COVID-19 pandemic

Miguel Sierra Hoffman MD

 Diplomate, American Board of Internal Medicine
 Diplomate, American Board of Infectious Disease
 Diplomate, American Board of Pulmonary / CC
 Wound care certified
135 Day Story:
 Professor of Medicine, UNAH , Internal Medicine
Post graduate program Lessons Learned
 Associate Professor of Infectious disease, Baylor Scott
& White, Temple Tx, Infectious disease fellowship
 Texas A&M Research Director, Family Medicine ,
Residency program, Victoria Tx
 Objectives
• Time Line
• Virology
• Epidemiology
• Clinical presentation
• Hospital variants
• Pathophysiology
• ICU management
• Potential therapeutics
• PPE
• What works , what may work , what doesn’t
• Out Look
• Conclusions
 Disclosures
 Dr. Sierra-Hoffman has nothing to disclose
 Appreciation To:
 Dr. Rafael Deliz
 Dr. Michael Lin
 Hospital Metropolitano de Quito, Dra. Cisneros
 University of California-San Francisco
 Stanford University
 Harvard Medical School
 University of Miami
 Society of Critical Care Medicine (SCCM)
 American Thoracic Society (ATS)
 European Society of Critical Care
 MedCram
 Britt Glaunsinger PhD
 Maria Elena Botazzi PhD
 Onset of Illness among the First 425 Confirmed
Cases of Novel Coronavirus (2019-nCoV)–Infected
Pneumonia (NCIP) in Wuhan, China.

Q Li et al. N Engl J Med 2020. DOI: 10.1056/NEJMoa2001316

ENDEMIC VS
EPIDEMIC
HCO-V
The “ Spillover “
5
5
5
 Viability of SARS-CoV-1 and SARS-CoV-2 in Aerosols and on
Various Surfaces.

N van Doremalen et al. N Engl J Med 2020. DOI: 10.1056/NEJMc2004973

 Diagnostic Confirmation of COVID-19

 RT-PCR : most commonly used method for diagnosis

 Sens 32%–93% in the nasopharynx and upper respiratory tract
(lowest in the pharynx, and highest in bronchoalveolar lavage fluid
specimen), while nasal swabs had a 63% sens
 Serum immunoglobulins (IgM and IgG) can be used to diagnose
recent infection to COVID-19
 Timeline of Exposure to Index Patient with
Asymptomatic 2019-CoV Infection in Germany.
Symptoms and Maximum Body Temperatures According
to Day of Illness and Day of Hospitalization, January 16
to January 30, 2020.

ML Holshue et al. N Engl J Med 2020;382:929-936.

 The Spectrum of COVID-19 Disease
As the cases illustrate, and as you have heard:
Wide spectrum of COVID-19 disease

?
Asymptomatic

80%
Mild

Moderate 14%

Severe 6%

Verity et al. Lancet ID. 2020

 Laboratory testing
 Lymphopenia, elevated CRP,
cytokines, D-dimer,
procalcitonin and ferritin,
LDH, IL-6
 IL-6 may identify cases with
poor prognosis and prompt
intervention in order to
improve outcomes IL-6 and survival
 No magic biomarker or
combination for absolutely
predicting bad outcomes
 Age

Children have very low morbidity

 From: Association of Cardiac Injury With Mortality in Hospitalized Patients
With COVID-19 in Wuhan, China
JAMA Cardiol. Published online March 25, 2020. doi:10.1001/jamacardio.2020.0950

Figure Legend:
Mortality During Hospitalization Between Patients With vs Without Cardiac Injury A-B, Kaplan-Meier survival curves for mortality
during the time from symptom onset (A) and admission (B). In (B), the maximum duration was 16 days. C, Patients with cardiac
injury had a higher rate of mortality in log-rank test, both from symptom onset and from admission.
 Risk Prediction
 Risk factors from UK NHS data
(17 million – 5,000+ deaths
 Strongest risk factors: age, male
sex, obesity, diabetes,
hematologic malignancy, organ
transplantation history
 Not hypertension

 Consistent with NYC

experience

Williamson et al. Preprint: https://www.medrxiv.org/content/10.1101/2020.05.06.20092999v1.full.pdf

 CT SCAN findings of COVID-19

33 years old
female in
Wuhan, China

Ground-glass opacities 3 days after follow-up shows

bilaterally without subpleural progressive ground-glass
sparing opacities

Radiology 2020
Heterogenous disease
 COVID-19 CT Scan in Laredo Hospitals
40 years old female

Bilateral patchy
ground glass
infiltrates with
consolidations
without subpleural
sparring
 3D Reconstruction CT chest in COVID-19

Images in a 41-year-old woman who presented with fever and positive polymerase chain
reaction assay for the 2019 novel coronavirus (2019-nCoV). Three-dimensional volume-rendered
reconstruction shows the distribution of the ground-glass opacities (arrows). See also three-dimensional
Movie (online).

