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1.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-313436

ABSTRACT

COVID-19 patients can recover with a median SARS-CoV-2 clearance of 20 days post initial symptoms (PIS). However, we observed some COVID-19 patients with existing SARS-CoV-2 for more than 50 days PIS. This study aimed to investigate the cause of viral clearance delay and the infectivity in these patients. Demographic data and clinical characteristics of 22 long-term COVID-19 patients were collected. SARS-CoV-2 nucleic acid, peripheral lymphocyte count, and functionality were assessed. SARS-CoV-2-specific and neutralization antibodies were detected, followed by virus isolation and genome sequencing. The median age of the studied cohort was 59.83±12.94 years. All patients were clinically cured after long-term SARS-CoV-2 infection ranging from 53 to 112 days PIS. Peripheral lymphocytes counts were normal. Interferon gamma (IFN-ƴ)-generated CD4+ and CD8+ cells were normal as 24.68±9.60% and 66.41±14.87%. However, the number of IFN-ƴ-generated NK cells diminished (58.03±11.78%). All patients presented detectable IgG, which positively correlated with mild neutralizing activity (ID50=157.2, P=0.05). SARS-CoV-2 was not isolated, and a cytopathic effect was lacking. Only three synonymous variants were identified in spike protein coding regions. In conclusion, decreased IFN-γ production by NK cells and low neutralizing antibodies might favor SARS-CoV-2 long-term existence. Further, low viral load and weak viral pathogenicity was observed in COVID-19 patients with long-term SARS-CoV-2 infection.

2.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-309524

ABSTRACT

Background: :The emergence of Corona Virus Disease 2019 (COVID-19) in Wuhan, China at the end of 2019 is a major public health issue, causing to a large global outbreak. However, the information regarding the clinical characteristic and progression of severe and critically ill patients with COVID-19 is scarce. Methods: We conducted a single-center, retrospective, observational study and enrolled 126 severe and critically ill adult patients who were admitted to the intensive care unit (ICU) of Tongji hospital, between Feb 1 and Feb 20, 2020. Results: Of 126 patients, 85 patients with the positive of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were included. The mean age of 85 patients was 68.3 (SD 10.5) years. More than half were men, 55 (62.4%) had chronic illness. 57 (66.3%) patients had died before Feb 28, 2020. the median duration from onset of illness to death, hospitalization to death and ICU admission to death were 22 (17.0-26.0) days, 9.0 (6.0-13.0) days and 5.0 (2.0-6.0) days, respectively. Compared with survivors, non-survivors were more likely old (69.6 [SD 10.22] vs 65.6 [10.9]). Furthermore, the non-survivors had higher white blood cell (WBC) and neutrophil count, neutrophil percentage, high-sensitive C-reactive protein (hs-CRP) and lower lymphocyte and platelet count, lymphocyte percentage and albumin. Notably, arbidol may improve the survival of severe and critically ill patients. Conclusions: Our study reveals the non-survivors had worse blood routine and other clinical monitors. Additionally, arbidol may play useful role in the survival of severe and critically ill patients, which needs further validation.

3.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-308036

ABSTRACT

Background: COVID-19 Emerged as a novel zoonotic disease in late 2019 and quickly spread across Wuhan before spreading to other parts of China and rest of the world. Due to the rapid spread of the disease, local hospitals were inundated with COVID-19 patients putting a strain on the healthcare system. Little was known about the transmission and potential clinical management of COVID-19 at that time.Methods: A temporary COVID-19 hospital was built within one week. The confirmed COVID-19 cases were either directly recruited to the hospital or were transferred from other hospitals. Patients were admitted for both quarantine and treatment, as required. Data were collected as part of standard clinical care and retrospectively analyzed.Findings: A total of 2,959 patients were recruited during the operation period of this hospital between February 4, 2020, and April 8, 2020. These patients included 838 severe patients of which 72 were classified as critical, and 66 patients died. No infection was reported among healthcare workers.Interpretation: Setting up a dedicated hospital for COVID-19 provided a critical resource during the peak of the pandemic in Wuhan by enabling both quarantine and treatment for the infected patients. The mortality in this hospital was comparable to other hospitals at the time. These data suggest that this approach may prove beneficial in controlling infectious disease spread and limit mortality and prevent strain on existing healthcare system to enable them to care for non-COVID-19 patients.Funding Statement: This study was supported by funding from Beijing Nova Program Interdisciplinary Cooperation Project (DC;No. Z191100001119021), Chinese PLA General Hospital Youth Project (DC;No.QNF19074), Beijing Nova Program Project (DC;No. Z171100001117012), and China 13th Five-year National Key Grant (LXX;No.2018ZX09201013).Declaration of Interests: The authors declare that there are no competing interests.Ethics Approval Statement: This study was approved by the ethics committee of the Chinese PLA General Hospital, with a waiver of informed consent.

