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1.
Stem Cell Rev Rep ; 2022 Jan 11.
Article in English | MEDLINE | ID: covidwho-1620352

ABSTRACT

Type 2 diabetes mellitus (T2DM), one of the most common carbohydrate metabolism disorders, is characterized by chronic hyperglycemia and insulin resistance (IR), and has become an urgent global health challenge. Mesenchymal stem cells (MSCs) originating from perinatal tissues such as umbilical cord (UC) and amniotic membrane (AM) serve as ideal candidates for the treatment of T2DM due to their great advantages in terms of abundant source, proliferation capacity, immunomodulation and plasticity for insulin-producing cell differentiation. However, the optimally perinatal MSC source to treat T2DM remains elusive. This study aims to compare the therapeutic efficacy of MSCs derived from AM and UC (AMMSCs and UCMSCs) of the same donor in the alleviation of T2DM symptoms and explore the underlying mechanisms. Our results showed that AMMSCs and UCMSCs displayed indistinguishable immunophenotype and multi-lineage differentiation potential, but UCMSCs had a much higher expansion capacity than AMMSCs. Moreover, we uncovered that single-dose intravenous injection of either AMMSCs or UCMSCs could comparably reduce hyperglycemia and improve IR in T2DM db/db mice. Mechanistic investigations revealed that either AMMSC or UCMSC infusion could greatly improve glycolipid metabolism in the liver of db/db mice, which was evidenced by decreased liver to body weight ratio, reduced lipid accumulation, upregulated glycogen synthesis, and increased Akt phosphorylation. Taken together, these data indicate that the same donor-derived AMMSCs and UCMSCs possessed comparable effects and shared a similar hepatoprotective mechanism on the alleviation of T2DM symptoms.

2.
Front Immunol ; 12: 627844, 2021.
Article in English | MEDLINE | ID: covidwho-1573949

ABSTRACT

Background: The effective treatment of coronavirus disease 2019 (COVID-19) remains unclear. We reported successful use of high-dose intravenous immunoglobulin (IVIg) in cases of severe COVID-19, but evidence from larger case series is still lacking. Methods: A multi-center retrospective study was conducted to evaluate the effectiveness of IVIg administered within two weeks of disease onset at a total dose of 2 g/kg body weight, in addition to standard care. The primary endpoint was 28-day mortality. Efficacy of high-dose IVIg was assessed by using the Cox proportional hazards regression model and the Kaplan-Meier curve adjusted by inverse probability of treatment weighting (IPTW) analysis, and IPTW after multiple imputation (MI) analysis. Results: Overall, 26 patients who received high-dose IVIg with standard therapy and 89 patients who received standard therapy only were enrolled in this study. The IVIg group was associated with a lower 28-day mortality rate and less time to normalization of inflammatory markers including IL-6, IL-10, and ferritin compared with the control. The adjusted HR of 28-day mortality in high-dose IVIg group was 0.24 (95% CI 0.06-0.99, p<0.001) in IPTW model, and 0.27 (95% CI 0.10-0.57, p=0.031) in IPTW-MI model. In subgroup analysis, patients with no comorbidities or treated in the first week of disease were associated with more benefit from high-dose IVIg. Conclusions: High-dose IVIg administered in severe COVID-19 patients within 14 days of onset was linked to reduced 28-day mortality, more prominent with those having no comorbidities or treated at earlier stage.


