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1.
EBioMedicine ; 85: 104296, 2022 Nov.
Article in English | MEDLINE | ID: covidwho-2158739

ABSTRACT

BACKGROUND: COVID-19 is characterized by a heterogeneous clinical presentation, ranging from mild symptoms to severe courses of disease. 9-20% of hospitalized patients with severe lung disease die from COVID-19 and a substantial number of survivors develop long-COVID. Our objective was to provide comprehensive insights into the pathophysiology of severe COVID-19 and to identify liquid biomarkers for disease severity and therapy response. METHODS: We studied a total of 85 lungs (n = 31 COVID autopsy samples; n = 7 influenza A autopsy samples; n = 18 interstitial lung disease explants; n = 24 healthy controls) using the highest resolution Synchrotron radiation-based hierarchical phase-contrast tomography, scanning electron microscopy of microvascular corrosion casts, immunohistochemistry, matrix-assisted laser desorption ionization mass spectrometry imaging, and analysis of mRNA expression and biological pathways. Plasma samples from all disease groups were used for liquid biomarker determination using ELISA. The anatomic/molecular data were analyzed as a function of patients' hospitalization time. FINDINGS: The observed patchy/mosaic appearance of COVID-19 in conventional lung imaging resulted from microvascular occlusion and secondary lobular ischemia. The length of hospitalization was associated with increased intussusceptive angiogenesis. This was associated with enhanced angiogenic, and fibrotic gene expression demonstrated by molecular profiling and metabolomic analysis. Increased plasma fibrosis markers correlated with their pulmonary tissue transcript levels and predicted disease severity. Plasma analysis confirmed distinct fibrosis biomarkers (TSP2, GDF15, IGFBP7, Pro-C3) that predicted the fatal trajectory in COVID-19. INTERPRETATION: Pulmonary severe COVID-19 is a consequence of secondary lobular microischemia and fibrotic remodelling, resulting in a distinctive form of fibrotic interstitial lung disease that contributes to long-COVID. FUNDING: This project was made possible by a number of funders. The full list can be found within the Declaration of interests / Acknowledgements section at the end of the manuscript.


Subject(s)
COVID-19 , Lung Diseases, Interstitial , Humans , Lung/diagnostic imaging , Lung/pathology , Lung Diseases, Interstitial/pathology , Fibrosis , Biomarkers/analysis , Ischemia/pathology
2.
Dental Research Journal ; 19:43, 2022.
Article in English | MEDLINE | ID: covidwho-1970496

ABSTRACT

Background: Over the past year, patients infected by severe acute respiratory syndrome coronavirus-2 presented with severe gustatory dysfunction, the prevalence of which varies among different populations. Furthermore, there have been sporadic reports of oral ulceration observed in coronavirus disease-19 (COVID-19) patients due to varied reasons. The aim of this study was to investigate and characterize the presence of gustatory disorders, oral ulceration, and other oral changes in patients with laboratory-confirmed COVID-19 infection. Materials and Methods: In this cross-sectional observational study, a total of 402 participants who were detected COVID-19 positive by reverse transcription-polymerase chain reaction were included. Their demographic and clinical data were recorded through hospital records. The participants were interviewed either in person or on the telephone to record any change in taste and/or changes within the oral cavity. t-test for independent means was used to compare mean age, while other characteristics were compared by Chi-square test and Z-score test. P < 0.05 was taken as significant. Results: Out of the total sample of 402 individuals, 262 were male and 140 were female. The prevalence of gustatory dysfunction and oral ulceration was 43.53% and 15.67%, respectively, in the studied sample. Significantly more females had gustatory dysfunction than males and older subjects more commonly than younger. The symptom of loss/change of taste and oral ulceration were more probable to occur together. In addition, the tongue was the most common site for ulceration in our studied sample. Conclusion: Loss of taste is a common symptom of COVID-19 patients, whereas oral ulceration is not so commonly reported. However, the presence of both these symptoms could impair the quality of life of patients and hamper adequate nutritional uptake.

