Read on for our highlighted selection of Covid-related cross-sectional case control studies from the scientific press for April 2022:
- Short- and long-term outcome and predictors in an international cohort of patients with neuro-COVID-19
- SARS-CoV-2 is associated with changes in brain structure in UK Biobank
- Cellular and humoral immunity to SARS-CoV-2 infection in multiple sclerosis patients on ocrelizumab and other disease-modifying therapies: a multi-ethnic observational study
- Trends in Mortality Rates Among Medicare Enrollees With Alzheimer Disease and Related Dementias Before and During the Early Phase of the COVID-19 Pandemic (Submitted by the EAN Scientific Panel on Dementia and Cognitive Disorders)
Short- and long-term outcome and predictors in an international cohort of patients with neuro-COVID-19
Despite the increasing number of reports on the spectrum of neurological manifestations of COVID-19 (neuro-COVID), few studies have assessed short- and long-term outcome of the disease. This cohort study enrolled adult patients with neuro-COVID seen in neurological consultation. Data were collected prospectively or retrospectively in the European Academy of Neurology NEuro-covid ReGistrY ((ENERGY). The outcome at discharge was measured using the modified Rankin Scale and defined as ‘stable/improved’ if the modified Rankin Scale score was equal to or lower than the pre-morbid score, ‘worse’ if the score was higher than the pre-morbid score. Status at 6 months was also recorded. Demographic and clinical variables were assessed as predictors of outcome at discharge and 6 months. From July 2020 to March 2021, 971 patients from 19 countries were included. 810 (83.4%) were hospitalized. 432 (53.3%) were discharged with worse functional status. Older age, stupor/coma, stroke and intensive care unit (ICU) admission were predictors of worse outcome at discharge. 132 (16.3%) died in hospital. Older age, cancer, cardiovascular complications, refractory shock, stupor/coma and ICU admission were associated with death. 262 were followed for 6 months. Acute stroke or ataxia, ICU admission and degree of functional impairment at discharge were predictors of worse outcome. 65/221 hospitalized patients (29.4%) and 10/32 non-hospitalized patients (24.4%) experienced persisting neurological symptoms/signs. 10/262 patients (3.8%) developed new neurological complaints during the 6 months of follow-up. The authors concluded that neuro-COVID is a severe disease associated with worse functional status at discharge, particularly in older subjects and those with comorbidities and acute complications of infection.
Beghi E, Helbok R, Ozturk S, Karadas O, Lisnic V, Grosu O, Kovács T, Dobronyi L, Bereczki D, Cotelli MS, Turla M, Davidescu EI, Popescu BO, Valzania F, Cavallieri F, Ulmer H, Maia LF, Amodt AH, Armon C, Brola W, Victoria G, Riahi A, Krehan I, von Oertzen T, Azab MA, Crean M, Lolich M, Lima MJ, Sellner J, Perneczky J, Jenkins T, Meoni S, Bianchi E, Moro E, Bassetti CLA; ENERGY Study Group. Short- and long-term outcome and predictors in an international cohort of patients with neuro-COVID-19. Eur J Neurol. 2022 Feb 23. doi: 10.1111/ene.15293.
SARS-CoV-2 is associated with changes in brain structure in UK Biobank
There is strong evidence for brain-related abnormalities in COVID-19. It remains unknown however whether the impact of SARS-CoV-2 infection can be detected in milder cases, and whether this can reveal possible mechanisms contributing to brain pathology. In this article the authors investigated brain changes in 785 UK Biobank participants (aged 51–81) imaged twice, including 401 cases who tested positive for infection with SARS-CoV-2 between their two scans, with 141 days on average separating their diagnosis and second scan, and 384 controls. The availability of pre-infection imaging data reduces the likelihood of pre-existing risk factors being misinterpreted as disease effects. The authors identified significant longitudinal effects when comparing the two groups, including: (i) greater reduction in grey matter thickness and tissue-contrast in the orbitofrontal cortex and parahippocampal gyrus, (ii) greater changes in markers of tissue damage in regions functionally-connected to the primary olfactory cortex, and (iii) greater reduction in global brain size. The infected participants also showed on average larger cognitive decline between the two timepoints. Importantly, these imaging and cognitive longitudinal effects were still seen after excluding the 15 cases who had been hospitalised. These mainly limbic brain imaging results may be the in vivo hallmarks of a degenerative spread of the disease via olfactory pathways, of neuroinflammatory events, or of the loss of sensory input due to anosmia. Whether this deleterious impact can be partially reversed, or whether these effects will persist in the long term, remains to be investigated with additional follow up.
Douaud, G., Lee, S., Alfaro-Almagro, F. et al. SARS-CoV-2 is associated with changes in brain structure in UK Biobank. Nature (2022). https://doi.org/10.1038/s41586-022-04569-5.
