Coronavirus Outcomes

Acute Hypoxemic Respiratory Failure (AHRF)

• Definition: Hypoxemia (PaO2 <60 mmHg) with a PaCO2 that is low or normal
• Present when O2 saturation is <90% despite FiO2 >0.6.

• In COVID-19 this is initially caused by viral pneumonia

Acute Hypoxemic Respiratory Failure

• 17-29% of patients with COVID-19 pneumonia then progress to ARDS

• Impending ARDS is suggested by an increase in inflammatory markers:
• IL-6 > 40-100
• CRP >10x normal
• Ferritin >1000

Acute Respiratory Distress Syndrome (ARDS)

Berlin Criteria

Timing

Within 1 wk of known clinical insult or new or worsening respiratory symptoms

Origin

Acute onset pulmonary edema not explained by fluid overload or CHF (PCWP <18mmHg)

Acute Respiratory Distress Syndrome

Oxygenation

Hypoxemia (PaO2 < 60mmHg) refractory to oxygen therapy with an abnormal PaO2 / FiO2 ratio.

• 200-300: mild ARDS
• 100-200: moderate ARDS
• <100 severe ARDS

ARDS is heterogenous, with different clinical features and outcomes determined by the pathogenesis and immunologic response.

COVID-19 ARDS

• Between 20-42% of hospitalized COVID-19 patients develop ARDS

• Median time between initial symptoms & ARDS: 8 days

• CT findings demonstrate more advanced ground glass opacities, often with consolidation (predominantly in the subpleural region of the lower lobes)

COVID-19 ARDS

75 yo M with COVID-19. Axial lung window submitted to Radiopedia by Dr. Macori.

Secondary Bacterial Pneumonia

• Early studies show that secondary bacterial pneumonia is not a major feature of COVID-19. However, cohorts from China reported this complication in 12% of patients (may be related to the use of glucocorticoids).

Secondary Bacterial Pneumonia

• Critically ill patients with COVID-19 who are intubated for extended periods of time (1-2 weeks or longer) are at risk for developing Ventilator-Associated Pneumonia and other infections typical of critically ill patients(UTIs and central line infections).

• Bacterial and influenza co-infections are difficult to distinguish from COVID-19 alone but early reports indicate these are uncommon.

Pathophysiology

Myocardial dysfunction results from:

• Critical illness stress: an acute hyper-inflammatory response can lead to plaque destabilization, myocardial inflammation, and demand ischemia, leading to myocardial damage.

Pathophysiology

• Direct viral effect: there have been multiple reports of COVID-19 viral-mediated myocarditis.
• A recently published case from Italy demonstrates histopathologic evidence of myocardial infiltration of SARS-CoV-2 in a patient with myocarditis.

• Prior reports from outbreaks of SARS and MERS suggest some viral tropism for cardiac tissue.

Clinical Presentation

Clinical Manifestations of Myocardial Dysfunction

• Electrocardiographic abnormalities (ST-T changes)

• Elevations in cardiac enzymes

Presentation

• Echocardiographic evidence of diastolic and systolic impairments

• Signs and symptoms of cardiogenic shock

Take Home Point: outcomes for advanced stages of COVID-19 include respiratory collapse, shock, and cardiogenic failure as multiple organ systems are affected

Review: AKI

1. Increase in SCr greater than or equal to 0.3mg/dL within 48hrs compared to baseline;

OR

2. Increase in SCr greater than or equal to 50% (known or presumed to have occurred during the previous 7 days);

OR

3. Urine volume <0.5 mL/kg/h for 6 hrs

Mortality by Country

Presently, global mortality

is reported at 4.7%

but CFR varies

widely by location

Mortality

Disclaimer: data based on crude CFR for all cases reported through 04/07/2020.

