Discussion
During the first five months of the COVID-19 epidemic in Vietnam, we
characterized all upper respiratory specimens received by NIHE coming
from cities and provinces in the north of Vietnam. Just over one percent
of all samples received yielded positive results by real-time RT-PCR and
yet, by the end of May 2020, fewer than 400 cases had been identified in
total in Vietnam, with no deaths and with no community transmission
after 14 April 2020.
Rapid scale-up and decentralization of testing was a key component to
Vietnam’s response to minimize entry and transmission of SARS-CoV-2.
Another component of Vietnam’s response was its implementation of
centralized quarantine for all persons entering the country from
affected countries
since
early February 2020 (4). Travelers in quarantine were required to
provide upper respiratory specimens for testing upon arrival and before
the end of the 14-day quarantine period. Among these travelers in
quarantine centers, we identified 89 laboratory-confirmed cases, 78
(88%) of which were positive on their first sampling and 11 during
quarantine. Lastly, quarantining and testing of first- and second-degree
exposed community members was implemented to stop further transmission
of virus from primary cases who had not been detected on entry and
subsequent cases. These data suggest that centralized quarantine coupled
with testing upon arrival and quarantine based on exposure rather than
symptoms is an effective measure for preventing exposure of communities
and transmission of SARS-CoV-2 imported from other countries.
Although viral culture remains the gold standard for confirmation of
viral infection, because of shorter turn-around time and higher
sensitivity,
detection
of SARS-CoV-2 by real-time RT-PCR is the accepted gold standard for
detecting SARS-CoV-2 for purposes of isolation and contact tracing.
Semi-quantitation of viral nucleic acids using Ct value can be used to
select samples for virus isolation (2,10–12). We observed a strong
correlation between Ct values and cell culture positivity rate (table
4). This suggests viral load data may be used as a rough proxy for the
infectivity of infected patients.
There is concern about prolonged viral nucleic acid detection in samples
from patients recovered from COVID-19. The large majority of these
samples, both in the literature and in our collection, have high Ct
values and so far culture attempts have not been successful. This
observation supports the hypothesis that prolonged shedding or
re-positivity of samples is not associated with continued replication,
but rather an indicator of removal of damaged lung tissue containing
intact stretches of viral RNA by coughing or ciliary transport.
Among these 158 confirmed COVID-19 cases, we also identified seven
individuals with positive real-time RT-PCR results after two consecutive
negative results within 15 days (Table 3). We were unable to culture
virus from these specimens, all of which had Ct values greater than 33,
suggesting that these cases represent viral remnants rather than
infectious virus. These findings are consistent with findings from South
Korea and China (13–15). Positive real-time RT-PCR results can be
confusing for patients and hospital staff who understandably wish to
prevent continued transmission, either among patients and healthcare
workers or among the general community. Our findings should provide
reassurance that patients with positive real-time RT-PCR results with Ct
values >30 more than 10 days after onset or first positive
result and after having had a negative result are at extremely low risk
of transmission. These findings also support a strategy of testing based
on signs of clinical recovery, rather than a “test-of-cure” strategy.
Our study had several limitations. First, the specimens we received were
collected as part of the national strategy for prevention and control of
COVID-19 without accompanying systematic clinical metadata and we were
thus unable to stratify between asymptomatic, mild and severe cases.
Second, we were not able to systematically assess the possible duration
of viral shedding because most of our cases were detected
upon
arrival, through contact tracing, and by the quarantine process. Thus,
sampling times were determined by disease control staff in the field,
rather than in the context of a rigorously designed study. Third, the
source of specimens for viral isolation was upper respiratory tract
specimens only. We did not receive any sputum or tracheal aspirate
fluids, which may have different characteristics in terms of Ct values
or culturable virus.
In summary, we describe here the virologic and epidemiology
characteristics of cases of laboratory-confirmed COVID-19 in northern
Vietnam from two clusters of cases during the first months of the
pandemic. We determined that most cases that will be
laboratory-confirmed are confirmed within the first few samplings. We
also determined that most cases that are positive very late in their
clinical course are extremely unlikely to represent active infection
but, rather, remnants of viral RNA.