4.
View ; 3(1), 2022.
Article in English | ProQuest Central | ID: covidwho-1661642

ABSTRACT

Corona virus disease 2019 (COVID‐19) is a serious contagious disease that arises from severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). The disease is transmitted primarily through droplets transmission, which does not exclude the possibility of transmission through aerosols and digestive tract and other means. The majority of COVID‐19 cases present as common and mild, while a few cases progress rapidly to the severe and critical stage, making it more difficult to save the disease. Current laboratory diagnostic approaches for COVID‐19 are on the basis of pathogenic tests for viral nucleic acids, serological tests by specific antibody detection, and general tests. For now, Real‐time quantitative PCR (qRT‐PCR) is the gold standard for the detection of COVID‐19, but the method is complicated and may have false‐negative results. Therefore, in order to diagnose and prevention COVID‐19 more effectively, it is needful to develop highly sensitive diagnostic methods with portable instruments and visualized results. This mini‐review provides an overview of the current portable and visual assays of detection of COVID‐19, in order to achieve early effective and more accurate diagnosis of COVID‐19.

5.
View ; 3(1), 2022.
Article in English | ProQuest Central | ID: covidwho-1661525
6.
Cell Rep Phys Sci ; 3(2): 100740, 2022 Feb 16.
Article in English | MEDLINE | ID: covidwho-1639470

ABSTRACT

Accurate and rapid detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is significant for early tracing, isolation, and treatment of infected individuals, which will efficiently prevent large-scale transmission of coronavirus disease 2019 (COVID-19). Here, two kinds of test strips for receptor binding domain (RBD) and N antigens of SARS-CoV-2 are established with high sensitivity and specificity, in which AIE luminogens (AIEgens) are utilized as reporters. Because of the high brightness and resistance to quenching in aqueous solution, the limit of detection can be as low as 6.9 ng/mL for RBD protein and 7.2 ng/mL for N protein. As an antigen collector, an N95 mask equipped with a test strip with an excellent enrichment effect would efficiently simplify the sampling procedures. Compared with a test strip based on Au nanoparticles or fluorescein isothiocyanate (FITC), the AIEgen-based test strip shows high anti-interference capacity in complex biosamples. Therefore, an AIEgen-based test strip assay could be built as a promising platform for emergency use during the pandemic.

7.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-296422

ABSTRACT

\Accurate and rapid detection of SARS-CoV-2 is significant for early tracing, isolating and treating the infected patients, which will efficiently prevent the virus large-scale spread from human to human. In this paper, two kinds of novel quantitative lateral flow test strip for N and RBD antigens of SARS-CoV-2 were established with high sensitivity, which utilize AIE luminogens (AIEgens) as reporter. Because of the high brightness and resistance of quenching property in aqueous of the AIEgens, the limit of detection of 7.2 ng/mL for N protein and 6.9 ng/mL for RBD protein could be achieved with the AIEgens-based lateral flow test strip. Furthermore, it was negative for other protein or antigen samples assay, which demonstrated the great specificity of the test strategy. A N95 mask equipped with the test strip was designed to employ as the antigen collector with excellent enrichment effect. Compared with the other two test strips based on the Au nanoparticle and FITC, the well-designed AIEgens-based lateral flow test strip presented high sensitivity and excellent anti-interference capacity in complex bio-samples. Furthermore, the AIEgens-based lateral flow test strip assay could be built as a promising platform for the emergency usage at pandemic.<br><br>Funding: This work was supported by the NSFC (51961160730, 51873092, and 81921004), the National Key R&D Program of China (Intergovernmental Cooperation Project, 2017YFE0132200), the Fundamental Research Funds for the Central Universities, and the Tianjin Science Fund for Distinguished Young Scholars (19JCJQJC61200).<br><br>Declaration of Interests: The authors declare no competing interests.

