As COVID-19 cases continue to climb globally, a common misconception spreading with the illness is that it mainly affects the elderly while sparing younger people.
By now, most people have heard the statistics from China that said that 80 percent of COVID-19 cases are mild, only 20 percent are severe or critical, and that the vast majority of deaths occur in the elderly and those with underlying health conditions.
But these numbers belie how sick the disease can make just about anyone, of any age. “That’s the challenge of looking at numbers in aggregate,” said Kirsten Bibbins-Domingo, Ph.D., M.D., M.A.S., a general internist and chair of the Department of Epidemiology and Biostatistics at UC San Francisco.
New numbers from the U.S. Centers for Disease Control and Prevention (CDC) tell a different story about who is getting sick, especially in the United States.
We talked to Bibbins-Domingo, infectious disease specialist Peter Chin-Hong, M.D., and geriatrician Kenneth Covinsky, M.D., M.P.H., to take a closer look at the numbers and what they reveal about who’s getting sick, what the virus does to the body, and when we’ll know if social distancing works.
Anyone can become severely ill from COVID-19
“Everybody is capable of having a severe form of this disease. Every age group can end up in the hospital,” said Bibbins-Domingo. In fact, in the reports from China, the “mild” cases encompassed a range of severity, from no symptoms to pneumonia.
A new report from the CDC confirms that COVID-19 does not spare millennials and Gen Z. Among the first 4,226 cases in the U.S., more than half of patients who were hospitalized were under the age of 65, and one in five were aged 20 to 44.
Chin-Hong, said the report was “a wake-up call that it can happen to all ages,” and that he had already seen young and critically ill patients at UCSF.
“They had no medical risk factors, no past medical history, and went straight into the ICU,” he said.
In California, the majority of confirmed cases so far have been in people younger than 50.
While it’s true that younger people are less likely to die from the illness, they could still require the ventilators and ICU beds that are in short supply.
Bibbins-Domingo worries that “we have emphasized the harmful effects in older adults, and so older adults are taking precautions, while younger adults are not taking precautions.”
“It’s important that younger adults understand that they are part of the solution,” she said.
Gen Z may be driving transmission
If the packed spring break beaches are any indication, younger adults are feeling less vulnerable to COVID-19 and many are not heeding the calls for social distancing.
Not only are they risking their own health, they could be a major factor driving transmission rates, said Bibbins-Domingo.
In South Korea, where diagnostic testing has been widespread and available to people with no symptoms, nearly 27 percent of the confirmed cases are people in their 20s, by far the age group with the most infections. That suggests young adults may be spreading COVID-19 without realizing it.
“It is clear that part of the epidemiology includes people who are asymptomatic or mildly symptomatic being able to transmit,” said Bibbins-Domingo.
She pointed to a recent Science paper, which estimated that, before travel restrictions were put in place in China, 86 percent of infections there were undiagnosed because they had no severe symptoms, yet they were the infection source for 79 percent of diagnosed infections.
The high proportion of undiagnosed infections “appears to have facilitated the rapid spread of the virus throughout China,” the authors wrote.
Act as if you are already infected
“Absolutely there are people walking around who have no idea they have it,” said Bibbins-Domingo. “Some will go on to have symptoms in three days, and some will never have symptoms.”
The belief among most public health professionals is that many, many Americans are already infected. Yet because widespread testing isn’t yet available, it’s impossible to know who they are.
That’s why social distancing measures like California’s shelter-in-place order are essential to slowing the spread and flattening the curve, said Chin-Hong. “Everyone should act as if they are already infected.”
What does the novel coronavirus do to the body?
The novel coronavirus is transmitted by respiratory droplets that can travel several feet in the air and survive on some surfaces for three days.
The virus enters the body through mucosal areas such as the mouth, nose or eyes.
Unlike viruses that cause the common cold, which tend to stay in the upper respiratory tract, the novel coronavirus can “zoom down to the lungs,” said Chin-Hong.
In the lungs, the virus attaches to specific receptors on cells, called ACE2 receptors.
The virus uses the ACE2 receptors to gain entry inside the cells, hijacking the cells’ machinery to produce more viruses.