Subject(s)
COVID-19/drug therapy , COVID-19/mortality , Immunoglobulins, Intravenous/administration & dosage , SARS-CoV-2/metabolism , Adult , Aged , COVID-19/blood , China/epidemiology , Disease-Free Survival , Female , Ferritins/blood , Humans , Interleukin-10/blood , Interleukin-6/blood , Male , Middle Aged , Retrospective Studies , Survival Rate
3.
Front Chem ; 9: 689521, 2021.
Article in English | MEDLINE | ID: covidwho-1435982

ABSTRACT

The densely glycosylated spike (S) proteins that are highly exposed on the surface of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) facilitate viral attachment, entry, and membrane fusion. We have previously reported all the 22 N-glycosites and site-specific N-glycans in the S protein protomer. Herein, we report the O-glycosylation landscapes of SARS-CoV-2 S proteins, which were characterized through high-resolution mass spectrometry. Following digestion with trypsin and trypsin/Glu-C, and de-N-glycosylation using PNGase F, we determined the GalNAc-type O-glycosylation pattern of S proteins, including O-glycosites and the six most common O-glycans occupying them, via Byonic identification and manual validation. Finally, 255 intact O-glycopeptides composed of 50 peptides sequences and 43 O-glycosites were discovered by higher energy collision-induced dissociation (HCD), and three O-glycosites were confidently identified by electron transfer/higher energy collision-induced dissociation (EThcD) in the insect cell-expressed S protein. Most glycosites were modified by non-sialylated O-glycans such as HexNAc(1) and HexNAc(1)Hex (1). In contrast, in the human cell-expressed S protein S1 subunit, 407 intact O-glycopeptides composed of 34 peptides sequences and 30 O-glycosites were discovered by HCD, and 11 O-glycosites were unambiguously assigned by EThcD. However, the measurement of O-glycosylation occupancy hasn't been made. Most glycosites were modified by sialylated O-glycans such as HexNAc(1)Hex (1)NeuAc (1) and HexNAc(1)Hex (1)NeuAc (2). Our results reveal that the SARS-CoV-2 S protein is an O-glycoprotein; the O-glycosites and O-glycan compositions vary with the host cell type. These comprehensive O-glycosylation landscapes of the S protein are expected to provide novel insights into the viral binding mechanism and present a strategy for the development of vaccines and targeted drugs.

5.
Signal Transduct Target Ther ; 6(1): 304, 2021 08 17.
Article in English | MEDLINE | ID: covidwho-1361622

ABSTRACT

A comprehensive analysis of the humoral immune response to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is essential in understanding COVID-19 pathogenesis and developing antibody-based diagnostics and therapy. In this work, we performed a longitudinal analysis of antibody responses to SARS-CoV-2 proteins in 104 serum samples from 49 critical COVID-19 patients using a peptide-based SARS-CoV-2 proteome microarray. Our data show that the binding epitopes of IgM and IgG antibodies differ across SARS-CoV-2 proteins and even within the same protein. Moreover, most IgM and IgG epitopes are located within nonstructural proteins (nsps), which are critical in inactivating the host's innate immune response and enabling SARS-CoV-2 replication, transcription, and polyprotein processing. IgM antibodies are associated with a good prognosis and target nsp3 and nsp5 proteases, whereas IgG antibodies are associated with high mortality and target structural proteins (Nucleocapsid, Spike, ORF3a). The epitopes targeted by antibodies in patients with a high mortality rate were further validated using an independent serum cohort (n = 56) and using global correlation mapping analysis with the clinical variables that are associated with COVID-19 severity. Our data provide fundamental insight into humoral immunity during SARS-CoV-2 infection. SARS-CoV-2 immunogenic epitopes identified in this work could also help direct antibody-based COVID-19 treatment and triage patients.


Subject(s)
Antibodies, Viral/immunology , COVID-19/immunology , Immunity, Humoral , SARS-CoV-2/immunology , Viral Nonstructural Proteins/immunology , COVID-19/mortality , Critical Illness , Disease-Free Survival , Epitopes/immunology , Female , Humans , Immunoglobulin G/immunology , Immunoglobulin M/immunology , Male , Protein Array Analysis , Survival Rate
6.
Front Immunol ; 12: 677957, 2021.
Article in English | MEDLINE | ID: covidwho-1337637

