How clinically serious is SARS-CoV-2 infection for children and young adults?
In their editorial, Yamey and Walensky suggest that Covid-19 is a clinically serious disease for a substantial proportion of young adults. They write:
“A multistate US survey found that about a quarter of people with symptomatic covid-19 aged 18-34 years develop post-acute covid,[1] a potentially disabling illness that can cause severe complications.[2],[3] One regional US college football competition was cancelled after at least 15 healthy student players developed covid related myocarditis.[4]” (citations have been renumbered)
We have reviewed the references cited and are concerned that the evidence appears less clear cut than described.
The cited multistate US survey,[1] which was led by the CDC, did indeed find that 26% of individuals aged 18-34 years reported not having “returned to their usual state of health 14-21 days after testing.” However, little additional detail is provided for this age group; the CDC’s report does not contain information regarding which exact symptoms persisted, nor the frequency and severity of those symptoms. We contacted the corresponding author of the study for these data, but he declined, citing an inability to share patient level datasets (personal correspondence with Mark Tenforde, Sep 16, 2020). Without these data, it is impossible to judge the nature and seriousness of the unresolved symptoms.
The editorial authors also suggest that post-acute Covid-19 is a “potentially disabling illness that can cause severe complications” within 18-34 year olds. However the two papers [2,3] referenced in support of this statement, which were about neurological complications and Covid-19 related new-onset diabetes, did not evaluate these severe complications within young adults.
Finally, although myocarditis can be a serious and potentially life threatening condition, the clinical significance of the link between Covid-19 and myocarditis is a subject of ongoing debate. Others have analyzed the report of US college football players that is cited in the editorial and argued that this finding may be an artifact of increased awareness and diagnostic sensitivity rather than a clinically significant finding. [5, 6] Notably, there was no control/reference group. Moreover, myocarditis after viral infections are not unique to Covid-19. Intense exercise, like those required of college athletes, can exacerbate inflammation that is present in the lungs and heart after a viral infection, which can consequently cause myocarditis. A definitive diagnosis of myocarditis also requires a heart biopsy, something that is rarely done in otherwise healthy college students, for obvious reasons. [5]
Taken together, the data suggest that a quarter of college aged students with symptomatic Covid-19 may have one or more symptoms that persist for a few weeks, but it is far from clear that this translates into a significant risk of severe Covid-19 complications.
There is room for a more optimistic interpretation of the data. The New York Times states that among more than 1,600 U.S. colleges, there have been “at least 130,000 cases and at least 70 deaths since the pandemic began. Most of the cases have been announced since students returned to campus for the fall term. Most of the deaths were reported in the spring and involved college employees, not students.” [7] Thus college “outbreaks” do not seem associated with increases in outbreaks of severe Covid-19.
Although there always exists a potential for severe Covid-19 risk in any population, based on the existing evidence, it is not clear that Covid-19 can be generalized as a clinically serious disease for young adults.
The editorial authors make several good points regarding taking a “harm reduction” approach. And it is not simply an approach, it is a legal requirement in many jurisdictions. Unfortunately, many universities have not stepped up to this challenge, and instead taken what is beginning to feel like the easy way out: fully virtual learning with no clear criteria for reopening. The unintended consequences of social isolation, remote learning, and remote teaching in college age students need to be measured and taken into account as well.
Sarah Tanveer
Peter Doshi
Department of Pharmaceutical Health Services Research
University of Maryland School of Pharmacy
Baltimore, Maryland, USA
References
[1] Tenforde MW, Kim SS, Lindsell CJ, et al., IVY Network Investigators, CDC COVID-19 Response Team, IVY Network Investigators. Symptom duration and risk factors for delayed return to usual health among outpatients with COVID-19 in a multistate health care systems network—United States, March–June 2020. MMWR Morb Mortal Wkly Rep 2020;69:993-8. doi:10.15585/mmwr.mm6930e1 pmid:32730238 https://doi.org/10.15585/mmwr.mm6930e1
[2] Ellul MA, Benjamin L, Singh B, et al. Neurological associations of COVID-19. Lancet Neurol2020;19:767-83. doi:10.1016/S1474-4422(20)30221-0 pmid:32622375 https://doi.org/10.1016/S1474-4422(20)30221-0
[3] Rubino F, Amiel SA, Zimmet P, et al. New-onset diabetes in COVID-19. N Engl J Med2020;383:789-90. doi:10.1056/NEJMc2018688 pmid:32530585 https://doi.org/10.1056/NEJMc2018688
Rapid Response:
How clinically serious is SARS-CoV-2 infection for children and young adults?
In their editorial, Yamey and Walensky suggest that Covid-19 is a clinically serious disease for a substantial proportion of young adults. They write:
“A multistate US survey found that about a quarter of people with symptomatic covid-19 aged 18-34 years develop post-acute covid,[1] a potentially disabling illness that can cause severe complications.[2],[3] One regional US college football competition was cancelled after at least 15 healthy student players developed covid related myocarditis.[4]” (citations have been renumbered)
We have reviewed the references cited and are concerned that the evidence appears less clear cut than described.
