Long-Term Symptoms Among Adults Tested for SARS-CoV-2

United States, January 2020-April 2021

Valentine Wanga, PhD; Jennifer R. Chevinsky, MD; Lina V. Dimitrov, MPH; Megan E. Gerdes, MPH; Geoffrey P. Whitfield, PhD; Robert A. Bonacci, MD; Miriam A.M. Nji, MD; Alfonso C. Hernandez-Romieu, MD; Jessica S. Rogers-Brown, PhD; Tim McLeod, MPH; Julie Rushmore, PhD, DVM; Caitlyn Lutfy, MPH; Dena Bushman, MSN, MPH; Emilia Koumans, MD; Sharon Saydah, PhD; Alyson B. Goodman, MD; Sallyann M. Coleman King, MD; Brendan R. Jackson, MD; Jennifer R. Cope, MD

Disclosures

Morbidity and Mortality Weekly Report. 2021;70(36):1235-1241.

Discussion

In this convenience sample of U.S. adults, the prevalence of long-term symptoms often associated with SARS-CoV-2 infection was higher among respondents who ever received a positive test result than among those who always received a negative test result, and symptoms in these persons tended to persist for >4 weeks. Previous studies have found that nonhospitalized persons with SARS-CoV-2 infection have higher prevalence of some long-term symptoms or conditions than nonhospitalized persons with negative SARS-CoV-2 test results.^[2–5] Similarly, in this investigation, more respondents who received a positive test result (65.9%) than those who received a negative test result (42.9%) experienced any long-term symptoms, and approximately one half of these symptoms were more likely to be reported among those who received a positive test result.

Early data on post-COVID conditions primarily came from hospitalized cohorts;^[1,6] more recent reports describe post-COVID conditions among nonhospitalized, asymptomatic, or mildly ill patients.^[1,7] The prevalence of the most common long-term symptoms among respondents who received a positive test result in this investigation was similar to that in earlier studies.^[1,8] Many studies on post-COVID conditions lack comparisons with the general population of adults with negative test results for SARS-CoV-2; however, this investigation included a comparison group, allowing for assessment of background symptom frequencies. Estimating population-level frequency of specific long-term symptoms among the general population and patients infected with SARS-CoV-2 could help health care professionals better understand the types and prevalences of symptoms their patients might experience and could help guide health systems in preparing care management strategies for patients with post-COVID conditions.

Among respondents who initially reported symptoms during the month of their first positive test results, >75% reported persistence of any symptoms >4 weeks, with hair loss, cognitive dysfunction, shortness of breath, and postexertional malaise persisting in approximately one half of respondents. This finding is consistent with findings from other studies reported in a systematic review^[1] and provides patient-level perspective on long-term symptoms associated with COVID-19; taken together, these studies highlight the importance of continued monitoring and clinical care for long-term symptoms among patients who have these symptoms early in the course of their illness.

With the increasing availability of COVID-19 vaccines, how vaccination affects post-COVID conditions remains unclear. Compared with respondents who received a negative test result, a higher proportion of those who received a positive test result believed that receiving a COVID-19 vaccine made their long-term symptoms better, and no difference was found in reported beliefs that receiving a vaccine made long-term symptoms worse. Early findings indicate that vaccination is not associated with worsening of post-COVID conditions^§§§.^[9] However, because no data were collected on the trajectory of long-term symptoms in persons who had not been vaccinated, whether any of the observed changes in symptoms are attributable to vaccination is uncertain. More data are needed to fully understand the effects of COVID-19 vaccines on persons with post-COVID conditions.

The findings in this report are subject to at least six limitations. First, the study used a nonprobability-based sample, which limits its generalizability. Second, responses were self-reported and thus subject to recall bias. Third, new symptoms occurring after the month when the first positive COVID-19 test result was received among those who received a positive test result were not assessed, and the reported symptoms could not be linked directly to SARS-CoV-2. Fourth, because the survey did not ask about symptom duration or severity, differences in duration or severity of long-term symptoms in respondents who received a positive rather than a negative test result could not be assessed. Fifth, respondents who always received a negative test result generally had a longer period in which to report symptoms, potentially inflating prevalence of their health care use and long-term symptoms. Finally, this study could not assess validity of SARS-CoV-2 tests, and some false-positive or false-negative test results might have resulted in misclassification of some respondents.

These findings can help guide public health preparedness efforts, resource needs for care and management of persons with post-COVID conditions, and communication about experiences with vaccination. The findings can also aid efforts to address post-COVID conditions, including helping health care professionals recognize the most common symptoms and optimize care for patients whose symptoms persist. Future research to assess long-term symptoms and risk factors, including disease severity, disease duration, and sociodemographic characteristics, will be important to help guide current and future health care services.

