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1.
Placenta ; 121: 79-81, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1730029

ABSTRACT

SARS-CoV-2 infection in pregnancy and COVID placentitis are associated with an increased risk of stillbirth. We sought to investigate the presence of maternal viremia in people with SARS-CoV-2 infection during pregnancy who had histologic placentitis versus those without placentitis. SARS-CoV-2 qRT-PCR was performed on plasma from 6 patients with COVID placentitis and 12 matched controls without placentitis. SARS-CoV-2 infection occurred between 4/2020-1/2021; the latency between SARS-CoV-2 diagnosis and delivery was 0-76 days. Two placentitis cases demonstrated viremia (1 stillbirth and 1 well infant), while 12/12 controls were negative. Future research may consider viremia as a possible marker of COVID placentitis.


Subject(s)
COVID-19 , Pregnancy Complications, Infectious , COVID-19/complications , COVID-19 Testing , Female , Humans , Pregnancy , Pregnancy Complications, Infectious/diagnosis , Pregnancy Complications, Infectious/pathology , SARS-CoV-2 , Stillbirth , Viremia
2.
Lancet Gastroenterol Hepatol ; 7(5): 396-415, 2022 May.
Article in English | MEDLINE | ID: covidwho-1683802

ABSTRACT

BACKGROUND: Since the release of the first global hepatitis elimination targets in 2016, and until the COVID-19 pandemic started in early 2020, many countries and territories were making progress toward hepatitis C virus (HCV) elimination. This study aims to evaluate HCV burden in 2020, and forecast HCV burden by 2030 given current trends. METHODS: This analysis includes a literature review, Delphi process, and mathematical modelling to estimate HCV prevalence (viraemic infection, defined as HCV RNA-positive cases) and the cascade of care among people of all ages (age ≥0 years from birth) for the period between Jan 1, 2015, and Dec 31, 2030. Epidemiological data were collected from published sources and grey literature (including government reports and personal communications) and were validated among country and territory experts. A Markov model was used to forecast disease burden and cascade of care from 1950 to 2050 for countries and territories with data. Model outcomes were extracted from 2015 to 2030 to calculate population-weighted regional averages, which were used for countries or territories without data. Regional and global estimates of HCV prevalence, cascade of care, and disease burden were calculated based on 235 countries and territories. FINDINGS: Models were built for 110 countries or territories: 83 were approved by local experts and 27 were based on published data alone. Using data from these models, plus population-weighted regional averages for countries and territories without models (n=125), we estimated a global prevalence of viraemic HCV infection of 0·7% (95% UI 0·7-0·9), corresponding to 56·8 million (95% UI 55·2-67·8) infections, on Jan 1, 2020. This number represents a decrease of 6·8 million viraemic infections from a 2015 (beginning of year) prevalence estimate of 63·6 million (61·8-75·8) infections (0·9% [0·8-1·0] prevalence). By the end of 2020, an estimated 12·9 million (12·5-15·4) people were living with a diagnosed viraemic infection. In 2020, an estimated 641 000 (623 000-765 000) patients initiated treatment. INTERPRETATION: At the beginning of 2020, there were an estimated 56·8 million viraemic HCV infections globally. Although this number represents a decrease from 2015, our forecasts suggest we are not currently on track to achieve global elimination targets by 2030. As countries recover from COVID-19, these findings can help refocus efforts aimed at HCV elimination. FUNDING: John C Martin Foundation, Gilead Sciences, AbbVie, ZeShan Foundation, and The Hepatitis Fund.


Subject(s)
COVID-19 , Hepatitis A , Hepatitis C , COVID-19/epidemiology , Hepacivirus , Hepatitis C/epidemiology , Humans , Infant, Newborn , Pandemics , Prevalence , Viremia/epidemiology
3.
Front Immunol ; 12: 784145, 2021.
Article in English | MEDLINE | ID: covidwho-1674332

