Silent symptomless COVID-19 infection may be much higher than thought

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The prevalence of ‘silent’ symptomless COVID-19 infection may be much higher than thought, reveals a study charting the enforced isolation of cruise ship passengers during the current pandemic, and published online in the journal Thorax.

More than eight out of 10 of passengers and crew who tested positive for the infection had no symptoms.

This has implications for the easing of lockdown restrictions, says Professor Alan Smyth, joint editor in chief of the journal, in a linked blog.

And the findings emphasise the pressing need for accurate global data on how many people have been infected.

The researchers, all of whom were on board the vessel, describe events on an expedition cruise ship carrying 128 passengers and 95 crew.

The ship departed from Ushuaia, Argentina, for a planned 21 day cruise of the Antarctic, taking a similar route to that of Ernest Shackleton in 1915-17. It set sail in mid-March after the World Health Organization had declared COVID-19 a global pandemic.

Passengers who, in the previous three weeks, had passed through countries where COVID-19 infection rates were already high, were not allowed to board.

And everyone’s temperature was taken before embarkation. Hand sanitising stations were plentiful aboard ship, particularly in the dining room.

The first case of fever was reported on day 8, prompting the immediate adoption of infection control measures. This included confining passengers to their cabins, stopping daily servicing, apart from the delivery of meals, and the wearing of personal protective equipment for any crew member in contact with sick passengers.

As Argentina had closed its borders, the ship sailed to Montevideo, Uruguay, arriving on day 13. Eight passengers and crew eventually required medical evacuation to hospital at this point for respiratory failure.

On day 20 all the remaining 217 passengers and crew were swab tested for coronavirus. More than half (128; 59%) tested positive.

In 10 instances, two passengers sharing the same cabin didn’t have the same test result, possibly because the current swab test returns a substantial number of false negative results, say the authors.

Of those testing positive, 24 (19%) had symptoms, but 108 (81%) didn’t.

The ship had no contact with other people for 28 days after its departure, so was the equivalent of a hermetically sealed environment.

The study authors conclude that the prevalence of COVID-19 infection on cruise ships is likely to be “significantly underestimated,” prompting them to recommend that passengers should be monitored after disembarkation to ward off potential community spread of the virus.

And the potentially high rate of false negative results obtained with the current swab tests suggests that secondary testing is warranted, they add.

In a linked blog, Professor Smyth acknowledges: “It is difficult to find a reliable estimate of the number of COVID positive patients who have no symptoms.”

But the figure of 1% suggested by the WHO in early March falls far short of that found on the cruise ship, he points out.

“As countries progress out of lockdown, a high proportion of infected, but asymptomatic, individuals may mean that a much higher percentage of the population than expected may have been infected with COVID,” he suggests.

But whether or not those who have been infected are immune, the findings emphasise a pressing need for accurate global data on how many people have been infected, he concludes.


“There is evidence that SARS-CoV-2 has this ability to spread silently,” says Shweta Bansal, an infectious disease modeler at Georgetown University.

Indeed, cases of COVID-19 among nursing home residents, choir groups and families fuel a growing concern about people who are infected, yet feel generally OK and go about their daily lives, giving the virus to friends, family members and strangers without knowing that they themselves have it.

But there are wide gaps in our understanding of how many people fit this category of “silent spreaders” — as they’re called by some public health researchers — and how much they contribute to transmission of the disease.

Silent spreaders can be divided into three categories: asymptomatic, presymptomatic and very mildly symptomatic. Here’s what we know about these variations.

Asymptomatic: people who carry the active virus in their body but never develop any symptoms

“Nothing at all,” says Tara C. Smith, an epidemiologist at Kent State University’s College of Public Health. “No fever, no gastrointestinal issues, no breathing issues, no coughing, none of that.”

As you might imagine, it’s hard to figure out when someone has a disease but shows no signs of it.

