key: cord-0729801-6bt9kzqr authors: Nersesjan, V.; Amiri, M.; Lebech, A.-M.; Roed, C.; Mens, H.; Russell, L.; Fonsmark, L.; Berntsen, M.; Sigurdsson, S. T.; Carlsen, J.; Langkilde, A.; Martens, P.; Lund, E. L.; Hansen, K.; Jespersen, B.; Folke, M. N.; Meden, P.; Hejl, A.-M.; Warmberg, C.; Benros, M.; Kondziella, D. title: Central and peripheral nervous system complications of COVID-19: A prospective tertiary center cohort with 3-month follow-up date: 2020-11-17 journal: nan DOI: 10.1101/2020.11.15.20231001 sha: 983c2c6fea94904dfa487719f9622fe0bc4ce972 doc_id: 729801 cord_uid: 6bt9kzqr Objective: To systematically describe CNS and PNS complications in hospitalized COVID-19 patients. Methods: We conducted a prospective, consecutive, observational study of adult patients from a tertiary referral center with confirmed COVID-19. All patients were screened daily for neurological and neuropsychiatric symptoms during admission, at discharge and at 3-month follow-up. We classified complications as caused by SARS-CoV-2 neurotropism, immune-mediated or critical illness-related. Results: From April-September 2020, we enrolled 61 consecutively admitted COVID-19 patients, 35 (57%) of whom were referred to ICU for respiratory failure. Evaluation revealed a higher frequency of CNS/PNS symptoms in ICU patients compared to non-ICU patients. The most common CNS complication was encephalopathy (n=22, 36.1%), which was severe in 13 patients (GCS[≤]12), including 8 with akinetic mutism. Length of ICU admission was an independent predictor of encephalopathy (OR=1.23). Other CNS complications included ischemic stroke, a biopsy-proven acute necrotizing encephalitis, and transverse myelitis. The most common PNS complication was critical illness polyneuromyopathy (13.1%), with prolonged ICU stay as independent predictor (OR=1.14). Treatment-related PNS complications included meralgia paresthetica. Of 41 complications in total, 3 were classified as para/post-infectious. The remainder included cases secondary to critical illness or other causes (n=34) or without sufficient investigations (n=4). Cerebrospinal fluid was negative for SARS-CoV-2 RNA in all 5 patients investigated. Conclusions: CNS/PNS complications were common in hospitalized COVID-19 patients, particularly in ICU patients, and often attributable to critical illness. In cases with COVID-19 as the primary cause for neurological disease, there were no signs of viral neurotropism, but laboratory changes suggested autoimmune-mediated mechanisms. A prospective tertiary center cohort with 3-month follow-up T o s y s t e m a t i c a l l y d e s c r i b e C N S a n d P N S c o m p l i c a t i o n s i n h o s p i t a l i z e d C O V I D -1 9 p a t i e n t V I D -1 9 p a t i e n t s , p a r t i c u l a r l y i n I C U p a t i e n t s , a n d o f t e n a t t r i b u t a b l e t o c r i t i c a l i l l n e s s . I n c a s e s w i t h C O V I D -1 9 a s t h e p r i m a r y c a u s e f o r n e u r o l o g i c a l d i s e a s e , t h e r e w e r e n o s i g n s o f v i r a l n e u r o t r o p i s m , b u t l a b o r a t o r y c h a n g e s s u g g e s t e d a u t o i m m u n e -m e d i a t e d m e c h a n i s m s . 