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1.
Front Microbiol ; 13: 782421, 2022.
Article in English | MEDLINE | ID: covidwho-1742229

ABSTRACT

While IgM and IgG response to SARS-CoV-2 has been extensively studied, relatively little is known about secretory IgA (sIgA) response in respiratory mucosa. Here we report IgA response to the SARS-CoV-2 in sputum, throat swabs, and serum with nucleocapsid protein (NP) enzyme-linked immunosorbent assays (ELISA) in a cohort of 28 COVID-19 patients and 55 vaccine recipients. The assays showed sIgA in respiratory mucosa could be detected on the first day after illness onset (AIO), and the median conversion time for sIgA in sputum, throat swabs, and serum was 3, 4, and 10 days, respectively. The positive rates of sIgA first week AIO were 100% (24/28) and 85.7% (24/28) in sputum and throat swabs, respectively, and were both 100% during the mid-onset (2-3 weeks AIO). During the recovery period, sIgA positive rates in sputum and throat swabs gradually decreased from 60.7% (17/28) and 57.1% (16/28) 1 month AIO and the sIgA antibodies were all undetectable 6 months AIO. However, serum IgA positive rate was still 100% at 4 months and 53.6% (15/28) at 6 months. Throat swabs obtained from volunteers who received inactivated SARS-CoV-2 vaccines by intramuscular delivery all showed negative results in IgA ELISA. These findings will likely improve our understanding of respiratory mucosal immunity of this emerging disease and help in containing the pandemic and developing vaccines.

2.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-322629

ABSTRACT

Objective: This study aimed to investigate the value of high-flow nasal cannula (HNFC) oxygen therapy in treating patients with severe novel coronavirus pneumonia (COVID-19). Methods The clinical data of 22 patients with severe COVID-19 were collected. The heart rate (HR), respiratory rate (RR) and oxygenation index (PO 2 /FiO 2 ) at 0, 6, 24 and 72 hours after treatment were compared between the HFNC oxygen therapy group and the conventional oxygen therapy (COT) group. In addition, the white blood cell (WBC) count, lymphocyte (L) count, C-reactive protein (CRP) and procalcitonin (PCT) were compared before and at 72 hours after oxygen therapy treatment. Results Of the included patients, 12 were assigned to the HFNC oxygen therapy group and 10 were assigned to the COT group. The differences in HR, RR, PaO 2 /FiO 2 , WBC, L, CRP and PCT at 0 hours between the two groups were not statistically significant. At 6 hours after treatment with the two oxygen therapies, HR, RR and PaO 2 /FiO 2 were better in the HFNC oxygen therapy group than in the COT group (p < 0.05), while at 24 and 72 hours after treatment with the two oxygen therapies, PaO 2 /FiO 2 was better in the HFNC oxygen therapy group than in the COT group (p < 0.05), but the differences in HR and RR were not statistically significant. At 72 hours after treatment, L and CRP had significantly improved in the HFNC oxygen therapy group compared with the COT group, but the differences in WBC and PCT were not statistically significant. The length of stay in the intensive care unit (ICU) and the total length of hospitalization were shorter in the HFNC oxygen therapy group than in the COT group, and the differences between the two groups were statistically significant. Conclusion Compared with COT, early application of HFNC oxygen therapy in patients with severe COVID-19 can significantly improve oxygenation and RR, and HFNC oxygen therapy can improve the infection indexes of patients and reduce the length of stay in the ICU of patients. Therefore, it has high clinical application value.

3.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-311943

ABSTRACT

The magnitude of SARS-CoV-2 infection, the dynamic changes of immune parameters in patients with the novel coronavirus disease (COVID-19) and their correlation with the disease severity remain unclear. The clinical and laboratory results from 154 confirmed COVID-19 patients were collected. The SARS-CoV-2 RNA levels in patients were estimated using the Ct values of specific RT-PCR tests. The lymphocyte subsets and cytokines profiles in the peripheral blood were analyzed by flow cytometry and specific immunoassays. 154 confirmed COVID-19 patients were clinically examined up to 4 weeks after admission. The initial SARS-CoV-2 RNA Ct values at admission varied but were comparable in the patient groups classified according to the age, gender, underlying diseases, and disease severity. Three days after admission significant higher Ct values were found in severe cases. Significantly reduced counts of T cells and T cell subsets were found in patients with old age and underlying diseases at admission and were characteristic for the development of severe COVID-19. Severe COVID-19 developed preferentially in patients with underlying compromised immunity and was not associated with initial virus levels. Higher SARS-CoV-2 RNA levels in severe cases were apparently a result of impaired immune control associated with dysregulation of inflammation.

