CLINICAL DESCRIPTION & EPIDEMIOLOGY

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• Data presented on April 28, 2020, reported that individuals aged ≥60 years account for 36% of COVID-19 cases in Canada, yet comprise the majority of hospitalizations (66%), ICU admissions (63%), and deaths (95%).(1) Those aged ≤19 make up 5% of overall COVID-19 cases and individuals aged 20-59 account for the remaining 59%. A slim majority (55%) of Canadian COVID-19 cases are female. Most cases have resulted from community spread (81%), with the remaining 19% travel-related.(2)

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• There has been growing global concern that ethnicity may play a role in COVID-19 susceptibility and outcome. In the UK, observational data suggests ethnic minority groups make up a disproportionately high number of ICU admissions due to COVID-19.(3) Preliminary data from Connecticut report Black Americans have higher rates of both COVID-19 infection and mortality compared to the general population.(4) Further analysis is required to determine if there is an interplay between SARS-CoV-2 and ethnicity, but this is likely complicated by prevalence of comorbidities, socioeconomic status, or cultural practices.(5)

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• Canada had not been reporting epidemiological data based on ethnicity, but in Manitoba, racial, ethnic, and Indigenous identifiers are being collected for all COVID-19 cases as of May 1, 2020.

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1. Canada.ca [Internet]. Ottawa: Public Health Agency of Canada. COVID-19 in Canada: Modelling Update; 2020 Apr 28 [cited 2020 May 5].

2. Public Health Agency of Canada. Epidemiological summary of COVID-19 cases in Canada [Internet]. 6 May 2020 [cited 2020 May 6].

3. Khunti K, Singh AK, Pareek M, Hanif W. Is ethnicity linked to incidence or outcomes of covid-19? BMJ [Internet]. 2020 Apr 20 [cited 2020 May 6];369.  

4. Laurencin CT, McClinton A. The COVID-19 pandemic: a call to action to identify and address racial and ethnic disparities. J Racial Ethn Health Disparities. 2020 Apr 18;1–5.  

5. Pareek M, Bangash MN, Pareek N, Pan D, Sze S, Minhas JS, et al. Ethnicity and COVID-19: an urgent public health research priority. The Lancet. 2020 May 2;395(10234):1421–2.

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• As of May 6, 2020, there were 164 cases of COVID-19 on First Nations reserves including 17 hospitalizations and two deaths.(1) Recently, there has been an outbreak in the Dene village of La Loche, Saskatchewan, resulting in the death of two elders living in long-term care facilities.(2) The virus appears to have been introduced into the community by travel from an oilsands work camp in northern Alberta. Discrepancies between official reporting and community reports have been raised by the Yellowhead Institute.(3)

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• Potential impacts and challenges to managing outbreaks in remote communities were discussed in the April 17, 2020 newsletter. Due to these concerns, many communities have closed their borders, allowing only food and essential workers into the community, with precautions.(4) 

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• Although the mental health impacts of the COVID-19 pandemic are unknown, there have been concerns that it will further compound the already precarious pre-pandemic situations in some Indigenous communities.(5) There continues to be a call for more permanent trauma support, in particular training of local trauma counsellors is needed in the context of a community lockdown. In an attempt to address some of these concerns, there has been an increase in the number of counsellors available at the Hope for Wellness helpline, a telephone and online support for First Nations, Inuit, and Metis in a few different languages. 

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• In a statement, the United Nations Forum on Indigenous Issues urged that states take steps to ensure indigenous people are informed, protected, and prioritized during the COVID-19 pandemic.(6) It is important that information sharing is community-driven, culturally appropriate and delivered in Indigenous languages to ensure accessibility.(6,7)

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1. Indigenous Services Canada. Coronavirus (COVID-19) and Indigenous communities. Government of Canada [Internet]. May 6, 2020 [cited May 7, 2020]. 

2. Taylor S. COVID 19 outbreak in northern Saskatchewan ‘of concern’ says Canada’s chief health officer. Global News [Internet]. May 6, 2020 [cited May 7, 2020].

3. Eggertson L. May 6: Gaps in data on COVID-19 in Indigenous communities. CMAJ News [Internet]. May 6, 2020 [cited May 7, 2020] [about 3 screens] 

4. Yellowhead Institute. COVID-19 In Community: How Are First Nations Responding? [Internet] April 7, 2020 [cited May 6, 2020] 

5. Wright T. First Nations chiefs raise alarm over mental health impacts of COVID-19. Global News [Internet]. May 3, 2020 [cited May 6, 2020].

6. Nuorgam A. Message from the Chair of the Permanent Forum on Indigenous Issues to ensure indigenous peoples are informed, protected and prioritized during the global COVID-19 pandemic. United Nations Permanent Forum on Indigenous Issues (UNPFII). (Statement) April 6, 2020 [cited May 6, 2020]

7. Kiddell-Monroe R, et al. Inuit communities can beat COVID-19 and tuberculosis. The Lancet Public Health. 2020. published online April 24, 2020. (Correspondence).

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• Indirect health impacts of the COVID-19 pandemic will likely be seen in all areas of medicine. Although data is scarce at this point in time, current and anticipated impacts include negative mental health outcomes,(1) reduced access to abortion,(2) delayed cancer diagnoses and therapies,(3) negative impacts on care of the elderly,(4) and impacts on non-COVID-19 research.(5) There is also the backlog of elective surgical procedures and patients not seeking timely medical care because of concern that they will become infected with SARS-CoV-2 by visiting a healthcare facility.

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• The COVID-19 pandemic appears to be impacting access to cardiac care as the number of patients treated with cardiac catheterization for myocardial infarction (MI) has declined by up to 40% in the United States and Spain.(6) Numerous theories have been postulated to explain the decline, but the overall impact is not clear because COVID-19 has made mortality data more difficult to interpret.(7,8)

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• Mitigation strategies to lessen the impact of COVID-19 on other health conditions should include encouragement of basic health maintenance practices such as exercise, structured activities and good sleep hygiene. Physicians are encouraged to practice preventive medicine and make an effort to maintain connections with vulnerable patients.(4,5) Preparedness and planning for post-pandemic surges in healthcare demands are common themes in the literature. As well, advocacy for continuity of health services during the pandemic is important.

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• Mitigation strategies to lessen the negative impact on mental health include information sharing, especially around the altruistic necessity of isolation, encouraging regular social interaction while respecting physical distancing, and keeping quarantine as short as possible.

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1. Brooks, S. et al. The psychological impact of quarantine and how to reduce it: rapid review of the evidence. Lancet. 2020 February 20. 395:912-20.

2. Bayefsky, M. Abortion during the Covid-19 Pandemic – Ensuring Access to an Essential Health Service. NEJM. April 9, 2020 DOI: 10.1056/NEJMp2008006

3. Jones, D. et al. Impact of the COVID-19 pandemic on the symptomatic diagnosis of cancer: the view from primary care. Lancet. 2020 April 30.

4. Heckman, G. et al. COVID-19 outbreak measures may indirectly lead to greater burden on hospitals. CMAJ. Apr 2020, 192 (14) E384.

5. Brown, S. et al. Anticipating and Mitigating the Impact of the COVID-19 Pandemic on Alzheimer's Disease and Related Dementias. The American Journal of Geriatric Psychiatry. 2020 April 15.

6. Garcia, S. et al. Reduction in ST-Segment Elevation Cardiac Catheterization Laboratory Activations in the United States during COVID-19 Pandemic. Journal of the American College of Cardiology. 7 April 2020.

