First hospitalized case of laboratory-confirmed coronavirus disease 2019 (COVID-19) in Alberta, Canada

Abstract

As the pandemic of coronavirus disease 2019 (COVID-19) continues to evolve globally and within our Canadian borders, hospitals will begin to see an increasing number of confirmed or suspected cases at their doors. Although many patients can be managed at home, a reasonable proportion will experience progression of disease requiring hospitalization and potentially mechanical ventilation and intensive care. Herein, we report the presentation of the first case of COVID-19 admitted to hospital in Alberta. While The patient's course was mild, this case highlights a number of key points—namely the importance of widespread testing in the community to help inform emergency services (ambulance) workers and receiving front-line health care staff. Other important points include in-hospital monitoring and pharmacologic treatment.

Introduction

On December 31, 2020, the World Health Organization (WHO) was informed of several cases of unexplained severe pneumonia from Hubei, China, with the causative agent subsequently identified as a novel coronavirus (CoV) by January 7, 2020 (1). The virus, named severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) (2), causes the condition termed coronavirus disease 2019 (COVID-19) (3). In response to a rapid rise in international cases and local transmission within multiple countries, the WHO declared the outbreak a pandemic on March 11, 2020 (4). As of March 23, 2020, there have been a total of 311,989 cases of COVID-19 infection reported in 169 countries/regions with 13,407 deaths (5). Canada confirmed its first case of COVID-19 in a traveller returning from Wuhan, China, on January 25, 2020, in Toronto, Ontario (4). The western Canadian province of Alberta confirmed its first two cases of COVID-19 on March 4 and March 5, 2020, in the cities of Calgary and Edmonton, respectively. The case in Edmonton was initially diagnosed and managed in the community by Public Health, but the case ultimately worsened, becoming the first instance of a patient hospitalized in Alberta with COVID-19.

Case Presentation

On March 9, 2020, our hospital Emergency and Infection Control teams were notified by regional Public Health that a patient with laboratory-confirmed COVID-19 in the community was being brought to hospital. He was a 48-year-old male with a medical history significant for obesity, hypertension, hyperlipidemia, and sleep apnea who had returned from a one-week business trip to the United States on February 28. He had visited cities in Ohio, Illinois, and Michigan. He travelled there with a business associate who had returned from a Princess Cruises vacation that stopped in San Francisco several days before the associate departed on the business trip. While abroad, the patient’s business associate became ill with fevers, rigors, and dyspnea around February 25. Upon returning to Alberta, our patient began to feel unwell with malaise and myalgias. This progressed to fever, sore throat, pleuritic chest pain, dyspnea, and abdominal discomfort with diarrhea on March 3, when he visited his family physician. A chest x-ray from this visit showed some bronchial wall thickening (Figure 1). He returned to his family physician on March 5, reporting that his work colleague was now admitted to an intensive care unit (ICU) in an adjacent province. Due to suspicion of COVID-19, related to his exposure history, a nasopharyngeal swab was collected. Testing at the provincial laboratory was positive for SARS-CoV-2 using a laboratory-developed real-time reverse transcriptase polymerase chain reaction (rRT-PCR) targeting the E- and RNA-dependent RNA polymerase (RdRP) genes; it was negative for other respiratory viruses (NxTAG® Respiratory Pathogen Panel, Luminex®). Public Health was notified and placed the patient and his close contacts on home isolation. The patient was deemed well enough that hospitalization was not required.

Figure 1:

Chest x-ray on date of symptom onset (A: March 3) and date of admission (B: March 9; 2-views available)

On March 9, he was found to be unwell with fever (temperature 38.8^oC), progressive dyspnea, and oxygen desaturation on exertion. Upon arrival, a surgical mask was immediately placed on the patient, and he was placed in a single room on contact and droplet precautions. Upon assessment, he was afebrile with no evidence of tachycardia or hypotension and was saturating 88%–90% on room air. He became short of breath while speaking and was found to have increased crackles and adventitious sounds on examination of the right lung field. Chest x-ray revealed bilateral bronchopneumonic airspace disease (Figure 1). Due to worsening respiratory function, the patient was admitted for observation. He was not deemed to require an ICU level of care. Upon evaluation by the Infectious Diseases service upon admission, he was initiated on a 14-day course of lopinavir/ritonavir 200 mg twice daily and intravenous (IV) ceftriaxone for possible concomitant bacterial pneumonia. Otherwise, he was provided with supportive treatment (IV hydration and acetaminophen for fever). We advised systemic and inhaled steroids be avoided. Figure 2 outlines his hospital course.

