key: cord-0866578-qcxfd209 authors: Qureshi, Adnan I; Baskett, William I; Huang, Wei; Naqvi, S Hasan; Shyu, Chi-Ren title: New Onset Dementia Among Survivors of Pneumonia Associated with Severe Acute Respiratory Syndrome Coronavirus 2 Infection date: 2022-03-07 journal: Open Forum Infect Dis DOI: 10.1093/ofid/ofac115 sha: 093445713aa0cb5b4f34170d71583a21dd5e922d doc_id: 866578 cord_uid: qcxfd209 BACKGROUND: Case series without control groups suggest that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may result in cognitive deficits and dementia in the post-infectious period. METHODS: Adult pneumonia patients with SARS-CoV-2 infection (index hospitalization) and age, gender, and race/ethnicity matched contemporary control pneumonia patients without SARS-CoV-2 infection were identified from 110 healthcare facilities in United States. The risk of new diagnosis of dementia following >30 days after the index hospitalization event without any previous history of dementia was identified using logistic regression analysis to adjust for potential confounders. RESULTS: Among 10,403 patients with pneumonia associated with SARS-CoV-2 infection, 312 patients (3%; 95% confidence interval, 2.7%-3.4%) developed new onset dementia over a median period of 182 days (interquartile range Q1=113 days, Q3=277 days). After adjustment for age, gender, race/ethnicity, hypertension, diabetes mellitus, hyperlipidemia, nicotine dependence/tobacco use, alcohol use/abuse, atrial fibrillation, previous stroke, and congestive heart failure, the risk of new onset dementia was significantly higher with pneumonia associated with SARS-CoV-2 infection compared with pneumonia unrelated to SARS-CoV-2 infection (odds ratio, 1.3; 95% confidence interval, 1.1-1.5). The association remained significant after further adjustment for occurrence of stroke, septic shock, and intubation/mechanical ventilation during index hospitalization (odds ratio, 1.3; 95% confidence interval, 1.1-1.5). CONCLUSIONS: Approximately 3% of patients with pneumonia associated with SARS-CoV-2 infection developed new onset dementia which was significantly higher than the rate seen with other pneumonias. Understanding the long-term burden of disability among survivors of severe acute respiratory 30 syndrome coronavirus 2 (SARS-CoV-2) infection is one of the current priorities.[1, 2] There are 31 several reports of mild to severe cognitive impairment including decline in memory, 32 concentration, executive functioning, and visuospatial functioning after recovery from SARS-CoV-2 33 8 / 35 We attempted to reduce confounders resulting from differences in the population of patients with 88 SARS-CoV-2 infection and control patients by selecting a control group with an identical 89 demographic distribution to the SARS-CoV-2 infected patients. We identified control patients from 90 sample of patients admitted to the hospital without SARS-CoV-2 infection with lack of infection 91 confirmed by one of the previously listed tests. Each SARS-CoV-2 infected patient was matched with 92 a pneumonia patient using age, gender, race/ethnicity, and index encounter admission date. This 93 resulted in two cohorts with nearly identical distributions of demographics and hospitalization dates. 94 We used the ICD-10-CM primary diagnosis codes F01.5, F02.8, F03.9, G30, G31, G32 to identify the 97 patients diagnosed with new onset dementia. Our analysis included only patients with significant 98 recent medical history to ensure completeness of the records of potential comorbidities. We excluded 99 all patients with previous medical encounter diagnosis of dementia in any encounters prior to index 100 Patients with routine discharges were considered to have none or mild disability while 127 patients discharged to non-routine locations such as skilled nursing facilities or nursing 128 homes were considered to have moderate to severe disability, as previously described and 129 validated. [ There was a significantly higher rate of hyperlipidemia, diabetes mellitus and hypertension among 159 pneumonia patients with SARS-CoV-2 infection compared with those without SARS-CoV-2 infection 160 (see Table 1 ). The proportions of patients with of nicotine dependence/tobacco use, alcohol use or 161 abuse, atrial fibrillation, previous stroke, congestive heart failure, mental disorders due to drug use, 162 depression and encephalopathy were significantly lower among patients with SARS-CoV-2 infection 163 12 / 35 compared with those without SARS-CoV-2 infection. The proportion of patients who had septic 164 shock (4.3% versus 2.7%, p<0.001) 165 or stroke (3.9% versus 2.3%, p<.001) during index hospitalization was significantly higher among 166 pneumonia patients without SARS-CoV-2 infection. There were no differences in the proportion of 167 patients with delirium between the two groups. 168 There was a significantly higher rate of new onset dementia among patients with SARS-CoV-2 170 infection compared with those without SARS-CoV-2 infection (3% versus 2.5%, P=.04). After 171 adjustment for age, gender, race/ethnicity, hypertension, diabetes mellitus, hyperlipidemia, 172 nicotine dependence/tobacco use, alcohol use or abuse, atrial fibrillation, previous stroke, 173 congestive heart failure, mental disorders due to drug use, depression, encephalopathy, multiple 174 sclerosis, delirium, other mental disorders due to known physiological condition and personality 175 and behavioral disorders due to known physiological condition. The risk of new onset dementia 176 was significantly higher in patients with pneumonia associated with SARS-CoV-2 infection compared 177 in patients with pneumonia unrelated to SARS-CoV-2 infection (odds ratio, 1.3; 95% CI, 1.1-1.5, 178 p=.003) (see Table 2 ). After adjusting for septic shock, intubation/mechanical ventilation and 179 occurrence of stroke during index encounter in addition to the abovementioned confounders, the risk 180 of new onset dementia was significantly higher with pneumonia associated with SARS-CoV-2 181 infection (OR, 1.3; 95% CI, 1.1-1.5. p=.004). 