Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 19 de 19
Filter
1.
Signal Transduct Target Ther ; 6(1): 427, 2021 12 16.
Article in English | MEDLINE | ID: covidwho-1795805

ABSTRACT

Abnormal glucose and lipid metabolism in COVID-19 patients were recently reported with unclear mechanism. In this study, we retrospectively investigated a cohort of COVID-19 patients without pre-existing metabolic-related diseases, and found new-onset insulin resistance, hyperglycemia, and decreased HDL-C in these patients. Mechanistically, SARS-CoV-2 infection increased the expression of RE1-silencing transcription factor (REST), which modulated the expression of secreted metabolic factors including myeloperoxidase, apelin, and myostatin at the transcriptional level, resulting in the perturbation of glucose and lipid metabolism. Furthermore, several lipids, including (±)5-HETE, (±)12-HETE, propionic acid, and isobutyric acid were identified as the potential biomarkers of COVID-19-induced metabolic dysregulation, especially in insulin resistance. Taken together, our study revealed insulin resistance as the direct cause of hyperglycemia upon COVID-19, and further illustrated the underlying mechanisms, providing potential therapeutic targets for COVID-19-induced metabolic complications.


Subject(s)
COVID-19/blood , Hyperglycemia/blood , Insulin Resistance , Lipid Metabolism , Lipids/blood , SARS-CoV-2/metabolism , Adult , Aged , Biomarkers/blood , COVID-19/complications , Female , Humans , Hyperglycemia/etiology , Male , Middle Aged , Retrospective Studies
2.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-325321

ABSTRACT

Background: Coronavirus Disease 2019 (COVID-19) has become a global pandemic and caused over one hundred thousand death. Chloroquine (CQ) and hydroxychloroquine (HCQ) were recommended for off-label use in the treatment of COVID-19 in some countries despite their unclear benefit. However, the toxicity of these agents has been ignored, so the investigation of their safety in the treatment of COVID-19 is crucial for providing a reference for the rational use. Methods: The medical records obtained from the information management system of Guangzhou Eighth People’s Hospital were reviewed to extract data about patients who received chloroquine phosphate tablets for COVID-19 treatment from January 20th to March 5th, 2020. The data were assessed to determine the correlation of adverse reaction with chloroquine phosphate based on Chinese CFDA standards as well as the severity of adverse events based on American CTCAE5.0 standard, and evaluate the safety of this medication. Results: A total of 42 patients (23 males and 19 females, average 42.19±14.29 years old) with COVID-19 were treated with low-dose chloroquine phosphate (oral, 500 mg, once per day). Totally 18 patients(42.86%)experienced 20 adverse events. The mean duration of CQ administration was 6.57 days (SD, 3.16 days;range: 1 day to 16 days) and 52.4% received CQ for 7 to 9 days. The adverse events occurred within 6–8 days of treatment. For the 20 adverse events, 19 were not higher than grade 2 and only one was grade 3 because of the severely limited self-care ability in one patient. The most common adverse events were related to the digestive, circulatory, hepatic, and nervous systems. Conclusion: Oral chloroquine phosphate tablets resulted in a high incidence of adverse reactions. In the clinical trial of chloroquine phosphate for COVID-19 treatment, it should be used under pharmaceutical care;timely evaluation of the drug safety during the treatment process is necessary and a randomized controlled clinical trial should be conducted.

3.
Cell Metab ; 34(3): 424-440.e7, 2022 03 01.
Article in English | MEDLINE | ID: covidwho-1676683

ABSTRACT

Coronavirus disease 2019 (COVID-19) represents a systemic disease that may cause severe metabolic complications in multiple tissues including liver, kidney, and cardiovascular system. However, the underlying mechanisms and optimal treatment remain elusive. Our study shows that impairment of ACE2 pathway is a key factor linking virus infection to its secondary metabolic sequelae. By using structure-based high-throughput virtual screening and connectivity map database, followed with experimental validations, we identify imatinib, methazolamide, and harpagoside as direct enzymatic activators of ACE2. Imatinib and methazolamide remarkably improve metabolic perturbations in vivo in an ACE2-dependent manner under the insulin-resistant state and SARS-CoV-2-infected state. Moreover, viral entry is directly inhibited by these three compounds due to allosteric inhibition of ACE2 binding to spike protein on SARS-CoV-2. Taken together, our study shows that enzymatic activation of ACE2 via imatinib, methazolamide, or harpagoside may be a conceptually new strategy to treat metabolic sequelae of COVID-19.


