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1.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 50(6): 748-754, 2021 Dec 25.
Article in English | MEDLINE | ID: covidwho-1753705

ABSTRACT

To explore the application value of nanopore sequencing technique in the diagnosis and treatment of secondary infections in patients with severe coronavirus disease 2019 (COVID-19). A total of 77 clinical specimens from 3 patients with severe COVID-19 were collected. After heat inactivation, all samples were subjected to total nucleic acid extraction based on magnetic bead enrichment. The extracted DNA was used for DNA library construction, then nanopore real-time sequencing detection was performed. The sequencing data were subjected to Centrifuge software database species matching and R program differential analysis to obtain potential pathogen identification. Nanopore sequencing results were compared with respiratory pathogen qPCR panel screening and conventional microbiological testing results to verify the effectiveness of nanopore sequencing detection. Nanopore sequencing results showed that positive pathogen were obtained in 44 specimens (57.1%). The potential pathogens identified by nanopore sequencing included , , and , et al. , , were also detected in clinical microbiological culture-based detection; was detected in respiratory pathogen screening qPCR panel; was only detected by the nanopore sequencing technique. Comprehensive considerations with the clinical symptoms, the patient was treated with antibiotics against , and the infection was controlled. Nanopore sequencing may assist the diagnosis and treatment of severe COVID-19 patients through rapid identification of potential pathogens.


Subject(s)
COVID-19 , Coinfection , Nanopore Sequencing , Nanopores , COVID-19/diagnosis , Humans , Sequence Analysis, DNA/methods
2.
Chin Med J (Engl) ; 133(9): 1039-1043, 2020 May 05.
Article in English | MEDLINE | ID: covidwho-1722619

ABSTRACT

BACKGROUND: A patient's infectivity is determined by the presence of the virus in different body fluids, secretions, and excreta. The persistence and clearance of viral RNA from different specimens of patients with 2019 novel coronavirus disease (COVID-19) remain unclear. This study analyzed the clearance time and factors influencing 2019 novel coronavirus (2019-nCoV) RNA in different samples from patients with COVID-19, providing further evidence to improve the management of patients during convalescence. METHODS: The clinical data and laboratory test results of convalescent patients with COVID-19 who were admitted to from January 20, 2020 to February 10, 2020 were collected retrospectively. The reverse transcription polymerase chain reaction (RT-PCR) results for patients' oropharyngeal swab, stool, urine, and serum samples were collected and analyzed. Convalescent patients refer to recovered non-febrile patients without respiratory symptoms who had two successive (minimum 24 h sampling interval) negative RT-PCR results for viral RNA from oropharyngeal swabs. The effects of cluster of differentiation 4 (CD4)+ T lymphocytes, inflammatory indicators, and glucocorticoid treatment on viral nucleic acid clearance were analyzed. RESULTS: In the 292 confirmed cases, 66 patients recovered after treatment and were included in our study. In total, 28 (42.4%) women and 38 men (57.6%) with a median age of 44.0 (34.0-62.0) years were analyzed. After in-hospital treatment, patients' inflammatory indicators decreased with improved clinical condition. The median time from the onset of symptoms to first negative RT-PCR results for oropharyngeal swabs in convalescent patients was 9.5 (6.0-11.0) days. By February 10, 2020, 11 convalescent patients (16.7%) still tested positive for viral RNA from stool specimens and the other 55 patients' stool specimens were negative for 2019-nCoV following a median duration of 11.0 (9.0-16.0) days after symptom onset. Among these 55 patients, 43 had a longer duration until stool specimens were negative for viral RNA than for throat swabs, with a median delay of 2.0 (1.0-4.0) days. Results for only four (6.9%) urine samples were positive for viral nucleic acid out of 58 cases; viral RNA was still present in three patients' urine specimens after throat swabs were negative. Using a multiple linear regression model (F = 2.669, P = 0.044, and adjusted R = 0.122), the analysis showed that the CD4+ T lymphocyte count may help predict the duration of viral RNA detection in patients' stools (t = -2.699, P = 0.010). The duration of viral RNA detection from oropharyngeal swabs and fecal samples in the glucocorticoid treatment group was longer than that in the non-glucocorticoid treatment group (15 days vs. 8.0 days, respectively; t = 2.550, P = 0.013) and the duration of viral RNA detection in fecal samples in the glucocorticoid treatment group was longer than that in the non-glucocorticoid treatment group (20 days vs. 11 days, respectively; t = 4.631, P < 0.001). There was no statistically significant difference in inflammatory indicators between patients with positive fecal viral RNA test results and those with negative results (P > 0.05). CONCLUSIONS: In brief, as the clearance of viral RNA in patients' stools was delayed compared to that in oropharyngeal swabs, it is important to identify viral RNA in feces during convalescence. Because of the delayed clearance of viral RNA in the glucocorticoid treatment group, glucocorticoids are not recommended in the treatment of COVID-19, especially for mild disease. The duration of RNA detection may relate to host cell immunity.


