How Do You Know You Are Asymptomatic for Covid

Key Summary Points

The likelihood that approximately 40% to 45% of those infected with SARS-CoV-ii volition remain asymptomatic suggests that the virus might take greater potential than previously estimated to spread silently and securely through homo populations.
Asymptomatic persons can transmit SARS-CoV-ii to others for an extended menses, perhaps longer than xiv days.
The absence of COVID-xix symptoms in persons infected with SARS-CoV-2 might not necessarily imply an absence of harm. More than inquiry is needed to decide the significance of subclinical lung changes visible on computed tomography scans.
The focus of testing programs for SARS-CoV-2 should be substantially broadened to include persons who practice not have symptoms of COVID-19.

In the early months of the coronavirus illness 2019 (COVID-19) pandemic, an iconic epitome has been the "proned" patient in intensive care, gasping for breath, in imminent need of artificial ventilation. This is the mortiferous face of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-two), which every bit of 26 May 2020 had claimed more than 348 000 lives worldwide (1). But it is not the only face, considering SARS-CoV-2 now seems to have a dual nature: tragically lethal in some persons and surprisingly benign in others.

Since February 2020 (ii, 3), at that place have been reports of persons who were infected with SARS-CoV-2 simply did not develop symptoms of COVID-19. In some cases (4, 5), the viral load of such asymptomatic persons has been equal to that of symptomatic persons, suggesting similar potential for viral transmission. The prevalence of asymptomatic SARS-CoV-2 infection, however, has remained uncertain. Nosotros sought to review and synthesize the bachelor evidence on testing for SARS-CoV-two infection, carried out by real-fourth dimension reverse transcriptase polymerase chain reaction using nasopharyngeal swabs in all studies that specified the method of testing.

Nigh information from the 16 cohorts in this narrative review are not the output of large, advisedly designed studies with randomly selected, representative samples. They exercise not more often than not purport to depict anything more than certain circumscribed cohorts at specific moments in time. Nosotros take not attempted to pool them for the purposes of statistical assay. When viewed as a collection, though—as a kind of mosaic or patchwork—these data may offering potentially valuable insights into SARS-CoV-ii incidence and the highly variable effect of infection.

The difficulty of distinguishing asymptomatic persons from those who are only presymptomatic is a stumbling block. To exist clear, the asymptomatic individual is infected with SARS-CoV-ii but will never develop symptoms of COVID-19. In contrast, the presymptomatic individual is similarly infected but eventually will develop symptoms. The simple solution to this conundrum is longitudinal testing—that is, repeated observations of the individual over time. Unfortunately, simply five of our cohorts include longitudinal information. We must therefore acknowledge the possibility that some of the proportions of asymptomatic persons are lower than reported.

Methods

From 19 April through 26 May 2020, using the keywords COVID-19, SARS-CoV-2, symptoms, and asymptomatic, we periodically searched the published medical literature using the PubMed service maintained by the U.S. National Library of Medicine of the National Institutes of Health. We besides searched for unpublished manuscripts using the bioRxiv and medRxiv services operated by Cold Spring Harbor Laboratory. In addition, nosotros searched for news reports using Google and monitored relevant data shared on Twitter.

Cohorts

Iceland

In the largest accomplice in our set up (6), researchers in Iceland used the post-obit 2 methods to screen the general population for SARS-CoV-two infection: an open invitation for interested parties to register online then provide biosamples at a Reykjavik location, and a text message sent to "randomly chosen Icelanders between the ages xx and 70 years" inviting them to participate in the same way as the starting time group (Table) (7–19). In all, xiii 080 persons volunteered for the screening, 100 (0.viii%) of whom tested positive for SARS-CoV-ii. All who tested positive were aged 10 years or older. None of the 848 children younger than ten years in the sample tested positive. Amidst those with positive results, 43 (43%) had no symptoms of COVID-19 at the time of testing. As the researchers note, though, "symptoms nigh certainly adult later on in some of them" (vi).