Subject(s)
COVID-19/drug therapy , Imatinib Mesylate/therapeutic use , Metabolic Diseases/drug therapy , Methazolamide/therapeutic use , SARS-CoV-2/drug effects , Angiotensin-Converting Enzyme 2/drug effects , Angiotensin-Converting Enzyme 2/metabolism , Animals , COVID-19/complications , COVID-19/metabolism , COVID-19/virology , Cells, Cultured , Chlorocebus aethiops , Down-Regulation/drug effects , HEK293 Cells , Human Umbilical Vein Endothelial Cells , Humans , Imatinib Mesylate/pharmacology , Male , Metabolic Diseases/metabolism , Metabolic Diseases/virology , Methazolamide/pharmacology , Mice , Mice, Inbred C57BL , Mice, Obese , Mice, Transgenic , SARS-CoV-2/physiology , Vero Cells , Virus Internalization/drug effects
4.
Zhongguo Bingdubing Zazhi = Chinese Journal of Viral Diseases ; - (6):438, 2021.
Article in English | ProQuest Central | ID: covidwho-1675353

ABSTRACT

:Objective To study the kinetics of IgM and IgG antibodies based on nucleocapsid(N) and spike(S) protein of SARS-Co V2-in COVID-19 patients. Methods Immunofluorescent kits were used to detect N and S protein specific IgM and IgG antibodies from Jan.21 to Feb.11, 2020 for the 60 hospitalized COVID-19 patients(48 mild, 12 severe cases) with a total of 290 plasma samples collected 9 weeks after the onset of the disease. Results The level of antibodies specific for S protein varied significantly with the course of disease(Ig M from 27.32 to 110.10 TU/ml, IgG from 56.85 to 135.00 TU/ml), but not for N protein.Higher level of Ig M/Ig G antibodies specific to S protein was observed during the 2-7 week than that to N protein.The seropositive rate of antibodies gradually increased during the early stage of disease.IgM/IgG antibodies specific to N protein changed from 12.50% at the first week to peak level(51.72% and 86.21% respectively) at the 4 th week and those for S protein from 25.00% and 14.58% to 100.00%, and then declined.The seropositive rate of Ig M antibody specific to S protein was higher than that for N protein during 2-8 th week and that for Ig G antibody at 2, 3, 4, 6 and 7 th week.The seropositive rate of Ig G antibody specific to N protein in severe patients at the third week was higher than that in mild patients(100.00% vs 59.52%,χ2=9.67, P=0.001 9), and the same as to Ig G antibody for S protein at the second week after disease onset(80.00% vs 46.58%, χ2=5.57, P=0.018 2). Conclusions SARS-Co V2-S protein can induc stronger antibody response than N protein, and the antibody level was related to the severity of the disease.

5.
Zhongguo Bingdubing Zazhi = Chinese Journal of Viral Diseases ; - (4):266, 2021.
Article in Chinese | ProQuest Central | ID: covidwho-1576016

ABSTRACT

Objective To study the kinetics of SARS-CoV-2 antibodies in COVID-19 patients and the correlation with disease severity. Methods A total of 290 plasma samples were collected from 60 hospitalized patients including 48 mild cases and 12 severe cases within 63 days after disease onset in Guangzhou Eighth People′s Hospital affiliated to Guangzhou Medical University during January 21 to April 11, 2020.SARS-CoV-2 specific antibodies were determined by four commercial colloidal gold serologic reagents validated by National Medical Products Administration in China. Results The seropositive rate ranged from 19.23% to 34.62% by four assays within one week after disease onset, and rapidly increased within the following two weeks.The seropositive rates were 52.27% to 68.18% and 83.05% to 98.31%, respectively.IgM antibody peaked within the fourth week and maintained high level for 1 to 2 weeks, and decreased significantly until the 9 th week.But no obvious decreasing trend of the seropositive rate of IgG antibody was observed during two months after disease onset.The seropositive rates of antibodies between mild and severe cases showed no statistical difference.Four assays demonstrated a sensitivity of 78.33%to 91.67%in 60 COVID-19 patients.The difference was statistically significant between the highest and the lowest values(χ2=4.183,P=0.041). Conclusions The colloidal gold serologic reagents show good sensitivity during the late stage of disease but not at the early stage.There is no correlation between seropositive and disease severity.The sensitivity of different reagents is different