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^§§§ https://www.medrxiv.org/content/10.1101/2021.03.11.21253225v2

Table 1. Demographic characteristics of respondents aged ≥18 years who received at least one positive SARS-CoV-2 test result or only negative SARS-CoV-2 test results since January 2020 (N = 3,135), by selected characteristics — Porter Novelli Internet survey, United States, April 2021
Characteristic	Testing status, weighted % (95% CI)		p-value^†
Characteristic	At least one positive SARS-CoV-2 test result (n = 698)*	All negative SARS-CoV-2 test results (n = 2,437)*	p-value^†
Overall	22.2 (20.6–23.8)	77.8 (76.2–79.4)	—
Age group, yrs
18–29	26.3 (22.8–29.7)	23.2 (21.4–24.9)	<0.001
30–39	25.4 (22.0–28.8)	19.0 (17.4–20.6)	<0.001
40–49	18.6 (15.1–22.1)	16.4 (14.7–18.2)	<0.001
50–59	15.0 (11.8–18.2)	16.6 (14.8–18.4)	<0.001
60–69	10.3 (7.8–12.8)	16.4 (14.8–18.0)	<0.001
≥70	4.4 (2.8–6.0)	8.4 (7.2–9.5)	<0.001
Sex
Male	51.5 (47.4–55.7)	48.5 (46.3–50.7)	0.204
Female	48.5 (44.3–52.6)	51.5 (49.3–53.7)	0.204
Marital status
Married	54.0 (49.9–58.1)	49.2 (47.0–51.4)	0.197
Living with a partner	10.2 (7.7–12.6)	10.2 (8.8–11.6)	0.197
Single and never been married	22.2 (18.7–25.6)	24.4 (22.6–26.3)	0.197
Other^§	13.6 (10.6–16.6)	16.1 (14.5–17.8)	0.197
Highest level of education completed
Some high school or less	4.7 (2.8–6.6)	5.2 (4.1–6.3)	0.545
High school graduate/some college	50.7 (46.6–54.8)	49.2 (47.0–51.3)	0.545
2-year college/technical school	7.8 (5.7–10.0)	8.5 (7.3–9.8)	0.545
4-year college/some postgraduate education	19.6 (16.6–22.5)	21.7 (20.1–23.3)	0.545
Postgraduate degree	17.2 (14.4–19.9)	15.4 (14.1–16.8)	0.545
Employment status ^¶
Employed	70.5 (66.6–74.3)	61.6 (59.5–63.8)	<0.001
Unemployed	17.8 (14.5–21.1)	19.8 (17.9–21.6)	<0.001
Retired	11.7 (9.0–14.4)	18.6 (16.9–20.3)	<0.001
Household income in 2020, USD
<25,000	14.5 (11.4–17.5)	20.4 (18.5–22.2)	0.016
25,000–49,999	28.2 (24.4–32.0)	27.8 (25.8–29.9)	0.016
50,000–74,999	17.2 (14.0–20.4)	17.3 (15.7–19.0)	0.016
75,000–99,999	12.0 (9.5–14.5)	11.3 (9.9–12.6)	0.016
100,000–149,999	16.3 (13.5–19.2)	14.4 (13.0–15.7)	0.016
≥150,000	11.8 (9.2–14.3)	8.9 (7.8–10.0)	0.016
Race/Ethnicity
White, non-Hispanic	59.8 (55.5–64.0)	62.0 (59.7–64.2)	0.190
Black or African-American, non-Hispanic	12.4 (9.6–15.3)	12.3 (10.8–13.9)	0.190
Other,** non-Hispanic	6.2 (4.1–8.4)	8.2 (6.9–9.5)	0.190
Hispanic	21.6 (17.6–25.5)	17.5 (15.6–19.4)	0.190
U.S. Census region^††
Northeast	21.5 (18.1–24.9)	19.0 (17.3–20.6)	0.156
Midwest	21.1 (17.7–24.5)	19.5 (17.7–21.2)	0.156
South	38.1 (34.1–42.1)	38.4 (36.3–40.5)	0.156
West	19.3 (16.1–22.5)	23.1 (21.3–25.0)	0.156
Community type
Urban	43.8 (39.8–47.9)	37.6 (35.5–39.7)	0.028
Suburban	39.8 (35.7–43.9)	44.1 (41.9–46.3)	0.028
Rural	16.4 (13.3–19.5)	18.3 (16.6–20.0)	0.028

