| 1. |
- Sourander, Birger, et al.
(författare)
-
No effect of remdesivir or betamethasone on upper respiratory tract SARS-CoV-2 RNA kinetics in hospitalised COVID-19 patients: a retrospective observational study
- 2022
-
Ingår i: Infectious Diseases. - : Informa UK Limited. - 2374-4235 .- 2374-4243. ; 54:10, s. 703-712
-
Tidskriftsartikel (refereegranskat)abstract
- Background The viral kinetics of SARS-CoV-2 has been considered clinically important. While remdesivir and corticosteroids are recommended for COVID-19 patients requiring oxygen support, there is a limited number of published reports on viral kinetics in hospitalised patients with COVID-19 treated with remdesivir or corticosteroids. Methods We conducted a retrospective study by collecting longitudinal samples from the nasopharynx/throat of 123 hospitalised patients (median age 55 years, 74% male) with COVID-19, to evaluate the effects of remdesivir and corticosteroid treatment on viral RNA levels. The subjects were divided into four groups: those receiving remdesivir (n = 25), betamethasone (n = 41), both (n = 15), or neither (n = 42). Time to viral RNA clearance was analysed using Kaplan-Meier plots, categorical data were analysed using Fisher's exact test, and Kruskal-Wallis for continuous data. Viral RNA decline rate was analysed using a mixed effect model. Results We found no significant difference in SARS-CoV-2 RNA decline rate or time to SARS-CoV-2 RNA clearance between the groups. Moreover, clinical status at baseline was not correlated with time to viral clearance. Conclusions Since SARS-CoV-2 RNA kinetics was not affected by treatment, repeated sampling from the upper respiratory tract cannot be used to evaluate treatment response.
|
|
| 2. |
- Edén, Arvid, 1975, et al.
(författare)
-
CSF biomarkers in patients with COVID-19 and neurological symptoms: A case series.
- 2021
-
Ingår i: Neurology. - 1526-632X. ; 96:2
-
Tidskriftsartikel (refereegranskat)abstract
- To explore whether hospitalized patients with SARS-CoV-2 and neurologic symptoms have evidence of CNS infection, inflammation and injury using CSF biomarker measurements.We assessed CSF SARS-CoV-2 RNA along with CSF biomarkers of intrathecal inflammation (CSF white blood cell count, neopterin, β2-microglobulin (β2M) and immunoglobulin G-index), blood-brain-barrier (BBB) integrity (albumin ratio), and axonal injury (CSF neurofilament light chain protein [NfL]) in 6 patients with moderate to severe COVID-19 and neurologic symptoms who had undergone a diagnostic lumbar puncture. Neurologic symptoms and signs included features of encephalopathies (4/6), suspected meningitis (1/6) and dysgeusia (1/6). SARS-CoV-2 infection was confirmed by rtPCR analysis of nasopharyngeal swabs.SARS-CoV-2 RNA was detected in the plasma of 2 patients (Cycle threshold [Ct] value 35.0-37.0) and in CSF at low levels (Ct 37.2, 38.0, 39.0) in 3 patients in one but not in a second rtPCR assay. CSF neopterin (median, 43.0 nmol/L) and β2-microglobulin (median, 3.1 mg/L) were increased in all. Median IgG-index (0.39), albumin ratio (5.35) and CSF white blood cell count (<3 cells/µL) were normal in all, while CSF NfL was elevated in 2 patients.Our results on patients with COVID-19 and neurologic symptoms suggest an unusual pattern of marked CSF inflammation in which soluble markers were increased but white cell response and other immunologic features typical of CNS viral infections were absent. While our initial hypothesis centered on CNS SARS-CoV-2 invasion, we could not convincingly detect SARS-CoV-2 as the underlying driver of CNS inflammation. These features distinguish COVID-19 CSF from other viral CNS infections, and raise fundamental questions about the CNS pathobiology of SARS-CoV-2 infection.
|
|
| 3. |
- Kanberg, Nelly, et al.
(författare)
-
Neurochemical evidence of astrocytic and neuronal injury commonly found in COVID-19.