The viral invasion can lead to serious inflammation of the lungs, known as pneumonia, and characterized by cough, fever, and shortness of breath.
Part of the damage, said Chin-Hong, is caused by your own body trying to fight off the infection, sending an army of immune cells that release inflammatory signals know as cytokines.
ACE2 receptors are also found in other parts of the body, including the cardiovascular and gastrointestinal systems, and may explain some of the complications associated with COVID-19, said Chin-Hong.
Bibbins-Domingo said that the novel coronavirus is unusual in how contagious it is, even more so than influenza A viruses that have caused flu pandemics. It is also unusual for the spectrum of illness it causes, including a higher rate of death, and its ability to transmit asymptomatically, she said.
Chin-Hong agreed that the novel coronavirus is unusual in how fast it spreads. “The virus is really crafty and thrives by people spreading it when they are not sick,” he said.
‘High-risk’ includes a lot of people
The known risk factors for developing serious illness from COVID-19 include heart disease, lung disease, cancer, diabetes, and any condition that weakens the immune system.
Likely there are other risk factors that we don’t yet know about, said Chin-Hong.
Moreover, it’s hard to tell who is at high risk. “You don’t know who among the people you hang around has an underlying condition, and even people who have no identifiable underlying condition can still end up severely ill,” said Bibbins-Domingo.
A recent report by the Kaiser Family Foundation found that 40 percent of Americans may be at high risk for serious illness if infected with COVID-19.
This includes anyone over the age of 60, some 76.3 million Americans, as well as younger adults with underlying health conditions, another 29.3 million Americans.
If the packed spring break beaches are any indication, younger adults are feeling less vulnerable to COVID-19 and many are not heeding the calls for social distancing. Not only are they risking their own health, they could be a major factor driving transmission rates, said Bibbins-Domingo.
As we age, our immune systems become more sluggish and less able to fight off infections, said Covinsky.
And it’s nearly impossible to disentangle the risk of old age itself from the underlying health conditions that tend to come with it.
More than half of Americans older than 60 and nearly two-thirds of those older than 80 have an underlying health condition, according to the Kaiser Family Foundation report.
“We know any illness in older persons tends to be more serious,” said Covinsky. “Acute illness in an older person who’s frail is more likely to have a bad outcome.”
Many older adults depend on the help of younger family members or caregivers, especially now that the CDC has urged anyone over 65 to stay at home.
“For older people who rely on caregivers, what happens if caregivers get sick?,” said Covinsky. “COVID-19 can have a direct effect, but if they lose caregivers and support, that can also have a devastating effect.”
“It’s a community effort and we’re all in this together,” he said.
Will social distancing work?
Experts are certain that without social distancing measures, the virus would spread quickly and infect a high proportion of the population. They agree there are already more cases than we know.
“The cases we see today reflect transmission that happened one to two weeks ago. We’re always seeing just the tip of the iceberg — the iceberg we know for sure is much larger,” said Bibbins-Domingo.
That also means that the success of social distancing measures — if people comply — will only become apparent after about two weeks.
Chin-Hong worries that even if we begin to flatten-the-curve, people may become fatigued from long-term social distancing and drop their guard, causing a second spike in infections.
Covinsky compared these preventive measures to counseling a patient to quit smoking.
“You’re not likely to hear from that patient 30 years on, saying ‘thank you’ for the heart attacks I’ve never had,” he said. “If this works as we hope, no one will thank the public health authorities for the epidemics we never had.”
From Jan 17 to March 1, 2020, 36 children (mean age 8·3 [SD 3·5] years) were identified to be infected with severe acute respiratory syndrome coronavirus 2.
The route of transmission was by close contact with family members (32 [89%]) or a history of exposure to the epidemic area (12 [33%]); eight (22%) patients had both exposures. 19 (53%) patients had moderate clinical type with pneumonia; 17 (47%) had mild clinical type and either were asymptomatic (ten [28%]) or had acute upper respiratory symptoms (seven [19%]).
Common symptoms on admission were fever (13 [36%]) and dry cough (seven [19%]). Of those with fever, four (11%) had a body temperature of 38·5°C or higher, and nine (25%) had a body temperature of 37·5–38·5°C.