7. Appleby, J. What is happening to non-covid deaths? BMJ. 24 April 2020. doi: 10.1136/bmj.m1607.

8. Wood, S. The Mystery of the Missing STEMIs During the COVID-19 Pandemic. 2 April 2020. [accessed 2020 May 5].

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• Based on the best available evidence, the rate of acute stroke in patients with COVID-19 appears to be low, between 2.5-2.8%.(1,2) Of note, in Canada, the age-standardized occurrence of stroke was 2.6% in 2012-2013.(3)

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• A retrospective case series of 214 hospitalized patients with COVID-19 from Wuhan, China observed acute stroke in six patients (2.8%) at presentation or during hospital admission (five ischemic and one hemorrhagic).(1) Five of these patients had severe COVID-19 disease upon admission.

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• A retrospective case series of 362 hospitalized patients with COVID-19 from Milan, Italy observed acute ischemic stroke in nine patients (2.5%).(2) Two of these patients had atrial fibrillation, one had cancer, and another had both cancer and disseminated intravascular coagulation. Stroke was the reason for admission in six of these patients.

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• Viral respiratory infections such as RSV and human metapneumovirus are associated with increased risk of stroke and myocardial infarction in the elderly.(4) Cases of stroke were also seen with SARS. In a study of 206 patients with SARS in Singapore, five developed large artery ischemic stroke.(5)

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1. Mao L, Jin H, Wang M, Hu Y, Chen S, He Q, et al. Neurologic Manifestations of Hospitalized Patients with Coronavirus Disease 2019 in Wuhan, China. JAMA Neurol. 2020. 

2. Lodigiani C, Iapichino G, Carenzo L, Cecconi M, Ferrazzi P, Sebastian T, et al. Venous and arterial thromboembolic complications in COVID-19 patients admitted to an academic hospital in Milan, Italy. Thromb Res. 2020 Jul 1;191:9–14.  

3. Public Health Agency of Canada. Stroke in Canada: Highlights from the Canadian chronic disease surveillance system [Internet]. Date modified: 9 Dec 2019. [cited 8 May 2020].

4. Blackburn R, Zhao H, Pebody R, Hayward A, Warren-Gash C. Laboratory-Confirmed Respiratory Infections as Predictors of Hospital Admission for Myocardial Infarction and Stroke: Time-Series Analysis of English Data for 2004–2015. Clin Infect Dis. 2018 Jun 18;67(1):8–17.  

5. Umapathi T, Kor AC, Venketasubramanian N, Lim CCT, Pang BC, Yeo TT, et al. Large artery ischaemic stroke in severe acute respiratory syndrome (SARS). J Neurol [Internet]. 2004 Oct [cited 2020 May 7];251(10):1227–31.

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• A recent meta-analysis showed that hypertension correlates with increased risk of severe COVID-19, however causation has yet to be proven, with age and lifestyle as potential confounding factors.(1,2)

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• Previous literature suggests a theoretical increased risk of infection associated with the use of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs), due to the upregulation of angiotensin-converting enzyme II, the receptor through which SARS-CoV-2 invades host cells.(2) However, a study of patients with hypertension and admitted for COVID-19 (n=1,128) found that the use of ACEI/ARBs was associated with reduced all-cause mortality.(3) An additional study (n=362) found no association between ACEI/ARB use and outcome of COVID-19 infection.(4) 

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• Presently, there is no definitive answer as to why hypertension may increase the risk of severe COVID-19, or if hypertension is simply a surrogate for age.(2) Current Canadian guidelines recommend the continuation of ACEI/ARBs for control of hypertension in patients with COVID-19.(5)

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1. Hu Y, Sun J, Dai Z, Deng H, Li X, Huang Q, et al. Prevalence and severity of coronavirus disease 2019 (COVID-19): A systematic review and meta-analysis. Journal of Clinical Virology. 2020 Apr 14;104371.  

2. Schiffrin EL, Flack JM, Ito S, Muntner P, Webb RC. Hypertension and COVID-19. Am J Hypertens. 2020 Apr 29;33(5):373–4.  

3. Zhang P, Zhu L, Cai J, Lei F, Qin J-J, Xie J, et al. Association of inpatient use of angiotensin converting enzyme inhibitors and angiotensin ii receptor blockers with mortality among patients with hypertension hospitalized with COVID-19. Circulation Research [Internet]. 2020 Apr 17 [cited 2020 Apr 29]. 

4. Li J, Wang X, Chen J, Zhang H, Deng A. Association of renin-angiotensin system inhibitors with severity or risk of death in patients with hypertension hospitalized for coronavirus disease 2019 (COVID-19) infection in Wuhan, China. JAMA Cardiol [Internet]. 2020 Apr 23 [cited 2020 Apr 29]. 

5. Hypertension Canada. Hypertension, ACE-Inhibitors and Angiotensin Receptor Blockers and COVID-19. March 13, 2020. Accessed April 28, 2020.

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• In a retrospective case series of 214 patients hospitalized with COVID-19, common neurologic features included dizziness (17%), headache (13%), skeletal muscle injury (10.7%), impaired consciousness (7.5%), and impaired taste (5.6%) or smell (5.1%).(1) Other features included stroke (2.8%), nerve pain (2.3%), impaired vision (1.4%), ataxia (0.5%), and seizure (0.5%). In a prospective study of 41 hospitalized patients with COVID-19, 3/38 (8%) patients had headache.(2)

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• An observational study of 58 patients published as a letter to the editor reported encephalopathy, agitation and corticospinal tract signs associated with acute respiratory distress syndrome due to SARS-CoV-2 infection.(3) Published case studies have also reported meningitis/encephalitis(4) and Guillain-Barré syndrome(5) with COVID-19.

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• There is evidence that other coronaviruses, including SARS and MERS, may be capable of CNS invasion through a transsynaptic pathway from respiratory airways, thereby inducing neurological disease. Given the high homogeneity between SARS-CoV-2 and SARS-CoV, it is possible SARS-CoV-2 is capable of neuroinvasion and that neurologic factors may contribute to respiratory failure in infected patients.(6)

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1. Mao L, Jin H, Wang M, Hu Y, Chen S, He Q, et al. Neurologic Manifestations of Hospitalized Patients with Coronavirus Disease 2019 in Wuhan, China. JAMA Neurol. 2020.  

2. Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020 Feb 15;395(10223):497–506.  

3. Helms J, Kremer S, Merdji H, Clere-Jehl R, Schenck M, Kummerlen C, et al. Neurologic Features in Severe SARS-CoV-2 Infection. N Engl J Med. 2020 Apr 15.  

4. Moriguchi T, Harii N, Goto J, Harada D, Sugawara H, Takamino J, et al. A first case of meningitis/encephalitis associated with SARS-Coronavirus-2. Int J Infect Dis. 2020 May 1;94:55–8.  

5. Zhao H, Shen D, Zhou H, Liu J, Chen S. Guillain-Barré syndrome associated with SARS-CoV-2 infection: causality or coincidence? The Lancet Neurology.2020; 19: 383–4.  

6. Li Y, Bai W, Hashikawa T. The neuroinvasive potential of SARS‐CoV2 may play a role in the respiratory failure of COVID‐19 patients. J Med Virol [Internet]. 2020 Jun 11 [cited 2020 Apr 28];92(6):552–5.

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• The development of long-term immunity to viruses is estimated by serology testing for establishment of virus-specific antibodies. A letter describing a study which followed 34 Chinese patients admitted to hospital for COVID-19 in early February found a typical humoral response of IgM followed by the emergence of IgG antibodies.(1) In the third week after symptom onset, all patients were positive for IgM and IgG antibodies with sustained IgG levels out to seven weeks after symptom onset, the end of the observation period. Another preprint study found similar results reaffirming the presence of SARS-CoV-2 specific IgM and IgG following symptomatic COVID-19 infection.(2) 

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• 56 patients who recovered from SARS in 2003 were followed for several years to determine long-term immunity. The studies showed antibodies peaked four months post-infection and in the initial study, nearly 90% of patients still had detectable IgG levels at two years post-infection.(3) Follow-up studies from the same group showed that the presence of detectable antibodies tapered from roughly 80% of recovered patients at three years(4) to less than 10% at 6 years.(5)

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• Notably, the immune system is complex and antibody presence alone does not guarantee immunity. Despite antibody development, the question of post-infectious SARS-CoV-2 immunity is inconclusive given the lack of long-term immunological and epidemiological data. 