Subject(s)
Betacoronavirus/genetics , Coronavirus Infections/genetics , Pneumonia, Viral/genetics , RNA, Viral/genetics , Adult , Aged , COVID-19 , COVID-19 Testing , Clinical Laboratory Techniques , Coronavirus Infections/diagnosis , Coronavirus Infections/rehabilitation , Female , Humans , Male , Middle Aged , Pandemics , Pneumonia, Viral/rehabilitation , Real-Time Polymerase Chain Reaction , Retrospective Studies , SARS-CoV-2
3.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-323671

ABSTRACT

Background: Existing literatures demonstrated that meteorological factors could be of importance in affecting the spread patterns of the respiratory infectious diseases. However, how ambient temperature may influence the transmissibility of COVID-19 remains unclear. Objectives: We explore the association between ambient temperature and transmissibility of COVID-19 in different regions across China. Methods: : The surveillance data on COVID-19 and meteorological factors were collected from 28 provincial level regions in China, and estimated the instantaneous reproductive number ( R t ). The generalized additive model was used to assess the relationship between mean temperature and R t . Results: : There were 12745 COVID-19 cases collected in the study areas. We report the effect of temperature on R t is not of statistical significance, which holds for most of included regions except for those in North China. Conclusions: We found little statistical evidence for that the higher temperature may reduce the transmissibility of COVID-19.

4.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-322743

ABSTRACT

Background: Towards the end of December 2019, the Wuhan health commission declared an outbreak of clusters of pneumonia in patients. Sequencing indicated that this disease (COVID-19) was caused by a novel coronavirus (SARS-CoV-2). The outbreak of COVID-19 is currently still underway. Methods We recruited 75 SARS-CoV-2 infected patients admitted to the Center of Infectious Disease division 2 of Beijing Ditan Hospital from Jan 20 to Mar 20, 2020. Epidemiological, demographic, clinical, radiological features, laboratory data were analyzed. Results Of the 75 patients, 42(56%) patients were male and 33(44%) patients were female. The mean age of all patients was 41.5 ± 19.4 years. Male patients were more likely to become severe. There were 9 family clusters accounted for 44 patients. Patients classified as being severe had a higher frequency of fever upon admission than patients classified as moderate cases. For moderate patients, the median duration of viral shedding was 25(9.5, 42) days (range 1–63 days) from the first positive nucleic acid test compared to 14(9, 21.25) days (range 2–62 days) for severe cases. The difference between the two groups was statistically significant (p = 0.041). Cox regression analyses indicated that disease status and CRP were the factors that affect the duration of viral shedding. Virus clearance was significantly faster in severe patients compared to moderate patients(p = 0.011), and patients with CRP range in 2–10 times higher than upper limit of normal value had longer duration of viral shedding(p = 0.012). CRP and CD4 + T lymphocyte was negative correlated, and the relationship between CRP and CD4 + T lymphocyte was statistically significant (P = 0.003), with a correlation coefficient of -0.564. During the second week following the onset of illness, severe cases had higher WBC, NEU and CRP, but lower LYM, MON and EOS as compared with moderate cases (all P < 0.05). Severe cases still had lower lymphocyte counts and higher CRP than moderate cases in the third week. Conclusions Viral clearance was significantly prolonged in moderate patients, and those CRP in 2–10 times higher than upper limit of normal value. Immune response may affect the duration of viral shedding. Severe cases had a persistence lower lymphocyte count and higher CRP than moderate cases.

5.
Cell Rep Methods ; 2(2): 100173, 2022 Feb 28.
Article in English | MEDLINE | ID: covidwho-1670392

ABSTRACT

SARS-CoV-2 variants of concern (VOCs) that increase transmission or disease severity or reduce diagnostic or vaccine efficacy continue to emerge across the world. Current methods available to rapidly detect these can be resource intensive and thus sub-optimal for large-scale deployment needed during a pandemic response. Here, we describe a CRISPR-based assay that detects mutations in spike gene CRISPR PAM motif or seed regions to identify a pan-specific VOC single-nucleotide polymorphism (SNP)) ((D614G) and Alpha- and Delta-specific (S982A and D950N) SNPs. This assay exhibits good diagnostic sensitivity and strain specificity with nasal swabs and is designed for use in laboratory and point-of-care settings. This should enable rapid, high-throughput VOC identification required for surveillance and characterization efforts to inform clinical and public health decisions. Furthermore, the assay can be adapted to target similar SNPs associated with emerging SARS-CoV-2 VOCs, or other rapidly evolving viruses.

