HFH NEUROLOGY COVID-19 SCIENTIFIC ADVISORY BOARD 03/31/20 UPDATE Editorial board: Amer Aboukasem MD, Hassan Aboul Nour MD, Muhammad Affan MD, Owais Alsrouji MD, Ximena ​ Arcila-Londono MD, Gregory Barkley MD, Arun Chandok MD, Alex Bou Chebl MD, Song Chen MS, Michael Chopp PhD, Omar Danoun MD, Elissa Fory MD, Shailaja Gaddam MD, Kavita Grover MD, Mohammed Ismail MD, Holly Lorigan MD, Ghada Mahmoud Mohamed MD, Shaneela Malik MD, Daniel Newman MD, Neepa Patel MD, Phillip Ross MD, Bin Rui PhD, Naganand Sripathi MD, Aarushi Suneja MD, Vibhangini Wasade MD, Iram Zaman MD Chairs: Gamal Osman MD, Ahmad Riad Ramadan MD ​ COVID-19 PANDEMIC: THE NUMBERS (as of 3/31/20, confirmed in the symptomatic mother by PCRs. 23 1pm EST) days later, she was delivered by C-section. Two ● World:1 823,479 confirmed cases. Total deaths: hours post-delivery, the baby had positive IgM and ​ ​ ​ 40,635. (CFR 4.93%). Total recovered:166,999 IgG titers but negative PCRs. Importantly, IgM does 1 ● US: ​ 175,669 confirmed cases. Total deaths: not cross the placenta so this was not transmitted ​ ​ ​ 3,424; 661 new deaths in the past 24 hours. immunity.6 ​ Highest number of deaths remains in NY: 932. ● Michigan:2 7,615 confirmed cases. Total deaths: DISCOVERIES IN SARS-COV-2 PATHOGENICITY ​ ​​ 259 (CFR 3.4%). 75 new deaths in the past 24 ● Similarly to CoV (SARS epidemic), CoV-2 uses the hours. ACE2 receptor for entry into cells via its spike protein. ● NEW! Peak resource use and peak deaths in the ● ACE2 is expressed in human airway epithelia, lung US is projected on April 15, 2020. Visit parenchyma, vascular endothelium, kidney cells, and covid19.healthdata.org for prediction on deaths, small intestine cells. Also expressed in some need for ICU bed and ventilators.3 neuronal populations - cardiorespiratory centers in ​ ● Evolution of the pandemic:4 The US remains in the brainstem, raphe nucleus, hypothalamus and ​ ​​ the acceleration phase of the pandemic with motor cortex. exponential growth of confirmed cases and ● CoV-2, like CoV, may gain access to the CNS via the deaths. The number of deaths increased 2.4 times olfactory receptor neurons (may explain anosmia in the past 4 days. common in these infections), spreading to the olfactory bulbs and then to other parts of the brain via BEST EXPOSURE PREVENTION PRACTICES trans-synaptic transfer (e.g., thalamus, hypothalamus, ● CoV-2 was detected in aerosols for up to 3 hours, 4 brainstem). The medullary cardiorespiratory centers hours on copper, 24 hours on cardboard and 2-3 appear to be highly infected, which may play a role in days on plastic and stainless steel.4 central respiratory failure in these patients.7 ​ ​ ● Continue to perform basic hygiene and apply droplet Coronaviruses infect both neurons and glia. precautions (cover cough, wash hands for at least 20 Neuroinfection, along with the systemic sec, do not touch face/eyes, disinfect the inflammatory response, leads to a breakdown of surroundings with 60-95% alcohol, social distancing the blood-brain barrier and contributes to the of at least 6 feet).5 activation of microglia and astroglia.8 ​ ​ ● Before entering in contact with suspected or known ● Mild disease in 81% of cases, severe disease COVID-19 infected patients, familiarize yourself with (respiratory failure, ARDS, requiring oxygen +/- the donning and doffing procedures. Proper PPE ventilatory support) in 14% cases, and critical disease includes: respirator or facemask (N95, P100; or (shock, MOSD, MOSF) in 5% cases.9 ​ PAPR), gloves, gown, and eye protection (e.g., ● Cytokine storm: A hallmark of severe CoV-2 disease reusable goggles or disposable face shield).5 is the development of a potent “cytokine storm”. This ​ ● A case of possible vertical mother-to-fetus is not unique to COVID-19 and has been described in transmission was reported in China. Infection was MERS and SARS, both of which are closely-related 1 HFH NEUROL COVID-19 SAB UPDATE 3/31/20 coronaviruses. IL-6, a proinflammatory cytokine, is state, and the cytokine storm all contribute to central in this process. direct myocardial injury, mismatch ● Is there a CNS control of the immune system? The myocardial oxygen supply/demand and answer is yes. The autonomic system is an important plaque rupture, leading to increase in the risk modulator of the immune system. Dysregulating the of myocardial infarction, arrhythmias and autonomic system stimulates the inflammatory heart failure. response of both innate and adaptive immune systems. There is strong evidence to support the UPDATES ON SARS-COV2 TESTING direct sympathetic innervation of immune organs ● Per the CDC,16 priority for testing goes to 1) ​ such as the spleen. Sympathetic activation causes hospitalized patients with signs/symptoms compatible splenic cytokine production (IL-1β, IL-2, IL-5, IL-16 with COVID-19, 2) vulnerable patient populations and TGFβ1), whereas vagal nerve stimulation (older adults, immunocompromised state, chronic quiesces the immune response.10 One wonders medical conditions (e.g., HTN, DM, CKD, lung, heart ​ whether blocking the sympathetic outflow may halt or disease), 3) HCP who had close contact with a prevent the development of this exuberant COVID19 suspect or positive patient within 14 days of inflammatory response. symptom onset (close contact= being within 6 feet for ​ ● Important clinical features of the disease: a prolonged period of time or direct contact with ○ A minority of patients will develop hypoxia and secretions of COVID-19 case, while not using deteriorate very quickly, going from oxygen recommended PPE). ​ supplementation by oxygen to high flow nasal ● Methods for sample collection: nasopharyngeal cannula to intubation within a few hours. (NP) swab, tracheal aspirate/BAL (intubated patients, ○ Initial CT chest made the right diagnosis in but increases exposure risk), sputum (induction not 96.1% of cases in one series.11 Most common recommended).17 At this point, HFH only tests via NP ​ ​ ​ findings were ground glass opacities, swabs. consolidations, vascular enlargement, ● rRT-PCR: Almost all diagnostic testing for CoV-2 is interlobular septal thickening, and air done using rRT-PCR. In the US, testing is performed bronchogram sign. by the CDC, hospital and public health laboratories. ○ 2-10% of COVID-19 presented with GI Turnaround time varies, continues to take up to 4-5 symptoms, such as diarrhea, abdominal pain, days due to the low availability of 12​ st and vomiting in 2% to 10% of cases. reagents/batching/prioritization. On March 21 ,​ the ​ ​ ○ Elevation of several serum inflammatory markers- FDA approved a point-of-care (POC) test by Cepheid IL-6, ferritin, LDH, CRP, D-dimer, and with a turnaround time of 45 minutes, which should triglycerides, indicating the presence of a potent be commercially available at the end of March.18 ​ cytokine storm and secondary hemophagocytic Abbott has been granted emergency use lymphohistiocytosis. authorization by the FDA for its POC test that will ○ Neutrophil-to-lymphocyte ratio (NLR) of ≥3.13 detect CoV-2 in “as little as 5 min” and “negative predicts disease progression results in 13 min”, making it the fastest POC test ○ Lymphopenia and thrombocytopenia for the virus at this stage. The company claims ○ Myocardial injury: in one study of 416 patients they will produce 5 million tests per month.19 ​ admitted with COVID-19, 20% had evidence of ● Serology: IgM and IgG provide information about the cardiac injury as defined as elevated immune response of the host to the virus antigens. In troponin.13 Patients with underlying one study, antibodies were detected in all patients 5 ​ cardiovascular disease and elevated troponin days after symptom onset. Faster to get results, but were found to have the highest mortality.14 less accurate than PCR. ​ Autopsies have revealed infiltration of ● Immunoassays: monoclonal antibody tests that ​ myocardium by interstitial mononuclear detect viral antigens such as the nucleocapsid (N) inflammatory cells, evidencing a protein, spike protein of the virus or multiple antigens. 15 myocarditis. A​ RDS, myocarditis, Faster results (20-60 min) but longer to develop and ​ sympathetic hyperactivity, hypercoagulable less accurate than PCR.20 ​ 2 HFH NEUROL COVID-19 SAB UPDATE 3/31/20 ● FDA has not approved at-home test kits and warns Vessels were patent on CT angiogram and CT the public against the marketing of fraudulent venogram.26 ​ COVID-19 test kits.21 ○ PNS symptoms: In one study, 8.9% of patients ​ ● To date, there is no reliable data on the false positive (hypogeusia, hyposmia, neuralgia).24 Myalgias ​ and false negative rates of the various testing were found in 10.7% of cases. It remains to be methods. seen whether we will encounter cases of ● A South Korea hospital launched a phone-booth-style motor-predominant peripheral neuropathy, CoV-2 testing- a row of 4 negative-pressure, myopathy and rhabdomyolysis, as we saw during single-occupancy plastic booths under a tent outside the SARS pandemic in 2002. So far, no reported the hospital. The patient gets inside the booth and a movement disorders as a result of the infection. consultation takes place with a HCP who, from ● Laboratory findings: Patients with CNS symptoms ​ outside of the booth, can obtain samples via were more likely to have lower lymphocyte and arm-length rubber gloves built into the plastic panel. platelet counts, and elevated BUN levels. There were Process takes about 7 min to complete and the booth no characteristic laboratory findings in patients with is easy to disinfect.22 PNS symptoms. Patients with muscle injury had ​ ● NEW! Kinsa Health smart thermometers are able higher neutrophil counts, lower lymphocyte counts ​ to track fever across the US via a web-based app. and higher CRP levels and D-dimer levels as well as Although it cannot discriminate fever from evidence of multiorgan system failure.24 ​ different etiologies, it can identify new clusters of ● No specific neuroimaging or electrophysiological fever, track fever curve and gauge the response characteristics described in COVID-19 patients yet.