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1. Xiao AT, Gao C, Zhang S. Profile of specific antibodies to SARS-CoV-2: The first report. Journal of Infection [in press]. 11 March 2020.  

2. Hu Q, Cui X, Liu X, Peng B. et al. The production of antibodies for SARS-CoV-2 and its clinical implication. medRxiv [preprint]. 2020 April 20.  

3. Liu W, Fontanet A, Zhang P, Zhan L et al. Two-Year Prospective Study of the Humoral Immune Response of Patients with Severe Acute Respiratory Syndrome.The Journal of Infectious Diseases 2006;193(6) 792–795.  

4. Cao WC, Liu W, Zhang P, Zhang F et al. Disappearance of Antibodies to SARS-Associated Coronavirus after Recovery. N Engl J Med 2007; 357:1162-1163. DOI: 10.1056/NEJMc070348.  

5. Tang F, Quan Y, Xin Z, Wrammert J et al. Lack of Peripheral Memory B Cell Responses in Recovered Patients with Severe Acute Respiratory Syndrome: A Six-Year Follow-Up Study. The Journal of Immunology. 2011; 186(12)7264-7268.

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• At this time, cutaneous manifestations seen in COVID-19 are incompletely characterized. A large descriptive study from China found unspecified rash to be rare (0.2%).(1) However, a more recent descriptive study from Italy with a specific focus on dermatologic manifestations described 18 of 88 (20.4%) patients with cutaneous manifestations. Of these, 14 patients had an erythematous rash, 3 had generalized urticaria, and 1 had a chicken pox-like vesicular rash.(2) There was no clear correlation with disease severity.

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• There are numerous case reports detailing ischemic and coagulopathic cutaneous manifestations of COVID-19. A case report from China noted dermatologic changes associated with ischemia and coagulopathy in the limbs and digits of critically ill adult COVID-19 patients, but the pathogenesis of these changes remains unclear.(3) The report noted the possibility of antiphospholipid syndrome, disseminated intravascular coagulation, heparin induced thrombocytopenia, or thrombotic microangiopathy developing in the context of COVID-19. A case series describing three purpuric skin rashes showed complement-mediated microvascular injury on biopsy.(4) Diffuse, petechial rash was noted in the context of thrombocytopenia in a case report from Thailand.(5) 

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• COVID-19 associated acro-ischemia has been noted in more than a dozen otherwise asymptomatic Italian children including a 13-year-old boy in Italy with acrocyanosis on the toes.(6) There was progression to bullous lesions, followed by the development of black crusting, and finally regression.

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1. Guan W, Ni Z, Hu Y, Liang W et al. Clinical Characteristics of Coronavirus Disease 2019 in China. New Engl J Med. 2020 March 6; 1-13. 

2. Recalcati S. Cutaneous manifestations in COVID-19: a first perspective. J Eur Acad Dermatol Venereol. 2020 March 26. Not paginated. 

3. Zhang Y, Xiao M, Zhang S, Xia P et al. Coagulopathy and Antiphospholipid Antibodies in Patients with Covid-19. NEJM. 9 April 2020. 1-3. 

4. Magro S, Mulvey J, Berlin D, Nuovo G et al. Complement associated microvascular injury and thrombosis in the pathogenesis of severe COVID-19 infection: A report of five cases. Translational Research.2020 April 15. 1-13. 

5. Joob, B. and Wiwanitkit V. Hemorrhagic Problem Among the Patients With COVID-19: Clinical Summary of 41 Thai Infected Patients. Clinical and Applied Thrombosis/Hemostasis. 2020 April 6 in preprint. 6:1. 

6. Mazzotta, F. et al. Acute Acro-Ischemia in a child at the time of COVID-19. Dermatologica Pediatrica. 2020 April 11. 1-4

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• Like other RNA viruses, SARS-CoV-2 appears to undergo frequent mutations. There are several “hot spots” for mutation within the SARS-CoV-2 genome.(1)

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• Many SARS-CoV-2 strains and sub-strains have been identified but estimates of the exact number vary significantly. Homology is high among these strains at the nucleotide level (99.9-100%) and amino acid level (99.79%-100%).(1) Preprint in vitro data of 11 Chinese SARS-CoV-2 isolates suggest certain mutations may cause a 270-fold increase in viral load, correlating with higher rates of cell death.(2) However, there is no data on whether mutations in SARS-CoV-2 strains correlate with changes in clinical presentation or outcome. 

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• SARS-CoV-2 will continue to evolve. Mutations may lead to increased transmissibility and virulence as well as immune evasion.(3,4) Further research on diagnosis, treatment, and vaccine development should take strain variability into account.(4)

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1. Wang C, Liu Z, Chen Z, Huang X, Xu M, He T, et al. The establishment of reference sequence for SARS-CoV-2 and variation analysis. Journal of Medical Virology. 2020;92(6):667–74. 

2. Yao H, Lu X, Chen Q, Xu K, Chen Y, Cheng L, et al. Patient-derived mutations impact pathogenicity of SARS-CoV-2. medRxiv. [preprint]. [posted 2020 April 19; cited 2020 April 21].

3. Zhang J, Ma K, Li H, Liao M, Qi W. The continuous evolution and dissemination of 2019 novel human coronavirus. Journal of Infection [Internet]. 2020 Feb 22 [cited 2020 Apr 22].

4. Koyama T, Weeraratne D, Snowdon JL, Parida L. Emergence of Drift Variants That May Affect COVID-19 Vaccine Development and Antibody Treatment. Life Sciences [preprint]; 2020.

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• Incidence of cardiac injury (defined as elevation of high-sensitivity cardiac troponin I to >99th percentile of the upper reference limit) ranges from 7-28% in hospitalized COVID-19 patients. Cardiac injury appears to be associated with significantly higher mortality in affected patients (51% vs. 4.5% in one review).(1)

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• The incidence of arrhythmia was 16.7% in a Chinese cohort of 138 hospitalized COVID-19 patients.(2) In another cohort of 191 inpatients from China, prevalence of heart failure was 23%.(3)  A report of critically ill COVID-19 patients from Washington state found that 7 of 21 (33%) had evidence of de novo cardiomyopathy.(4) 

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• SARS-CoV and MERS were also associated with cardiac complications. In a review, SARS was associated with tachycardia (72%) and reversible cardiomegaly (10.7%) with no clinical evidence of heart failure.(5) Reports on MERS also noted cardiac arrhythmias in up to 15.7% of patients.

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• On April 20, 2020, the American College of Cardiology, the Society for Cardiovascular Angiography and Interventions, and the American College of Emergency Physicians released a consensus statement on the management of acute myocardial infarction during the COVID-19 pandemic. They emphasize that percutaneous coronary intervention (PCI) remains the standard of care in managing patients with ST-elevation MI, with appropriate personal protective equipment utilized by healthcare providers.(6)

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1. Atri D, Siddiqi H, Lang J, Nauffal V, Morrow D, Bohula E. COVID-19 for the Cardiologist: A Current Review of the Virology, Clinical Epidemiology, Cardiac and Other Clinical Manifestations and Potential Therapeutic Strategies. JACC: Basic to Translational Science [preproof]. [posted 2020 April 10; cited 2020 April 22].

2. Wang D, Hu B, Hu C, et al. Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus–Infected Pneumonia in Wuhan, China. JAMA. 2020;323(11):1061–1069.