- 2020
-
Ingår i: Neurology. - 1526-632X .- 0028-3878. ; 95:12
-
Tidskriftsartikel (refereegranskat)abstract
- To test the hypothesis that coronavirus disease 2019 (COVID-19) has an impact on the CNS by measuring plasma biomarkers of CNS injury.We recruited 47 patients with mild (n = 20), moderate (n = 9), or severe (n = 18) COVID-19 and measured 2 plasma biomarkers of CNS injury by single molecule array, neurofilament light chain protein (NfL; a marker of intra-axonal neuronal injury) and glial fibrillary acidic protein (GFAp; a marker of astrocytic activation/injury), in samples collected at presentation and again in a subset after a mean of 11.4 days. Cross-sectional results were compared with results from 33 age-matched controls derived from an independent cohort.The patients with severe COVID-19 had higher plasma concentrations of GFAp (p = 0.001) and NfL (p < 0.001) than controls, while GFAp was also increased in patients with moderate disease (p = 0.03). In patients with severe disease, an early peak in plasma GFAp decreased on follow-up (p < 0.01), while NfL showed a sustained increase from first to last follow-up (p < 0.01), perhaps reflecting a sequence of early astrocytic response and more delayed axonal injury.We show neurochemical evidence of neuronal injury and glial activation in patients with moderate and severe COVID-19. Further studies are needed to clarify the frequency and nature of COVID-19-related CNS damage and its relation to both clinically defined CNS events such as hypoxic and ischemic events and mechanisms more closely linked to systemic severe acute respiratory syndrome coronavirus 2 infection and consequent immune activation, as well as to evaluate the clinical utility of monitoring plasma NfL and GFAp in the management of this group of patients.
|
|
| 4. |
- Marklund, Emelie, et al.
(författare)
-
Serum-IgG responses to SARS-CoV-2 after mild and severe COVID-19 infection and analysis of IgG non-responders.
- 2020
-
Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 15:10
-
Tidskriftsartikel (refereegranskat)abstract
- To accurately interpret COVID-19 seroprevalence surveys, knowledge of serum-IgG responses to SARS-CoV-2 with a better understanding of patients who do not seroconvert, is imperative. This study aimed to describe serum-IgG responses to SARS-CoV-2 in a cohort of patients with both severe and mild COVID-19, including extended studies of patients who remained seronegative more than 90 days post symptom onset.SARS-CoV-2-specific IgG antibody levels were quantified using two clinically validated and widely used commercial serological assays (Architect, Abbott Laboratories and iFlash 1800, YHLO), detecting antibodies against the spike and nucleocapsid proteins.Forty-seven patients (mean age 49 years, 38% female) were included. All (15/15) patients with severe symptoms and 29/32 (90.6%) patients with mild symptoms of COVID-19 developed SARS-CoV-2-specific IgG antibodies in serum. Time to seroconversion was significantly shorter (median 11 vs. 22 days, P = 0.04) in patients with severe compared to mild symptoms. Of the three patients without detectable IgG-responses after >90 days, all had detectable virus-neutralizing antibodies and in two, spike-protein receptor binding domain-specific IgG was detected with an in-house assay. Antibody titers were preserved during follow-up and all patients who seroconverted, irrespective of the severity of symptoms, still had detectable IgG levels >75 days post symptom onset.Patients with severe COVID-19 both seroconvert earlier and develop higher concentrations of SARS-CoV-2-specific IgG than patients with mild symptoms. Of those patients who not develop detectable IgG antibodies, all have detectable virus-neutralizing antibodies, suggesting immunity. Our results showing that not all COVID-19 patients develop detectable IgG using two validated commercial clinical methods, even over time, are vital for the interpretation of COVID-19 seroprevalence surveys.
|
|
| 5. |
- Söfteland, John M., 1977, et al.
(författare)
-
Longevity of anti-spike and anti-nucleocapsid antibodies after COVID-19 in solid organ transplant recipients compared to immunocompetent controls.
- 2022
-
Ingår i: American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons. - : Elsevier BV. - 1600-6143. ; 22:4, s. 1245-1252
-
Tidskriftsartikel (refereegranskat)abstract
- Solid organ transplant recipients (SOTRs) are on lifelong immunosuppression, which may interfere with adaptive immunity to COVID-19. The data on dynamics and duration of antibody response in SOTRs are limited. This longitudinal study examined the longevity of both anti-spike (S)- and anti-nucleocapsid (N)-specific IgG-antibodies after COVID-19 in SOTRs compared to matched immunocompetent persons. SOTRs (n=65) were matched with controls (n=65) for COVID-19 disease severity, age, and sex in order of priority. Serum-IgG-antibodies against N- and S-antigens of SARS-CoV-2 were analyzed. At 1 and 9 months after COVID-19, anti-S-IgG detectability decreased from 91% to 82% in SOTRs versus 100% to 95% in controls, whereas the anti-N-IgG decreased from 63% to 29% in SOTRs versus 89% to 46% in controls. A matched paired analysis showed SOTRs having significantly lower levels of anti-N-IgG at all time points (1-month P=0.007, 3-months P<0.001, 6-months P=0.019 and 9-months P=0.021) but not anti-S-IgG at any time points. A mixed-model analysis confirmed these findings except for anti-S-IgG at one month (p=0.005) and identified severity score as the most important predictor of antibody response. SOTRs mount comparable S-specific, but not N-specific, antibody responses to SARS-CoV-2 infection compared to immunocompetent controls.
|
|
| 6. |
- Yilmaz, Aylin, 1974, et al.