Table. Summary of SARS-CoV-2 Testing Studies

Vo', Italy

At the beginning and end of a 14-24-hour interval lockdown imposed by authorities in the northern Italian town of Vo' (7), researchers collected nasopharyngeal swabs from 2812 residents during the first sampling try and 2343 during the 2nd; this represented 85.9% and 71.v%, respectively, of the entire population. In the showtime group, 30 (41.1%) of 73 persons who tested positive for SARS-CoV-two had no symptoms. In the 2d, 13 (44.8%) of 29 who tested positive were asymptomatic. According to the researchers, in the roughly ii-calendar week catamenia between the sampling efforts, none of the asymptomatic persons developed whatever symptoms of COVID-xix. In addition, through contact tracing, they confirmed that several new cases of SARS-CoV-2 infection that appeared during the second sampling had been acquired by exposure to asymptomatic persons. In Vo' during the 14-twenty-four hour period menses studied, young children seemed to play no part in the transmission of SARS-CoV-2: "No infections were detected in either survey in 234 tested children ranging from 0 to 10 years, despite some of them living in the same household as infected people" (7).

Diamond Princess

On 3 February 2020, the Diamond Princess cruise send returned to Yokohama, Japan, for quarantine (eight), having transferred an ill passenger to shore in Hong Kong on 25 January who afterwards tested positive for SARS-CoV-2. As of sixteen March, 712 (19.2%) of 3711 passengers and crew had tested positive. At the time of testing, 331 (46.five%) of those with positive results were asymptomatic. Although the latter infected persons reported no symptoms, some actually had subclinical changes in their lungs. When computed tomography scans for 76 of these persons were examined, 54% showed lung opacities (20).

An independent statistical modeling analysis (21) based on information available as of 21 February claimed to judge—with "a Bayesian framework using Hamiltonian Monte Carlo algorithm"—the proportion of asymptomatic persons on the Diamond Princess; information technology arrived at a figure of 17.9%. Considering, though, that data for asymptomatic persons were available merely for 15 through xx February and that the actual proportions of asymptomatic persons amid those tested on these dates were 56.vii%, 54.iii%, 70.7%, 73.nine%, 86.ane%, and 46.2%, this estimate seems puzzling. In a carve up news account (22), 1 of the coauthors of this analysis was reported to have estimated that "xl% of the full general population might exist able to be infected [with SARS-CoV-2] without showing any signs."

Boston Homeless Shelter

After a cluster of 15 COVID-nineteen cases was identified over 5 days at a big homeless shelter in Boston, Massachusetts, the infected persons were removed from the shelter, and all occupants were subsequently tested over a 2-mean solar day menses (ix). Among 408 occupants, 147 (36.0%) tested positive for SARS-CoV-2, of whom 129 (87.8%) were asymptomatic (23). The researchers concluded that "front-door symptom screening in homeless shelter settings volition likely miss a substantial number of COVID-nineteen cases in this high-hazard population" (ix).

Los Angeles Homeless Shelter

On 28 March, an initial case of COVID-xix was diagnosed with a positive examination result at a homeless shelter in downtown Los Angeles, California (10). Later on a cluster of symptomatic persons was identified early on in the week of 20 April, the shelter was closed to new occupants and testing was started for current occupants. As of 22 April, 43 (24.two%) of 178 completed tests were positive for SARS-CoV-2 and 27 (63.viii%) of the persons who tested positive were asymptomatic.

New York City Obstetric Patients

Between 22 March and 4 Apr 2020, women who delivered infants at 2 New York Metropolis hospitals were tested for SARS-CoV-2 (11). Among 214 patients, 33 (15.4%) tested positive, 29 (87.nine%) of whom were asymptomatic. The researchers note that "fever developed in 3 (10%) earlier postpartum belch (median length of stay, 2 days)" (11). Two of those patients, though, were presumed to have endomyometritis, for which they were treated with antibiotics.

U.Due south.Southward. Theodore Roosevelt

The first case of SARS-CoV-2 infection aboard the American shipping carrier U.S.S. Theodore Roosevelt was diagnosed on 22 March 2020 (24). As of 24 Apr, 4954 crew members had been tested for the virus; 856 (17.three%) tested positive (12). According to a news report, nigh 60% of those with positive results were asymptomatic (25). After an extended menses of isolation, many of these asymptomatic persons continued to examination positive for SARS-CoV-2. An internal U.S. Navy certificate stated, "Results of out-testing portions of the [Theodore Roosevelt] crew following 14 days of quarantine leads us to reevaluate our assessment of how the virus can remain agile in an asymptomatic host" (26).