1 . I n t r o d u c t i o n C e n t r a l ( C N S ) a n d p e r i p h e r a l ( P N S ) n e r v o u s s y s t e m m a n i f e s t a t i o n s c a n o c c u r d u r i n g a n d a f t e r c o r o n a v i r u s d i s e a s e 2 0 1 9 ( C O V I D -1 9 ) [ 1 -6 ] , b u t t h e u n d e r l y i n g m e c h a n i s m s , t h e s e m i o l o g y a n d t h e f r e q u e n c y o f t h e s e c o m p l i c a t i o n s r e m a i n p o o r l y u n d e r s t o o d [ 7 , 8 ] . w e c o n d u c t e d a p r o s p e c t i v e o b s e r v a t i o n a l s t u d y o f a c o m p l e t e a n d c o n s e c u t i v e s a m p l e o f C O V I D -1 9 p a t i e n t s f r o m a t e r t i a r y r e f e r r a l c e n t e r , i n c l u d i n g 3 -m o n t h f o l l o w -u p . O u r a i m w a s t o d e s c r i b e t h e f r e q u e n c y a n d p h e n o m e n o l o g y o f C N S a n d P N S c o m p l i c a t i o n s , a s w e l l a s t h e i r p r e s u m e d o r i g i n a s d e t e r m i n e d b y n e u r o l o g i c a l w o r k -u p , d u r i n g a n d a f t e r S A R S -C o V -2 i n f e c t i o n . T h e p r i m a r y e n d p o i n t s w e r e t h e n u m b e r , c l i n i c a l p h e n o t y p e s a n d m e c h a n i s m s i n p a t i e n t s w i t h C O V I D -1 9 -r e l a t e d C N S a n d P N S c o m p l i c a t i o n s c o m p a r e d t o a l l p a t i e n t s a d m i t t e d w i t h C O V I D -1 9 . W e h y p o t h e s i z e d t h a t t h e s e c o m p l i c a t i o n s w o u l d b e m o r e f r e q u e n t a n d s e r i o u s i n t h e m o s t s e v e r e l y a f f e c t e d C O V I D -1 9 p a t i e n t s a n d t h a t i m m u n e -m e d i a t e d a n d t r e a t m e n t -r e l a t e d c o m p l i c a t i o n s w o u l d b e m o r e p r e v a l e n t t h a n t h o s e r e l a t e d t o S A e p t e m b e r 2 0 2 0 , w e p r o s p e c t i v e l y e n r o l l e d S A R S -C o V -2 p o s i t i v e p a t i e n t s ≥ 1 8 y e a r s o f a g e , a d m i t t e d t o R i g s h o s p i t a l e t , C o p e n h a g e n U n i v e r s i t y H o s p i t a l , a t e r t i a r y r e f e r r a l c e n t e r i n C o p e n h a g e n , D e n m a r k . P a t i e n t s w e r e e n r o l l e d f r o m t h e h o s p i t a l ' s n e w l y e s t a b l i s h e d C O V I D -1 9 i n t e n s i v e c a r e u n i t ( C O V I T A ) , t h e C O V I D -1 9 i n t e r m e d i a t e c a r e u n i t ( C O V I M A ) a n d t h e n e u r o l o g i c a l d e p a r t m e n t . T w o o f t h e a u t h o r s ( V N , M A ) , s u p e r v i s e d b y a b o a r d -c e r t i f i e d n e u r o l o g i s t w i t h e x p e r i e n c e i n n e u r o c r i t i c a l c a r e ( D K ) , s c r e e n e d a l l t h r e e . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) preprint d e p a r t m e n t s e a c h m o r n i n g f o r n e w l y a d m i t t e d p a t i e n t s w i t h C O V I D -1 9 . A l l i n c l u d e d p a t i e n t s h a d p o s i t i v e S A R S -C o V -2 p o l y m e r a s e -c h a i n r e a c t i o n ( P C R ) b y n a s o p h a r y n g e a l / t r a c h e a l t e s t i n g , e x c e p t f o r 1 p a t i e n t i n w h o m a c l i n i c a l s u s p i c i o n o f C O V I D -1 9 w a s c o n f i r m e d 2 7 d a y s a f t e r s y m p t o m o n s e t b y a s t r o n g l y p o s i t i v e S A R S -C o V -2 I g G a n t i b o d y t i t e r . W e f o l l o w e d a l l p a t i e n t s p r o s p e c t i v e l y f r o m t h e t i m e o f e n r o l l m e n t t o d i s c h a r g e a n d 3 -m o n t h f o l l o w -u p o r d e a t h . P a t i e n t s w e r e p r o s p e c t i v e l y s c r e e n e d f o r n e u r o l o g i