6.
J Med Virol ; 94(5): 2237-2249, 2022 May.
Article in English | MEDLINE | ID: covidwho-1664417

ABSTRACT

As the coronavirus disease 2019 (COVID-19) pandemic is still ongoing and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants are circulating worldwide, an increasing number of breakthrough infections are being detected despite the good efficacy of COVID-19 vaccines. Data on 88 COVID-19 breakthrough cases (breakthrough infections group) and 41 unvaccinated cases (unvaccinated group) from June 1 to August 22, 2021, were extracted from a cloud database established at Beijing Ditan Hospital to evaluate the clinical, immunological, and genomic characteristics of COVID-19 breakthrough infections. Among these 129 COVID-19 cases, 33 whole genomes were successfully sequenced, of which 23 were Delta variants, including 15 from the breakthrough infections group. Asymptomatic and mild cases predominated in both groups, but two patients developed severe disease in the unvaccinated group. The median time of viral shedding in the breakthrough infections group was significantly lower than that in the unvaccinated group (p = 0.003). In the breakthrough infections group, the IgG titers showed a significantly increasing trend (p = 0.007), and the CD4 + T lymphocyte count was significantly elevated (p = 0.018). For people infected with the Delta variant in the two groups, no significant difference was observed in either the quantitative reverse-transcription polymerase chain reaction results or viral shedding time. In conclusion, among vaccinated patients, the cases of COVID-19 vaccine breakthrough infections were mainly asymptomatic and mild, IgG titers were significantly increased and rose rapidly, and the viral shedding time was shorter.


Subject(s)
COVID-19 , Beijing/epidemiology , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19 Vaccines , Genomics , Humans , SARS-CoV-2/genetics
8.
J Mol Diagn ; 23(9): 1078-1084, 2021 09.
Article in English | MEDLINE | ID: covidwho-1386076

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is highly contagious and has caused significant medical/socioeconomic impacts. Other than vaccination, effective public health measures, including contact tracing, isolation, and quarantine, is critical for deterring viral transmission, preventing infection progression and resuming normal activities. Viral transmission is affected by many factors, but the viral load and vitality could be among the most important ones. Although in vitro studies have indicated that the amount of virus isolated from infected individuals affects the successful rate of virus isolation, whether the viral load carried at the individual level would determine the transmissibility was unknown. We examined whether the cycle threshold (Ct) value, a measurement of viral load by RT-PCR assay, could differentiate the spreaders from the non-spreaders in a population of college students. Our results indicate that while at the population level the Ct value is lower, suggesting a higher viral load, in the symptomatic spreaders than that in the asymptomatic non-spreaders, there is a significant overlap in the Ct values between the two groups. Thus, Ct value, or the viral load, at the individual level could not predict the transmissibility. Instead, a sensitive method to detect the presence of virus is needed to identify asymptomatic individuals who may carry a low viral load but can still be infectious.


Subject(s)
COVID-19 Nucleic Acid Testing/methods , COVID-19/transmission , COVID-19/virology , Multiplex Polymerase Chain Reaction/methods , Universities/statistics & numerical data , COVID-19/epidemiology , Carrier State/virology , Contact Tracing , Female , Humans , Louisiana/epidemiology , Male , Nasopharynx/virology , Public Health , Quarantine , Retrospective Studies , Students/statistics & numerical data , Viral Load , Young Adult
9.
J Mol Diagn ; 23(9): 1078-1084, 2021 09.
Article in English | MEDLINE | ID: covidwho-1349527

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is highly contagious and has caused significant medical/socioeconomic impacts. Other than vaccination, effective public health measures, including contact tracing, isolation, and quarantine, is critical for deterring viral transmission, preventing infection progression and resuming normal activities. Viral transmission is affected by many factors, but the viral load and vitality could be among the most important ones. Although in vitro studies have indicated that the amount of virus isolated from infected individuals affects the successful rate of virus isolation, whether the viral load carried at the individual level would determine the transmissibility was unknown. We examined whether the cycle threshold (Ct) value, a measurement of viral load by RT-PCR assay, could differentiate the spreaders from the non-spreaders in a population of college students. Our results indicate that while at the population level the Ct value is lower, suggesting a higher viral load, in the symptomatic spreaders than that in the asymptomatic non-spreaders, there is a significant overlap in the Ct values between the two groups. Thus, Ct value, or the viral load, at the individual level could not predict the transmissibility. Instead, a sensitive method to detect the presence of virus is needed to identify asymptomatic individuals who may carry a low viral load but can still be infectious.


