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We know health care providers are busy working incredibly hard to respond to the pandemic. This is why Canadian medical students have decided to come together to provide you with daily updates on the state of literature on COVID-19. Each day, we search for new, relevant academic articles and summarize them for you, so you can focus on the important things.

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Tuesday, March 17th, 2020

Highlights from today's edition:
  • There is insufficient evidence at this time to know whether CODIV-19 reinfection is possible.
  • Combining RT-PCR and clinical/epidemiological evidence with chest CT results may improve diagnostic accuracy.
  • There is no evidence to support vertical transmission (i.e. from a pregnant woman to her fetus) of the novel coronavirus.
  • High fever has been associated with higher likelihood of ARDS, but lower likelihood of death.
  • An open-label RCT in China will evaluate the efficacy and safety of adjunctive systemic glucocorticoid therapy for patients with severe COVID-19 pneumonia.
  • Telemedicine could allow a patient to bypass the emergency department and go straight to a hospital bed.
Question of the day: Can someone be reinfected with the novel coronavirus?
  • The LA Times recently reported that ~100 Chinese patients with COVID-19 tested positive a second time after being discharged from the hospital with symptom resolution. This accounts for less than 0.2% of China’s total infections. 
  • One case series describes four medical workers in Wuhan with positive RT-PCR results at baseline. They received antiviral treatment and were discharged with 2 negative RT-PCR results once their clinical symptoms resolved. 5-13 days after being released from quarantine, they all tested positive again with 3 repeated tests over the next 4-5 days (1).
  • A case report from China describes a COVID-19 patient whose RT-PCR turned positive after two consecutive negative tests (2).
  • These findings suggest that a proportion of patients who recovered clinically may continue to test positive on RT-PCR testing.
  • Currently there is no evidence of re-emergence of symptoms after a negative test.
  • Per the CDC, “the immune response to COVID-19 is not yet understood. Patients with MERS-CoV infection are unlikely to be reinfected shortly after they recover, but it is not yet known whether similar immune protection will be observed for patients with COVID-19.”

1. Lan, Lan, et al. “Positive RT-PCR Test Results in Patients Recovered From COVID-19.” JAMA, 2020, doi:10.1001/jama.2020.2783.)  
2. Chen, Dabiao, et al. “Recurrence of Positive SARS-CoV-2 RNA in COVID-19: A Case Report.” International Journal of Infectious Diseases, 2020, doi:10.1016/j.ijid.2020.03.003) 

Email your question of the day to:

Lippi, Giuseppe, et al. “Potential Preanalytical and Analytical Vulnerabilities in the Laboratory Diagnosis of Coronavirus Disease 2019 (COVID-19).” Clinical Chemistry and Laboratory Medicine (CCLM), 16 Mar. 2020, doi:10.1515/cclm-2020-0285.

This opinion paper from Italy and Croatia highlights the vulnerabilities of SARS-CoV-2 laboratory diagnosis and presents recommendations to address them. Key points:
  • RT-PCR on respiratory tract specimens is the current diagnostic gold standard for SARS-CoV-2.
  • Pre-analytical vulnerabilities that may impact testing results include:
    • Lack of identification/misidentification of samples.
    • Inadequate sample transportation/storage.
    • Testing patients taking anti-retrovirals.
  • Analytical vulnerabilities that may impact testing results include:
    • Testing outside diagnostic window (when asymptomatic, mildly symptomatic or on the tail end of the infection).
    • Active viral recombination.
    • Misinterpretation of RT-PCR expression profiles.
  • Measures to improve diagnostic accuracy include:
    • Combining RT-PCR, clinical and epidemiological evidence, and chest CT results.
    • Repeating RT-PCR if a high index of suspicion remains after a negative result.
    • Disseminating clear instructions for specimen collection and handling and ensuring compliance with analytical procedures.

Elwood, Chelsea, et al. “Updated SOGC Committee Opinion – COVID-19 in Pregnancy.” Infectious Disease Committee of the Society of Obstetricians and Gynaecologists of Canada.

This consensus of experts from Canada highlights the risks and recommendations for obstetrical patients with suspected or confirmed COVID-19 as of March 10, 2020:
  • The vast majority of infected women in China had mild to moderate pneumonia. There was one case of severe maternal morbidity (31 yo F at 34 weeks gestational age with severe respiratory compromise and multi-organ dysfunction requiring ECMO).
  • Spontaneous and iatrogenic preterm labour are the most commonly reported adverse pregnancy outcomes. 
  • There is currently no evidence to support vertical transmission.
  • Maternal infection with SARS, MERS, or COVID-19 has not been associated with teratogenicity. However, the risk of congenital anomaly associated with COVID-19 cannot be completely excluded.
  • Antepartum recommendations include timely triage, testing and isolation for suspected cases of COVID-19, as well as monthly fetal surveillance.
  • Newborn infants should be tested for COVID-19 at birth.
  • Routine postnatal care should be delivered. The infant should not be isolated from the mother and breastfeeding should not be withheld. 