3.
Scandinavian Journal of Immunology ; 95(6), 2022.
Article in English | EMBASE | ID: covidwho-1968191

ABSTRACT

The outbreak of the COVID-19 pandemic in late 2019 has so far caused more than 6 million deaths worldwide according to WHO. Currently, there is only one FDA-approved novel antiviral drug therapy (Paxlovid, Pfizer) for treatment of critically ill patients from COVID-19 infection. However, there is a need for a great diversity of antiviral therapies because of the constant mutations of the virus and the possibility of other similar viruses causing similar symptoms in patients. By utilizing natural products from medicinal plants, it is possible to provide a drug, or drug leads for a future novel antiviral therapy. Currently, we are testing isolated and characterized natural products (some novel and some already elucidated) from water lily (Nuphar lutea) and eagle fern (Pteridium aquilinum) on the SARS-CoV-2 virus where we are working on developing a good pipeline to test these compounds in vitro. So far, we have tested the effect of the compounds on inhibition of cell entry using a pseudovirus system and HEK293-FT cells transiently transfected with SARS-CoV-2 receptors ACE-2 and TMPRSS2. Some of the compounds showed a slightly inhibitory effect. Next steps will be to establish a cell line with stable expression of ACE-2 and TMPRSS2 and confirm the results in cells with endogenous expression of these receptors. We will proceed working with different variants of the hospital isolates of the virus within the next months, where we will further analyse the potential effect of these compounds on viral replication. The goal is to determine and understand the mechanism of inhibitory action of the natural products on the virus. In conclusion, we are at an early stage of researching the abundant possibilities of antiviral effects of these natural products on SARS-CoV-2.

4.
J Laryngol Otol ; : 1-3, 2022 Apr 27.
Article in English | MEDLINE | ID: covidwho-1882700

ABSTRACT

OBJECTIVES: This study aimed: to evaluate the association between coronavirus disease 2019 infection and olfactory and taste dysfunction in patients presenting to the out-patient department with influenza-like illness, who underwent reverse transcription polymerase chain reaction testing for coronavirus; and to determine the sensitivity, specificity, and positive and negative predictive values of olfactory and taste dysfunction and other symptoms in these patients. METHODS: Patients presenting with influenza-like illness to the study centre in September 2020 were included in the study. The symptoms of patients who tested positive for coronavirus on reverse transcription polymerase chain reaction testing were compared to those with negative test results. RESULTS: During the study period, 909 patients, aged 12-70 years, presented with influenza-like illness; of these, 316 (34.8 per cent) tested positive for coronavirus. Only the symptoms of olfactory and taste dysfunction were statistically more significant in patients testing positive for coronavirus than those testing negative. CONCLUSION: During the pandemic, patients presenting to the out-patient department with sudden loss of sense of smell or taste may be considered as positive for coronavirus disease 2019, until proven otherwise.

5.
Eur J Cancer ; 160: 261-272, 2022 01.
Article in English | MEDLINE | ID: covidwho-1719649

ABSTRACT

AIM OF THE STUDY: The coronavirus disease 2019 (COVID-19) pandemic significantly impacted cancer care. In this study, clinical patient characteristics related to COVID-19 outcomes and advanced care planning, in terms of non-oncological treatment restrictions (e.g. do-not-resuscitate codes), were studied in patients with cancer and COVID-19. METHODS: The Dutch Oncology COVID-19 Consortium registry was launched in March 2020 in 45 hospitals in the Netherlands, primarily to identify risk factors of a severe COVID-19 outcome in patients with cancer. Here, an updated analysis of the registry was performed, and treatment restrictions (e.g. do-not-intubate codes) were studied in relation to COVID-19 outcomes in patients with cancer. Oncological treatment restrictions were not taken into account. RESULTS: Between 27th March 2020 and 4th February 2021, 1360 patients with cancer and COVID-19 were registered. Follow-up data of 830 patients could be validated for this analysis. Overall, 230 of 830 (27.7%) patients died of COVID-19, and 60% of the remaining 600 patients with resolved COVID-19 were admitted to the hospital. Patients with haematological malignancies or lung cancer had a higher risk of a fatal outcome than other solid tumours. No correlation between anticancer therapies and the risk of a fatal COVID-19 outcome was found. In terms of end-of-life communication, 50% of all patients had restrictions regarding life-prolonging treatment (e.g. do-not-intubate codes). Most identified patients with treatment restrictions had risk factors associated with fatal COVID-19 outcome. CONCLUSION: There was no evidence of a negative impact of anticancer therapies on COVID-19 outcomes. Timely end-of-life communication as part of advanced care planning could save patients from prolonged suffering and decrease burden in intensive care units. Early discussion of treatment restrictions should therefore be part of routine oncological care, especially during the COVID-19 pandemic.


