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1.
Lancet Microbe ; 3(5): e348-e356, 2022 05.
Article in English | MEDLINE | ID: covidwho-1984300

ABSTRACT

Background: The memory immune response is crucial for preventing reinfection or reducing disease severity. However, the robustness and functionality of the humoral and T-cell response to SARS-CoV-2 remains unknown 12 months after initial infection. The aim of this study is to investigate the durability and functionality of the humoral and T-cell response to the original SARS-CoV-2 strain and variants in recovered patients 12 months after infection. Methods: In this longitudinal cohort study, we recruited participants who had recovered from COVID-19 and who were discharged from the Wuhan Research Center for Communicable Disease Diagnosis and Treatment at the Chinese Academy of Medical Sciences, Wuhan, China, between Jan 7 and May 29, 2020. Patients received a follow-up visit between Dec 16, 2020, and Jan 27, 2021. We evaluated the presence of IgM, IgA, and IgG antibodies against the SARS-CoV-2 nucleoprotein, Spike protein, and the receptor-binding domain 12 months after initial infection, using ELISA. Neutralising antibodies against the original SARS-CoV-2 strain, and the D614G, beta (B.1.351), and delta (B.1.617.2) variants were analysed using a microneutralisation assay in a subset of plasma samples. We analysed the magnitude and breadth of the SARS-CoV-2-specific memory T-cell responses using the interferon γ (IFNγ) enzyme-linked immune absorbent spot (ELISpot) assay and intracellular cytokine staining (ICS) assay. The antibody response and T-cell response (ie, IFN-γ, interleukin-2 [IL-2], and tumour necrosis factor α [TNFα]) were analysed by age and disease severity. Antibody titres were also analysed according to sequelae symptoms. Findings: We enrolled 1096 patients, including 289 (26·4%) patients with moderate initial disease, 734 (67·0%) with severe initial disease, and 73 (6·7%) with critical initial disease. Paired plasma samples were collected from 141 patients during the follow-up visits for the microneutralisation assay. PBMCs were collected from 92 of 141 individuals at the 12-month follow-up visit, of which 80 were analysed by ELISpot and 92 by ICS assay to detect the SARS-CoV-2-specific memory T-cell responses. N-IgG (899 [82·0%]), S-IgG (1043 [95·2%]), RBD-IgG (1032 [94·2%]), and neutralising (115 [81·6%] of 141) antibodies were detectable 12 months after initial infection in most individuals. Neutralising antibodies remained stable 6 and 12 months after initial infection in most individuals younger than 60 years. Multifunctional T-cell responses were detected for all SARS-CoV-2 viral proteins tested. There was no difference in the magnitude of T-cell responses or cytokine profiles in individuals with different symptom severity. Moreover, we evaluated both antibody and T-cell responses to the D614G, beta, and delta viral strains. The degree of reduced in-vitro neutralising antibody responses to the D614G and delta variants, but not to the beta variant, was associated with the neutralising antibody titres after SARS-CoV-2 infection. We also found poor neutralising antibody responses to the beta variant; 83 (72·2%) of 115 patients showed no response at all. Moreover, the neutralising antibody titre reduction of the recovered patient plasma against the delta variant was similar to that of the D614G variant and lower than that of the beta variant. By contrast, T-cell responses were cross-reactive to the beta variant in most individuals. Importantly, T-cell responses could be detected in all individuals who had lost the neutralising antibody response to SARS-CoV-2 12 months after the initial infection. Interpretation: SARS-CoV-2-specific neutralising antibody and T-cell responses were retained 12 months after initial infection. Neutralising antibodies to the D614G, beta, and delta viral strains were reduced compared with those for the original strain, and were diminished in general. Memory T-cell responses to the original strain were not disrupted by new variants. This study suggests that cross-reactive SARS-CoV-2-specific T-cell responses could be particularly important in the protection against severe disease caused by variants of concern whereas neutralising antibody responses seem to reduce over time. Funding: Chinese Academy of Medical Sciences, National Natural Science Foundation, and UK Medical Research Council.


Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies, Neutralizing , Antibodies, Viral , COVID-19/epidemiology , Cohort Studies , Cytokines , Humans , Immunoglobulin G , Longitudinal Studies , T-Lymphocytes
2.
Lancet Respir Med ; 10(9): e82, 2022 09.
Article in English | MEDLINE | ID: covidwho-1886191
3.
Lancet ; 399(10334): 1442-1443, 2022 04 16.
Article in English | MEDLINE | ID: covidwho-1867911

Subject(s)
COVID-19 , Humans , SARS-CoV-2
4.
Open Forum Infect Dis ; 9(6): ofac170, 2022 Jun.
Article in English | MEDLINE | ID: covidwho-1860897

ABSTRACT

Background: Detailed characteristics of rheumatic symptoms of coronavirus disease 2019 (COVID-19) were still unknown. We aim to investigate the proportions, characteristics, and risk factors of this condition. Methods: In this prospective, longitudinal cohort study, discharged patients with COVID-19 were interviewed face-to-face at 12 months after symptom onset. Rheumatic symptoms following COVID-19 included newly occurring joint pain and/or joint swelling. The risk factors of developing rheumatic symptoms were identified by multivariable logistic regression analysis. Results: In total, 1296 of 2469 discharged patients with COVID-19 were enrolled in this study. Among them, 160 (12.3% [95% confidence interval {CI}, 10.6%-14.3%]) suffered from rheumatic symptoms following COVID-19 at 12-month follow-up. The most frequently involved joints were the knee joints (38%), followed by hand (25%) and shoulder (19%). Rheumatic symptoms were independent of the severity of illness and corticosteroid treatment during the acute phase, while elderly age (odds ratio [OR], 1.22 [95% CI, 1.06-1.40]) and female sex (OR, 1.58 [95% CI, 1.12-2.23]) were identified as the risk factors for this condition. Conclusions: Our investigation showed a considerable proportion of rheumatic symptoms following COVID-19 in discharged patients, which highlights the need for continuing attention. Notably, rheumatic symptoms following COVID-19 were independent of the severity of illness and corticosteroid treatment during the acute phase.

5.
Open forum infectious diseases ; 2022.
Article in English | EuropePMC | ID: covidwho-1787130

ABSTRACT

Background Detailed characteristics of rheumatic symptoms of COVID-19 were still unknown. We aim to investigate the proportions, characteristics, and risk factors of this condition. Methods In this prospective, longitudinal cohort study, discharged patients with COVID-19 were face-to-face interviewed at 12 months after symptom onset. Rheumatic symptoms following COVID-19 included newly occurring joint pain, and (/or) joint swelling after COVID-19. The risk factors of developing rheumatic symptoms were identified by multivariable logistic regressions. Results In total, 1296 of 2469 discharged patients with COVID-19 were enrolled in this study. Among them, 160 (12.3% [95% CI 10.6, 14.3]) suffered from rheumatic symptoms following COVID-19 at 12-month follow-up. The most frequently involved joints were the knee joints (38%), followed by hand (25%) and shoulder (19%). Rheumatic symptoms were independent of the severity of illness and corticosteroid treatment during acute phase, while elderly (OR 1.22, 95%CI 1.06, 1.40) and women (OR 1.58, 95%CI 1.12, 2.23) were identified as the risk factors for this condition. Conclusions Our investigation showed a considerable proportion of rheumatic symptoms following COVID-19 in discharged patients, which highlights the need for continuing attention. Notably, rheumatic symptoms following COVID-19 were independent of the severity of illness and corticosteroid treatment during acute phase.

6.
Chin Med J (Engl) ; 133(9): 1015-1024, 2020 May 05.
Article in English | MEDLINE | ID: covidwho-1722617

ABSTRACT

BACKGROUND: Human infections with zoonotic coronaviruses (CoVs), including severe acute respiratory syndrome (SARS)-CoV and Middle East respiratory syndrome (MERS)-CoV, have raised great public health concern globally. Here, we report a novel bat-origin CoV causing severe and fatal pneumonia in humans. METHODS: We collected clinical data and bronchoalveolar lavage (BAL) specimens from five patients with severe pneumonia from Wuhan Jinyintan Hospital, Hubei province, China. Nucleic acids of the BAL were extracted and subjected to next-generation sequencing. Virus isolation was carried out, and maximum-likelihood phylogenetic trees were constructed. RESULTS: Five patients hospitalized from December 18 to December 29, 2019 presented with fever, cough, and dyspnea accompanied by complications of acute respiratory distress syndrome. Chest radiography revealed diffuse opacities and consolidation. One of these patients died. Sequence results revealed the presence of a previously unknown ß-CoV strain in all five patients, with 99.8% to 99.9% nucleotide identities among the isolates. These isolates showed 79.0% nucleotide identity with the sequence of SARS-CoV (GenBank NC_004718) and 51.8% identity with the sequence of MERS-CoV (GenBank NC_019843). The virus is phylogenetically closest to a bat SARS-like CoV (SL-ZC45, GenBank MG772933) with 87.6% to 87.7% nucleotide identity, but is in a separate clade. Moreover, these viruses have a single intact open reading frame gene 8, as a further indicator of bat-origin CoVs. However, the amino acid sequence of the tentative receptor-binding domain resembles that of SARS-CoV, indicating that these viruses might use the same receptor. CONCLUSION: A novel bat-borne CoV was identified that is associated with severe and fatal respiratory disease in humans.