8.
BMJ Health Care Inform ; 28(1)2021 May.
Article in English | MEDLINE | ID: covidwho-1220030

ABSTRACT

New York City quickly became an epicentre of the COVID-19 pandemic. An ability to triage patients was needed due to a sudden and massive increase in patients during the COVID-19 pandemic as healthcare providers incurred an exponential increase in workload,which created a strain on the staff and limited resources. Further, methods to better understand and characterise the predictors of morbidity and mortality was needed. METHODS: We developed a prediction model to predict patients at risk for mortality using only laboratory, vital and demographic information readily available in the electronic health record on more than 3395 hospital admissions with COVID-19. Multiple methods were applied, and final model was selected based on performance. A variable importance algorithm was used for interpretability, and understanding of performance and predictors was applied to the best model. We built a model with an area under the receiver operating characteristic curve of 83-97 to identify predictors and patients with high risk of mortality due to COVID-19. Oximetry, respirations, blood urea nitrogen, lymphocyte per cent, calcium, troponin and neutrophil percentage were important features, and key ranges were identified that contributed to a 50% increase in patients' mortality prediction score. With an increasing negative predictive value starting 0.90 after the second day of admission suggests we might be able to more confidently identify likely survivors DISCUSSION: This study serves as a use case of a machine learning methods with visualisations to aide clinicians with a better understanding of the model and predictors of mortality. CONCLUSION: As we continue to understand COVID-19, computer assisted algorithms might be able to improve the care of patients.


Subject(s)
COVID-19/mortality , Hospital Mortality/trends , Machine Learning , Algorithms , Forecasting/methods , Humans , New York City , Retrospective Studies , Risk Assessment , SARS-CoV-2
9.
Virol Sin ; 35(6): 793-802, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-911957

ABSTRACT

COVID-19 patients can recover with a median SARS-CoV-2 clearance of 20 days post initial symptoms (PIS). However, we observed some COVID-19 patients with existing SARS-CoV-2 for more than 50 days PIS. This study aimed to investigate the cause of viral clearance delay and the infectivity in these patients. Demographic data and clinical characteristics of 22 long-term COVID-19 patients were collected. The median age of the studied cohort was 59.83 ± 12.94 years. All patients were clinically cured after long-term SARS-CoV-2 infection ranging from 53 to 112 days PIS. Peripheral lymphocytes counts were normal. The ratios of interferon gamma (IFN-γ)-secreting cells to total CD4+ and CD8+ cells were normal as 24.68% ± 9.60% and 66.41% ± 14.87% respectively. However, the number of IFN-γ-secreting NK cells diminished (58.03% ± 11.78%). All patients presented detectable IgG, which positively correlated with mild neutralizing activity (Mean value neutralisation antibodies titers = 157.2, P = 0.05). No SARS-CoV-2 virus was isolated in Vero E6 cells inoculated with nasopharyngeal swab samples from all patients 50 days PIS, and the cytopathic effect was lacking. But one sample was positive for SARS-CoV-2 nucleic acid test in cell supernatants after two passages. Genome sequencing revealed that only three synonymous variants were identified in spike protein coding regions. In conclusion, decreased IFN-γ production by NK cells and low neutralizing antibodies might favor SARS-CoV-2 long-term existence. Further, low viral load and weak viral pathogenicity were observed in COVID-19 patients with long-term SARS-CoV-2 infection.


Subject(s)
COVID-19/immunology , COVID-19/transmission , SARS-CoV-2/immunology , Aged , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , COVID-19/physiopathology , Female , Humans , Immunoglobulin G/immunology , Interferon-gamma/immunology , Killer Cells, Natural/immunology , Male , Middle Aged , SARS-CoV-2/pathogenicity , Viral Load , Virulence
10.
Lancet ; 395(10236): 1569-1578, 2020 05 16.
Article in English | MEDLINE | ID: covidwho-824547