Subject(s)
COVID-19/mortality , Hospitalization/statistics & numerical data , Life Support Care/statistics & numerical data , Mortality/trends , Neoplasms/mortality , SARS-CoV-2/isolation & purification , Withholding Treatment/statistics & numerical data , Aged , Aged, 80 and over , COVID-19/epidemiology , COVID-19/therapy , COVID-19/virology , Female , Humans , Male , Middle Aged , Neoplasms/epidemiology , Neoplasms/therapy , Neoplasms/virology , Netherlands/epidemiology , Prognosis , Risk Factors , Survival Rate
6.
Am J Transplant ; 22(2): 634-639, 2022 02.
Article in English | MEDLINE | ID: covidwho-1434623

ABSTRACT

Kidney transplant recipients (KTRs) are extremely vulnerable to SARS-CoV-2 infection and show an impaired immune response to SARS-CoV-2 vaccination. We analyzed factors related to vaccination efficiency in KTRs. In a multicenter prospective observational study (NCT04743947), IgG antibodies levels against SARS-CoV-2 spike S1 subunit and their neutralization capacity after SARS-CoV-2 vaccination were analyzed in 225 KTRs and compared to 176 controls. After the vaccination, 56 (24.9%) KTRs became seropositive of whom 68% had neutralizing antibodies. This immune response was significantly lower compared to controls (239 [78-519] BAU/ml versus 1826 [560-3180] BAU/ml for KTRs and controls, p < .0001). The strongest predictor for an impaired response was mycophenolate mofetil (MMF) treatment. Multivariate regression analysis revealed that MMF-free regimen was highly associated with seroconversion (OR 13.25, 95% CI 3.22-54.6; p < .001). In contrast, other immunosuppressive drugs had no significant influence. 187 out of 225 KTRs were treated with MMF of whom 26 (13.9%) developed antibodies. 23 of these seropositive KTRs had a daily MMF dose ≤1 g. Furthermore, higher trough MMF concentrations correlated with lower antibody titers (R -0.354, p < .001) supporting a dose-dependent unfavorable effect of MMF. Our data indicate that MMF dose modification could lead to an improved immune response.


Subject(s)
COVID-19 , Kidney Transplantation , Antibodies, Viral , COVID-19 Vaccines , Humans , Immunity , Kidney Transplantation/adverse effects , Mycophenolic Acid/therapeutic use , SARS-CoV-2 , Transplant Recipients , Vaccination
7.
Eur J Cancer ; 141: 171-184, 2020 12.
Article in English | MEDLINE | ID: covidwho-915424

ABSTRACT

AIM OF THE STUDY: Patients with cancer might have an increased risk for severe outcome of coronavirus disease 2019 (COVID-19). To identify risk factors associated with a worse outcome of COVID-19, a nationwide registry was developed for patients with cancer and COVID-19. METHODS: This observational cohort study has been designed as a quality of care registry and is executed by the Dutch Oncology COVID-19 Consortium (DOCC), a nationwide collaboration of oncology physicians in the Netherlands. A questionnaire has been developed to collect pseudonymised patient data on patients' characteristics, cancer diagnosis and treatment. All patients with COVID-19 and a cancer diagnosis or treatment in the past 5 years are eligible. RESULTS: Between March 27th and May 4th, 442 patients were registered. For this first analysis, 351 patients were included of whom 114 patients died. In multivariable analyses, age ≥65 years (p < 0.001), male gender (p = 0.035), prior or other malignancy (p = 0.045) and active diagnosis of haematological malignancy (p = 0.046) or lung cancer (p = 0.003) were independent risk factors for a fatal outcome of COVID-19. In a subgroup analysis of patients with active malignancy, the risk for a fatal outcome was mainly determined by tumour type (haematological malignancy or lung cancer) and age (≥65 years). CONCLUSION: The findings in this registry indicate that patients with a haematological malignancy or lung cancer have an increased risk of a worse outcome of COVID-19. During the ongoing COVID-19 pandemic, these vulnerable patients should avoid exposure to severe acute respiratory syndrome coronavirus 2, whereas treatment adjustments and prioritising vaccination, when available, should also be considered.


Subject(s)
COVID-19/epidemiology , Neoplasms/epidemiology , Neoplasms/virology , Aged , Cohort Studies , Female , Humans , Incidence , Male , Middle Aged , Neoplasms/therapy , Netherlands/epidemiology , Pandemics , Registries , Risk Factors , Treatment Outcome
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