ABSTRACT
ObjectivesTo test the main hypothesis that anticoagulation reduces risk of hospitalization, intensive care unit (ICU) admission and death in COVID-19.DesignNested case-control study among patients with atrial fibrillation (AF) in Stockholm. Cases were matched to five controls with same sex, born within +/- 1 years, and without COVID-19.SettingSource population was individuals in Stockholm with AF 1997-2020. Swedish regional and national registers are used. National registers cover hospitals and outpatient clinics, local registers cover primary care. Records were linked through the personal identity number assigned to each Swedish resident.ParticipantsCases were individuals with diagnosis of, ICU admission for, or death with COVID-19. The source population consisted of 179,381 individuals from which 7,548 cases were identified together with 37,145 controls. The number of cases (controls) for hospitalization, ICU admission and death were 5,916 (29,035), 160 (750) and 1,472 (7,360). The proportion of women was 40% for hospitalization and death, but 20% and 30% for admission to ICU in wave one and two, respectively. Main outcome measuresPrimary outcome was mortality, secondary outcome was hospitalization, tertiary outcome was ICU admission, all with COVID-19.ResultsOdds ratios (95% confidence interval) for antithrombotics were 0.79 (0.66 to 0.95) for the first wave and 0.80 (0.64 to 1.01) for the second wave.ConclusionsUse of anticoagulation among patients with COVID-19 and arrythmias is associated with lower risk of hospitalization and death. If further COVID-variants emerge, or other infections with prothrombotic properties, this emphasize need for physicians to ensure compliance among vulnerable patients.
Subject(s)
COVID-19ABSTRACT
Effective humoral immune responses require well-orchestrated cellular interactions between B and T follicular helper (Tfh) cells. Whether this interaction is impaired and associated with COVID-19 disease severity is unknown. Here, longitudinal acute and convalescent blood samples from 49 COVID-19 patients across mild to severe disease were analysed. We found that during acute infection activated and SARS-CoV-2-specific circulating Tfh (cTfh) cell frequencies expanded with increasing disease severity. The frequency of activated and SARS-CoV-2-specific cTfh cells correlated with plasmablast frequencies and SARS-CoV-2 antibody titers, avidity and neutralization. Furthermore, cTfh cells but not other memory CD4 T cells, isolated from severe patients induced more pronounced differentiation of autologous plasmablast and antibody production in vitro compared to cTfh cells isolated from mild patients. However, the development of virus-specific cTfh cells was delayed in patients that displayed or later developed severe disease compared to those that maintained a mild or moderate disease. This correlated with a delayed induction of high-avidity and neutralizing virus-specific antibodies. Our study therefore suggests that impaired generation of functional virus-specific cTfh cells delays the production of high-quality antibodies to combat the infection at an early stage and thereby enabling progression to more severe COVID-19 disease.
Subject(s)
COVID-19 , Acute DiseaseABSTRACT
Since the beginning of the Covid-19 pandemic, the scientific community has explored determinants of Covid 19 disease severity. However, the majority of studies are based on in-hospital patients with high risk of collider- or selection bias. The present investigation details risk factors associated with overall mortality, hospitalization and intensive care unit (ICU) admission in Covid-19 infections, with complete population coverage and high-resolution data on patient characteristics and comorbid conditions. Methods: This population-based observational study comprises all residents 18 years and older in Stockholm Region – 1.8 million inhabitants - using the real-time Covid-19 monitoring framework. The observation period lasted between March 1 to December 31, 2020. Hazard ratios (HR) for risk factors of Covid-19 disease severity were assessed using Cox proportional hazard models. Results: In total, 3,322 deaths, 11,508 hospitalizations and 1,423 ICU-admissions related to Covid-19 occurred during the study period. Kidney failure, diabetes and obesity increased risk of mortality and so did heart failure and ischemic heart disease. However, atrial fibrillation and hypertension did not. Risk of hospitalization follow a similar pattern, whereas admission to intensive care differs; triage processes where clearly present as certain co-morbid conditions were associated with lower ICU-admission. Conclusions: Observed differences in risk of mortality and hospitalization among patients with Covid 19 raise important questions about potentially protective co-medication which will be further addressed using the real-time Covid-19 monitoring framework.
