SARS-CoV-2 infection induces hyaluronan production and hyaluronan levels in COVID-19 patients relate to morbidity and long-term lung impairment: a prospective cohort study.

We previously demonstrated that the lungs of deceased COVID-19 patients were filled with a clear hydrogel consisting of hyaluronan (HA). In this translational study, we investigated the role of HA at all stages of COVID-19 disease to map the consequences of elevated HA on morbidity and identify the mechanism of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced HA production. A reduced alveolar surface area was observed in the lungs of deceased COVID-19 patients compared to healthy controls, as visualized by a 3D rendering of lung morphology using light-sheet fluorescence microscopy.

Covid-19 Across Professions-Infection, Hospitalization, and Intensive Care Unit Patterns in a Swedish County.

Objective: The aim of the study was to study infection, hospitalization, and admission to intensive care unit for COVID-19 in different occupations and pandemic waves in a Swedish county.

Methods: Individual registry data of infection and hospitalization were merged with occupational data in this cross-sectional study. Infected, hospital-, and intensive care unit-admission were analyzed by occupational groups.

Modulation of innate immune response to mRNA vaccination after SARS-CoV-2 infection or sequential vaccination in humans.

mRNA vaccines are likely to become widely used for the prevention of infectious diseases in the future. Nevertheless, a notable gap exists in mechanistic data, particularly concerning the potential effects of sequential mRNA immunization or preexisting immunity on the early innate immune response triggered by vaccination. In this study, healthy adults, with or without documented prior SARS-CoV-2 infection, were vaccinated with the BNT162b2/Comirnaty mRNA vaccine.

Profiling the dysregulated immune response in sepsis: overcoming challenges to achieve the goal of precision medicine.

Sepsis is characterised by a dysregulated host immune response to infection. Despite recognition of its significance, immune status monitoring is not implemented in clinical practice due in part to the current absence of direct therapeutic implications. Technological advances in immunological profiling could enhance our understanding of immune dysregulation and facilitate integration into clinical practice.

Design of a national patient-centred clinical pathway for sepsis in Sweden.

Background: The World Health Organization has adopted a resolution on sepsis and urged member states to develop national processes to improve sepsis care. In Sweden, sepsis was selected as one of the ten first diagnoses to be addressed, when the Swedish government in 2019 allocated funds for patient-centred clinical pathways in healthcare. A national multidisciplinary working group, including a patient representative, was appointed to develop the patient-centred clinical pathway for sepsis.

High prevalence of persistent symptoms and reduced health-related quality of life 6 months after COVID-19.

Background: The long-term sequelae after COVID-19 constitute a challenge to public health and increased knowledge is needed. We investigated the prevalence of self-reported persistent symptoms and reduced health-related quality of life (HRQoL) in relation to functional exercise capacity, 6 months after infection, and explored risk factors for COVID-19 sequalae.

Methods: This was a prospective, multicenter, cohort study including 434 patients.

Risk factors for impaired respiratory function post COVID-19: A prospective cohort study of nonhospitalized and hospitalized patients.

Background: Severe COVID-19 increases the risk for long-term respiratory impairment, but data after mild COVID-19 are scarce. Our aims were to determine risk factors for reduced respiratory function 3-6 months after COVID-19 infection and to investigate if reduced respiratory function would relate to impairment of exercise performance and breathlessness.

Methods: Patients with COVID-19 were enrolled at the University Hospitals of Umeå and Örebro, and Karlstad Central Hospital, Sweden.

Serum concentration of extracellular cold-inducible RNA-binding protein is associated with respiratory failure in COVID-19.

Unlabelled: Uncontrolled release of damage-associated molecular patterns (DAMPs) is suggested to be a major trigger for the dysregulated host immune response that leads to severe COVID-19. Cold-inducible RNA-binding protein (CIRP), is a newly identified DAMP that aggravates inflammation and tissue injury, and induces respiratory failure in sepsis. Whether CIRP contributes to the pathogenesis of respiratory failure in COVID-19 has not yet been explored.

Sustained elevation of soluble B- and T- lymphocyte attenuator predicts long-term mortality in patients with bacteremia and sepsis.

Soluble B and T lymphocyte attenuator (sBTLA) has been shown to be associated with severity and outcome, in critically ill septic patients. We aimed to assess the dynamic expression of sBTLA, as a prognostic biomarker of long-term mortality in patients with bloodstream infection (BSI) and sepsis, and to evaluate its association with biomarkers indicative of inflammation and immune dysregulation. Secondarily, sBTLA was evaluated in association with severity and bacterial etiology.

Clinical measurement of cellular DNA damage hypersensitivity in patients with DNA repair defects.

Background: DNA repair deficiency disorders are rare inherited diseases arising from pathogenic (disease-causing) variants in genes involved in DNA repair. There are no standardized diagnostic assays for the investigation of pathological significance of unknown variants in DNA repair genes. We hypothesized that our assays for measuring in vitro patient blood cell hypersensitivity to DNA-damaging agents can be used to establish the pathological significance of unknown variants in DNA repair genes.