c a l a n d p s y c h i a t r i c s y m p t o m s d u r i n g a d m i s s i o n s a t C O V I T A a n d C O V I M A a n d e v a l u a t e d f o r c o g n i t i v e s t a t u s a n d n e u r o l o g i c a l d e f i c i t s a t d i s c h a r g e . P a t i e n t s e n r o l l e d f r o m t h e n e u r o l o g i c a l d e p a r t m e n t w e r e s c r e e n e d f o r s u s p e c t e d n e u r o l o g i c a l c o m p l i c a t i o n s d u r i n g / a f t e r a C O V I D -1 a p p r o p r i a t e , s e d a t e d I C U p a t i e n t s w e r e a s s e s s e d f o l l o w i n g a w a k e -u p c a l l a n d c a t e g o r i z e d a s s h o w i n g e i t h e r ' r a p i d r e c o v e r y ' , ' s l o w a w a k e n i n g ' ( d e f i n e d a s p r o l o n g e d r e c o v e r y f o l l o w i n g > 2 4 h c l i n i c a l u n r e s p o n s i v e n e s s a f t e r s t o p o f s e d a t i o n ) a n d ' n o a w a k e n i n g ' ( d e f i n e d a s c o m a o r v e g e t a t i v e s t a t e / u n r e s p o n s i v e w a k e f u l n e s s s y n d r o m e p e r s i s t i n g f o r ≥ 2 4 h ) . I I . C o m p l a i n t s o f h e a d a c h e a n d s o m a t o s e n s o r y s y m p t o m s , i . e . a n o s m i a a n d / o r a g e u s i a , p a i n , a n d p a r e s t h e s i a . I I I . C o g n i t i v e d e f i c i t s , m o t o r p a l s i e s , s e n s o r y d e f i c i t s , c r a n i a l n e r v e d e f i c i t s a n d c e r e b e l l a r a f f e c t i o n ( e . g . a t a x i a o r n y s t a g m u s ) a s d e t e r m i n e d b y c l i n i c a l n e u r o l o g i c a l e x a m . I V . S e i z u r e s , i r r e s p e c t i v e o f s u p p o s e d o r i g i n ( i . e . e p i l e p t i c v e r s u s n o n -e p i l e p t i c ) . V . P r e s e n c e o f d e l i r i u m , d e f i n e d a s p r e s e n c e o f a u d i t o r y o r v i s u a l h a l l u c i n a t i o n s , d e l u s i o n a l t h o u g h t s s u c h a s p a r a n o i a , p s y c h o m o t o r a g i t a t i o n o r r e d u c t i o n a n d / o r f l u c t u a t i n g c o n s c i o u s n e s s w i t h d i s o r i e n t a t i o n . V I . E m o t i o n a l l a b i l i t y d e f i n e d a s e x a g g e r a t e d o r u n c o n t r o l l a b l e l a u g h i n g , c r y i n g o r a n g e r d i s p r o p o r t i o n a t e t o t h e c i r c u m s t a n c e s . F u r t h e r , w e c o l l e c t e d r o u t i n e c l i n i c a l a n d l a b o r a t o r y d a t a i n c l u d i n g a g e , s e x , m e d i c a t i o n , p r e v i o u s m e d i c a l h i s t o r y , a n d r e s u l t s f r o m b r a i n i m a g i n g ( C T o r M R I ) d u r i n g a d m i s s i o n , c e r e b r o s p i n a l f l u i d ( C S F ) r e s u l t s , e l e c t r o e n c e p h a l o g r a p h y ( E E G ) f i n d i n g s , n e r v e c o n d u c t i o n s s t u d i e s ( E N G ) a n d e l e c t r o m y o g r a p h y ( E M G ) , a s w e l l a s m o d i f i e d R a n k i n S c a l e ( m R S ) p r i o r t o a d m i s s i o n , a t d i s c h a r g e a n d a t 3 -m o n t h f o l l o w -u p . T w o b o a r d -c e r t i f i e d n e u r o r a d i o l o g i s t s s y s t e m a t i c a l l y r e -e v a l u a t e d a l l c l i n i c a l n e u r o i m a g i n g ( i f p r e s e n t ) o f a l l e n r o l l e d p a t i e n t s d u r i n g a d m i s s i o n a n d a f t e r d i s c h a r g e , i n c l u d i n g C T , C T a n g i o g r a p h y a n d M R I , a c c o r d i n g t o a p r e s p e c i f i e d p r o t o c o l , c l a s s i f y i n g b u r d e n , l o c a l i z a t i o n , a n d ( p o s s i b l e ) e t i o l o g y o f a c u t e a n d c h r o n i c ( i . e . u n r e l a t e d t o t h e p r e s e n t a d m i s s i o n ) . