95% CI, 1.70-1.87]), black (aOR, 2.15 [95% CI, 2.05-2.26]) or American Indian/Alaska Native Hawaiian/Pacific Islander (aOR, 1.26 [95% CI, 1.05-1.52]) vs white race, and Hispanic ethnicity (aOR, 1.52 [95% CI, 1.40-1.65]). Obesity and diabetes were the only 2 medical conditions associated with testing positive. Documented fevers, chills, cough, and diarrhea were also associated with testing positive. The population attributable fraction of positive tests was highest for geographic location (35.3%), followed by demographic variables (27.1%), symptoms (12.0%), obesity (10.5%), and diabetes (0.4%). CONCLUSIONS: The majority of positive SARS-CoV-2 tests were attributed to geographic location, demographic characteristics, and obesity, with a minor contribution of chronic comorbid conditions.


Subject(s)
COVID-19 , SARS-CoV-2 , Aged , Cross-Sectional Studies , Delivery of Health Care , Humans , Male , Risk Factors , United States/epidemiology
6.
Life Sci Alliance ; 4(1)2021 01.
Article in English | MEDLINE | ID: covidwho-1389961

ABSTRACT

Viruses rely on their host for reproduction. Here, we made use of genomic and structural information to create a biomass function capturing the amino and nucleic acid requirements of SARS-CoV-2. Incorporating this biomass function into a stoichiometric metabolic model of the human lung cell and applying metabolic flux balance analysis, we identified host-based metabolic perturbations inhibiting SARS-CoV-2 reproduction. Our results highlight reactions in the central metabolism, as well as amino acid and nucleotide biosynthesis pathways. By incorporating host cellular maintenance into the model based on available protein expression data from human lung cells, we find that only few of these metabolic perturbations are able to selectively inhibit virus reproduction. Some of the catalysing enzymes of such reactions have demonstrated interactions with existing drugs, which can be used for experimental testing of the presented predictions using gene knockouts and RNA interference techniques. In summary, the developed computational approach offers a platform for rapid, experimentally testable generation of drug predictions against existing and emerging viruses based on their biomass requirements.


Subject(s)
Host-Pathogen Interactions , Lung , SARS-CoV-2 , Virus Replication , Antiviral Agents/pharmacology , Biomass , COVID-19/prevention & control , COVID-19/virology , Cells, Cultured , Culture Media/chemistry , Culture Media/metabolism , Glycolysis/physiology , Host-Pathogen Interactions/drug effects , Host-Pathogen Interactions/physiology , Humans , Lung/cytology , Lung/metabolism , Metabolic Flux Analysis , Models, Biological , SARS-CoV-2/drug effects , SARS-CoV-2/metabolism , SARS-CoV-2/pathogenicity , Systems Biology , Virus Replication/drug effects , Virus Replication/physiology
7.
iScience ; 24(6): 102523, 2021 Jun 25.
Article in English | MEDLINE | ID: covidwho-1385758

ABSTRACT

Nucleocapsid (N) protein of the SARS-CoV-2 virus packages the viral genome into well-defined ribonucleoprotein particles, but the molecular pathway is still unclear. N-protein is dimeric and consists of two folded domains with nucleic acid (NA) binding sites, surrounded by intrinsically disordered regions that promote liquid-liquid phase separation. Here, we use biophysical tools to study N-protein interactions with oligonucleotides of different lengths, examining the size, composition, secondary structure, and energetics of the resulting states. We observe the formation of supramolecular clusters or nuclei preceding growth into phase-separated droplets. Short hexanucleotide NA forms compact 2:2 N-protein/NA complexes with reduced disorder. Longer oligonucleotides expose additional N-protein interactions and multi-valent protein-NA interactions, which generate higher-order mixed oligomers and simultaneously promote growth of droplets. Phase separation is accompanied by a significant change in protein secondary structure, different from that caused by initial NA binding, which may contribute to the assembly of ribonucleoprotein particles within macromolecular condensates.

