key: cord-0966348-dlszuben authors: Munblit, D.; Bobkova, P.; Spiridonova, E.; Shikhaleva, A.; Gamirova, A.; Blyuss, O.; Nekliudov, N. A.; Bugaeva, P.; Andreeva, M.; DunnGalvin, A.; Comberiati, P.; Apfelbacher, C.; Genuneit, J.; Avdeev, S.; Kapustina, V.; Guekht, A.; Fomin, V.; Svistunov, A. A.; Timashev, P.; Drake, T. M.; Hanson, S. W.; Merson, L.; Horby, P.; Sigfrid, L.; Scott, J. T.; Semple, M. G.; Warner, J. O.; Vos, T.; Olliaro, P.; Glybochko, P.; Butnaru, D.; Team, Sechenov StopCOVID Research title: Risk factors for long-term consequences of COVID-19 in hospitalised adults in Moscow using the ISARIC Global follow-up protocol: StopCOVID cohort study date: 2021-02-19 journal: nan DOI: 10.1101/2021.02.17.21251895 sha: de0b276f5efa033ff3f60ade9402fc18ce15631f doc_id: 966348 cord_uid: dlszuben Background The long-term sequalae of COVID-19 remain poorly characterised. In this study, we aimed to assess long-standing symptoms (LS) (symptoms lasting from the time of discharge) in previously hospitalised patients with COVID-19 and assess associated risk factors. Methods This is a longitudinal cohort study of adults (18 years of age and above) with clinically diagnosed or laboratory-confirmed COVID-19 admitted to Sechenov University Hospital Network in Moscow, Russia. Data were collected from patients discharged between April 8 and July 10, 2020. Participants were interviewed via telephone using Tier 1 ISARIC Long-term Follow-up Study CRF and the WHO CRF for Post COVID conditions. Reported symptoms were further categorised based on the system(s) involved. Additional information on dyspnoea, quality of life and fatigue was collected using validated instruments. Multivariable logistic regressions were performed to investigate risk factors for development of LS categories. Findings Overall, 2,649 of 4,755 patients discharged from the hospitals were available for the follow-up and included in the study. The median age of the patients was 56 years (IQR, 46-66) and 1,353 (51.1%) were women. The median follow-up time since hospital discharge was 217.5 (200.4-235.5) days. At the time of the follow-up interview 1247 (47.1%) participants reported LS. Fatigue (21.2%, 551/2599), shortness of breath (14.5%, 378/2614) and forgetfulness (9.1%, 237/2597) were the most common LS reported. Chronic fatigue (25%, 658/2593) and respiratory (17.2% 451/2616) were the most common LS categories. with reporting of multi-system involvement (MSI) less common (11.3%; 299). Female sex was associated with LS categories of chronic fatigue with an odds ratio of 1.67 (95% confidence interval 1.39 to 2.02), neurological (2.03, 1.60 to 2.58), mood and behaviour (1.83, 1.41 to 2.40), dermatological (3.26, 2.36 to 4.57), gastrointestinal (2.50, 1.64 to 3.89), sensory (1.73, 2.06 to 2.89) and respiratory (1.31, 1.06 to 1.62). Pre-existing asthma was associated with neurological (1.95, 1.25 to 2.98) and mood and behavioural changes (2.02, 1.24 to 3.18) and chronic pulmonary disease was associated with chronic fatigue (1.68, 1.21 to 2.32). Interpretation 6 to 8 months after acute infection episode almost a half of patients experience symptoms lasting since hospital discharge. One in ten individuals experiences MSI. Female sex is the main risk factor for majority of the LS categories. chronic pulmonary disease is associated with a higher risk of chronic fatigue development, and asthma with neurological and mood and behaviour changes. Individuals