Some cases of asymptomatic carriers have been confirmed by finding and testing people who were in close contact with COVID-19 patients. For those who tested positive without symptoms, follow-up exams confirmed that about 25% continued to show no signs, World Health Organization officials said on April 1, citing data from China.

No one can truly determine the impact of asymptomatic cases on spread until there’s more testing. But so far, they have made up a sliver of the total number of people who’ve tested positive.

And the affected individuals seem to skew young. A small clinical study from Nanjing, China, followed 24 people who tested positive but didn’t show overt symptoms at the time. In the one to three weeks after diagnosis, seven continued showing no symptoms. Their median age was 14.

“Can those people who are completely asymptomatic, who never develop any symptoms, transmit the infection? That’s still kind of an open question,” says Smith.

Presymptomatic: people who have been infected and are incubating the virus but don’t yet show symptoms

After infection, symptoms might not develop for five to six days — or even two weeks, according to the Annals of Internal Medicine. The time between catching the virus and showing symptoms is called the presymptomatic phase.

How do these individuals figure into transmission?

People appear to be most infectious right around the time when symptoms start, said Maria Van Kerkhove, technical lead for the WHO’s Health Emergencies Programme, at an April 1 news conference.

However, “we do have evidence, from testing and modeling studies, that suggest people who are presymptomatic can definitely transmit this virus,” says Smith, the epidemiologist, most likely in the one to three days before they start showing symptoms, according to the WHO.

So far, presymptomatic is a much more common category than asymptomatic. About 75% of people who test positive without showing symptoms turn out to be presymptomatic, displaying coughing, fatigue, fever and other signs of COVID-19 in a later follow-up exam, said Van Kerkhove.

At a nursing home in King County, Washington, about a third of its 82 residents tested positive for the coronavirus in mid-March. Half of those were free of fever, malaise and coughing when they were swabbed for the virus, though most went on to develop symptoms.

The coronavirus spread rapidly through the facility just two weeks after it was introduced by a health care provider, despite the nursing home’s policy of isolating residents with signs of COVID-19.

This suggests that “transmission from asymptomatic and presymptomatic residents, who were not recognized as having SARS-CoV-2 infection and therefore not isolated, might have contributed to further spread,” according to research published in the CDC’s April 3 “Morbidity and Mortality Weekly Report.”

A study in Singapore found similar evidence of presymptomatic spread among people who went to church, took singing classes or puttered at home with their spouses.

Very mildly symptomatic: people who feel a little unwell from a COVID-19 infection but continue to come in close contact with others

“We’re very lucky that this isn’t a severe infection for everyone, but because of that, some people feel a little sick and power through,” says Seema Lakdawala, a flu researcher at the University of Pittsburgh.

Spreading COVID-19 while having a cough or very mild fever doesn’t fully count as silent transmission, says Bansal, the infectious disease modeler: “There’s some signal there at least.”

But people who continue to frequent communal and public places with a light cough or mild fever may unwittingly spread the disease in the early days of symptom onset — the time they’re thought to be most infectious.

Even when a person’s own symptoms remain mild, others they infect can become very sick. In mid-January, a man returned to his home in Nanjing from a trip to Hubei province, the epicenter of China’s epidemic. T

en days later, his wife started running a fever and vomiting; soon, she developed severe pneumonia and required care in the intensive care unit. The man was tested for the coronavirus, and the test came back positive; he’s presumed to have spread the virus to his wife. X-ray scans showed signs of the virus in his lungs — but he consistently reported feeling fine, according to epidemiological research published in Science China Life Sciences.

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Clinical manifestations of coronavirus disease 2019 (COVID-19) are rare or absent in children and adolescents;1, 2 hence, early clinical detection is fundamental to prevent further spreading.

We report three young patients presenting with chilblain-like lesions who were diagnosed with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Two of them were asymptomatic and potentially contagious.

