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Clinical findings in a group of patients infected with the 2019 novel coronavirus (SARS-Cov-2) outside of Wuhan, China: retrospective case series

BMJ 2020; 368 doi: https://doi.org/10.1136/bmj.m606 (Published 19 February 2020) Cite this as: BMJ 2020;368:m606

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Linked Editorial

Covid-19: a puzzle with many missing pieces

Rapid Response:

Why Novel Coronavirus Fatality is Likely Overestimated

Dear Editor,

While the case fatality rate (CFR) of 2019-nCoV, the virus that causes COVID19, remains unknown, recently published figures likely overestimate the true rate.(1) Previous reviews of H1N1, MERS, and SARS highlight the difficulty of early estimation of CFR of novel viruses related to an absence of consensus on defining and measuring incidences and severities of infection.(2,3) Early estimates of H1N1’s CFR were susceptible to uncertainty regarding asymptomatic and subclinical infections, heterogeneity in approaches to diagnostic testing, as well as biases in ascertainment, survivorship, confounding and selection, and reporting.(2,3) These biases are difficult to overcome early in a pandemic.(3)

In this regard, we read Xu et al’s report of 62 cases of COVID-19 outside of Wuhan, China with great interest since no patients died throughout the study period.(4) In comparison with Wu and McGoogan’s (5) report of the 72,314 cases of COVID-19 throughout China, the marked differences in outcomes among cases from Hubei compared to those from all other Provinces (5) provide insight into the severity of this disease.

The CFR amongst all confirmed cases in China (through February 11) is reported as 2.3%.(1,5) The CFR among the initial Wuhan cohort was reported as 4.3%, and 2.9% in Hubei.(1,5) However, in subsequent cases outside of Hubei, the CFR has been 0.4%. Deaths occurred only in cases deemed “critical.” No deaths were observed among asymptomatic carriers, nor in patients with mild or even severe presentations of confirmed disease. Importantly, the CFR from these reports are from infected, syndromic persons presenting to health care facilities, with higher CFRs among older, hospitalized patients (8% - 14.8% in the Wuhan cohort).

Given the non-specific symptoms of patients with confirmed COVID-19,(6) and the absence of deaths among asymptomatic, mild, and severe cases,(1,6) many if not most cases of 2019-nCoV likely remain unaccounted for in the denominator of current CFR estimates. Additionally, the number of patients who die from the virus as opposed to with the virus is unknown.

There are increasing reports of confirmed COVID-19 cases in individuals without travel history or risk factors for transmission in the U.S, representing community spread among asymptomatic carriers and undiagnosed mild cases. Though systemic testing capacity for 2019-nCoV is increasing, forthcoming weekly reports of CFR are unlikely to capture asymptomatic and mild cases that never present to health care facilities, especially since milder and asymptomatic cases will be identified at a slower pace than severe and critical cases.(7)

As with other epidemics, the final CFR for COVID-19 will likely be significantly lower than both the currently reported rates, and those announced in the coming weeks. Accurate CFRs are only possible after the rates of asymptomatic infection and mild otherwise unreported cases are determined.

References
1. Wang D, Hu B, Hu C, et al. Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China [published online ahead of print, 2020 Feb 7]. JAMA. 2020; DOI: 10.1001/jama.2020.1585.
2. Wong JY, Kelly H, Ip DK, Wu JT, Leung GM, Cowling BJ. Case fatality risk of influenza A (H1N1pdm09): a systematic review. Epidemiology. 2013;24(6):830–841. doi:10.1097/EDE.0b013e3182a67448
3. Lipsitch M, Donnelly CA, Fraser C, et al. Potential Biases in Estimating Absolute and Relative Case-Fatality Risks during Outbreaks. PLoS Negl Trop Dis. 2015;9(7):e0003846. Published 2015 Jul 16. doi:10.1371/journal.pntd.0003846
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 [published online ahead of print, 2020 Feb 24]. JAMA. 2020. DOI:10.1001/jama.2020.2648
5. Xu XW, Wu XX, Jiang XG, et al. Clinical findings in a group of patients infected with the 2019 novel coronavirus (SARS-Cov-2) outside of Wuhan, China: retrospective case series [published correction appears in BMJ. 2020 Feb 27;368:m792]. BMJ. 2020;368:m606. Published 2020 Feb 19. doi:10.1136/bmj.m606
6. Guan W, Ni Z, Hu Y. Clinical Characteristics of Coronavirus Disease 2019 in China [published online ahead of print, 2020 Feb 28]. NEJM. DOI: 10.1056/NEJMoa2002032
7. Majumder M. Case fatality rate (CFR) is time- & population-varying (Tweet). 2020. https://twitter.com/maiamajumder/status/1235219601232887808. Accessed March 4, 2020.

Competing interests: No competing interests

04 March 2020
Joshua D. Niforatos
Emergency Medicine Resident Physician
Edward R Melnick, MD, MHS, Assistant Professor, Department of Emergency Medicine, Yale School of Medicine, New Haven, CT, USA; Jeremy S. Faust MD MS Brigham and Women’s Hospital Department of Emergency Medicine, Division of Health Policy and Public Health, Instructor, Harvard Medical School
Department of Emergency Medicine, The Johns Hopkins Hospital
1830 E Monument St.,, Suite 6-100, Baltimore, MD, 21205