6.
BMJ ; 369: m1849, 2020 05 14.
Article in English | MEDLINE | ID: covidwho-1495142

ABSTRACT

OBJECTIVE: To assess the efficacy and safety of hydroxychloroquine plus standard of care compared with standard of care alone in adults with coronavirus disease 2019 (covid-19). DESIGN: Multicentre, open label, randomised controlled trial. SETTING: 16 government designated covid-19 treatment centres in China, 11 to 29 February 2020. PARTICIPANTS: 150 patients admitted to hospital with laboratory confirmed covid-19 were included in the intention to treat analysis (75 patients assigned to hydroxychloroquine plus standard of care, 75 to standard of care alone). INTERVENTIONS: Hydroxychloroquine administrated at a loading dose of 1200 mg daily for three days followed by a maintenance dose of 800 mg daily (total treatment duration: two or three weeks for patients with mild to moderate or severe disease, respectively). MAIN OUTCOME MEASURE: Negative conversion of severe acute respiratory syndrome coronavirus 2 by 28 days, analysed according to the intention to treat principle. Adverse events were analysed in the safety population in which hydroxychloroquine recipients were participants who received at least one dose of hydroxychloroquine and hydroxychloroquine non-recipients were those managed with standard of care alone. RESULTS: Of 150 patients, 148 had mild to moderate disease and two had severe disease. The mean duration from symptom onset to randomisation was 16.6 (SD 10.5; range 3-41) days. A total of 109 (73%) patients (56 standard of care; 53 standard of care plus hydroxychloroquine) had negative conversion well before 28 days, and the remaining 41 (27%) patients (19 standard of care; 22 standard of care plus hydroxychloroquine) were censored as they did not reach negative conversion of virus. The probability of negative conversion by 28 days in the standard of care plus hydroxychloroquine group was 85.4% (95% confidence interval 73.8% to 93.8%), similar to that in the standard of care group (81.3%, 71.2% to 89.6%). The difference between groups was 4.1% (95% confidence interval -10.3% to 18.5%). In the safety population, adverse events were recorded in 7/80 (9%) hydroxychloroquine non-recipients and in 21/70 (30%) hydroxychloroquine recipients. The most common adverse event in the hydroxychloroquine recipients was diarrhoea, reported in 7/70 (10%) patients. Two hydroxychloroquine recipients reported serious adverse events. CONCLUSIONS: Administration of hydroxychloroquine did not result in a significantly higher probability of negative conversion than standard of care alone in patients admitted to hospital with mainly persistent mild to moderate covid-19. Adverse events were higher in hydroxychloroquine recipients than in non-recipients. TRIAL REGISTRATION: ChiCTR2000029868.


Subject(s)
Antiviral Agents/therapeutic use , Coronavirus Infections/drug therapy , Hydroxychloroquine/therapeutic use , Pneumonia, Viral/drug therapy , Adult , COVID-19 , China , Female , Humans , Male , Middle Aged , Pandemics , Treatment Outcome
8.
International Journal of Infectious Diseases ; 95:421-428, 2020.
Article in English | CAB Abstracts | ID: covidwho-1409670

ABSTRACT

Objective: To investigate the epidemiological and clinical features of patients with COVID-19 in Anhui province of China. Method In this descriptive study, we obtained epidemiological, demographic, manifestations, laboratory data and radiological findings of patients confirmed by real-time RT-PCR in the NO.2 People's Hospital of Fuyang City from Jan 20 to Feb 9, 2020. Clinical outcomes were followed up to Feb 18, 2020.