ABSTRACT

As the coronavirus disease 2019 (COVID-19) pandemic is ongoing and new variants of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) are emerging, there is an urgent need for vaccines to protect individuals at high risk for complications and to potentially control disease outbreaks by herd immunity. Surveillance of rare safety issues related to these vaccines is progressing, since more granular data emerge about adverse events of SARS-CoV-2 vaccines during post-marketing surveillance. Varicella zoster virus (VZV), Epstein-Barr virus (EBV) and cytomegalovirus (CMV) reactivation has already been reported in COVID-19 patients. In addition, adverse events after SARS-CoV-2 mRNA vaccination have also been in the context of varicella zoster virus (VZV) reactivation and directly associated with the mRNA vaccine. We present the first case of CMV reactivation and pericarditis in temporal association with SARS-CoV-2 vaccination, particularly adenovirus-based DNA vector vaccine ChAdOx1 nCoV-19 against SARS-CoV-2. After initiation of antiviral therapy with oral valganciclovir, CMV viremia disappeared and clinical symptoms rapidly improved. Since huge vaccination programs are ongoing worldwide, post-marketing surveillance systems must be in place to assess vaccine safety that is important for the detection of any events. In the context of the hundreds of millions of individuals to be vaccinated against SARS-CoV-2, a potential causal association with CMV reactivation may result in a considerable number of cases with potentially severe complications.


Subject(s)
/adverse effects , Cytomegalovirus/drug effects , Pericarditis/chemically induced , SARS-CoV-2/immunology , Virus Activation/drug effects , Aged , Antiviral Agents/therapeutic use , COVID-19/prevention & control , Cytomegalovirus/physiology , Cytomegalovirus Infections/chemically induced , Cytomegalovirus Infections/drug therapy , Cytomegalovirus Infections/virology , Female , Humans , Pericarditis/drug therapy , Pericarditis/virology , Treatment Outcome , Valganciclovir/therapeutic use , Viremia/chemically induced , Viremia/drug therapy , Viremia/virology
4.
J Infect Dis ; 225(5): 856-861, 2022 Mar 02.
Article in English | MEDLINE | ID: covidwho-1666006

ABSTRACT

We tested the combination of a broadly neutralizing HIV antibody with the latency reversal agent vorinostat (VOR). Eight participants received 2 month-long cycles of VRC07-523LS with VOR. Low-level viremia, resting CD4+ T-cell-associated HIV RNA (rca-RNA) was measured, and intact proviral DNA assay (IPDA) and quantitative viral outgrowth assay (QVOA) were performed at baseline and posttreatment. In 3 participants, IPDA and QVOA declines were accompanied by significant declines of rca-RNA. However, no IPDA or QVOA declines clearly exceeded assay variance or natural decay. Increased resistance to VRC07-523LS was not observed. This combination therapy did not reduce viremia or the HIV reservoir. Clinical Trials Registration. NCT03803605.


Subject(s)
HIV Infections , HIV-1 , Broadly Neutralizing Antibodies , CD4-Positive T-Lymphocytes , HIV-1/genetics , Humans , Viremia/drug therapy , Virus Latency , Vorinostat/therapeutic use
5.
J Infect Dis ; 225(2): 208-213, 2022 01 18.
Article in English | MEDLINE | ID: covidwho-1635423

ABSTRACT

The burden of coronavirus disease 2019 (COVID-19) in children represents a fraction of cases worldwide, yet a subset of those infected are at risk for severe disease. We measured plasma severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA in a cohort of 103 children hospitalized with COVID-19 with diverse clinical manifestations. SARS-CoV-2 RNAemia was detected in 27 (26%) of these children, lasted for a median of 6 (interquartile range, 2-9) days, and was associated with higher rates of oxygen administration, admission to the intensive care unit, and longer hospitalization.


Subject(s)
COVID-19 Nucleic Acid Testing/methods , COVID-19/diagnosis , SARS-CoV-2/isolation & purification , Adolescent , COVID-19/epidemiology , Child , Child, Preschool , Female , Hospitalization , Humans , Infant , Intensive Care Units , Male , Nasopharynx/virology , RNA, Viral/genetics , SARS-CoV-2/genetics , Severity of Illness Index , Viremia/epidemiology
6.
Open Heart ; 8(2)2021 12.
Article in English | MEDLINE | ID: covidwho-1582998