RT-PCR cycle threshold value in combination with visual scoring of chest computed tomography at hospital admission predicts outcome in COVID-19.

Background: COVID-19 has a most variable prognosis. Several risk factors for an unfavourable outcome have been identified including extensive lung involvement on chest CT and high viral load estimated by RT-PCR cycle threshold (Ct) values. We investigated Ct value for outcome prediction, relation between Ct value and extent of lung involvement on chest CT and the combination of Ct value and chest CT lung involvement to predict outcome in COVID-19.

The COVID-19 puzzle: deciphering pathophysiology and phenotypes of a new disease entity.

The zoonotic SARS-CoV-2 virus that causes COVID-19 continues to spread worldwide, with devastating consequences. While the medical community has gained insight into the epidemiology of COVID-19, important questions remain about the clinical complexities and underlying mechanisms of disease phenotypes. Severe COVID-19 most commonly involves respiratory manifestations, although other systems are also affected, and acute disease is often followed by protracted complications.

Efficacy of the TMPRSS2 inhibitor camostat mesilate in patients hospitalized with Covid-19-a double-blind randomized controlled trial.

Background: The trans-membrane protease serine 2 (TMPRSS2) is essential for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cell entry and infection. Efficacy and safety of TMPRSS2 inhibitors in patients with coronavirus disease 2019 (Covid-19) have not been evaluated in randomized trials.

Methods: We conducted an investigator-initiated, double-blind, randomized, placebo-controlled multicenter trial in patients hospitalized with confirmed SARS-CoV-2 infection from April 4, to December 31, 2020.

Visual scoring of chest CT at hospital admission predicts hospitalization time and intensive care admission in Covid-19.

Background: Chest CT is prognostic in Covid-19 but there is a lack of consensus on how to report the CT findings. A chest CT scoring system, ÖCoS, was implemented in clinical routine on 1 April 2020, in Örebro Region, Sweden. The ÖCoS-severity score measures the extent of lung involvement.

Bridging animal and clinical research during SARS-CoV-2 pandemic: A new-old challenge.

Many milestones in medical history rest on animal modeling of human diseases. The SARS-CoV-2 pandemic has evoked a tremendous investigative effort primarily centered on clinical studies. However, several animal SARS-CoV-2/COVID-19 models have been developed and pre-clinical findings aimed at supporting clinical evidence rapidly emerge.

Undiagnosed SARS-CoV-2 infection and outcome in patients with acute MI and no COVID-19 symptoms.

Objective: We aimed to determine the prevalence and outcome of occult infection with SARS-CoV-2 and influenza in patients presenting with myocardial infarction (MI) without COVID-19 symptoms.

Methods: We conducted an observational study from 28 June to 11 August 2020, enrolling patients admitted to the National Institute of Cardiovascular Disease Hospital, Dhaka, Bangladesh, with ST-segment elevation MI (STEMI) or non-ST-segment elevation MI who did not meet WHO criteria for suspected COVID-19. Samples were collected by nasopharyngeal swab to test for SARS-CoV-2 and influenza virus by real-time reverse transcriptase PCR.

Early prediction of blood stream infection in a prospectively collected cohort.

Background: Blood stream infection (BSI) and sepsis are serious clinical conditions and identification of the disease-causing pathogen is important for patient management. The RISE (Rapid Identification of SEpsis) study was carried out to collect a cohort allowing high-quality studies on different aspects of BSI and sepsis. The aim of this study was to identify patients at high risk for BSI who might benefit most from new, faster, etiological testing using neutrophil to lymphocyte count ratio (NLCR) and Shapiro score.

Presence of hyaluronan in lung alveoli in severe Covid-19: An opening for new treatment options?

Severe coronavirus disease 2019 (Covid-19) is characterized by inflammation of the lungs with increasing respiratory impairment. In fatal Covid-19, lungs at autopsy have been filled with a clear liquid jelly. However, the nature of this finding has not yet been determined.

Trends in sepsis mortality over time in randomised sepsis trials: a systematic literature review and meta-analysis of mortality in the control arm, 2002-2016.

Background: Epidemiologic data have shown an increasing incidence and declining mortality rate in sepsis. However, confounding effects due to differences in disease classification might have contributed to these trends. To assess if a declining mortality over time could be supported by data derived from high-quality prospective studies, we performed a meta-analysis using data from randomised controlled trials (RCTs) on sepsis.

Plasma concentrations of secretory leukocyte protease inhibitor (SLPI) differ depending on etiology and severity in community-onset bloodstream infection.

The severity of bloodstream infections (BSI) depends on pathogen, source, and host factors. Secretory leukocyte protease inhibitor (SLPI) counteracts tissue damage, balances inflammation, and is increased in pneumonia and sepsis. We aimed to evaluate whether SLPI production differs depending on etiology, disease severity, and sex in BSI and to correlate SLPI with markers of inflammation and immunosuppression.