Asymmetric Cerebral Perfusion in Comatose Extracorporeal Membrane Oxygenation Patients

Asymmetric cerebral perfusion can occur when extracorporeal membrane oxygenation (ECMO) flow competes with native cardiac circulation. It is unclear whether this phenomenon associates with brain injury. Diffuse correlation spectroscopy (DCS) provides continuous, laser-based, non-invasive, bedside monitoring of relative cerebral blood flow (rCBF). This study measured rCBF in ECMO patients via DCS to determine whether comatose patients experience asymmetric cerebral perfusion. Adults receiving ECMO for any indication were prospectively recruited from 12/2019-3/2021. Patients with prior neurologic injury, scalp/facial lacerations, and SARS-CoV-2 infection were excluded. DCS monitoring was performed daily during ECMO support with sensors placed on bilateral foreheads. Mean arterial pressure (MAP) was continuously recorded from the bedside monitor. The Glasgow Coma Scale (GCS) was assessed by clinical staff multiple times daily with sedation pauses, if possible, per standard of care. rCBF was calculated by comparing continuous cerebral blood flow (CBF) measurements to the daily median CBF, then averaged at each MAP value. Daily rCBF asymmetry was calculated by summing the absolute difference of rCBF between the two hemispheres at each MAP value, normalized for the total MAP range experienced by the patient that day. Twelve subjects were enrolled in this study (ages 21-78, 6 with cardiac arrest, 4 with acute heart failure, 2 with ARDS) and grouped by maximum GCS motor (GCS-M) score during ECMO, with 3 "comatose" subjects (GCS-M <= 4), and 9 "awake" subjects (GCS-M > 4). DCS was performed over 66 sessions with a mean duration of 131.83 +/- 1.13 minutes. Comatose subjects exhibited more rCBF asymmetry than awake subjects (0.28 +/- 0.06 mmHg-1 vs. 0.10 +/- 0.001 mmHg-1, p=0.045). No difference in asymmetry was noted between patients with or without cardiac arrest. We found that comatose ECMO subjects exhibited higher inter-hemispheric rCBF asymmetry over a range of blood pressures than awake subjects. Though our comatose sample is small, further validation of this finding and its causes, such as cerebrovascular dysregulation, is warranted.

Detection of Infectious SARS-CoV-2 in Specimens with High CT Values Is More Common for Omicron than for Delta Variants

Background. Although not validated, cycle threshold (Ct) values from real-time (r)RT-PCR are sometimes used as a proxy for infectiousness to inform public health decision-making. A better understanding of variant-specific viral dynamics, including RNA and infectious virus relationships, is needed to clarify implications for diagnostics and transmission. Methods. Non-hospitalized SARS-CoV-2-infected individuals were recruited <= 5 days post-onset and self-collected nasal swabs daily for two weeks. Sequencing was used to determine variant, an in-house quantitative rRT-PCR targeting N gene was used to produce Ct values and determine RNA load, and cytopathic effect was used to assess the presence or absence of infectious virus (binary outcome). We used a Ct threshold of 30 to define high-Ct (Ct > 30) or low-Ct (Ct <= 30) specimens and assessed the percentage of RNA-positive specimens that had infectious virus;variantspecific percentages were compared by chi2 test. Results. We included 113 and 200 RNA-positive specimens from 18 and 28 Omicron- and Delta-infected participants, respectively;timing of RNA-positive specimen collection was similar in both groups (median = 8d post-onset). Maximum observed RNA levels occurred at median of 5 days post-onset for both variants but were lower for participants with Omicron vs Delta [mean RNA copies/mL = 105.2 vs 107.9]. Despite lower RNA levels, infectious virus was frequently detected for both variants [Omicron: median duration = 4.5d;Delta: median = 6d;p = 0.13]. Omicron specimens with infectious virus had higher Cts vs Delta specimens [mean Ct = 29.9 vs 23.2, p < 0.001]. In high-Ct specimens (Ct > 30;Table), the percentage of specimens with infectious virus was typically higher for Omicron vs Delta, and was significantly higher in adults [27.3% vs 9.5%]. In low-Ct specimens (Ct <= 30), the percentage with infectious virus was similar or higher for Omicron vs Delta, and was significantly higher in children [87.5% vs 53.8%] and in those unvaccinated [94.1% vs 47.4%]. Conclusion. CDC does not recommend the use of Ct values as a proxy for infectiousness. These data further highlight that Ct values may not provide a reliable or consistent proxy for infectiousness across variants.