ABSTRACT

BACKGROUND: No specific antiviral drug has been proven effective for treatment of patients with severe coronavirus disease 2019 (COVID-19). Remdesivir (GS-5734), a nucleoside analogue prodrug, has inhibitory effects on pathogenic animal and human coronaviruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in vitro, and inhibits Middle East respiratory syndrome coronavirus, SARS-CoV-1, and SARS-CoV-2 replication in animal models. METHODS: We did a randomised, double-blind, placebo-controlled, multicentre trial at ten hospitals in Hubei, China. Eligible patients were adults (aged ≥18 years) admitted to hospital with laboratory-confirmed SARS-CoV-2 infection, with an interval from symptom onset to enrolment of 12 days or less, oxygen saturation of 94% or less on room air or a ratio of arterial oxygen partial pressure to fractional inspired oxygen of 300 mm Hg or less, and radiologically confirmed pneumonia. Patients were randomly assigned in a 2:1 ratio to intravenous remdesivir (200 mg on day 1 followed by 100 mg on days 2-10 in single daily infusions) or the same volume of placebo infusions for 10 days. Patients were permitted concomitant use of lopinavir-ritonavir, interferons, and corticosteroids. The primary endpoint was time to clinical improvement up to day 28, defined as the time (in days) from randomisation to the point of a decline of two levels on a six-point ordinal scale of clinical status (from 1=discharged to 6=death) or discharged alive from hospital, whichever came first. Primary analysis was done in the intention-to-treat (ITT) population and safety analysis was done in all patients who started their assigned treatment. This trial is registered with ClinicalTrials.gov, NCT04257656. FINDINGS: Between Feb 6, 2020, and March 12, 2020, 237 patients were enrolled and randomly assigned to a treatment group (158 to remdesivir and 79 to placebo); one patient in the placebo group who withdrew after randomisation was not included in the ITT population. Remdesivir use was not associated with a difference in time to clinical improvement (hazard ratio 1·23 [95% CI 0·87-1·75]). Although not statistically significant, patients receiving remdesivir had a numerically faster time to clinical improvement than those receiving placebo among patients with symptom duration of 10 days or less (hazard ratio 1·52 [0·95-2·43]). Adverse events were reported in 102 (66%) of 155 remdesivir recipients versus 50 (64%) of 78 placebo recipients. Remdesivir was stopped early because of adverse events in 18 (12%) patients versus four (5%) patients who stopped placebo early. INTERPRETATION: In this study of adult patients admitted to hospital for severe COVID-19, remdesivir was not associated with statistically significant clinical benefits. However, the numerical reduction in time to clinical improvement in those treated earlier requires confirmation in larger studies. FUNDING: Chinese Academy of Medical Sciences Emergency Project of COVID-19, National Key Research and Development Program of China, the Beijing Science and Technology Project.


Subject(s)
Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , Antiviral Agents/therapeutic use , Coronavirus Infections/drug therapy , Pneumonia, Viral/drug therapy , Adenosine Monophosphate/adverse effects , Adenosine Monophosphate/therapeutic use , Aged , Alanine/adverse effects , Alanine/therapeutic use , Antiviral Agents/adverse effects , Betacoronavirus , COVID-19 , China , Double-Blind Method , Female , Humans , Infusions, Intravenous , Male , Middle Aged , Negative Results , Pandemics , SARS-CoV-2
11.
J Clin Lab Anal ; 34(9): e23411, 2020 Sep.
Article in English | MEDLINE | ID: covidwho-624944

ABSTRACT

BACKGROUND: The detection of serum antibodies to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is emerging as a new tool for the coronavirus disease 2019 (COVID-19) diagnosis. Since many coronaviruses are sensitive to heat, heating inactivation of samples at 56°C prior to testing is considered a possible method to reduce the risk of transmission, but the effect of heating on the measurement of SARS-CoV-2 antibodies is still unclear. METHODS: By comparing the levels of SARS-CoV-2 antibodies before and after heat inactivation of serum at 56°C for 30 minutes using a quantitative fluorescence immunochromatographic assay RESULTS: We showed that heat inactivation significantly interferes with the levels of antibodies to SARS-CoV-2. The IgM levels of all the 34 serum samples (100%) from COVID-19 patients decreased by an average level of 53.56%. The IgG levels were decreased in 22 of 34 samples (64.71%) by an average level of 49.54%. Similar changes can also be observed in the non-COVID-19 disease group (n = 9). Of note, 44.12% of the detected IgM levels were dropped below the cutoff value after heating, suggesting heat inactivation can lead to false-negative results of these samples. CONCLUSION: Our results indicate that heat inactivation of serum at 56°C for 30 minutes interferes with the immunoanalysis of antibodies to SARS-CoV-2. Heat inactivation prior to immunoanalysis is not recommended, and the possibility of false-negative results should be considered if the sample was pre-inactivated by heating.


Subject(s)
Antibodies, Viral/immunology , Betacoronavirus/immunology , Coronavirus Infections/blood , Coronavirus Infections/immunology , Hot Temperature , Immunoassay/methods , Pneumonia, Viral/blood , Pneumonia, Viral/immunology , Serum/immunology , COVID-19 , Coronavirus Infections/virology , Humans , Immunoglobulin G/blood , Immunoglobulin M/blood , Pandemics , Pneumonia, Viral/virology , SARS-CoV-2
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