11.
Pediatr Investig ; : e12282, 2021 Aug 12.
Article in English | MEDLINE | ID: covidwho-1353594

ABSTRACT

IMPORTANCE: The Coronavirus disease 2019 (COVID-19) global pandemic poses a considerable challenge for pediatricians. OBJECTIVE: This study aimed to identify the epidemiological characteristics and clinical features of pediatric patients with COVID-19 in China. METHODS: This multicenter retrospective study included pediatric patients from 46 hospitals in China, covering 12 provinces and two municipalities. Epidemiological, demographic, clinical, laboratory, treatment, and outcome data were analyzed. RESULTS: In total, 211 pediatric patients with COVID-19 were included in this study. The median age was 7.0 years (range: 22 days to 18 years). Approximately 16.3% of the patients exhibited asymptomatic infections, 23.0% had upper respiratory tract infections, and 60.7% had pneumonia, including two with severe pneumonia and one with critical illness. Approximately 78.7% of the pediatric patients occurred in familial clusters. The most three common symptoms or signs at onset in children with COVID-19 were fever (54.5%), cough (49.3%), and pharyngeal congestion (20.8%). Only 17.6% of the patients presented with decreased lymphocyte count, whereas 13.6% had increased lymphocyte count. Among the patients with pneumonia who exhibited abnormal chest computed tomography findings, 18.2% (23/127) of the patients had no other symptoms. Generally, the chest radiographs showed abnormalities that affected both lungs (49.6%); ground-glass opacity (47.2%) was the most common manifestation. The cure and improvement rates were 86.7% (183/211) and 13.3% (28/211), respectively. Only one patient with an underlying condition received invasive mechanical ventilation; none of the patients died. INTERPRETATION: Similar to adults, children of all age groups are susceptible to COVID-19. Fortunately, most pediatric patients have mild symptoms or remain asymptomatic, despite the high incidence of pneumonia. Decreased proportions of white blood cells and lymphocytes are less frequent in children than in adults.

12.
Chinese Journal of Emergency Medicine ; 29(7):901-907, 2020.
Article in Chinese | CAB Abstracts | ID: covidwho-1344408

ABSTRACT

Objective: To analyze the clinical characteristics of patients with novel coronavirus pneumonia (COVID-19) and the factors influencing mild eases developing into severe cases, so as to provide a basis for clinical screening, prevention and treatment of potential severe cases.

13.
Front Cell Infect Microbiol ; 11: 663884, 2021.
Article in English | MEDLINE | ID: covidwho-1317217

ABSTRACT

Background: The pandemic of Coronavirus Disease 2019 (COVID-19) brings new challenges for pediatricians, especially in the differentiation with non-COVID-19 pneumonia in the peak season of pneumonia. We aimed to compare the clinical characteristics of pediatric patients with COVID-19 and other respiratory pathogens infected pneumonias. Methods: We conducted a multi-center, cross-sectional study of pediatric inpatients in China. Based on pathogenic test results, pediatric patients were divided into three groups, including COVID-19 pneumonia group, Non-COVID-19 viral (NCV) pneumonia group and Non-viral (NV) pneumonia group. Their clinical characteristics were compared by Kruskal-Wallis H test or chi-square test. Results: A total of 636 pediatric pneumonia inpatients, among which 87 in COVID-19 group, 194 in NCV group, and 355 in NV group, were included in analysis. Compared with NCV and NV patients, COVID-19 patients were older (median age 6.33, IQR 2.00-12.00 years), and relatively fewer COVID-19 patients presented fever (63.2%), cough (60.9%), shortness of breath (1.1%), and abnormal pulmonary auscultation (18.4%). The results were verified by the comparison of COVID-19, respiratory syncytial virus (RSV) and influenza A (IFA) pneumonia patients. Approximately 42.5%, 44.8%, and 12.6% of the COVID-19 patients presented simply ground-glass opacity (GGO), simply consolidation, and the both changes on computed tomography (CT) scans, respectively; the proportions were similar as those in NCV and NV group (p>0.05). Only 47.1% of COVID-19 patients had both lungs pneumonia, which was significantly lower than that proportion of nearly 80% in the other two groups. COVID-19 patients presented lower proportions of increased white blood cell count (16.5%) and abnormal procalcitonin (PCT) (10.7%), and a higher proportion of decreased lymphocyte count (44.0%) compared with the other two groups. Conclusion: Majority clinical characteristics of pediatric COVID-19 pneumonia patients were milder than non-COVID-19 patients. However, lymphocytopenia remained a prominent feature of COVID-19 pediatric pneumonia.


