To the Editor: As the number of cases of infection with the novel coronavirus (SARS-CoV-2)
has continued to increase, many countries have established restrictions regarding
travelers who have recently visited China.
With lockdown measures imposed in Hubei Province, China,
and a public health emergency of international concern declared by the World Health
foreign nationals have sought to return to their home countries from China, and public
health authorities are racing to contain the spread of Covid-19 (the disease caused
by SARS-CoV-2 infection) around the world. This process is complicated by epidemiologic
uncertainty regarding possible transmission of the virus by asymptomatically or subclinically
symptomatic infected persons. It is unclear whether persons who show no signs or symptoms
of respiratory infection shed SARS-CoV-2.
In this context, a group of predominantly German nationals who had stayed in Hubei
Province was evacuated to Frankfurt, Germany, on February 1, 2020. They were to be
transferred to Germersheim, Germany, and quarantined for 14 days, since this period
is thought to be the upper limit of the incubation period of SARS-CoV-2. Screening
for symptoms and clinical signs of infection was performed before their departure
from China. A total of 126 travelers were allowed to board an aircraft operated by
the German air force (Figure 1).
During the flight, 10 passengers were isolated. Two passengers had had contact with
1 person who had a confirmed case of SARS-CoV-2 infection, 6 had reported symptoms,
were deemed to be clinically symptomatic, or both, and 2 passengers had accompanied
family members who had been isolated on the flight because of suspected SARS-CoV-2
infection or because of other symptoms (i.e., symptoms related to pregnancy). These
10 passengers were transferred to University Hospital Frankfurt immediately after
arrival. All 10 tested negative for SARS-CoV-2 by real-time reverse-transcription–polymerase-chain-reaction
of throat swabs and sputum.
The remaining 116 passengers (5 months to 68 years of age), including 23 children,
were sent to the medical assessment center at Frankfurt Airport, where each was evaluated
by a medical team of physicians. Each passenger was asked to report current symptoms
of fever, fatigue, sore throat, cough, runny nose, muscle aches, and diarrhea, and
each one was screened for signs of infection in the nose and throat. The temperature
of all passengers was taken. All were afebrile except for 1 passenger who had a temperature
of 38.4°C and reported dyspnea and cough. He was transferred to University Hospital
Frankfurt for evaluation. However, testing to detect SARS-CoV-2 by RT-PCR of a throat
swab and sputum was negative.
In addition to the preplanned multistep process of screening for signs and symptoms
of infection and observing the asymptomatic cohort in quarantine, we decided to offer
a throat swab to test for SARS-CoV-2 in each of the 115 travelers who had passed triage.
A total of 114 passengers consented to the test.
Two of the 114 persons (1.8%) in this cohort of travelers who had passed the symptoms-based
screening tested positive for SARS-CoV-2 by RT-PCR (cycle threshold value in the two
samples, 24.39 and 30.25, respectively). Testing with a second protocol consisting
of two commercial sets (LightMix Modular SARS and Wuhan CoV E-gene, and LightMix Modular
Wuhan CoV RdRP-gene, both produced by TIB MOLBIOL) and retesting of the positive samples
at the Institute of Virology, Philipps University Marburg, in Marburg, Germany, confirmed
the results. In addition, the isolation of SARS-CoV-2 from both samples in cell culture
of Caco-2 cells indicated potential infectivity (see the Supplementary Appendix, available
with the full text of this letter at NEJM.org).
These two persons were subsequently isolated from the cohort and transferred to the
Infectious Disease Unit at University Hospital Frankfurt for further evaluation and
observation on the following day. After a thorough evaluation in the hospital ward,
a faint rash and minimal pharyngitis were observed in one patient. Both patients remained
well and afebrile 7 days after admission.
In this effort to evacuate 126 people from Wuhan to Frankfurt, a symptom-based screening
process was ineffective in detecting SARS-CoV-2 infection in 2 persons who later were
found to have evidence of SARS-CoV-2 in a throat swab. We discovered that shedding
of potentially infectious virus may occur in persons who have no fever and no signs
or only minor signs of infection.