8.
ACS Appl Mater Interfaces ; 12(50): 55614-55623, 2020 Dec 16.
Article in English | MEDLINE | ID: covidwho-1387129

ABSTRACT

Multiplexed detection of viral nucleic acids is important for rapid screening of viral infection. In this study, we present a molybdenum disulfide (MoS2) nanosheet-modified dendrimer droplet microarray (DMA) for rapid and sensitive detection of retroviral nucleic acids of human immunodeficiency virus-1 (HIV-1) and human immunodeficiency virus-2 (HIV-2) simultaneously. The DMA platform was fabricated by omniphobic-omniphilic patterning on a surface-grafted dendrimer substrate. Functionalized MoS2 nanosheets modified with fluorescent dye-labeled oligomer probes were prepatterned on positively charged amino-modified omniphilic spots to form a fluorescence resonance energy transfer (FRET) sensing microarray. With the formation of separated microdroplets of sample on the hydrophobic-hydrophilic micropattern, prepatterned oligomer probes specifically hybridized with the target HIV genes and detached from the MoS2 nanosheet surface due to weakening of the adsorption force, leading to fluorescence signal recovery. As a proof of concept, we used this microarray with a small sample size (<150 nL) for simultaneous detection of HIV-1 and HIV-2 nucleic acids with a limit of detection (LOD) of 50 pM. The multiplex detection capability was further demonstrated for simultaneous detection of five viral genes (HIV-1, HIV-2, ORFlab, and N genes of SARS-COV-2 and M gene of Influenza A). This work demonstrated the potential of this novel MoS2-DMA FRET sensing platform for high-throughput multiplexed viral nucleic acid screening.


Subject(s)
Biosensing Techniques , COVID-19/diagnosis , HIV Infections/diagnosis , HIV/isolation & purification , COVID-19/genetics , COVID-19/virology , Disulfides/chemistry , Fluorescence , Fluorescence Resonance Energy Transfer , HIV/pathogenicity , HIV Infections/genetics , HIV Infections/virology , Humans , Molybdenum/chemistry , Nanostructures/chemistry , Nucleic Acids/genetics , Nucleic Acids/isolation & purification , SARS-CoV-2/isolation & purification , SARS-CoV-2/pathogenicity
9.
Mini Rev Med Chem ; 21(14): 1888-1908, 2021.
Article in English | MEDLINE | ID: covidwho-1323038

ABSTRACT

Virus is a type of noncellular organism, which is simple in structure, small in size and contains only one kind of nucleic acid (RNA or DNA). It must be parasitized in living cells and proliferates by replication. Viruses can infect plants or animals, which leads to many epidemic diseases, such as the current pandemic COVID-19. Viral infectious diseases have brought serious threats to the health of people around the world. Natural products are chemical substances that are usually produced by living organisms and have biological or pharmacological activity. Many of these natural products show antiviral activity. Based on the increasing importance of antiviral research, this paper focuses on the discovery and development of antiviral natural products since 2010.


Subject(s)
Antiviral Agents/pharmacology , Biological Products/pharmacology , COVID-19/drug therapy , Drug Discovery , SARS-CoV-2 , Animals , Antiviral Agents/chemistry , Biological Products/chemistry , Humans , Plant Viruses/drug effects
10.
Clin Infect Dis ; 73(1): 68-75, 2021 07 01.
Article in English | MEDLINE | ID: covidwho-1292116

ABSTRACT

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide and has the ability to damage multiple organs. However, information on serum SARS-CoV-2 nucleic acid (RNAemia) in patients affected by coronavirus disease 2019 (COVID-19) is limited. METHODS: Patients who were admitted to Zhongnan Hospital of Wuhan University with laboratory-confirmed COVID-19 were tested for SARS-COV-2 RNA in serum from 28 January 2020 to 9 February 2020. Demographic data, laboratory and radiological findings, comorbidities, and outcomes data were collected and analyzed. RESULTS: Eighty-five patients were included in the analysis. The viral load of throat swabs was significantly higher than of serum samples. The highest detection of SARS-CoV-2 RNA in serum samples was between 11 and 15 days after symptom onset. Analysis to compare patients with and without RNAemia provided evidence that computed tomography and some laboratory biomarkers (total protein, blood urea nitrogen, lactate dehydrogenase, hypersensitive troponin I, and D-dimer) were abnormal and that the extent of these abnormalities was generally higher in patients with RNAemia than in patients without RNAemia. Organ damage (respiratory failure, cardiac damage, renal damage, and coagulopathy) was more common in patients with RNAemia than in patients without RNAemia. Patients with vs without RNAemia had shorter durations from serum testing SARS-CoV-2 RNA. The mortality rate was higher among patients with vs without RNAemia. CONCLUSIONS: In this study, we provide evidence to support that SARS-CoV-2 may have an important role in multiple organ damage. Our evidence suggests that RNAemia has a significant association with higher risk of in-hospital mortality.


