A disturbed balance between blood complement protective factors (FH, ApoE) and common pathway effectors (C5a, TCC) in acute COVID-19 and during convalesce.

A complement effect on homeostasis during infection is determined by both cytotoxic (activate complement component 5 (C5a) terminal cytotoxic complex (TCC)), and cytoprotective elements (complement factor H (FH), as well as apolipoprotein E (ApoE)). Here, we investigated the gap in knowledge in their blood milieu during SARS-CoV-2 infection with respect to the viral burden, level of tissue necrosis, and immunological response. 101 patients hospitalized with a PCR-confirmed diagnosis of COVID-19 had blood collected at H1 (48 h), H2 (3-4 Days), H3 (5-7 days), H4 (more than 7 days up to 93 days). Pre-existing conditions, treatment, the incidence of cerebrovascular events (CVA), a history of deep venous thrombosis (DVT) and pulmonary embolism (PE), and mortality was collected using electronic medical records. Plasma C5a, TCC, FH, and ApoE were considered as a complement milieu. Tissue necrosis (HMGB1, RAGE), non-specific inflammatory responses (IL-6, C-reactive protein), overall viral burden (SARS-CoV-2 spike protein), and specific immune responses (IgG, IgA, IgM directed αS- & N-proteins) were assessed simultaneously. C5a remained elevated across all time points, with the peak at 5-7 days. Studied elements of complement coalesced around three clusters: #0 (↑↑↑C5a, ↑↑TCC, ↓↓ApoE), #1 ↑C5a, ↑TCC, ↑↑↑FH); #2 (↑C5a, ↑TCC, ↑FH, ↑↑↑ApoE). The decline in FH and ApoE was a predictor of death, while TCC and C5a correlated with patient length of stay, APACHE, and CRP. Increased levels of C5a (Δ = 122.64; p = 0.0294; data not shown) and diminished levels of FH (Δ = 836,969; p = 0.0285; data not shown) co-existed with CVA incidence. C5a correlated storngly with blood RAGE and HMGB1, but not with viral load and immunological responsiveness. Remdesivir positively affected FH preservation, while convalescent plasma treatment elevated C5a levels. Three clusters of complement activation demonstrated a various milieu of ApoE & FH vs C5a & TCC in COVID-19 patients. Complement activation is linked to increased necrosis markers but not to viral burden or immune system response.

PATTERNS OF URINARY BIOMARKERS OF IMMUNOLOGIC ACTIVATION AND SEPSIS IN PATIENTS WITH COVID-19

B Background: b In the past, few studies have utilized urine to assess the state of the immune system. Here, we hypothesize that urine biomarkers can assess immune activation and the effect of antiviral treatment in patients infected with COVID-19. With regards to treatments, Remdesivir had a more profound impact on the urine biomarkers than steroids. [Extracted from the article] Copyright of Critical Care Medicine is the property of Lippincott Williams & Wilkins and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Dynamic Changes in Central and Peripheral Neuro-Injury vs. Neuroprotective Serum Markers in COVID-19 Are Modulated by Different Types of Anti-Viral Treatments but Do Not Affect the Incidence of Late and Early Strokes.

The balance between neurodegeneration, neuroinflammation, neuroprotection, and COVID-19-directed therapy may underly the heterogeneity of SARS-CoV-2's neurological outcomes. A total of 105 patients hospitalized with a diagnosis of COVID-19 had serum collected over a 6 month period to assess neuroinflammatory (MIF, CCL23, MCP-1), neuro-injury (NFL, NCAM-1), neurodegenerative (KLK6, τ, phospho τ, amyloids, TDP43, YKL40), and neuroprotective (clusterin, fetuin, TREM-2) proteins. These were compared to markers of nonspecific inflammatory responses (IL-6, D-dimer, CRP) and of the overall viral burden (spike protein). Data regarding treatment (steroids, convalescent plasma, remdasavir), pre-existing conditions, and incidences of strokes were collected. Amyloid ß42, TDP43, NF-L, and KLK6 serum levels declined 2-3 days post-admission, yet recovered to admission baseline levels by 7 days. YKL-40 and NCAM-1 levels remained elevated over time, with clusters of differential responses identified among TREM-2, TDP43, and YKL40. Fetuin was elevated after the onset of COVID-19 while TREM-2 initially declined before significantly increasing over time. MIF serum level was increased 3-7 days after admission. Ferritin correlated with TDP-43 and KLK6. No treatment with remdesivir coincided with elevations in Amyloid-ß40. A lack of convalescent plasma resulted in increased NCAM-1 and total tau, and steroidal treatments did not significantly affect any markers. A total of 11 incidences of stroke were registered up to six months after initial admission for COVID-19. Elevated D-dimer, platelet counts, IL-6, and leukopenia were observed. Variable MIF serum levels differentiated patients with CVA from those who did not have a stroke during the acute phase of COVID-19. This study demonstrated concomitant and opposite changes in neurodegenerative and neuroprotective markers persisting well into recovery.

