Am J Emerg Med undefined

Silent hypoxia: A harbinger of clinical deterioration in patients with COVID-19

^{Department of Emergency Medicine, University of Maryland School of Medicine, Baltimore, MD, United States of America}

^{Division of Pulmonary & Critical Care, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, United States of America}

^{Department of Emergency Medicine, University of Maryland Medical Center, Baltimore, MD, United States of America}

R. Gentry Wilkerson: ude.dnalyramu.mos@nosrekliwg

^{Corresponding author at: Department of Emergency Medicine, University of Maryland School of Medicine, 110 S Paca St, 6th Floor, Suite 200, Baltimore, MD 21201, United States of America.}ude.dnalyramu.mos@nosrekliwg

Received 2020 May 5; Revised 2020 May 13; Accepted 2020 May 14.

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Infection with the novel coronavirus, SARS-CoV-2, leads to development of the syndrome COVID-19 [²]. The clinical manifestations of infection range from entirely asymptomatic to severe respiratory failure and death [³]. The SARS-CoV-2 virus infects the host using the angiotensin-converting enzyme 2 (ACE2) receptor [⁴]. The ACE2 receptor is a membrane-bound aminopeptidase expressed in numerous organs such as the lung, brain, intestines, and heart [⁵6]. Published reports of histopathological examination of lung tissue describe alveolar and interstitial exudative inflammation with macrophage and monocyte predominance, as well as focal respiratory epithelial desquamation, hemorrhage, and type 2 pneumocyte proliferation [⁷8]. Patients may develop a hyperinflammatory syndrome with a cytokine profile similar to secondary hemophagocytic lymphohistiocytosis [⁹]. An unusual clinical picture has emerged in some patients with SARS-CoV-2 infection: the development of hypoxia that is out of proportion to the patient's symptoms. This has been called silent or apathetic hypoxia [¹1011]. Gattinoni et al. proposed that this clinical picture may represent a phenotype of COVID pneumonia (Type L), where there is low elastance and near normal compliance. The alternative phenotype, Type H, is similar to what is seen in acute respiratory distress syndrome (ARDS) [¹²]. In contrast, Ziehr et al. described a cohort of patients intubated early in the disease process. This cohort had low compliance and a uniform presentation consistent with the Berlin definition for ARDS [¹³]. Undoubtedly, our understanding of the respiratory mechanics found in COVID-19 will continue to evolve as additional research is reported. In the following case summary, we describe a patient who presented with minimal symptoms but was found to have a dramatic decrease in oxygen saturation.

A 72-year-old male with a history of diabetes, hypertension, and obesity presented to the emergency department for evaluation of shortness of breath. Three weeks prior to presentation the patient was diagnosed with influenza based on clinical symptoms and treated with oseltamivir. The patient reports that his symptoms continued to be mild with cough productive of minimal blood-tinged sputum. He denied having fevers, myalgias, headache, diarrhea, or loss of taste or smell. On the day of presentation, the patient was visited by his daughter who felt that he was having difficulty breathing. On arrival to the patient's house, paramedics found him to have an oxygen saturation (SpO₂) of 85% with normal respiratory rate and effort. The patient was given supplemental oxygen and brought to the emergency department (ED). On arrival to the ED, his vital signs were as follows: blood pressure, 118/77 mm Hg; heart rate, 80 beats/min; respiratory rate, 14 breaths/min; SpO₂ 88% on room air, and temperature, 38.8 °C. On examination, he was in no acute distress and conversant with unlabored speech. His breath sounds were unremarkable. The remainder of his examination was absent of any acute abnormality. Supplemental oxygen via non-rebreather mask at 15 L/min was administered as well as albuterol via metered dose inhaler. His oxygen saturation improved to 97% after these interventions.

Laboratory studies demonstrated the following values: blood glucose, 170 mg/dL; bicarbonate, 25 mEq/L; creatinine, 4.06 mg/dL; lactic acid, 0.4 mg/dL; white blood cell count, 6.6 × 10^{/μL. The white blood cell differential demonstrated lymphopenia of 10.5% (normal, 20–40%). A portable chest radiograph demonstrated perihilar pulmonary opacities bilaterally. The patient was admitted to the medical intensive care unit (MICU) for multifocal pneumonia, possible SARS-CoV-2 infection, and acute kidney injury (}Fig. 1).