Subject(s)
COVID-19 , Nucleic Acids , Cohort Studies , Humans , RNA, Viral , SARS-CoV-2
11.
Lancet Infect Dis ; 21(7): 950-961, 2021 07.
Article in English | MEDLINE | ID: covidwho-1290388

ABSTRACT

BACKGROUND: BBV152 is a whole-virion inactivated SARS-CoV-2 vaccine (3 µg or 6 µg) formulated with a toll-like receptor 7/8 agonist molecule (IMDG) adsorbed to alum (Algel). We previously reported findings from a double-blind, multicentre, randomised, controlled phase 1 trial on the safety and immunogenicity of three different formulations of BBV152 (3 µg with Algel-IMDG, 6 µg with Algel-IMDG, or 6 µg with Algel) and one Algel-only control (no antigen), with the first dose administered on day 0 and the second dose on day 14. The 3 µg and 6 µg with Algel-IMDG formulations were selected for this phase 2 study. Herein, we report interim findings of the phase 2 trial on the immunogenicity and safety of BBV152, with the first dose administered on day 0 and the second dose on day 28. METHODS: We did a double-blind, randomised, multicentre, phase 2 clinical trial to evaluate the immunogenicity and safety of BBV152 in healthy adults and adolescents (aged 12-65 years) at nine hospitals in India. Participants with positive SARS-CoV-2 nucleic acid and serology tests were excluded. Participants were randomly assigned (1:1) to receive either 3 µg with Algel-IMDG or 6 µg with Algel-IMDG. Block randomisation was done by use of an interactive web response system. Participants, investigators, study coordinators, study-related personnel, and the sponsor were masked to treatment group allocation. Two intramuscular doses of vaccine were administered on day 0 and day 28. The primary outcome was SARS-CoV-2 wild-type neutralising antibody titres and seroconversion rates (defined as a post-vaccination titre that was at least four-fold higher than the baseline titre) at 4 weeks after the second dose (day 56), measured by use of the plaque-reduction neutralisation test (PRNT50) and the microneutralisation test (MNT50). The primary outcome was assessed in all participants who had received both doses of the vaccine. Cell-mediated responses were a secondary outcome and were assessed by T-helper-1 (Th1)/Th2 profiling at 2 weeks after the second dose (day 42). Safety was assessed in all participants who received at least one dose of the vaccine. In addition, we report immunogenicity results from a follow-up blood draw collected from phase 1 trial participants at 3 months after they received the second dose (day 104). This trial is registered at ClinicalTrials.gov, NCT04471519. FINDINGS: Between Sept 5 and 12, 2020, 921 participants were screened, of whom 380 were enrolled and randomly assigned to the 3 µg with Algel-IMDG group (n=190) or 6 µg with Algel-IMDG group (n=190). Geometric mean titres (GMTs; PRNT50) at day 56 were significantly higher in the 6 µg with Algel-IMDG group (197·0 [95% CI 155·6-249·4]) than the 3 µg with Algel-IMDG group (100·9 [74·1-137·4]; p=0·0041). Seroconversion based on PRNT50 at day 56 was reported in 171 (92·9% [95% CI 88·2-96·2] of 184 participants in the 3 µg with Algel-IMDG group and 174 (98·3% [95·1-99·6]) of 177 participants in the 6 µg with Algel-IMDG group. GMTs (MNT50) at day 56 were 92·5 (95% CI 77·7-110·2) in the 3 µg with Algel-IMDG group and 160·1 (135·8-188·8) in the 6 µg with Algel-IMDG group. Seroconversion based on MNT50 at day 56 was reported in 162 (88·0% [95% CI 82·4-92·3]) of 184 participants in the 3 µg with Algel-IMDG group and 171 (96·6% [92·8-98·8]) of 177 participants in the 6 µg with Algel-IMDG group. The 3 µg with Algel-IMDG and 6 µg with Algel-IMDG formulations elicited T-cell responses that were biased to a Th1 phenotype at day 42. No significant difference in the proportion of participants who had a solicited local or systemic adverse reaction in the 3 µg with Algel-IMDG group (38 [20·0%; 95% CI 14·7-26·5] of 190) and the 6 µg with Algel-IMDG group (40 [21·1%; 15·5-27·5] of 190) was observed on days 0-7 and days 28-35; no serious adverse events were reported in the study. From the phase 1 trial, 3-month post-second-dose GMTs (MNT50) were 39·9 (95% CI 32·0-49·9) in the 3µg with Algel-IMDG group, 69·5 (53·7-89·9) in the 6 µg with Algel-IMDG group, 53·3 (40·1-71·0) in the 6 µg with Algel group, and 20·7 (14·5-29·5) in the Algel alone group. INTERPRETATION: In the phase 1 trial, BBV152 induced high neutralising antibody responses that remained elevated in all participants at 3 months after the second vaccination. In the phase 2 trial, BBV152 showed better reactogenicity and safety outcomes, and enhanced humoral and cell-mediated immune responses compared with the phase 1 trial. The 6 µg with Algel-IMDG formulation has been selected for the phase 3 efficacy trial. FUNDING: Bharat Biotech International. TRANSLATION: For the Hindi translation of the abstract see Supplementary Materials section.


