COVID 19 and Cycling: Panel Discussion October 28, 2020 Mark - PowerPoint PPT Presentation

COVID 19 and Cycling: Panel Discussion October 28, 2020 Mark Greve, MD Moderator Michael Roshon, MD/PhD Kevin Sprouse, MD Aaron Baggish, MD

Agenda Virology of SARS CoV-2 Transmission Testing Clinical Course Cycling and Covid: Tales from the Tour Cardiac Sequelae Discussion

Entry via the ACE2 receptor – Explains the tropism for the lung – Highly expressed on type 2 pneumocytes – Surfactant production is decreased ARDS – Also expressed in intestinal epithelium and vascular endothelium – Increased expression with hypertension, Diabetes, heart failure, age May explain the increased susceptibility and disease severity with age and comorbidity

Goldsmith, CS et al. Ultrastructural Characterization of SARS Coronavirus, February 2004 Emerging infectious diseases 10(2):320-6

Replicase – Virus replication depends on the viral replicase Minimal error detection Very high mutation rate Viral strains – Potential for therapy

https://nextstrain.org/ncov Accessed 5/5/2020

Incubation and Symptoms Incubation Period: Within 14 days. Onset of symptoms usually within 2-7 days of exposure with median of 4-5 days Symptoms – Fever 99% over course of disease – Dry cough (45-80%) – URI Sx (5-25%) – GI Sx (10-20%) – Taste/Smell alterations

Spectrum of Disease  81%: No/mild sx  14% Severe  5% with critical disease and resp failure, shock, MOF  Case Fatality 0.7- 5.8% Verity, R et.al. Estimates of the severity of coronavirus disease 2019: a model-based analysis. Lancet 3/30/2020. https://doi.org/10.1016/S1473-3099(20)30243-7

Spectrum of Disease: Cyclists  Almost all have symptoms  Almost all have mild sx  GI symptoms may be more frequent  Multiple studies of pts with mild symptoms  Up to 25% may have diarrhea only  My anecdotal experience

Disease Course Zhou, Fei et.al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet 3/11/2020. DOI:https://doi.org/10.1016/S0140-6736(20)30566-3

Disease Phases Siddiq et al. COVID-19 illness in native and immunosuppressed states: A clinical − therapeutic staging proposal. http://www.jhltonline.org

Phases Guide Therapy Decrease Replication Reduce Lung Damage Decrease Cytokines Remdesivir Supportive Anti IL-6 Tociluzimab Conv. Plasma? ? Steroids Anti IL-1R Anakinra Monoclonal Ab / HI IVIG BTK Inhibitors Calquence Reduce immune suppression Steroids No Steroids! Siddiq et al. COVID-19 illness in native and immunosuppressed states: A clinical − therapeutic staging proposal. http://www.jhltonline.org

Disease Course Zhou, Fei et.al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet 3/11/2020. DOI:https://doi.org/10.1016/S0140-6736(20)30566-3

Therapy The Trump Way Test Frequently / Treat Early Remdesir Regeneron (2 anti-spike Monoclonal Ab) Steroids It works!

Transmission Reproduction number – R0 – Average number of people infected by one sick person – Generally if that number is greater than one, then the virus will spread SARS CoV-2 features that contribute to spread – Presymptomatic carriers – Period of spreading before symptoms – Very high susceptibility- no herd immunity

Influenza

How the SARS-CoV-2 compares with other infectious diseases Image credit: (New York Times)

Transmission paradox While the initial Reproduction number (R0) was 2.4... – Extensive contact tracing studies confirm that 70% of patients transmit the virus to 0 others – Attack rate among close family contacts of infected individuals remains at around 15- 20% Yet there are “superspreader” events that transmit to large numbers

Modes of Transmission Viral respiratory infections can be transmitted by contact, droplet or respiratory (airborne) modes. – Typically not more than 3 feet Airborne transmission is driven by the droplet size: If less than 5 microns then it floats Examples of naturally occurring airborne viruses: – Varicella, Smallpox, measles

SARS CoV-2 Transmission Droplet and Contact - confirmed – ? Stool – ? Airborne

Aerosol and surface stability of SARS-CoV-2 Virus detected up to 72 hours on hard sufaces, 4 hours on cardboard 3 hours in aerosols Experimental creation of aerosolized SARS CoV-2 – “In short, aerosols (<5 μ m) containing HCoV-19 were generated using a 3-jet Collison nebulizer and fed into a Goldberg drum to create an aerosolized environment” – Experimentally produced aerosols Does not represent the clinical scenario van Doremalen N, Bushmaker T, Morris DH, et al. Aerosol and surface stability of SARS-CoV-2 as compared with SARS-CoV-1. N Engl J Med

Droplet?