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) preprint The copyright holder for this this version posted November 17, 2020. ; https://doi.org/10.1101/2020.11.15.20231001 doi: medRxiv preprint e n t s h a d d e l i r i u m d u r i n g a d m i s s i o n l a s t i n g 7 . 1 d a y s ( m e a n , s t a n d a r d d e v i a t i o n ( S D ) 6 . 9 ) , w h i c h w a s s i g n i f i c a n t l y m o r e f r e q u e n t i n I C U -p a t i e n t s ( 5 4 . 3 % ) c o m p a r e d t o n o n -I C U p a t i e n t s ( 7 . 7 % ) , . . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) preprint The copyright holder for this this version posted November 17, 2020. ; https://doi.org/10.1101/2020.11.15.20231001 doi: medRxiv preprint t h e r e m a i n i n g p a t i e n t s ( m R S = 1 , I Q R : 1 -2 ) . S e v e n t e e n p a t i e n t s ( 3 7 . 8 % ) w e r e r e -h o s p i t a l i z e d a f t e r d i s c h a r g e , a n d 4 o f t h e s e ( 2 3 . 5 % ) w e r e r e -h o s p i t a l i z e d a t a n e u r o l o g i c a l d e p a r t m e n t : O n e p a t i e n t h a d a n e w -o n s e t i s c h e m i c s t r o k e ; 1 h a d r e c u r r e n t g e n e r a l i z e d t o n i c -c l o n i c s e i z u r e s d u e t o h y p o m a g n e s e m i a s e c o n d a r y t o a r e f e e d i n g s y n d r o m e ; 1 h a d m e m o r y d e c l i n e a n d g a i t d i f f i c u l t i e s w i t h b r a i n M R I s h o w i n g n o r m a l p r e s s u r e h y d r o c f i b r i n o u s t h r o m b o s i s i n t h e m i c r o v a s c u l a t u r e i n k e e p i n g w i t h a h i s t o l o g i c a l d i a g n o s i s o f h e m o r r h a g i c n e c r o t i z i n g e n c e p h a l i t i s . T h e p a t i e n t w a s d i a g n o s e d a s h a v i n g C O V I D -1 9 a s s o c i a t e d a c u t e n e c r o t i z i n g e n c e p h a l i t i s a n d r e f e r r e d f o r n e u r o r e h a b i l i t a t i o n . T h e s e c o n d p a t i e n t w i t h e n c e p h a l i t i s h a d a m e d i c a l h i s t o r y o f k i d n e y t r a n s p l a n t a t i o n a n T w o I C U p a t i e n t s c o m p l a i n e d o f b u r n i n g p a r a n e s t h e s i a a n d n u m b n e s s o f t h e l a t e r a l t h i g h ( b i l a t e r a l l y i n o n e c a s e ) a n d w e r e d i a g n o s e d a s h a v i n g m e r a l g i a p a r e s t h e t i c a . B o t h p a t i e n t s h a d b e e n v e n t i l a t e d i n t h e p r o n e p o s i t i o n l e a d i n g t o c o m p r e s s i o n o f t h e l a t e r a l f e m o r a l c u t a n e o u s n e r v c l a s s i f i e d a s e i t h e r s e c o n d a r y t o c r i t i c a l i l l n e s s o r o t h e r c a u s e s o r w e r e i n s u f f i c i e n t l y i n v e s t i g a t e d . o n C S F h a d u n d e t e c t e d l e v e l s o f S A R S -C o V -2 [ 8 ] . T h i s w a s c o n s i s t e n t w i t h o u r f i n d i n g t h a t a l l 5 C S F s a m p l e s i n v e s t i g a t e d f o r S A R S -C o V -2 w e r e P C R n e g a t i v e . O u r t h i r d c a s e o f p r o b a b l e i m m u n e -m e d i a t e d C N S i n f l a m m a t i o n w a s a p a t i e n t w i t h m o n o p h a s i c m y e l i t i