ABSTRACT

Patients with inflammatory bowel disease, psoriasis or other rheumatic diseases treated with corticosteroids, immunomodulators and biologics might face additional risk during COVID-19 epidemic due to their immunocompromised status. However, there was still no unanimous opinion on the use of these therapy during COVID-19 epidemic. Current studies suggested that systemic corticosteroids might increase the risk of hospitalization, as well as risks of ventilation, ICU, and death among patients with immune-mediated inflammatory diseases. Anti-TNF agent was associated with lower rate of hospitalization, as well as lower risks of ventilation, ICU, and death. No significant changes in rates of hospitalization, ventilation, ICU and mortality were observed in patients treated with immunomodulators or biologics apart from anti-TNF agents. The underlying mechanism of these results might be related to pathway of antiviral immune response and cytokine storm induced by SARS-COV-2 infection. Decision on the use of corticosteroids, immunomodulators and biologics should be made after weighing the benefits and potential risks based on individual patients.


Subject(s)
Adrenal Cortex Hormones/therapeutic use , Biological Products/therapeutic use , COVID-19/drug therapy , Cytokine Release Syndrome/drug therapy , Immunosuppressive Agents/therapeutic use , Inflammatory Bowel Diseases/drug therapy , Psoriasis/drug therapy , Rheumatic Diseases/drug therapy , SARS-CoV-2/physiology , Tumor Necrosis Factor Inhibitors/therapeutic use , COVID-19/mortality , Cytokine Release Syndrome/mortality , Hospitalization , Humans , Immunity , Inflammatory Bowel Diseases/mortality , Psoriasis/mortality , Rheumatic Diseases/mortality , Risk , Survival Analysis
7.
Ren Fail ; 43(1): 1104-1114, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1303829

ABSTRACT

BACKGROUND: The clinical use of serum creatine (sCr) and cystatin C (CysC) in kidney function evaluation of critically ill patients has been in continuous discussion. The difference between estimated glomerular filtration rate calculated by sCr (eGFRcr) and CysC (eGFRcysc) of critically ill COVID-19 patients were investigated in this study. METHODS: This is a retrospective, single-center study of critically ill patients with COVID-19 admitted in intensive care unit (ICU) at Wuhan, China. Control cases were moderate COVID-19 patients matched in age and sex at a ratio of 1:1. The eGFRcr and eGFRcysc were compared. The association between eGFR and death were analyzed in critically ill cases. The potential factors influencing the divergence between eGFRcr and eGFRcysc were explored. RESULTS: A total of 76 critically ill COVID-19 patients were concluded. The mean age was 64.5 ± 9.3 years. The eGFRcr (85.45 (IQR 60.58-99.23) ml/min/1.73m2) were much higher than eGFRcysc (60.6 (IQR 34.75-79.06) ml/min/1.73m2) at ICU admission. About 50 % of them showed eGFRcysc < 60 ml/min/1.73 m2 while 25% showed eGFRcr < 60 ml/min/1.73 m2 (χ2 = 10.133, p = 0.001). This divergence was not observed in moderate group. The potential factors influencing the divergence included serum interleukin-6 (IL-6), tumor necrosis factor (TNF-α) level as well as APACHEII, SOFA scores. Reduced eGFRcr (<60 mL/min/1.73 m2) was associated with death (HR = 1.939, 95%CI 1.078-3.489, p = 0.027). CONCLUSIONS: The eGFRcr was generally higher than eGFRcysc in critically ill COVID-19 cases with severe inflammatory state. The divergence might be affected by inflammatory condition and illness severity. Reduced eGFRcr predicted in-hospital death. In these patients, we advocate for caution when using eGFRcysc.