3. Zhou F, Yu T, Dui R, Fan G et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020. 395(10229):1054 - 1062 

4. Arentz M, Yim E, Klaff L, Lokhandwala S, Riedo F, Chong M et al. Characteristics and Outcomes of 21 Critically Ill Patients With COVID-19 in Washington State. JAMA. 2020. (Letter). 

5. Kochi A, Tagliari A, Forleo G, Fassini G, Tondo C. Cardiac and arrhythmic complications in patients with COVID-19. Journal of Cardiovascular Electrophysiology. 2020; 1-6. 

6. Mahmud E, Dauerman HL, Welt FG, Messenger JC, et al. Management of Acute Myocardial Infarction During the COVID-19 Pandemic, Journal of the American College of Cardiology (2020).

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• As of April 22, 2020, a global total of seven companion and captive animals (four cats, two dogs, and a tiger) are reported to have tested positive for SARS-CoV-2 following close contact with infected humans.(1,2) Four of the felines showed mild respiratory symptoms.(1)

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• A recent laboratory study suggested cats and ferrets are susceptible to SARS-CoV-2 infection and may be capable of transmitting the virus to other cats under ideal laboratory conditions.(3) The cats in the study did not develop clinical signs of disease. The same study reported dogs, pigs, chickens, and ducks were less susceptible to SARS-CoV-2 infection and incapable of transmission of the virus under laboratory settings. To date, there is no evidence of transmission between companion animals outside of the laboratory setting.

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• There is currently no evidence that companion animals or livestock transmit SARS-CoV-2 to humans or participate in the spread of the pandemic.(1,2)

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• The CDC has provided interim guidance for pet owners(4) and the Canadian Food Inspection Agency has provided recommendations for livestock producers regarding the management of domestic and farm animals during the COVID-19 pandemic.(5) They recommend that people with confirmed or suspected COVID-19 should restrict their interactions with animals.​

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1. American Veterinary Medical Association. SARS-CoV-2 in pets [Internet]. American Veterinary Medical Association. 2020 Apr 22 [cited 2020 Apr 22].

2. World Organization for Animal Health. Questions and answers on the 2019 coronavirus disease (COVID-19) [Internet]. World Organization for Animal Health. 2020 Apr 21 [cited 2020 Apr 22].

3. Shi J, Wen Z, Zhong G, Yang H, Wang C, Huang B, et al. Susceptibility of ferrets, cats, dogs, and other domesticated animals to SARS–coronavirus 2. Science (80- ) [Internet]. 2020 Apr 8 [cited 2020 Apr 21];7015(April):eabb7015.

4. Centres for Disease Control and Prevention. Interim guidance for public health professionals managing people with COVID-19 in home care and isolation who have pets or other animals [Internet]. Centres for Disease Control and Prevention. 2020 Mar 16 [cited 2020 Apr 22].

5. Canadian Food Inspection Agency. Coronavirus (COVID-19): information for consumers about food safety and animal health [Internet]. Canadian Food Inspection Agency. 2020 Apr 17 [cited 2020 Apr 22].

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• Cardiovascular disease, underlying respiratory disease, and hypertension were noted early in the course of the COVID-19 pandemic to be risk factors for severe disease (see March 21, 2020 Newsletter). 

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• Recent descriptive studies using national data from China and the United States have identified older age, malignancy, multiple comorbidities, and diabetes as consistent risk factors for severe disease.(1,2,3) Worse outcomes are also seen in immunocompromised patients and those with renal disease.(1,2) A recent New York area study reviewed over 4,000 cases of COVID-19 found obesity to be a risk factor for severe disease.(3) 

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• It should be noted that descriptive studies can be limited by the comorbidities selected for inclusion in the analysis. 

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1. Guan W-jie, Liang W-hua, Zhao Y, et al. Comorbidity and its impact on 1590 patients with Covid-19 in China: A Nationwide Analysis. Eur Respir J; 2020 March 26, in press.

2. CDC COVID-19 Response Team. Preliminary Estimates of Prevalence of Selected Underlying Health Conditions Among Patients with Coronavirus Disease 2019 - United States February 12 - March 28, 2020. Morbidity and Mortality Weekly Report. 3 April 2020. 69(13);382–386. 

3. Petrilli, C. et al. Factors associated with hospitalization and critical illness among 4,103 patients with Covid-19 disease in New York City. medRxiv [preprint]. 11 April 2020 in press.

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• Coronaviruses, in general, tend to have a seasonal pattern of infection. For SARS-CoV-2, a study using modelling and statistical analysis has suggested that rising temperature may lower transmission in the Northern Hemisphere in the coming months.(1)

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• In one laboratory study, a reduction in SARS-CoV virus strain infectivity was observed at high temperatures (38°C with >95% relative humidity).(2) In another study, inactivation of SARS-CoV-2 was shown at 56°C and 70°C after 30 mins and 5 mins incubation, respectively.(3)

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• Respiratory viruses remain stable and transmissible at low relative humidity (RH) and low temperature. Interestingly, more rapid viral inactivation is observed at a moderate RH of ~50% (typical in summer afternoons) compared to a low RH (20%) or high RH (80%). This might explain why areas in China with high humidity still saw high transmission of SARS-CoV-2.(4)

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• It is difficult to predict the impact of seasonal variations in temperature and humidity on the future course of SARS-CoV-2. Factors such as herd immunity, host behavior, and infection control measures will all play a role in altering the trajectory of the pandemic.(5)

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1. Carleton T, Meng K. Causal empirical estimates suggest COVID-19 transmission rates are highly seasonal; medRxiv [preprint]. [posted 2020 March 30; cited 2020 April 15]. 

2. Chan K, Peiris J, Lam S, Poon L, Yuen K, Seto W. The Effects of Temperature and Relative Humidity on the Viability of the SARS Coronavirus. Advances in Virology. 2011;2011:1-7.  

3. Chin A, Chu J, et al. Stability of SARS-CoV-2 in different environmental conditions. The Lancet Microbe 2020; published online April 2. (Correspondence).

4. Moriyama M, Hugentobler W, Iwasaki A. Seasonality of Respiratory Viral Infections. Annual Review of Virology. 2020;7(1).  

5. Neher R, Dyrdak R, Druelle V, Hodcroft E, Albert J. Potential impact of seasonal forcing on a SARS-CoV-2 pandemic. Swiss Medical Weekly. 2020; published online 16 March 2020.

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• Canada’s COVID-19 case fatality rate (CFR) is 3.1% as of April 14th.(1) A preprint meta-analysis of 29 international studies reported an adjusted CFR of 7.4%.(2)

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• The CDC recently reported an American healthcare worker CFR of 0.3% compared to 3.6% in the general population.(3) A study of 72,315 COVID-19 patients in China also described a healthcare worker CFR lower than the general population (0.3% vs. 2.3%).(4)

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• CFR is difficult to calculate in rapidly evolving pandemics such as COVID-19, due to biases introduced through diagnostics, surveillance, and analytic variability.(2) Thus far, initial reports indicate that healthcare worker CFR may be lower than the general population, but this may be related to differences in testing as well as underlying characteristics of the affected population.

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1. Canada.ca. Coronavirus Disease 2019 (COVID-19) Daily Epidemiology Update [Internet]. April 14, 2020. Accessed April 14, 2020. 

2. Kahathuduwa CN, Dhanasekara CS, Chin S-H. Case fatality rate in COVID-19: a systematic review and meta-analysis. medRxiv [preprint]. [posted 2020 April 06; cited 2020 April 14]. 

3. CDC COVID-19 Response Team. Characteristics of health care personnel with COVID-19 — United States, February 12–April 9, 2020. MMWR Morb Mortal Wkly Rep [Internet]. 2020 [cited 2020 Apr 13];69. 

4. Wu Z, McGoogan JM. Characteristics 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 Apr 7;323(13):1239–42.

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• Several reports indicate that abnormal coagulation parameters including elevated D-dimer and fibrin degradation products, prolonged prothrombin time, and thrombocytopenia often occur in COVID-19.(1,2,3,4,5) They are also associated with increased disease severity, development of ARDS, and mortality.