ABSTRACT

OBJECTIVE: Soluble ST2 (sST2) reflects inflammation, endothelial dysfunction and myocardial fibrosis, is produced in the lungs and is an established biomarker in heart failure. We sought to determine the role of sST2 in COVID-19 by assessing pathophysiological correlates and its association to in-hospital outcomes. METHODS: We enrolled 123 consecutive, hospitalised patients with COVID-19 in the prospective, observational COVID-19 MECH study. Biobank samples were collected at baseline, day 3 and day 9. The key exposure variable was sST2, and the outcome was ICU treatment with mechanical ventilation or in-hospital death. RESULTS: Concentrations of sST2 at baseline was median 48 (IQR 37-67) ng/mL, and 74% had elevated concentrations (>37.9 ng/mL). Higher baseline sST2 concentrations were associated with older age, male sex, white race, smoking, diabetes, hypertension and chronic kidney disease. Baseline sST2 also associated with the presence of SARS-CoV-2 viraemia, lower oxygen saturation, higher respiratory rate and increasing concentrations of biomarkers reflecting inflammation, thrombosis and cardiovascular disease. During the hospitalisation, 8 (7%) patients died and 27 (22%) survivors received intensive care unit (ICU) treatment. Baseline sST2 concentrations demonstrated a graded association with disease severity (median, IQR): medical ward 43 (36-59) ng/mL; ICU 67 (39-104) ng/mL and non-survivors 107 (72-116) ng/mL (p<0.001 for all comparisons). These associations persisted at day 3 and day 9 . CONCLUSIONS: sST2 concentrations associate with SARS-CoV-2 viraemia, hypoxaemia and concentrations of inflammatory and cardiovascular biomarkers. There was a robust association between baseline sST2 and disease severity that was independent of, and superior to, established risk factors. sST2 reflects key pathophysiology and may be a promising biomarker in COVID-19. TRIAL REGISTRATION NUMBER: NCT04314232.


Subject(s)
COVID-19 , Hypoxia , Interleukin-1 Receptor-Like 1 Protein/analysis , SARS-CoV-2/isolation & purification , Viremia , Aged , Biomarkers/analysis , COVID-19/blood , COVID-19/mortality , COVID-19/physiopathology , Comorbidity , Correlation of Data , Female , Hospital Mortality , Humans , Hypoxia/diagnosis , Hypoxia/etiology , Intensive Care Units/statistics & numerical data , Male , Middle Aged , Norway/epidemiology , Prognosis , Risk Factors , Severity of Illness Index , Smoking/epidemiology , Viremia/diagnosis , Viremia/etiology
7.
J Med Virol ; 94(4): 1734-1737, 2022 04.
Article in English | MEDLINE | ID: covidwho-1568202

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load dynamics in respiratory samples have been studied, but knowledge about changes in serial serum samples of infected patients in relation to their immunological response is lacking. We investigated the dynamics of SARS-CoV-2 viral load and antibody response in sequential serum of coronavirus disease 2019 (COVID-19) patients and attempted to culture the virus in the serum. A total of 81 sequential serum samples from 10 confirmed COVID-19 patients (5 with mild and 5 with moderate symptoms) were analyzed. Samples were collected during hospitalization and after discharge (median follow-up of 35 days). SARS-CoV-2 ribonucleic acid in the serum was detected by real-time polymerase chain reaction. Total antibody and IgG to SARS-CoV-2 Spike protein were analyzed by Chemiluminescent Immunoassays, and neutralizing antibodies were detected using a Surrogate Virus Neutralization Test. Viremia was observed in all cases at admission, and viral copy gradually dropped to undetectable levels in patients with mild symptoms but fluctuated and remained persistent in moderate cases. The viral culture of samples with the highest viral load for each patient did not show any cytopathic change. The antibody response was faster and higher in moderate cases. This study provides a basic clue for infectious severity-dependent immune response, viremia, and antibody acquisition pattern.


Subject(s)
COVID-19/immunology , COVID-19/virology , Viremia/immunology , Viremia/virology , Adult , Aged , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , Female , Follow-Up Studies , Humans , Immunoglobulin G/blood , Male , Middle Aged , RNA, Viral/blood , RNA, Viral/genetics , SARS-CoV-2/genetics , SARS-CoV-2/immunology , SARS-CoV-2/isolation & purification , Severity of Illness Index , Viral Load
8.
J Med Virol ; 93(12): 6788-6793, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1562395

ABSTRACT

This study aimed to report a case of mild novel coronavirus disease (COVID-19) in a pregnant woman with probable viremia, as reverse transcription-polymerase chain reaction (RT-PCR) testing of endometrial and placental swabs for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was positive. A 26-year-old multigravida at 35 weeks 2 days of gestation, who had extensive thigh and abdominal cellulitis, tested SARS-CoV-2 positive by RT-PCR performed on samples from the endometrium and maternal side of the placenta. However, other samples (amniotic fluid, fetal side of the placenta, umbilical cord, maternal vagina, and neonatal nasopharynx) tested negative for SARS-CoV-2. This is one of the rare reports of probable SARS-CoV-2 viremia with the presence of SARS-CoV-2 in the endometrium and placenta, but not leading to vertical transmission and neonatal infection. Because knowledge about transplacental transmission and results is very limited, we conclude that more RT-PCR tests on placental and cord blood samples are needed in order to safely make definite conclusions.