Cellular and humoral immunity to SARS-CoV-2 infection in multiple sclerosis patients on ocrelizumab and other disease-modifying therapies: a multi-ethnic observational study
To determine the impact of MS disease-modifying therapies (DMTs) on the development of cellular and humoral immunity to SARS-CoV-2 infection.
MS patients aged 18-60 were evaluated for anti-nucleocapsid and anti-Spike RBD antibody with electro-chemiluminescence immunoassay; antibody responses to Spike protein, RBD, N-terminal domain with multiepitope bead-based immunoassays (MBI); live virus immunofluorescence-based microneutralization assay; T-cell responses to SARS-CoV-2 Spike using TruCulture ELISA; and IL-2 and IFNγ ELISpot assays. Assay results were compared by DMT class. Spearman correlation and multivariate analyses were performed to examine associations between immunologic responses and infection severity. Between 1/6/2021 and 7/21/2021, 389 MS patients were recruited (mean age 40.3 years; 74% female; 62% non-White). Most common DMTs were ocrelizumab (OCR) – 40%; natalizumab – 17%, Sphingosine 1-phosphate receptor (S1P) modulators -12%; and 15% untreated. 177 patients (46%) had laboratory evidence of SARS-CoV-2 infection; 130 had symptomatic infection, 47 – asymptomatic. Antibody responses were markedly attenuated in OCR compared to other groups (p≤0.0001). T-cell responses (IFNγ) were decreased in S1P (p=0.03), increased in natalizumab (p<0.001), and similar in other DMTs, including OCR. Cellular and humoral responses were moderately correlated in both OCR (r=0.45, p=0.0002) and non-OCR (r=0.64, p<0.0001). Immune responses did not differ by race/ethnicity. COVID-19 clinical course was mostly non-severe and similar across DMTs; 7% (9/130) were hospitalized. The authors concluded that DMTs had differential effects on humoral and cellular immune responses to SARS-CoV-2 infection. Immune responses did not correlate with COVID-19 clinical severity in this relatively young and non-disabled group of MS patients.
Ilya Kister, Yury Patskovsky, Ryan Curtin, Jinglan Pei, Katherine Perdomo, Zoe Rimler, Iryna Voloshyna, Marie I. Samanovic, Amber R. Cornelius, Yogambigai Velmurugu, Samantha Nyovanie, Joseph Kim, Ethan Tardio, Tamar E. Bacon, Lana Zhovtis Ryerson, Pranil Raut, Pedotti Rosetta, Kathleen Hawker, Catarina Raposo, Jessica Priest, Mark Cabatingan, Ryan C. Winger, Mark J. Mulligan, Michelle Krogsgaard, Gregg J. Silverman. Cellular and humoral immunity to SARS-CoV-2 infection in multiple sclerosis patients on ocrelizumab and other disease-modifying therapies: a multi-ethnic observational study. Annals of Neurology. First published: 15 March 2022 https://doi.org/10.1002/ana.26346.
Trends in Mortality Rates Among Medicare Enrollees With Alzheimer Disease and Related Dementias Before and During the Early Phase of the COVID-19 Pandemic
The authors compared mortality rates in 2020 (March-December) with rates in 2019 for the same period among 53 640 888 Medicare enrollees > 65-year-old, categorized into 4 prespecified cohorts: enrollees with or without Alzheimer’s Disease and related Dementias (ADRD), and enrollees with or without ADRD residing in nursing homes. Estimates were age and sex-adjusted, and by using largely overlapping populations during 2019 and 2020 within each of the 306 hospital referral regions analysed, underlying initial health conditions and other potential confounders were considered as being implicitly accounted for. Compared with 2019, mortality in 2020 was 12.4% higher among enrollees without ADRD and 25.7% higher among enrollees with ADRD. Higher rates in 2020 were seen in Asian (36.0%), Black (36.7%), and Hispanic (40.1%) populations with ADRD, with similar rates seen also in subjects without ADRD. Among nursing home residents without ADRD mortality was 24.2% higher, and among nursing home residents with ADRD mortality was 33.4% higher. In areas with low COVID-19 prevalence (lowest quintile for COVID-19 infections in 2020), there was no excess mortality among enrollees without ADRD, but 8.8% higher mortality among community-dwelling enrollees with ADRD and 14.2% higher mortality among enrollees with ADRD living in nursing homes.
Gilstrap L, Zhou W, Alsan M, Nanda A, Skinner JS. Trends in Mortality Rates Among Medicare Enrollees With Alzheimer Disease and Related Dementias Before and During the Early Phase of the COVID-19 Pandemic. JAMA Neurol. Published online February 28, 2022. doi:10.1001/jamaneurol.2022.0010.