Incidence and risk factors of peri-operative stroke in major non-cardiovascular, non-neurologic surgery-A retrospective register-based cohort study.

BACKGROUND: Peri-operative stroke is a rare but serious surgical complication. Both overt and covert stroke, occurring in approximately 0.1% and 7% of cases, respectively, are associated with significant long-term effects and increased morbidity. METHODS: Retrospective register data for patients >18 years old, presenting for major non-cardiovascular, non-neurosurgical and non-ambulatory surgical procedures at 23 hospitals in Sweden between 2007 and 2014 was collected and linked with various quality registers. The primary outcome was stroke within 30 days from surgery. Using multivariable logistic regression, significant independent risk factors influencing the primary outcome were identified and their adjusted odds ratios (ORs) were calculated. Mortality was assessed, along with the composite score of days alive and at home within 30 days after surgery (DAH 30). RESULTS: In total, 318,017 patients were included, with 687 (0.22%) suffering a stroke within 30 days of surgery. The strongest significant risk factors included: increasing ASA-class (OR [95% confidence interval, CI]: 2.23 [1.53-3.36], 3.91 [2.68-5.93] and 7.82 [5.03-12.5] for ASA 2, 3 and 4, respectively) and age (OR [95% CI]: 4.47 [2.21-10.3], 9.9 [5.15-22.1], 16.3 [8.48-36.5] and 21 [10.6-48.1], for age 45-59, 60-74, 75-89 and >90, respectively), along with non-elective procedures, male gender and a history of cerebrovascular disease (OR [95%]: 2.72 [2.25-3.27]). Mortality was increased and DAH 30 was reduced in patients suffering a stroke. CONCLUSIONS: Increasing ASA-class and age was clearly associated with an increased risk of peri-operative stroke, which in turn was associated with increased mortality and poorer outcome. Detailed pre-operative risk stratification and individualised peri-operative management could potentially improve patient-centred outcomes and, in turn, have positive implications for public health.

Shedding of infectious SARS-CoV-2 by hospitalized COVID-19 patients in relation to serum antibody responses.

BACKGROUND: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a global pandemic. The understanding of the transmission and the duration of viral shedding in SARS-CoV-2 infection is still limited. OBJECTIVES: To assess the timeframe and potential risk of SARS-CoV-2 transmission from hospitalized COVID-19 patients in relation to antibody response. METHOD: We performed a cross-sectional study of 36 COVID-19 patients hospitalized at Karolinska University Hospital. Patients with more than 8 days of symptom duration were sampled from airways, for PCR analysis of SARS-CoV-2 RNA and in vitro culture of replicating virus. Serum SARS-CoV-2-specific immunoglobulin G (IgG) and neutralizing antibodies titers were assessed by immunofluorescence assay (IFA) and microneutralization assay. RESULTS: SARS-CoV-2 RNA was detected in airway samples in 23 patients (symptom duration median 15 days, range 9-53 days), whereas 13 patients were SARS-CoV-2 RNA negative (symptom duration median 21 days, range 10-37 days). Replicating virus was detected in samples from 4 patients at 9-16 days. All but two patients had detectable levels of SARS-CoV-2-specific IgG in serum, and SARS-CoV-2 neutralizing antibodies were detected in 33 out of 36 patients. Total SARS-CoV-2-specific IgG titers and neutralizing antibody titers were positively correlated. High levels of both total IgG and neutralizing antibody titers were observed in patients sampled later after symptom onset and in patients where replicating virus could not be detected. CONCLUSIONS: Our data suggest that the presence of SARS-Cov-2 specific antibodies in serum may indicate a lower risk of shedding infectious SARS-CoV-2 by hospitalized COVID-19 patients.

Delayed generation of functional virus-specific circulating T follicular helper cells correlates with severe COVID-19.

Effective humoral immune responses require well-orchestrated B and T follicular helper (Tfh) cell interactions. Whether these interactions are impaired and associated with COVID-19 disease severity is unclear. Here, longitudinal blood samples across COVID-19 disease severity are analysed. We find that during acute infection SARS-CoV-2-specific circulating Tfh (cTfh) cells expand with disease severity. SARS-CoV-2-specific cTfh cell frequencies correlate with plasmablast frequencies and SARS-CoV-2 antibody titers, avidity and neutralization. Furthermore, cTfh cells but not other memory CD4 T cells, from severe patients better induce plasmablast differentiation and antibody production compared to cTfh cells from mild patients. However, virus-specific cTfh cell development is delayed in patients that display or later develop severe disease compared to those with mild disease, which correlates with delayed induction of high-avidity neutralizing antibodies. Our study suggests that impaired generation of functional virus-specific cTfh cells delays high-quality antibody production at an early stage, potentially enabling progression to severe disease.

Functional monocytic myeloid-derived suppressor cells increase in blood but not airways and predict COVID-19 severity.

The immunopathology of coronavirus disease 2019 (COVID-19) remains enigmatic, causing immunodysregulation and T cell lymphopenia. Monocytic myeloid-derived suppressor cells (M-MDSCs) are T cell suppressors that expand in inflammatory conditions, but their role in acute respiratory infections remains unclear. We studied the blood and airways of patients with COVID-19 across disease severities at multiple time points. M-MDSC frequencies were elevated in blood but not in nasopharyngeal or endotracheal aspirates of patients with COVID-19 compared with healthy controls. M-MDSCs isolated from patients with COVID-19 suppressed T cell proliferation and IFN-γ production partly via an arginase 1-dependent (Arg-1-dependent) mechanism. Furthermore, patients showed increased Arg-1 and IL-6 plasma levels. Patients with COVID-19 had fewer T cells and downregulated expression of the CD3ζ chain. Ordinal regression showed that early M-MDSC frequency predicted subsequent disease severity. In conclusion, M-MDSCs expanded in the blood of patients with COVID-19, suppressed T cells, and were strongly associated with disease severity, indicating a role for M-MDSCs in the dysregulated COVID-19 immune response.

Airway antibodies emerge according to COVID-19 severity and wane rapidly but reappear after SARS-CoV-2 vaccination.

Understanding the presence and durability of antibodies against SARS-CoV-2 in the airways is required to provide insights into the ability of individuals to neutralize the virus locally and prevent viral spread. Here, we longitudinally assessed both systemic and airway immune responses upon SARS-CoV-2 infection in a clinically well-characterized cohort of 147 infected individuals representing the full spectrum of COVID-19 severity, from asymptomatic infection to fatal disease. In addition, we evaluated how SARS-CoV-2 vaccination influenced the antibody responses in a subset of these individuals during convalescence as compared with naive individuals. Not only systemic but also airway antibody responses correlated with the degree of COVID-19 disease severity. However, although systemic IgG levels were durable for up to 8 months, airway IgG and IgA declined significantly within 3 months. After vaccination, there was an increase in both systemic and airway antibodies, in particular IgG, often exceeding the levels found during acute disease. In contrast, naive individuals showed low airway antibodies after vaccination. In the former COVID-19 patients, airway antibody levels were significantly elevated after the boost vaccination, highlighting the importance of prime and boost vaccinations for previously infected individuals to obtain optimal mucosal protection.