Chief Complaint:

Altered Mental Status

HPI:

69-year-old male with history of diabetes brought in by his son to the emergency department with altered mental status. Patient is unresponsive and all history is from his son and chart review. Son reports that he had increasing shortness of breath and confusion since last night at 8pm so he brought him to ED.

Review of Systems:

Not obtained secondary to mental status.

Pertinent Exam Findings:

General Appearance: Patient is tachypneic, acutely ill-appearing, eyes are closed, grimaces to sternal rub.
Head: Atraumatic.
Eyes: Pupils equal round and reactive to light, eye movements normal.
ENT: Mucous membranes are dry
Respiratory: Tachypneic
Cardiovascular: Tachycardic rate and regular rhythm, extremities well perfused
Gastrointestinal: Abdomen is soft, nontender
Skin: Warm, dry, no rashes
Musculoskeletal: Neck is supple, non-tender. Extremities without deformity
Neurological: Patient grimaces to sternal rub, keeps eyes closed, does not have any verbal sounds to painful stimuli

Data Interpretation:

CBC: Lymphocytopenia and leukocytosis
BMP: Anion gap metabolic and acidosis
ABG: Profound metabolic acidemia with pH 6.8
Urine: Ketones consistent with DKA
Chest x-ray: Bilateral infiltrates suspicious for multifocal pneumonia versus COPD, appropriate endotracheal tube placement

Relevant Prior Records:

Seen 4 days prior in our ED for 4 days of cough, chest pain, headache, body aches. Pulse ox was 92% on RA that visit. CBC, BMP unremarkable except for lymphocytopenia. Flu negative. COVID-19 test sent. Nonspecific patchy bilateral lower lobe airspace disease. Didn’t meet admission criteria though it was discussed with the admitting team. Patient was sent home with quarantine instructions.

ED Course:

Blood sugar was checked and is in the 500s. Clinically the patient was in DKA, chart review showed the patient was recently here for URI symptoms on Monday. Patient was intubated for airway protection and impending resp failure. Given IV broad spectrum antibiotics, treated for DKA with IVF, IV insulin drip and supplemental IV Potassium. Patient was admitted to the ICU under COVID-19 precautions.

Figure 1: CXR from initial ED visit on 3/16 showing bilateral patchy consolidations.

Figure 2: CXR from 2nd ED visit on 3/20 showing worsening bilateral patchy consolidations from prior with ETT in place.

Hospital Course:

Positive COVID test took 7 days to result from the sample sent from the initial ED visit. Remained intubated and treated with vancomycin and zosyn for coinfection from aspiration. Completed a 5 day course of hydroxychloroquine. Peg and Trach performed. Still intubated and in ICU when this was written on day 25 of hospital course.

DISCUSSION:

Background:

Coronavirus Disease 2019 (COVID-19) caused by the Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) was first identified after 27 patients developed pneumonia in Wuhan, Hubei Province, China in December 2019. This novel virus continued to spread, leading the World Health Organization (WHO) to declare a global pandemic on March 11th, 2020. As of April 20th, 2,422,525 cases of SARS-CoV-2 infection were reported worldwide and 760,245 cases were reported in the United States.

The virus is believed to be primarily transmitted person-to-person by respiratory droplets while within 6 feet distance. The droplets can persist on surfaces as well for up to 3 days, depending on the material, increasing community spread via fomite-to-face transmission. Typical presenting symptoms include fever, cough, dyspnea, chest pain or tightness and fatigue. Progression of the disease can result in acute respiratory distress syndrome and cytokine storm. There are currently no definitive treatments or vaccinations for COVID-19. Because of the community transmission rates, hospitals are facing difficulties in treating the initial surplus of patients safely.

Diagnosis:

Diagnosis is important in the treatment of COVID-19 as well as for epidemiological purposes, but many patients can be presumed infected due to the widespread nature of the virus. A presumptive positive diagnosis of COVID-19 in a patient can be made if the patient arrives in the ED with symptoms like fever, shortness of breath, or a dry cough. Importantly, the virus has an incubation period of 2-14 days, though case reports of longer have been documented. Additional common symptoms reported in COVID-19 patients include anosmia and diarrhea. Labs can help establish concurrent issues but have limited utility in diagnosing a COVID-19 infection. However, a lab test that can support a presumptive diagnosis is lymphocytopenia which is found in 70-80% of cases. Other nonspecific but common findings include, elevated d-dimer, CRP, LDH, thrombocytopenia, leukopenia.