Charles de Gaulle Shipping Carrier

On viii April 2020, crew members aboard the French naval vessel Charles de Gaulle starting time began showing symptoms of COVID-nineteen, 24 days after final having had contact with those outside the ship while docked on 15 March (27). On 10 April, 50 crew members received positive test results for SARS-CoV-2. The unabridged crew of 1760 was subsequently tested. Equally of 18 April, 1046 (59.iv%) had tested positive, and of these, virtually 50% were asymptomatic (13).

Japanese Citizens Evacuated From Wuhan, Prc

As of 6 February 2020, a total of 565 Japanese citizens had been repatriated from Wuhan, China, on charter flights. Thirteen (2.3%) tested positive for SARS-CoV-ii, of whom 4 (30.8%) were asymptomatic. As of six March, none of the latter persons had developed COVID-nineteen symptoms (two).

Greek Citizens Evacuated From Kingdom of spain, Turkey, and the United Kingdom

From 20 through 25 March 2020, a total of 783 Greek citizens were repatriated from Espana, Turkey, and the United Kingdom on 7 flights. Forty (5.1%) tested positive for SARS-CoV-2 (14). At the time of testing, 39 (97.5%) were asymptomatic. At follow-upwardly nearly 2 weeks afterwards, 35 (87.5%) had remained asymptomatic (Lytras T. Personal communication.).

Nursing Facility Residents in King County, Washington

On 1 March 2020, a staff member who had worked at a 116-bed skilled-nursing facility in King County, Washington, on 26 and 28 February tested positive for SARS-CoV-2 (15). On 13 March, 76 (92.six%) of the facility's 82 current residents were tested; 23 (thirty.iii%) tested positive. At the time of testing, 12 (52.2%) of the latter persons were asymptomatic. On 19 and xx March, 49 residents were retested, including those who had previously received negative results and those who had tested positive but were asymptomatic or had atypical symptoms. In this second circular of testing, 24 residents (49.0%) had positive results. Of these, 15 (63.v%) were asymptomatic. After a median of 4 days of follow-up, 24 (88.ix%) of the 27 asymptomatic persons developed symptoms of COVID-19.

The researchers note, "More than half of residents with positive examination results were asymptomatic at the time of testing and most likely contributed to manual. Infection-control strategies focused solely on symptomatic residents were not sufficient to forbid transmission after SARS-CoV-2 introduction into this facility" (fifteen).

Inmates in Arkansas, North Carolina, Ohio, and Virginia

Widespread outbreaks of COVID-19 in the correctional facilities of several states have led to large-scale screening programs. According to inquiry by Reuters journalists (xvi), as of 25 April 2020, SARS-CoV-ii test results that include information on symptom condition were available for 4693 inmates in the state prison systems of Arkansas, North Carolina, Ohio, and Virginia. Amongst these inmates, 3277 (69.8%) tested positive, of whom 3146 (96%) had no symptoms at the fourth dimension of testing.

Rutgers University Students and Employees

From 24 March through 7 April 2020, researchers recruited 829 students and employees at Rutgers University and 2 affiliated hospitals for SARS-CoV-ii testing (17); 546 were health care workers. In full, 41 (4.9%) tested positive. Among wellness intendance workers, xl (seven.3%) tested positive, compared with i (0.4%) of those in other fields. Of all who tested positive, 27 (65.9%) reported no symptoms when they were tested.

Indiana Residents

From 25 Apr through 1 May 2020, the Indiana State Department of Health and the Indiana University Richard M. Fairbanks School of Public Health tested 4611 residents of Indiana for SARS-CoV-ii (18, 28). "This number includes more three,600 people who were randomly selected and an boosted 900 volunteers recruited through outreach to the African American and Hispanic communities to more accurately represent state demographics" (28). In total, 78 (1.vii%) tested positive; 35 (44.8%) of these persons were asymptomatic.

