More than half of residents of a Seattle-area nursing home had no symptoms when they tested positive for COVID-19 and had probably already spread the disease, according to a study published late last week in the New England Journal of Medicine (NEJM).

Also, a study in Emerging Infectious Diseases (EID) found that all five household contacts of a mildly symptomatic doctor in Wuhan, China infected with the novel coronavirus had the disease but no symptoms.

Shortcomings of symptom-based screening, cohorting

In the NEJM study, officials with Public Health–Seattle and King County and the Centers for Disease Control and Prevention conducted two serial point-prevalence surveys 10 and 17 days after an outbreak was identified at the nursing home in early March.

The nursing home is in King County but is not the Life Care facility in Kirkland that was one of the first US hot spots for the novel coronavirus.

Fifty-seven (64%) of 89 residents in this second nursing home tested positive for COVID-19. Of the 76 residents who participated in the surveys, 48 (63%) tested positive. Twenty-seven (56%) of the 48 had no symptoms when tested, and 24 of them later had symptoms within a median of 4 days.

Seventeen (35%) reported typical symptoms such as fever, cough, and shortness of breath, and four (8%) reported only atypical symptoms, such as chills, malaise, confusion, nasal discharge or congestion, sore throat, muscle pain, dizziness, headache, nausea, or diarrhea.

Live virus was recovered from 17 presymptomatic residents (71%) 1 to 6 days before symptom onset. Similarly high viral loads were found in all residents with confirmed disease, regardless of whether they had symptoms and whether their symptoms were atypical.

The authors estimated an infection doubling time of 3.4 days, compared with 5.5 days in the surrounding community. Because patients who tested negative often had typical symptoms, the rapid speed of transmission could have been partly due to symptom-based cohorting strategies that could have inadvertently spread SARS-CoV-2, the virus that causes COVID-19, to uninfected residents.

As of Apr 3, 11 of the infected patients had been hospitalized (3 in the intensive care unit), and 15 had died, a death rate of 26%, despite early implementation of infection-control procedures. Twenty-seven (79%) of the 34 residents with sequenced specimens were identified as being part of two clusters of cases.

The authors said that coronavirus infection can be difficult to detect in nursing home residents because of their impaired immune response and high prevalence of underlying illnesses such as dementia and chronic cough.

Twenty-six staff members (19%) tested positive for COVID-19 in the first 23 days of the outbreak and likely contributed to the spread, the authors concluded.

"Our data suggest that symptom-based strategies for identifying residents with SARS-CoV-2 are insufficient for preventing transmission in skilled nursing facilities," they wrote. "Once SARS-CoV-2 has been introduced, additional strategies should be implemented to prevent further transmission, including use of recommended personal protective equipment, when available, during all resident care activities regardless of symptoms."

In a commentary in the same journal, Monica Gandhi, MD, MPH; Deborah Yokoe, MD, MPH; and Diane Havlir, MD, of the University of California at San Francisco, call asymptomatic spread of the virus the "Achilles' heel of current strategies to control COVID-19."

Noting that 1 in 10 US nursing homes have reported COVID-19 cases, the authors said that the failure of symptom-based screening to identify a high proportion of contagious residents highlights the need to find other ways to control spread in all congregate settings.

"A new approach that expands COVID-19 testing to include asymptomatic persons residing or working in skilled nursing facilities needs to be implemented now," they wrote. "This unprecedented pandemic calls for unprecedented measures to achieve its ultimate defeat."

Questionable findings from single throat swab test

In the EID study, a 39-year-old hospital nephrologist who began having a dry cough on Jan 31 was hospitalized with fever on Feb 7 and diagnosed as having coronavirus on Feb 10. He lived with his wife, a lab physician with no patient contact; their 7-year-old twins with only family contact due to school closures; and the twins' retired 62-year-old grandfather and 64-year-old grandmother.

All family members were hospitalized on Feb 11 and remained asymptomatic throughout their 21-day stay. All tested positive for COVID-19 except one who tested negative on four consecutive throat swabs but was positive on stool specimen testing and had high liver enzyme levels but no jaundice.

Another family member had a high D-dimer level, indicating blood clots. All abnormal lab findings normalized during the hospital stay. Three family members had abnormal chest computed tomography (CT) scans.

The wife, who had 11 serial throat swabs, showed negative results on two consecutive occasions and then reverted to a positive result. She also underwent serologic testing, which showed low levels of B lymphocytes but no coronavirus antibodies. The authors said that her case illustrates the challenges of interpreting the results of quantitative reverse transcription polymerase chain reaction (qRT-PCR) for COVID-19.

A study published Feb 24 in JAMA of 72,314 patients in China found a 1% rate of infection in asymptomatic patients, but the authors of the EID study noted that asymptomatic patients were not routinely tested in that investigation.

The authors called for further research on asymptomatic and fecal-oral transmission of the coronavirus. "Moreover, our experience indicates that screening symptomatic contacts with a single throat swab test for SARS-CoV-2 might lead to an underestimate of the rate of infection and that asymptomatic persons can repeatedly revert between positive and negative PCR results on throat specimens."