s w h o m a d e a n u n e v e n t f u l r e c o v e r y , w i t h n e u r o l o g i c a l s y m p t o m o n s e t w i t h i n 1 b e n e f i t o f a t t r i b u t i n g n e u r o l o g i c a l d i s e a s e t o C O V I D -1 9 o n l y w h e n e x t e n s i v e l a b o r a t o r y i n v e s t i g a t i o n s h a v e b e e n p e r f o r m e d a n d o t h e r k n o w n c a u s e s h a v e b e e n e x c l u d e d . T h i s i s i m p o r t a n t t o a v o i d f a l s e l y a s s i g n i n g s y m p t o m s a n d s i g n s t o C O V I D -1 9 w h e n i n f a c t t h e r e i s u n r e l a t e d p a t h o l o g y : W e e n c o u n t e r e d a r e m a r k a b l e p a t i e n t w h o w a s d i a g n o s e d a s h a v i n g c e r e b r a l a u t o s o m a l d o m i n a n t a r t e r i o p a t h y w i t h s u b c o r t i c a l i n f a r c t s a n . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) preprint . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) preprint The copyright holder for this this version posted November 17, 2020. . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) preprint The copyright holder for this this version posted November 17, 2020. ; https://doi.org/10.1101/2020.11.15.20231001 doi: medRxiv preprint T a b l e 2 -S y m p t o m s a n d s i g n s d u r i n g a d m i s s i o n a A l l , N = 6 1 N o I C U a d m i s s i o n , N = 2 6 I C U a d m i s s i o n , N = 3 5 N e u r o l o g i c a l s y m p t o m s N % / S D N % / S D N % / S D P v a l u V I D -1 9 p o s i t i v e p a t i e n t s d i c h o t o m i z e d i n I C U a n d n o n -I C U p a t i e n t s . a F o r c a t e g o r i c a l v a l u e s w e t e s t e d w i t h F i s h e r ' s e x a c t t e s t ; f o r n o r m a l d i s t r i b u t e d v a l u e s w e u s e d a s t u d e n t ' s t -t e s t a n d f o r n o n n o r m a l d i s t r i b u t e d v a l u e s w e c a l c u l a t e d m e d i a n a n d t e s t e d w i t h a n o n -p a r a m e t r i c t e s t f o r p -v a l u e . b T e t r a p a r e s i s = C l e a r w e a k n e s s d e s p i t e m a x i m a l e f f o r t ; U n i v e r s a l w e a k n e s s = r e d u c e d m o t o r f u n c t i o n d u e t o f a t i g u e o r p a i n . c D e l i r i u m = h a l l u c i n a t e d / p s y c h o m o t o r a g i t a t i o n o r r e d u c t i o n / f l u c t u a t i n g c o n s c i o u s n e s s a n d d i s o r i e n t a t i o n . T o t a l d a y s c a l c u l a t e d f r o m p r o s p e c t i v e o b s e r v a t i o n s . d P e r c e n t a g e o f t o t a l I C U p a t i e n t s . I C U , I n t e n s i v e c a r e u n i t . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) preprint The copyright holder for this this version posted November 17, 2020. ; https://doi.org/10.1101/2020.11.15.20231001 doi: medRxiv preprint T a b l e 3 -D i s c h a r g e e v a l u a t i o n a A l l , N = 6 1 N o I C U a d m i s s i o n , N = 2 6 I C U a d m i s s i o n , N = 3 5 P v a l u e I n -h o s p i t a l d e a t h , N ( % ) 1 0 1 6 . 4 1 3 . 8 9 2 5 . 7 0 . 0 1 7 m R S a t d i s c h a r g e , m e d i a n ( I Q R ) 3 2 -5 2 1 -3 4 4 -6 < 0 . 0 0 1 M O C A t e s t p e r f o r m e d , N ( % ) 3 2 5 2 . 5 1 8 6 9 . 2 1 4 4 0 . 0 0 . 0 3 M O C A s c o r e , m e d i a n ( I Q R ) 2 2 1 8 . 5 -2 8 2 5 2 2 -2 9 1 9 . 