Subject(s)
COVID-19/virology , Fetus/virology , Placenta/virology , Pregnancy Complications, Infectious/virology , SARS-CoV-2/genetics , Viremia/virology , Adult , Female , Humans , Infectious Disease Transmission, Vertical , Pregnancy , Pregnant Women
9.
Diagn Microbiol Infect Dis ; 102(3): 115595, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1531172

ABSTRACT

SARS-CoV-2 viremia at admission is associated with high risk for mortality. However, longitudinal data on viremia duration are limited. Viremic patients hospitalized for COVID-19 were included in a cohort. Time to serum viral clearance and the effect of viremia duration on the odds of mortality were calculated. One hundred and twenty-one viremic patients were included. Median age was 62 (IQR 52-71) years and 68% were males. The total in-hospital mortality of the cohort was 33%. Median time from admission to serum viral clearance was 7 (95% CI 6-8) days. Duration of viremia showed a relative risk ratio of 1.40 (95% CI 1.02-1.92) for the odds of mortality in an adjusted multinomial logistic regression. Serum viral clearance coincided with defervescence and decreasing C-reactive protein. Median time to serum viral clearance was 7 days after admission. The odds of mortality increased with 40% for each additional day of viremia.


Subject(s)
COVID-19 , SARS-CoV-2 , Cohort Studies , Hospitalization , Humans , Male , Middle Aged , Viremia
10.
Anal Bioanal Chem ; 413(29): 7251-7263, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1460298

ABSTRACT

Supply shortage for the development and production of preventive, therapeutic, and diagnosis tools during the COVID-19 pandemic is an important issue affecting the wealthy and poor nations alike. Antibodies and antigens are especially needed for the production of immunological-based testing tools such as point-of-care tests. Here, we propose a simple and quick magnetic nanoparticle (MNP)-based separation/isolation approach for the repurposing of infected human samples to produce specific antibodies and antigen cocktails. Initially, an antibody cocktail was purified from serums via precipitation and immunoaffinity chromatography. Purified antibodies were conjugated onto MNPs and used as an affinity matrix to separate antigens. The characterization process was performed by ELISA, SDS-PAGE, electrochemistry, isothermal titration calorimetry, and LC-Q-TOF-MS/MS analyses. The MNP-separated peptides can be used for mass spectrometry-based as well as paper-based lateral flow assay diagnostic. The exploitation of the current workflow for the development of efficient diagnostic tools, specific treatments, and fundamental research can significantly impact the present or eventual pandemic. This workflow can be considered as a two birds, one stone-like strategy.


Subject(s)
Antibodies, Viral/isolation & purification , Antigens, Viral/isolation & purification , COVID-19/diagnosis , Cost-Benefit Analysis , Immunoassay/economics , SARS-CoV-2/isolation & purification , Viremia/virology , Antibodies, Viral/blood , Antigens, Viral/blood , COVID-19/virology , Calorimetry , Electrophoresis, Polyacrylamide Gel , Enzyme-Linked Immunosorbent Assay , Humans , SARS-CoV-2/immunology , Specimen Handling , Tandem Mass Spectrometry , Viremia/blood , Workflow
11.
Sci Rep ; 11(1): 19458, 2021 09 30.
Article in English | MEDLINE | ID: covidwho-1447326

ABSTRACT

Efficacious therapeutics for Ebola virus disease are in great demand. Ebola virus infections mediated by mucosal exposure, and aerosolization in particular, present a novel challenge due to nontypical massive early infection of respiratory lymphoid tissues. We performed a randomized and blinded study to compare outcomes from vehicle-treated and remdesivir-treated rhesus monkeys in a lethal model of infection resulting from aerosolized Ebola virus exposure. Remdesivir treatment initiated 4 days after exposure was associated with a significant survival benefit, significant reduction in serum viral titer, and improvements in clinical pathology biomarker levels and lung histology compared to vehicle treatment. These observations indicate that remdesivir may have value in countering aerosol-induced Ebola virus disease.