Subject(s)
Betacoronavirus , Coronavirus Infections/virology , Pneumonia, Viral/virology , Adult , Aged , Betacoronavirus/genetics , Betacoronavirus/isolation & purification , COVID-19 , Coronavirus Infections/diagnostic imaging , Coronavirus Infections/therapy , Female , Humans , Male , Middle Aged , Pandemics , Pneumonia, Viral/diagnostic imaging , Pneumonia, Viral/therapy , SARS-CoV-2 , Tomography, X-Ray , Treatment Outcome
7.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-311704

ABSTRACT

Background: Seasonal human coronaviruses (HCoVs) including HCoV-229E, -OC43, -NL63 and -HKU1 are widely spreading in global human populations. However, the relevance of humoral response against seasonal HCoVs to COVID-19 pathogenesis is elusive.Methods: We profiled the temporal changes of IgG antibodies against spike (S;S-IgG) proteins of SARS-CoV-2 and seasonal HCoVs in 838 plasma samples collected from 344 COVID-19 patients. We tested the antigenic cross-reactivity of S protein between SARS-CoV-2 and seasonal HCoVs and evaluated the correlations between HCoV-OC43 S-IgG antibody and disease severity in COVID-19 patients.Findings: SARS-CoV-2 S-IgG titers mounted until days 22–28, whereas HCoV-OC43 antibody titers increased until days 15–21 and then plateaued until day 46. However, IgG antibody titers against HCoV-NL63, -229E, and -HKU1 showed no significant increasing. A two-way cross-reactivity was identified between SARS-CoV-2 and HCoV-OC43. Neutralizing antibodies against SARS-CoV-2 were not detected in healthy controls who were positive for HCoV-OC43 S-IgG. HCoV-OC43 S-IgG titers were significantly higher in patients with severe disease than those in mild/moderate patients at days 1–21 post symptom onset (PSO). Higher levels of HCoV-OC43 S-IgG were also observed in patients requiring mechanical ventilation and the elderly. At days 1–10 PSO, HCoV-OC43 S-IgG titers correlated to disease severity in all age groups, and to fatality in over 60-year group.Interpretation: Our data indicate that there exist a humoral cross-reactive response between HCoV-OC43 and SARS-CoV-2. The cross-reactive HCoV-OC43 S-IgG antibody is not protective against SARS-CoV-2, but may be a risk factor for the severity and adverse outcome of COVID-19.Funding Statement: This study was funded in part by the National Major Science & Technology Project for Control and Prevention of Major Infectious Diseases in China (2017ZX10204401, 2018ZX10734404), Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Sciences (2016-I2M-1–014, 2018-I2M-1-003, 2020-I2M-1-001, 2020-I2M-CoV19-005), Natural Science Foundation of China (82041011/H0104), and National Key R&D Program of China (2020YFA0707600). Declaration of Interests: The authors declare no competing interests.Ethics Approval Statement: This study was approved by the Ethical Review Board of Wuhan Jinyintan Hospital, Infectious Disease Hospital of Heilongjiang Province (Harbin), and Institute of Pathogen Biology, Chinese Academy of Medical Sciences. Written informed consent was obtained from each healthy volunteer and COVID-19 patients in cohort 4. Written informed consents from the remaining patients were waived in light of the emerging infectious disease of high public health relevance.

