Table 2.
Diagnostic performance indicators for individual COVID-19 symptoms, existing case definitions, and derived compound symptom combinations for a community cohort of 185 people with household COVID-19 exposure in Utah and Wisconsin, United States, March–May 2020
| SARS-CoV-2-negative (n = 136) |
SARS-CoV-2-positive (n = 49) |
Specificitya | Sensitivityb | NPVc | PPVd | Youden’s indexe | F-1 scoref | Difference in prevalenceg | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| TNh | FPi | FNj | TPk | Value | (95% CI) | Value | (95% CI) | Value | (95% CI) | Value | (95% CI) | Value | (95% CI) | Value | (95% CI) | Value | (95% CI) | |
| Individual symptoms | ||||||||||||||||||
| Upper respiratory | ||||||||||||||||||
| Nasal congestion or rhinorrhea | 66 | 70 | 5 | 44 | 49 | (38, 59) | 90 | (80, 96) | 93 | (85, 97) | 39 | (27, 50) | 38 | (26, 50) | 54 | (42, 65) | 133 | (78, 227) |
| Sore throat | 96 | 40 | 22 | 27 | 71 | (61, 79) | 55 | (40, 68) | 81 | (72, 88) | 40 | (26, 56) | 26 | (10, 40) | 47 | (33, 59) | 37 | (0, 98) |
| Lower respiratory | ||||||||||||||||||
| Cough | 103 | 33 | 13 | 36 | 76 | (65, 84) | 74 | (60, 85) | 89 | (81, 94) | 52 | (37, 67) | 49 | (36, 62) | 61 | (49, 72) | 41 | (8, 94) |
| Chest pain | 122 | 14 | 35 | 14 | 90 | (83, 94) | 29 | (15, 42) | 78 | (69, 85) | 50 | (24, 70) | 18 | (5, 33) | 36 | (21, 51) | − 43 | (−62, −15) |
| Shortness of breath | 125 | 11 | 36 | 13 | 92 | (86, 96) | 27 | (15, 40) | 78 | (67, 85) | 54 | (31, 75) | 18 | (6, 32) | 36 | (22, 49) | −51 | (− 68, − 24) |
| Discomfort while breathing | 132 | 4 | 37 | 12 | 97 | (93, 99) | 25 | (14, 39) | 78 | (69, 85) | 75 | (40, 92) | 22 | (10, 36) | 37 | (22, 54) | −67 | (−80, −49) |
| Wheezing | 133 | 3 | 44 | 5 | 98 | (94, 99) | 10 | (4, 21) | 75 | (65, 83) | 63 | (20, 100) | 8 | (1, 19) | 18 | (7, 33) | −84 | (−92, −68) |
| Neurological | ||||||||||||||||||
| Headache | 86 | 50 | 7 | 42 | 63 | (52, 73) | 86 | (75, 93) | 93 | (85, 97) | 46 | (33, 59) | 49 | (35, 60) | 60 | (47, 70) | 88 | (44, 160) |
| Taste and/or smell dysfunction | 130 | 6 | 18 | 31 | 96 | (90, 99) | 63 | (47, 77) | 88 | (80, 93) | 84 | (64, 94) | 59 | (42, 73) | 72 | (57, 83) | −25 | (−43, −5) |
| Constitutional | ||||||||||||||||||
| Fever or chills | 113 | 23 | 18 | 31 | 83 | (75, 89) | 63 | (49, 76) | 86 | (78, 92) | 57 | (40, 72) | 46 | (30, 60) | 60 | (46, 72) | 10 | (−15, 51) |
| Fatigue | 94 | 42 | 20 | 29 | 69 | (59, 79) | 59 | (41, 74) | 83 | (74, 89) | 41 | (25, 57) | 28 | (10, 44) | 48 | (33, 63) | 45 | (8, 106) |
| Myalgia | 116 | 20 | 21 | 28 | 85 | (77, 91) | 57 | (42, 70) | 85 | (77, 90) | 58 | (41, 74) | 42 | (28, 56) | 58 | (44, 69) | −2 | (−28, 37) |
| Gastrointestinal | ||||||||||||||||||
| Diarrhea | 108 | 28 | 31 | 18 | 79 | (69, 88) | 37 | (20, 55) | 78 | (66, 86) | 39 | (22, 59) | 16 | (−3, 36) | 38 | (23, 54) | −6 | (−40, 48) |
| Abdominal pain | 120 | 16 | 34 | 15 | 88 | (80, 94) | 31 | (19, 45) | 78 | (68, 85) | 48 | (27, 73) | 19 | (4, 35) | 38 | (23, 53) | −37 | (−59, −2) |
| Nausea | 124 | 12 | 40 | 9 | 91 | (85, 95) | 18 | (10, 31) | 76 | (65, 83) | 43 | (20, 67) | 10 | (−1, 22) | 26 | (14, 40) | − 57 | (−74, −30) |
| Existing case definitions | ||||||||||||||||||
| COVID-19 and respiratory illness surveillance case definitions | ||||||||||||||||||
| CDC symptom listl | 40 | 96 | 0 | 49 | 29 | (17, 45) | 100 | NAw | 100 | NA | 34 | (24, 45) | 29 | (17, 45) | 51 | (38, 62) | 196 | (122, 322) |
| ARIm | 52 | 84 | 2 | 47 | 38 | (26, 51) | 96 | (86, 100) | 96 | (88, 100) | 36 | (25, 48) | 34 | (23, 45) | 52 | (40, 64) | 167 | (102, 279) |
| CSTE combination 1n | 79 | 57 | 3 | 46 | 58 | (47, 69) | 94 | (82, 98) | 96 | (91, 99) | 45 | (32, 58) | 52 | (39, 63) | 61 | (47, 72) | 110 | (64, 190) |
| CSTE combination 2o | 59 | 77 | 1 | 48 | 43 | (35, 52) | 98 | (88, 100) | 98 | (90, 100) | 38 | (30, 47) | 41 | (32, 50) | 55 | (46, 64) | 155 | (110, 225) |
| CLIp | 93 | 43 | 7 | 42 | 68 | (57, 79) | 86 | (70, 94) | 93 | (88, 97) | 49 | (35, 64) | 54 | (40, 65) | 63 | (48, 75) | 74 | (35, 141) |
| ILIq | 122 | 14 | 24 | 25 | 90 | (83, 94) | 51 | (35, 65) | 84 | (75, 90) | 64 | (45, 79) | 41 | (25, 55) | 57 | (42, 69) | −20 | (−41, 9) |