Typical abnormal laboratory findings were elevated creatine kinase MB (11 [31%]), decreased lymphocytes (11 [31%]), leucopenia (seven [19%]), and elevated procalcitonin (six [17%]). Besides radiographic presentations, variables that were associated significantly with severity of COVID-19 were decreased lymphocytes, elevated body temperature, and high levels of procalcitonin, D-dimer, and creatine kinase MB.
All children received interferon alfa by aerosolisation twice a day, 14 (39%) received lopinavir–ritonavir syrup twice a day, and six (17%) needed oxygen inhalation. Mean time in hospital was 14 (SD 3) days. By Feb 28, 2020, all patients were cured.
Evidence before this study
We searched PubMed from Nov 1, 2019, to March 1, 2020, for studies published in any language using the terms “COVID-19”, “coronavirus disease 2019”, “novel coronavirus”, “pediatric patients”, “children”, “transmission”, “clinical feature”, and “epidemiological features”. We found 13 studies about coronavirus disease 2019 (COVID-19) in children.
These studies were related to treatment recommendations, CT features in 15 children, case reports, and COVID-19 in infants. To our knowledge, no study has been done to comprehensively investigate a cohort of paediatric patients with COVID-19 and their distinctive clinical features.
Published work about adult patients has shown that manifestations vary strikingly by individual. Since children are different from adults in many aspects, such as immunological development, we aimed to investigate the clinical and epidemiological features of paediatric patients with COVID-19.
Added value of this study
Between Jan 17 and March 1, 2020, 661 cases of COVID-19 were reported in Ningbo and Wenzhou (Zhejiang province, China). Of these cases, 36 were in children. All children with COVID-19 had been infected either by close contact with adults infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or by exposure to the epidemic area.
Although fever, cough, and pneumonia were the most common signs, about half the children had mild disease with no presenting symptoms. Fewer children with COVID-19 had obvious symptoms compared with adult patients with COVID-19 and paediatric patients with H1N1 influenza described in previous studies.
Implications of all the available evidence
By contrast with findings in adults, children with COVID-19 had milder clinical manifestations; nearly half of paediatric patients were asymptomatic (ie, no fever and no cough). This asymptomatic condition is relevant if community-acquired transmission becomes the primary mode; identification of paediatric patients without presenting symptoms will become a great challenge.
Fortunately, the number of children infected with SARS-CoV-2 accounted for a small proportion of total people infected, and paediatric patients also had clear epidemiological information. Devising measures to protect children from infection with SARS-CoV-2 is very important.
Between Jan 17 and March 1, 2020, 661 COVID-19 cases were reported in Ningbo and Wenzhou in China; of these cases, 36 (5%) were in children (aged 1–16 years; mean age 8·3 [3·5] years). 13 (36%) of 36 patients were female (table 1).
The route of transmission for paediatric patients was either by close contact with family members with COVID-19 (32 [89%]) or a history of exposure to epidemic areas (12 [33%]), or both (eight [22%]). 17 (47%) of 36 children had mild clinical type, with ten (28%) patients asymptomatic and seven (19%) showing acute upper respiratory symptoms. The remaining 19 (53%) paediatric patients had moderate clinical type, characteristic of mild pneumonia (table 1).
No severe and critically ill cases were seen.