Biological Determinants of Post-Acute Sequelae of SARS-CoV-2

Background. The biological determinants of post-acute sequelae of SARS-CoV-2 infection (PASC), defined as the persistence or recurrence of symptoms not explained by an alternative medical diagnosis, are poorly understood. We assessed viral and immunological determinants during acute SARS-CoV-2 infection for an association with PASC at 4 to 8 months. Methods. From September 2020 to February 2022, symptomatic nonhospitalized individuals with laboratory-confirmed SARS-CoV-2 infection were identified within 5 days of symptom onset. We used anterior nasal biospecimens to measure the magnitude and duration of RNA and infectious viral shedding as well as blood samples to measure soluble markers of inflammation during the acute phase (first 28 days post-enrollment). PASC was defined as self-report of 1 or more COVID-19 attributed symptoms between 4 and 8 months after initial illness. We compared virologic and inflammatory markers, GFAP (a marker of neuronal damage) and neutralizing antibody levels from the acute phase between those with and without PASC using Mann-Whitney U tests or repeated measures mixed effects linear models. Results. Among 71 SARS-CoV-2-positive participants with a completed follow-up visit between 4 to 8 months, we included 69 with virologic data and 61 with inflammatory marker data. Median age was 37 (IQR: 29 to 48) Overall, 16/72 (23%) reported at least one qualifying PASC symptom. Report of PASC was associated with >9 days of RNA shedding (p=0.04);all participants stopped RNA shedding by day 20. During acute illness, those with subsequent PASC had increased levels of INF-alpha, INF-gamma, IP-10, IL-10, and MCP-1;these differences were greatest in the early period and normalized over 2 to 3 weeks post-illness onset. Compared to those without PASC, during the acute illness those with PASC had increased levels of GFAP and decreased levels of neutralizing antibodies but these differences were not statistically significant. Conclusion. We found indications that viral and immunological factors during acute illness may be associated with PASC, suggesting acute immunologic response to SARS-CoV-2 may have longer term effects and play a role in PASC. Further understanding of the clinically significance of these observations is needed.

Fall prevention among veterans in a skilled nursing facility

Background: In skilled nursing facilities (SNF), 50-70% of residents fall per year. SNF residents with dementia are more prone to fall, with an annual incidence of 60%. The Community Living Center (CLC) at the San Francisco Veterans Affairs Medical Center (SFVAMC), reported annual fall rate of 50%, compared to the national VA fall rate of 42%. Our goal was to reduce the rate of fall by 20% compared to fiscal year 2019. Methods: We conducted process mapping with CLC interdisciplinary team members to identify barriers to fall prevention. The barriers included staff, patient population-specific challenges, environmental obstacles, and documentation, communication, and care protocol. Studies have shown that multi-pronged approaches yield the best results. We implemented 3 interventions: fall education, purposeful huddles, and toilet seat risers. Physical therapists and occupational therapists stated that low toilet seats were fall risk for Veterans. Results: We partnered with the CLC's nurse educator to adapt the “5 P's Proactive Patient Rounding” education tool as a pocket card for the CLC nursing staff. By end of May 2020, all CLC nurses were educated in these 5 P's and fall prevention. Watch List Huddle was started in January 2020, to discussed care plans for residents who nurses were concerned about. Every resident who fell were discussed during these rounds which met three times a week. Lastly, toilet seat risers were placed in each bathroom in July 2020. Implementation of our interventions lead to 40% decrease in the average number of falls. Conclusion: Re-training in fall prevention, improving communication and care plan after fall and raising the toilet seats significantly reduce the rate of falls by 40%. This result was much larger than our goal 20% reduction. An increase in nursing staff hiring and a decreased census within the CLC due to COVID-19 quarantine may have contributed to better than expected outcome.