| 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. |
- 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.
|
|
| 3. |
- 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.
|
|
| 4. |
- Yilmaz, Aylin, et al.
(författare)
-
Upper Respiratory Tract Levels of Severe Acute Respiratory Syndrome Coronavirus 2 RNA and Duration of Viral RNA Shedding Do Not Differ Between Patients With Mild and Severe/Critical Coronavirus Disease 2019
- 2021
-
Ingår i: 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 the nasopharynx/throat in patients with mild and severe/critical coronavirus disease 2019 (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.
|
|
| 5. |
- Lundgren, Anna, 1974, et al.
(författare)
-
Plasmablasts in previously immunologically naive COVID-19 patients express markers indicating mucosal homing and secrete antibodies cross-reacting with SARS-CoV-2 variants and other beta-coronaviruses
- 2023
-
Ingår i: Clinical and Experimental Immunology. - 0009-9104 .- 1365-2249. ; 213:2, s. 173-89
-
Tidskriftsartikel (refereegranskat)abstract
- Antigen-specific class-switched antibodies are detected at the same time or even before IgM in serum of non-vaccinated individuals infected with SARS-CoV-2. These derive from the first wave of plasmablasts formed. Hence, the phenotype and specificity of plasmablasts can reveal information about early B-cell activation. Here we have analyzed B cells and plasmablasts circulating in blood of COVID-19 patients not previously exposed to SARS-CoV-2 during and after disease. We find that during infection with the original Wuhan strain, plasmablasts in blood produce IgA1, IgG1, and IgM, and that most express CCR10 and integrin beta 1, only some integrin beta 7, while the majority lack CCR9. Plasmablast-secreted antibodies are reactive to the spike (S) and nucleocapsid (N) proteins of the Wuhan strain as well as later variants of concern, but also bind S proteins from endemic and non-circulating betacoronaviruses. In contrast, after recovery, antibodies produced from memory B cells target variants of SARS-CoV-2 and SARS-CoV-1 but compared to previously non-infected individuals do not show increased binding to endemic coronaviruses. This suggests that the early antibody response to a large extent stems from pre-existing cross-reactive class-switched memory B cells, and that although newly formed memory cells target the novel SARS-CoV-2 virus the numbers of broadly cross-reactive memory B cells do not increase extensively. The observations give insight into the role of pre-existing memory B cells in early antibody responses to novel pathogens and may explain why class-switched antibodies are detected early in the serum of COVID-19 patients. During an infection, plasmablasts circulating in blood represent ongoing formation of antibody-producing cells from activated B cells. Here we study the early plasmablasts in previously naive COVID-19 patients arriving at hospital. We find extensive cross-reactivity to circulating and non-circulating beta-coronaviruses, that IgA1 responses dominate, and that the cells express markers suggesting mucosal homing.
|
|
| 6. |
- Marklund, Emelie, et al.
(författare)
-
Longitudinal Follow Up of Immune Responses to SARS-CoV-2 in Health Care Workers in Sweden With Several Different Commercial IgG-Assays, Measurement of Neutralizing Antibodies and CD4+ T-Cell Responses.
- 2021
-
Ingår i: Frontiers in immunology. - : Frontiers Media SA. - 1664-3224. ; 12
-
Tidskriftsartikel (refereegranskat)abstract
- The risk of SARS-CoV-2 infection among health care workers (HCWs) is a concern, but studies that conclusively determine whether HCWs are over-represented remain limited. Furthermore, methods used to confirm past infection vary and the immunological response after mild COVID-19 is still not well defined.314 HCWs were recruited from a Swedish Infectious Diseases clinic caring for COVID-19 patients. IgG antibodies were measured using two commercial assays (Abbot Architect nucleocapsid (N)-assay and YHLO iFlash-1800 N and spike (S)-assays) at five time-points, from March 2020 to January 2021, covering two pandemic waves. Seroprevalence was assessed in matched blood donors at three time-points. More extensive analyses were performed in 190 HCWs in September/October 2020, including two additional IgG-assays (DiaSorin LiaisonXL S1/S2 and Abbot Architect receptor-binding domain (RBD)-assays), neutralizing antibodies (NAbs), and CD4+ T-cell reactivity using an in-house developed in vitro whole-blood assay based on flow cytometric detection of activated cells after stimulation with Spike S1-subunit or Spike, Membrane and Nucleocapsid (SMN) overlapping peptide pools.Seroprevalence was higher among HCWs compared to sex and age-matched blood donors at all time-points. Seropositivity increased from 6.4% to 16.3% among HCWs between May 2020 and January 2021, compared to 3.6% to 11.9% among blood donors. We found significant correlations and high levels of agreement between NAbs and all four commercial IgG-assays. At 200-300 days post PCR-verified infection, there was a wide variation in sensitivity between the commercial IgG-assays, ranging from <30% in the N-assay to >90% in the RBD-assay. There was only moderate agreement between NAbs and CD4+ T-cell reactivity to S1 or SMN. Pre-existing CD4+ T-cell reactivity was present in similar proportions among HCW who subsequently became infected and those that did not.HCWs in COVID-19 patient care in Sweden have been infected with SARS-CoV-2 at a higher rate compared to blood donors. We demonstrate substantial variation between different IgG-assays and propose that multiple serological targets should be used to verify past infection. Our data suggest that CD4+ T-cell reactivity is not a suitable measure of past infection and does not reliably indicate protection from infection in naive individuals.
|
|
| 7. |
- Scharf, Lydia, et al.