Abbreviations: CI = confidence interval; USD = U.S. dollars.
*Unweighted number of persons who received positive or negative SARS-CoV-2 test results.
^†p-value for weighted Wald chi-square test; all p-values <0.05 indicate significant differences.
^§Other marital status includes separated, divorced, and widowed.
^¶Employed includes full-time or part-time work and self-employment; unemployed includes students, homemakers, and those who were not employed currently or were unable to work.
**Other race/ethnicity includes Native American or Alaskan Native, Asian, and other (unspecified).
^†† Northeast: Connecticut, Maine, Massachusetts, New Hampshire, New Jersey, New York, Pennsylvania, Rhode Island, and Vermont; Midwest: Illinois, Indiana, Iowa, Kansas, Michigan, Minnesota, Missouri, Nebraska, North Dakota, Ohio, South Dakota, and Wisconsin; South: Alabama, Arkansas, Delaware, District of Columbia, Florida, Georgia, Kentucky, Louisiana, Maryland, Mississippi, North Carolina, Oklahoma, South Carolina, Tennessee, Texas, Virginia, and West Virginia; West: Alaska, Arizona, California, Colorado, Hawaii, Idaho, Montana, Nevada, New Mexico, Oregon, Utah, Washington, and Wyoming.

Table 2. Prevalence of symptoms lasting >4 weeks among respondents aged ≥18 years who received at least one positive SARS-CoV-2 test result or only negative SARS-CoV-2 test results since January 2020 — Porter Novelli Internet survey, United States, April 2021
Symptom	SARS-CoV-2 test result, weighted % (95% CI)
	Symptom prevalence among all persons receiving testing		Symptom prevalence among persons receiving testing who reported a symptom lasting >4 weeks since onset
	Respondents who received a positive test result (n = 698)*	Respondents who received a negative test result (n = 2,437)*	Respondents who received a positive test result (n = 465)*	Respondents who received a negative test result (n = 1,058)*
Any symptom	65.9^† (61.9–69.8)	42.9 (40.8–45.1)	—	—
1 symptom only	27.2^† (23.7–30.8)	18.7 (17.0–20.4)	41.4 (36.5–46.3)	43.6 (40.3–46.9)
2 symptoms	14.0^† (11.1–16.8)	9.5 (8.2–10.7)	21.2 (17.1–25.3)	22.1 (19.3–24.8)
≥3 symptoms	24.7^† (21.0–28.3)	14.7 (13.2–16.3)	37.4 (32.5–42.4)	34.3 (31.1–37.5)
Fatigue/Tired/Weakness	22.5^† (19.0–26.1)	12.0 (10.6–13.4)	34.2^† (29.3–39.1)	28.0 (25.0–31.0)
Change in smell or taste	17.3^† (14.1–20.4)	1.7 (1.1–2.3)	26.2^† (21.8–30.7)	3.9 (2.6–5.3)
Shortness of breath or breathlessness	15.5^† (12.4–18.7)	5.2 (4.2–6.2)	23.6^† (19.1–28.1)	12.1 (9.9–14.2)
Cough	14.5^† (11.6–17.4)	4.9 (4.0–5.9)	22.0^† (17.8–26.2)	11.5 (9.4–13.6)
Headache	13.8^† (10.9–16.7)	9.9 (8.6–11.2)	20.9 (16.7–25.1)	23.0 (20.2–25.8)
Problems sleeping	12.0^† (9.3–14.7)	16.5 (14.8–18.1)	18.1^† (14.2–22.1)	38.3 (35.1–41.6)
Joint or muscle pain	11.1 (8.4–13.9)	12.4 (10.9–13.9)	16.9^† (12.9–20.9)	28.9 (25.8–32.0)
Cognitive dysfunction^§	10.2^† (7.7–12.8)	7.3 (6.1–8.4)	15.5 (11.8–19.3)	16.9 (14.4–19.4)
Chest pain or pressure	7.3^† (5.2–9.4)	2.3 (1.6–2.9)	11.0^† (7.9–14.2)	5.3 (3.7–6.8)
Change in mood	6.6 (4.6–8.7)	8.8 (7.6–10.0)	10.1^† (7.1–13.1)	20.6 (17.9–23.2)
Postexertional malaise^¶	6.1^† (4.1–8.0)	2.4 (1.7–3.0)	9.2^† (6.3–12.2)	5.5 (3.9–7.0)
Stomach pain	5.8 (3.9–7.7)	5.1 (4.1–6.1)	8.9 (6.0–11.7)	11.9 (9.7–14.1)
Hair loss	5.6 (3.7–7.5)	4.1 (3.3–5.0)	8.5 (5.6–11.3)	9.7 (7.6–11.7)
Diarrhea	5.3 (3.3–7.2)	3.3 (2.6–4.1)	8.0 (5.0–10.9)	7.8 (6.0–9.5)
Sore throat	4.9^† (3.1–6.8)	1.7 (1.1–2.2)	7.5^† (4.7–10.3)	3.9 (2.7–5.1)
Fever or chills	4.9^† (3.0–6.8)	1.9 (1.4–2.5)	7.5 (4.7–10.3)	4.5 (3.2–5.8)
Palpitations (heart racing or pounding)	4.5 (2.7–6.3)	2.5 (1.9–3.2)	6.8 (4.1–9.5)	5.9 (4.3–7.5)
Nausea/Vomiting	4.1^† (2.5–5.8)	1.9 (1.3–2.4)	6.3 (3.8–8.8)	4.3 (3.0–5.7)
Other symptom	1.3 (0.3–2.2)**	1.0 (0.6–1.5)	2.0 (0.5–3.4)**	2.4 (1.4–3.4)