Imaging, while not diagnostic, can be used as a part of the whole clinical picture to aid in diagnosis. Chest x-rays are frequently normal in the early stages of the infection, however bilateral ground glass opacities and consolidations are commonly seen on CXR usually peaking at days 10-12 of infection. Chest computerized tomography has been frequently used in clinical practice but is not routinely recommended and should not be used as a screening tool.

Currently the best laboratory method for COVID-19 diagnosis is a real time polymerase chain reaction (RT-PCR) test. Nasopharyngeal or oropharyngeal swabs are recommended for sample collection, but bronchiolar lavage and stool samples can also be used. Initially, RT-PCR testing could take up to a week before resulting; however, since the initial outbreak of the novel coronavirus, testing has improved and some tests can result as quickly as the same day the sample is collected. Sensitivity of this test is not yet known but has been suggested to be as low as 60%.

Management in ED:

The first step in treating or addressing a patient with confirmed or suspected COVID-19 is taking the correct personal precautions. While the proper personal protective equipment (PPE) may not be readily available due to global shortages, every attempt should be made to limit the virus’s infectious spread and protect medical providers on the front lines. The CDC and WHO recommend gown, gloves, eye protection/shield, and a mask/respirator (N95) depending on clinical situation and availability. If possible, infected patients or patients presumed infected should be placed in negative pressure rooms to help limit the nosocomial spread of the virus.

The mainstay of COVID-19 treatment is supportive care, allowing the virus to run its course. Like any other patient, vitals must be monitored, but with COVID-19 patients close monitoring of oxygen saturation is essential due to the respiratory nature of the virus. Oxygen support may be the most important therapeutic intervention clinicians can make. Consensus for the best approach in management of the hypoxic patient has remained a moving target over the course of the COVID-19 pandemic. Initially early intubation for suspected acute respiratory distress syndrome (ARDS) was thought to be the best course of action. This was partly because intubation was the recommended course in prior coronavirus epidemics (SARS/MERS), but also because it is the standard course of action for ARDS. We are seeing variations from typical ARDS, such as better lung compliance with COVID-19 than typical ARDS. Currently, it’s recommended that hypoxic patients are initially managed with non-invasive oxygen therapies like high flow nasal cannula, Venturi mask, or non-rebreather masks and even CPAP/BIPAP unless intubation and mechanical ventilation is necessary. Viral filters are recommended for non-invasive ventilation and bag-valve-mask. Many physicians are now looking towards work of breathing as an indication for intubation rather than just treating hypoxemia. Having patients lay prone takes advantage of better ventilation of the lungs. Delaying intubation as long as possible is important as mortality rates range between 60-80% of ventilated COVID-19 patients.

The use of NSAIDs has been controversial in the management of COVID-19 due to reports saying it may have negative effects on infected patients. While none of those reports have been clinically proven, acetaminophen is reasonably recommended for fever control. Same for ACE inhibitors and ACE receptor blockers. IV fluid boluses are not recommended in the treatment of COVID-19 as to not promote the development or worsening of ARDS. There are some clinicians, recommending diuresing these patients by giving 40mg multiplied by the creatinine level of IV Lasix twice a day. Conservative fluid management is still recommended for volume depletion, however. Finally, glucocorticoids are not conclusively recommended in the treatment of COVID-19 due to prior studies showing increased mortality with glucocorticoid use in treating viral pneumonia. Some recent data does suggest that steroids may be helpful towards later progression during cytokine storm.

Multiple pharmacological treatments are being tested currently in an effort to fight COVID-19. Hydroxychloroquine has been studied in early clinical trials. This medication is an antimalarial medication with immunomodulatory anti-inflammatory benefits. There is very limited data that may support their use. A study in Italy reported earlier undetectable viral loads in patients treated with hydroxychloroquine, and a study in China reported less progression to severe disease burden with hydroxychloroquine treatment. This medication should be used cautiously as it prolongs the QT and can lead to fatal cardiac arrhythmias. Remdesivir, a novel antiviral that functions as a nucleotide analog and blocks viral RNA polymerase, this is also being trialed after it showed promise in treating COVID-19 in vitro. Currently, Remdesivir is not commercially available and has limited availability through compassionate use. Interleukin-6 (IL-6) is another target being studied. Tocilizuma is an anti-IL-6 monoclonal antibody that has been around for years to treat things such as autoimmune diseases. It is thought to treat cytokine storm in COVID-19. Unfortunately, the truth of the matter is there is no large or reliable study that has definitively shown there to be an effective medication in reducing the COVID-19 disease burden.