8.
Front Med (Lausanne) ; 8: 800492, 2021.
Article in English | MEDLINE | ID: covidwho-1686495

ABSTRACT

BACKGROUND: Cytokine storm observed in patients with severe Coronavirus Disease 2019 (COVID-19) contributes to poor clinical outcomes and increased mortality. Janus kinases (JAKs) are important mediators in the cytokine storm. Therefore, we conduct a living systematic review and meta-analysis of the literature investigating efficacy and safety of JAK inhibitors for patients with COVID-19. METHODS: Databases were searched up to December 1, 2021 for interventional and observational studies comparing JAK inhibitor treatment with concurrent control in patients with COVID-19. Efficacy and safety outcomes were evaluated by pooled risk ratio (RR). RESULTS: Of 3,170 records retrieved, 15 studies were eligible and 13 were evaluated in the meta-analysis (n = 3,977). Based on data from three randomized controlled trials (RCTs), baricitinib treatment significantly decreased mortality by day 28 in hospitalized patients with COVID-19 (RR = 0.64, 95% CI 0.51-0.80) without increasing the incidence of adverse outcomes. In subgroup analysis, patients who required supplemental oxygen (RR = 0.62, 95% CI 0.41-0.95) or high-flow oxygen/non-invasive ventilation (RR = 0.59, 95% CI 0.42-0.85) at baseline benefited most. Pooled analysis of all eligible studies for JAK inhibitors (baricitinib, ruxolitinib, tofacitinib, and nezulcitinib) demonstrated a significant decrease in mortality (RR = 0.62, 95% CI 0.49-0.78) with no increase in the risk of adverse events. CONCLUSION: Baricitinib probably decreases mortality in hospitalized adult patients with COVID-19, especially for patients who required supplemental oxygen or high-flow oxygen/non-invasive ventilation at baseline. The efficacy and safety of other JAK inhibitors, such as ruxolitinib, tofacitinib, and nezulcitinib, await more evidence. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021261414, identifier: CRD42021261414.

9.
EBioMedicine ; 76: 103817, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1632870

ABSTRACT

BACKGROUND: Kidney damage in COVID-19 patients has been of special concern. The association of acute kidney injury (AKI) with post-acute kidney function among COVID-19 survivors was not sufficiently elucidated. METHODS: An ambidirectional cohort study was conducted with enrollment of COVID-19 survivors discharged from hospital between Jan 7, and May 29, 2020. Study participants were invited to follow-up visits at 6 and 12 months after symptom onset. The primary outcome was percentage of estimated glomerular filtration rate (eGFR) decreased from acute phase (between symptom onset and hospital discharge) to follow-up, and secondary outcome was reduced renal function at follow-up. FINDINGS: In total, 1,734 study participants were included in this study. Median follow-up duration was 342.0 days (IQR, 223.0-358.0) after symptom onset. After multivariable adjustment, percentage of eGFR decreased from acute phase to follow-up was 8.30% (95% CI, 5.99-10.61) higher among AKI participants than those without AKI at acute phase. Participants with AKI had an odds ratio (OR) of 4.60 (95% CI, 2.10-10.08) for reduced renal function at follow-up. The percentage of eGFR decreased for participants with AKI stage 1, stage 2, and stage 3 was 6.02% (95% CI, 3.48-8.57), 15.99% (95% CI, 10.77-21.22), and 17.79% (95% CI, 9.14-26.43) higher compared with those without AKI, respectively. INTERPRETATION: AKI at acute phase of COVID-19 was closely related to the longitudinal decline and post-acute status of kidney function at nearly one-year after symptom onset. Earlier and more intense follow-up strategies on kidney function management could be beneficial to COVID-19 survivors. FUNDING: Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences (CIFMS 2020-I2M-CoV19-005, 2018-I2M-1-003, and 2020-I2M-2-013); National Natural Science Foundation of China (82041011); National Key Research and Development Program of China (2018YFC1200102); Major Projects of National Science and Technology on New Drug Creation and Development of Pulmonary Tuberculosis (2020ZX09201001).


Subject(s)
Acute Kidney Injury/diagnosis , COVID-19/pathology , Kidney/physiology , Acute Kidney Injury/etiology , Aged , COVID-19/complications , COVID-19/virology , Cohort Studies , Female , Follow-Up Studies , Glomerular Filtration Rate , Humans , Male , Middle Aged , Odds Ratio , Risk Factors , SARS-CoV-2/isolation & purification , Severity of Illness Index , Survivors
10.
Lancet ; 398(10314): 1872-1873, 2021 11 20.
Article in English | MEDLINE | ID: covidwho-1521621

Subject(s)
COVID-19 , Humans , SARS-CoV-2 , Survivors
11.
BMC Pulm Med ; 21(1): 308, 2021 Sep 28.
Article in English | MEDLINE | ID: covidwho-1439539