(författare)
-
Longitudinal single-cell analysis of SARS-CoV-2-reactive B cells uncovers persistence of early-formed, antigen specific clones.
- 2023
-
Ingår i: JCI insight. - : American Society for Clinical Investigation. - 2379-3708. ; 8:1
-
Tidskriftsartikel (refereegranskat)abstract
- Understanding persistence and evolution of B cell clones after COVID-19 infection and vaccination is crucial for predicting responses against emerging viral variants and optimizing vaccines. Here, we collected longitudinal samples from severe COVID-19 patients every third to seventh day during hospitalization and every third month after recovery. We profiled the antigen-specific immune cell dynamics by combining single cell RNA-Seq, Cellular Indexing of Transcriptomes and Epitopes by Sequencing (CITE)-Seq, B cell receptor (BCR)-Seq with oligo-tagged antigen baits. While the proportion of Spike Receptor Binding Domain-specific memory B cells (MBC) increased from 3 months after infection, the other Spike- and Nucleocapsid-specific B cells remained constant. All patients showed ongoing class switching and sustained affinity maturation of antigen specific cells, which was not significantly increased early after vaccine. B cell analysis revealed a polyclonal response with limited clonal expansion; nevertheless, some clones detected during hospitalization, as plasmablasts, persisted for up to one year, as MBC. Monoclonal antibodies derived from persistent B cell families increased their binding and neutralization breadth and started recognizing viral variants by 3 months after infection. Overall, our findings provide important insights into the clonal evolution and dynamics of antigen specific B cell responses in longitudinally sampled COVID-19 infected patients.
|
|
| 8. |
|
|
| 9. |
- Andersson, Jim, et al.
(författare)
-
Methanol production via pressurized entrained flow biomass gasification : Techno-economic comparison of integrated vs. stand-alone production
- 2014
-
Ingår i: Biomass and Bioenergy. - : Elsevier BV. - 0961-9534 .- 1873-2909. ; 64, s. 256-268
-
Tidskriftsartikel (refereegranskat)abstract
- The main objective with this work was to investigate techno-economically the opportunity for integrated gasification-based biomass-to-methanol production in an existing chemical pulp and paper mill. Three different system configurations using the pressurized entrained flow biomass gasification (PEBG) technology were studied, one stand-alone plant, one where the bark boiler in the mill was replaced by a PEBG unit and one with a co-integration of a black liquor gasifier operated in parallel with a PEBG unit. The cases were analysed in terms of overall energy efficiency (calculated as electricity-equivalents) and process economics. The economics was assessed under the current as well as possible future energy market conditions. An economic policy support was found to be necessary to make the methanol production competitive under all market scenarios. In a future energy market, integrating a PEBG unit to replace the bark boiler was the most beneficial case from an economic point of view. In this case the methanol production cost was reduced in the range of 11-18 Euro per MWh compared to the stand-alone case. The overall plant efficiency increased approximately 7%-units compared to the original operation of the mill and the non-integrated stand-alone case. In the case with co-integration of the two parallel gasifiers, an equal increase of the system efficiency was achieved, but the economic benefit was not as apparent. Under similar conditions as the current market and when methanol was sold to replace fossil gasoline, co-integration of the two parallel gasifiers was the best alternative based on received IRR.
|
|
| 10. |
- Aronsson, Gunnar, et al.
(författare)
-
The changing nature of work - Job strain, job support and sickness absence among care workers and in other occupations in Sweden 1991-2013
- 2021
-
Ingår i: SSM - Population Health. - : Elsevier BV. - 2352-8273. ; 15
-
Tidskriftsartikel (refereegranskat)abstract
- This study examined exposure changes in three psychosocial dimensions - job demands, job control, and social support - and the associations between these dimensions and sickness absence throughout the period 1991-2013. The analyses covered periods of economic ups and downs in Sweden and periods involving major fluctuations in sickness absence. Data on care workers (n = 16,179) and a comparison group of employees in other occupations (n = 82,070) were derived from the biennial Swedish Work Environment Survey and linked to register data on sickness absence. Eight exposure profiles, based on combinations of demands, control, and support, were formed. The proportion of individuals with work profiles involving high demands doubled among care workers (14%-29%) while increasing modestly in the comparison group (17%-21%) 1991-2013. The work profile that isolated high-strain (iso-strain), i.e., high demands, low control, and low social support, was more prevalent among care workers, from 4% in 1991 to 11% in 2013. Individuals with work profiles involving highdemand jobs had the highest number of days on sickness absence during the study period and those with the isostrain work profile had the highest increase in sickness absence, from 15 days per year during 1993-1994, to 42 days during 2000-2002. Employees with a passive work profile (low job demands and low job control) had the lowest rate and the lowest increase in sickness absence. Individuals with active work profiles, where high demands are supposed to be balanced by high job control, had a rather high increase in sickness days around 2000. A conclusion is that there is a long-term trend towards jobs with high demands. This trend is stronger among care workers than among other occupations. These levels of job demands seem to be at such a level that it is difficult to compensate for with higher job control and social support.
|
|