182 Other variables associated with new onset dementia (see Table 2 We found an increased rate of new onset dementia among survivors of pneumonia associated with 189 included new onset dementia associated with hospital admission with a short follow up period. 191 Therefore, minor cognitive deficits and dementia diagnosis over longer period are not ascertained. 192 There are several reports of cognitive impairment ranging from mild to severe after recovery from with the brain endothelium, communicating directly across the blood-brain barrier and to perivascular 257 Prostaglandin E 2 is an inflammatory mediator with small size and lipophilic properties that can diffuse 259 into the brain parenchyma. Approximately 3% of patients with a hospitalization containing pneumonia associated with SARS-336 CoV-2 infection developed new onset dementia in the post-infectious period which was significantly 337 higher than the rate seen with other pneumonias. Future studies should investigate the underlying 338 pathophysiological processes associated with SARS-CoV-2 infection to identify optimal strategies to 339 prevent long-term disabling sequelae like new onset dementia. Physical, cognitive and 353 mental health impacts of COVID-19 following hospitalisation -a multi-centre prospective cohort 354 study High-dimensional characterization of post-acute sequelae of 356 COVID-19 SARS-CoV-2 emergency and long-term cognitive impairment in older 358 people Persistent COVID-19-associated neurocognitive 360 symptoms in non-hospitalized patients Pattern of cognitive deficits in severe Post-discharge persistent symptoms and health-364 related quality of life after hospitalization for COVID-19 Natural history of cognitive impairment in critical 366 illness survivors. A systematic review Long-term cognitive impairment after 368 critical illness COVID-19 coronavirus pandemic Integrating research data capture into the 372 electronic health record workflow: real-world experience to advance innovation Cerner Provides Access to De-Identified Patient Data for COVID-19 Accessed September 16. 378 12. van der Flier WM, Scheltens P. Epidemiology and risk factors of dementia Dementia prevention, intervention, and care: 381 2020 report of the Lancet Commission A prediction rule to identify low-risk patients with 383 community-acquired pneumonia Stroke and 385 dementia risk: A systematic review and meta-analysis 6-month neurological and 387 psychiatric outcomes in 236 379 survivors of COVID-19: a retrospective cohort study using electronic 388 health records Validation of a case definition for depression in 390 administrative data against primary chart data as a reference standard Discharge destination as a 393 surrogate for Modified Rankin Scale defined outcomes at 3-and 12-months poststroke among stroke 394 survivors Frequent neurologic manifestations and encephalopathy-396 associated morbidity in Covid-19 patients Delirium and encephalopathy in severe COVID-19: a 398 cohort analysis of ICU patients Long-term cognitive impairment after 400 hospitalization for community-acquired pneumonia: a prospective cohort study SARS-CoV-2 and cardiovascular 403 complications: From molecular mechanisms to pharmaceutical management Risk of ischemic stroke in patients with coronavirus 406 disease 2019 (COVID-19) vs patients with influenza Clinical characteristics of coronavirus disease 2019 in China Acute ischemic stroke and COVID-19: An analysis 410 of 27 676 patients Neuropathological features of covid-19 Early postmortem brain MRI findings in COVID-19 non-414 survivors Neurochemical evidence of astrocytic and 416 neuronal injury commonly found in COVID-19 Network medicine links SARS-CoV-2/COVID-19 infection to 418 brain microvascular injury and neuroinflammation in dementia-like cognitive impairment Immunological dysfunction persists for 8 months 421 following initial mild-moderate SARS-CoV-2 infection The inflammatory reflex The cholinergic anti-inflammatory pathway Effects of systemic immunogenic insults and circulating 426 proinflammatory cytokines on the transcription of the inhibitory factor kappaB alpha within specific 427 cellular populations of the rat brain Toll-like receptor 4 on nonhematopoietic cells sustains CNS 429 inflammation during endotoxemia, independent of systemic cytokines University mental status examination and the mini-mental state examination for detecting dementia 433 and mild neurocognitive disorder--a pilot study Biden says long-term effects of covid-19 can be considered a disability under 435 federal civil rights laws Social security disability and SSI for post-COVID syndrome Risk factors for dementia after critical illness in 441 elderly Medicare beneficiaries Infection hospitalization increases risk of dementia in 443 the elderly The diagnosis of young-onset 445 dementia Validity of 447 dementia diagnoses in the Danish hospital registers Diagnostic and Statistical Manual of Mental Disorders Practice parameter for diagnosis and evaluation of dementia. (summary statement) Report of 451 the Quality Standards Subcommittee of the American Academy of Neurology Population-based norms for the Mini Mental State Examination by age and educational level Codex (cognitive disorders examination) decision tree modified for the 456 detection of dementia and MCI Assessing validity of ICD-9 administrative data in recording clinical conditions in a unique dually coded database Diagnosing dementia --ICD-10 not so bad after all: a comparison 461 between dementia criteria according to DSM-IV and ICD-10 Recommendations for optimal ICD 464 codes to study neurologic conditions: a systematic review Reducing the stigma associated with dementia: approaches and 466 goals Declining prevalence of dementia in the U.S. elderly 468 population COVID-19 and dementia: Analyses of risk, disparity, 470 and outcomes from electronic health records in the US