Subject(s)
COVID-19 Vaccines/adverse effects , COVID-19 Vaccines/immunology , COVID-19/immunology , Immunogenicity, Vaccine/immunology , SARS-CoV-2/immunology , Vaccines, Inactivated/adverse effects , Vaccines, Inactivated/immunology , Adolescent , Adult , Aged , Antibodies, Neutralizing/immunology , Child , Double-Blind Method , Drug-Related Side Effects and Adverse Reactions/immunology , Female , Follow-Up Studies , Humans , Male , Middle Aged , Th1 Cells/immunology , Th2 Cells/immunology , Vaccination/adverse effects , Young Adult
12.
Sci Rep ; 11(1): 12425, 2021 06 14.
Article in English | MEDLINE | ID: covidwho-1268002

ABSTRACT

Saliva has significant advantages as a test medium for detection of SARS-CoV-2 infection in patients, such as ease of collection, minimal requirement of supplies and trained personnel, and safety. Comprehensive validation in a large cohort of prospectively collected specimens with unknown SARS-CoV-2 status should be performed to evaluate the potential and limitations of saliva-based testing. We developed a saliva-based testing pipeline for detection of SARS-CoV-2 nucleic acids using real-time reverse transcription PCR (RT-PCR) and droplet digital PCR (ddPCR) readouts, and measured samples from 137 outpatients tested at a curbside testing facility and 29 inpatients hospitalized for COVID-19. These measurements were compared to the nasal swab results for each patient performed by a certified microbiology laboratory. We found that our saliva testing positively detects 100% (RT-PCR) and 93.75% (ddPCR) of curbside patients that were identified as SARS-CoV-2 positive by the Emergency Use Authorization (EUA) certified nasal swab testing assay. Quantification of viral loads by ddPCR revealed an extremely wide range, with 1 million-fold difference between individual patients. Our results demonstrate for both community screening and hospital settings that saliva testing reliability is on par with that of the nasal swabs in detecting infected cases, and has potential for higher sensitivity when combined with ddPCR in detecting low-abundance viral loads that evade traditional testing methods.


Subject(s)
COVID-19/diagnosis , SARS-CoV-2/genetics , Saliva/virology , Adult , COVID-19/virology , Female , Humans , Male , Middle Aged , RNA, Viral/analysis , RNA, Viral/genetics , RNA, Viral/metabolism , Reagent Kits, Diagnostic , Real-Time Polymerase Chain Reaction , Reverse Transcriptase Polymerase Chain Reaction , SARS-CoV-2/isolation & purification , Viral Load
13.
ACS Nano ; 15(6): 10309-10317, 2021 06 22.
Article in English | MEDLINE | ID: covidwho-1261990