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• Severe COVID-19 appears to be associated with high rates of thrombotic events. In a descriptive study of 184 ICU patients with COVID-19 from three Dutch hospitals, the cumulative incidence of venous or arterial thromboembolism was 31%, despite all patients receiving at least prophylactic doses of anticoagulation.(6) 81% of those events were pulmonary embolism and none of the patients had disseminated intravascular coagulation (DIC). In contrast, 5.9% of hospitalized patients with pandemic H1N1 Influenza developed arterial or venous thromboembolism.(7)

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• DIC appears to be common in fatal cases of COVID-19 and rare among those that survive, though the actual incidence is still unclear. In a retrospective study of 183 COVID-19 patients in a Wuhan hospital, 71.4% of non-survivors developed DIC during hospitalization compared to only 0.6% of survivors.1 In another retrospective study of 225 patients in Wuhan, DIC occurred in 6.4% of non-survivors and 0% of survivors.(8)

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1. Tang N, Li D, Wang X, Sun Z. Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. J Thromb Haemost. 2020 Apr 1 [cited 2020 Apr 16]. 

2. Lippi G, Favaloro EJ. D-dimer is Associated with Severity of Coronavirus Disease 2019: A Pooled Analysis. Thromb Haemost. 2020 Apr 3 [cited 2020 Apr 16].

3. Lippi G, Plebani M, Henry BM. Thrombocytopenia is associated with severe coronavirus disease 2019 (COVID-19) infections: A meta-analysis. Clin Chim Acta [Internet]. 2020 Jul 1 [cited 2020 Apr 17];506:145–8. 

4. Wu C, Chen X, Cai Y, Xia J, Zhou X, Xu S, et al. Risk Factors Associated with Acute Respiratory Distress Syndrome and Death in Patients with Coronavirus Disease 2019 Pneumonia in Wuhan, China. JAMA Intern Med. 2020 [cited 2020 Apr 13]. 

5. Han H, Yang L, Liu R, Liu F, Wu K, Li J, et al. Prominent changes in blood coagulation of patients with SARS-CoV-2 infection. Clin Chem Lab Med. 2020 Mar 15 [cited 2020 Apr 13];0(0). 

6. Klok FA, Kruip MJHA, van der Meer NJM, Arbous MS, Gommers DAMPJ, Kant KM, et al. Incidence of thrombotic complications in critically ill ICU patients with COVID-19. Thromb Res [Internet]. 2020 Apr 10 [cited 2020 Apr 17]. 

7. Bunce PE, High SM, Nadjafi M, Stanley K, Liles WC, Christian M. Pandemic H1N1 Influenza Infection and Vascular Thrombosis, Clin Inf Dis. 2011;52(2):e14–e17. 

8. Deng Y, Liu W, Liu K, Fang Y-Y, Shang J, zhou L, et al. Clinical characteristics of fatal and recovered cases of coronavirus disease 2019 (COVID-19) in Wuhan, China. Chin Med J (Engl). 2020 Mar [cited 2020 Apr 13];1.

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• Studies are limited, but current data suggests that pregnant women are not at greater risk of developing severe COVID-19 than the general population. Clinical characteristics are similar to non-pregnant adults with most having mild to moderate symptoms.(1) Some were asymptomatic until they developed postpartum fever and/or mild respiratory symptoms.(2) Two cases from Iran reported maternal death after delivery due to acute respiratory distress syndrome (ARDS).(3)

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• A systematic review identified 32 pregnant women of which 15 (47%) had preterm delivery.(4) As well, only 23 of the 32 women had reported maternal outcome, of which two required ICU admission.

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• No cases of severe disease or fatal outcome was reported in nine generally healthy Chinese women infected with SARS-CoV-2 during late third trimester.(5) Of note, six were given an antiviral and all of the women were provided with oxygen support and empiric antibiotics. Post infection onset, two women experienced premature rupture of membrane and fetal distress was noted in two other women. Four of the women had preterm labour, although all were past 36 gestational weeks and the etiology was felt to be unrelated to COVID-19.

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• Although there is limited data, and most are from women infected in their third trimester, the outcomes of COVID-19 in pregnancy appear less severe compared to SARS and MERS.(6)

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1. Asadi L, Tabatabaei R, Safi Nejad H, Mohammadi M. New Corona Virus (COVID-19) Management in Pregnancy and Childbirth. Archives of Clinical Infectious Diseases. 2020; Uncorrected Proof (In Press).

2. Chen S, Liao E, Shao Y. Clinical analysis of pregnant women with 2019 novel coronavirus pneumonia. Journal of Medical Virology. 2020;(Accepted article). [published 2020 March 28; cited 2020 April 9].

3. Karimi-Zarchi M, Neamatzadeh H, Dastgheib S, Abbasi H, Mirjalili S, Behforouz A et al. Vertical Transmission of Coronavirus Disease 19 (COVID-19) from Infected Pregnant Mothers to Neonates: A Review. Fetal and Pediatric Pathology. 2020;:1-5. 

4. Mullins E, Evans D, Viner R, O'Brien P, Morris E. Coronavirus in pregnancy and delivery: rapid review. Ultrasound in Obstetrics & Gynecology. 2020; (Accepted article). [published 2020 March 17; cited 2020 April 9].

5. Chen H, Guo J, Wang C, Luo F, Yu X, Zhang W et al. Clinical characteristics and intrauterine vertical transmission potential of COVID-19 infection in nine pregnant women: a retrospective review of medical records. The Lancet. 2020;395(10226):809-815.

6. Dashraath P, Jing Lin Jeslyn W, Mei Xian Karen L, Li Min L, Sarah L, Biswas A, Arjandas Choolani M, Mattar C, Lin SL, Coronavirus Disease 2019 (COVID-19) Pandemic and Pregnancy, American Journal of Obstetrics and Gynecology (2020). 2020 March 17 in pre-proof. ​

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• Malignancy: In a Chinese prospective cohort study of 1,590 symptomatic COVID-19 patients, 1% (18 patients) had malignancy, most commonly lung cancer. There was an increased risk of severe disease and mortality in those with a history of cancer. Active disease, chemotherapy or surgery within a month of infection increased likelihood of poor outcomes.(1) A preprint retrospective cohort study of 28 COVID-19 patients with cancer from Wuhan had similar findings.(2)

  

• Organ recipients: Nine COVID-19 case studies following a total of 17 organ transplant recipients: two cardiac,(3) four hepatic,(4,5) ten renal,(6,7,8,9,10,11) and an allogeneic bone marrow transplant(11) were reviewed. In general, presentations and timeline were similar to immunocompetent populations. Two died, three were intubated, and most required adjustment of immunosuppressive regimen. Currently, there is little data to support increased or decreased risk of severe disease or mortality for COVID-19 patients on immunosuppressive therapy for organ transplantation. Opinions are divided as to whether immuno-suppressive therapy may be somewhat protective from severe disease and adverse outcomes, while recommendations to minimize exposure to COVID-19 for immunosuppressed patients are consistent.

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1. Liang, W. et al. Cancer patients in SARS-CoV-2 infection: a nationwide analysis in China. The Lancet Oncology. 2020 February 14. 335-337.

2. Zhang, L. Clinical characterisrics of COVID-19-infected cancer patients: A retrospective case study in three hospitals within Wuhan, China. Annals of Oncology. 2020 March 23 in pre-proof.

3. Li, F. et al. First Cases of COVID-19 in Heart Transplantation from China. Journal of Heart and Lung Transplantation. 2020 March 17 in Pre-Print.

4. D’Antiga, L. Coronaviruses and immunosuppressed patients. The facts during the third epidemic. Liver transplantation. 2020 March 20 in press.