7.
JMIR Public Health Surveill ; 7(10): e31125, 2021 10 21.
Article in English | MEDLINE | ID: covidwho-1430625

ABSTRACT

BACKGROUND: HIV infection is a significant independent risk factor for both severe COVID-19 presentation at hospital admission and in-hospital mortality. Available information has suggested that people living with HIV and AIDS (PLWHA) could benefit from COVID-19 vaccination. However, there is a dearth of evidence on willingness to receive COVID-19 vaccination among PLWHA. OBJECTIVE: The aim of this study was to investigate willingness to receive COVID-19 vaccination among a national sample of PLWHA in China. METHODS: This cross-sectional online survey investigated factors associated with willingness to receive COVID-19 vaccination among PLWHA aged 18 to 65 years living in eight conveniently selected Chinese metropolitan cities between January and February 2021. Eight community-based organizations (CBOs) providing services to PLWHA facilitated the recruitment. Eligible PLWHA completed an online survey developed using a widely used encrypted web-based survey platform in China. We fitted a single logistic regression model to obtain adjusted odds ratios (aORs), which involved one of the independent variables of interest and all significant background variables. Path analysis was also used in the data analysis. RESULTS: Out of 10,845 PLWHA approached by the CBOs, 2740 completed the survey, and 170 had received at least one dose of the COVID-19 vaccine. This analysis was performed among 2570 participants who had never received COVID-19 vaccination. Over half of the participants reported willingness to receive COVID-19 vaccination (1470/2570, 57.2%). Perceptions related to COVID-19 vaccination were significantly associated with willingness to receive COVID-19 vaccination, including positive attitudes (aOR 1.11, 95% CI 1.09-1.12; P<.001), negative attitudes (aOR 0.96, 95% CI 0.94-0.97; P<.001), perceived support from significant others (perceived subjective norm; aOR 1.53, 95% CI 1.46-1.61; P<.001), and perceived behavioral control (aOR 1.13, 95% CI 1.11-1.14; P<.001). At the interpersonal level, receiving advice supportive of COVID-19 vaccination from doctors (aOR 1.99, 95% CI 1.65-2.40; P<.001), CBO staff (aOR 1.89, 95% CI 1.51-2.36; P<.001), friends and/or family members (aOR 3.22, 95% CI 1.93-5.35; P<.001), and PLWHA peers (aOR 2.38, 95% CI 1.85-3.08; P<.001) was associated with higher willingness to receive COVID-19 vaccination. The overall opinion supporting COVID-19 vaccination for PLWHA on the internet or social media was also positively associated with willingness to receive COVID-19 vaccination (aOR 1.59, 95% CI 1.31-1.94; P<.001). Path analysis indicated that interpersonal-level variables were indirectly associated with willingness to receive COVID-19 vaccination through perceptions (ß=.43, 95% CI .37-.51; P<.001). CONCLUSIONS: As compared to PLWHA in other countries and the general population in most parts of the world, PLWHA in China reported a relatively low willingness to receive COVID-19 vaccination. The internet and social media as well as interpersonal communications may be major sources of influence on PLWHA's perceptions and willingness to receive COVID-19 vaccination.


Subject(s)
COVID-19 , HIV Infections , COVID-19 Vaccines , China/epidemiology , Cross-Sectional Studies , Humans , SARS-CoV-2 , Vaccination
8.
Front Immunol ; 12: 724763, 2021.
Article in English | MEDLINE | ID: covidwho-1399141

ABSTRACT

Characterizing the serologic features of asymptomatic SARS-CoV-2 infection is imperative to improve diagnostics and control of SARS-CoV-2 transmission. In this study, we evaluated the antibody profiles in 272 plasma samples collected from 59 COVID-19 patients, consisting of 18 asymptomatic patients, 33 mildly ill patients and 8 severely ill patients. We measured the IgG against five viral structural proteins, different isotypes of immunoglobulins against the Receptor Binding Domain (RBD) protein, and neutralizing antibodies. The results showed that the overall antibody response was lower in asymptomatic infections than in symptomatic infections throughout the disease course. In contrast to symptomatic patients, asymptomatic patients showed a dominant IgG-response towards the RBD protein, but not IgM and IgA. Neutralizing antibody titers had linear correlations with IgA/IgM/IgG levels against SARS-CoV-2-RBD, as well as with IgG levels against multiple SARS-CoV-2 structural proteins, especially with anti-RBD or anti-S2 IgG. In addition, the sensitivity of anti-S2-IgG is better in identifying asymptomatic infections at early time post infection compared to anti-RBD-IgG. These data suggest that asymptomatic infections elicit weaker antibody responses, and primarily induce IgG antibody responses rather than IgA or IgM antibody responses. Detection of IgG against the S2 protein could supplement nucleic acid testing to identify asymptomatic patients. This study provides an antibody detection scheme for asymptomatic infections, which may contribute to epidemic prevention and control.