ABSTRACT

BACKGROUND: Whether procalcitonin (PCT) or C-reactive protein (CRP) combined with certain clinical characteristics can better distinguish viral from bacterial infections remains unclear. The aim of the study was to assess the ability of PCT or CRP combined with clinical characteristics to distinguish between viral and bacterial infections in hospitalized non-intensive care unit (ICU) adults with lower respiratory tract infection (LRTI). METHODS: This was a post-hoc analysis of a randomized clinical trial previously conducted among LRTI patients. The ability of PCT, CRP and PCT or CRP combined with clinical symptoms to discriminate between viral and bacterial infection were assessed by portraying receiver operating characteristic (ROC) curves among patients with only a viral or a typical bacterial infection. RESULTS: In total, 209 infected patients (viral 69%, bacterial 31%) were included in the study. When using CRP or PCT to discriminate between viral and bacterial LRTI, the optimal cut-off points were 22 mg/L and 0.18 ng/mL, respectively. When the optimal cut-off for CRP (≤ 22 mg/L) or PCT (≤ 0.18 ng/mL) combined with rhinorrhea was used to discriminate viral from bacterial LRTI, the AUCs were 0.81 (95% CI: 0.75-0.87) and 0.80 (95% CI: 0.74-0.86), which was statistically significantly better than when CRP or PCT used alone (p < 0.001). When CRP ≤ 22 mg/L, PCT ≤ 0.18 ng/mL and rhinorrhea were combined, the AUC was 0.86 (95% CI: 0.80-0.91), which was statistically significantly higher than when CRP (≤ 22 mg/L) or PCT (≤ 0.18 ng/mL) was combined with rhinorrhea (p = 0.011 and p = 0.021). CONCLUSIONS: Either CRP ≤ 22 mg/L or PCT ≤ 0.18 ng/mL combined with rhinorrhea could help distinguish viral from bacterial infections in hospitalized non-ICU adults with LRTI. When rhinorrhea was combined together, discrimination ability was further improved.


Subject(s)
C-Reactive Protein/metabolism , Procalcitonin/blood , Respiratory Tract Infections/microbiology , Rhinorrhea/complications , Virus Diseases/diagnosis , Aged , Area Under Curve , Bacterial Infections/diagnosis , Female , Hospitalization , Humans , Male , Middle Aged , ROC Curve , Respiratory Tract Infections/blood , Retrospective Studies , Virus Diseases/blood
12.
Lancet ; 398(10302): 747-758, 2021 08 28.
Article in English | MEDLINE | ID: covidwho-1376121

ABSTRACT

BACKGROUND: The full range of long-term health consequences of COVID-19 in patients who are discharged from hospital is largely unclear. The aim of our study was to comprehensively compare consequences between 6 months and 12 months after symptom onset among hospital survivors with COVID-19. METHODS: We undertook an ambidirectional cohort study of COVID-19 survivors who had been discharged from Jin Yin-tan Hospital (Wuhan, China) between Jan 7 and May 29, 2020. At 6-month and 12-month follow-up visit, survivors were interviewed with questionnaires on symptoms and health-related quality of life (HRQoL), and received a physical examination, a 6-min walking test, and laboratory tests. They were required to report their health-care use after discharge and work status at the 12-month visit. Survivors who had completed pulmonary function tests or had lung radiographic abnormality at 6 months were given the corresponding tests at 12 months. Non-COVID-19 participants (controls) matched for age, sex, and comorbidities were interviewed and completed questionnaires to assess prevalent symptoms and HRQoL. The primary outcomes were symptoms, modified British Medical Research Council (mMRC) score, HRQoL, and distance walked in 6 min (6MWD). Multivariable adjusted logistic regression models were used to evaluate the risk factors of 12-month outcomes. FINDINGS: 1276 COVID-19 survivors completed both visits. The median age of patients was 59·0 years (IQR 49·0-67·0) and 681 (53%) were men. The median follow-up time was 185·0 days (IQR 175·0-198·0) for the 6-month visit and 349·0 days (337·0-361·0) for the 12-month visit after symptom onset. The proportion of patients with at least one sequelae symptom decreased from 68% (831/1227) at 6 months to 49% (620/1272) at 12 months (p<0·0001). The proportion of patients with dyspnoea, characterised by mMRC score of 1 or more, slightly increased from 26% (313/1185) at 6-month visit to 30% (380/1271) at 12-month visit (p=0·014). Additionally, more patients had anxiety or depression at 12-month visit (26% [331/1271] at 12-month visit vs 23% [274/1187] at 6-month visit; p=0·015). No significant difference on 6MWD was observed between 6 months and 12 months. 88% (422/479) of patients who were employed before COVID-19 had returned to their original work at 12 months. Compared with men, women had an odds ratio of 1·43 (95% CI 1·04-1·96) for fatigue or muscle weakness, 2·00 (1·48-2·69) for anxiety or depression, and 2·97 (1·50-5·88) for diffusion impairment. Matched COVID-19 survivors at 12 months had more problems with mobility, pain or discomfort, and anxiety or depression, and had more prevalent symptoms than did controls. INTERPRETATION: Most COVID-19 survivors had a good physical and functional recovery during 1-year follow-up, and had returned to their original work and life. The health status in our cohort of COVID-19 survivors at 12 months was still lower than that in the control population. FUNDING: Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, the National Natural Science Foundation of China, the National Key Research and Development Program of China, Major Projects of National Science and Technology on New Drug Creation and Development of Pulmonary Tuberculosis, the China Evergrande Group, Jack Ma Foundation, Sino Biopharmaceutical, Ping An Insurance (Group), and New Sunshine Charity Foundation.