Argentine Prowl Ship Passengers and Crew

In mid-March 2020, a cruise ship departed Ushuaia, Argentina, for a planned 21-mean solar day expedition (19). Later the emergence of a febrile rider on the 8th day of the cruise, the ship's itinerary was contradistinct, and it eventually docked at Montevideo, Uruguay, on the 13th day. All 217 passengers and crew members were tested; 128 (59.0%) tested positive, of whom 104 (81.3%) were asymptomatic.

San Francisco Residents

During 4 days in late April 2020, "4,160 adults and children, including more than than half of the residents in the xvi foursquare blocks that make upward San Francisco Census Tract 229.01" in the Mission Commune, were tested (29). Seventy-four (one.viii%) tested positive, of whom 39 (52.7%) were asymptomatic.

Word

Despite concerns about distinguishing asymptomatic from presymptomatic persons, data from 4 of 5 of the cohorts with longitudinal reporting suggest that a small fraction of asymptomatic persons may somewhen develop symptoms. In the Italian and Japanese cohorts, 0% of asymptomatic persons became symptomatic. In the Greek and New York cohorts, ten.iii% of asymptomatic persons became symptomatic. In the New York accomplice, the figure might exist as low as iii.4% because of the presumed diagnosis of endomyometritis in 2 of the 3 women who developed fevers. The observation menstruum in this cohort, however, was extremely brief: a median of ii days.

The King County accomplice—in a skilled-nursing facility—is an outlier. Of 27 initially asymptomatic residents, 24 (88.ix%) somewhen developed symptoms and were therefore recategorized as having been presymptomatic. These persons were presumably much older and had more comorbid conditions than those in the other 4 longitudinal cohorts. In add-on, they resided together in a single facility, which might accept allowed for repeated exposures to infected persons. More research is needed to ascertain the event of historic period and ecology factors on the natural history of COVID-19.

The Vo' accomplice seems to ostend that asymptomatic persons can indeed transmit SARS-CoV-2 to others, and the experience aboard the The statesS. Theodore Roosevelt suggests that they might exist able to transmit the virus to others for longer than fourteen days. These worrisome findings could explicate, in part, the rapid spread of the virus effectually the globe. Persons who do not feel or look ill are probable to accept far more interaction with others than those who have symptoms. If asymptomatic transmission is indeed common, testing just those with symptoms would seem to be folly.

The finding that 54% of the 76 asymptomatic persons on the Diamond Princess who were examined by computed tomography appeared to accept significant subclinical abnormalities in their lungs is agonizing. Further research will exist required to confirm this potentially important finding, taking into business relationship possible confounding factors, including the age of passengers aboard the Diamond Princess. If confirmed, this finding suggests that the absence of symptoms might not necessarily hateful the absence of harm. The subclinical nature of the finding raises the possibility that SARS-CoV-2 infection causes subtle deficits in lung function that might non exist immediately apparent.

Does the relatively high proportion (60.v%) of asymptomatic cases on the UsaS. Theodore Roosevelt—whose coiffure members, presumably, are by and large in their 20s and 30s—suggest that asymptomatic infection is more than probable in younger persons? Possibly, only it must be noted that the proportion of asymptomatic infection (47.viii%) on the Charles de Gaulle aircraft carrier seems to be but marginally higher than average. A instance series from Wuhan, Mainland china, from 24 December 2019 to 24 February 2020 included data for "78 patients from 26 cluster cases of exposure to the Hunan seafood market or close contact with other patients with COVID-19" (xxx). Asymptomatic patients "were younger (median [interquartile range] age, 37 [26-45] years vs 56 [34-63] years; P < .001), and had a higher proportion of women (22 [66.7%] women vs 14 [31.%] [sic] women; P = .002)."

As noted earlier, the data and studies reviewed hither are imperfect in many ways. The ideal report of asymptomatic SARS-CoV-ii infection has yet to be done. What might that study look similar? About important, information technology must include a large, representative sample of the general population, similar to the U.S. serosurvey for which the National Institutes of Health is currently recruiting (31). In contrast to the narrowly divers cohorts here, it volition be illuminating to take data that accurately reflect the population at large. In addition, longitudinal data must exist collected over a sufficiently long time to distinguish betwixt asymptomatic and presymptomatic cases.