5. Bin, L. et al. Successful treatment of severe COVID-19 pneumonia in a liver transplant recipient. American Journal of Transplantation. 2020 April 3 in press.  

6. Zhang, H. et al. Identification of Kidney Transplant Recipients with Coronavirus Disease 2019. European Association of Urology. 2020 March 20 in press. 1-6.

7. Chen, S. et al. A familial cluster, including a kidney transplant recipient of Coronavirus Disease 2019 (COVID-19) in Wuhan, China. American Journal of Transplantation in press. 2020 April 3.

8. Zhu, L. et al. Successful recovery of COVID-19 pneumonia in a renal transplant recipient with long-term immunosuppression. American Journal of Transplantation. 2020 March 15. 1-5.

9. Guillen, E. et al. Case report of COVID-19 in a kidney transplant recipient: Does immunosuppression alter the clinical presentation?. American Journal of Transplantation. 20 March 2020 in press.

10. Seminari, E. et al. SARS Cov2 infection in a renal transplanted patients. A case report. American Journal of Transplantation. 2020 April 3 in press.

11. Huang, J. COVID-19 in post-transplantation patients - report of two cases. American Journal of Transplantation. 2020 April 3 in press

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• As of April 8, 2020, there have been no reported cases of laboratory-acquired infection (LAI) with SARS-CoV-2 in Canada with the completion of approximately 360,000 tests.

​​

• There have been four cases of laboratory-acquired SARS-CoV infection since 2003.(1) All of these were attributed to a lack of understanding or adherence to safety procedures and involved laboratories where virus was being grown in cell culture. No LAI has been reported for MERS-CoV.(2)

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• The WHO has provided interim guidance on laboratory safety related to COVID-19.(3) Public health labs across Canada are processing SARS-CoV-2 specimens for molecular detection in containment level 2 labs with use of appropriate PPE and biosafety cabinets.

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1. Canada.ca [Internet]. Ottawa: Public Health Agency of Canada. Pathogen Safety Data Sheets: Infectious Substances – Severe acute respiratory syndrome (SARS) associated coronavirus; 2019 Dec 6 [cited 2020 Apr 7]; [Section VI - Laboratory hazards].  

2. Canada.ca [Internet]. Ottawa: Public Health Agency of Canada. Pathogen Safety Data Sheet: Infectious substances - Middle east respiratory syndrome (MERS)-related Coronavirus; 2019 Dec 6 [cited 2020 Apr 7]; [Section VI - Laboratory hazards].

3. World Health Organization [internet]. World Health Organization; 2020. Laboratory biosafety guidance related to coronavirus disease 2019 (COVID-19): interim guidance, 12 February 2020. 2020 Feb 12 [cited 2020 Apr 7].  

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• 1,257 healthcare workers in China surveyed during the COVID-19 outbreak reported symptoms of depression (50.4%), anxiety (44.6%), insomnia (34.0%), and distress (71.5%).(1)

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• During the SARS outbreak in 2003, health care workers in Toronto reported feelings of anxiety, anger, frustration, as well as fear of contagion and infection of loved ones.(2) Mental distress was exacerbated by uncertainty, changes in isolation procedures, and colleagues entering quarantine or treatment. Approximately 10% of hospital employees, at an affected Beijing hospital, reported post-traumatic stress symptoms at some point during the three year period post SARS outbreak.(3)

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• For protection of mental well-being during the COVID-19 pandemic, staff should be provided with realistic, timely situational updates to allow for psychological preparedness. Health care workers should seek early interventions from informal support networks (such as peer supports or colleagues) with swift escalation to professional support as needed, and self-care should be practiced.(4,5)

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1. Lai J, Ma S, Wang Y, Cai Z, Hu J, Wei N, et al. Factors associated with mental health outcomes among health care workers exposed to coronavirus disease 2019. JAMA Netw Open [Internet]. 2020 Mar 23 [cited 2020 Apr 7];3(3).

2. Maunder R, Hunter J, Vincent L, Bennett J, Peladeau N, Leszcz M, et al. The immediate psychological and occupational impact of the 2003 SARS outbreak in a teaching hospital. CMAJ Can Med Assoc J. 2003 May 13;168(10):1245–51.

3. Wu P, Fang Y, Guan Z, Fan B, Kong J, Yao Z, et al. The psychological impact of the SARS epidemic on hospital employees in China: exposure, risk perception, and altruistic acceptance of risk. Can J Psychiatry Rev Can Psychiatr. 2009 May;54(5):302–11.

4. Xiang Y-T, Yang Y, Li W, Zhang L, Zhang Q, Cheung T, et al. Timely mental health care for the 2019 novel coronavirus outbreak is urgently needed. Lancet Psychiatry. 2020 Mar 1;7(3):228–9.

5. Williamson V, Murphy D, Greenberg N. COVID-19 and experiences of moral injury in front-line key workers. Occup Med [Internet]. [cited 2020 Apr 6]

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• Evidence of viral shedding is limited to studies using real-time PCR to detect viral RNA. The significance of detected viral RNA is clinically unclear. Viral culture to determine if the RNA represents viable virus is rarely found in the literature.(1)

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• A retrospective cohort study of 191 patients from numerous Wuhan hospitals showed, of the 118 who survived with complete follow-up data, the median time of viral shedding from symptom onset was 20 days (longest = 37 days) determined by PCR (throat swab). Survivors who were in critical condition had a median shed time of 24 days.(2)

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• 1 asymptomatic and 9 symptomatic children with COVID-19 were followed by RT-PCR on nasopharyngeal (NP) and rectal swabs. Of the 8 positives on initial rectal swab, 5 had subsequent positive rectal swabs at least 2 weeks after NP swabs tested negative (most >3 weeks). This suggests that fecal shedding can occur even after negative NP swabs are documented.(3) However, to date there is no evidence for fecal-oral transmission.

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1. Hoehl S, Rabenau H, Berger A, Kortenbusch M, Cinatl J, Bojkova D et al. Evidence of SARS-CoV-2 Infection in Returning Travelers from Wuhan, China. New England Journal of Medicine. 2020;382(13):1278-1280.

2. Zhou, F. et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. The Lancet. 2020 March 9.

3. Xu, Y. et al. Characteristics of pediatric SARS-CoV-2 infection and potential evidence for persistent fecal viral shedding. Nature Medicine. 2020 March 13.

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• In a group of German evacuees from Wuhan, China, 2 patients remained well for 7 days after testing positive for SARS-CoV-2 by RT-PCR. Samples from these patients were cytopathogenic to Caco-2 cells, an indication of potential infectivity.(1)

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• In a report detailing screening of close contacts from China, time between first positive RT-PCR to first negative was up to 21 days in asymptomatic patients with a median time of 9.5 days.(2) Viral load in asymptomatic patient swabs was also similar to patients with symptoms.(3)

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• Using contact information from 94 patients, an estimate of incubation time, and RT-PCR data, a preprint article notes that the viral load peaks around symptom onset and decreases thereafter. Authors estimate that infectiousness starts 2-3 days before symptom onset, peaking on or just before the onset and declining rapidly within 7 days of illness onset.(4)

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1. Hoehl S, Rabenau H, Berger A, Kortenbusch M, Cinatl J, Bojkova D et al. Evidence of SARS-CoV-2 Infection in Returning Travelers from Wuhan, China. New England Journal of Medicine. 2020;382(13):1278-1280.

2. Hu, Z., Song, C., Xu, C., Jin, G., Chen, Y., Xu, X., Ma, H., Chen, W., Lin, Y., Zheng, Y., et al. (2020). Clinical characteristics of 24 asymptomatic infections with COVID-19 screened among close contacts in Nanjing, China. Sci China Life Sci 63.