ABSTRACT

The global SARS-CoV-2 coronavirus pandemic has led to a surging demand for rapid and efficient viral infection diagnostic tests, generating a supply shortage in diagnostic test consumables including nucleic acid extraction kits. Here, we develop a modular method for high-yield extraction of viral single-stranded nucleic acids by using "capture" ssDNA sequences attached to carbon nanotubes. Target SARS-CoV-2 viral RNA can be captured by ssDNA-nanotube constructs via hybridization and separated from the liquid phase in a single-tube system with minimal chemical reagents, for downstream quantitative reverse transcription polymerase chain reaction (RT-qPCR) detection. This nanotube-based extraction method enables 100% extraction yield of target SARS-CoV-2 RNA from phosphate-buffered saline in comparison to ∼20% extraction yield when using a commercial silica-column kit. Notably, carbon nanotubes enable extraction of nucleic acids directly from 50% human saliva with a similar efficiency as achieved with commercial DNA/RNA extraction kits, thereby bypassing the need for further biofluid purification and avoiding the use of commercial extraction kits. Carbon nanotube-based extraction of viral nucleic acids facilitates high-yield and high-sensitivity identification of viral nucleic acids such as the SARS-CoV-2 viral genome with a reduced reliance on reagents affected by supply chain obstacles.


Subject(s)
COVID-19 , Nanotubes, Carbon , Nucleic Acids , Humans , RNA, Viral/genetics , Real-Time Polymerase Chain Reaction , Reverse Transcriptase Polymerase Chain Reaction , Reverse Transcription , SARS-CoV-2 , Sensitivity and Specificity
14.
Build Environ ; 201: 108009, 2021 Aug 15.
Article in English | MEDLINE | ID: covidwho-1252536

ABSTRACT

In previous reports, the positive SARS-CoV-2 nucleic acid was detected in the fecal samples from confirmed pneumonia patients, suggesting a high probability of the fecal-oral transmission. To date, however, the role played by the drainage system of a high-rise building in the virus transmission is not clear and especially studies on the dynamics mechanism behind is scarce. From this point of view, the present work carries out a computational fluid dynamics (CFD) modeling to investigate the effects of the water seal effectiveness of the floor drain, the negative/positive pressures (P 1 , P 2 ) in the bathroom, temperature differential (ΔT), outside wind velocity (v), the piping fittings and the negative pressure at the cowl (P 3 ) on the transmission of the virus-laden aerosol particles in a drainage system of a typical 7-storeys residential building. The CFD models are first validated by the previous experiments in literature. Numerical results imply that the drainage system might play an essential role to the virus transmission. Then, results indicate that, the leakage risk of the aerosol particles via the floor drain with inefficient water-seal (UFD) mainly exists at the upper floors above the neutral pressure level (NPL). Besides, the negative and positive pressures at the bathroom can enhance and reduce the exposure risk of aerosol particles from the corresponding UFD, respectively. The ΔT increasing does not modify the location of the NPL. Moreover, the exposure risk of aerosol particles can be effectively avoided by the well water-sealed floor drains and/or the presence of a proper negative pressure at the cowl on the top floor. Finally, based on the CFD results, several protection suggestions on the drainage system and human activities are provided.

15.
Ital J Pediatr ; 47(1): 123, 2021 Jun 02.
Article in English | MEDLINE | ID: covidwho-1255951

ABSTRACT

OBJECTIVES: To describe clinical characteristics, laboratory tests, radiological data and outcome of pediatric cases with SARS-CoV-2 infection complicated by neurological involvement. STUDY DESIGN: A computerized search was conducted using PubMed. An article was considered eligible if it reported data on pediatric patient(s) with neurological involvement related to SARS-CoV-2 infection. We also described a case of an acute disseminated encephalomyelitis (ADEM) in a 5-year-old girl with SARS-CoV-2 infection: this case was also included in the systematic review. RESULTS: Forty-four articles reporting 59 cases of neurological manifestations in pediatric patients were included in our review. Most (32/59) cases occurred in the course of a multisystem inflammatory syndrome in children (MIS-C). Neurological disorders secondary to cerebrovascular involvement were reported in 10 cases: 4 children with an ischemic stroke, 3 with intracerebral hemorrhage, 1 with a cerebral sinus venous thrombosis, 1 with a subarachnoid hemorrhage, 1 with multiple diffuse microhemorrhages. Reversible splenial lesions were recognized in 9 cases, benign intracranial hypertension in 4 patients, meningoencephalitis in 4 cases, autoimmune encephalitis in 1 girl, cranial nerves impairment in 2 patients and transverse myelitis in 1 case. Five cases had Guillain-Barré syndrome (GBS) and two, including ours, had ADEM. Radiological investigations were performed in almost all cases (45/60): the most recurrent radiological finding was a signal change in the splenium of the corpus callosum. The presence of SARS-CoV-2 viral nucleic acid in the cerebrospinal fluid was proved only in 2 cases. The outcome was favorable in almost all, except in 5 cases. CONCLUSIONS: Our research highlights the large range of neurological manifestations and their presumed pathogenic pathways associated with SARS-CoV-2 infection in children. Nervous system involvement could be isolated, developing during COVID-19 or after its recovery, or arise in the context of a MIS-C. The most reported neurological manifestations are cerebrovascular accidents, reversible splenial lesions, GBS, benign intracranial hypertension, meningoencephalitis; ADEM is also a possible complication, as we observed in our patient. Further studies are required to investigate all the neurological complications of SARS-CoV-2 infection and their underlying pathogenic mechanism.