Subject(s)
COVID-19/complications , Survivors , Aged , Anxiety/etiology , COVID-19/physiopathology , COVID-19/psychology , Depression/etiology , Exercise Tolerance , Fatigue/etiology , Female , Follow-Up Studies , Humans , Longitudinal Studies , Lung/physiopathology , Male , Middle Aged , Muscle Weakness/etiology , Quality of Life , SARS-CoV-2 , Walk Test
13.
BMJ Open ; 11(8): e049515, 2021 08 05.
Article in English | MEDLINE | ID: covidwho-1346064

ABSTRACT

INTRODUCTION: Current antibiotic prescription for acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is generally based on the Anthonisen criteria in The Global Initiative for Chronic Obstructive Pulmonary Disease (GOLD) guideline that have a potential risk of antibiotics overuse. The dilemma is to identify patients who are most likely to benefit from antibiotics while avoiding unnecessary antibiotic use. Procalcitonin (PCT), a more sensitive and specific biomarker of bacterial infection than other conventional laboratory tests, has the potential to determine those patients in whom antibiotics would be beneficial. It is unclear whether PCT-guided antibiotic therapy is safe and effective for patients hospitalised with AECOPD. The study hypothesis is that PCT-guided antibiotic therapy could reduce the antibiotic prescription rate for AECOPD, compared with the GOLD guideline recommendations, without negatively impacting the treatment success rate. METHODS AND ANALYSIS: In this multicenter, open-label, randomised controlled trial, we aim to enrol 500 hospitalised patients with AECOPD that will be randomly assigned to either a PCT-guided group or a GOLD guideline-guided group. The coprimary endpoints are antibiotic prescription rate for AECOPD within 30 days post randomisation and treatment success rate at day 30 post randomisation. The secondary outcomes include: antibiotic prescription rate at day 1 post randomisation; hospital antibiotic exposure; length of hospital stay; rate of subsequent exacerbation and hospital readmission; overall mortality within 30 days post randomisation; changes in lung function and the score of COPD assessment test and modified Medical Research Council; and rate of intensive care unit admission. ETHICS AND DISSEMINATION: This trial has been approved by the ethic committee of China-Japan Friendship Hospital. The findings of the study will be disseminated in peer-reviewed journals. If the results of the study are positive, PCT-guided antibiotic therapy is likely to change the guidelines for antibiotic recommendations for patients with AECOPD. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov: NCT04682899.


Subject(s)
Bacterial Infections , Pulmonary Disease, Chronic Obstructive , Anti-Bacterial Agents/therapeutic use , Bacterial Infections/drug therapy , Humans , Inpatients , Multicenter Studies as Topic , Procalcitonin , Pulmonary Disease, Chronic Obstructive/drug therapy , Randomized Controlled Trials as Topic
14.
Lancet ; 398(10296): 188-190, 2021 07 17.
Article in English | MEDLINE | ID: covidwho-1313500
15.
Med Phys ; 48(8): 4334-4349, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1265402

