How Do You Know if You Have Covid if Your Asymptomatic

Fundamental Summary Points

The likelihood that approximately 40% to 45% of those infected with SARS-CoV-2 will remain asymptomatic suggests that the virus might have greater potential than previously estimated to spread silently and deeply through human populations.
Asymptomatic persons can transmit SARS-CoV-2 to others for an extended menstruum, perchance longer than 14 days.
The absence of COVID-19 symptoms in persons infected with SARS-CoV-2 might not necessarily imply an absence of harm. More research is needed to determine 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 practise not have symptoms of COVID-xix.

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

Since February 2020 (2, iii), there have been reports of persons who were infected with SARS-CoV-2 only 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 like potential for viral transmission. The prevalence of asymptomatic SARS-CoV-ii infection, however, has remained uncertain. We sought to review and synthesize the available evidence on testing for SARS-CoV-2 infection, carried out by real-time reverse transcriptase polymerase chain reaction using nasopharyngeal swabs in all studies that specified the method of testing.

Nigh information from the xvi cohorts in this narrative review are not the output of large, carefully designed studies with randomly selected, representative samples. They do not generally purport to depict anything more certain circumscribed cohorts at specific moments in time. We accept not attempted to pool them for the purposes of statistical assay. When viewed equally a collection, though—equally a kind of mosaic or patchwork—these information may offering potentially valuable insights into SARS-CoV-two incidence and the highly variable upshot of infection.

The difficulty of distinguishing asymptomatic persons from those who are but presymptomatic is a stumbling block. To be clear, the asymptomatic individual is infected with SARS-CoV-2 simply will never develop symptoms of COVID-xix. In dissimilarity, the presymptomatic private is similarly infected but eventually volition develop symptoms. The simple solution to this puzzler is longitudinal testing—that is, repeated observations of the private over time. Unfortunately, only 5 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 Apr through 26 May 2020, using the keywords COVID-nineteen, SARS-CoV-two, 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 Wellness. We also searched for unpublished manuscripts using the bioRxiv and medRxiv services operated past Cold Leap Harbor Laboratory. In addition, we searched for news reports using Google and monitored relevant information shared on Twitter.

Cohorts

Iceland

In the largest cohort in our set (6), researchers in Iceland used the following 2 methods to screen the general population for SARS-CoV-2 infection: an open up invitation for interested parties to register online then provide biosamples at a Reykjavik location, and a text bulletin sent to "randomly chosen Icelanders between the ages twenty and lxx years" inviting them to participate in the aforementioned manner as the start group (Table) (7–nineteen). In all, 13 080 persons volunteered for the screening, 100 (0.8%) of whom tested positive for SARS-CoV-2. All who tested positive were aged 10 years or older. None of the 848 children younger than ten years in the sample tested positive. Amongst those with positive results, 43 (43%) had no symptoms of COVID-19 at the time of testing. As the researchers annotation, though, "symptoms almost certainly developed subsequently in some of them" (6).

Tabular array. Summary of SARS-CoV-2 Testing Studies

Vo', Italia

At the beginning and end of a 14-day lockdown imposed by regime in the northern Italian town of Vo' (7), researchers nerveless nasopharyngeal swabs from 2812 residents during the kickoff sampling effort and 2343 during the 2d; this represented 85.9% and 71.5%, respectively, of the entire population. In the kickoff group, 30 (41.1%) of 73 persons who tested positive for SARS-CoV-two had no symptoms. In the second, 13 (44.8%) of 29 who tested positive were asymptomatic. According to the researchers, in the roughly two-week menstruation between the sampling efforts, none of the asymptomatic persons adult any symptoms of COVID-19. In addition, through contact tracing, they confirmed that several new cases of SARS-CoV-ii infection that appeared during the second sampling had been caused by exposure to asymptomatic persons. In Vo' during the 14-twenty-four hours catamenia studied, young children seemed to play no role in the transmission of SARS-CoV-2: "No infections were detected in either survey in 234 tested children ranging from 0 to x years, despite some of them living in the same household as infected people" (7).