Subject(s)
COVID-19/complications , Nervous System Diseases/virology , Pneumonia, Viral/complications , Child , Humans , Pneumonia, Viral/virology , SARS-CoV-2
16.
Nanoscale ; 13(22): 10133-10142, 2021 Jun 14.
Article in English | MEDLINE | ID: covidwho-1249216

ABSTRACT

Efficient point-of-care diagnosis of severe acute respiratory syndrome-corovavirus-2 (SARS-CoV-2) is crucial for the early control of novel coronavirus infections. At present, polymerase chain reaction (PCR) is primarily used to detect SARS-CoV-2. Despite the high sensitivity, the PCR process is time-consuming and complex which limits its applicability for rapid testing of large-scale outbreaks. Here, we propose a rapid and easy-to-implement approach for SARS-CoV-2 detection based on surface enhanced infrared absorption (SEIRA) spectroscopy. The evaporated gold nano-island films are used as SEIRA substrates which are functionalized with the single-stranded DNA probes for specific binding to selected SARS-CoV-2 genomic sequences. The infrared absorption spectra are analyzed using the principal component analysis method to identify the key characteristic differences between infected and control samples. The SEIRA-based biosensor demonstrates rapid detection of SARS-CoV-2, completing the detection of 1 µM viral nucleic acids within less than 5 min without any amplification. When combined with the recombinase polymerase amplification treatment, the detection capability of 2.98 copies per µL (5 aM) can be completed within 30 min. This approach provides a simple and economical alternative for COVID-19 diagnosis, which can be potentially useful in monitoring and controlling future pandemics in a timely manner.


Subject(s)
COVID-19 , Nucleic Acids , COVID-19 Testing , Humans , Nucleic Acid Amplification Techniques , RNA, Viral , SARS-CoV-2 , Sensitivity and Specificity , Spectrum Analysis
17.
Biomed Pharmacother ; 140: 111772, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1244709

ABSTRACT

The recent pandemic of novel coronavirus disease (COVID-19) has spread globally and infected millions of people. The quick and specific detection of the nucleic acid of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) remains a challenge within healthcare providers. Currently, quantitative reverse transcription-polymerase chain reaction (RT-qPCR) is the widely used method to detect the SARS-CoV-2 from the human clinical samples. RT-qPCR is expensive equipment and needs skilled personnel as well as lengthy detection time. RT-qPCR limitation needed an alternative healthcare technique to overcome with a fast and cheaper detection method. By applying the principles of CRISPR technology, several promising detection methods giving hope to the healthcare community. CRISPR-based detection methods include SHERLOCK-Covid, STOP-Covid, AIOD-CRISPR, and DETECTR platform. These methods have comparative advantages and drawbacks. Among these methods, AIOD-CRISPR and DETECTR are reasonably better diagnostic methods than the others if we compare the time taken for the test, the cost associated with each test, and their capability of detecting SARS-CoV-2 in the clinical samples. It may expect that the promising CRISPR-based methods would facilitate point-of-care (POC) applications in the CRISPR-built next-generation novel coronavirus diagnostics.


Subject(s)
COVID-19/virology , CRISPR-Cas Systems/genetics , Clustered Regularly Interspaced Short Palindromic Repeats/genetics , SARS-CoV-2/genetics , COVID-19 Testing/methods , Humans , Pandemics/prevention & control
18.
Front Med (Lausanne) ; 8: 620727, 2021.
Article in English | MEDLINE | ID: covidwho-1241175