Subject(s)
Antibodies, Viral/blood , Asymptomatic Infections , Immunoglobulin G/blood , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , Viral Structural Proteins/immunology , Adolescent , Adult , Antibodies, Neutralizing/immunology , Antibodies, Viral/physiology , Binding Sites, Antibody , Female , Humans , Immunoglobulin G/classification , Immunoglobulin M/immunology , Kinetics , Male , Middle Aged , Neutralization Tests/statistics & numerical data , SARS-CoV-2/chemistry , Young Adult
10.
J Med Virol ; 93(2): 794-802, 2021 02.
Article in English | MEDLINE | ID: covidwho-1196404

ABSTRACT

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA was found in the intestines and feces, but its clinical significance is not completely clear. We aim to characterize the longitudinal test results of SARS-CoV-2 RNA in anal swabs and to explore the association with disease severity. METHODS: We included laboratory-confirmed coronavirus disease 2019 (COVID-19) patients, who were hospitalized in Guangzhou Eighth People's Hospital and excluded those who had not received anal swabs for SARS-COV-2 RNA testing. Epidemiological, clinical, and laboratory data were obtained. Throat swabs and anal swabs were collected periodically for SARS-COV-2 RNA detection. RESULTS: Two hundred and seventeen eligible patients (median aged 50 years, 50.2% were females) were analyzed. 21.2% (46/217) of the patients were detected with SARS-CoV-2 RNA in anal swabs. The duration of viral RNA was longer, but the viral load was lower in anal swabs than throat swabs in the early stage of the disease. During a median follow-up of 20 days, 30 (13.8%) patients were admitted to the intensive care unit (ICU) for high-flow nasal cannula or higher-level oxygen support measures to correct hypoxemia. Detectable viral RNA in anal swabs (adjusted hazard ratio [aHR], 2.50; 95% confidence interval [CI], 1.20-5.24), increased C-reactive protein (aHR, 3.14; 95% CI, 1.35-7.32) and lymphocytopenia (aHR, 3.12; 95% CI, 1.46-6.67) were independently associated with ICU admission. The cumulative incidence of ICU admission was higher among patients with detectable viral RNA in anal swabs (26.3% vs 10.7%, P = .006). CONCLUSION: Detectable SARS-CoV-2 RNA in the digestive tract was a potential warning indicator of severe disease.


Subject(s)
Anal Canal/virology , COVID-19/diagnosis , Lymphopenia/diagnosis , RNA, Viral/genetics , SARS-CoV-2/genetics , Adult , Antiviral Agents/therapeutic use , C-Reactive Protein/metabolism , COVID-19/pathology , COVID-19/therapy , COVID-19/virology , COVID-19 Testing , Chloroquine/therapeutic use , Female , Hospitalization/statistics & numerical data , Humans , Indoles/therapeutic use , Intensive Care Units/statistics & numerical data , Lymphopenia/pathology , Lymphopenia/therapy , Lymphopenia/virology , Male , Middle Aged , Oseltamivir/therapeutic use , Pharynx/virology , Retrospective Studies , SARS-CoV-2/pathogenicity , Severity of Illness Index , Viral Load/drug effects
11.
Open Forum Infect Dis ; 7(6): ofaa187, 2020 Jun.
Article in English | MEDLINE | ID: covidwho-1109308

ABSTRACT

BACKGROUND: The clinical manifestations and factors associated with the severity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections outside of Wuhan are not clearly understood. METHODS: All laboratory-confirmed cases with SARS-Cov-2 infection who were hospitalized and monitored in Guangzhou Eighth People's Hospital were recruited from January 20 to February 10. RESULTS: A total of 275 patients were included in this study. The median patient age was 49 years, and 63.6% had exposure to Wuhan. The median virus incubation period was 6 days. Fever (70.5%) and dry cough (56.0%) were the most common symptoms. A decreased albumin level was found in 51.3% of patients, lymphopenia in 33.5%, and pneumonia based on chest computed tomography in 86%. Approximately 16% of patients (n = 45) had severe disease, and there were no deaths. Compared with patients with nonsevere disease, those with severe disease were older, had a higher frequency of coexisting conditions and pneumonia, and had a shorter incubation period (all P < .05). There were no differences between patients who likely contacted the virus in Wuhan and those who had no exposure to Wuhan. Multivariate logistic regression analysis indicated that older age, male sex, and decreased albumin level were independently associated with disease severity. CONCLUSIONS: Most of the patients infected with SARS-CoV-2 in Guangzhou, China are not severe cases and patients with older age, male, and decreased albumin level were more likely to develop into severe ones.