Subject(s)
Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , Antiviral Agents/pharmacology , Ebolavirus/drug effects , Hemorrhagic Fever, Ebola/drug therapy , Adenosine Monophosphate/administration & dosage , Adenosine Monophosphate/pharmacology , Administration, Intravenous , Aerosols , Alanine/administration & dosage , Alanine/pharmacology , Animals , Antiviral Agents/administration & dosage , Disease Models, Animal , Female , Hemorrhagic Fever, Ebola/blood , Kaplan-Meier Estimate , Liver/drug effects , Liver/virology , Lung/pathology , Lung/virology , Lymph Nodes/drug effects , Lymph Nodes/pathology , Lymph Nodes/virology , Macaca mulatta , Male , Random Allocation , Systemic Inflammatory Response Syndrome/drug therapy , Systemic Inflammatory Response Syndrome/virology , Viral Load/drug effects , Viremia/drug therapy
12.
Int J Lab Hematol ; 43(6): 1334-1340, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1443280

ABSTRACT

INTRODUCTION: Coronavirus disease 2019 (COVID-19) caused by SARS-CoV2 can present from mild flu-like symptoms to acute respiratory distress syndrome. There is multi-organ involvement; particularly, hematopoietic system can be associated with morphological changes in blood cells of COVID-19 patients. METHOD: We conducted a cross-sectional study on a cohort of 50 COVID-19 patients, confirmed on RT-PCR with documented cycle threshold (Ct) value. Peripheral blood sample of these patients was collected and examined for complete blood counts (CBC) on automated haematological analyser as well as Leishman-stained blood smears to look for morphological changes in blood cells. Morphological changes were evaluated with reference to clinical severity and Ct value. Additionally, association between Ct value and clinical severity was also performed. Statistical tests were performed, and P value <.05 was considered significant. RESULTS: Mean age of our study group was 42.16 ± 15.55 years, with male preponderance. Most commonly observed peripheral blood changes were hypolobation (P value = .002) and toxic granules (P value = .005) in neutrophils, atypical granules with nucleolar prominence in lymphocytes, cytoplasmic granulation with clumped nuclear chromatin in monocytes, giant platelets and thrombocytopenia and normocytic normochromic anaemia. CONCLUSION: No association was found between clinical severity and Ct value as well as peripheral blood morphological changes with Ct value. We conclude that examination of peripheral smear coupled with complete blood count (CBC) is only partially supportive of disease pathogenesis and to assess the viral load other parameters should be utilised instead of relying solely on Ct value.


Subject(s)
Blood Cells/ultrastructure , COVID-19 Nucleic Acid Testing/methods , COVID-19/blood , SARS-CoV-2/isolation & purification , Viral Load , Viremia/blood , Adult , Aged , Aged, 80 and over , Blood Cell Count , COVID-19/virology , Cell Shape , Cell Size , Cross-Sectional Studies , Cytoplasmic Granules/ultrastructure , Female , Hematopoiesis , Humans , Male , Middle Aged , Nasopharynx/virology , Oropharynx/virology , Prospective Studies , RNA, Viral/blood , Severity of Illness Index , Young Adult
13.
Int J Environ Res Public Health ; 18(18)2021 Sep 18.
Article in English | MEDLINE | ID: covidwho-1430864

ABSTRACT

Infectivity and neutralizing antibody titers of flavivirus and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are frequently measured using the conventional plaque assay. While the assay is useful in the determination of infectivity, conventional plaque assays generally possess lower sensitivity and are time-consuming compared to nucleic acid amplification tests. In this study, a microcrystalline cellulose (MCC), Avicel, was evaluated as an alternative to the conventional virus overlay medium, methylcellulose, for a plaque assay. The plaque assay was performed using dengue and COVID-19 clinical samples and laboratory-established flavivirus and SARS-CoV-2 strains. In virus titration of clinical samples, the plaques were significantly larger, and the virus titers were higher when Avicel MCC-containing overlay medium was used than with conventional methylcellulose overlay medium. In addition, for some clinical samples and laboratory virus strains, infectious particles were detected as plaques in the Avicel MCC-containing medium, but not in the conventional methylcellulose medium. The results suggest that the viremia titer determined using the new overlay medium containing Avicel MCC may better reflect the innate infectious and plaque-forming capabilities of clinical samples and better reflect virus infectivity.


