Heterologous COVID-19 Booster Vaccination in the Chronic Disorder of Consciousness: A Pilot Study.

Significant anti-spike protein receptor-binding domain (S-RBD) antibody responses have been demonstrated in patients with chronic disorder of consciousness (DOC) completing a COVID-19 vaccine regime with BNT162b2 (Pfizer-BioNTech). We now provide further prospective data on the immunogenicity of these patients followed by heterologous booster injection with mRNA-1273 (Moderna). These patients were compared with two different demographically comparable healthcare workers (HCW) groups who underwent homologous booster injection with BNT162b2 vaccine or heterologous booster injection with mRNA-1273. Antibody responses were evaluated at 21 days after the administration of the booster dose of vaccination. Results: No severe adverse reactions were reported after each type of vaccination. Heterologous boosting with mRNA-1273 elicited a higher increase of S-RBD IgG levels than homologous boosting with BNT162b2 both in DOC patients and HCW who had previously received two doses of BNT162b2. No significant difference was detected between DOC and HCW patients who received heterologous boosting. Conclusions: Despite the small sample size, our preliminary results suggest that heterologous boosting with mRNA-1273, following initial vaccination with BNT162b2, is safe and tends to be more immunogenic than homologous boosting, either in fragile people or in healthy controls.

Anti-SARS-CoV-2 S-RBD IgG Antibody Responses after COVID-19 mRNA Vaccine in the Chronic Disorder of Consciousness: A Pilot Study.

OBJECTIVE: In the last year, a large amount of research has investigated the anti-spike protein receptor-binding domain (S-RBD) antibody responses in patients at high risk of developing severe acute respiratory syndrome because of COVID-19 infection. However, no data are available on the chronic disorder of consciousness (DOC). METHODS: Here, we evaluated anti-S-RBD IgG levels after vaccination in chronic DOC patients compared with demographically matched healthy controls (HC) by indirect chemiluminescence immunoassay. All individuals completed a two-dose-cycle vaccination with Pfizer mRNA vaccine (BNT162b2), and antibody responses were evaluated at 30 and 180 days after the administration of the second dose of vaccination. RESULTS: We compared 32 DOC patients with 34 demographically matched healthy controls. Both DOC and HC groups showed a similar antibody response at 30 days, whereas at follow-up (180 days) DOC patients were characterized by lower S-RBD IgG levels with respect to controls. Additional multiple regression analyses including demographical and clinical comorbidities as predictors revealed that age was the only factor associated with the decrease in S-RBD IgG levels at follow-up (180 days). Elderly individuals of both groups were characterized by a reduction in the antibody responses with respect to younger individuals. CONCLUSIONS: Our results show an efficacy seroconversion in DOC patients in the first period after vaccination, which significantly declines over time with respect to healthy controls.

COVID-19 and hospital restrictions: physical disconnection and digital re-connection in disorders of consciousness.

Purpose: The coronavirus disease 2019 (COVID-19) pandemic forced hospitals to adopt tighter restrictions, the most impacting is no access to visitors. Disorder of consciousness (DOC) due to severe acquired brain injury is a condition needing neurorehabilitation and the role of relatives is essential, hence besides physical "disconnection" digital "re-connection" is crucial. We aimed to assess whether digital communication benefits in patients with DOC, considering the sensorial and emotional deprivation due to the COVID-19 emergency lock-down.Methods: For eleven consecutive patients with DOC admitted to our Intensive Neurorehabilitation Care (mean age: 45; females: 9), two observers registered neurobehavioral changes during a video-calls with their relatives. Heart-rate variability was measured before and during the calls. The video-call was performed by using two displays of different sizes: tablet (T-video-call) and large screen (LS-Video-call).Results: The video-calls impacted on the patients' vigilance and in the relationship with relatives. Moreover, positively impacted on their relatives. The current results showed significant greater impact on patients during the LS-video-call than when they are exposed to T-video-call.Conclusions: During the COVID-19 pandemic, besides the physical disconnection to stop the contagion spread, a "digital re-connection" is needed for all and especially for fragile population groups as patients with DOC.

