In January 2022, at the height of the COVID-19 Omicron pandemic, a 63-year-old Iranian woman was referred to our hospital showing symptoms of confusion, disorientation, severe agitation, visual and auditory hallucinations, and impaired sleep. She had a 2-year history of dementia with progressive behavioral and psychological disturbances being treated with rivastigmine, memantine, risperidone, nortriptyline, and fluvoxamine; however, her family reported an acute deterioration in her cognitive state beginning 2 weeks before admission. Five days before admission, she was visited at a neurology clinic, where she was diagnosed with delirium superimposed on dementia, and her previous medications were discontinued and clonazepam (1 mg at bedtime), haloperidol (0.5 mg three times a day), and quetiapine (100 mg, twice a day) were administered. Nonetheless, her mental state continued to deteriorate. Past medical history was unremarkable except for chronic hypertension, for which she took amlodipine (5mg once daily) and losartan (25mg twice a day). There was no remarkable family history for psychiatric or medical illnesses.
On admission, she was confused, restless, incoherent, and disorientated to time, place, and person. Her vital signs included a temperature of 36.8°C, heart rate of 96 beats per minute (bpm), blood pressure of 120/70 mmHg, respirations of 18 breaths per minute, and oxygen saturation of 92% on room air. Her systemic physical examination was normal except for a body mass index (BMI) of 32. There were no focal neurological deficits but she did not follow commands.
Baseline laboratory investigations were significant for hypokalemia, elevated C-reactive protein (CRP), elevated erythrocyte sedimentation rate (ESR), increased creatine phosphokinase (CPK), increased lactate dehydrogenase (LDH), and a mild respiratory alkalosis (Table 1). Complete blood count (CBC) with differential, fasting plasma glucose (FPG), Hemoglobin A1c, lipid profile, coagulation profile, alkaline phosphatase, urea, creatinine, urinalysis as well as liver and thyroid function test results were in the normal range. Urine testing for drugs of abuse (methamphetamine, amphetamine, cannabis, methadone, and morphine) was negative. Cultures of the blood, urine, and sputum were obtained. Quetiapine, clonazepam, and haloperidol were discontinued and treatment with intravenous infusion of 15% potassium chloride (KCl) solution and unfractionated heparin as venous thromboembolism prophylaxis (5000IU two times a day) was begun.
Table 1
Laboratory data on admission
|
Variable
|
Reference Range
|
On Presentation
|
Complete blood count
|
Hemoglobin (g/dl)
|
12–16
|
14.1
|
Hematocrit (%)
|
36–46
|
40.7
|
Red-cell count (per mm3)
|
4500000–6300000
|
4980000
|
Mean corpuscular volume (µm3)
|
77–97
|
81.7
|
White-cell count (per mm3)
|
4500–11000
|
5500
|
Differential count (%)
Mixed
Segment
Lymphocytes
|
0–10
40–70
22–42
|
4.6
69.7
23.7
|
Platelet count (per mm3)
|
140000–440000
|
141000
|
Electrolytes
|
Sodium (mmol/L)
|
136–145
|
143
|
Potassium (mmol/L)
|
3.7–5.5
|
3.2*
|
Phosphate (mg/dl)
|
2.5-5
|
3.2
|
Calcium (mg/dl)
|
8.6–10.6
|
9.1
|
Magnesium (mg/dl)
|
1.8–2.6
|
2.1
|
Liver Enzymes
|
Alanine aminotransferase (IU/L)
|
5–40
|
22
|
Aspartate aminotransferase (IU/L)
|
5–40
|
39
|
|
Erythrocyte sedimentation rate (mm/hr.)
|
< 20
|
23*
|
|
C-reactive protein (mg/L)
|
< 6
|
24*
|
|
Lactate dehydrogenase (U/L)
|
225–500
|
639*
|
|
Creatine phosphokinase (IU/L)
|
24–195
|
923*
|
Venous blood gases
|
pH
pCO2 (mm Hg)
pO2 (mm Hg)
Bicarbonate (mmol/L)
Base excess
|
7.31–7.41
35–40
41–51
22–26
-2-+2
|
7.47*
34.7*
153.2*
25.3*
2.7*
|
*Abnormal value |
Throat swab samples were sent for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by real-time reverse-transcriptase–polymerase-chain-reaction assay (RT-PCR). High-resolution computed tomography (HRCT) of the lungs showed bilateral predominantly perihilar ground-glass opacities (Fig. 1). Brain magnetic resonance imaging (MRI) revealed moderate global atrophy and no acute abnormality that could explain the patient's current condition was found.
The next day, she developed a low-grade fever (37.7°C), tachycardia (103 beats/min), tachypnea (24 breaths/min), and shortness of breath. Oxygen saturation dropped to 90% on room air. No evidence of myocardial ischemia was discovered on electrocardiography. Initial nasopharyngeal swabs came back negative for SARS-CoV-2. Because of the high index of suspicion for COVID-19 despite the negative initial nasopharyngeal RT-PCR result, a second RT-PCR was done. Lumbar puncture was performed and empiric antimicrobial therapy with intravenous ampicillin (2 mg every 4hours), vancomycin (1mg every 12hours), ceftriaxone (2mg every 8hours), and acyclovir (500mg IV every 8hours) was started.
Over the two following days, the patient’s condition continued to deteriorate. On the fourth hospital day, she was intermittently confused and increasingly lethargic. The temperature was 38.1°C, the pulse rate was 130 bpm, the respirations were 26, the blood pressure was 90/60 mm Hg, and the oxygen saturation was 88% while she was breathing ambient air. The repeated RT-PCR test for SARS-CoV-2 came back negative. Cultures of the blood, urine, and sputum showed negative results. Analysis of the cerebrospinal fluid (CSF) was normal. Arterial blood gas test revealed a compensated metabolic acidosis (PH 7.27, pCO2 25.2 mmHg, and HCO3 11.6meq/L. Troponin level was 673.5(ng/ml) (normal < 19 ng/ml). D-dimer test was not performed because of the low clinical suspicion of PE. Transthoracic echocardiography revealed a hypokinetic and enlarged right ventricle suggestive of massive PE. While the patient was prepared for transfer to the intensive care unit (ICU), she developed a sudden cardiac arrest, and though resuscitation was started immediately, subsequently died.