The distribution of acquired peripheral nerve injuries associated with severe COVID-19 implicate a mechanism of entrapment neuropathy: a multicenter case series and clinical feasibility study of a wearable, wireless pressure sensor

We report on a large case series of 34 patients with 66 PNIs associated with survival from severe COVID-19. In majority of these cases there are ≥ 2 PNIs affecting the same person (Table 1). When taken in the context of our literature review of nerve injury case series associated with COVID-19 (n = 5–15 patients/study), plus the predominantly severe/axonal nerve injury characteristics (93% of current cases), these data imply that acquired PNIs are an important contributor to prolonged neurological impairments in survivors of COVID-19. The mechanisms underlying the propensity for PNI in COVID-19 critical illness is difficult to establish, but the anatomical distribution (Fig. 1) of these injuries implicate mechanical forces such as prolonged pressure against bony prominence leading to axonal injury from local ischemia [19]. As a potential strategy to address the risk of prolonged mechanical loading of peripheral nerves in the ICU, we demonstrate the feasibility of a wearable, wireless pressure sensor system to provide real time monitoring at the medial elbow (Fig. 2), which is most common site of compressive neuropathy in severe COVID-19 (Fig. 1).

The risk for focal PNIs in critically ill patients is well known [20], but the incidence has not been defined. In part this may be because these injuries may overlap with ICU-AW and not get the dedicated attention needed to diagnose with imaging [7] or electrodiagnostics [5]. In certain cases, like phrenic nerve injuries, the best diagnostic option may be a neuromuscular ultrasound study [21] but not all hospital systems have access to equipment and expertise for this diagnostic modality. Occasionally nerve compression in severe COVID-19 survivors may be accounted for by a hematoma [7] or an iatrogenic cause such as focal neuritis adjacent to central line site [21] that can be diagnosed by advanced imaging modalities.

Early results in severe COVID-19 survivors from single center case series put the incidence reported incidences between 14.5 and 16% [8, 9]. In the present report we report an incidence for a subset of the patients admitted to a single rehabilitation center of 10.7%, which is slightly lower than these prior reports. There were high rates of diabetes mellitus, obesity, male sex, and older age seen in our cohort which are characteristics of severe COVID-19-related ARDS patients [2], and risk factors for PNI in these patients [19, 22]. On a cellular level, a combination of inflammatory and immune-mediated injury caused by COVID-19 may increase susceptibility to nerve injury when patients have severe disease [23]. There is a paucity of evidence for direct SARS-CoV-2 of peripheral nerves, but this can’t be dismissed as a factor in a small subset of cases. [24]

Our use of wireless pressure sensors to monitor areas of ulnar nerve compression demonstrates a future approach to preventing prone positioning-related nerve injury. The sensors can provide real-time pressure information and can be used to adjust positioning at known compression sites before a compressive neuropathy occurs, while being used for extended periods of time (Fig. 2). Patients with severe COVID-19 appear particularly susceptible to positioning related PNIs [6, 7]. For example, the prone positioning intervention has been recommended for 12 to 16 h per day in mechanically ventilated adults with COVID-19 and refractory hypoxemia [25], but has associated with increase rates of acquired peripheral PNIs [6,7,8, 10,11,12]. Unfortunately, accurate details on ICU course were missing for the majority of patients in this case series since 27 out of 34 patients were diagnosed in free standing rehabilitation hospitals, rather than the original acute care hospitals so we did not attempt to associate PNIs with specific ICU positioning or protocols.

Other limitations of this study include lack of a control group, and the retrospective design, which precludes establishment of a causal relationship between patient positioning and peripheral nerve injury. Additionally, some patients with less severe PNIs may not have had advanced imaging or electrodiagnostic studies ordered, which may have led to a bias towards more severe PNIs and underestimation of PNI incidence.

Given the ongoing COVID-19 pandemic, and risks of new variants causing a resurgence of hospital admissions, further attention should be paid to the long-term sequela including PNIs. These injuries require long-term follow up and care with therapy and rehabilitation. Prevention and early identification of these injuries could help decrease additional morbidity of the disease. This study shows how the most common sites for nerve injury in severe COVID-19 patients map to known nerve entrapment sites vulnerable to mechanical loading (e.g. elbow, knee, ischium etc.), which highlights the handful of key anatomical locations that require extra attention to protect nerve health in the hospital setting as well as demonstrates the feasibility of a wearable, wireless pressure sensing system that can provide real time feedback in the ICU setting.

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