Subject(s)
COVID-19 , Flavivirus , Humans , SARS-CoV-2 , Viremia , Virus Shedding
15.
Viruses ; 13(8)2021 08 20.
Article in English | MEDLINE | ID: covidwho-1367923

ABSTRACT

Strategies to combat COVID-19 require multiple ways to protect vulnerable people from infection. SARS-CoV-2 is an airborne pathogen and the nasal cavity is a primary target of infection. The K18-hACE2 mouse model was used to investigate the anti-SARS-CoV-2 efficacy of astodrimer sodium formulated in a mucoadhesive nasal spray. Animals received astodrimer sodium 1% nasal spray or PBS intranasally, or intranasally and intratracheally, for 7 days, and they were infected intranasally with SARS-CoV-2 after the first product administration on Day 0. Another group was infected intranasally with SARS-CoV-2 that had been pre-incubated with astodrimer sodium 1% nasal spray or PBS for 60 min before the neutralisation of test product activity. Astodrimer sodium 1% significantly reduced the viral genome copies (>99.9%) and the infectious virus (~95%) in the lung and trachea vs. PBS. The pre-incubation of SARS-CoV-2 with astodrimer sodium 1% resulted in a significant reduction in the viral genome copies (>99.9%) and the infectious virus (>99%) in the lung and trachea, and the infectious virus was not detected in the brain or liver. Astodrimer sodium 1% resulted in a significant reduction of viral genome copies in nasal secretions vs. PBS on Day 7 post-infection. A reduction in the viral shedding from the nasal cavity may result in lower virus transmission rates. Viraemia was low or undetectable in animals treated with astodrimer sodium 1% or infected with treated virus, correlating with the lack of detectable viral replication in the liver. Similarly, low virus replication in the nasal cavity after treatment with astodrimer sodium 1% potentially protected the brain from infection. Astodrimer sodium 1% significantly reduced the pro-inflammatory cytokines IL-6, IL-1α, IL-1ß, TNFα and TGFß and the chemokine MCP-1 in the serum, lung and trachea vs. PBS. Astodrimer sodium 1% nasal spray blocked or reduced SARS-CoV-2 replication and its sequelae in K18-hACE2 mice. These data indicate a potential role for the product in preventing SARS-CoV-2 infection or for reducing the severity of COVID-19.


Subject(s)
Antiviral Agents/administration & dosage , COVID-19/drug therapy , Dendrimers/administration & dosage , Nasal Cavity/virology , Nasal Sprays , Polylysine/administration & dosage , SARS-CoV-2/drug effects , Angiotensin-Converting Enzyme 2/genetics , Angiotensin-Converting Enzyme 2/metabolism , Animals , Antiviral Agents/therapeutic use , Brain/virology , COVID-19/prevention & control , COVID-19/virology , Dendrimers/therapeutic use , Disease Models, Animal , Female , Liver/virology , Male , Mice , Mice, Transgenic , Polylysine/therapeutic use , Respiratory System/virology , SARS-CoV-2/isolation & purification , SARS-CoV-2/physiology , Viral Load/drug effects , Viremia , Virus Replication/drug effects
16.
J Med Virol ; 94(1): 147-153, 2022 01.
Article in English | MEDLINE | ID: covidwho-1363704

ABSTRACT

This study aimed to determine the frequency of SARS-CoV-2 RNA in serum and its association with the clinical severity of COVID-19. This retrospective cohort study performed at Toyama University Hospital included consecutive patients with confirmed COVID-19. The prevalence of SARS-CoV-2 RNAemia and the strength of its association with clinical severity variables were examined. Fifty-six patients were included in this study. RNAemia was detected in 19.6% (11/56) patients on admission, and subsequently in 1.0% (1/25), 50.0% (6/12), and 100.0% (4/4) moderate, severe, and critically ill patients, respectively. Patients with RNAemia required more frequent oxygen supplementation (90.0% vs. 13.3%), ICU admission (81.8% vs. 6.7%), and invasive mechanical ventilation (27.3% vs. 0.0%). Among patients with RNAemia, the median viral loads of nasopharyngeal (NP) swabs that were collected around the same time as the serum sample were significantly higher in critically ill (5.4 log10 copies/µl; interquartile range [IQR]: 4.2-6.3) than in moderate-severe cases (2.6 log10 copies/µl; [IQR: 1.1-4.5]; p = 0.030) and were significantly higher in nonsurvivors (6.2 log10 copies/µl [IQR: 6.0-6.5]) than in survivors (3.9 log10 copies/µl [IQR: 1.6-4.6]; p = 0.045). This study demonstrated a relatively high proportion of SARS-CoV-2 RNAemia and an association between RNAemia and clinical severity. Moreover, among the patients with RNAemia, the viral loads of NP swabs were correlated with disease severity and mortality, suggesting the potential utility of combining serum testing with NP tests as a prognostic indicator for COVID-19, with higher quality than each separate test.