Viral Shedding vs RT PCR Virological assessment of hospitalized cases of coronavirus disease 2019. Wolfel, R et al.

Real World Experience With SARS CoV-2 Transmission Primarily Droplet and Contact – Analysis of more than 75,000 cases did not indicate airborne transmission – Air sampling of cases of patients with high viral load did not detect airborne virus 10cm (4 inches) from coughing patient - Negative 4 hours x 5L/ min – Negative – Nebraska study: Air samples positive by rt-PCR – Samples collected near the patient (bedside desk) – NO viral culture medRxiv preprint doi: https://doi.org/10.1101/2020.03.23.20039446

PPE- Actual experience Wuhan- 1300 healthcare workers infected – 3X the normal population – Imported 42,000 additional HCW None became infected – strict PPE Singapore (0) / Hong Kong (0) – Basic mask, hand hygiene, distance – N95, goggles and gown only high risk cases and for aerosolizing procedure

Case Report- Hong Kong Patient with a high viral load – 11 unprotected exposures no transmission – Samples from air with coughing, no mask (10cm) Negative Samples from room – 12/13 negative, 1/13 positive – Cheng, V., Wong, S., Chen, J., Yip, C., Chuang, V., Tsang, O., . . . Yuen, K. (n.d.). Escalating infection control response to the rapidly evolving epidemiology of the Coronavirus disease 2019 (COVID-19) due to SARS-CoV-2 in Hong Kong. Infection Control & Hospital Epidemiology, 1-24. doi:10.1017/ice.2020.58

Case report - Singapore Pt intubated x 3 days, then extubated, bipap – Then tested positive for SARS CoV-2 41 HCW exposed to aerosol generating procedure for over 10 minutes – No positives – 85% surgical mask only ” Our observation is consistent with previous studies that have been unable to – show that N95 masks were superior to surgical masks for preventing influenza infection in health care workers” Ng K, Poon BH, Kiat Puar TH, et al. COVID-19 and the Risk to Health Care Workers: A Case Report. Ann Intern Med. 2020; [Epub ahead of print 16 March 2020]. doi: https://doi.org/10.7326/L20-0175

US experience UC Davis – 85 HCW quarantined after exposure to Covid19 patient without protection All tested negative Sacramento, Seattle, and San Francisco became coronavirus hot spots – significant occupational transmission has not been found. “Transmission seems to occur primarily through sustained exposure in the absence of basic protection or through the lack of hand hygiene after contact with secretions.” Gawande, The New Yorker. 3/21/2020

Flattening the Curve When early intervention does not happen, transmission accelerates and peaks prior to management and/or independent decrease in Ro. VOX.COM

Testing Three basic methods – Viral culture: Inoculate a sample into a cell culture that is know to support viral replication Slow – but correlated to infectivity – PCR – Polymerase Chain Reaction. Amplifies fragments of the viral genome (RNA) Faster – 4-6 hours, but typically batched – Antigen detection

RT-PCR Test Performance Sample site / Severity / Timing Mild Severe 0-7 days Sputum 82% 89% Nasal 73 72 Throat 61 60 8-14 days Sputum 83 74 Nasal 53 72 Throat 30 50 Bronchoalveolar Lavage 100% except mild disease / late testing – Yang et almedRxiv preprint doi: https://doi.org/10.1101/2020.02.11.20021493

• Abbott Labs isothermal nucleic acid amplification / detection system • Promises positive results in as little as 8 minutes • negative results in 30 minutes • Same caveats as RT=PCR, but faster. • Accuracy not known

Real-World Performance or Abbott ID Now 545 Paired swabs – Positive agreement = 75% – Negative agreement = 99% – “Overall, the ID Now COVID-19 assay was associated with lower performance characteristics compared to the Abbott RealTime SARS-CoV-2 assay.” Comparison of Abbott ID Now (IDNCOV) and Abbott m2000 Methods for the Detection of SARS-CoV-2 from Nasopharyngeal and Nasal Swabs from Symptomatic Patients (Harrington, August 2020).