12.
Int J Med Sci ; 18(1): 29-41, 2021.
Article in English | MEDLINE | ID: covidwho-994132

ABSTRACT

Rationale: Previous studies of coronavirus disease 2019 (COVID-19) were mainly focused on cross-sectional analysis. In this study, we sought to evaluate the dynamic changes of immunological and radiographic features, and the association with the outcome of pulmonary lesions in COVID-19 patients. Methods: Peripheral blood samples and radiographic data were collected longitudinally for up to 8 weeks from 158 laboratory-confirmed COVID-19 patients. The chest computed tomography (CT) scans were scored based on a semi-quantification assessment according to the extent of pulmonary abnormalities; the temporal change of the immunological and radiographic features was analyzed. Results: Compared with mild and moderate patients, severe patients had significantly decreased counts of lymphocytes, CD4+ T cells, CD8+ T cells, and CD19+ B cells but dramatically elevated counts of neutrophils and levels of interleukin (IL)-6. Sequential monitoring showed a sustained increase in lymphocytes counts and significantly decreased levels of IL-6 in severe patients during the disease course. Notably, patients with persistent pulmonary lesions (CT score ≥ 5 in week 8) showed high levels of IL-6 during the follow-up period, compared with those with recovery lesions (CT score < 5 in week 8). More importantly, the peak expression of IL-6 prior to the aggravated lung injury was mainly found in patients with persistent lesions, and multivariate analysis showed that IL-6 level upon admission was an independent factor associated with the persistent pulmonary injury. Conclusion: Prolonged elevation of IL-6 is associated with persistent pulmonary lesions in COVID-19 patients. Sequential monitoring and timely intervention of IL-6 may favor the clinical management of COVID-19.


Subject(s)
COVID-19/immunology , Interleukin-6/blood , Lung Injury/blood , Adolescent , Adult , Aged , Aged, 80 and over , Biomarkers/blood , COVID-19/blood , COVID-19/complications , COVID-19/diagnostic imaging , Female , Humans , Longitudinal Studies , Lung Injury/diagnostic imaging , Lung Injury/virology , Lymphocyte Count , Male , Middle Aged , Radiography, Thoracic , Retrospective Studies , SARS-CoV-2 , Tomography, X-Ray Computed , Young Adult
13.
Front Med (Lausanne) ; 7: 557453, 2020.
Article in English | MEDLINE | ID: covidwho-890338

ABSTRACT

Approximately 15-20% of COVID-19 patients will develop severe pneumonia, and about 10% of these will die if not properly managed. Earlier discrimination of potentially severe patients basing on routine clinical and laboratory changes and commencement of prophylactical management will not only save lives but also mitigate the otherwise overwhelming healthcare burden. In this retrospective investigation, the clinical and laboratory features were collected from 125 COVID-19 patients who were classified into mild (93 cases) or severe (32 cases) groups according to their clinical outcomes after 3-7 days post-admission. The subsequent analysis with single-factor and multivariate logistic regression methods indicated that 17 factors on admission differed significantly between mild and severe groups but that only comorbidity with underlying diseases, increased respiratory rate (>24/min), elevated C-reactive protein (CRP >10 mg/L), and lactate dehydrogenase (LDH >250 U/L) were independently associated with the later disease development. Finally, we evaluated their prognostic values with receiver operating characteristic curve (ROC) analysis and found that the above four factors could not confidently predict the occurrence of severe pneumonia individually, though a combination of fast respiratory rate and elevated LDH significantly increased the predictive confidence (AUC = 0.944, sensitivity = 0.941, and specificity = 0.902). A combination consisting of three or four factors could further increase the prognostic value. Additionally, measurable serum viral RNA post-admission independently predicted the severe illness occurrence. In conclusion, a combination of general clinical characteristics and laboratory tests could provide a highly confident prognostic value for identifying potentially severe COVID-19 pneumonia patients.

