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Background: COVID-19 is a multi-organ disease affecting the kidneys, but the extent of persistent kidney injury and the utility of novel biomarkers remain unclear. We investigated patients with COVID-19 regarding initial impairment and recovery of glomerular and tubular function during six months. 

Methods: We conducted a prospective cohort study comprising 77 hospitalized and 141 non-hospitalized patients with COVID-19 in Sweden. Plasma samples collected during the acute phase and at three- and six-month follow-up were analyzed for glomerular markers creatinine and cystatin C to estimate glomerular filtration rate (eGFR). Tubular markers included kidney injury molecule-1, osteoactivin, trefoil factor 3, and vascular endothelial growth factor-A.

Results: Hospitalized versus non-hospitalized patients demonstrated lower eGFRcystatin C across time-points, while eGFRcreatinine was less specific. Kidney injury molecule-1 and vascular endothelial growth factor-A were persistently higher in hospitalized patients. Osteoactivin was lower at the acute phase and higher at three- and six-months follow-up in hospitalized patients. Recovery from the acute phase to six months was observed in both groups, although the biomarker levels were consistently worse for hospitalized patients.  

Conclusion: Glomerular and tubular kidney functions remained more impaired in hospitalized COVID-19 patients compared to non-hospitalized for six months. We recommend eGFRcystatin C for evaluation of glomerular function during COVID-19. The tubular injury markers kidney injury molecule-1 and vascular endothelial growth factor-A were markedly elevated in hospitalized patients, consistent with more sustained interstitial inflammation. This finding suggests that these patients may require closer clinical monitoring. 

We evaluated the magnitude and function of antibody responses to seasonal influenza vaccination in individuals with HIV receiving ART compared with individuals without HIV. In a prospective cohort of 78 adults, influenza strain-specific IgG levels were measured up to one-year post-vaccination. Linear mixed-effects models assessed longitudinal trends. IgG levels peaked at two weeks and declined gradually in both groups. HIV status did not significantly influence antibody magnitude or neutralizing activity, and H1N1 antibody levels correlated with neutralization titers. These findings demonstrate robust, durable, and functional humoral response in well-controlled HIV, supporting the effectiveness of annual influenza vaccination in this population.

Background: Older adults (> 65 years) residing in long-term care facilities (LTCFs) are at elevated risk of severe outcomes from respiratory infections. Infections often remain undetected or present atypically in this population, leading to underdiagnosis. Our study aimed to estimate the respiratory virus infection burden, independent of symptom presentation, among older adults in Swedish LTCFs in the post-pandemic period (2021–2024).

Methods: We leveraged capillary blood samples and coupled national registry data from 1622 LTCF residents (median age = 87). A multiplex platform was used to quantify antigen-specific IgG and IgM responses to RSV (pre-/post-F, strain A-specific G-protein), influenza-A (H1N1 and H3N2 HA), influenza-B (HA) and SARS-CoV-2 (spike). Linear mixed-effects models were used to demonstrate the dynamics of antibody levels over time, adjusted for age, sex and comorbidities.

Results: RSV-specific antibody responses peaked in spring 2022 (p < 0.001), suggesting an impact of relaxed COVID-19-related restrictions on RSV exposure at LTCFs. RSV-specific antibodies subsequently declined over time until an increase during autumn 2023 (p < 0.001). Geographic variation in pre-F antibody levels suggested localised RSV outbreaks. The total estimated RSV burden at LTCFs was markedly higher than official reports of the Swedish Public Health Agency. Influenza antibody dynamics reflected seasonal trends and were strongly influenced by annual vaccination. A random forest classifier incorporating serological profiles with demographics, location and comorbidities significantly outperformed a model without serological data (AUC-ROC = 0.67 vs. 0.58), although discriminatory performance remained modest. Higher levels of RSV pre-F antibodies in autumn 2021 were associated with increased one-year mortality in logistic regression (OR = 1.43, p = 0.024). Exploratory survival analysis indicated a trend that elevated levels of RSV pre-F antibodies during low population immunity may confer a transiently elevated early hazard of death, although this did not reach statistical significance (HR = 4.50, p = 0.087).

Conclusions: We observed substantial respiratory virus circulation among older adults in Swedish LTCFs and show that RSV burden is under-reported. The results highlight a need for further research into the role of RSV pre-F antibody levels in preventing severe outcomes, potentially via vaccination of LTCF residents. Our scalable serological surveillance system is a valuable approach to detect respiratory infections in LTCFs, independent of symptom presentation or healthcare-seeking behaviour.