Subject(s)
COVID-19 Nucleic Acid Testing/methods , COVID-19/transmission , COVID-19/virology , Multiplex Polymerase Chain Reaction/methods , Universities/statistics & numerical data , COVID-19/epidemiology , Carrier State/virology , Contact Tracing , Female , Humans , Louisiana/epidemiology , Male , Nasopharynx/virology , Public Health , Quarantine , Retrospective Studies , Students/statistics & numerical data , Viral Load , Young Adult
10.
Microbiol Spectr ; 9(1): e0027321, 2021 09 03.
Article in English | MEDLINE | ID: covidwho-1341310

ABSTRACT

The SARS-CoV-2 B.1.1.7 variant has increased sharply in numbers worldwide and is reported to be more contagious than the nonvariant. Little is known regarding the detailed clinical features of B.1.1.7 variant infection. Data on 74 COVID-19 cases from two outbreaks in two districts of Beijing, China were extracted from a cloud database, including 41 cases from Shunyi District (Shunyi B.1.470 group) and 33 from Daxing (Daxing B.1.1.7 group) from December 25, 2020 to January 17, 2021. We conducted a comparison of the clinical characteristics. Seven clinical indicators of the Daxing B.1.1.7 group were significantly higher than those of the Shunyi group, including the proportion with fever over 38°C, the levels of C-reactive protein (CRP), serum amyloid A (SAA), creatine kinase (CK), d-dimer (DD), and CD4+ T lymphocytes (CD4+ T), and the proportion with ground-glass opacity (GGO) in the lung (P values of ≤0.05). After adjusting for age, B.1.1.7 variant infection was a risk factor for elevated CRP (P = 0·045), SAA (P = 0·011), CK (P = 0·034), and CD4+ T (P = 0.029) and for the presence of GGO (P = 0.005). The median threshold cycle (CT) value of reverse transcriptase quantitative PCR (RT-qPCR) tests of the N gene target in the Daxing B.1.1.7 group was significantly lower (P = 0.036) than that in the Shunyi B.1.470 group. Clinical features, including a more serious inflammatory response, pneumonia, and a possibly higher viral load, were detected in the cases infected with B.1.1.7 SARS-CoV-2. The B.1.1.7 variant may have increased pathogenicity. IMPORTANCE The SARS-CoV-2 B.1.1.7 variant, which was first identified in the United Kingdom, has increased sharply in numbers worldwide and was reported to be more contagious than the nonvariant. To our knowledge, no studies investigating the detailed clinical features of COVID-19 cases infected with the B.1.1.7 variant have been published. Local epidemics have rarely occurred in China, but occasionally, a small clustered outbreak triggered by an imported SARS-CoV-2 strain with only one chain of transmission could happen. From late 2020 to early 2021, two clustered COVID-19 outbreaks occurred in Beijing, one of which was caused by the B.1.1.7 variant. The COVID-19 patients from the two outbreaks received similar clinical tests, diagnoses, and treatments. We found that the B.1.1.7 variant infection could lead to a more serious inflammatory response, acute response process, more severe pneumonia, and probably higher viral loads. This therefore implies that the B.1.1.7 variant may have increased pathogenicity.


Subject(s)
COVID-19/epidemiology , COVID-19/virology , Disease Outbreaks , SARS-CoV-2/classification , SARS-CoV-2/genetics , Adult , CD4-Positive T-Lymphocytes , China/epidemiology , Cohort Studies , Female , Humans , Lung/virology , Male , Middle Aged , Prospective Studies , Risk Factors , Viral Load , Whole Genome Sequencing
11.
Viruses ; 13(7)2021 06 23.
Article in English | MEDLINE | ID: covidwho-1289015

ABSTRACT

A 59-year-old male with follicular lymphoma treated by anti-CD20-mediated B-cell depletion and ablative chemotherapy was hospitalized with a COVID-19 infection. Although the patient did not develop specific humoral immunity, he had a mild clinical course overall. The failure of all therapeutic options allowed infection to persist nearly 300 days with active accumulation of SARS-CoV-2 virus mutations. As a rescue therapy, an infusion of REGEN-COV (10933 and 10987) anti-spike monoclonal antibodies was performed 270 days from initial diagnosis. Due to partial clearance after the first dose (2.4 g), a consolidation dose (8 g) was infused six weeks later. Complete virus clearance could then be observed over the following month, after he was vaccinated with the Pfizer-BioNTech anti-COVID-19 vaccination. The successful management of this patient required prolonged enhanced quarantine, monitoring of virus mutations, pioneering clinical decisions based upon close consultation, and the coordination of multidisciplinary experts in virology, immunology, pharmacology, input from REGN, the FDA, the IRB, the health care team, the patient, and the patient's family. Current decisions to take revolve around patient's follicular lymphoma management, and monitoring for virus clearance persistence beyond disappearance of REGEN-COV monoclonal antibodies after anti-SARS-CoV-2 vaccination. Overall, specific guidelines for similar cases should be established.