14.
J Clin Virol ; 133: 104661, 2020 12.
Article in English | MEDLINE | ID: covidwho-856844

ABSTRACT

BACKGROUND: Coronavirus Disease 2019 (COVID-19) is threatening billions of people. We described the clinical characteristics and explore virological and immunological factors associated with clinical outcomes. METHODS: 297 COVID-19 patients hospitalized in Guangzhou Eighth People's Hospital between January 20 and February 20, 2020 were included. Epidemiological, clinical and laboratory data were collected and analyzed. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) RNA in respiratory tract, blood samples and digestive tract was detected and lymphocyte subsets were tested periodically. RESULT: Among the 297 patients (median age of 48 years), 154 (51.9 %) were female, 245 (82.5 %) mild/moderate cases, and 52 (17.5 %) severe/critical cases. 270 patients were detected for SARS-CoV-2 RNA in anal swabs and/or blood samples, and the overall positive rate was 23.0 % (62/270), higher in severe/critical cases than in mild/moderate cases (52.0 % vs. 16.4 %, P < 0.001). The CD4/CD8 ratio on admission was significantly higher in severe/critical cases than in mild/moderate cases (1.84 vs. 1.50, P = 0.022). During a median follow-up period of 17 days, 36 (12.1 %) patients were admitted to intensive care unit (ICU), 16 (5.4 %) patients developed respiratory failure and underwent mechanical ventilation, four (1.3 %) patients needed extracorporeal membrane oxygenation (ECMO), only one (0.34 %) patients died of multiple organ failure. Detectable SARS-CoV-2 RNA in anal swabs and/or blood samples, as well as higher CD4/CD8 ratio were independent risk factors of respiratory failure and ICU admission. CONCLUSIONS: Most of COVID-19 patients in Guangzhou are mild/moderate, and presence of extrapulmonary virus and higher CD4/CD8 ratio are associated with higher risk of worse outcomes.


Subject(s)
COVID-19/epidemiology , Hospitalization/statistics & numerical data , Adult , CD4-CD8 Ratio , COVID-19/mortality , COVID-19/therapy , China , Female , Humans , Intensive Care Units , Male , Middle Aged , Respiration, Artificial/statistics & numerical data , Retrospective Studies , Risk Factors
15.
Cell Mol Immunol ; 17(11): 1119-1125, 2020 11.
Article in English | MEDLINE | ID: covidwho-841899

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been redetected after discharge in some coronavirus disease 2019 (COVID-19) patients. The reason for the recurrent positivity of the test and the potential public health concern due to this occurrence are still unknown. Here, we analyzed the viral data and clinical manifestations of 289 domestic Chinese COVID-19 patients and found that 21 individuals (7.3%) were readmitted for hospitalization after detection of SARS-CoV-2 after discharge. First, we experimentally confirmed that the virus was involved in the initial infection and was not a secondary infection. In positive retests, the virus was usually found in anal samples (15 of 21, 71.4%). Through analysis of the intracellular viral subgenomic messenger RNA (sgmRNA), we verified that positive retest patients had active viral replication in their gastrointestinal tracts (3 of 16 patients, 18.7%) but not in their respiratory tracts. Then, we found that viral persistence was not associated with high viral titers, delayed viral clearance, old age, or more severe clinical symptoms during the first hospitalization. In contrast, viral rebound was associated with significantly lower levels of and slower generation of viral receptor-binding domain (RBD)-specific IgA and IgG antibodies. Our study demonstrated that the positive retest patients failed to create a robust protective humoral immune response, which might result in SARS-CoV-2 persistence in the gastrointestinal tract and possibly in active viral shedding. Further exploration of the mechanism underlying the rebound in SARS-CoV-2 in this population will be crucial for preventing virus spread and developing effective vaccines.