Objectives: Vaccine responses in haematopoietic stem cell transplant (alloHCT) recipients vary, with different degrees of B-cell reconstitution likely playing a key role. However, mechanistic understanding of the B-cell receptor (BCR) repertoire and its functional impact post-alloHCT remain limited.

Methods: Within the scope of a mRNA SARS-CoV-2 vaccine phase IV clinical trial in alloHCT recipients (n = 77), we have measured antibody titers and avidity, and performed B-cell immunophenotyping and B-cell receptor repertoire sequencing in sub-populations.

Results: AlloHCT patients receiving prime-boost mRNA vaccination within 12 months post-transplant exhibited lower vaccine-specific antibody levels and memory B-cell frequencies than vaccinated healthy controls. Responses were comparable to healthy controls in patients vaccinated later than 12 months post transplant. BCR repertoire sequencing showed reduced somatic hypermutation (SHM) levels in bulk IgG+ B cells from alloHCT patients. Although some alloHCT patients showed exceptional expansion of a few IgG clones of unknown specificity, their overall B-cell repertoires remained polyclonal. Vaccine-specific B-cell clonotypes detected in patients responding to vaccination showed similar proportional expansion and SHM as in controls. The level of immature CD24hiCD38hi transitional B cells pre-vaccination was negatively correlated to the vaccine response, and can be used as a predictor of antibody titres.

Conclusion: Our data indicate that mRNA vaccination can stimulate expansion of vaccine-specific B cells to affinity mature in many alloHCT recipients, though restricted by the presence of immature B-cell populations.

Although adenoviruses (AdVs) possess advantageous features as vectors, several challenges remain. These include a high prevalence of neutralizing antibodies against certain AdV types and the inability to efficiently transduce CAR-deficient cells and tissues. We showed previously that lactoferricin (Lfcin) enhances CAR-independent HAdV-C5 infection of epithelial and T-cells. Here, we assessed the ability of Lfcin to enable HAdV-C5 infection and transduction of human skeletal muscle cells. Lfcin increases HAdV-C5 infection and transduction of muscle myoblasts and myotubes by 10- to 30-fold. Enhanced infection correlates with increased cell binding, which differs mechanistically from that of coagulation factor X-mediated binding, as it remains unaffected by the removal of heparan sulfate. Additionally, Lfcin reduces the neutralizing effects of serum against HAdV-C5, suggesting it may shield key epitopes. By enabling viral binding to muscle cells and mitigating serum neutralization, Lfcin offers a novel strategy to improve the efficiency and durability of HAdV-C5-based gene delivery systems.

Objectives: COVID-19 impacts physical and respiratory health, and the clinical presentation ranges from asymptomatic cases to severe infections requiring hospitalisation. While the long-term effects on lung function and physical capacity are well-documented in moderate to severe cases, the long-term outcome for individuals with mild COVID-19 remains poorly understood. This study investigates the long-term recovery of physical capacity and breathlessness among both hospitalised and non-hospitalised individuals.

Methods: This prospective cohort study enrolled individuals with confirmed SARS-CoV-2 infection between April 2020 and May 2021 through the CoVUm-study. Participants underwent assessments of lung function at 3–6 months after infection and attended follow-ups up to three years post-infection. Physical capacity was evaluated at follow-ups, using the one-minute sit-to-stand test and the modified Medical Research Council scale to assess breathlessness.

Results: The cohort included 291 participants, 35% of whom were hospitalised during SARS-CoV-2 infection. At the 3-year follow-up, 191 participants completed the physical capacity test and 179 had an assessment of breathlessness. Physical capacity improved significantly in the total cohort up to two years post-infection, where improvement plateaued. Hospitalisation and impaired diffusing capacity were significantly associated with reduced physical capacity (beta –6.4, p < 0.001; beta –8.9, p < 0.001, respectively) and breathlessness (beta 3.9, p < 0.001; beta 1.6, p = 0.012, respectively). While non-hospitalised participants demonstrated improvements in physical capacity for up to two years, improvement for hospitalised individuals plateaued by six months.

Conclusion: Hospitalisation and impaired diffusing capacity are strong independent predictors of reduced physical capacity and persistent breathlessness up to three years post-infection. Non-hospitalised individuals also experience long-term reductions in physical capacity, underscoring the need for targeted rehabilitation strategies.

Background: Current evidence indicates that Post COVID-19 Condition (PCC) is multifaceted with distinct phenotypes. While previous studies have identified symptom clusters—commonly featuring fatigue, respiratory symptoms, and cognitive impairment—findings have been inconsistent, and no clear consensus exists. Moreover, how these symptom clusters evolve over time, particularly beyond the first year post-infection, remains poorly understood.