Diamond Princess

On 3 Feb 2020, the Diamond Princess cruise ship returned to Yokohama, Nihon, for quarantine (8), having transferred an sick passenger to shore in Hong Kong on 25 Jan who afterward tested positive for SARS-CoV-ii. Equally of 16 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 really 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 bachelor as of 21 Feb claimed to estimate—with "a Bayesian framework using Hamiltonian Monte Carlo algorithm"—the proportion of asymptomatic persons on the Diamond Princess; it arrived at a effigy of 17.9%. Considering, though, that data for asymptomatic persons were available only for 15 through xx February and that the bodily proportions of asymptomatic persons among those tested on these dates were 56.7%, 54.iii%, 70.7%, 73.9%, 86.ane%, and 46.2%, this judge seems puzzling. In a dissever news account (22), one of the coauthors of this analysis was reported to take estimated that "40% of the full general population might be able to be infected [with SARS-CoV-two] without showing any signs."

Boston Homeless Shelter

Later a cluster of 15 COVID-xix cases was identified over 5 days at a large homeless shelter in Boston, Massachusetts, the infected persons were removed from the shelter, and all occupants were subsequently tested over a two-day period (9). Among 408 occupants, 147 (36.0%) tested positive for SARS-CoV-ii, of whom 129 (87.eight%) were asymptomatic (23). The researchers concluded that "front-door symptom screening in homeless shelter settings will likely miss a substantial number of COVID-xix cases in this loftier-risk population" (9).

Los Angeles Homeless Shelter

On 28 March, an initial case of COVID-19 was diagnosed with a positive test result at a homeless shelter in downtown Los Angeles, California (10). After a cluster of symptomatic persons was identified early in the calendar week of xx Apr, the shelter was closed to new occupants and testing was started for current occupants. As of 22 Apr, 43 (24.two%) of 178 completed tests were positive for SARS-CoV-2 and 27 (63.8%) of the persons who tested positive were asymptomatic.

New York City Obstetric Patients

Betwixt 22 March and four April 2020, women who delivered infants at two New York City hospitals were tested for SARS-CoV-two (11). Amidst 214 patients, 33 (15.4%) tested positive, 29 (87.9%) of whom were asymptomatic. The researchers note that "fever adult in 3 (10%) earlier postpartum discharge (median length of stay, 2 days)" (11). Two of those patients, though, were presumed to accept endomyometritis, for which they were treated with antibiotics.

U.S.South. Theodore Roosevelt

The starting time case of SARS-CoV-2 infection aboard the American shipping carrier U.S.Southward. Theodore Roosevelt was diagnosed on 22 March 2020 (24). Every bit of 24 April, 4954 crew members had been tested for the virus; 856 (17.3%) tested positive (12). According to a news report, about lx% of those with positive results were asymptomatic (25). Later on an extended period of isolation, many of these asymptomatic persons connected to test 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 active in an asymptomatic host" (26).

Charles de Gaulle Shipping Carrier

On 8 April 2020, crew members aboard the French naval vessel Charles de Gaulle first began showing symptoms of COVID-19, 24 days after last having had contact with those outside the ship while docked on 15 March (27). On x April, 50 crew members received positive test results for SARS-CoV-2. The unabridged crew of 1760 was subsequently tested. As of eighteen April, 1046 (59.4%) had tested positive, and of these, well-nigh 50% were asymptomatic (13).

Japanese Citizens Evacuated From Wuhan, Communist china

As of vi February 2020, a full of 565 Japanese citizens had been repatriated from Wuhan, People's republic of china, on charter flights. Thirteen (2.3%) tested positive for SARS-CoV-2, of whom 4 (30.eight%) were asymptomatic. Equally of vi March, none of the latter persons had developed COVID-19 symptoms (ii).

Greek Citizens Evacuated From Spain, Turkey, and the United Kingdom

From 20 through 25 March 2020, a total of 783 Greek citizens were repatriated from Spain, Turkey, and the U.k. on 7 flights. Twoscore (5.1%) tested positive for SARS-CoV-2 (14). At the time of testing, 39 (97.5%) were asymptomatic. At follow-upwards about 2 weeks later, 35 (87.5%) had remained asymptomatic (Lytras T. Personal advice.).

Nursing Facility Residents in King Canton, 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.half-dozen%) of the facility'southward 82 current residents were tested; 23 (xxx.three%) tested positive. At the time of testing, 12 (52.two%) of the latter persons were asymptomatic. On xix and 20 March, 49 residents were retested, including those who had previously received negative results and those who had tested positive just were asymptomatic or had singular symptoms. In this second circular of testing, 24 residents (49.0%) had positive results. Of these, xv (63.5%) were asymptomatic. After a median of 4 days of follow-up, 24 (88.9%) of the 27 asymptomatic persons developed symptoms of COVID-nineteen.

