key: cord-0984139-7y9bdzpd authors: Lopez, Marielisa; Bell, Kathleen; Annaswamy, Thiru; Juengst, Shannon; Ifejika, Nneka title: COVID-19 Guide for the Rehabilitation Clinician: A Review of Non-Pulmonary Manifestations and Complications date: 2020-05-26 journal: Am J Phys Med Rehabil DOI: 10.1097/phm.0000000000001479 sha: 0c501761fcfab754dcfc729ee6875e8c44a6c2c2 doc_id: 984139 cord_uid: 7y9bdzpd Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) – also known as COVID-19 – is primarily known for respiratory illness. While it is clear that patients with moderate to severe cases of COVID-19 will require pulmonary rehabilitation, physiatrists will need to consider effective management plans for COVID-19 survivors with extra-pulmonary involvement. This report will summarize key non-pulmonary considerations to guide rehabilitation clinicians who may be involved in the care of COVID-19 survivors with the best available early evidence. SARS-CoV2 have high similarity, SARS-CoV2 may also have the potential to invade the nervous system 4 . Brain tissue is reported to have angiotensin converting enzyme -2 (ACE-2) receptors. The SARS-CoV-2 uses the SARS-CoV receptor ACE2 for host cell entry at the myocardial cell membrane. Some researchers have proposed access of SARS-COV-2 through the cribriform plate to the brain with the potential of endothelial capillary damage, resulting in hemorrhage within the cerebral tissues. Further confirmatory investigation is needed 5 . • Some patients with severe COVID-19 (78 in a study of 214) have had neurological manifestations including altered consciousness, central nervous system symptoms (headache, dizziness, impaired consciousness, ataxia, acute cerebrovascular events and epilepsy), and PNS symptoms (hypogeusia, hyposmia, hypopsia, and neuralgia) 6 . While there are new reports of young healthy patients sustaining strokes due to coagulopathy (https://www.washingtonpost.com/health/2020/04/24/strokescoronavirus-young-patients/), these data have not yet been published and true incidence of stroke is not yet known. • An observational series of 58 consecutive patients in France admitted with acute respiratory distress syndrome (ARDS) due to Covid-19, reported agitation and confusion (40/58), dysexecutive syndrome (14 of 39 discharged patients) and corticospinal tract signs (39/58). Two of 13 patients who underwent brain MRI because of unexplained encephalopathic features, had single acute ischemic strokes. Data is lacking to determine which features were specific to SARS-CoV-2 infection 7 . Copyright © 2020 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited. In a multi-institutional observational series in Italy comprising approximately 1200 patients admitted with COVID-19, five patients were diagnosed with Guillain-Barré syndrome after the onset of disease. Four had positive nasopharyngeal swab for SARS-CoV-2 at onset of disease and one had a negative nasopharyngeal swab but subsequently converted to positive on serologic testing. All the patients had negative real-time polymerase-chain-reaction SARS-CoV-2 assay of the CSF. The findings were generally consistent with an axonal variant of Guillain-Barré syndrome in three of the patients and with a demyelinating process in the remaining two 8 . • A case series of 3 patients with confirmed SARS-CoV-2 described positive antiphospholipid antibodies and subsequent multiple cerebral infarctions. One patient also had evidence of ischemia in lower limbs and several digits of the hand 9 . • A Netherlands report evaluated thrombotic complications in 184 ICU patents with COVID-19 infection in which the incidence was found to be 31%. Pulmonary embolism was the most frequent thromboembolic complication 10 . • Skeletal muscle injury has been seen in 17 out of 214 patients with severe COVID-19 disease, characterized by elevated creatinine kinase and lactate dehydrogenase 6 . Prolonged immobility in the intensive care unit could be the etiologic cause of these symptoms. positive tenderness. Myoglobin, creatinine kinase and lactate dehydrogenase were elevated along with liver enzymes, suggesting rhabdomyolysis. No confirmation of pathology consistent with rhabdomyolysis was available 11 . • In a meta-analysis with three studies including 1167 patients, it was reported the overall rate of conjunctivitis at admission to the hospital was 1.1% (3% and 0.7% in severe and non-severe COVID-19 patients), respectively 12 . There was a single case report of bilateral acute conjunctivitis and positive reverse transcription-polymerase chain reaction (RT-PCR) SARS-CoV-2 in conjunctival swabs, with swabs remaining positive for 17 days 13 . • ACE-2 is expressed in the cardiovascular system during severe infections. Patients with underlying cardiovascular disease can be especially susceptible to the