Methods: This multicentre prospective cohort study included 470 hospitalised and non-hospitalised adult individuals from the CoVUm study across four sites in Sweden between 2020 and 2021. Follow-ups were conducted up to 3 years after infection to assess persistent symptoms, health-related quality of life (HRQoL), and work capacity. Symptom clusters at 6 months were identified via hierarchical cluster analysis, and participants were tracked using a k-nearest neighbour algorithm.

Results: The most common symptoms at 6 months were fatigue (33 %), dyspnoea (32 %), mental fatigue (30 %), and concentration difficulties (28 %), with a median EQ-5D-5L index of 0.98 (IQR 0.93–1). Four distinct symptom clusters were identified: (i) “Few Symptoms” (n = 265, 57 %), (ii) “Respiratory Symptoms” (n = 66, 14 %), (iii) “Neurocognitive Symptoms” (n = 75, 16 %), and (iv) “Multisystem Symptoms” (n = 52, 11 %). Participants in the latter three clusters were older, had more comorbidities, and were more often hospitalised during primary COVID-19 infection. These clusters also had significantly lower HRQoL compared to the “Few Symptoms” cluster. Over time, more than half of participants transitioned to a cluster with fewer or no symptoms, with significant perceived HRQoL improvement in the “Multisystem Symptoms” cluster.

Conclusion: While many patients with PCC improved over time, a subset had persistent symptoms at 3 years, especially if primary infection required hospitalisation. The identification of symptom clusters and their trajectories over time contributes to a better understanding of PCC heterogeneity, ultimately bringing the field closer to consensus on the classification and long-term impact of PCC.

Single-cell RNA-seq methods can be used to delineate cell types and states at unprecedented resolution but do little to explain why certain genes are expressed. Single-cell ATAC-seq and multiome (ATAC + RNA) have emerged to give a complementary view of the cell state. It is however unclear what additional information can be extracted from ATAC-seq data besides transcription factor binding sites. Here, we show that ATAC-seq telomere-like reads counter-inituively cannot be used to infer telomere length, as they mostly originate from the subtelomere, but can be used as a biomarker for chromatin condensation. Using long-read sequencing, we further show that modern hyperactive Tn5 does not duplicate 9 bp of its target sequence, contrary to common belief. We provide a new tool, Telomemore, which can quantify nonaligning subtelomeric reads. By analyzing several public datasets and generating new multiome fibroblast and B-cell atlases, we show how this new readout can aid single-cell data interpretation. We show how drivers of condensation processes can be inferred, and how it complements common RNA-seq-based cell cycle inference, which fails for monocytes. Telomemore-based analysis of the condensation state is thus a valuable complement to the single-cell analysis toolbox.

Thrombocytopenia is a cardinal symptom of hantavirus-induced diseases including Puumala virus (PUUV)-induced hemorrhagic fever with renal syndrome (HFRS), which is associated with impaired platelet function, bleeding manifestations and augmented thrombotic risk. However, the underlying mechanisms causing thrombocytopenia and platelet hypo-responsiveness are unknown. Thus, we investigated the direct and indirect impact of PUUV on platelet production, function and degradation. Analysis of PUUV-HFRS patient blood revealed that platelet hypo-responsiveness in PUUV infection was cell-intrinsic and accompanied by reduced platelet-leukocyte aggregates (PLAs) and upregulation of monocyte tissue factor (TF), whereas platelet vasodilator-stimulated phosphoprotein (VASP) phosphorylation was comparable to healthy controls. Plasma CXCL4 levels followed platelet count dynamics throughout disease course. PUUV activated both neutrophils and monocytes in vitro, but platelet desialylation, degranulation and GPIIb/IIIa activation as well as PLA formation and endothelial adhesion under flow remained unaltered in the presence of PUUV. Further, MEG-01 megakaryocytes infected with PUUV displayed unaltered polyploidization, expression of surface receptors and platelet production. However, infection of endothelial cells with PUUV significantly increased platelet sequestration. Our data thus demonstrate that although platelet production, activation or degradation are not directly modulated, PUUV indirectly fosters thrombocytopenia by sequestration of platelets to infected endothelium. Upregulation of immunothrombotic processes in PUUV-HFRS may further contribute to platelet dysfunction and consumption. Given the pathophysiologic similarities of hantavirus infections, our findings thus provide important insights into the mechanisms underlying thrombocytopenia and highlight immune-mediated coagulopathy as potential therapeutic target.