The researchers note, "More than half of residents with positive examination results were asymptomatic at the time of testing and nearly likely contributed to transmission. Infection-control strategies focused solely on symptomatic residents were not sufficient to foreclose transmission after SARS-CoV-two introduction into this facility" (15).

Inmates in Arkansas, North Carolina, Ohio, and Virginia

Widespread outbreaks of COVID-19 in the correctional facilities of several states have led to large-calibration screening programs. Co-ordinate to enquiry by Reuters journalists (16), every bit of 25 Apr 2020, SARS-CoV-2 test results that include data on symptom status were available for 4693 inmates in the state prison systems of Arkansas, North Carolina, Ohio, and Virginia. Amid these inmates, 3277 (69.8%) tested positive, of whom 3146 (96%) had no symptoms at the time of testing.

Rutgers University Students and Employees

From 24 March through 7 Apr 2020, researchers recruited 829 students and employees at Rutgers University and ii affiliated hospitals for SARS-CoV-2 testing (17); 546 were wellness intendance workers. In full, 41 (iv.ix%) tested positive. Among health care workers, 40 (7.three%) tested positive, compared with one (0.four%) 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 Wellness and the Indiana University Richard M. Fairbanks School of Public Wellness tested 4611 residents of Indiana for SARS-CoV-2 (xviii, 28). "This number includes more than than iii,600 people who were randomly selected and an additional 900 volunteers recruited through outreach to the African American and Hispanic communities to more accurately represent state demographics" (28). In total, 78 (ane.7%) 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-twenty-four hours expedition (19). Subsequently the emergence of a febrile passenger on the eighth solar day of the cruise, the ship'southward itinerary was altered, and it somewhen docked at Montevideo, Uruguay, on the 13th twenty-four hours. All 217 passengers and coiffure members were tested; 128 (59.0%) tested positive, of whom 104 (81.3%) were asymptomatic.

San Francisco Residents

During 4 days in belatedly April 2020, "4,160 adults and children, including more than than half of the residents in the 16 foursquare blocks that make up San Francisco Census Tract 229.01" in the Mission District, were tested (29). Seventy-four (1.8%) tested positive, of whom 39 (52.7%) were asymptomatic.

Discussion

Despite concerns most distinguishing asymptomatic from presymptomatic persons, data from 4 of five of the cohorts with longitudinal reporting suggest that a small fraction of asymptomatic persons may eventually develop symptoms. In the Italian and Japanese cohorts, 0% of asymptomatic persons became symptomatic. In the Greek and New York cohorts, 10.three% of asymptomatic persons became symptomatic. In the New York cohort, the figure might be equally low as 3.4% because of the presumed diagnosis of endomyometritis in 2 of the 3 women who developed fevers. The ascertainment period in this cohort, nevertheless, was extremely brief: a median of 2 days.

The King County cohort—in a skilled-nursing facility—is an outlier. Of 27 initially asymptomatic residents, 24 (88.ix%) eventually 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 unmarried facility, which might have allowed for repeated exposures to infected persons. More enquiry is needed to ascertain the effect of age and environmental factors on the natural history of COVID-xix.

The Vo' cohort seems to confirm that asymptomatic persons tin indeed transmit SARS-CoV-2 to others, and the experience aboard the United statesSouthward. Theodore Roosevelt suggests that they might exist able to transmit the virus to others for longer than 14 days. These worrisome findings could explain, in part, the rapid spread of the virus around the globe. Persons who do not feel or expect ill are probable to have far more than interaction with others than those who accept symptoms. If asymptomatic manual is indeed common, testing only those with symptoms would seem to be folly.

The finding that 54% of the 76 asymptomatic persons on the Diamond Princess who were examined past computed tomography appeared to have significant subclinical abnormalities in their lungs is disturbing. Further research will exist required to ostend this potentially important finding, taking into account possible misreckoning factors, including the historic period of passengers aboard the Diamond Princess. If confirmed, this finding suggests that the absenteeism of symptoms might not necessarily mean the absence of damage. The subclinical nature of the finding raises the possibility that SARS-CoV-2 infection causes subtle deficits in lung function that might non be immediately credible.