Subject(s)
COVID-19/physiopathology , Creatine/blood , Cystatin C/blood , Glomerular Filtration Rate , Renal Insufficiency, Chronic/diagnosis , Aged , Biomarkers/blood , COVID-19/complications , COVID-19/mortality , China/epidemiology , Critical Illness/therapy , Female , Hospital Mortality , Humans , Kidney Function Tests , Male , Middle Aged , Renal Insufficiency, Chronic/blood , Renal Insufficiency, Chronic/etiology , Retrospective Studies , Survival Analysis
8.
Chin Med Sci J ; 36(2): 85-96, 2021 Jun 30.
Article in English | MEDLINE | ID: covidwho-1299806

ABSTRACT

ObjectiveTo describe the epidemiologic, clinical, laboratory, and radiological characteristics and prognoses of COVID-19 confirmed patients in a single center in Beijing, China. Methods The study retrospectively included 19 patients with nucleic acid-confirmed SARS-CoV-2 infection at our hospital from January 20 to March 5, 2020. The final follow-up date was March 14, 2020. The epidemiologic and clinical information was obtained through direct communication with the patients or their family members. Laboratory results retrieved from medical records and radiological images were analyzed both qualitatively by two senior chest radiologists as well as quantitatively via an artificial intelligence software. Results We identified 5 family clusters (13/19, 68.4%) from the study cohort. All cases had good clinical prognoses and were either mild (3/19) or moderate (16/19) clinical types. Fever (15/19, 78.9%) and dry cough (11/19, 57.9%) were common symptoms. Two patients received negative results for more than three consecutive viral nucleic acid tests. The longest interval between an initial CT abnormal finding and a confirmed diagnosis was 30 days. One patient's nucleic acid test turned positive on the follow-up examination after discharge. The presence of radiological abnormalities was non-specific for the diagnosis of COVID-19. Conclusions COVID-19 patients with mild or no clinical symptoms are common in Beijing, China. Radiological abnormalities are mostly non-specific and massive CT examinations for COVID-19 screening should be avoided. Analyses of the contact histories of diagnosed cases in combination with clinical, radiological and laboratory findings are crucial for the early detection of COVID-19. Close monitoring after discharge is also recommended.


Subject(s)
COVID-19 Nucleic Acid Testing , COVID-19 , Lung/diagnostic imaging , SARS-CoV-2 , Tomography, X-Ray Computed , Adult , COVID-19/diagnosis , COVID-19/diagnostic imaging , Child , China , Female , Humans , Male , Middle Aged , Retrospective Studies
9.
Front Immunol ; 12: 671443, 2021.
Article in English | MEDLINE | ID: covidwho-1172967

ABSTRACT

[This corrects the article DOI: 10.3389/fimmu.2021.627844/full.].

10.
Emerg Microbes Infect ; 9(1): 727-732, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-1169498

ABSTRACT

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with droplets and contact as the main means of transmission. Since the first case appeared in Wuhan, China, in December 2019, the outbreak has gradually spread nationwide. Up to now, according to official data released by the Chinese health commission, the number of newly diagnosed patients has been declining, and the epidemic is gradually being controlled. Although most patients have mild symptoms and good prognosis after infection, some patients developed severe and die from multiple organ complications. The pathogenesis of SARS-CoV-2 infection in humans remains unclear. Immune function is a strong defense against invasive pathogens and there is currently no specific antiviral drug against the virus. This article reviews the immunological changes of coronaviruses like SARS, MERS and other viral pneumonia similar to SARS-CoV-2. Combined with the published literature, the potential pathogenesis of COVID-19 is inferred, and the treatment recommendations for giving high-doses intravenous immunoglobulin and low-molecular-weight heparin anticoagulant therapy to severe type patients are proposed.