(författare)
-
Upper respiratory tract levels of SARS-CoV-2 RNA and duration of viral RNA shedding do not differ between patients with mild and severe/critical COVID-19.
- 2021
-
Ingår i: The Journal of infectious diseases. - : Oxford University Press (OUP). - 1537-6613 .- 0022-1899. ; 223:1, s. 15-18
-
Tidskriftsartikel (refereegranskat)abstract
- This study reports longitudinal viral RNA loads from nasopharynx/throat in patients with mild and severe/critical COVID-19. We also investigated whether the duration of symptoms correlated with the duration of viral RNA shedding. A total of 56 patients were included. The highest viral loads occurred early after onset of symptoms. Neither the viral RNA loads in the upper respiratory tract, nor the time to viral RNA clearance differed between patients with mild or severe/critical disease. There was a moderate correlation between number of days with symptoms and number of days with viral RNA shedding in patients with mild COVID-19.
|
|
| 7. |
- Beck-Friis, Thomas, et al.
(författare)
-
Comparison of SARS-CoV-2 spike RNA sequences in feces and nasopharynx indicates intestinal replication
- 2022
-
Ingår i: Gut Pathogens. - : Springer Science and Business Media LLC. - 1757-4749. ; 14:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background Little is known of possible selection and replication of SARS-CoV-2 in the intestines and if viral load in feces is associated with severity of disease. Therefore, sequence variations of the spike region in strains collected from feces and nasopharynx (NPH) from the same patients were compared. It was also investigated whether viral load in feces related to severity of COVID-19 in hospitalized patients. Results SARS-CoV-2 RNA was found in 88 (79%) fecal samples from 112 patients. The complete spike region could be sequenced in 15 fecal and 14 NPH samples. Fourteen Alpha-variants and one Beta-variant of SARS-CoV-2 were identified. The majority of the viral genetic variants (viral populations) in two fecal samples, but none in NPH, had a reversion of the H69/V70 amino acid deletion normally seen in the Alpha variants. Nine fecal samples contained up to nine minority variants, each which may constitute a separate viral population. Five NPH samples had one genetic variant each, and one NPH sample contained nine minority populations of SARS-CoV-2 spike genes. Conclusions The higher genomic diversity of SARS-CoV-2 in feces compared to NPH, and the reversion of the H69/V70 deletion in Alpha variants from feces indicate a selection of viral strains and replication of SARS-CoV-2 in the gastrointestinal tract.
|
|
| 8. |
- Bonander, Carl, et al.
(författare)
-
A Capture-Recapture-based Ascertainment Probability Weighting Method for Effect Estimation With Under-ascertained Outcomes.
- 2024
-
Ingår i: Epidemiology (Cambridge, Mass.). - : Lippincott Williams & Wilkins. - 1531-5487 .- 1044-3983. ; 35:3, s. 340-348
-
Tidskriftsartikel (refereegranskat)abstract
- Outcome under-ascertainment, characterized by the incomplete identification or reporting of cases, poses a substantial challenge in epidemiologic research. While capture-recapture methods can estimate unknown case numbers, their role in estimating exposure effects in observational studies is not well established. This paper presents an ascertainment probability weighting framework that integrates capture-recapture and propensity score weighting. We propose a nonparametric estimator of effects on binary outcomes that combines exposure propensity scores with data from two conditionally independent outcome measurements to simultaneously adjust for confounding and under-ascertainment. Demonstrating its practical application, we apply the method to estimate the relationship between health care work and coronavirus disease 2019 testing in a Swedish region. We find that ascertainment probability weighting greatly influences the estimated association compared to conventional inverse probability weighting, underscoring the importance of accounting for under-ascertainment in studies with limited outcome data coverage. We conclude with practical guidelines for the method's implementation, discussing its strengths, limitations, and suitable scenarios for application.
|
|
| 9. |
- Bruhn-Olszewska, Bozena, et al.
(författare)
-
Loss of Y in leukocytes as a risk factor for critical COVID-19 in men.