3. Zou L, Ruan F, Huang M, Liang L, Huang H, Hong Z et al. SARS-CoV-2 Viral Load in Upper Respiratory Specimens of Infected Patients. N Engl J Med. 2020;382(12):1177-1179.

4. He X, Lau E, Wu P, Deng X, Wang J, Hao X et al. Temporal dynamics in viral shedding and transmissibility of COVID-19; medRxiv [preprint]. [posted 2020 March 18; cited 2020 April 1].

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• Anosmia and impaired taste are known to occur in viral URTIs.(1) Recent media attention has focused on the utility of using these symptoms to predict infection with SARS-CoV-2.

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• A recent survey of 59 hospitalized patients in Italy reported 20 (34%) complained of at least one taste or olfactory disorder, and 11 (19%) complained of both.(2) In a preprint retrospective case series of 214 hospitalized patients with COVID-19 in Wuhan, China, 12 patients (5.6%) had hypogeusia and 11 patients (5.1%) had hyposmia.(3)

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• Researchers at Kings College in London have estimated the rate of anosmia in COVID-19, using self-reported symptoms from 400,000 people via an online app, may be as high as 59%, but this data lacks scientific validation.(4)

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• At this time, there is no robust evidence that supports using these symptoms to accurately predict COVID-19 infection.

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1. Suzuki M, Saito K, Min WP, Vladau C, Toida K, Itoh H, et al. Identification of viruses in patients with postviral olfactory dysfunction. Laryngoscope [Internet]. 2007 Feb [cited 2020 Apr 2];117(2):272–7.

2. Giacomelli A, Pezzati L, Conti F, Bernacchia D, Siano M, Oreni L, et al. Self-reported olfactory and taste disorders in SARS-CoV-2 patients: a cross-sectional study. Clin Infect Dis [Internet]. 2020 Mar 26 [cited 2020 Mar 31].

3. Mao L, Wang M, Chen S, He Q, Chang J, Hong C, et al. Neurological Manifestations of Hospitalized Patients with COVID-19 in Wuhan, China: a retrospective case series study. medRxiv [preprint]. [posted 2020 Feb 25; cited 2020 Mar 31].

4. COVID Symptom Tracker [Internet]. Domains By Proxy, LLC. Research update: April 1 2020. 2020 Apr 1 [cited 2020 Apr 2].

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• No research is available regarding exact risk of transmissibility of SARS-CoV-2 from donor to recipient in the process of transplantation, but expert opinion indicates plausibility.(1)

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• Numerous guidelines have been produced on this topic and there is consensus that donor and recipients should be screened prior to transplant. 

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• From a Canadian perspective, the Organ Donation and Transplantation Expert Advisory Committee (ODTEAC) has made recommendations to consider postponing or suspending renal transplants, and to assess medical urgency for liver transplant on a case-by-case basis. It is recommended to screen both donor and recipient and to not use organs from donors who are confirmed positive for COVID-19 or who meet high-risk criteria. Transplants are to be deferred for positive recipients.(2)

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• In Manitoba, latest updates can be found at Shared Health Manitoba. Of note, all non-urgent surgical procedures in Manitoba were suspended effective March 23, 2020.

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1. American Society of Transplantation. COVID 19 Organ Donation and Transplant Town Hall [Webinar]. AST Transplantation. March 23, 2020. Accessed March 30, 2020.

2. Organ Donation and Transplantation Expert Advisory Committee (ODTEAC). Consensus guidance for organ donation and transplantation services during COVID-19 pandemic. March 27, 2020. Accessed March 30, 2020.

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• There is limited data regarding co-infection of patients with COVID-19. One study from China indicated that 6.5% of adults with COVID-19 were possibly co-infected with another respiratory tract virus.(1) Another, also from China, indicated that up to 4.35% of adults with COVID-19 were co-infected with Influenza.(2)

​​

• Co-infection rate among the pediatric population is potentially higher (see the pediatric section below for details).(3)

​​

• There is insufficient data to conclude the clinical relevance of co-infection with multiple respiratory pathogens. Rates of concurrent bacterial pneumonia are also unclear. It is important to be mindful that a patient could still be positive for COVID-19 even if they have tested positive for another respiratory tract virus.

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1. Lin D, Liu L, Zhang M, Hu Y, Yang Q, Guo J, Guo Y, Dai Y, Xu Y, Cai Y, Chen X. Co-infections of SARS-CoV-2 with multiple common respiratory pathogens in infected patients. Science China Life Sciences. [Epub ahead of print 2020 Mar 5:1-4]. 

2. Ding Q, Lu P, Fan Y, Xia Y, Liu M. The clinical characteristics of pneumonia patients co-infected with 2019 novel coronavirus and influenza virus in Wuhan, China. Journal of Medical Virology. [Epub ahead of print 2020 Mar 20]. Note: Accepted and peer-reviewed, but not through final proofreading. 

3. Xia W, Shao J, Guo Y, Peng X, Li Z, Hu D. Clinical and CT features in pediatric patients with COVID‐19 infection: Different points from adults. Pediatric Pulmonology. [Epub ahead of print 2020 Mar 5].

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• Among 44,415 cases (hospitalized and non-hospitalized, 62% lab-confirmed) in China, 81% were classified as mild (non-pneumonia or mild pneumonia). 14% were classified as severe (dyspnea, RR >30, SpO2 <93%, PaO2/FiO2 <300, and/or lung infiltrates >50% within 24-48 hours). Critical cases (respiratory failure, septic shock, and/or multiple organ dysfunction/failure) comprised 5% of cases. All recorded deaths occurred in the critical category.(1)

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• In another study of 1,099 hospitalized patients in China with lab-confirmed COVID-19, 84.3% met IDSA/ATS criteria for non-severe community-acquired pneumonia.(2) 17.9% of non-severe patients had no radiographic or CT abnormality, and only 2.6% eventually developed disease severe enough to result in ICU admission, invasive mechanical ventilation, or death.(3)

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1. Novel Coronavirus Pneumonia Emergency Response Epidemiology Team. The epidemiological characteristics of an outbreak of 2019 novel coronavirus diseases (COVID-19) in China. Zhonghua Liu Xing Bing Xue Za Zhi. 2020;41(2):145-151. Abstract in English.

2. Metlay JP, Waterer GW, Long AC, Anzueto A, Brozek J, Crothers K, Cooley LA, Dean NC, Fine MJ, Flanders SA, et al. Diagnosis and treatment of adults with community-acquired pneumonia. Am J Respir Crit Care Med. 2019;200(7):E45-E67. 

3. Guan W-J, Ni Z-Y, Hu Y, Liang W-H, Ou C-Q, He J-X, Liu L, Shan H, Lei C-L, Hui DSC, et al. Clinical Characteristics of Coronavirus Disease 2019 in China. N Engl J Med. 2020:1-13.

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• There have been news/government reports of some recently discharged patients apparently relapsing and requiring re-admission,(1) these reports are anecdotal. Thus far, no proven cases of reinfection have been published in the scientific literature.

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• Two papers have documented cases of patients who recovered and were discharged after negative nasopharyngeal RT-PCR tests, but later tested positive on follow-up swab. These patients remained well with no clinical recurrence of disease, no new chest CT findings, and no new exposures.(2,3) The significance of these findings is unclear.

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• In a small preprint trial involving rhesus macaques, two monkeys who recovered from COVID-19 did not become reinfected when re-exposed to the virus 28 days after the initial infection.(4)

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1. Su A. They survived the coronavirus. Then they tested positive again. Why? Los Angeles Times [newspaper on the internet]. 2020 Mar 13 [cited 2020 Mar 24]:World & Nation. 

2. Lan L, Xu D, Ye G, Xia C, Wang S, Li Y, et al. Positive RT-PCR Test Results in Patients Recovered From COVID-19. JAMA [Internet]. 2020 Feb [cited 2020 Mar 24]; DOI:10.1001/jama.2020.2783. 