proarrhythmic effects, with co-existing fever, electrolyte disturbances, stress and the use of antiviral drugs. Aggressive antipyretic treatment and electrocardiogram (ECG) monitoring is recommended in some patients 14 . • There is an additional case report of a patient with positive SARS-CoV-2 with acute myopericarditis, with signs and symptoms of heart failure a week after upper respiratory tract symptoms began 15 . • While the mechanism of cardiac injury is not fully described, several mechanisms have been proposed, including immune inflammatory response, viral invasion to Copyright © 2020 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited. cardiomyocytes, severe hypoxia and oxidative stress with myocardial injury from increased myocardial oxygen demand 16 . • There is one case series of patients (n=3) who showed decompensation of underlying heart failure, ST segment elevation, and cardiogenic shock concurrent with COVID-19 17 . • Like patients with exacerbations of COPD and/or community acquired pneumonia, survivors of COVID will likely be at high risk of cardiovascular events and mortality, especially in the 30 days following the resolution of the acute phase of the virus 18 . • In a single-center series in China involving 138 patients with COVID-19 pneumonia, 10 were found with laboratory evidence of acute myocardial injury via significantly higher cardiac biomarkers CK-MB (creatine kinase myocardial band) and hs-cTnI (high sensitivity cardiac troponin I) 19 . and with systemic illnesses, there may be non-specific elevations of liver enzymes as well. • In a large cohort including 1099 patients from 552 hospitals in 31 provinces or provincial municipalities and of those with available results of liver enzymes, patients with more severe disease had abnormal liver aminotransferase levels than did patients with non-severe disease 22 . • In 52 patients with COVID-19 pneumonia, the incidence was 33% for heart injury (abnormal LDH or CK), 29% for liver injury (any abnormality in AST, ALT, GGT or ALP), 17% for pancreatic injury, 8% for renal injury (abnormal creatinine), and 2% for diarrhea. There is potential for mild pancreatic injury patterns in patients with COVID-19 pneumonia, and these may be related to direct viral involvement of the pancreas or from secondary enzyme abnormalities in the context of severe illness without substantial pancreatic injury. These patients also had abnormal blood glucose 23 with implications for patients with pre-existing diabetes mellitus. Manifestations included erythematous rash, urticarial and chickenpox-like vesicles. Lesions seemed to heal within a few days 26 . It will be imperative for continued data to be collected on these patients during the recovery and rehabilitation stage in order to sort acute reactions to sepsis from intrinsic actions of the novel coronavirus. Additionally, many of these patients will be experiencing symptoms related to stress disorders, anxiety, or depression. It is highly likely that many of these patients will be cared for on inpatient rehabilitation units and as outpatients in physical medicine and rehabilitation clinics and early establishment of registries to document symptom clusters and recovery trajectories will inform rehabilitation management during the next year. This brief report can serve as a guide for the rehabilitation clinician in different scenarios we have considered including: 1) Determining screening criteria for admission to the post-acute setting with the knowledge that there can be many extra-pulmonary symptoms and viral shedding can occur outside of the respiratory system. According to the CDC "SARS-CoV-2 can cause asymptomatic, pre-symptomatic, and minimally symptomatic infections, leading to viral shedding that may result in transmission to others who are particularly vulnerable to severe disease and death" 27 . In consideration of this, identifying any of the clinical findings discussed in Copyright © 2020 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited. this report during the pre-admission assessment in a patient with no documented respiratory symptoms leading to acute care hospital, along with clinical judgement, can prompt testing prior to admission and also justify medical complexity for admission to an inpatient rehab facility (IRF). Even though viral shedding in stool has been identified even after throat swabs are negative 25 , at this time the CDC reports that the risk of infection through stool is low 28 Pulmonary Pathology of Early-Phase 2019 Novel Coronavirus (COVID-19) Pneumonia in Two Patients with Lung Cancer COVID-19 infection: the perspectives on immune responses Human Coronaviruses and Other Respiratory Viruses: Underestimated Opportunistic Pathogens of the Central Nervous System? 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