Table 1 Epidemiological and clinical features of paediatric patients with COVID-19 stratified by two clinical types
|Total (n=36)||Mild cases (n=17)||Moderate cases (n=19)||p value*|
|Female patients||13 (36%)||7 (41%)||6 (32%)||0·70|
|Male patients||23 (64%)||10 (59%)||13 (68%)||..|
|Age, years (SD, range)||8·3 (3·5, 1–16)||7·5 (3·2, 1–16)||9·0 (3·6, 3–16)||0·099|
|Age ≤5 years||10 (28%)||8 (80%)||2 (20%)||..|
|History of exposure to epidemic area||12 (33%)||5 (29%)||7 (37%)||0·70|
|Family members with COVID-19||32 (89%)||16 (94%)||16 (84%)||0·60|
|Dry cough||7 (19%)||3 (18%)||4 (21%)||..|
|Dyspnoea or tachypnoea||1 (3%)||..||1 (5%)||..|
|Pharyngeal congestion||1 (3%)||1 (6%)||..||..|
|Sore throat||2 (6%)||1 (6%)||1 (5%)||..|
|Vomiting or diarrhoea||2 (6%)||..||2 (10%)||..|
|Body temperature, °C||37·8 (0·4)||37·6 (0·3)||38·0 (0·4)||0·0020|
|Fever (body temperature >37°C)||13 (36%)||4 (24%)||9 (47%)||..|
|Headache||3 (8%)||1 (6%)||2 (10%)||..|
|Laboratory tests (reference values)|
|White blood cells (4–10 × 109 cells per L)||6·1 (2·1)||6·5 (2·3)||5·8 (1·9)||0·32|
|Lymphocytes (1·1–3·2 × 109 cells per L)||2·4 (0·8)||2·8 (1·0)||2·0 (0·7)||0·0083|
|Procalcitonin (<0·5 ng/mL)||0·24 (0·17)||0·15 (0·13)||0·32 (0·19)||0·0039|
|C-reactive protein (<8 mg/L)||5 (2)||4 (1)||5 (2)||0·072|
|D-dimer (<0·5 μg/mL)||0·29 (0·20)||0·21 (0·18)||0·36 (0·21)||0·028|
|Erythrocyte sedimentation rate (0–20 mm/h)||7 (2)||6 (2)||7 (2)||0·14|
|Creatine kinase (55–170 U/L)||96 (47)||80 (44)||110 (56)||0·085|
|Creatine kinase MB (<18 U/L)||19 (10)||14 (9)||24 (12)||0·0084|
|Alanine aminotransferase (<40 U/L)||21 (14)||21 (12)||20 (13)||0·82|
|Aspartate transferase (<40 U/L)||30 (11)||32 (10)||28 (11)||0·26|
|Creatinine (40–110 μmol/L)||56 (12)||58 (11)||54 (13)||0·32|
|Blood urea nitrogen (3–7 mmol/L)||3·8 (0·5)||3·7 (0·4)||3·9 (0·5)||0·20|
|Oxygen saturation (92–100%)||98·1 (0·4)||98·2 (0·3)||98 (0·3)||0·054|
|Pulmonary ground-glass opacities||19 (53%)||..||19 (100%)||..|
|Oxygen inhalation||6 (17%)||1 (6%)||5 (26%)||..|
|Interferon alfa||36 (100%)||17 (100%)||19 (100%)||..|
|Lopinavir–ritonavir||14 (39%)||2 (12%)||12 (63%)||..|
|Time taken to become SARS-CoV-2 PCR-negative, days (SD, range)||10 (2, 7–22)||9 (2, 7–12)||11 (2, 8–22)||0·0050|
|Duration of fever after admission, days (SD, range)†||3 (2, 2–5)||2 (2, 2–4)||3 (2, 2–5)||0·14|
|Duration of hospitalisation, days (SD, range)||14 (3, 10–20)||12 (3, 10–16)||15 (4, 12–20)||0·017|
Data are n (%) or mean (SD), unless otherwise indicated. COVID-19=coronavirus disease 2019. SARS-CoV-2=severe acute respiratory syndrome coronavirus 2.* p values indicate the difference between paediatric patients with mild clinical type (asymptomatic or upper respiratory infection) and those with moderate clinical type with pneumonia.† Data for 13 patients.
On admission, frequent symptoms were fever (13 [36%]) and dry cough (seven [19%]). Of 13 patients with fever, four (11%) had a body temperature of 38·5°C or higher and nine (25%) had a body temperature of 37·5–38·5°C.
Other symptoms were recorded infrequently, including sore throat (two [6%]), pharyngeal congestion (one [3%]), dyspnoea or tachypnoea (one [3%]), and vomiting or diarrhoea (two [6%]).
Neither neurological symptoms nor signs of cardiac, liver, or renal failure were recorded.Generally, two types of abnormal radiographic presentations were seen: multiple opacities and patchy opacities. 19 (53%) paediatric patients had pulmonary ground-glass opacities on CT scan, suggesting pneumonia (figure 1).