- 2022
-
Ingår i: Genome medicine. - : Springer Science and Business Media LLC. - 1756-994X. ; 14:1
-
Tidskriftsartikel (refereegranskat)abstract
- The COVID-19 pandemic, which has a prominent social and economic impact worldwide, shows a largely unexplained male bias for the severity and mortality of the disease. Loss of chromosome Y (LOY) is a risk factor candidate in COVID-19 due to its prior association with many chronic age-related diseases, and its impact on immune gene transcription.Publicly available scRNA-seq data of PBMC samples derived from male patients critically ill with COVID-19 were reanalyzed, and LOY status was added to the annotated cells. We further studied LOY in whole blood for 211 COVID-19 patients treated at intensive care units (ICU) from the first and second waves of the pandemic. Of these, 139 patients were subject to cell sorting for LOY analysis in granulocytes, low-density neutrophils (LDNs), monocytes, and PBMCs.Reanalysis of available scRNA-seq data revealed LDNs and monocytes as the cell types most affected by LOY. Subsequently, DNA analysis indicated that 46%, 32%, and 29% of critically ill patients showed LOY above 5% cut-off in LDNs, granulocytes, and monocytes, respectively. Hence, the myeloid lineage that is crucial for the development of severe COVID-19 phenotype is affected by LOY. Moreover, LOY correlated with increasing WHO score (median difference 1.59%, 95% HDI 0.46% to 2.71%, p=0.025), death during ICU treatment (median difference 1.46%, 95% HDI 0.47% to 2.43%, p=0.0036), and history of vessel disease (median difference 2.16%, 95% HDI 0.74% to 3.7%, p=0.004), among other variables. In 16 recovered patients, sampled during ICU stay and 93-143 days later, LOY decreased significantly in whole blood and PBMCs. Furthermore, the number of LDNs at the recovery stage decreased dramatically (median difference 76.4 per 10,000 cell sorting events, 95% HDI 55.5 to 104, p=6e-11).We present a link between LOY and an acute, life-threatening infectious disease. Furthermore, this study highlights LOY as the most prominent clonal mutation affecting the myeloid cell lineage during emergency myelopoiesis. The correlation between LOY level and COVID-19 severity might suggest that this mutation affects the functions of monocytes and neutrophils, which could have consequences for male innate immunity.
|
|
| 10. |
- Edén, Arvid, 1975, et al.
(författare)
-
Viral Antigen and Inflammatory Biomarkers in Cerebrospinal Fluid in Patients With COVID-19 Infection and Neurologic Symptoms Compared With Control Participants Without Infection or Neurologic Symptoms.
- 2022
-
Ingår i: JAMA network open. - : American Medical Association (AMA). - 2574-3805. ; 5:5
-
Tidskriftsartikel (refereegranskat)abstract
- Neurologic symptoms are common in COVID-19, but the central nervous system (CNS) pathogenesis is unclear, and viral RNA is rarely detected in cerebrospinal fluid (CSF).To measure viral antigen and inflammatory biomarkers in CSF in relation to neurologic symptoms and disease severity.This cross-sectional study was performed from March 1, 2020, to June 30, 2021, in patients 18 years or older who were admitted to Sahlgrenska University Hospital, Gothenburg, Sweden, with COVID-19. All patients had CSF samples taken because of neurologic symptoms or within a study protocol. Healthy volunteer and prepandemic control groups were included.SARS-CoV-2 infection.Outcomes included CSF SARS-CoV-2 nucleocapsid antigen (N-Ag) using an ultrasensitive antigen capture immunoassay platform and CSF biomarkers of immune activation (neopterin, β2-microglobulin, and cytokines) and neuronal injury (neurofilament light protein [NfL]).Forty-four patients (median [IQR] age, 57 [48-69] years; 30 [68%] male; 26 with moderate COVID-19 and 18 with severe COVID-19 based on the World Health Organization Clinical Progression Scale), 10 healthy controls (median [IQR] age, 58 [54-60] years; 5 [50%] male), and 41 patient controls (COVID negative without evidence of CNS infection) (median [IQR] age, 59 [49-70] years; 19 [46%] male) were included in the study. Twenty-one patients were neuroasymptomatic and 23 were neurosymptomatic (21 with encephalopathy). In 31 of 35 patients for whom data were available (89%), CSF N-Ag was detected; viral RNA test results were negative in all. Nucleocapsid antigen was significantly correlated with CSF neopterin (r=0.38; P=.03) and interferon γ (r=0.42; P=.01). No differences in CSF N-Ag concentrations were found between patient groups. Patients had markedly increased CSF neopterin, β2-microglobulin, interleukin (IL) 2, IL-6, IL-10, and tumor necrosis factor α compared with controls. Neurosymptomatic patients had significantly higher median (IQR) CSF interferon γ (86 [47-172] vs 21 [17-81] fg/mL; P=.03) and had a significantly higher inflammatory biomarker profile using principal component analysis compared with neuroasymptomatic patients (0.54; 95% CI, 0.03-1.05; P=.04). Age-adjusted median (IQR) CSF NfL concentrations were higher in patients compared with controls (960 [673-1307] vs 618 [489-786] ng/L; P=.002). No differences were seen in any CSF biomarkers in moderate compared with severe disease.In this study of Swedish adults with COVID-19 infection and neurologic symptoms, compared with control participants, viral antigen was detectable in CSF and correlated with CNS immune activation. Patients with COVID-19 had signs of neuroaxonal injury, and neurosymptomatic patients had a more marked inflammatory profile that could not be attributed to differences in COVID-19 severity. These results highlight the clinical relevance of neurologic symptoms and suggest that viral components can contribute to CNS immune responses without direct viral invasion.
|
|