Subject(s)
Antibodies, Monoclonal/therapeutic use , B-Lymphocytes/immunology , COVID-19/immunology , COVID-19/therapy , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , COVID-19/complications , Humans , Immunity, Humoral , Lymphocyte Depletion , Lymphoma, Follicular/drug therapy , Lymphoma, Follicular/therapy , Male , Middle Aged , SARS-CoV-2/genetics , Viral Vaccines/administration & dosage , Viral Vaccines/immunology
12.
Biosci Trends ; 15(2): 93-99, 2021 May 11.
Article in English | MEDLINE | ID: covidwho-1154737

ABSTRACT

As the COVID-19 epidemic is still ongoing, a more rapid detection of SARS-CoV-2 infection such as viral antigen-detection needs to be evaluated for early diagnosis of COVID-19 disease. Here, we report the dynamic changes of SARS-CoV-2 viral antigens in nasopharyngeal swabs of COVID-19 patients and its association with the viral nucleic acid clearance and clinical outcomes. Eighty-five COVID-19 patients were enrolled for detection of SARS-CoV-2 viral antigens, including 57 anti-SARS-CoV-2 antibody negative cases and 28 antibody positive cases. The viral antigen could be detected in 52.63% (30/57) patients with SARS-CoV-2 antibody negative at the early stage of SARS-CoV-2 infection, especially in the first 5 days after disease onset (p = 0.0018) and disappeared in about 8 days after disease onset. Viral antigens were highly detectable in patients with low Ct value (less than 30) of SARS-CoV-2 nucleic acid RT-PCT assay, suggesting the expression of viral antigen was associated with high viral load. Furthermore, positive antigen detection indicated disease progression, nine cases with positive antigen (9/30, 30.0%), in contrast to two cases (2/27, 7.40%) (p = 0.0444) with negative antigen, which progressed into severe disease. Thus, the viral antigens were persistent in early stages of infection when virus was in highly replicating status, and viral antigen detection promises to rapidly screen positive patients in the early stage of SARS-CoV-2 infection.


Subject(s)
Antigens, Viral/analysis , COVID-19 Testing/methods , COVID-19/diagnosis , SARS-CoV-2/immunology , Adolescent , Adult , Aged , Antigens, Viral/blood , COVID-19/immunology , COVID-19/virology , COVID-19 Nucleic Acid Testing , COVID-19 Serological Testing , COVID-19 Testing/trends , China/epidemiology , Disease Progression , Early Diagnosis , False Negative Reactions , Female , Humans , Male , Middle Aged , Nasopharynx/immunology , Nasopharynx/virology , Pandemics , SARS-CoV-2/genetics , SARS-CoV-2/isolation & purification , Time Factors , Viral Load , Young Adult
13.
Sci Adv ; 7(2)2021 01.
Article in English | MEDLINE | ID: covidwho-1066788

ABSTRACT

Point-of-care COVID-19 assays that are more sensitive than the current RT-PCR (reverse transcription polymerase chain reaction) gold standard assay are needed to improve disease control efforts. We describe the development of a portable, ultrasensitive saliva-based COVID-19 assay with a 15-min sample-to-answer time that does not require RNA isolation or laboratory equipment. This assay uses CRISPR-Cas12a activity to enhance viral amplicon signal, which is stimulated by the laser diode of a smartphone-based fluorescence microscope device. This device robustly quantified viral load over a broad linear range (1 to 105 copies/µl) and exhibited a limit of detection (0.38 copies/µl) below that of the RT-PCR reference assay. CRISPR-read SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) RNA levels were similar in patient saliva and nasal swabs, and viral loads measured by RT-PCR and the smartphone-read CRISPR assay demonstrated good correlation, supporting the potential use of this portable assay for saliva-based point-of-care COVID-19 diagnosis.