Subject(s)
COVID-19ABSTRACT
Understanding immune responses following SARS-CoV-2 infection in relation to COVID-19 severity is critical to predicting the effects of long-term immunological memory on viral spread. Here we longitudinally assessed systemic and airway immune responses against SARS-CoV-2 in a well-characterized cohort of 147 infected individuals representing the full spectrum of COVID-19 severity; from asymptomatic infection to fatal disease. High systemic and airway antibody responses were elicited in patients with moderate to severe disease, and while systemic IgG levels were maintained after acute disease, airway IgG and IgA declined significantly. In contrast, individuals with mild symptoms showed significantly lower antibody responses but their levels of antigen-specific memory B cells were comparable with those observed in patients with moderate to severe disease. This suggests that antibodies in the airways may not be maintained at levels that prevent local virus entry upon re-exposure and therefore protection via activation of the memory B cell pool is critical.
Subject(s)
COVID-19 , Acute DiseaseABSTRACT
Background: Renal resistive index (RRI) is a promising tool for prediction of acute kidney injury (AKI) in critically ill patients but is not described among patients with Coronavirus disease 2019 (COVID-19). The aim of this study was to describe the pattern of RRI in relation to AKI in patients with COVID-19 treated in the intensive care unit. Methods: : In this observational cohort study, RRI was measured in COVID-19 patients in six ICUs at two sites of a Swedish University Hospital. AKI was defined by the creatinine criteria in the Kidney Disease Improving Global Outcome classification. We investigated the association between RRI and AKI diagnosis, different AKI stages and urine output. Results: : RRI was measured in 51 patients, of which 23 patients (45%) had AKI at the time of measurement. Median RRI in patients with AKI was 0.80 (IQR 0.71-0.85) compared to 0.72 (IQR 0.67-0.78) in patients without AKI (p=0.004). Compared to patients without AKI, RRI was higher in patients with AKI stage 3 (median 0.83, IQR 0.71-0.85, p=0.006) but not in patients with AKI stage 1 (median 0.76, IQR 0.71-0.83, p=0.347) or AKI stage 2 (median 0.79, min/max 0.79/0.80, n=2, p=0.134). RRI was higher in patients with an ongoing AKI episode compared to patients who never developed AKI (median 0.72, IQR 0.69-0.78, p=0.015) or patients who developed AKI but had recovered at the time of measurement (median 0.68, IQR 0.67-0.81, p=0.021). Oliguric patients had higher RRI (median 0.84, IQR 0.83-0.85) compared to non-oliguric patients (median 0.74, IQR 0.69-0.81) (p=0.009). Conclusions: : Critically ill COVID-19 patients with AKI have higher RRI compared to those without AKI, and elevated RRI may have a role in identifying severe and oliguric AKI in these patients.
Subject(s)
COVID-19 , Kidney Diseases , Acute Kidney InjuryABSTRACT
To understand the risk of transmission of SARS-CoV-2 in hospitalized COVID-19 patients we simultaneously assessed the presence of SARS-CoV-2 RNA, live infectious virus in the airways, and virus-specific IgG and neutralizing antibodies in sera in 36 hospitalized COVID-19 patients. SARS-CoV-2 could be cultured from four patients, all with low or undetectable antibody response. Our data suggests that the level of SARS-CoV-2 antibodies may correlate to risk for shedding live SARS-CoV-2 virus in hospitalized COVID-19 patients.
Subject(s)
COVID-19ABSTRACT
The immunopathology of COVID-19 remains enigmatic, exhibiting immunodysregulation and T cell lymphopenia. Monocytic myeloid-derived suppressor cells (M-MDSC) are T cell suppressors that expand in inflammatory conditions, but their role in acute respiratory infections remains unclear. We studied blood and airways of COVID-19 patients across disease severity at multiple timepoints. M-MDSC frequencies were elevated in blood but not in nasopharyngeal or endotracheal aspirates of COVID-19 patients compared to controls. M-MDSCs isolated from COVID-19 patients suppressed T cell proliferation and IFN{gamma} production partly via an arginase-1 (Arg-1) dependent mechanism. Furthermore, patients showed increased Arg-1 and IL-6 plasma levels. COVID-19 patients had fewer T cells, and displayed downregulated expression of the CD3{zeta} chain. Ordinal regression showed that early M-MDSC frequency predicted subsequent disease severity. In conclusion, M-MDSCs expand in blood of COVID-19 patients, suppress T cells and strongly associate with disease severity, suggesting a role for M-MDSCs in the dysregulated COVID-19 immune response.