Prognosis:

While early data may not be entirely reliable, the observed case fatality rates range between 2.4% in Germany to 12.7% in Italy. The United States is currently reporting a 4.0% case fatality rate. Factors such as advanced age, chronic medical conditions, immunocompromised states, and malignancy, all increase the risk of morbidity and mortality associated with the disease.

COVID-19 has been described as having three trajectories: mild upper respiratory symptoms, non-severe pneumonia, and severe pneumonia with ARDS requiring resuscitation. Of those that are symptomatic with COVID-19, anywhere from 17%-29% present with ARDS and are grouped into this most severe category.

While symptoms are one way of characterizing the prognosis of COVID-19, there is some evidence that suggests laboratory values correlate with mortality outcomes. An elevated d-dimer (greater than 1 μg/mL), high Sequential Organ Failure Assessment (SOFA) score, and lymphocytopenia are associated with greater mortality rates. Other laboratory values that may help with prognosis include lactate dehydrogenase, serum ferritin, and C-reactive protein.

Differential Diagnoses:

In the setting of a global pandemic it is easy to jump to a COVID-19 diagnosis, but it’s important to consider a broad differential diagnosis especially because of the broad nature of COVID-19 symptoms. Other etiologies of viral pneumonia should be considered. The COVID-19 outbreak is happening congruently with flu season. Bacterial pneumonia should also remain high on the differential and depending on the duration of illness, a superimposed infection occurring in addition to COVID-19 is not unreasonable. Obtaining a good history is key to rule out exacerbations of chronic conditions especially those involving the pulmonary or cardiovascular system like COPD or CHF for example.

Clinical Pearls:

• • Data is constantly changing and data is being shared prior to peer review
  • Coronavirus Disease 2019 (COVID-19) caused by the Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2).
  • Classic symptoms include cough, fever, and shortness of breath.
  • Lab diagnosis is via PCR and has low sensitivity.
  • Classic lab finding includes lymphocytopenia and imaging is bilateral opacities on CXR.
  • Management is primarily supportive but several therapies are under investigation.

To stay up to date on COVID-19 news and research, be sure to check our dedicated COVID-19 Page!

References:

1. Yi-Wei Tang, Jonathan E. Schmitz, David H. Persing, Charles W. Stratton. The Laboratory Diagnosis of COVID-19 Infection: Current Issues and Challenges. Journal of Clinical Microbiology Apr 2020, JCM.00512-20; DOI: 10.1128/JCM.00512-20
2. Xie, M. Chen, Q. Insight into 2019 novel coronavirus – an updated interim review and lessons from SARS-CoV and MERS-CoV. Int J Infect Dis. 2020 Apr 1. pii: S1201-9712(20)30204-6. doi: 10.1016/j.ijid.2020.03.071. [Epub ahead of print]
3. Chavez S, Long B, Koyfman A, Liang SY. Coronavirus Disease (COVID-19): A primer for emergency physicians. AJEM. 2020 Mar 22.
   
4. Van Doremalen N, Bushmaker T, Morris DH, et al. Aerosol and Surface Stability of SARS-CoV-2 as Compared with SARS-CoV-1 [published online ahead of print, 2020 Mar 17]. N Engl J Med. 2020;NEJMc2004973. doi:10.1056/NEJMc2004973
5. Coronavirus COVID-19 Global Cases by the Center for Systems Science and Engineering (CSSE) at Johns Hopkins University (JHU). Johns Hopkins University. https://www.arcgis.com/apps/opsdashboard/index.html?fbclid=IwAR1950JCcisWUnacfDvPx-EVoYEY-JfsqJcVSGtmW2x_rthSNTVZH-A-v0k#/bda7594740fd40299423467b48e9ecf6
6. Bordi L. et al. Differential diagnosis of illness in patients under investigation for the novel coronavirus (SARS-CoV-2), Italy, February 2020. Euro Surveill. 2020;25(8):pii=2000170. https://doi-org.libproxy.tulane.edu/10.2807/1560-7917.ES.2020.25.8.2000170
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Authors

Aaron Wolfe, DO, FACEP

Jackson Roos, MSIII

John Spartz, MSII