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1.
J Clin Virol Plus ; 2(1): 100060, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1734709

ABSTRACT

Background: Measures to reduce spread of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) during the Covid-19 pandemic 2020-2021 may impact other microbiological agents. We aimed to investigate the incidence of infectious diseases and the incidence of viruses other than SARS-CoV-2 amongst children at The Department of Paediatric and Adolescent Medicine, Oslo University Hospital, Norway during 2020-2021 compared to previous years. Methods: Data from April 1st 2020 - March 31st 2021 were compared to data from corresponding 12-months periods 2017-2020. ICD-10 infectious disease diagnoses were collected from the Hospital Diagnosis and Procedure Registry and results of virus PCR analyses of different specimens (mainly nasopharyngeal (NF) and faecal samples) were collected from the Laboratory System at the Department of Microbiology. Results: The number of hospital contacts with acute bronchiolitis, viral pneumonia, gastroenteritis and viral central nervous system infections were reduced by 90% (p<0.0001), 89% (p<0.0001), 74% (p<0.0001) and 78% (p<0.01), respectively. Respiratory syncytial virus (RSV), influenza virus A and B and Human metapneumovirus (HMPV) were almost completely absent during the pandemic period. The proportions of rhinovirus positive NF samples were 31.7% vs. 34.9% (p<0.05), but not significantly different for adenovirus. The proportions of positive faecal samples were 1% vs. 10% for adenovirus (p<0.00001) and 3.3% vs. 12% for norovirus (p<0.00001), but not significantly different for rotavirus. The proportions of enterovirus positive samples were 3.5% vs. 21.6% (p<0.00001). Conclusion: The incidence of several paediatric infectious diseases mainly of viral aetiology declined significantly during the Covid-19 pandemic. Some common respiratory viruses were almost completely absent.

2.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-313539

ABSTRACT

Background: In SARS-CoV-2 infection there is an urgent need to identify patients that will progress to severe COVID-19 and may benefit from targeted treatment. Objectives: Analyze plasma cytokines in COVID-19 patients and investigate their association with respiratory failure (RF) and treatment in Intensive Care Unit (ICU). Method: Hospitalized patients (n=34) with confirmed COVID-19 were recruited into a prospective cohort study. Clinical data and blood samples were collected at inclusion and after 2-5 and 7-10 days. RF was defined as PaO2/FiO2 ratio (P/F) <40kPa. Plasma cytokines were analyzed by a Human Cytokine 27-plex assay. Measurements and Results: COVID-19 patients with RF and/or treated in ICU showed overall increased systemic cytokine levels. Plasma IL-6, IL-8, G-CSF, MCP-1, MIP-1α levels were negatively correlated with P/F, whereas combinations of IL-6, IP-10, IL-1ra and MCP-1 showed the best association with RF in ROC analysis (AUC 0.79-0.80, p<0.05). During hospitalization the decline was most significant for IP-10 (P<0.001). Conclusion: Elevated levels of pro-inflammatory cytokines were present in patients with severe COVID-19. IL-6 and MCP-1 were inversely correlated with P/F with the largest AUC in ROC analyses and should be further explored as biomarkers to identify patients at risk for severe RF and as targets for improved treatment strategies.

3.
EuropePMC;
Preprint in English | EuropePMC | ID: ppcovidwho-327209

ABSTRACT

ABSTRACT Background The Omicron variant of SARS-CoV-2 is now overtaking the Delta variant in many countries. Results showing that sera from double vaccinated individuals have minimal neutralizing activity against Omicron may indicate that the higher rate of transmission is due to evasion from vaccine-induced immunity. However, there is little information about activation of recall responses to Omicron in vaccinated individuals. Methods We measured inflammatory mediators, antibodies to the SARS-CoV-2 spike and nucleocapsid proteins, and spike peptide-induced release of interferon gamma in whole blood in 51 vaccinated individuals infected with Omicron, in 14 infected with Delta, and in 18 healthy controls. The median time points for the first and second samples were 7 and 14 days after symptom onset, respectively. Findings Infection with Omicron or Delta led to a rapid and similar increase in antibodies to the SARS-CoV-2 spike and nucleocapsid proteins and spike peptide-induced interferon gamma in whole blood. Both the Omicron and the Delta infected patients had a mild and transient increase in inflammatory parameters. Interpretation The results suggest that vaccine-induced immunological memory yields similar coverage for the Omicron and Delta variants.