Does the relatively high proportion (lx.5%) of asymptomatic cases on the UsaS. Theodore Roosevelt—whose crew members, presumably, are mostly in their 20s and 30s—suggest that asymptomatic infection is more likely in younger persons? Perchance, but it must be noted that the proportion of asymptomatic infection (47.viii%) on the Charles de Gaulle aircraft carrier seems to be only marginally college than boilerplate. A case series from Wuhan, 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 shut contact with other patients with COVID-19" (30). 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.vii%] women vs 14 [31.%] [sic] women; P = .002)."

Equally noted earlier, the information and studies reviewed here are imperfect in many ways. The platonic report of asymptomatic SARS-CoV-2 infection has however to exist washed. What might that study look like? Most of import, it must include a large, representative sample of the general population, similar to the U.Due south. serosurvey for which the National Institutes of Health is currently recruiting (31). In contrast to the narrowly defined cohorts hither, information technology volition be illuminating to accept data that accurately reflect the population at big. In add-on, longitudinal data must be collected over a sufficiently long time to distinguish betwixt asymptomatic and presymptomatic cases.

Closed cohorts, such as prowl ships, aircraft carriers, and correctional facilities, offer both advantages and disadvantages. Considering the likelihood of viral exposure is and so much greater than in other settings, the "treatment" that participants receive may be close to compatible. As a outcome, we may learn more nearly the boilerplate incidence of asymptomatic infection. Simply the confined environs—which ensures frequent, overlapping interaction betwixt 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 information gathered through random choice of participants, and Vo', with information for nigh all residents—the asymptomatic infection charge per unit may exist as high as 40% to 45%. A conservative estimate would be 30% or college to business relationship for the presymptomatic admixture that has thus far non been adequately quantified. In any instance, these high rates are not aligned with 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 amidst thousands of inmates in iv state prison systems is remarkable. Without whatsoever longitudinal data, we cannot estimate the number of presymptomatic cases. If the missing information prove to exist similar to the Italian, Japanese, Greek, and New York cohorts, though, the vast bulk of these persons will remain asymptomatic. Why, then, might the asymptomatic infection rate in this setting exist and then anomalously loftier?

One plausible gene could exist cross-immunity imparted by the betacoronaviruses HCoV-OC43 and HCoV-HKU1, which has been proposed as a mitigating factor in the spread of SARS-CoV-2 (32). According to the U.S. Centers for Disease Control and Prevention, HCoV-HKU1 was agile across the United States from tardily November 2019 through mid-February 2020 (33). In a locked-downward besiege setting like a prison, it seems possible that contagious respiratory viruses could spread rapidly, so it would be interesting to do a serosurvey for antibodies to these betacoronaviruses. Still, 96% is very high. Information technology would be prudent to review the source data carefully for errors.

What individual differences might business relationship for why 2 persons of the same age, sex activity, and health condition, for example, accept idiosyncratic responses to SARS-CoV-2 infection? Why does one come through with nary a symptom, while the other lies nearly death in intensive care? At the moment, we simply do not know. If ever there were a demand for precision medicine—for deeply and thoroughly understanding the multitudinous "-omics" that shape each of us—this is it. Perhaps there will be not but 1 therapy or vaccine for SARS-CoV-2 simply versions that are individualized to maximize their efficacy.

In countries similar the Us that take been hardest hit by the SARS-CoV-two pandemic, information technology has been apparent for some time that the amount of testing must be significantly and quickly increased—perhaps by an society of magnitude or more than. With this new knowledge that a large proportion of those infected with SARS-CoV-two take no symptoms, the urgency for more testing becomes fifty-fifty greater.

In a perfect world, perhaps using unproblematic, accurate, inexpensive technology that is nonetheless on the drawing lath (34), we would test each person every day for SARS-CoV-ii. Until that is possible, innovative surveillance tactics might provide useful data for public health officials. Self-monitoring with internet-continued thermometers and smart watches that monitor center charge per unit, then crowdsourcing the resulting data, has been shown to accurately predict the incidence of influenza-similar disease every bit reported by the California Section of Public Wellness and the Centers for Illness Command and Prevention (35–37). Similarly, monitoring sewage sludge provided "SARS-CoV-two RNA concentrations [that] were a 7-day leading indicator ahead of compiled COVID-19 testing data and led local infirmary admissions data by three days" (38).

The early data that we have assembled on the prevalence of asymptomatic SARS-CoV-2 infection suggest that this is a significant factor in the rapid progression of the COVID-xix 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