Radiology 2020
 COVID 19 Negative by NAA but has the
disease

Figure d: Images in a 36-year-old man with a 2-day history of fever, sore throat, and fatigue 5 days after visiting Wuhan, China, and a negative sputum real-
time fluorescence polymerase chain reaction assay for the 2019 novel coronavirus. (a, b) Chest CT scans obtained at presentation show ground-glass
opacities (red box) in the right upper lobe and the lingular segment and left lower lobe (b). (c) Volume rendering of chest CT scan obtained at admission. (d,
e) CT scans obtained 3 days after admission show progression of ground-glass opacities to an atoll sign in the right upper lobe (red boxes in d) and left
lower lobe consolidation (red boxes in e). (f) Volume rendering of chest CT scan obtained 3 days after admission shows the new areas of consolidation.
See also Movies 1 and 2 (online)
Radiology 2020
COVID 19 Negative by NAA but has the
disease

Figure e: Images in a 36-year-old man with a 2-day history of fever, sore throat, and fatigue 5 days after visiting Wuhan, China, and a negative sputum real-
time fluorescence polymerase chain reaction assay for the 2019 novel coronavirus. (a, b) Chest CT scans obtained at presentation show ground-glass
opacities (red box) in the right upper lobe and the lingular segment and left lower lobe (b). (c) Volume rendering of chest CT scan obtained at admission. (d,
e) CT scans obtained 3 days after admission show progression of ground-glass opacities to an atoll sign in the right upper lobe (red boxes in d) and left
lower lobe consolidation (red boxes in e). (f) Volume rendering of chest CT scan obtained 3 days after admission shows the new areas of consolidation. See
also Movies 1 and 2 (online)

Radiology 2020
Natural History

Oberfeld et al. Cell. 2020

 Immune Response

Successful Immune response involves both cell-

mediated and innate immunity

Some evidence that cross reactivity of cell mediated

immunity to other beta-coronaviruses may be
associated with milder course

Some mild cases seem to have lower antibody

responses

Are antibodies always measureable?

 The Huge roll of Inflammation

Semin Immunopathol (2017) 39:517–528

Nature Medicine | VOL 24 | JUNE 2018 | 703–710 | www.nature.com/naturemedicine
61
Interferon Role
5
Anti
Coagulation
Role
Thrombophilia

Cell Research (2020) 30:367–369; https://doi.org/10.1038/s41422-020-0327-4

 Hypercoagulability
 In severe cases, late:
 Increase in thrombotic events (micro and macro)
 Elevated d-dimer, increased pro-thrombin time, decrease in fibrinogen
 Has prompted some use of tPa and anticoagulation

This concerning report from our institution; 5 cases of

patients <50 years [NEJM April 2020]

Also seeing large pulmonary emboli in severe COVID-19

 Outcomes: The New York Experience
 First large paper from a NYC health system from the Northwell (Long Island) system
 5700 hospitalized patients
 When comparing patients who were discharged alive vs died, death proportion was 21%
 No measure of COVID-19 severity
 [Davidson et al. JAMA. April 22 2020]

 For our large health system:

 Between 2/27/20 – 4/2/20 at 5 of the largest hospitals we admitted 2,199 COVID-19 patients

Admissions peaked ~4/10

 COVID-19 in Special Populations
 Since the outset in China –
severe disease clearly impacts From China
certain groups more 105 cancer
500+ age matched comparators
 Key comorbidities include: (Cancer Discovery, April 2020)
obesity, diabetes, cancer

 Organ transplant patients also

signals towards worse
outcomes (NEJM April 2020)

 Our data for HIV (88 HIV+,

405 comparators no difference
in outcomes

Sigel et al. under review

JAMA. doi:10.1001/jama.2020.6019
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MEDCRAM
Potential & Science behind Ivermectin
Ivermectin

Patel, Amit, Usefulness of Ivermectin in COVID-19 Illness (April 19, 2020).

Natural History – Hospitalized Patients

Zhao et al. Lancet – March 28

2020
 5

Jama March 2020

Therapy for ARDS in COVID-19 patients

The Lancet Respiratory Medicine DOI: (10.1016/S2213-2600(20)30127-2)

Copyright © 2020 Elsevier Ltd Terms and Conditions
 Proning, a
technique for
improving Proning
oxygenation in
ARDS patients, has
been adapted to
COVID-19
 NYC ER published
series of 50 patients
with COVID-19
hypoxia; significant
improvement with
awake proning
From Massachusetts
General Hospital
Careful fluid management is also advocated from
observational experiences
5
 Resumen

Tay, M. Z., Poh, C. M., Rénia, L., MacAry, P. A., & Ng, L. (2020). The trinity of COVID-19: immunity, inflammation and intervention. Nature
reviews. Immunology, 1–12. Advance online publication. https://doi.org/10.1038/s41577-020-0311-8
What does not work

• H02
• 02H
• 2HO
Fernando Valerio MD
Oscar Diaz MD
Bryan Contreras MD
Daniel Espinoza MD
Miguel Sierra Hoffman MD
VIVA Ecuador