Figure 2:

Timeline of patient’s history, symptom onset, testing, and hospitalization. NP = Nasopharyngeal; C_t = Cycle threshold of rRT-PCR; LPV/r = Lopinavir/ritonavir

The patient experienced a gradual improvement over the course of one week. His oxygen saturation on a daily basis ranged from 89%–94% on room air. He was slowly able to mobilize without limiting breathlessness by day five with a saturation of 95% on room air by discharge. Blood cultures were negative. Laboratory investigations are shown in Table 1, with subsequent testing for SARS-CoV-2 shown in Figure 2. A repeat chest x-ray on March 13 revealed patchy bilateral airspace opacities but with slight improvement on the left. He completed the remainder of the lopinavir/ritonavir course as an outpatient, citing the only major adverse effect experienced was diarrhea that resolved seven days after initiation.

Table 1:

Laboratory investigation results during hospital course

Test	Reference Range	March 9	March 10	March 11	March 12	March 15	March 16	March 17
ALT	<50 U/L	25	22	20	30	69	67	57
AST	<40 U/L	27	24	24	36	—	36	29
CK	<250 U/L	235	185	145	123	62	63	61
Troponin I	<0.04 µg/L	<0.04	<0.04	<0.04	<0.04	—	—	<0.04
Total bilirubin	<20 µmol/L	12	9	10	—	10	10	12
CRP	<8 mg/L	22.6	31.3	36.6	22.4	20.1	19.8	12.6
Creatinine	50–120 µmol/L	93	86	82	75	66	67	67
Lactate	0.5–2.2 mmol/L	1.4	—	—	—	—	—	—
Lipase	0–60 U/L	—	—	—	—	31	36	35
LDH	100–225 U/L	—	—	—	—	172	—	—
D-dimer	<0.50 mg/L	—	<0.27	—	—	—	0.29	0.28
Hb	135–175 g/L	165	155	151	150	144	154	149
WBC	4–11 (109/L)	5.6	4.4	4.5	5.6	5.6	7.2	5.4
ALC	1–4.5 (109/L)	1.6	1.9	2.0	2.1	1.6	2.5	1.9
ANC	1.8–7.5 (109/L)	3.5	2.2	2.0	2.9	3.1	3.8	2.6
Platelet	140–450 (109/L)	285	251	276	283	382	438	452
Stool for CDIFF	Negative	—	—	—	Negative	—	—	—

Note: Dash indicates test was not carried out that day

ALT = Alanine aminotransferase; AST = Aspartate aminotransferase; CK = Creatinine kinase; CRP = C-reactive protein; LDH = Lactate dehydrogenase; Hb = Hemoglobin; WBC = White blood cell count; ALC = Absolute lymphocyte count; ANC = Absolute neutrophil count; CDIFF = Clostridioides difficile toxin testing

Discussion

This case represents the first patient to require hospital admission due to COVID-19 (infection with SARS-CoV-2) in Alberta, Canada. SARS-CoV-2 is genetically similar to other respiratory β-coronaviruses known to cause respiratory distress syndromes (such as SARS and Middle East respiratory syndrome [MERS]). It shares up to 80% sequence similarity with SARS-CoV, and both viruses have up to 96% sequence homology with a bat coronavirus (6).

SARS-CoV-2 is spread between people via aerosol droplets and direct contact (via inhalation or contact with mucosal surfaces of a susceptible individual) (4,7). Our patient most likely contracted COVID-19 via close contact with his business associate (and travel companion) who had recently been on a cruise ship with confirmed cases and who was himself diagnosed and admitted to an ICU. This is especially likely given that cruise ships have emerged as an important risk factor for COVID-19 acquisition and outbreaks (8).

Due to advance notification from local public health officials and laboratory confirmation of infection in the community, our hospital was prepared to receive this patient. Emergency department personnel were able to prepare an appropriate isolation room, notify the ICU in case of clinical decompensation, and have the appropriate personal protective equipment (PPE) to prevent transmission of the virus to health care staff (4). As this patient was on contact and droplet isolation precautions, staff were required to wear a combination of a disposable gown, gloves, a surgical mask, and eye protection (either in the form of a face shield or a mask with visor attachment) to enter the room. Use of a fit-tested N95 respirator was only required if a health care worker planned to conduct an aerosol-generating procedure. These local PPE practices were in accordance with the Public Health Agency of Canada recommendations (4).