Subject(s)
Betacoronavirus/physiology , Clinical Laboratory Techniques/methods , Coronavirus Infections/diagnosis , Gastrointestinal Tract/virology , Pneumonia, Viral/diagnosis , Antibodies, Viral/metabolism , COVID-19 , COVID-19 Testing , Coronavirus Infections/immunology , Epitopes/immunology , Humans , Immunity, Humoral , Immunoglobulin A/metabolism , Immunoglobulin G/metabolism , Pandemics , Pneumonia, Viral/immunology , Protein Binding , Protein Domains/immunology , SARS-CoV-2 , Serologic Tests , Spike Glycoprotein, Coronavirus/immunology , Viral Load , Virus Shedding
16.
Virology ; 551: 26-35, 2020 12.
Article in English | MEDLINE | ID: covidwho-799506

ABSTRACT

BACKGROUND: SARS-CoV-2 is a novel coronavirus and the cause of COVID-19. More than 80% of COVID-19 patients exhibit mild or moderate symptoms. In this study, we investigated the dynamics of viral load and antibodies against SARS-CoV-2 in a longitudinal cohort of COVID-19 patients with severe and mild/moderate diseases. METHODS: Demographic and clinical information were obtained. Serial samples of blood, nasal and pharyngeal and anal swabs were collected at different time points post-onset. SARS-CoV-2 RNA and anti-SARS-CoV-2 antibodies were measured by qRT-PCR and immunoassays, respectively. RESULTS: Respiratory SARS-CoV-2 RNA was detectable in 58.0% (58/100) COVID-19 patients upon admission and lasted for a median of 13 days post-onset. In addition, 5.9% (1/17) and 20.2% (19/94) of the blood and anal swab specimens were positive for SARS-CoV-2 RNA, respectively. Anal viral RNA was more frequently detected in the patients who were positive for viral RNA in the respiratory samples upon admission. Specific anti-SARS-CoV-2 antibody developed within two weeks after onset, reached peak approximately 17 days post-onset and then maintained at relatively high level up to 50 days we analyzed in most patients. However, the levels of antibodies were variable among the patients. High titers of antibodies appeared to be associated with the severity of the disease. Furthermore, viral proteins from different sources showed significant difference of serological sensitivity especially during the first week post-onset. CONCLUSIONS: Our results indicate rapid clearance or self-elimination of viral RNA in about half of the COVID-19 patients upon admission. Viral RNA shedding of SARS-CoV-2 occurred in multiple tissues including the respiratory system, blood, and intestine. Variable levels of specific anti-SARS-CoV-2 antibody may be associated with disease severity. These findings have shed light on viral kinetics and antibody response in COVID-19 patients and provide scientific evidence for infection control and patient management.


Subject(s)
COVID-19/virology , SARS-CoV-2/genetics , SARS-CoV-2/immunology , Adult , Antibodies, Viral/blood , Antibodies, Viral/immunology , Antigens, Viral/immunology , COVID-19/blood , COVID-19/diagnosis , Female , Humans , Kinetics , Longitudinal Studies , Male , Middle Aged , Nasopharynx/virology , RNA, Viral/analysis , SARS-CoV-2/isolation & purification , Viral Load , Virus Shedding
17.
Front Med (Lausanne) ; 7: 321, 2020.
Article in English | MEDLINE | ID: covidwho-633920

ABSTRACT

Background: Coronavirus disease 2019 (COVID-19) was first identified in Wuhan, China, in December 2019 and quickly spread throughout China and the rest of the world. Many mathematical models have been developed to understand and predict the infectiousness of COVID-19. We aim to summarize these models to inform efforts to manage the current outbreak. Methods: We searched PubMed, Web of science, EMBASE, bioRxiv, medRxiv, arXiv, Preprints, and National Knowledge Infrastructure (Chinese database) for relevant studies published between 1 December 2019 and 21 February 2020. References were screened for additional publications. Crucial indicators were extracted and analysed. We also built a mathematical model for the evolution of the epidemic in Wuhan that synthesised extracted indicators. Results: Fifty-two articles involving 75 mathematical or statistical models were included in our systematic review. The overall median basic reproduction number (R0) was 3.77 [interquartile range (IQR) 2.78-5.13], which dropped to a controlled reproduction number (Rc) of 1.88 (IQR 1.41-2.24) after city lockdown. The median incubation and infectious periods were 5.90 (IQR 4.78-6.25) and 9.94 (IQR 3.93-13.50) days, respectively. The median case-fatality rate (CFR) was 2.9% (IQR 2.3-5.4%). Our mathematical model showed that, in Wuhan, the peak time of infection is likely to be March 2020 with a median size of 98,333 infected cases (range 55,225-188,284). The earliest elimination of ongoing transmission is likely to be achieved around 7 May 2020. Conclusions: Our analysis found a sustained Rc and prolonged incubation/ infectious periods, suggesting COVID-19 is highly infectious. Although interventions in China have been effective in controlling secondary transmission, sustained global efforts are needed to contain an emerging pandemic. Alternative interventions can be explored using modelling studies to better inform policymaking as the outbreak continues.