4.
Ann Intern Med ; 174(9): 1261-1269, 2021 09.
Article in English | MEDLINE | ID: covidwho-1547664

ABSTRACT

BACKGROUND: New treatment modalities are urgently needed for patients with COVID-19. The World Health Organization (WHO) Solidarity trial showed no effect of remdesivir or hydroxychloroquine (HCQ) on mortality, but the antiviral effects of these drugs are not known. OBJECTIVE: To evaluate the effects of remdesivir and HCQ on all-cause, in-hospital mortality; the degree of respiratory failure and inflammation; and viral clearance in the oropharynx. DESIGN: NOR-Solidarity is an independent, add-on, randomized controlled trial to the WHO Solidarity trial that included biobanking and 3 months of clinical follow-up (ClinicalTrials.gov: NCT04321616). SETTING: 23 hospitals in Norway. PATIENTS: Eligible patients were adults hospitalized with confirmed SARS-CoV-2 infection. INTERVENTION: Between 28 March and 4 October 2020, a total of 185 patients were randomly assigned and 181 were included in the full analysis set. Patients received remdesivir (n = 42), HCQ (n = 52), or standard of care (SoC) (n = 87). MEASUREMENTS: In addition to the primary end point of WHO Solidarity, study-specific outcomes were viral clearance in oropharyngeal specimens, the degree of respiratory failure, and inflammatory variables. RESULTS: No significant differences were seen between treatment groups in mortality during hospitalization. There was a marked decrease in SARS-CoV-2 load in the oropharynx during the first week overall, with similar decreases and 10-day viral loads among the remdesivir, HCQ, and SoC groups. Remdesivir and HCQ did not affect the degree of respiratory failure or inflammatory variables in plasma or serum. The lack of antiviral effect was not associated with symptom duration, level of viral load, degree of inflammation, or presence of antibodies against SARS-CoV-2 at hospital admittance. LIMITATION: The trial had no placebo group. CONCLUSION: Neither remdesivir nor HCQ affected viral clearance in hospitalized patients with COVID-19. PRIMARY FUNDING SOURCE: National Clinical Therapy Research in the Specialist Health Services, Norway.


Subject(s)
Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , Antiviral Agents/therapeutic use , COVID-19/drug therapy , COVID-19/virology , Hydroxychloroquine/therapeutic use , Viral Load/drug effects , Adenosine Monophosphate/therapeutic use , Alanine/therapeutic use , Antibodies, Viral/blood , Biomarkers/blood , COVID-19/complications , COVID-19/mortality , Cause of Death , Female , Hospital Mortality , Humans , Inflammation/virology , Male , Middle Aged , Norway/epidemiology , Oropharynx/virology , Respiratory Insufficiency/virology , SARS-CoV-2/immunology , Severity of Illness Index , Standard of Care , Treatment Outcome
6.
Sci Rep ; 10(1): 21697, 2020 12 10.
Article in English | MEDLINE | ID: covidwho-1059940

ABSTRACT

In SARS-CoV-2 infection there is an urgent need to identify patients that will progress to severe COVID-19 and may benefit from targeted treatment. In this study we analyzed plasma cytokines in COVID-19 patients and investigated their association with respiratory failure (RF) and treatment in Intensive Care Unit (ICU). Hospitalized patients (n = 34) with confirmed COVID-19 were recruited into a prospective cohort study. Clinical data and blood samples were collected at inclusion and after 2-5 and 7-10 days. RF was defined as PaO2/FiO2 ratio (P/F) < 40 kPa. Plasma cytokines were analyzed by a Human Cytokine 27-plex assay. COVID-19 patients with RF and/or treated in ICU showed overall increased systemic cytokine levels. Plasma IL-6, IL-8, G-CSF, MCP-1, MIP-1α levels were negatively correlated with P/F, whereas combinations of IL-6, IP-10, IL-1ra and MCP-1 showed the best association with RF in ROC analysis (AUC 0.79-0.80, p < 0.05). During hospitalization the decline was most significant for IP-10 (p < 0.001). Elevated levels of pro-inflammatory cytokines were present in patients with severe COVID-19. IL-6 and MCP-1 were inversely correlated with P/F with the largest AUC in ROC analyses and should be further explored as biomarkers to identify patients at risk for severe RF and as targets for improved treatment strategies.