5 1 6 -2 D i s c h a r g e e v a l u a t i o n o f C O V I D -1 9 p o s i t i v e p a t i e n t s d i c h o t o m i z e d i n I C U a n d n o n -I C U p a t i e n t s . a F o r c a t e g o r i c a l v a l u e s w e t e s t e d w i t h F i s h e r ' s e x a c t t e s t ; f o r n o r m a l d i s t r i b u t e d v a l u e s w e u s e d a s t u d e n t ' s t -t e s t a n d f o r n o n n o r m a l d i s t r i b u t e d v a l u e s w e c a l c u l a t e d m e d i a n a n d t e s t e d w i t h n o n -p a r a m e t r i c t e s t f o r . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) preprint . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) preprint . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) preprint The copyright holder for this this version posted November 17, 2020. ; https://doi.org/10.1101/2020.11.15.20231001 doi: medRxiv preprint T a b l e 6 -D i a g n o s e s b a s e d o n c o m p l i c a t i o n s d u r i n g a d m i s s i o n a n d a f t e r 3 m o n t h s a A l l , N = 6 1 D u r i n g a d m i s s i o n , N = 6 1 A f t e r d i s c h a r g e , N = 4 5 C e r e b r o v a s c u l . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) preprint The copyright holder for this this version posted November 17, 2020. ; https://doi.org/10.1101/2020.11.15.20231001 doi: medRxiv preprint F i g u r e l e g e n d s F i g u r e 1 -F l o w -c h a r t o f p a t i e n t i n c l u s i o n a n d o b s e r v e d n e u r o l o g i c a l c o m p l i c a t i o n p a r a i n f l u e n z a v i r u s , a t y p i c a l p n e u m o n i a , m y c o b a c t e r i a , p n e u m o c y s t i s , f u n g i a n d C M V , e x c e p t f o r a p o s i t i v e a s p e r g i l l u s g a l a c t o m a n n a n a n t i g e n . C y t o l o g i c e x a m i n a t i o n o f t h e l u n g b i o p s y r e v e a l e d t y p e I I p n e u m o c y t e h y p e r p l a s i a a n d c a p i l l a r y i n f l a m m a t i o n w i t h m a c r o p h a g e s a n d n e u t r o p h i l s . N o h y a l i n e m e m b r a n e s , g r a n u l o m a s , n e c r o s i s , f i b r o s i s o r v a s c u l i t i s w e r e o b s e r v e d . T h e r e w a s n o m i c r o s c o p i c e v i d e n c e o f m a l i g n a n c y o r f u n c a p i l l a r i e s , h e m o s i d e r i n i n m a c r o p h a g e s a n d g l i o s i s ( h e m a t o x y l i n a n d e o s i n s t a i n ) , ( . A s t e r i x : t h r o m b u s . T h e t e a m o f n e u r o p a t h o l o g i s t s c o n c l u d e d t h e f i n d i n g s i n t h e b r a i n b i o p s y t i s s u e t o b e c o n s i s t e n t w i t h s m a l l n e c r o t i c l e s i o n s / i n f a r c t i o n s , l i k e l y c a u s e d b y f i b r i n t h r o m b i i n t h e v e s s e l s . T h e c l i n i c a l s u s p i c i o n o f C O V I D -1 9 w a s c o n f i r m e d b y a p o s i t i v e s e r u m t e s t f o r S A R S -C o V -2 is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) preprint The copyright holder for this this version posted November 17, 2020. ; ( b o t h i n t r a t h e c a l a n d p e r i p h e r a l t e s t i n g ) , L y m e ' s d i s e a s e , J C v i r u s , 1 8 S -R N A , f l o w c y t o m e t r y , a n d L G I 1 , N M D A , G A B A -B , a n d C A S P R 2 a n t i b o d y s c r e e n i n g f o r a u t o i m m u n e e n c e p h a l i t i s w e r e a l l n e g a t i v e . H I V a n d h e p a t i t i s B t e s t i n g , t r a n s e s o p h a g e a l e c h o c a r d i o g r a p h y , w h o l e b o d y F D G -P E T f o r o c c u l t m a l i g n a n c y w e r e a l s o u n r e m a r k a b l e . T h e r e w e r e a p o s i t i v e P C R a n d i n t r a t h e . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) preprint The copyright holder for this this version posted November 17, 2020. ; https://doi.org/10.1101/2020.11.15.20231001 doi: medRxiv preprint Neurologic Features in Severe SARS-CoV-2 Infection Neurologic manifestations in hospitalized patients with COVID-19: The ALBACOVID registry New onset neurologic events in people with COVID-19 in 3 regions in China Neurologic Manifestations of Hospitalized Patients With Coronavirus Disease A prospective clinical study of detailed neurological manifestations in patients with COVID-19 Neurological manifestations and COVID-19: Experiences from a tertiary care center at the Frontline Neurological associations of COVID-19 Lifting the mask on neurological manifestations of COVID-19 Neuropathological Features of Covid-19 Neuropathology of patients with COVID-19 in Germany: a post-mortem case series A first case of meningitis/encephalitis associated with SARS-Coronavirus-2 First case of SARS-COV-2 sequencing in cerebrospinal fluid of a patient with suspected demyelinating disease Sepsis-associated encephalopathy The impairment of small nerve fibers in severe sepsis and septic shock A Prospective Study of Neurologic Disorders in Hospitalized COVID-19 Patients Updated nomenclature of delirium and acute encephalopathy: statement of ten Societies Case definitions, diagnostic algorithms, and priorities in encephalitis: Consensus statement of the international encephalitis consortium Diagnostic evaluation of rhabdomyolysis. Muscle and Nerve The emerging spectrum of COVID-19 neurology: clinical, radiological and laboratory findings Frontal encephalopathy related to hyperinflammation in COVID-19 COVID-19-related encephalopathy: a case series with brain FDG-positron-emission tomography/computed tomography findings On the pathophysiology and treatment of akinetic mutism Clinical Features Associated with Delirium Motor Subtypes in Older Inpatients: Results of a Multicenter Study 2-18F-fluoro-2-deoxyglucose positron emission tomography in delirium COVID-19-associated Acute Hemorrhagic Necrotizing Encephalopathy: CT and MRI Features COVID-19-related acute necrotizing encephalopathy with brain stem involvement in a patient with aplastic anemia Acute necrotizing encephalopathy with SARS-CoV-2 RNA confirmed in cerebrospinal fluid COVID-19: consider cytokine storm syndromes and immunosuppression Neurological manifestations of influenza infection in children and adults: Results of a national british surveillance study Influenza virus and CNS manifestations Acute transverse myelitis after COVID-19 pneumonia Clinical review: Intensive care unit acquired weakness Neuromuscular presentations in patients with COVID-19 Meralgia Paresthetica after Prone Positioning Ventilation in the Intensive Care Unit Lessons from an ICU recovery clinic: Two cases of meralgia paresthetica after prone positioning to treat COVID-19-associated ARDS and modification of unit practices An official American Thoracic Society/European Society of intensive care medicine/society of critical care medicine clinical practice guideline: Mechanical ventilation in adult patients with acute respiratory distress syndrome The down Side of Prone Positioning: The Case of a Coronavirus 2019 Survivor