Guillain–Barré Syndrome in COVID-19—The Potential Role of NCAM-1 and Immunotherapy

Coronavirus disease 2019 (COVID-19) interacts with the nervous system directly and indirectly by affecting the activation of the immune system. Guillain–Barré syndrome (GBS) is triggered by an inappropriate immune system activation that overlaps with the neurotoxic mechanism of an invading pathogen. Here, we discuss the complexity of an abnormal immune system response leading to the generation of autoimmunity in the setting of acute viral infection. A 67-year-old male patient with COVID-19 developed a sensory motor acute polyneuropathy with respiratory failure. Several serum inflammatory and neurodegeneration markers were collected during hospital days 1, 3, 8, and 67 and compared to healthy individuals. Neural cell adhesion molecule 1 (NCAM-1) and neurofilament light chain (NfL) values were highly variable when compared to healthy individuals, but not to the reference COVID-19 group. We focused our attention on NCAM-1 as a possible target for antibodies directed at COVID-19 in silico.

The Characterization of the Toll of Caring for Coronavirus Disease 2019 on ICU Nursing Staff.

OBJECTIVES: Coronavirus disease 2019 pandemic exercised a significant demand on healthcare workers. We aimed to characterize the toll of caring for coronavirus disease 2019 patients by registered nurses. DESIGN: An observational study of two registered nurses cohorts. SETTING: ICUs in a large academic center. SUBJECTS: Thirty-nine ICU registered nurses assigned to coronavirus disease 2019 versus noncoronavirus disease 2019 patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Skin temperature (t [°C]), galvanic skin stress response (GalvStress), blood pulse wave, energy expenditure (Energy [cal]), number of steps (hr-1), heart rate (min-1), and respiratory rate (min-1) were collected using biosensors during the shift. National Aeronautics and Space Administration Task Loading Index measured the subjective perception of an assignment load. Elevated skin temperatures during coronavirus disease 2019 shifts were recorded (ΔtCOVID vs tnon-COVID = +1.3 [°C]; 95% CI, 0.1-2.5). Registered nurses staffing coronavirus disease patients self-reported elevated effort (ΔEffortCOVID vs Effortnon-COVID = +28.6; 95% CI, 13.3-43.9) concomitant with higher energy expenditure (ΔEnergyCOVID vs Energynon-COVID = +21.5 [cal/s]; 95% CI, 4.2-38.7). Galvanic skin stress responses were more frequent among coronavirus disease registered nurse (ΔGalStressCOVID vs GalvStressnon-COVID = +10.7 [burst/hr]; 95% CI, 2.6-18.7) and correlated with self-reported increased mental burden (ΔTLXMentalCOVID vs ΔTLXMentalnon-COVID = +15.3; 95% CI, 1.0-29.6). CONCLUSIONS: There are indications that registered nurses providing care for coronavirus disease 2019 in the ICU reported increased thermal discomfort coinciding with elevated energy expenditure and a more pronounced self-perception of effort, stress, and mental demand.

Remote Monitoring of Critically-Ill Post-Surgical Patients: Lessons from a Biosensor Implementation Trial.

Biosensors represent one of the numerous promising technologies envisioned to extend healthcare delivery. In perioperative care, the healthcare delivery system can use biosensors to remotely supervise patients who would otherwise be admitted to a hospital. This novel technology has gained a foothold in healthcare with significant acceleration due to the COVID-19 pandemic. However, few studies have attempted to narrate, or systematically analyze, the process of their implementation. We performed an observational study of biosensor implementation. The data accuracy provided by the commercially available biosensors was compared to those offered by standard clinical monitoring on patients admitted to the intensive care unit/perioperative unit. Surveys were also conducted to examine the acceptance of technology by patients and medical staff. We demonstrated a significant difference in vital signs between sensors and standard monitoring which was very dependent on the measured variables. Sensors seemed to integrate into the workflow relatively quickly, with almost no reported problems. The acceptance of the biosensors was high by patients and slightly less by nurses directly involved in the patients' care. The staff forecast a broad implementation of biosensors in approximately three to five years, yet are eager to learn more about them. Reliability considerations proved particularly troublesome in our implementation trial. Careful evaluation of sensor readiness is most likely necessary prior to system-wide implementation by each hospital to assess for data accuracy and acceptance by the staff.