Subject(s)
COVID-19 , Pneumonia , Child , China/epidemiology , Cross-Sectional Studies , Humans , Lung/diagnostic imaging , Pneumonia/epidemiology , Retrospective Studies , SARS-CoV-2
14.
Virol Sin ; 35(6): 758-767, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-1217478

ABSTRACT

Reverse transcription-polymerase chain reaction (RT-PCR) is an essential method for specific diagnosis of SARS-CoV-2 infection. Unfortunately, false negative test results are often reported. In this study, we attempted to determine the principal causes leading to false negative results of RT-PCR detection of SARS-CoV-2 RNAs in respiratory tract specimens. Multiple sputum and throat swab specimens from 161 confirmed COVID-19 patients were tested with a commercial fluorescent RT-PCR kit targeting the ORF1ab and N regions of SARS-CoV-2 genome. The RNA level of a cellular housekeeping gene ribonuclease P/MRP subunit p30 (RPP30) in these specimens was also assessed by RT-PCR. Data for a total of 1052 samples were retrospectively re-analyzed and a strong association between positive results in SARS-CoV-2 RNA tests and high level of RPP30 RNA in respiratory tract specimens was revealed. By using the ROC-AUC analysis, we identified Ct cutoff values for RPP30 RT-PCR which predicted false negative results for SARS-CoV-2 RT-PCR with high sensitivity (95.03%-95.26%) and specificity (83.72%-98.55%) for respective combination of specimen type and amplification reaction. Using these Ct cutoff values, false negative results could be reliably identified. Therefore, the presence of cellular materials, likely infected host cells, are essential for correct SARS-CoV-2 RNA detection by RT-PCR in patient specimens. RPP30 could serve as an indicator for cellular content, or a surrogate indicator for specimen quality. In addition, our results demonstrated that false negativity accounted for a vast majority of contradicting results in SARS-CoV-2 RNA test by RT-PCR.


Subject(s)
COVID-19 Testing/methods , COVID-19/diagnosis , RNA, Viral/genetics , SARS-CoV-2/genetics , Autoantigens/genetics , COVID-19/epidemiology , COVID-19/virology , China/epidemiology , Humans , Negative Results , Polyproteins/genetics , RNA, Viral/isolation & purification , Reference Standards , Retrospective Studies , Reverse Transcriptase Polymerase Chain Reaction/methods , Ribonuclease P/genetics , SARS-CoV-2/isolation & purification , Sensitivity and Specificity , Viral Proteins/genetics
15.
Clin Respir J ; 15(8): 904-914, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1199651

ABSTRACT

BACKGROUND: A pandemic caused by SARS-CoV-2 has infected more than 79 million people and killed exceeding 1.7 million people around the world by the end of 2020. METHOD: We obtained the clinical data of all diagnosed patients and lung function test of followed-up patients in Fuyang, Anhui province to investigate laboratory predictors of severe Coronavirus Disease 2019 (COVID-19) and the impairment of lung function. RESULTS: Of the 155 patients, 87 (56.13%) were males. The mean age was 41.95 (SD 15.34) years. Only 30 (19.35%) patients had the critical condition. Fever (84.52%) was the most common symptoms, and short of breath was more common in severe patients (p < 0.01). Lymphopenia was observed in most patients (74, 47.7%). It showed the elevation of CRP in 100 (64.5%) patients, the elevation of SAA or IL-6 in 104 (67.1%) patients. The calculated cut-off value of CRP was 19.35 mg/ml, the AUC was 0.777, sensitivity was 73.3%, specificity was 69.6%; SAA was 73.55 mg/L, 0.679, 83.3%, 56.8%, respectively; IL-6 was 18.85 pg/ml, 0.797, 83.3%, 64.8%; D-Dimer was 0.325 mg/L, 0.673, 66.7% and 68.8%. The combination of CRP, SAA, IL-6, and D-Dimer was 0.823 in AUC, 73.3% in sensitivity, and 78.4% in specificity. 12 (42.86%) followed-up patients had completely normal lung function indicators. CONCLUSION: Elevated CRP, SAA, IL-6 and D-Dimer can be predictors to severe COVID-19. The combination of these four indicators can improve the effectivity and specificity of assessing severe COVID-19. Most of the followed-up patients showed no abnormalities in lung function test. Abnormal lung function is mainly reflected in the diffusion function.