Wu, Chaomin, et al. “Risk Factors Associated With Acute Respiratory Distress Syndrome and Death in Patients With Coronavirus Disease 2019 Pneumonia in Wuhan, China.” JAMA Internal Medicine, 2020, doi:10.1001/jamainternmed.2020.0994.

This retrospective cohort study from China highlights the risk factors associated with ARDS and death in 201 patients with confirmed COVID-19 pneumonia. Key points:
  • Patients who developed ARDS were more likely to suffer from comorbidities such as hypertension and diabetes, and to have initially presented with dyspnea.
  • Risk factors associated with ARDS development and progression to death include older age, neutrophilia and elevated D-dimer.
  • High fever was associated with higher likelihood of developing ARDS but lower likelihood of death.
  • In patients who developed ARDS, treatment with methylprednisolone decreased the risk of death (hazard ratio 0.38). Editor's note: Other reports suggest that glucosteroids might actually be detrimental in COVID-19 infection.

Zhou, Yi-Hong, et al. “Effectiveness of Glucocorticoid Therapy in Patients with Severe Novel Coronavirus Pneumonia: Protocol of a Randomized Controlled Trial.” Chinese Medical Journal, 5 Mar. 2020, p. 1., doi:10.1097/cm9.0000000000000791.

This protocol for an open-label RCT in China outlines the details a study to evaluate the efficacy and safety of adjunctive systemic glucocorticoid therapy for patients with severe COVID-19 pneumonia. Key points:
  • Adjunctive systemic glucocorticoid therapy is commonly used in patients infected with COVID-19 who develop severe lower respiratory disease, but its efficacy and safety remain unclear.
  • Study characteristics: 
    • Population: 48 Adult patients from one center with RT-PCR-confirmed COVID-19 infection and who meet the diagnostic criteria for severe COVID-19 pneumonia -
    • Intervention: Conventional treatment plus adjunctive IV Methylprednisolone (1-2mg/kg/day x3 days).
    • Comparison: Conventional treatment without adjunctive glucocorticoid use. 
    • Outcome:
      • Primary endpoint: Change in Sequential Organ Failure Assessment (SOFA) at 3 days.
      • Secondary endpoints:
        • Proportion of mechanical ventilation use at 2 and 4 weeks.
        • Mortality at 2 and 4 weeks.
        • Duration of hospitalization.

Hollander, Judd E, and Brendan G Carr. “Virtually Perfect? Telemedicine for Covid-19.” The New England Journal of Medicine, U.S. National Library of Medicine, 11 Mar. 2020,

This perspective piece from the US examines the potential uses of telemedicine in the midst of the COVID-19 crisis. Key points:
  • A critical strategy to help control ED surges is forward triage, which involves sorting patients before they arrive to the hospital.
  • In a telemedicine approach to forward triage, automated systems could refer high-risk patients to in-person triage sites, while low-risk patients could schedule video visits with providers. 
  • Forward triage through telemedicine could allow a patient to bypass the ED and go directly to a hospital bed when deemed necessary.
  • This approach would also allow quarantined health care workers to participate in triage and intake, which would ease the load on in-person physicians.
  • There are many telemedicine networks already in place in the US that could be repurposed to fight COVID-19.
  • We first need to develop dedicated testing sites that are integrated into telemedicine workflows. 

This information is intended for health care professionals only. It is collected by medical students and may therefore be subject to error. Articles are hand-selected daily from a broad PubMed search.

Editor-in-chief: Ariane Litalien, fourth year medical student (McGill)

Senior Reviewer: Dr. Kylie Goodyear, Family Medicine PGY2 (MUN)

Contributors to today's edition:
Melanie Babinski, fourth year medical student (McGill) 
Geoffrey Ching, third year medical student (UBC)
Mohamed Eissa, fourth year medical student (Dalhousie)
Xiaoya Gao, third year medical student (McGill)

Leo Kadota, third year medical student (Ottawa) 
Arielle Springer, fourth year medical student (McGill) 

Peer-reviewers for today's edition:
Oana Jumanca, fourth year medical student (McGill)
Nicholas Koziris, third year medical student (McGill)
Emily Lostchuck, fourth year medical student (UBC)
Adhora Mir, third year medical student (McMaster)



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