The cited multistate US survey,[1] which was led by the CDC, did indeed find that 26% of individuals aged 18-34 years reported not having “returned to their usual state of health 14-21 days after testing.” However, little additional detail is provided for this age group; the CDC’s report does not contain information regarding which exact symptoms persisted, nor the frequency and severity of those symptoms. We contacted the corresponding author of the study for these data, but he declined, citing an inability to share patient level datasets (personal correspondence with Mark Tenforde, Sep 16, 2020). Without these data, it is impossible to judge the nature and seriousness of the unresolved symptoms.
The editorial authors also suggest that post-acute Covid-19 is a “potentially disabling illness that can cause severe complications” within 18-34 year olds. However the two papers [2,3] referenced in support of this statement, which were about neurological complications and Covid-19 related new-onset diabetes, did not evaluate these severe complications within young adults.
Finally, although myocarditis can be a serious and potentially life threatening condition, the clinical significance of the link between Covid-19 and myocarditis is a subject of ongoing debate. Others have analyzed the report of US college football players that is cited in the editorial and argued that this finding may be an artifact of increased awareness and diagnostic sensitivity rather than a clinically significant finding. [5, 6] Notably, there was no control/reference group. Moreover, myocarditis after viral infections are not unique to Covid-19. Intense exercise, like those required of college athletes, can exacerbate inflammation that is present in the lungs and heart after a viral infection, which can consequently cause myocarditis. A definitive diagnosis of myocarditis also requires a heart biopsy, something that is rarely done in otherwise healthy college students, for obvious reasons. [5]
Taken together, the data suggest that a quarter of college aged students with symptomatic Covid-19 may have one or more symptoms that persist for a few weeks, but it is far from clear that this translates into a significant risk of severe Covid-19 complications.
There is room for a more optimistic interpretation of the data. The New York Times states that among more than 1,600 U.S. colleges, there have been “at least 130,000 cases and at least 70 deaths since the pandemic began. Most of the cases have been announced since students returned to campus for the fall term. Most of the deaths were reported in the spring and involved college employees, not students.” [7] Thus college “outbreaks” do not seem associated with increases in outbreaks of severe Covid-19.
Although there always exists a potential for severe Covid-19 risk in any population, based on the existing evidence, it is not clear that Covid-19 can be generalized as a clinically serious disease for young adults.
The editorial authors make several good points regarding taking a “harm reduction” approach. And it is not simply an approach, it is a legal requirement in many jurisdictions. Unfortunately, many universities have not stepped up to this challenge, and instead taken what is beginning to feel like the easy way out: fully virtual learning with no clear criteria for reopening. The unintended consequences of social isolation, remote learning, and remote teaching in college age students need to be measured and taken into account as well.
Sarah Tanveer
Peter Doshi
Department of Pharmaceutical Health Services Research
University of Maryland School of Pharmacy
Baltimore, Maryland, USA
References
[1] Tenforde MW, Kim SS, Lindsell CJ, et al., IVY Network Investigators, CDC COVID-19 Response Team, IVY Network Investigators. Symptom duration and risk factors for delayed return to usual health among outpatients with COVID-19 in a multistate health care systems network—United States, March–June 2020. MMWR Morb Mortal Wkly Rep 2020;69:993-8. doi:10.15585/mmwr.mm6930e1 pmid:32730238 https://doi.org/10.15585/mmwr.mm6930e1
[2] Ellul MA, Benjamin L, Singh B, et al. Neurological associations of COVID-19. Lancet Neurol2020;19:767-83. doi:10.1016/S1474-4422(20)30221-0 pmid:32622375 https://doi.org/10.1016/S1474-4422(20)30221-0
[3] Rubino F, Amiel SA, Zimmet P, et al. New-onset diabetes in COVID-19. N Engl J Med2020;383:789-90. doi:10.1056/NEJMc2018688 pmid:32530585 https://doi.org/10.1056/NEJMc2018688
[4] Dodd D, Silverstein A. Big ten cancels college football season for fall 2020, hopes to play in spring 2021. CBS Sports 2020 Aug 11. https://www.cbssports.com/college-football/news/big-ten-cancels-college-...
[5] Koka, A., Don't Let Dubious Science Cancel College Football. Medscape. 2020 Aug 21. https://www.medscape.com/viewarticle/936098
[6] Yong, E. The Core Lesson of the COVID-19 Heart Debate. The Atlantic 2020 Sept 21.
https://www.theatlantic.com/health/archive/2020/09/covid-19-heart-pandem...
[7] Tracking Covid at U.S. Colleges and Universities. The New York Times 2020 Sept 25. https://www.nytimes.com/interactive/2020/us/covid-college-cases-tracker....
Competing interests: PD is an associate editor at The BMJ. PD and ST are both impacted by our university’s policies.