3. Xing Y, Mo P, Xiao Y, Zhao O, Zhang Y, Wang F. Post-discharge surveillance and positive virus detection in two medical staff recovered from coronavirus disease 2019 (COVID-19), China, January to February 2020. Euro Surveill Bull Eur sur les Mal Transm = Eur Commun Dis Bull. 2020 Mar [cited 2020 Mar 24];25(10). DOI:10.2807/1560-7917.ES.2020.25.10.2000191. 

4. Bao L, Deng W, Gao H, Xiao C, Liu J, Xue J, et al. Reinfection could not occur in SARS-CoV-2 infected rhesus macaques. BioRxiv [Preprint].  [Internet]. [Posted 2020 Mar 14; cited 2020 Mar 24]; DOI:10.1101/2020.03.13.990226.

• A descriptive article from China reported 1,716 healthcare workers (HCWs) diagnosed with COVID-19 as of February 11, 2020. Of the infected HCWs, 14.8% had severe or critical disease (vs. 14% in the general population) and 5 died (0.3% vs. 2.3% of confirmed cases in the general population).(1,2)  The WHO-China Joint Mission on COVID-19 on February 24, 2020 announced the infection of 2,055 HCWs and 22 deaths (1.1%).(3)

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• One case report from Singapore assessed 41 HCWs with exposure (aerosol-generating procedures for >10 minutes, distance <2m from patient) to a patient who ultimately was found to be infected with SARS-CoV-2, but at the time of care was not suspected to have COVID-19. Routine infection control procedures were followed (85% used surgical masks, 15% N95 masks). None of the HCWs became infected based on 14 days of surveillance.(4)

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• A preprint commentary from Chinese researchers suggests many infections of healthcare workers resulted from identifiable and potentially preventable deficits including lack of communication, lack of general preparedness, lack of infection control and prevention training, inappropriate or lack of appropriate PPE, lack of point of care testing and RT-PCR testing supplies, and patient misinformation related to exposure risk.(3)

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1. The Novel Coronavirus Pneumonia Emergency Response Epidemiology Team. The Epidemiological Characteristics of an Outbreak of 2019 Novel Coronavirus Diseases (COVID-19) - China, 2020. China CDC Weekly. 2020. 2(8):113-122.  

2. Wu Z, McGoogan J. Characteristics of and Important Lessons from the Coronavirus Disease 2019 (COVID-19) Outbreak in China; Summary of a Report of 72314 Cases from the Chinese Center for Disease Control and Prevention. JAMA. 2020 February 24: E1-E4. 

3. Wang J, Zhou M, Liu F. Exploring the reasons for healthcare workers infected with coronavirus disease 2019 (COVID-19) in China. Journal of Hospital Infection. 2020 [cited 2020 March 25 in Pre-proof]. 

4. Ng K, Poon BH, Kiat Puar TH, et al. COVID-19 and the Risk to Health Care Workers: A Case Report. Ann Intern Med. 2020; [Epub ahead of print 16 March 2020].

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• Based on the best available data, COVID-19 appears to have an incubation period between 2 and 12 days, with a median of about 5 days.(1) Rarely, it may be longer. This suggests that an active surveillance window of 14 days after exposure will catch the majority of symptomatic patients. 

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• This is generally consistent with SARS and MERS. Both had an incubation period of roughly 2 to 14 days.(2,3)

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1. Lauer SA, Grantz KH, Bi Q, et al. The Incubation Period of Coronavirus Disease 2019 (COVID-19) From Publicly Reported Confirmed Cases: Estimation and Application. Ann Intern Med. [Epub ahead of print 10 March 2020].

2. Varia M, Wilson S, Sarwal S, et al. Investigation of a nosocomial outbreak of severe acute respiratory syndrome (SARS) in Toronto, Canada. CMAJ. 2003 Aug;169(4):285-292.

3. Virlogeux V, Fang VJ, Park M, Wu JT, Cowling BJ. Comparison of incubation period distribution of human infections with MERS-CoV in South Korea and Saudi Arabia. Sci Rep. 2016 Oct;6:35839.

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• Asymptomatic carriers appear to be potential sources of infection, but data in this area is evolving.

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• Currently, the most robust data is from Italy where approximately 3,300 inhabitants of the town of Vò, near Venice, were tested regardless of symptoms. 50-75% of those testing positive were asymptomatic at the time. This data has not yet been formally published.(1,2)

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• In one study, median serial interval period (i.e. time from illness onset between two cases in a transmission chain) was 4.0 days in probable linked cases (95%CI: 3.1, 4.9) and 4.6 days in confirmed linked cases (95%CI: 3.5, 5.9).(3) This is shorter than or similar to the incubation period, raising the potential that people are infectious prior to developing symptoms.

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1. Cedrone G. «Scovare i positivi casa per casa: così abbiamo sconfitto il virus a Vo’». Il virologo Crisanti racconta il modello veneto. Sanita informazione al Tribunale di Roma. 12 March 2020 [cited 19 March 2020]. [Newspaper on the Internet]

2. La Repubblica. Coronavirus: "Il 50-75% dei casi a Vo' sono asintomatici. Una formidabile fonte di contagion. La Repubblica. 16 March 2020 [cited 19 March 2020]. [Newspaper on the Internet] 

3. Nishiura H, Linton NM, Akhmetzhanov AR. Serial interval of novel coronavirus (COVID-19) infections. International Journal of Infectious Diseases. [Epub ahead of print 04 March 2020]

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• Meta-analyses of cross-sectional studies show the most common symptoms in hospitalized patients are fever (89.1%) and cough (72.2%).(1) Dyspnea, myalgia, headache, chills, sore throat, sputum production, and fatigue were reported in fewer than half of cases. Rare symptoms (<10% of patients) include diarrhea, hemoptysis, nasal congestion, conjunctival congestion, nausea, or vomiting.(1,2,3)

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• The literature suggests that there are no symptoms or known combination of symptoms at illness onset that have sensitivity high enough to reasonably rule out COVID-19.

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1. Sun P, Qie S, Liu Z, Ren J, Xi JJ. Clinical characteristics of hospitalized patients with SARS‐CoV‐2 infection: A single arm meta‐analysis. Journal of Medical Virology. [Epub ahead of print 10 March 2020]

2. Guan W, Ni Z, Hu Y, Liang W, Ou C, He J, Liu L et al. Clinical Characteristics of Coronavirus Disease 2019 in China. New Eng J Med. [Epub ahead of print 28 February 2020].

3. Rodriguez-Morales AJ, Cardona-Ospina JA, Gutiérrez-Ocampo E, Villamizar-Peña R, Holguin-Rivera Y, Escalera-Antezana JP et al. Clinical, laboratory and imaging features of COVID-19: A systematic review and meta-analysis. Travel Medicine and Infectious Disease. [Epub ahead of print 13 March 2020][pre-proof].

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• A large (n=1099) cross-sectional study of COVID-19 from China showed an increased rate of severe disease (defined by the American Thoracic Society guidelines for community acquired pneumonia) in those with cardiovascular disease, hypertension, diabetes, and respiratory disease (specifically COPD).(1)

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• A preprint systematic review and meta-analysis reaffirmed the increased risk for cardiovascular disease, hypertension, and respiratory disease, but did not find a significant increased risk for those with diabetes.(2)

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1. Guan W, Ni Z, Hu Y, Liang W, Ou C, He J, Liu L et al. Clinical Characteristics of Coronavirus Disease 2019 in China. New England Journal of Medicine. [Epub ahead of print 28 February 2020].

2. Yang J, Zheng Y, Gou X, Pu K, Chen Z, Guo Q et al. Prevalence of comorbidities in the novel Wuhan coronavirus (COVID-19) infection: a systematic review and meta-analysis. International Journal of Infectious Diseases. [Epub ahead of print 12 March 2020].