• The majority of patients are able to recover from mild COVID-19, though there is little data available on long-term outcomes of this illness

COVID-19

Resolution

Resolution

• A case series on 1591 patients admitted to ICUs in Lombardy, Italy between Feb 20, 2020 and March 18, 2020 reported that by the end of this time period:
• 16% were discharged
• 26% had died
• 58% were still in the ICU

• The study’s authors expected the death rate to increase substantially had they continued to track patients who remained in the ICU

• Reports from China and Japan indicate that recovered patients who tested negative for the virus on RT-PCR later tested positive on hospital readmission

• It is unclear if these were true re-infections or if the tests were falsely negative at the time of discharge.

• Substantial seasonal mutation of SARS-CoV-2 has not been observed.

Re-Infection

Re-infection

• While other coronaviruses demonstrate evidence of reinfection, this usually does not happen for many months or years.

• Some reassuring evidence comes from a challenge study among rhesus macaques:

• After initial challenge and clearance of SARS-CoV-2, the animals were re-challenged with the virus but were not infected.

References (cont.)

• Omer SB, Malani P, del Rio C. The COVID-19 Pandemic in the US: A Clinical Update. JAMA.

Published online April 06, 2020. doi:10.1001/jama.2020.5788

• Oudit, G. Y., Kassiri, Z., Jiang, C., Liu, P. P., Poutanen, S. M., Penninger, J. M., & Butany, J. (2009).

SARS-coronavirus modulation of myocardial ACE2 expression and inflammation in patients with SARS. European Journal of Clinical Investigation, 39(7), 618–625. doi: 10.1111/j.1365-2362.2009.02153.x

• Pan, X.-W., Xu, D., Zhang, H., Zhou, W., Wang, L.-H., & Cui, X.-G. (2020). Identification of a

potential mechanism of acute kidney injury during the COVID-19 outbreak: a study based on single-cell transcriptome analysis. Intensive Care Medicine. doi: 10.1007/s00134-020-06026-1

• Phua, J., Weng, L., Ling, L., Egi, M., Lim, C.-M., Divatia, J. V., … Du, B. (2020). Intensive care

management of coronavirus disease 2019 (COVID-19): challenges and recommendations. The Lancet Respiratory Medicine. doi: 10.1016/s2213-2600(20)30161-2

• Ranieri, V. M., Rubenfeld, G. D., Thompson, B. T., Ferguson, N. D., Caldwell, E., Fan, E., … Slutsky,

A. S. (2012). Acute Respiratory Distress Syndrome. Jama, 307(23). doi: 10.1001/jama.2012.5669

• Reilly, J. P., & Meyer, N. J. (2014). Pattern recognition in ARDS: a crucial first step toward

personalised treatment. The Lancet Respiratory Medicine, 2(8), 594–595. doi: 10.1016/s2213-2600(14)70116-x

• Report of the WHO-China Joint Mission on Coronavirus Disease 2019 (COVID-19). (2020, February

28). Retrieved April 8, 2020, from https://www.who.int/publications-detail/report-of-the-who-china-joint-mission-on-coronavirus-disease-2019-(covid-19)

• Bialek, S., Boundy, E., Bowen, V., Chow, N., Cohn, A., Dowling, N., … Sauber-Schatz, E. (2020).

Severe Outcomes Among Patients with Coronavirus Disease 2019 (COVID-19) — United States, February 12–March 16, 2020. MMWR. Morbidity and Mortality Weekly Report, 69(12), 343–346. doi: 10.15585/mmwr.mm6912e2

• Yang, X., Yu, Y., Xu, J., Shu, H., Xia, J., Liu, H., … Shang, Y. (2020). Clinical course and outcomes

of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study. The Lancet Respiratory Medicine. doi: 10.1016/s2213-2600(20)30079-5

• Zhou, F., Yu, T., Du, R., Fan, G., Liu, Y., Liu, Z., … Cao, B. (2020). Clinical course and risk factors

for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. The Lancet, 395(10229), 1054–1062. doi: 10.1016/s0140-6736(20)30566-3

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