Closed cohorts, such equally cruise ships, aircraft carriers, and correctional facilities, offer both advantages and disadvantages. Because the likelihood of viral exposure is so much greater than in other settings, the "handling" that participants receive may be close to uniform. Equally a consequence, we may learn more about the average incidence of asymptomatic infection. But the bars surroundings—which ensures frequent, overlapping interaction between participants—makes it challenging to accurately trace contacts and elucidate the chain of viral transmission.

On the basis of the 3 cohorts with representative samples—Iceland and Indiana, with data gathered through random option of participants, and Vo', with data for virtually all residents—the asymptomatic infection rate may exist as high as forty% to 45%. A conservative estimate would be 30% or higher to account for the presymptomatic admixture that has thus far non been adequately quantified. In any case, these high rates are not aligned with electric current testing programs that take predominantly focused on symptomatic cases. Beyond expanding testing to those without symptoms or known exposure, our inability to recognize carriers might make necessary the broad adoption of preventive strategies, such as masks.

The 96% rate of asymptomatic infection among thousands of inmates in 4 state prison systems is remarkable. Without any longitudinal data, we cannot estimate the number of presymptomatic cases. If the missing data prove to be similar to the Italian, Japanese, Greek, and New York cohorts, though, the vast majority of these persons will remain asymptomatic. Why, then, might the asymptomatic infection rate in this setting be so anomalously high?

One plausible factor could exist cantankerous-immunity imparted by the betacoronaviruses HCoV-OC43 and HCoV-HKU1, which has been proposed as a mitigating cistron in the spread of SARS-CoV-2 (32). Co-ordinate to the U.South. Centers for Affliction Command and Prevention, HCoV-HKU1 was agile across the U.s.a. from late Nov 2019 through mid-February 2020 (33). In a locked-down congregate setting similar a prison, it seems possible that contagious respiratory viruses could spread chop-chop, and so it would exist interesting to practise a serosurvey for antibodies to these betacoronaviruses. Still, 96% is very loftier. Information technology would exist prudent to review the source data carefully for errors.

What private differences might account for why ii persons of the same age, sex, and health status, for example, take idiosyncratic responses to SARS-CoV-2 infection? Why does ane come through with nary a symptom, while the other lies almost expiry in intensive care? At the moment, we simply do not know. If always there were a need for precision medicine—for deeply and thoroughly agreement the multitudinous "-omics" that shape each of us—this is information technology. Perhaps there volition exist not just ane therapy or vaccine for SARS-CoV-2 but versions that are individualized to maximize their efficacy.

In countries like the United States that have been hardest hitting past the SARS-CoV-2 pandemic, it has been apparent for some time that the amount of testing must exist significantly and rapidly increased—maybe by an guild of magnitude or more. With this new cognition that a large proportion of those infected with SARS-CoV-2 have no symptoms, the urgency for more testing becomes even greater.

In a perfect earth, possibly using simple, accurate, inexpensive technology that is still on the drawing board (34), nosotros would test each person every day for SARS-CoV-2. Until that is possible, innovative surveillance tactics might provide useful data for public health officials. Self-monitoring with internet-connected thermometers and smart watches that monitor heart rate, then crowdsourcing the resulting information, has been shown to accurately predict the incidence of influenza-like affliction as reported by the California Department of Public Health and the Centers for Disease Control and Prevention (35–37). Similarly, monitoring sewage sludge provided "SARS-CoV-two RNA concentrations [that] were a seven-day leading indicator ahead of compiled COVID-nineteen testing data and led local infirmary admissions data past iii days" (38).

The early on data that we have assembled on the prevalence of asymptomatic SARS-CoV-2 infection propose that this is a significant factor in the rapid progression of the COVID-19 pandemic. Medical practice and public health measures should be modified to accost this challenge.

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Source: https://www.acpjournals.org/doi/10.7326/M20-3012