Subject(s)
COVID-19 , Adult , Female , Humans , Lung , Male , Middle Aged , Prognosis , ROC Curve , Retrospective Studies , SARS-CoV-2
16.
Aging (Albany NY) ; 13(7): 9265-9276, 2021 03 29.
Article in English | MEDLINE | ID: covidwho-1156226

ABSTRACT

BACKGROUND: Dysregulated immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are thought to underlie the progression of coronavirus disease 2019 (COVID-19). We sought to further characterize host antiviral and cytokine gene expression in COVID-19 patients based on illness severity. METHODS: In this case-control study, we retrospectively analyzed 46 recovered COVID-19 patients and 24 healthy subjects (no history of COVID-19) recruited from the Second People's Hospital of Fuyang City. Blood samples were collected from each study participant for RNA extraction and PCR. We assessed changes in antiviral gene expression between healthy controls and patients with mild/moderate (MM) and severe/critical (SC) disease. RESULTS: We found that type I interferon signaling (IFNA2, TLR8, IFNA1, IFNAR1, TLR9, IRF7, ISG15, APOBEC3G, and MX1) and genes encoding proinflammatory cytokines (IL12B, IL15, IL6, IL12A and IL1B) and chemokines (CXCL9, CXCL11 and CXCL10) were upregulated in patients with MM and SC disease. Moreover, we found that IFNA1, apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3G (APOBEC3G), and Fas-associated protein with death domain (FADD) were significantly downregulated (P < 0.05) in the SC group compared to the MM group. We also observed that microRNA (miR)-155 and miR-130a levels were markedly higher in the MM group compared to the SC group. CONCLUSION: COVID-19 is associated with the activation of host antiviral genes. Induction of the IFN system appears to be particularly important in controlling SARS-CoV-2 infection, as decreased expression of IFNA1, APOBEC3G and FADD genes in SC patients, relative to MM patients, may be associated with disease progression.


Subject(s)
COVID-19/genetics , COVID-19/immunology , Immunity, Innate , SARS-CoV-2/immunology , APOBEC-3G Deaminase/genetics , APOBEC-3G Deaminase/immunology , Adult , Aged , Case-Control Studies , Cytokines/genetics , Cytokines/immunology , Female , Humans , Interferon Type I/genetics , Interferon Type I/immunology , Male , Middle Aged , Retrospective Studies , Severity of Illness Index , Transcriptome , Up-Regulation
17.
Front Med ; 15(3): 486-494, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-1122810

ABSTRACT

Tocilizumab has been reported to attenuate the "cytokine storm" in COVID-19 patients. We attempted to verify the effectiveness and safety of tocilizumab therapy in COVID-19 and identify patients most likely to benefit from this treatment. We conducted a randomized, controlled, open-label multicenter trial among COVID-19 patients. The patients were randomly assigned in a 1:1 ratio to receive either tocilizumab in addition to standard care or standard care alone. The cure rate, changes of oxygen saturation and interference, and inflammation biomarkers were observed. Thirty-three patients were randomized to the tocilizumab group, and 32 patients to the control group. The cure rate in the tocilizumab group was higher than that in the control group, but the difference was not statistically significant (94.12% vs. 87.10%, rate difference 95% CI-7.19%-21.23%, P = 0.4133). The improvement in hypoxia for the tocilizumab group was higher from day 4 onward and statistically significant from day 12 (P = 0.0359). In moderate disease patients with bilateral pulmonary lesions, the hypoxia ameliorated earlier after tocilizumab treatment, and less patients (1/12, 8.33%) needed an increase of inhaled oxygen concentration compared with the controls (4/6, 66.67%; rate difference 95% CI-99.17% to-17.50%, P = 0.0217). No severe adverse events occurred. More mild temporary adverse events were recorded in tocilizumab recipients (20/34, 58.82%) than the controls (4/31, 12.90%). Tocilizumab can improve hypoxia without unacceptable side effect profile and significant influences on the time virus load becomes negative. For patients with bilateral pulmonary lesions and elevated IL-6 levels, tocilizumab could be recommended to improve outcome.