Subject(s)
COVID-19 Nucleic Acid Testing , COVID-19/diagnosis , Point-of-Care Testing , Saliva/virology , Smartphone , Animals , CRISPR-Cas Systems , Chlorocebus aethiops , Computer Simulation , Female , Humans , Limit of Detection , Macaca mulatta , Male , Molecular Diagnostic Techniques/instrumentation , Reverse Transcriptase Polymerase Chain Reaction , Sensitivity and Specificity , Vero Cells , Viral Load
14.
Sci Adv ; 7(2)2021 01.
Article in English | MEDLINE | ID: covidwho-1066787

ABSTRACT

Point-of-care COVID-19 assays that are more sensitive than the current RT-PCR (reverse transcription polymerase chain reaction) gold standard assay are needed to improve disease control efforts. We describe the development of a portable, ultrasensitive saliva-based COVID-19 assay with a 15-min sample-to-answer time that does not require RNA isolation or laboratory equipment. This assay uses CRISPR-Cas12a activity to enhance viral amplicon signal, which is stimulated by the laser diode of a smartphone-based fluorescence microscope device. This device robustly quantified viral load over a broad linear range (1 to 105 copies/µl) and exhibited a limit of detection (0.38 copies/µl) below that of the RT-PCR reference assay. CRISPR-read SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) RNA levels were similar in patient saliva and nasal swabs, and viral loads measured by RT-PCR and the smartphone-read CRISPR assay demonstrated good correlation, supporting the potential use of this portable assay for saliva-based point-of-care COVID-19 diagnosis.


Subject(s)
COVID-19 Nucleic Acid Testing , COVID-19/diagnosis , Point-of-Care Testing , Saliva/virology , Smartphone , Animals , CRISPR-Cas Systems , Chlorocebus aethiops , Computer Simulation , Female , Humans , Limit of Detection , Macaca mulatta , Male , Molecular Diagnostic Techniques/instrumentation , Reverse Transcriptase Polymerase Chain Reaction , Sensitivity and Specificity , Vero Cells , Viral Load
15.
Int J Infect Dis ; 103: 540-548, 2021 Feb.
Article in English | MEDLINE | ID: covidwho-965487

ABSTRACT

OBJECTIVES: This study intended to investigate the dynamics of anti-spike (S) IgG and IgM antibodies in COVID-19 patients. METHODS: Anti-S IgG/IgM was determined by a semi-quantitative fluorescence immunoassay in the plasma of COVID-19 patients at the manifestation and rehabilitation stages. The immunoreactivity to full-length S proteins, C-terminal domain (CTD), and N-terminal domain (NTD) of S1 fragments were determined by an ELISA assay. Clinical properties at admission and discharge were collected simultaneously. RESULTS: The positive rates of anti-S IgG/IgM in COVID-19 patients were elevated after rehabilitation compared to the in-patients. Anti-S IgG and IgM were not apparent until day 14 and day ten, respectively, according to Simple Moving Average analysis with five days' slide window deduction. More than 90% of the rehabilitation patients exhibited IgG and IgM responses targeting CTD-S1 fragments. Decreased total peripheral lymphocytes, CD4+ and CD8+ T cell counts were seen in COVID-19 patients at admission and recovered after the rehabilitation. CONCLUSIONS: Anti-S IgG and IgM do not appear at the onset with the decrease in T cells, making early serological screening less significant. However, the presence of high IgG and IgM to S1-CTD in the recovered patients highlights humoral responses after SARS-CoV-2 infection, which might be associated with efficient immune protection in COVID-19 patients.


Subject(s)
Antibodies, Viral/blood , COVID-19/diagnosis , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , Adult , Aged , Aged, 80 and over , COVID-19 Testing , Female , Humans , Immunoglobulin G/blood , Immunoglobulin M/blood , Male , Middle Aged
16.
Environ Res ; 193: 110576, 2021 02.
Article in English | MEDLINE | ID: covidwho-956049

ABSTRACT

BACKGROUND: Existing literatures demonstrated that meteorological factors could be of importance in affecting the spread patterns of the respiratory infectious diseases. However, how ambient temperature may influence the transmissibility of COVID-19 remains unclear. OBJECTIVES: We explore the association between ambient temperature and transmissibility of COVID-19 in different regions across China. METHODS: The surveillance data on COVID-19 and meteorological factors were collected from 28 provincial level regions in China, and estimated the instantaneous reproductive number (Rt). The generalized additive model was used to assess the relationship between mean temperature and Rt. RESULTS: There were 12,745 COVID-19 cases collected in the study areas. We report the associated effect of temperature on Rt is likely to be negative but not of statistical significance, which holds for most Chinese regions. CONCLUSIONS: We found little statistical evidence for that the higher temperature may reduce the transmissibility of COVID-19. Since intensive control measures against the COVID-19 epidemics were implemented in China, we acknowledge this may impact the underlying effect size estimation, and thus cautiousness should be taken when interpreting our findings.