Pneumonia plus either fever or cough was seen in 11 (30%) paediatric patients and eight (22%) had pneumonia as the only symptom. Ten (28%) children showed no symptoms of pneumonia, five (14%) reported fever only, and two (5%) only had a dry cough.
Table 1 shows findings of laboratory examinations related to immunological responses and cardiac, liver, and renal damage, according to mild or moderate clinical type.
Abnormal findings in paediatric patients were increased serum creatine kinase MB (11 [31%]), decreased lymphocytes (11 [31%]), leucopenia (seven [19%]), and increased procalcitonin (six [17%]). Some features differed significantly between mild and moderate clinical type of COVID-19, including decreased lymphocytes (p=0·0083), raised body temperature (p=0·0020), and high levels of procalcitonin (p=0·0039), D-dimer (p=0·028), and creatine kinase MB (p=0·0084).
Children with moderate clinical type also had a positive PCR result for longer (p=0·0050) and spent more days in hospital (p=0·017) than did those with mild clinical type.
Table 2 shows findings of laboratory examinations related to immunological responses and cardiac, liver, and renal damage, according to age group.
Ten patients were aged 5 years or younger and 26 patients were 16 years or younger but older than 5 years. The older children had decreased lymphocytes (p=0·029), elevated procalcitonin (p=0·032), and decreased creatine kinase (p=0·032) compared with the younger patients.Table 2Comparison of clinical features between paediatric patients, by age group
|Age 0 to ≤5 years (n=10)||Age >5 to ≤16 years (n=26)||p value|
|Female patients||4 (40%)||9 (35%)||..|
|Male patients||6 (60%)||17 (65%)||..|
|History of exposure to epidemic area||2 (20%)||10 (38%)||..|
|Family members with COVID-19||10 (100%)||22 (85%)||0·60|
|Dry cough||1 (10%)||6 (23%)||..|
|Body temperature, °C||37·7 (0·3)||37·9 (0·4)||0·16|
|Fever (body temperature >37°C)||3 (30%)||10 (38%)||..|
|Pulmonary ground-glass opacities||6 (60%)||13 (50%)||0·70|
|Laboratory tests (reference values)|
|White blood cells (4–10 × 109 cells per L)||6·5 (2·2)||5·9 (2·0)||0·44|
|Lymphocytes (1·1–3·2 × 109 cells per L)||2·9 (1·1)||2·2 (0·7)||0·029|
|Procalcitonin (<0·5 ng/mL)||0·13 (0·15)||0·28 (0·19)||0·032|
|C-reactive protein (<8 mg/L)||4 (1)||5 (2)||0·14|
|D-dimer (<0·5 μg/mL)||0·20 (0·18)||0·32 (0·20)||0·11|
|Creatine kinase (55–170 U/L)||124 (54)||85 (44)||0·032|
|Creatine kinase MB (<18 U/L)||21 (14)||18 (7)||0·40|
|Oxygen saturation (92–100%)||98·2 (0·3)||98·1 (0·3)||0·38|
|Mild cases||4 (40%)||13 (50%)||0·70|
|Therapy and outcomes|
|Oxygen inhalation||1 (10%)||5 (19%)||..|
|Interferon alfa||10 (100%)||26 (100%)||>0·99|
|Lopinavir–ritonavir||1 (10%)||13 (50%)||..|
|Time taken to become SARS-CoV-2 PCR-negative, days (SD, range)||9 (2, 7–14)||11 (2, 8–22)||0·011|
|Duration of hospitalisation, days (SD, range)||13 (3, 10–18)||15 (4, 13–20)||0·16|
Data are n (%) or mean (SD), unless otherwise indicated. COVID-19=coronavirus disease 2019. SARS-CoV-2=severe acute respiratory syndrome coronavirus 2.*p values indicate the difference between paediatric patients with mild clinical type (asymptomatic or upper respiratory infection) and those with moderate clinical type (mild pneumonia).