Skin lesions, such as erythematous rashes, urticaria, and chicken pox-like vesicles, were reported in 18 (20·4%) of 88 patients with COVID-19 in a previous study.3

These symptoms developed at the onset of SARS-CoV-2 infection or during hospital stay and did not correlate with disease severity.3 In our cases, lesions involved the acral sites, especially the dorsum of the digits of the feet, beginning as erythematous-violaceous patches that slowly evolved to purpuric lesions and then to blisters and ulceronecrotic lesions, with final complete return to normal.

Burning and itching were also present with some of the lesions. Informed consent was obtained from the parents of patients 1 and 2 and from patient 3 himself.

Patient 1 was a 14-year-old boy who presented to the hospital with erythematous-violaceous lesions involving the dorsum of all digits of both feet.

After 7 days, a few red macules and papules appeared on the lateral and plantar aspect of both feet and a small ulcer developed on the fifth digit of the left foot (figure ).

Because a family member had tested positive for SARS-CoV-2, the patient underwent nasopharyngeal swab and was found positive for SARS-CoV-2 on RT-PCR. The lesions disappeared in the following 7 days.

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Figure – Chilblain-like lesions on patient 1’s left foot

Patient 2 was a 14-year-old boy with no known contact with COVID-19 cases who had been asymptomatic since the beginning of the skin disease, for which his parents requested a teledermatology consultation.

Manifestations consisted of small erythematous-violaceous lesions on the dorsum of almost all digits of the feet, some of which were characterised by necrotic aspects with blackish crusts (appendix).

The lesions lasted 20 days, with complete healing. Nasopharyngeal swab taken by the family’s paediatrician 2 days after the skin manifestations appeared was positive for SARS-CoV-2.

Patient 3 was an 18-year-old boy whose grandfather had COVID-19 pneumonia. After 2 days with fever (38·5°C), the boy reported the appearance of chilblain-like lesions involving the distal part of all digits of the feet (appendix).

Skin manifestations remained unchanged for 10 days, suddenly disappearing without treatment. Nasopharyngeal swab taken 4 days after the skin manifestations appeared was positive. The patient was otherwise asymptomatic.

Acute acro-ischaemic manifestations along the course of SARS-CoV-2 infection seem to be different from classic acrocyanosis, erythema pernio, and vasculitis; however, they could represent a cutaneous expression of the typical thrombotic pattern of COVID-19 due to hyperinflammation4 and altered coagulation and endothelial damage.5

During this time, children and adolescents with chilblain-like lesions who are otherwise asymptomatic should undergo SARS-CoV-2 testing, which could help early detection of silent carriers.

References

1. Lee P-I, Hu Y-L, Chen P-Y, Huang Y-C, Hsueh P-R. Are children less susceptible to COVID-19? J Microbiol Immunol Infect. 2020 doi: 10.1016/j.jmii.2020.02.011. published online Jan 1. [CrossRef] [Google Scholar]

2. Pavone P, Giallongo A, La Rocca G, Ceccarelli M, Nunnari G. Recent COVID-19 outbreak—effect in childhood. Infectious Diseases & Tropical Medicine. 2020;6:e594. [Google Scholar]

3. Recalcati S. Cutaneous manifestations in COVID-19: a first perspective. J Eur Acad Dermatol Venereol. 2020 doi: 10.1111/jdv.16387. published online March 26. [CrossRef] [Google Scholar]

4. Zheng F, Liao C, Fan Q-H. Clinical characteristics of children with coronavirus disease 2019 in Hubei, China. Curr Med Sci. 2020;40:275–280. [PMC free article] [PubMed] [Google Scholar]

5. Zhang Y, Xiao M, Zhang S. Coagulopathy and antiphospholipid antibodies in patients with COVID-19. N Engl J Med. 2020;382:e38. [PMC free article] [PubMed] [Google Scholar]


More information: COVID-19: In the footsteps of Ernest Shackleton, Thorax (2020). DOI: 10.1136/thorax-jnl-2020-215091

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