Subject(s)
Coronavirus Infections/immunology , Pneumonia, Viral/immunology , Severe Acute Respiratory Syndrome/immunology , Animals , Antibodies, Viral/blood , Antibodies, Viral/immunology , Anticoagulants/therapeutic use , B-Lymphocytes/immunology , Betacoronavirus/pathogenicity , COVID-19 , Coronavirus Infections/drug therapy , Coronavirus Infections/therapy , Coronavirus Infections/virology , Cytokines/immunology , Cytokines/metabolism , Heparin, Low-Molecular-Weight/therapeutic use , Humans , Immunoglobulins, Intravenous/therapeutic use , Immunologic Factors/therapeutic use , Influenza A Virus, H1N1 Subtype , Influenza, Human/immunology , Mice , Middle East Respiratory Syndrome Coronavirus/immunology , Pandemics , Pneumonia, Viral/drug therapy , Pneumonia, Viral/therapy , Pneumonia, Viral/virology , SARS Virus/immunology , SARS-CoV-2 , T-Lymphocytes/immunology
11.
Asian J Criminol ; : 1-24, 2021 Jan 06.
Article in English | MEDLINE | ID: covidwho-1018436

ABSTRACT

The Covid-19 pandemic has given rise to stigma, discrimination, and even hate crimes against various populations in the Chinese language-speaking world. Using interview data with victims, online observation, and the data mining of media reports, this paper investigated the changing targets of stigma from the outbreak of Covid-19 to early April 2020 when China had largely contained the first wave of Covid-19 within its border. We found that at the early stage of the pandemic, stigma was inflicted by some non-Hubei Chinese population onto Wuhan and Hubei residents, by some Hong Kong and Taiwan residents onto mainland Chinese, and by some Westerners towards overseas Chinese. With the number of cases outside China surpassing that in China, stigmatization was imposed by some Chinese onto Africans in China. We further explore how various factors, such as the fear of infection, food and mask culture, political ideology, and racism, affected the stigmatization of different victim groups. This study not only improved our understanding of how stigmatization happened in the Chinese-speaking world amid Covid-19 but also contributes to the literature of how sociopolitical factors may affect the production of hate crimes.

12.
Preprint | SciFinder | ID: ppcovidwho-4971

ABSTRACT

Objective To observe the effect of peroxyacetic acid in the laboratoiy disinfection of SARS-CoV-2 nucleic acid detection, and to provide a reference for laboratoiy prevention and control of SARS-CoV-2 detection. Methods Using gene detection technol. the effectiveness of compound peroxyacetic acid disinfectant in sterilizing laboratoiy for SARS-CoV-2 was evaluated. Results The compound peroxyacetic acid contained about 2.5 g/L of peroxyacetic acid and 60 g/L of hydrogen peroxide. The stock solution was used in an aerosol elec. sprayer at a dosage of 22 mL/m3 in a specimen preparation room of laboratoiy for SARS-CoV-2 nucleic acid detection. Spraying disinfection was conducted and the room was sealed for 60 min. The laboratory had been spray - sterilized at the end of each work for 30 consecutive days, and all collected laboratoiy environmental specimens have not detected the pos. SARS-CoV-2 nucleic acid and there had never been any incident of staff infection with SARS-CoV-2. Conclusion The results prove that spray disinfection of laboratoiy for SARS-CoV-2 detection with the compound peroxyacetic acid can effectively kill the SARS-CoV-2 in laboratoiy environment and can effectively protect the safety of staff.

13.
J Cosmet Dermatol ; 20(2): 372-380, 2021 Feb.
Article in English | MEDLINE | ID: covidwho-991566

ABSTRACT

BACKGROUND: The emergence of COVID-19 has become a global health emergency. The transmissibility of the disease is of great interest to healthcare workers and scientists alike. The primary route of transmission is via respiratory droplets, but viral RNA has also been found in feces and body fluids such as urine, serum, and semen. So far, there has been no report on whether SARS-CoV-2 is present in the exudates of cutaneous lesions. This study was designed to investigate whether SARS-CoV-2 can be found in the pressure injury exudates in patients with severe COVID-19 infections. METHODS: 46 critically ill COVID-19 patients who were admitted to the ICU of the Sino-French New City Branch of Tongji Hospital in Wuhan between February 4 and April 12 developed pressure injuries. 22 patients with pressure injuries had wound exudates. Wound and pharyngeal swabs of the 22 patients were collected and RT-PCRs were conducted to detect SARS-CoV-2 viral RNA. RESULTS: At the time of pressure injury, 5 patients still tested positive by pharyngeal swabs, the rest of the 17 patients tested negative. However, none of the wound exudate swabs from the participants tested positive for SARS-CoV-2 by RT-PCR. CONCLUSION: Our study suggests that it is rather unlikely that COVID-19 can be transmitted via pressure injury exudates, but we still recommend standardized personal protective equipment, face shield and an additional pair of gloves when treating pressure injuries.