Abbreviation: CI = confidence interval.
*Unweighted number of persons who received at least one positive or only negative SARS-CoV-2 test results.
^†p-value for weighted Wald chi-square test <0.05, indicating significant differences between those receiving a positive test result and those receiving a negative SARS-CoV-2 test result.
^§Difficulty thinking clearly, concentrating, forgetfulness, memory loss, or "brain fog."
^¶Worsening of symptoms after even minor physical, mental, or emotional exertion.
** Estimate is unstable; relative standard error is >30%.

Table 3. Frequency of health care use, vaccination, and reported vaccine effects on symptoms lasting >4 weeks among respondents aged ≥18 years who received at least one positive SARS-CoV-2 test result or only negative SARS-CoV-2 test results since January 2020 — Porter Novelli Internet survey, United States, April 2021
Item	Weighted % (95% CI)		p-value*
Item	At least one positive SARS-CoV-2 test result	All negative SARS-CoV-2 test results	p-value*
Health care utilization among those with any initial symptom	603^†	1,526^†	N/A
Saw health care professional for symptoms	54.1 (49.7–58.6)	42.5 (39.8–45.2)	<0.001
Went to urgent or emergency care for symptoms	19.5 (16.0–23.0)	14.0 (12.1–15.9)	0.008
Hospitalized for symptoms	10.4 (7.8–13.0)	9.3 (7.6–11.0)	0.492
Health care utilization among those with symptoms lasting >4 wks (long-term symptoms)	465^†	1,058^†	N/A
Saw health care professional for long-term symptoms	24.7 (20.5–28.9)	35.8 (32.6–39.0)	<0.001
Saw health care professional more than once for long-term symptoms	17.6 (13.7–21.5)	27.9 (24.8–30.9)	<0.001
COVID-19 vaccination status	698^†	2,437^†	N/A
Received at least 1 dose of vaccine^§	28.3 (24.5–32.0)	39.4 (37.3–41.5)	<0.001
Having long-term symptoms was a motivator to receive or consider receiving vaccine	11.0 (8.0–14.0)	7.0 (5.3–8.7)	0.023
Reported vaccination effects on long-term symptoms^¶	100^†	285†	N/A
Vaccine made symptoms better**	28.7 (18.6–38.7)	15.7 (11.3–20.0)	0.023
Vaccine did not affect symptoms at all	26.4 (16.7–36.0)	59.2 (53.1–65.4)	<0.001
Vaccine made symptoms worse^††	16.1 (8.4–23.7)	11.2 (6.9–15.4)	0.271
Symptoms were gone before receiving vaccine	28.4 (18.4–38.5)	13.1 (8.9–17.3)	0.007

Abbreviations: CI = confidence interval; N/A = not applicable.
*p-value for weighted Wald chi-square test; all p-values <0.05 indicate significant differences.
^†Unweighted number of persons who received positive or negative SARS-CoV-2 test results.
^§189 of 698 respondents who received a positive test result and 961 of 2,437 respondents who received a negative test result reported receiving 1 dose of vaccine.
^¶Respondents who ever experienced a long-term symptom and received at least 1 vaccine dose.
**Includes those reporting receiving a vaccine made symptoms a lot better, somewhat better, or a little better.
^††Includes those reporting receiving a vaccine made symptoms a little worse, somewhat worse, or a lot worse.