Subject(s)
COVID-19 , China , Humans , Meteorological Concepts , SARS-CoV-2 , Temperature
17.
Nat Commun ; 11(1): 5859, 2020 11 17.
Article in English | MEDLINE | ID: covidwho-933687

ABSTRACT

The outbreak of COVID-19 has become a worldwide pandemic. The pathogenesis of this infectious disease and how it differs from other drivers of pneumonia is unclear. Here we analyze urine samples from COVID-19 infection cases, healthy donors and non-COVID-19 pneumonia cases using quantitative proteomics. The molecular changes suggest that immunosuppression and tight junction impairment occur in the early stage of COVID-19 infection. Further subgrouping of COVID-19 patients into moderate and severe types shows that an activated immune response emerges in severely affected patients. We propose a two-stage mechanism of pathogenesis for this unusual viral infection. Our data advance our understanding of the clinical features of COVID-19 infections and provide a resource for future mechanistic and therapeutics studies.


Subject(s)
Coronavirus Infections/immunology , Coronavirus Infections/pathology , Pneumonia, Viral/immunology , Pneumonia, Viral/pathology , Betacoronavirus/pathogenicity , Biomarkers/urine , COVID-19 , Coronavirus Infections/urine , Disease Progression , Humans , Immune Tolerance , Pandemics , Pneumonia/immunology , Pneumonia/pathology , Pneumonia/urine , Pneumonia, Viral/urine , Proteome/analysis , SARS-CoV-2 , Tight Junctions/pathology
18.
BMC Infect Dis ; 20(1): 779, 2020 Oct 20.
Article in English | MEDLINE | ID: covidwho-883565

ABSTRACT

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has become a public health emergency of international concern. SARS-CoV-2 RNA detection is the diagnostic criterion for coronavirus disease 2019 (COVID-19). Nevertheless, RNA detection has many limitations, such as being time-consuming and cost-prohibitive, and it must be performed in specialized laboratories. Virus antibody detection is a routine method for screening for multiple viruses, but data about SARS-CoV-2 antibody detection are limited. METHOD: Throat swabs and blood were collected from 67 suspected SARS-CoV-2 infection patients at the Affiliated Hospital of Zunyi Medical University and Zunyi Fourth People's Hospital isolated observation departments. Throat swab samples were subjected to SARS-CoV-2 RNA detection by real-time PCR. Blood was used subjected to SARS-CoV-2 IgG/IgM detection by an enzyme-linked immunosorbent assay (ELISA) and gold immunochromatography assay (GICA). Blood underwent C-reactive protein detection by immunoturbidimetry, and white blood cells, neutrophil percentages and lymphocyte percentages were counted and calculated, respectively. Clinical symptoms, age and lifestyle habits (smoking and drinking) in all patients were recorded. Data were analysed using SPSS version 19. The results were confirmed by T and χ2 tests; correlations with detection results were analysed by kappa coefficients. Odds ratio (OR) and corrected OR values were analysed by logistic regression. P < 0.05 was considered statistically significant. RESULTS: Of the 67 patients included in this study, 26 were SARS-CoV-2 RNA-positive. GICA IgM sensitivity was 50.9% (13/26), and specificity was 90.2% (37/41). ELISA IgM sensitivity was 76.9% (20/26), and specificity was 90.2% (37/41). ELISA IgG sensitivity was 76.9% (20/26), and specificity was 95.1% (39/41). The kappa coefficients between RNA detection and ELISA IgG, ELISA IgM, and GICA IgM results were 0.741 (P < 0.01), 0.681 (P < 0.01) and 0.430 (P < 0.01), respectively. CONCLUSION: Among the candidate blood indicators, serum IgG and IgM detected by ELISA had the best consistency and validity when compared with standard RNA detection; these indicators can be used as potential preliminary screening tools to identify those who should undergo nucleic acid detection in laboratories without RNA detection abilities or as a supplement to RNA detection.