Subject(s)
COVID-19/virology , Exudates and Transudates/virology , Pressure Ulcer/virology , SARS-CoV-2/isolation & purification , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged
14.
Arthritis Rheumatol ; 72(12): 1998-2004, 2020 12.
Article in English | MEDLINE | ID: covidwho-880254

ABSTRACT

OBJECTIVE: Coagulopathy is one of the characteristics observed in critically ill patients with coronavirus disease 2019 (COVID-19). Antiphospholipid antibodies (aPLs) contribute to coagulopathy, though their role in COVID-19 remains unclear. This study was undertaken to determine the prevalence and characteristics of aPLs in patients with COVID-19. METHODS: Sera collected from 66 COVID-19 patients who were critically ill and 13 COVID-19 patients who were not critically ill were tested by chemiluminescence immunoassay for anticardiolipin antibodies (aCLs), anti-ß2 -glycoprotein I (anti-ß2 GPI) (IgG, IgM, and IgA), and IgG anti-ß2 GPI-domain 1 (anti-ß2 GPI-D1) and IgM and IgG anti-phosphatidylserine/prothrombin (anti-PS/PT) antibodies were detected in the serum by enzyme-linked immunosorbent assay. RESULTS: Of the 66 COVID-19 patients in critical condition, aPLs were detected in 31 (47% ). Antiphospholipid antibodies were not present among COVID-19 patients who were not in critical condition. The IgA anti-ß2 GPI antibody was the most commonly observed aPL in patients with COVID-19 and was present in 28.8% (19 of 66) of the critically ill patients, followed by IgA aCLs (17 of 66, or 25.8%) and IgG anti-ß2 GPI (12 of 66, or 18.2%). For multiple aPLs, IgA anti-ß2 GPI + IgA aCLs was the most common antibody profile observed (15 of 66, or 22.7%), followed by IgA anti-ß2 GPI + IgA aCL + IgG anti-ß2 GPI (10 of 66, or 15.2%). Antiphospholipid antibodies emerge ~35-39 days after disease onset. A dynamic analysis of aPLs revealed 4 patterns based on the persistence or transient appearance of the aPLs. Patients with multiple aPLs had a significantly higher incidence of cerebral infarction compared to patients who were negative for aPLs (P = 0.023). CONCLUSION: Antiphospholipid antibodies were common in critically ill patients with COVID-19. Repeated testing demonstrating medium to high titers of aPLs and the number of aPL types a patient is positive for may help in identifying patients who are at risk of developing cerebral infarction. Antiphospholipid antibodies may be transient and disappear within a few weeks, but in genetically predisposed patients, COVID-19 may trigger the development of an autoimmune condition similar to the antiphospholipid syndrome (APS), referred to as "COVID-19-induced APS-like syndrome." Long-term follow-up of COVID-19 patients who are positive for aPLs would be of great importance in understanding the pathogenesis of this novel coronavirus.