with LS and MSI should be the main target for future research and intervention strategies. , T h e n a m e s o f t h e a u t h o r s a r e i n a l p h a b e t i c o r d e r 69 70 71 A B S T R A C T 72 B a c k g r o u n d T h e l o n g -t e r m s e q u a l a e o f C O V I D -1 9 r e m a i n p o o r l y c h a r a c t e r i s e d . I n t h i s 73 s t u d y , w e a i m e d t o a s s e s s l o n g -s t a n d i n g s y m p t o m s ( L S ) ( s y m p t o m s l a s t i n g f r o m t h e t i m e o f 74 d i s c h a r g e ) i n p r e v i o u s l y h o s p i t a l i s e d p a t i e n t s w i t h C O V I D -1 9 a n d a s s e s s a s s o c i a t e d r i s a n d f o r g e t f u l n e s s ( 9 . 1 % , 2 3 7 / 2 5 9 7 ) w e r e t h e m o s t c o m m o n L S r e p o r t e d . C h r o n i c f a t i g u e 91 ( 2 5 % , 6 5 8 / 2 5 9 3 ) a n d r e s p i r a t o r y ( 1 7 . 2 % 4 5 1 / 2 6 1 6 ) w e r e t h e m o s t c o m m o n L S c a t e g o r i e s . 92 w i t h r e p o r t i n g o f m u l t i -s y s t e m i n v o l v e m e n t ( M S I ) l e s s c o m m o n ( 1 1 . 3 % ; 2 9 9 ) . F e m a l e s e x 93 w a s a s s o c i a t e d w i t h L S c a t e g o r i e s o f c h r o n i c f a t i g u e w i t h a n o d d s r a t i o o I n t e r p r e t a t i o n 6 t o 8 m o n t h s a f t e r a c u t e i n f e c t i o n e p i s o d e a l m o s t a h a l f o f p a t i e n t s 101 e x p e r i e n c e s y m p t o m s l a s t i n g s i n c e h o s p i t a l d i s c h a r g e . O n e i n t e n i n d i v i d u a l s e x p e r i e n c e s 102 M S I . F e m a l e s e x i s t h e m a i n r i s k f a c t o r f o r m a j o r i t y o f t h e L S c a t e g o r i e s . c h r o n i c p u l m o n a r y 103 d i s e a s e i s a s s o c i a t e d w i t h a h i g h e r r i s k o f c h r o n i c f a t i g u e d e v e l o p m e n t , a n d a s t h m a w i t h 104 n e u r o l o g i c a l a n d m o o d a n d b e h a v i o u r c h a n g e s . I n d i v i d u a l s w i t h L S a n d M S I s h o u l d b e t h e 105 m a i n t a r g e t f o r f u t u r e r e s e a r c h a n d i n t e r v e n t i o n s t r a t e g i 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) . is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted February 19, 2021. ; c o l l e c t e d t h e f o l l o w -u p d a t a b e t w e e n D e c e m b e r 2 , 2 0 2 0 a n d J a n u a r y 1 4 , 2 0 2 1 f r o m p a t i e n t s 156 d i s c h a r g e d b e t w e e n A p r i l 8 , 2 0 2 0 a n d J u l y 1 0 , 2 0 2 0 . W e i n c l u d e d a d u l t p a t i e n t s ( ≥ 1 8 y e a r s 157 o f a g e ) , w i t h b o t h r e v e r s e t r a n s c r i p t a s e p o l y m e r a s e c h a i n r e a c t i o n ( R T -P C R ) c o n f i r m e d 158 S A R S -C o V -2 i n f e c t i o n , c o r r e s p o n d i n g t o U 0 7 . 1 a s p e r I n t e r n a t i o n a l C l a s s i f i c a t i o n o f D i s e a s e s 159 ( I C D ) , a n d 192 . 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. The copyright holder for this preprint this version posted February 19, 2021. ; D a t a c o l l e c t i o n a n d e n t r y w e r e p e r f o r m e d b y a t e a m o f m e d i c a l s t u d e n t s w h o s i g n e d 194 c o n f i d e n t i a l i t y a g r e e m e n t s , u n d e r w e n t t r a i n i n g i n b a s i c d a t a e n t r y i n t o R E D C a p a n d 195 t e l e p h o n e i n t e r v i e w s . S t u d e n t s h a v e a l r e a d y h a d e x t e n s i v e d a t a e x t r a c t i o n e x p e r i e n c e g a i n e 226 . 