Subject(s)
Betacoronavirus/genetics , Betacoronavirus/immunology , Clinical Laboratory Techniques , Coronavirus Infections/diagnosis , Enzyme-Linked Immunosorbent Assay/methods , Pneumonia, Viral/diagnosis , RNA, Viral/genetics , Real-Time Polymerase Chain Reaction/methods , Adult , Aged , Aged, 80 and over , Antibodies, Viral/blood , COVID-19 , COVID-19 Testing , Cohort Studies , Coronavirus Infections/virology , Female , Humans , Immunoglobulin G/blood , Immunoglobulin M/blood , Male , Middle Aged , Pandemics , Pneumonia, Viral/virology , SARS-CoV-2 , Sensitivity and Specificity
19.
Psychiatr Serv ; 71(12): 1285-1287, 2020 12 01.
Article in English | MEDLINE | ID: covidwho-835596

ABSTRACT

OBJECTIVE: This study aimed to explore the transmission of COVID-19 in a U.S. state psychiatric hospital setting. METHODS: Symptomatic and asymptomatic patients were tested throughout a large psychiatric hospital to determine penetrance. The hospital followed initial Centers for Disease Control and Prevention (CDC) guidelines. RESULTS: Seventy-eight percent (N=51 of 65) of tested patients in the building where the first positive patient was housed (building zero) tested positive for COVID-19. Eighty-eight percent (N=14 of 16) of tested asymptomatic patients in building zero were positive, compared with 12% (N=6 of 51) of randomly selected asymptomatic patients in a sample from the rest of the hospital. CONCLUSIONS: A high percentage of patients can become positive for COVID-19 despite following initial CDC guidelines. As such, use of masks by all patients in close-quarter settings prior to the first positive case appears warranted. Recent CDC guidelines align with this strategy.


Subject(s)
Asymptomatic Infections/epidemiology , COVID-19 , Cross Infection , Hospitals, Psychiatric/statistics & numerical data , Infection Control , Mental Disorders , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19/transmission , COVID-19 Testing/methods , COVID-19 Testing/statistics & numerical data , Cross Infection/diagnosis , Cross Infection/epidemiology , Cross Infection/prevention & control , Cross Infection/virology , Epidemiologic Studies , Female , Hospitals, State/statistics & numerical data , Humans , Infection Control/methods , Infection Control/standards , Inpatients/statistics & numerical data , Male , Mental Disorders/epidemiology , Mental Disorders/therapy , Middle Aged , Practice Guidelines as Topic , Random Allocation , SARS-CoV-2 , United States/epidemiology
20.
Biosens Bioelectron ; 164: 112316, 2020 Sep 15.
Article in English | MEDLINE | ID: covidwho-628702

ABSTRACT

Recent research suggests that SARS-CoV-2-infected individuals can be highly infectious while asymptomatic or pre-symptomatic, and that an infected person may infect 5.6 other individuals on average. This situation highlights the need for rapid, sensitive SARS-CoV-2 diagnostic assays capable of high-throughput operation that can preferably utilize existing equipment to facilitate broad, large-scale screening efforts. We have developed a CRISPR-based assay that can meet all these criteria. This assay utilizes a custom CRISPR Cas12a/gRNA complex and a fluorescent probe to detect target amplicons produced by standard RT-PCR or isothermal recombinase polymerase amplification (RPA), to allow sensitive detection at sites not equipped with real-time PCR systems required for qPCR diagnostics. We found this approach allowed sensitive and robust detection of SARS-CoV-2 positive samples, with a sample-to-answer time of ~50 min, and a limit of detection of 2 copies per sample. CRISPR assay diagnostic results obtained nasal swab samples of individuals with suspected COVID-19 cases were comparable to paired results from a CDC-approved quantitative RT-PCR (RT-qPCR) assay performed in a state testing lab, and superior to those produced by same assay in a clinical lab, where the RT-qPCR assay exhibited multiple invalid or inconclusive results. Our assay also demonstrated greater analytical sensitivity and more robust diagnostic performance than other recently reported CRISPR-based assays. Based on these findings, we believe that a CRISPR-based fluorescent application has potential to improve current COVID-19 screening efforts.


Subject(s)
Betacoronavirus/isolation & purification , CRISPR-Cas Systems , Coronavirus Infections/diagnosis , Pneumonia, Viral/diagnosis , Base Sequence , Betacoronavirus/genetics , Biosensing Techniques/methods , Biosensing Techniques/statistics & numerical data , COVID-19 , Coronavirus Infections/virology , Fluorescent Dyes , Genes, Viral , High-Throughput Nucleotide Sequencing/methods , High-Throughput Nucleotide Sequencing/statistics & numerical data , Humans , Nucleic Acid Amplification Techniques/methods , Nucleic Acid Amplification Techniques/statistics & numerical data , Pandemics , Pneumonia, Viral/virology , Predictive Value of Tests , RNA, Viral/analysis , RNA, Viral/genetics , Reproducibility of Results , Reverse Transcriptase Polymerase Chain Reaction/methods , Reverse Transcriptase Polymerase Chain Reaction/statistics & numerical data , SARS-CoV-2 , Sensitivity and Specificity
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