Subject(s)
COVID-19/virology , Nasopharynx/virology , RNA, Viral/blood , SARS-CoV-2/isolation & purification , Viral Load , Viremia , Adolescent , Adult , Aged , COVID-19/mortality , COVID-19/physiopathology , Child , Critical Illness , Female , Humans , Male , Middle Aged , Prognosis , Retrospective Studies , Severity of Illness Index , Young Adult
17.
J Clin Invest ; 131(13)2021 07 01.
Article in English | MEDLINE | ID: covidwho-1338896

ABSTRACT

BACKGROUNDSARS-CoV-2 plasma viremia has been associated with severe disease and death in COVID-19 in small-scale cohort studies. The mechanisms behind this association remain elusive.METHODSWe evaluated the relationship between SARS-CoV-2 viremia, disease outcome, and inflammatory and proteomic profiles in a cohort of COVID-19 emergency department participants. SARS-CoV-2 viral load was measured using a quantitative reverse transcription PCR-based platform. Proteomic data were generated with Proximity Extension Assay using the Olink platform.RESULTSThis study included 300 participants with nucleic acid test-confirmed COVID-19. Plasma SARS-CoV-2 viremia levels at the time of presentation predicted adverse disease outcomes, with an adjusted OR of 10.6 (95% CI 4.4-25.5, P < 0.001) for severe disease (mechanical ventilation and/or 28-day mortality) and 3.9 (95% CI 1.5-10.1, P = 0.006) for 28-day mortality. Proteomic analyses revealed prominent proteomic pathways associated with SARS-CoV-2 viremia, including upregulation of SARS-CoV-2 entry factors (ACE2, CTSL, FURIN), heightened markers of tissue damage to the lungs, gastrointestinal tract, and endothelium/vasculature, and alterations in coagulation pathways.CONCLUSIONThese results highlight the cascade of vascular and tissue damage associated with SARS-CoV-2 plasma viremia that underlies its ability to predict COVID-19 disease outcomes.FUNDINGMark and Lisa Schwartz; the National Institutes of Health (U19AI082630); the American Lung Association; the Executive Committee on Research at Massachusetts General Hospital; the Chan Zuckerberg Initiative; Arthur, Sandra, and Sarah Irving for the David P. Ryan, MD, Endowed Chair in Cancer Research; an EMBO Long-Term Fellowship (ALTF 486-2018); a Cancer Research Institute/Bristol Myers Squibb Fellowship (CRI2993); the Harvard Catalyst/Harvard Clinical and Translational Science Center (National Center for Advancing Translational Sciences, NIH awards UL1TR001102 and UL1TR002541-01); and by the Harvard University Center for AIDS Research (National Institute of Allergy and Infectious Diseases, 5P30AI060354).


Subject(s)
COVID-19/blood , COVID-19/virology , SARS-CoV-2 , Viremia/blood , Viremia/virology , Adult , Aged , Aged, 80 and over , Biomarkers/blood , Cohort Studies , Female , Host Microbial Interactions , Humans , Male , Middle Aged , Models, Biological , Pandemics , Prognosis , Proteome/metabolism , Proteomics , SARS-CoV-2/pathogenicity , SARS-CoV-2/physiology , Severity of Illness Index , Virus Internalization
18.
J Autoimmun ; 123: 102703, 2021 09.
Article in English | MEDLINE | ID: covidwho-1322182