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. The copyright holder for this preprint this version posted February 19, 2021. ; 227 T h e s e c o n d a r y o u t c o m e s i n c l u d e d a n y s y m p t o m p r e v a l e n c e a t f o l l o w -u p ( r e g a r d l e s s o f t h e i r 228 d u r a t i o n ) , a n d h e a l t h s t a t u s a s s e s s e d b y E u r o Q o L V A S , f a t i g u e s c a . 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) , o u t o f 5 , 0 4 0 p a t i e n t s h o s p i t a l i s e d w i t h s u s p e c t e d C O V I D -1 9 t o t h e 263 h o s p i t a l s b e f o r e J u l y 1 0 , 2 0 2 0 , 4 , 7 5 5 w e r e d i s c h a r g e d a l i v e o r t r a n s f e r r e d t o a n o t h e r f a c i l i t . It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this 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. The copyright holder for this preprint this version posted February 19, 2021. ; A d e g r e e o f o v e r l a p w a s f o u n d b e t w e e n t h e f i v e m o s t c o m m o n L S , w i t h 7 9 / 9 0 0 ( 8 . 8 % ) o f 308 p a t i e n t s e x p e r i e n c i n g b o t h p e r s i s t e n t f a t i g u e a n d b r e a t h l e s s n e s s , 5 4 ( 6 % ) p e r s i s t e n t f a t i g u e 309 a n d m u s c l e w e a k n e s s . A s m a l l e r p r o p o r t i o n o f p a t i e n t s r e p o r t e d a c o m b i n a t i o n o f p e r s i s t e n t 310 f a t i g u e , b r e a t h l e s s n e s s a n d m u s c l e w e a k n e s s -2 . 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. The copyright holder for this preprint this version posted February 19, 2021. ; D y s p n o e a o f d i f f e r e n t s e v e r i t y w a s r e p o r t e d b y 3 1 8 ( 1 2 % ) p a t i e n t s d u r i n g f o l l o w -u p w i t h 1 9 4 345 ( 7 . 3 % ) e q u i v a l e n t t o g r a d e 3 , 9 3 ( 3 . 5 % ) g r a d e 4 a n d 3 1 ( 1 . 2 % ) g r a d e 5 a c c o r d i n g t o M R C 346 D y s p n o e a S c a l e ( T a b l e S 3 . 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. The copyright holder for this preprint this version posted February 19, 2021. ; L o n g -s t a n d i n g s y m p t o m C a t e g o r y ( n † ) R i s k f a c t o r P r i m a r y a n a l y s i s O R ( 9 5 % C I ) S e n s i t i v i t y a n a l y s i s O R ( 9 5 % C I ) C o n s i s t e n t l y a s s o c i a t e d f a c . It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this 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) . 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. The copyright holder for this preprint this version posted February 19, 2021. ; 370 . 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) . 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. The copyright holder for this preprint this version posted February 19, 2021. ; T o o u r k n o w l e d g e , t h i s i s t h e p r o s p e c t i v e c o h o r t s t u d y w i t h t h e l a r g e s t s a m p l e s i z e a n d t h e 378 l o n g e s t f o l l o w -u p d u r a t i o n , a s s e s s i n g t h e l o n g -t e r m h e a l t h a n d p s y c h o -s o c i a l c o n s e q u e n c e c o n d i t i o n s w a s t h e c a u s e o f o n g o i n g s y m p t o m s . F u t u r e r e s e a r c h s h o u l d i n v e s t i g a t e C O V I D -414 1 9 c o n s e q u e n c e s i n t h i s g r o u p o f p a t i e n t s i n g r e a t e r d e t a i l . 