Based on early case series of patients with COVID-19, the illness presents in a biphasic manner. In the first week, most patients experience fever, cough, and mild influenza-like symptoms, after which they enter a period of progressive dyspnea, interstitial viral pneumonia, and/or respiratory distress (9). At this point, 20% of patients may require ICU admission (10). Our patient stabilized with a high percentage of supplemental oxygen. Given his underlying medical comorbidities, there was concern that he was at high risk of respiratory deterioration (9). We closely followed his transaminases, total bilirubin, D-dimer, troponin, and complete blood counts regularly, as worsening irregularities in these parameters may predict clinical worsening and need for ICU assessment (10,11).

Our patient was treated empirically for COVID-19 using lopinavir/ritonavir. To date, this combination of anti-retrovirals remains an investigational agent for treatment of infection with SARS-CoV-2. A recent randomized trial found no difference in pre-defined clinical improvement between patients with severe COVID-19 when treated with lopinavir/ritonavir versus standard care (12). However, compared with those in this study, our patient did not require ICU admission, and thus we hypothesize that perhaps there may be a role for lopinavir/ritonavir in early disease to help prevent progression to need for ICU. This would be best evaluated using a randomized controlled trial study design. Corticosteroids should be avoided in patients with suspected or confirmed COVID-19 infection (13). Potential therapeutics currently being evaluated for treatment of COVID-19 include hydroxychloroquine, chloroquine, remdesivir, lopinavir/ritonavir (alone or with interferon beta), and tocilizumab (2).

Repeat nasopharyngeal PCR testing of our patient detected ongoing presence of virus on March 12 (day 4 of admission, day 10 post onset of symptoms) but not on March 16 (day 8 of admission, day 14 post onset of symptoms). The progressively increasing cycle threshold values are consistent with a resolving infection in which the viral burden reduces to undetectable levels. Whether the virus was viable and could be transmitted on March 12 is not clear given that the PCR testing detects nucleic acid of both live and dead virus, and thus contact/droplet precautions were continued. This indicates that, should mild cases of COVID-19 improve quickly while admitted, discharge will likely have to occur before patients are formally “cleared” of infection. To declare a patient “resolved” using a “test-based strategy,” the Centers for Disease Control (USA) recommends that a patient should have improved symptoms, along with two separate nasopharyngeal swabs that are negative (collected ≥24 hours apart) (14). However, given limitations in accessing testing in some areas, a “non–test-based strategy” advises that patients may be considered resolved if at least three days have passed since recovery (defined as resolution of fever without anti-pyretics; improvement in respiratory symptoms; and at least seven days have passed since their symptom onset) (14). Our patient was discharged home to finish his self-isolation until Public Health could declare him “resolved.”

Several studies have noted detection of SARS-CoV-2 in a number of different samples (15,16). We did not find evidence of viral RNA in stool, urine, or plasma specimens collected on two separate occasions from our patient (Figure 2). The first set of these specimens was collected seven days after admission, and thus it is not known if these would have been positive on admission. Excretion in urine and stool is not consistently found in all patients (16). Transmission via stool is felt to be minimal and likely not clinically significant (15). This also raises the question of whether treatment with lopinavir/ritonavir, on admission, cleared the virus from the stool or, alternatively, whether the presence of negative extra-respiratory specimens may be associated with mild disease.

In summary, our patient fully recovered from COVID-19 complicated by bilateral viral pneumonia. He did not require mechanical ventilation or ICU care. Whether treatment with lopinavir/ritonavir prevented him from progressing to more severe disease is not known, but this question should be considered for future large-scale controlled trials. Our Occupational Health and Infection Control teams have confirmed this case did not result in any nosocomial or staff acquisition of COVID-19. Although mild, this case highlights the importance of active community screening for COVID-19 and its benefits, especially so hospital teams can be notified in advance and prepare (with respect to PPE, isolation room, and need for ICU care) if a patient requires urgent admission for worsening clinical status.

Competing Interests:

The authors have nothing to disclose.

Ethics Approval:

N/A

Informed Consent:

The authors obtained patient consent for publication of this report.

Registry and the Registration No. of the Study/Trial:

N/A

Animal Studies:

N/A

Funding:

No funding was received for this work.

Peer Review:

This article has been peer reviewed.