Subject(s)
COVID-19 , Antibodies, Monoclonal, Humanized , COVID-19/drug therapy , Humans , SARS-CoV-2 , Treatment Outcome
18.
Natl Sci Rev ; 7(10): 1527-1539, 2020 Oct.
Article in English | MEDLINE | ID: covidwho-1114859

ABSTRACT

In this population-based study, we identified 307 confirmed COVID-19 cases from massive surveillance, including 129 551 individuals screened at fever clinics or returning from Hubei and 3710 close contacts of confirmed COVID-19 patients. Among them, 17 patients were asymptomatic at initial clinical assessment. These asymptomatic patients on admission accounted for a small proportion of all patients (5.54%) with relatively weak transmissibility, and the detection rate was 0.35 per 100 close contacts. Moreover, the dynamics of symptoms of the 307 patients showed that the interval from symptom remission to the final negativity of viral nucleic acid was 5.0 days (interquartile range 2.0 to 11.0 days), with 14 patients (4.56%) having re-detectable viral RNA after discharge. Overall, our findings suggested asymptomatic carriers and presymptomatic patients only accounted for a small proportion of COVID-19 patients. Also, the asymptomatic phase during recovery from COVID-19 implied that negativity in viral RNA is necessary as a de-isolation criterion and follow-up is recommended.

19.
SSRN; 2020.
Preprint | SSRN | ID: ppcovidwho-5138

ABSTRACT

Background: Tocilizumab is reported to be able to attenuate the "cytokine storm" in COVID-19 patients. We tried to ascertain the effectiveness and safety of tocilizumab in COVID-19 and identify patients most likely to be benefit from the treatment. Methods: This was a randomized, controlled, open-label, multicenter trial at 6 hospitals in Anhui and Hubei. Patients were randomly assigned in a 1:1 ratio to receive either tocilizumab in addition to standard care, or standard care alone. The first dose of tocilizumab was 400 mg, diluted in 100 ml 0.9% saline, and intravenous dripped in more than 1 h. A second dose was given if a patient remained febrile for 24 hours after the first dose. The primary endpoint was the cure rate. Primary analysis was done in the intention -to -treat (ITT) population and safety analysis was done in all patients who started their assigned treatment. Findings: Between Feb 13, 2020, and March 13, 2020, 65 patients were enrolled and randomly assigned to a treatment group (33 to tocilizumab and 32 to the controls). One patient in the control group, who aggravated severely 3 days after randomization, was transferred to the tocilizumab group. The cure rate in tocilizumab group was higher than that in the controls but not significant (94.12% vs 87.10%, P=0.4133). Adverse events were recorded in 20 (58.82%) of 34 tocilizumab recipients versus 4 (12.90%) of 31 in the controls. No serious adverse events were reported in tocilizumab group. Interpretation: Tocilizumab treatment did not increase the cure rate of COVID-19. A large scale of study enrolling more patients is needed. However,tocilizumab can improve oxygenation without significant influence on the time virus load tunes negative. For patients with bilateral pulmonary lesions and elevated IL-6 levels, tocilizumab should be recommended for better disease management. Trial Registration: This trial was registered in Chinese Clinical Trial Registry (Number: ChiCTR2000029765). Funding: This work was supported by Department of Science and Technology of Anhui Province and Health Commission of Anhui Province (grant number: 202004a07020001) and the China National Center for Biotechnology Development (grant number: 2020YFC0843800).

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