ABSTRACT

OBJECTIVE: Coronavirus disease 2019 (COVID-19) has caused hundreds of thousands of infections and deaths. Efficient diagnostic methods could help curb its global spread. The purpose of this study was to develop and evaluate a method for accurately diagnosing COVID-19 based on computed tomography (CT) scans in real time. METHODS: We propose an architecture named "concatenated feature pyramid network" ("Concat-FPN") with an attention mechanism, by concatenating feature maps of multiple. The proposed architecture is then used to form two networks, which we call COVID-CT-GAN and COVID-CT-DenseNet, the former for data augmentation and the latter for data classification. RESULTS: The proposed method is evaluated on 3 different numbers of magnitude of COVID-19 CT datasets. Compared with the method without GANs for data augmentation or the original network auxiliary classifier generative adversarial network, COVID-CT-GAN increases the accuracy by 2% to 3%, the recall by 2% to 4%, the precision by 1% to 3%, the F1-score by 1% to 3%, and the area under the curve by 1% to 4%. Compared with the original network DenseNet-201, COVID-CT-DenseNet increases the accuracy by 1% to 3%, the recall by 4% to 9%, the precision by 1%, the F1-score by 1% to 3%, and the area under the curve by 2%. CONCLUSION: The experimental results show that our method improves the efficiency of diagnosing COVID-19 on CT images, and helps overcome the problem of limited training data when using deep learning methods to diagnose COVID-19. SIGNIFICANCE: Our method can help clinicians build deep learning models using their private datasets to achieve automatic diagnosis of COVID-19 with a high precision.


Subject(s)
COVID-19 , COVID-19 Testing , Humans , Radionuclide Imaging , SARS-CoV-2 , Tomography, X-Ray Computed
16.
Clin Infect Dis ; 72(11): e901-e913, 2021 06 01.
Article in English | MEDLINE | ID: covidwho-1249298

ABSTRACT

There have been arguments on whether angiotensin-converting enzyme inhibitor (ACEI) and angiotensin receptor blocker (ARB) treatment alters the risk of coronavirus disease 2019 (COVID-19) susceptibility and disease severity. We identified a total of 102 eligible studies for systematic review, in which 49 studies adjusting for confounders were included in the meta-analysis. We found no association between prior ACEI/ARB use and risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the general population (adjusted odds ratio [aOR], 1.00; 95% confidence interval [CI], .94-1.05). The risk of mortality (aOR, .87; 95% CI, .66-1.04) and severe outcomes (aOR, .95; 95% CI, .73-1.24) were also unchanged among COVID-19 patients taking ACEIs/ARBs. These findings remained consistent in subgroup analyses stratified by populations, drug exposures, and other secondary outcomes. This systematic review provides evidence-based support to current medical guidelines and position statements that ACEIs/ARBs should not be discontinued. Additionally, there has been no evidence for initiating ACEI/ARB regimen as prevention or treatment of COVID-19.


Subject(s)
COVID-19 , Hypertension , Angiotensin Receptor Antagonists/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Humans , SARS-CoV-2
17.
Clin Infect Dis ; 72(10): e545-e551, 2021 05 18.
Article in English | MEDLINE | ID: covidwho-1232187

ABSTRACT

BACKGROUND: The characteristics of neutralizing antibodies (NAbs) and antibody against major antigen proteins related to clinical outcomes in severe coronavirus disease 2019 (COVID-19) patients were still less known. METHODS: NAbs and antibodies targeting nucleocapsid (N), spike protein (S), and the receptor-binding domain (RBD) in longitudinal plasma samples from the LOTUS China trial were measured by microneutralization assay and enzyme-linked immunosorbent assay (ELISA). Viral load was determined by real-time reverse transcription polymerase chain reaction (RT-PCR). A total of 576 plasma and 576 throat swabs were collected from 191 COVID-19 patients. Antibody titers related to adverse outcome and clinical improvement were analyzed. Multivariable adjusted generalized linear mixed model for random effects were developed. RESULTS: After day 28 post symptoms onset, the rate of antibody positivity reached 100% for RBD-immunoglobulin M (IgM), 97.8% for S-IgM, 100% for N-immunoglobulin G (IgG), 100% for RBD-IgG, 91.1% for N-IgM, and 91.1% for NAbs. The NAbs titers increased over time in both survivors and nonsurvivors and correlated to IgG antibodies against N, S, and RBD, whereas its presence showed no statistical correlation with death. N-IgG (slope -2.11, 95% confidence interval [CI] -3.04 to -1.18, P < .0001), S-IgG (slope -2.44, 95% CI -3.35 to -1.54, P < .0001), and RBD-IgG (slope -1.43, 95% CI -1.98 to -.88, P < .0001) were negatively correlated with viral load. S-IgG titers were lower in nonsurvivors than survivors (P = .020) at week 4 after symptoms onset. CONCLUSIONS: IgM and IgG against N, S, and RBD and NAbs developed in most severe COVID-19 patients and do not correlate clearly with clinical outcomes. The levels of IgG antibodies against N, S, and RBD were related to viral clearance.