| Derived compound symptom combinationsr | ||||||||||||||||||
| Combination 1s | 129 | 7 | 12 | 37 | 95 | (89, 98) | 76 | (60, 87) | 92 | (85, 96) | 84 | (67, 94) | 70 | (54, 82) | 80 | (67, 88) | −10 | (−28, 9) |
| Combination 2t | 125 | 11 | 10 | 39 | 92 | (84, 97) | 80 | (65, 89) | 93 | (86, 96) | 78 | (59, 91) | 72 | (56, 83) | 79 | (66, 88) | 2 | (−17, 30) |
| Combination 3u | 126 | 10 | 11 | 38 | 93 | (85, 97) | 78 | (63, 88) | 92 | (86, 96) | 79 | (60, 91) | 70 | (54, 82) | 78 | (66, 87) | −2 | (−20, 24) |
| Combination 4v | 129 | 7 | 13 | 36 | 95 | (89, 98) | 74 | (59, 84) | 91 | (84, 95) | 84 | (67, 94) | 68 | (54, 80) | 78 | (67, 86) | −12 | (−29, 8) |
aSpecificity is the probability of testing negative when disease is absent
bSensitivity is the probability of testing positive when disease is present
cNPV negative predictive value. NPV is the probability of a patient not having disease when test is negative
dPPV positive predictive value. PPV is the probability of a patient having disease when test is positive
eYouden’s index is defined as sensitivity plus specificity minus 100 (perfect score = 100)
fF-1 score is defined as the harmonic mean of sensitivity and PPV (perfect score = 100)
gDifference in prevalence is defined as the difference in the number of positive symptom screens (i.e., true positive plus false positive) for each combination from the actual number of contacts who tested positive by RT-PCR
hTN true negative
iFP false positive
jFN false negative
kTP true positive
lU.S. Centers for Disease Control and Prevention (CDC) list of symptoms that may indicate COVID-19 infection (https://www.cdc.gov/coronavirus/2019-ncov/symptoms-testing/symptoms.html). This symptom list was last updated on 13 May 2020
mWorld Health Organization (WHO) acute respiratory infection (ARI) definition for community-based respiratory syncytial virus (RSV) surveillance (https://www.who.int/influenza/rsv/rsv_case_definition/en/). Last updated 04 February 2020
nU.S. Council of State and Territorial Epidemiologists (CSTE) original clinical criteria for COVID-19 reporting (https://cdn.ymaws.com/www.cste.org/resource/resmgr/2020ps/interim-20-id-01_covid-19.pdf). This interim position statement (Interim-20-ID-01) was approved on 05 April 2020 and was replaced by Interim-20-ID-02 on 07 August 2020
oU.S. Council of State and Territorial Epidemiologists (CSTE) revised clinical criteria for COVID-19 reporting (https://cdn.ymaws.com/www.cste.org/resource/resmgr/ps/positionstatement2020/interim-20-id-02_COVID-19.pdf). This interim position statement (Interim-20-ID-02) was approved on 07 August 2020 and replaced Interim-20-ID-01
pU.S. Centers for Disease Control and Prevention (CDC) COVID-19-like illness (CLI) definition was used to guide early diagnostic testing strategies from 17 January 2020–08 March 2020 (https://emergency.cdc.gov/han/han00426.asp)
qInfluenza-like illness (ILI) outpatient visit information collected through the U.S. Outpatient Influenza-like Illness Surveillance Network (ILINet) (https://www.cdc.gov/flu/weekly/overview.htm#anchor_1539281266932). This collaborative effort between CDC, state and local health departments, and healthcare providers has been tracking patients with ILI since the 1997–1998 influenza season
rCompound symptom combinations were derived from all symptoms recorded at any time prior to enrollment (and after the index case’s symptom onset date) through the end of the 14-day observation period
sDerived compound combination 1: Taste and/or smell dysfunction, OR one of the following: shortness of breath, myalgia, or fever or chills
tDerived compound combination 2: Taste and/or smell dysfunction or discomfort breathing, OR at least two of the following: shortness of breath, wheezing, or fever/chills
uDerived compound combination 3: Taste and/or smell dysfunction, OR at least two of the following: shortness of breath, wheezing, discomfort breathing, or fever/chills
vDerived compound combination 4: Taste and/or smell dysfunction, OR shortness of breath and fever/chills
wNA not applicable