Subject(s)
Antibodies, Antiphospholipid/blood , COVID-19/blood , Critical Illness , Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Young Adult
15.
J Vet Diagn Invest ; 32(4): 572-576, 2020 Jul.
Article in English | MEDLINE | ID: covidwho-823306

ABSTRACT

Porcine epidemic diarrhea, a disease caused by porcine epidemic diarrhea virus (PEDV), results in large economic losses to the global swine industry. To manage this disease effectively, it is essential to detect PEDV early and accurately. We developed a sensitive and accurate droplet digital PCR (ddPCR) assay to detect PEDV. The optimal primer-to-probe concentration and melting temperature were identified as 300:200 nM and 59.2°C, respectively. The specificity of the ddPCR assay was confirmed by negative test results for common swine pathogens. The detection limit for the ddPCR was 0.26 copies/µL, which is a 5.7-fold increase in sensitivity compared to that of real-time PCR (rtPCR). Both ddPCR and rtPCR assays exhibited good linearity, although ddPCR provided higher sensitivity for clinical detection compared to that of rtPCR. Our ddPCR methodology provides a promising tool for evaluating the PEDV viral load when used for clinical testing, particularly for detecting samples with low-copy viral loads.


Subject(s)
Coronavirus Infections/veterinary , Polymerase Chain Reaction/veterinary , Porcine epidemic diarrhea virus/isolation & purification , Swine Diseases/diagnosis , Viral Load/veterinary , Animals , Coronavirus Infections/diagnosis , Coronavirus Infections/virology , Polymerase Chain Reaction/methods , Sensitivity and Specificity , Sus scrofa , Swine , Swine Diseases/virology
17.
Emerg Microbes Infect ; 9(1): 2315-2321, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-799338

ABSTRACT

Prolonged presence of viral nucleic acid was reported in certain patients with coronavirus disease 2019 (COVID-19), with unclear clinical and epidemiological significance. We here described the clinical and epidemiological characteristics of 37 recovered COVID-19 patients with prolonged presence of viral RNA in Wuhan, China. For those who had been discharged and re-admitted, their close contacts outside the hospital were traced and evaluated. The median age of the 37 patients was 62 years (IQR 50, 68), and 24 (64.9%) were men. They had common or severe COVID-19. With prolonged positive RT-PCR, most patients were clinically stable, 29 (78.4%) denied any symptoms. A total of 431 PCR tests were carried out, with each patient at a median of 8 time points. The median time of PCR positivity to April 18 was 78 days (IQR 67.7, 84.5), and the longest 120 days. 22 of 37 patients had been discharged at a median of 44 days (IQR 22.3, 50) from disease onset, and 9 had lived with their families without personal protections for a total of 258 person-days and no secondary infection was identified through epidemiological investigation, nucleic acid and antibody screening. Infectiousness in COVID-19 patients with prolonged presence of viral nucleic acid should not solely be evaluated by RT-PCR. Those patients who have clinically recovered and whose disease course has exceeded four weeks were associated with very limited infectiousness. Reconsideration of disease control in such patients is needed.


Subject(s)
Betacoronavirus/physiology , Coronavirus Infections/virology , Pneumonia, Viral/virology , RNA, Viral/genetics , Aged , Betacoronavirus/genetics , COVID-19 , China/epidemiology , Coronavirus Infections/epidemiology , Female , Follow-Up Studies , Humans , Male , Middle Aged , Pandemics , Pneumonia, Viral/epidemiology , Polymerase Chain Reaction , RNA, Viral/metabolism , SARS-CoV-2
18.
J Am Soc Nephrol ; 31(9): 2205-2221, 2020 09.
Article in English | MEDLINE | ID: covidwho-725838