Fig. 1

Portable anteroposterior chest radiograph (CXR) demonstrating perihilar pulmonary opacities bilaterally.

The following day the patient's SARS-CoV-2 test result was positive. His clinical course deteriorated while he was in the MICU and he was endotracheally intubated approximately 24-h after initial presentation. On the following days, he had interval development of shock requiring vasopressor support with multi-organ system failure. With consultation from the palliative care service, the family decided to no longer escalate care and the patient died on hospital day 8.

In this report, we have described a patient with COVID-19 due to SARS-CoV-2 infection who presented with hypoxia out of proportion to his clinical presentation. This “silent hypoxia” may be a clinical sign that providers can look for to determine if patients are at increased risk of sudden decompensation. Further study would be required to determine if home monitoring with pulse oximetry devices provides earlier recognition of patients requiring medical evaluation and supportive care.

References

1. Ottestad W., Seim M., Mæhlen J.OCOVID-19 with silent hypoxemia. Tidsskr Nor Laegeforen. 2020;140(7) doi: 10.4045/tidsskr.20.0299.[PubMed][Google Scholar]
2. Zhu N., Zhang D., Wang WA novel coronavirus from patients with pneumonia in China, 2019. N Engl J Med. 2020;382(8):727–733. doi: 10.1056/NEJMoa2001017.] [[Google Scholar]
3. Wu Z., McGoogan J.MCharacteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72 314 cases from the Chinese Center for Disease Control and Prevention. JAMA. 2020 doi: 10.1001/jama.2020.2648. February. [[PubMed][Google Scholar]
4. Hoffmann M., Kleine-Weber H., Schroeder SSARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell. 2020;181(2):271–280.e278. doi: 10.1016/j.cell.2020.02.052.] [[Google Scholar]
5. Hamming I., Timens W., Bulthuis M.L.C., Lely A.T., Navis G.J., van Goor H. Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. J Pathol. 2004;203(2):631–637. doi: 10.1002/path.1570.] [
6. Chen L., Li X., Chen M., Feng Y., Xiong CThe ACE2 expression in human heart indicates new potential mechanism of heart injury among patients infected with SARS-CoV-2. Cardiovasc Res. 2020;116(6):1097–1100. doi: 10.1093/cvr/cvaa078.] [[Google Scholar]
7. Tian S., Hu W., Niu L., Liu H., Xu H., Xiao S.-YPulmonary pathology of early-phase 2019 novel coronavirus (COVID-19) pneumonia in two patients with lung cancer. J Thorac Oncol. 2020;15(5):700–704. doi: 10.1016/j.jtho.2020.02.010.] [[Google Scholar]
8. Xu Z., Shi L., Wang YPathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respir Med. 2020;8(4):420–422. doi: 10.1016/S2213-2600(20)30076-X.] [[Google Scholar]
9. Mehta P., McAuley D.F., Brown MCOVID-19: consider cytokine storm syndromes and immunosuppression. Lancet. 2020;395(10229):1033–1034. doi: 10.1016/S0140-6736(20)30628-0.] [[Google Scholar]
10. Gattinoni L., Coppola S., Cressoni M., Busana M., Rossi S., Chiumello DCovid-19 does not lead to a “typical” acute respiratory distress syndrome. Am J Respir Crit Care Med. March 2020 doi: 10.1164/rccm.202003-0817LE. rccm.202003–0817LE. [[PubMed][Google Scholar]
11. Ottestad W., Søvik SCOVID-19 patients with respiratory failure: what can we learn from aviation medicine? Br J Anaesthesia. April 2020 doi: 10.1016/j.bja.2020.04.012.[PubMed][Google Scholar]
12. Gattinoni L., Chiumello D., Caironi PCOVID-19 pneumonia: different respiratory treatments for different phenotypes? Intensive Care Med. 2020;382:727–734. doi: 10.1007/s00134-020-06033-2.[PubMed][Google Scholar]
13. Ziehr D.R., Alladina J., Petri C.RRespiratory pathophysiology of mechanically ventilated patients with COVID-19: a cohort study. Am J Respir Crit Care Med. 2020 doi: 10.1164/rccm.202004-1163LE. April. [[PubMed][Google Scholar]