Subject(s)
COVID-19/blood , Chemokine CCL2/blood , Interleukin-6/blood , Respiratory Insufficiency/blood , SARS-CoV-2/metabolism , Adult , Aged , Aged, 80 and over , Biomarkers/blood , COVID-19/complications , Female , Humans , Male , Middle Aged , Prospective Studies , Respiratory Insufficiency/etiology , Severity of Illness Index
8.
J Allergy Clin Immunol ; 147(1): 92-98, 2021 01.
Article in English | MEDLINE | ID: covidwho-779084

ABSTRACT

BACKGROUND: The pathogenesis of coronavirus disease 2019 (COVID-19) is still incompletely understood, but it seems to involve immune activation and immune dysregulation. OBJECTIVE: We examined the parameters of activation of different leukocyte subsets in COVID-19-infected patients in relation to disease severity. METHODS: We analyzed plasma levels of myeloperoxidase (a marker of neutrophil activation), soluble (s) CD25 (sCD25) and soluble T-cell immunoglobulin mucin domain-3 (sTIM-3) (markers of T-cell activation and exhaustion), and sCD14 and sCD163 (markers of monocyte/macrophage activation) in 39 COVID-19-infected patients at hospital admission and 2 additional times during the first 10 days in relation to their need for intensive care unit (ICU) treatment. RESULTS: Our major findings were as follows: (1) severe clinical outcome (ICU treatment) was associated with high plasma levels of sTIM-3 and myeloperoxidase, suggesting activated and potentially exhausted T cells and activated neutrophils, respectively; (2) in contrast, sCD14 and sCD163 showed no association with need for ICU treatment; and (3) levels of sCD25, sTIM-3, and myeloperoxidase were inversely correlated with degree of respiratory failure, as assessed by the ratio of Pao2 to fraction of inspired oxygen, and were positively correlated with the cardiac marker N-terminal pro-B-type natriuretic peptide. CONCLUSION: Our findings suggest that neutrophil activation and, in particular, activated T cells may play an important role in the pathogenesis of COVID-19 infection, suggesting that T-cell-targeted treatment options and downregulation of neutrophil activation could be of importance in this disorder.


Subject(s)
COVID-19/blood , Hepatitis A Virus Cellular Receptor 2/blood , SARS-CoV-2/metabolism , Aged , Antigens, CD/blood , Antigens, Differentiation, Myelomonocytic/blood , Female , Humans , Interleukin-2 Receptor alpha Subunit/blood , Lipopolysaccharide Receptors/blood , Lymphocyte Activation , Male , Middle Aged , Receptors, Cell Surface/blood , Severity of Illness Index , T-Lymphocytes/metabolism , Time Factors
9.
Proc Natl Acad Sci U S A ; 117(40): 25018-25025, 2020 10 06.
Article in English | MEDLINE | ID: covidwho-780138

ABSTRACT

Respiratory failure in the acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic is hypothesized to be driven by an overreacting innate immune response, where the complement system is a key player. In this prospective cohort study of 39 hospitalized coronavirus disease COVID-19 patients, we describe systemic complement activation and its association with development of respiratory failure. Clinical data and biological samples were obtained at admission, days 3 to 5, and days 7 to 10. Respiratory failure was defined as PO2/FiO2 ratio of ≤40 kPa. Complement activation products covering the classical/lectin (C4d), alternative (C3bBbP) and common pathway (C3bc, C5a, and sC5b-9), the lectin pathway recognition molecule MBL, and antibody serology were analyzed by enzyme-immunoassays; viral load by PCR. Controls comprised healthy blood donors. Consistently increased systemic complement activation was observed in the majority of COVID-19 patients during hospital stay. At admission, sC5b-9 and C4d were significantly higher in patients with than without respiratory failure (P = 0.008 and P = 0.034). Logistic regression showed increasing odds of respiratory failure with sC5b-9 (odds ratio 31.9, 95% CI 1.4 to 746, P = 0.03) and need for oxygen therapy with C4d (11.7, 1.1 to 130, P = 0.045). Admission sC5b-9 and C4d correlated significantly to ferritin (r = 0.64, P < 0.001; r = 0.69, P < 0.001). C4d, sC5b-9, and C5a correlated with antiviral antibodies, but not with viral load. Systemic complement activation is associated with respiratory failure in COVID-19 patients and provides a rationale for investigating complement inhibitors in future clinical trials.


Subject(s)
Betacoronavirus/immunology , Complement Activation , Coronavirus Infections/immunology , Pneumonia, Viral/immunology , Respiratory Insufficiency/immunology , Aged , Biomarkers/blood , COVID-19 , Case-Control Studies , Coronavirus Infections/blood , Coronavirus Infections/complications , Female , Host-Pathogen Interactions/immunology , Humans , Male , Mannose-Binding Lectin/blood , Middle Aged , Pandemics , Pneumonia, Viral/blood , Pneumonia, Viral/complications , Respiratory Insufficiency/virology , SARS-CoV-2 , Viral Load
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