ABSTRACT

BACKGROUND: The incidence, severity, and outcomes of AKI in COVID-19 varied in different reports. In patients critically ill with COVID-19, the clinicopathologic characteristics of AKI have not been described in detail. METHODS: This is a retrospective cohort study of 81 patients critically ill with COVID-19 in an intensive care unit. The incidence, etiologies, and outcomes of AKI were analyzed. Pathologic studies were performed in kidney tissues from ten deceased patients with AKI. RESULTS: A total of 41 (50.6%) patients experienced AKI in this study. The median time from illness to AKI was 21.0 (IQR, 9.5-26.0) days. The proportion of Kidney Disease Improving Global Outcomes (KDIGO) stage 1, stage 2, and stage 3 AKI were 26.8%, 31.7%, and 41.5%, respectively. The leading causes of AKI included septic shock (25 of 41, 61.0%), volume insufficiency (eight of 41, 19.5%), and adverse drug effects (five of 41, 12.2%). The risk factors for AKI included age (per 10 years) (HR, 1.83; 95% CI, 1.24 to 2.69; P=0.002) and serum IL-6 level (HR, 1.83; 95% CI, 1.23 to 2.73; P=0.003). KDIGO stage 3 AKI predicted death. Other potential risk factors for death included male sex, elevated D-dimer, serum IL-6 level, and higher Sequential Organ Failure Assessment score. The predominant pathologic finding was acute tubular injury. Nucleic acid tests and immunohistochemistry failed to detect the virus in kidney tissues. CONCLUSIONS: AKI was a common and multifactorial complication in patients critically ill with COVID-19 at the late stage of the disease course. The predominant pathologic finding was acute tubular injury. Older age and higher serum IL-6 level were risk factors of AKI, and KDIGO stage 3 AKI independently predicted death.


Subject(s)
Acute Kidney Injury/pathology , Betacoronavirus , Coronavirus Infections/complications , Kidney/pathology , Pneumonia, Viral/complications , Acute Kidney Injury/etiology , Aged , Aged, 80 and over , COVID-19 , Coronavirus Infections/pathology , Creatinine/blood , Critical Illness , Female , Humans , Intensive Care Units , Interleukin-6/blood , Kidney/ultrastructure , Kidney/virology , Male , Middle Aged , Pandemics , Pneumonia, Viral/pathology , Retrospective Studies , Risk Factors , SARS-CoV-2
20.
Front Immunol ; 11: 1660, 2020.
Article in English | MEDLINE | ID: covidwho-697898

ABSTRACT

The current outbreak of viral pneumonia, caused by novel coronavirus SARS-CoV-2, is the focus of worldwide attention. The WHO declared the COVID-19 outbreak a pandemic event on Mar 12, 2020, and the number of confirmed cases is still on the rise worldwide. While most infected individuals only experience mild symptoms or may even be asymptomatic, some patients rapidly progress to severe acute respiratory failure with substantial mortality, making it imperative to develop an efficient treatment for severe SARS-CoV-2 pneumonia alongside supportive care. So far, the optimal treatment strategy for severe COVID-19 remains unknown. Intravenous immunoglobulin (IVIg) is a blood product pooled from healthy donors with high concentrations of immunoglobulin G (IgG) and has been used in patients with autoimmune and inflammatory diseases for more than 30 years. In this review, we aim to highlight the known mechanisms of immunomodulatory effects of high-dose IVIg therapy, the immunopathological hypothesis of viral pneumonia, and the clinical evidence of IVIg therapy in viral pneumonia. We then make cautious therapeutic inferences about high-dose IVIg therapy in treating severe COVID-19. These inferences may provide relevant and useful insights in order to aid treatment for COVID-19.


Subject(s)
Antibodies, Neutralizing/therapeutic use , Betacoronavirus/immunology , Coronavirus Infections/drug therapy , Coronavirus Infections/immunology , Immunoglobulin G/therapeutic use , Immunoglobulins, Intravenous/therapeutic use , Immunologic Factors/therapeutic use , Pneumonia, Viral/drug therapy , Pneumonia, Viral/immunology , Adult , Animals , Antibodies, Neutralizing/administration & dosage , Antibody-Dependent Enhancement , COVID-19 , Child , Coronavirus Infections/virology , Cytokines/metabolism , Humans , Immunoglobulin Fab Fragments/metabolism , Immunoglobulin Fc Fragments/metabolism , Immunoglobulin G/administration & dosage , Immunoglobulins, Intravenous/administration & dosage , Immunologic Factors/administration & dosage , Pandemics , Pneumonia, Viral/virology , SARS-CoV-2
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