Treatments and primary manifestations were traced to assess disease progression and outcome, and four case types were identified: asymptomatic, upper respiratory symptoms or fever only, pneumonia only, and both pneumonia and upper respiratory symptoms or fever (figure 2). On admission, all children were treated with interferon alfa by aerosolisation twice a day, 14 (39%) received lopinavir–ritonavir syrup twice a day, and six (17%) needed oxygen inhalation (table 1). In the 13 patients with fever, mean duration of fever was 3 (SD 2) days. Improvement in pneumonia was seen 4–10 days after treatment initiation. SARS-CoV-2 RT-PCR results became negative after a mean of 10 (SD 2) days of treatment, regardless of the various initial manifestations of patients (figure 2). The mean number of days in hospital was 14 (SD 3) days. By Feb 28, 2020, all patients were cured, according to the criteria for cured outcome, and quarantined for a further 2 weeks. Follow-up is continuing every week, with samples taken to measure serum IgG and IgM and SARS-CoV-2 in blood, faeces, and nasopharyngeal swabs.
The comparison of paediatric patients with COVID-19 with adult patients with COVID-19 in the same city (table 3) showed that paediatric patients had a significantly lower prevalence of abnormal values of several variables indicating disease severity, such as fever (36% for children and 86% for adults), cough (19% and 62%), pneumonia (53% and 95%), elevated C-reactive protein (3% and 49%), and severe disease type (0% and 23%; p<0·0001 for all features). Nevertheless, no differences were noted between children and adults in prevalence of leucopenia, lymphopenia, and elevated myocardial enzymes. When compared with children with SARS, paediatric patients with COVID-19 had much milder disease in terms of the prevalence of fever, cough, pneumonia, and severe case type. Compared with children with H1N1 influenza, paediatric patients with COVID-19 had fewer upper respiratory symptoms (eg, cough and pharyngeal congestion) but pneumonia was more frequent. Notably, when the three groups of patients with coronavirus infections were compared with the paediatric patients with H1N1 influenza, the most striking difference was that patients with H1N1 influenza had a much higher prevalence of pharyngeal congestion and a lower prevalence of pneumonia.Table 3Comparison of prevalence of clinical features between children with COVID-19, adults with COVID-19, children with H1N1 influenza, and children with SARS
|Children with COVID-19 (n=36)||Adults with COVID-19 (n=175)17||Children with SARS (n=44)10||Children with H1N1 influenza (n=167)19|
|Age, years||8·3 (3·5)||45 (14)||12·2 (4·1)||4·1 (3·5)|
|Fever||13 (36%)||150 (86%)||44 (100%)||153 (92%)|
|Cough||7 (19%)||109 (62%)||28 (64%)||138 (83%)|
|Pharyngeal congestion or sore throat||1 (3%)||8 (5%)||6 (14%)||159 (95%)|
|Dyspnoea||1 (3%)||23 (13%)||4 (9%)||12 (7%)|
|Pneumonia||19 (53%)||166 (95%)||40/62 (65%)†||18 (11%)|
|Comorbidities or complications (except pneumonia and bronchitis)||0||10 (6%)||5 (11%)||7 (4%)|
|Mild and moderate cases||36 (100%)||136 (77%)||35 (79%)||135 (81%)|
|Severe cases||0||39 (23%)||9 (21%)||32 (19%)|
|Leucopenia||7 (19%)||44 (25%)||15 (34%)||65 (39%)|
|Lymphopenia||11 (31%)||61 (35%)||34 (77%)||NA|
|Myocardial enzymes elevated||11 (31%)||39 (22%)||3 (7%)||18 (11%)|
|Liver enzymes elevated||2 (6%)||32 (18%)||21 (48%)||12 (7%)|
|Elevated C-reactive protein||1 (3%)||86 (49%)||NA||42 (25%)|
|Antiviral therapy||14 (39%)||170 (97%)||42 (96%)||167 (100%)|
Data are n (%) or mean (SD). COVID-19=coronavirus disease 2019. SARS=severe acute respiratory syndrome. NA=not available.* No pneumonia, no upper respiratory symptoms, and no fever.† The prevalence of abnormal radiographic presentations in children with SARS was obtained from reference 18.
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