ABSTRACT

OBJECTIVES: Durability of the humoral immune response to SARS-CoV-2 has yet to be defined. We longitudinally evaluated during a 12-month period the antibody responses to SARS-CoV-2, and analysed predictors of antibody titres decline and seroreversion. METHODS: Prospective study conducted in a cohort of patients hospitalized for microbiologically-confirmed COVID-19. Blood and nasopharyngeal samples were sequentially obtained during hospital stay and at 1, 2, 6 and 12 months after patients' discharge for measuring anti-spike (S) and anti-nucleocapsid (N) IgG antibody levels and SARS-CoV-2 RNA, respectively. RESULTS: 80 non-vaccinated patients were analysed. At month 12 after discharge, 73 (91.2%) patients exhibited detectable S-IgG and 35 (43.8%) N-IgG antibody titres. A gradual wane was observed in S-IgG and N-IgG antibody titres. Linear regression showed that S-IgG decline was positively associated with peak antibody titres (coefficient [95% CI] 0.059 [0.05-0.067], p < 0.001), inversely with WHO severity score (coefficient [95% CI] -0.042 [-0.079/-0.004], p = 0.033), and there was a trivial positive association with age (coefficient [95% CI] 0.002 [0-0.005], p = 0.10); N-IgG decline was positively associated with peak antibody titres (coefficient [95% CI] 0.091 [0.078-0.105], p < 0.001). Logistic regression showed that seroreversion for S-IgG was inversely associated with peak S-IgG (OR 0.19; 95% CI, 0.04-0.45; p = 0.004); seroreversion for N-IgG was inversely associated with peak N-IgG (OR 0.71; 95% 0.53-0.90; p = 0.009) and positively with cycle threshold of RT-PCR (OR 1.14; 95% CI, 1.00-1.33; p = 0.062). CONCLUSION: Anti-spike IgG antibodies remain detectable one year after hospitalization for COVID-19. Higher peak antibody titres and disease severity were associated with increased durability of detectable antibodies.


Subject(s)
Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/immunology , Immunoglobulin G/immunology , SARS-CoV-2/immunology , Viremia/immunology , Adult , Aged , Antigens, Viral/immunology , Convalescence , Coronavirus Nucleocapsid Proteins/immunology , Female , Follow-Up Studies , Hospitalization , Humans , Male , Middle Aged , Phosphoproteins/immunology , Prospective Studies , RNA, Viral/blood , Spike Glycoprotein, Coronavirus/immunology , Time Factors , Viremia/blood
20.
PLoS One ; 16(7): e0254167, 2021.
Article in English | MEDLINE | ID: covidwho-1295525

ABSTRACT

Dexamethasone provides benefits in patients with coronavirus disease 2019 (COVID-19), although data regarding immunological profiles and viral clearance are limited. This study aimed to evaluate for differences in biomarkers among patients with severe COVID-19 who did and did not receive dexamethasone. We measured plasma biomarkers of lung epithelial/endothelial injury and inflammation in 31 patients with severe COVID-19 and in 13 controls. Changes in biomarkers and clinical parameters were compared during the 7-day period among COVID-19 patients, and also according to dexamethasone use. Thirty-two patients with severe COVID-19 who received mechanical ventilation (n = 6), high-flow nasal cannula (n = 11), and supplemental oxygen (n = 15) were analyzed. Relative to controls, patients with severe COVID-19 had significantly higher concentrations of biomarkers related to glycocalyx shedding (endocan and syndecan-1), endothelial injury (von Willebrand factor), and inflammation (soluble receptor for advanced glycation end-products [sRAGE] and interleukin-6). The 7-day decreases in biomarkers of endothelial injury (angiopoietin-2 [Ang-2] and intercellular adhesion molecule-1 [ICAM-1]) and sRAGE, but not in the biomarker of lung epithelial injury (surfactant protein D), were correlated with decreases in C-reactive protein and radiologic score at day 7. Twenty patients (63%) received dexamethasone, and the dexamethasone and non-dexamethasone groups differed in terms of disease severity. However, dexamethasone was associated marginally with increased SpO2/FiO2 and significantly with decreases in C-reactive protein and radiologic score after adjusting for baseline imbalances. Furthermore, the dexamethasone group exhibited a significant decrease in the concentrations of Ang-2, ICAM-1, soluble form of the Tie2 receptor (a biomarker of glycocalyx shedding), and sRAGE. Both groups exhibited a clinically insignificant increase in the cycle threshold value. Severe COVID-19 may be characterized by more severe endothelial injury and inflammation, and less severe lung epithelial injury. There is a possibility that dexamethasone improved severe COVID-19 and related endothelial injury without delaying viral clearance.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , COVID-19/drug therapy , Dexamethasone/therapeutic use , Endothelium, Vascular/drug effects , Inflammation/prevention & control , SARS-CoV-2 , Viremia/drug therapy , Adult , Aged , Anti-Inflammatory Agents/pharmacology , Biomarkers , COVID-19/blood , COVID-19/diagnostic imaging , Dexamethasone/pharmacology , Endothelium, Vascular/pathology , Female , Humans , Inflammation/blood , Inflammation/etiology , Lung Injury/blood , Lung Injury/diagnostic imaging , Lung Injury/etiology , Male , Oxygen/blood , Pilot Projects , Viral Load , Viremia/blood
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