18.
Med (N Y) ; 1(1): 105-113.e4, 2020 12 18.
Article in English | MEDLINE | ID: covidwho-72371

ABSTRACT

BACKGROUND: Antiviral therapies against the novel coronavirus SARS-CoV-2, which has caused a global pandemic of respiratory illness called COVID-19, are still lacking. METHODS: Our study (ClinicalTrials.gov: NCT04252885, named ELACOI), was an exploratory randomized (2:2:1) controlled trial assessing the efficacy and safety of lopinavir/ritonavir (LPV/r) or arbidol monotherapy for treating patients with mild/moderate COVID-19. FINDINGS: This study successfully enrolled 86 patients with mild/moderate COVID-19, with 34 randomly assigned to receive LPV/r, 35 to arbidol, and 17 with no antiviral medication as control. Baseline characteristics of the three groups were comparable. The primary endpoint, the rate of positive-to-negative conversion of SARS-CoV-2 nucleic acid, was similar between groups (all p > 0.05). There were no differences between groups in the secondary endpoints, the rates of antipyresis, cough alleviation, or improvement of chest computed tomography (CT) at days 7 or 14 (all p > 0.05). At day 7, 8 (23.5%) patients in the LPV/r group, 3 (8.6%) in the arbidol group, and 2 (11.8%) in the control group showed a deterioration in clinical status from moderate to severe/critical (p = 0.206). Overall, 12 (35.3%) patients in the LPV/r group and 5 (14.3%) in the arbidol group experienced adverse events during the follow-up period. No apparent adverse event occurred in the control group. CONCLUSIONS: LPV/r or arbidol monotherapy present little benefit for improving the clinical outcome of patients hospitalized with mild/moderate COVID-19 over supportive care. FUNDING: This study was supported by project 2018ZX10302103-002, 2017ZX10202102-003-004, and Infectious Disease Specialty of Guangzhou High-level Clinical Key Specialty (2019-2021).


Subject(s)
COVID-19 , Ritonavir , Adult , COVID-19/drug therapy , Humans , Indoles , Lopinavir/adverse effects , Ritonavir/adverse effects , SARS-CoV-2 , Sulfides
19.
J Infect ; 80(6): 656-665, 2020 06.
Article in English | MEDLINE | ID: covidwho-47365

ABSTRACT

OBJECTIVE: To better inform efforts to treat and control the current outbreak with a comprehensive characterization of COVID-19. METHODS: We searched PubMed, EMBASE, Web of Science, and CNKI (Chinese Database) for studies published as of March 2, 2020, and we searched references of identified articles. Studies were reviewed for methodological quality. A random-effects model was used to pool results. Heterogeneity was assessed using I2. Publication bias was assessed using Egger's test. RESULTS: 43 studies involving 3600 patients were included. Among COVID-19 patients, fever (83.3% [95% CI 78.4-87.7]), cough (60.3% [54.2-66.3]), and fatigue (38.0% [29.8-46.5]) were the most common clinical symptoms. The most common laboratory abnormalities were elevated C-reactive protein (68.6% [58.2-78.2]), decreased lymphocyte count (57.4% [44.8-69.5]) and increased lactate dehydrogenase (51.6% [31.4-71.6]). Ground-glass opacities (80.0% [67.3-90.4]) and bilateral pneumonia (73.2% [63.4-82.1]) were the most frequently reported findings on computed tomography. The overall estimated proportion of severe cases and case-fatality rate (CFR) was 25.6% (17.4-34.9) and 3.6% (1.1-7.2), respectively. CFR and laboratory abnormalities were higher in severe cases, patients from Wuhan, and older patients, but CFR did not differ by gender. CONCLUSIONS: The majority of COVID-19 cases are symptomatic with a moderate CFR. Patients living in Wuhan, older patients, and those with medical comorbidities tend to have more severe clinical symptoms and higher CFR.


Subject(s)
Coronavirus Infections/epidemiology , Pneumonia, Viral/epidemiology , COVID-19 , China/epidemiology , Coronavirus Infections/blood , Coronavirus Infections/diagnostic imaging , Coronavirus Infections/mortality , Humans , Pandemics , Pneumonia, Viral/blood , Pneumonia, Viral/diagnostic imaging , Pneumonia, Viral/mortality , Risk Factors
SELECTION OF CITATIONS
SEARCH DETAIL