ABSTRACT

Background and Objectives: Although the pathogenesis and treatment of coronavirus disease 2019 (COVID-19) have been gradually revealed, the risk for re-emergence of coronavirus nucleic acids in recovered patients remains poorly understood. Hence, this study evaluated the risk predictors associated with re-positivity for virus nucleic acid. Methods: Between February 1 and March 20, 2020, we retrospectively reviewed the clinical epidemiological data of 129 COVID-19 patients who were treated at Zhongxiang People's Hospital of Hubei Province in China. Subsequently, a risk prediction model for the re-positivity of virus nucleic acid was developed, and a receiver operating characteristic (ROC) curve was drawn for further validation. Results: In this study, the rate of re-positivity for virus nucleic acid was 17.8% (23/129) where all re-positivity cases were asymptomatic. The median time interval from discharge to nucleic acid re-positivity to discharge after being cured again was 11.5 days (range: 7-23 days). Multivariate logistic regression analysis showed that leukocytopenia [odds ratio (OR) 7.316, 95% confidence interval (CI) 2.319-23.080, p = 0.001], prealbumin < 150 mg/L (OR 4.199, 95% CI 1.461-12.071, p = 0.008), and hyperpyrexia (body temperature >39°C, OR 4.643, 95% CI 1.426-15.117, p = 0.011) were independent risk factors associated with re-positivity. The area under the ROC curve was 0.815 (95% CI, 0.729-0.902). Conclusion: COVID-19 patients with leukocytopenia, low prealbumin level, and hyperpyrexia are more likely to test positive for virus nucleic acid after discharge. Timely and effective treatment and appropriate extension of hospital stays and quarantine periods may be feasible strategies for managing such patients.

19.
Lancet Reg Health West Pac ; 4: 100045, 2020 Nov.
Article in English | MEDLINE | ID: covidwho-1235945

ABSTRACT

BACKGROUND: The possibility of 2019 novel coronavirus disease (COVID-19) transmission to neonates through breast milk remains unverified. METHODS: This paper presents the interim results of a longitudinal study being carried out in Hubei province. As of 1 April 2020, 24 mothers confirmed with COVID-19, 19 mothers suspected with COVID-19 but Polymerase chain reaction negative, and 21 mothers without COVID-19 and their neonates have been recruited. Telephone follow-up was conducted to collect information on breastfeeding practices. Forty-four breast milk samples were collected from 16 of the 24 mothers with confirmed COVID-19 for the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) ribonucleic acid (RNA) and antibodies (IgM and IgG) testing. FINDINGS: The average mother-child separation time was 36•7 ± 21•1 days among mothers confirmed with COVID-19, significantly longer than that of the suspected group (16•6 ± 13•1 days) and control group (10•5 ± 8•2 days). Both the COVID-19 confirmed (58•3%) and suspected (52•6%) groups presented significantly lower rates of breastfeeding as compared with the control group (95•2%). All 44 breast milk samples tested negative for the SARS-CoV-2 nucleic acid. Thirty-eight breast milk samples underwent antibody testing and all tested negative for IgG. Twenty-one breast milk samples from 8 women tested positive for IgM, while the remaining samples from 11 women tested negative. INTERPRETATION: Considering the lack of evidence for SARS-CoV-2 transmission through breast milk, breastfeeding counselling along with appropriate hand hygiene precautions and facemasks should be provided to all pregnant women. FUNDING: The study was funded by the Hong Kong Committee for UNICEF.

20.
Virol Sin ; 35(6): 699-712, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-1217487

ABSTRACT

The on-going global pandemic of coronavirus disease 2019 (COVID-19) caused by a novel coronavirus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been underway for about 11 months. Through November 20, 2020, 51 detection kits for SARS-CoV-2 nucleic acids (24 kits), antibodies (25 kits), or antigens (2 kits) have been approved by the National Medical Products Administration of China (NMPA). Convenient and reliable SARS-CoV-2 detection assays are urgently needed worldwide for strategic control of the pandemic. In this review, the detection kits approved in China are summarised and the three types of tests, namely nucleic acid, serological and antigen detection, which are available for the detection of COVID-19 are discussed in detail. The development of novel detection kits will lay the foundation for the control and prevention of the COVID-19 pandemic globally.


Subject(s)
COVID-19/diagnosis , Reagent Kits, Diagnostic , SARS-CoV-2/isolation & purification , COVID-19 Serological Testing/methods , COVID-19 Testing , China , Clinical Laboratory Techniques , Humans , Immunoassay/methods , Luminescent Measurements , Molecular Diagnostic Techniques/methods , Pandemics , Real-Time Polymerase Chain Reaction
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