Letter to the editor: COVID in patients with brain injury with a disorder of consciousness: a pathogenetic theory.

We recently published in this journal (Caronni and colleagues, Brain Injury, 2021-04-16) the first description of the spread of the SARS-CoV-2 infection in a cohort of brain injured patients with a disorder of consciousness (DOC). Surprisingly enough we showed that, in these patients, the COVID was moderate and did not result in fatalities. The pathogenesis of the COVID is characterized by the profound dysregulation of the immune system. To explain our findings, we speculated that the immunosuppression due to the brain injury could be protective against the development of the COVID in patients with DOC. More recently, a second group of authors (Marino and colleagues, PLoSOne, 2021-06-30) described the course of the COVID in an independent cohort of patients with DOC. Since our results were quite unexpected, we have been very comforted by the data reported by Marino and colleagues. Moreover, these data also offer a unique opportunity to further evaluate our theory regarding the COVID pathogenesis in patients with DOC. In the current Letter to the Editor it is shown that the independent data presented by Marino and colleagues do support our theory. Waiting for larger cohorts to further test it (and in case falsify it), our interpretation seems to remain valid.

COVID-19 Related Acute Hemorrhagic Necrotizing Encephalitis: A Report of Two Cases and Literature Review.

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel coronavirus, has proven neurotropism and causes a multitude of neurologic manifestations. Acute hemorrhagic necrotizing encephalitis (AHNE), though rare, can be seen in patients with severe infection and is associated with devastating neurologic outcomes. The true prevalence of this syndrome is unknown due to underrecognition, difficulty in timely acquisition of neuroimaging, and high mortality in this subset of patients escaping detection. It is a distinct clinicoradiological syndrome, with patients suffering from rapidly worsening encephalopathy and coma within the first two weeks of severe illness and hemorrhagic necrotizing parenchymal changes on neuroimaging. The pathophysiology of this syndrome is unclear but hypothesized to occur due to cytokine storm, blood-brain-barrier dysfunction, and direct viral-mediated endotheliopathy. Diagnosis requires a high index of suspicion in patients who have unexplained persistent severe encephalopathy associated with COVID-19 infection. Most patients have elevated systemic inflammatory markers and severe lung disease with hypoxic respiratory failure requiring mechanical ventilation. MRI is the imaging modality of choice, with a distinct neuroimaging pattern. CSF (cerebrospinal fluid) studies have a low yield for viral particle detection with currently available testing. While long-term outcomes are unclear, early immunomodulatory treatment with intravenous immunoglobulin, plasma exchange, and steroids may portend a favorable outcome. We discuss two cases of COVID-19 related AHNE and also include a pertinent literature search of similar cases in PubMed to consolidate the AHNE clinical syndrome, neuroimaging characteristics, management strategies, and reported short-term prognosis.

Clinical course of SARS-CoV-2 infection in patients with severe acquired brain injury and a disorder of consciousness: an observational study.

Purpose: SARS-CoV-2 infection can cause the coronavirus disease (COVID), ranging from flu-like symptoms to interstitial pneumonia. Mortality is high in COVID pneumonia and it is the highest among the frailest. COVID could be particularly serious in patients with severe acquired brain injury (SABI), such as those with a disorder of consciousness. We here describe a cohort of patients with a disorder of consciousness exposed to SARS-CoV-2 early after their SABI.Materials and methods: The full cohort of 11 patients with SABI hospitalized in March 2020 in the IRCCS Fondazione Don Gnocchi rehabilitation (Milan, Italy) was recruited. Participants received SARS-CoV-2 testing and different clinical and laboratory data were collected.Results: Six patients contracted SARS-CoV-2 and four of them developed the COVID. Of these, one patient had ground-glass opacities on the chest CT scan, while the remaining three developed consolidations. No patient died and the overall respiratory involvement was mild, requiring in the worst cases low-flow oxygen.Conclusions: Here we report the clinical course of a cohort of patients with SABI exposed to SARS-CoV-2. The infection spread among patients and caused COVID in some of them. Unexpectedly, COVID was moderate, caused at most mild respiratory distress and did not result in fatalities.