Subject(s)
COVID-19 , Adult , Antibodies, Viral , Antibody Formation , China/epidemiology , Humans , Immunoglobulin M , SARS-CoV-2
18.
Lancet ; 397(10287): 1807-1808, 2021 05 15.
Article in English | MEDLINE | ID: covidwho-1228178

Subject(s)
COVID-19 , Humans , Kidney , SARS-CoV-2
19.
The Lancet ; 397(10270):220-232, 2021.
Article in English | APA PsycInfo | ID: covidwho-1164655

ABSTRACT

Presents a study which aims to examine consequences of COVID-19 in patients discharged from hospital for 6-months. This ambidirectional cohort study was done at Jin Yin-tan Hospital, the first designated hospital for patients with COVID-19 in Wuhan, Hubei, China. Clinical data for acute phase were retrieved from electronic medical records, including demographic characteristics, clinical characteristics, laboratory test results;and treatment. The disease severity was characterized by the highest seven-category scale during the hospital stay. Data were managed using REDCap electronic data capture tools in order to minimize missing inputs and allow for real-time data validation and quality control. Follow-up consultations were done in the outpatient clinic of Jin Yin-tan Hospital. All participants were interviewed face-to-face by trained physicians and asked to complete a series of questionnaires. For the symptom questionnaire, participants were asked to report newly occurring and persistent symptoms, or any symptoms worse than before COVID-19 development. A total of 2469 patients with COVID-19 were discharged from Jin Yin-tan Hospital between Jan 7, and May 29, 2020, and the follow-up study was done from June 16, 2020, to Sept 3, 2020. This is the largest cohort study with the longest follow-up duration assessing the health consequences of adult patients discharged from hospital recovering from COVID-19. (PsycInfo Database Record (c) 2021 APA, all rights reserved)

20.
Emerg Microbes Infect ; 10(1): 664-676, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1139855

ABSTRACT

Seasonal human coronaviruses (HCoVs) including HCoV-229E, -OC43, -NL63, and -HKU1 widely spread in global human populations. However, the relevance of humoral response against seasonal HCoVs to COVID-19 pathogenesis is elusive. In this study, we profiled the temporal changes of IgG antibody against spike proteins (S-IgG) of SARS-CoV-2 and seasonal HCoVs in 838 plasma samples collected from 344 COVID-19 patients. We tested the antigenic cross-reactivities of S protein between SARS-CoV-2 and seasonal HCoVs and evaluated the correlations between the levels of HCoV-OC43 S-IgG and the disease severity in COVID-19 patients. We found that SARS-CoV-2 S-IgG titres mounted until days 22-28, whereas HCoV-OC43 antibody titres increased until days 15-21 and then plateaued until day 46. However, IgG titres against HCoV-NL63, -229E, and -HKU1 showed no significant increase. A two-way cross-reactivity was identified between SARS-CoV-2 and HCoV-OC43. Neutralizing antibodies against SARS-CoV-2 were not detectable in healthy controls who were positive for HCoV-OC43 S-IgG. HCoV-OC43 S-IgG titres were significantly higher in patients with severe disease than those in mild patients at days 1-21 post symptom onset (PSO). Higher levels of HCoV-OC43 S-IgG were also observed in patients requiring mechanical ventilation. At days 1-10 PSO, HCoV-OC43 S-IgG titres correlated to disease severity in the age group over 60. Our data indicate that there is a correlation between cross-reactive antibody against HCoV-OC43 spike protein and disease severity in COVID-19 patients.


Subject(s)
Antibodies, Viral/blood , COVID-19/immunology , Coronavirus OC43, Human/immunology , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , Adolescent , Adult , Aged , Aged, 80 and over , Antibodies, Neutralizing/blood , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/pathology , Cross Reactions/immunology , Enzyme-Linked Immunosorbent Assay , Female , Humans , Immunoglobulin G/blood , Immunoglobulin G/immunology , Male , Middle Aged , Severity of Illness Index , Young Adult
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