415 416 D a t a f r o m t h e C O V I D S y m p t o m S t u d y a p p i n t h e U K s u g g e s t e d t h a t a s t h m a m a y b e a r i s 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) The copyright holder for this preprint this version posted February 19, 2021. ; f r o m t h e m e d i c a l n o t e s . T h i r d , a l m o s t h a l f o f t h e p a t i e n t s i n o u r c o h o r t d i d n o t h a v e R T -P C R 451 c o n f i r m e d C O V I D -1 9 i n f e c t i o n , a l t h o u g h o u r p r e v i o u s w o r k 3 s h o w e d t h a t c l i n i c a l f e a t u r e s o f 452 C O V I D -1 9 a n d i n -h o s p i t a l m o r t a l i t y w e r e t h e s a m e i n C O V I D -1 9 c l i n i c a l l y d i a g n o s e d a n d 453 l a b o r a t o r y -c o n f i r m e d c a s e s . W e a l s o p e r f o r m e d s e n s i t i v i t y a n a l y s e s u s i n g d a t a f r o m t h . 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) The copyright holder for this preprint this version posted February 19, 2021. ; M a r k i n a , M r G e o r g i y N o v o s e l o v , M s A n n a P u s h k a r e v a , M s O l g a R o m a n o v a , M s M a r i a 488 S h o s h o r i n a , M s J a s m i n S i b k h a n , M s O l g a S p a s s k a y a , M s A n n a S u r k o v a , M s N a i l y a 489 U r m a n t a e v a , M s E k a t e r i n a V a r l a m o v a , M s M a r g a r i t a Y e g i y a n , M s M a r g a r i t a Z a i k i n a , M s 490 A n a s t a s i a Z o r i n a , M s E l e n a Z u i k o v a f o r a s s i s t a n c e i n d a t a e x t r a c t i o n , d o c u m e n t t r a n s l a t i o An interactive web-based dashboard to track COVID-19 in 497 real time Features of 20 133 UK patients in 499 hospital with covid-19 using the ISARIC WHO Clinical Characterisation Protocol: prospective 500 observational cohort study StopCOVID cohort: An observational 502 study of 3,480 patients admitted to the Sechenov University hospital network in Moscow city 503 for suspected COVID-19 infection COVID-19 symptoms at hospital admission vary with age and sex: 505 ISARIC multinational study Persistent Symptoms in 507 Patients After Acute COVID-19 6-month consequences of COVID-19 in patients 509 discharged from hospital: a cohort study Characterising long-term covid-19: a 511 rapid living systematic review National Institute for Health and Care Excelence (NICE) tSIGNSatRCoGPR. COVID-517 19 rapid guideline: managing the long-term effects of COVID-19 The World Health Organization. Global COVID-19 Clinical Platform Case Report 525 Form (CRF) for Post COVID condition (Post COVID-19 CRF) Characterizing Long COVID in an 529 International Cohort: 7 Months of Symptoms and Their Impact Management of post-acute 532 covid-19 in primary care Attributes and predictors of Long-COVID: 534 analysis of COVID cases and their symptoms collected by the Covid Symptoms Study App The impact of COPD and smoking history on the 537 severity of COVID-19: A systemic review and meta-analysis Determinants and impact of fatigue in patients with chronic obstructive pulmonary disease COVID-19 and COPD Low prevalence of bronchial asthma and 545 chronic obstructive lung disease among intensive care unit patients with COVID-19 Eosinophilia in Asthma Patients Is 548 Protective Against Severe COVID-19 Illness Covid-19 hyperinflammation and post-Covid-550 19 illness may be rooted in mast cell activation syndrome Patient outcomes after hospitalisation with 552 COVID-19 and implications for follow-up: results from a prospective UK cohort