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Cited by 702Long-Term Effects of COVID-19COVID-19 Clinical Research StudiesCOVID-19 and Mental Health

Assessment of the Frequency and Variety of Persistent Symptoms Among Patients With COVID-19: A Systematic Review

Open access
Nasserie, Tahmina, Hittle, Michael, Goodman, Steven N.·2021·JAMA Network Open
DOI 10.1001/jamanetworkopen.2021.11417PMC PMC8155823
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Abstract

Importance: Infection with COVID-19 has been associated with long-term symptoms, but the frequency, variety, and severity of these complications are not well understood. Many published commentaries have proposed plans for pandemic control that are primarily based on mortality rates among older individuals without considering long-term morbidity among individuals of all ages. Reliable estimates of such morbidity are important for patient care, prognosis, and development of public health policy. Objective: To conduct a systematic review of studies examining the frequency and variety of persistent symptoms after COVID-19 infection. Evidence Review: A search of PubMed and Web of Science was conducted to identify studies published from January 1, 2020, to March 11, 2021, that examined persistent symptoms after COVID-19 infection. Persistent symptoms were defined as those persisting for at least 60 days after diagnosis, symptom onset, or hospitalization or at least 30 days after recovery from the acute illness or hospital discharge. Search terms included COVID-19, SARS-CoV-2, coronavirus, 2019-nCoV, long-term, after recovery, long-haul, persistent, outcome, symptom, follow-up, and longitudinal. All English-language articles that presented primary data from cohort studies that reported the prevalence of persistent symptoms among individuals with SARS-CoV-2 infection and that had clearly defined and sufficient follow-up were included. Case reports, case series, and studies that described symptoms only at the time of infection and/or hospitalization were excluded. A structured framework was applied to appraise study quality. Findings: A total of 1974 records were identified; of those, 1247 article titles and abstracts were screened. After removal of duplicates and exclusions, 92 full-text articles were assessed for eligibility; 47 studies were deemed eligible, and 45 studies reporting 84 clinical signs or symptoms were included in the systematic review. Of 9751 total participants, 5266 (54.0%) were male; 30 of 45 studies reported mean or median ages younger than 60 years. Among 16 studies, most of which comprised participants who were previously hospitalized, the median proportion of individuals experiencing at least 1 persistent symptom was 72.5% (interquartile range [IQR], 55.0%-80.0%). Individual symptoms occurring most frequently included shortness of breath or dyspnea (26 studies; median frequency, 36.0%; IQR, 27.6%-50.0%), fatigue or exhaustion (25 studies; median frequency, 40.0%; IQR, 31.0%-57.0%), and sleep disorders or insomnia (8 studies; median 29.4%, IQR, 24.4%-33.0%). There were wide variations in the design and quality of the studies, which had implications for interpretation and often limited direct comparability and combinability. Major design differences included patient populations, definitions of time zero (ie, the beginning of the follow-up interval), follow-up lengths, and outcome definitions, including definitions of illness severity. Conclusions and Relevance: This systematic review found that COVID-19 symptoms commonly persisted beyond the acute phase of infection, with implications for health-associated functioning and quality of life. Current studies of symptom persistence are highly heterogeneous, and future studies need longer follow-up, improved quality, and more standardized designs to reliably quantify risks.

AI snapshot

Written from the paper’s full text.

TL;DR

This systematic review of 45 studies and 9751 participants found persistent COVID-19 symptoms were common, with a median 72.5% reporting at least 1 symptom at follow-up. However, study designs were highly heterogeneous and methodological improvements are needed to reliably quantify long-term risks.

Key findings

  • Among 16 studies reporting persistence of at least 1 symptom, the median frequency was 72.5% (IQR, 55.0%-80.0%); the abstract reports a median of 73%.
  • The most frequently examined persistent symptoms included dyspnea/shortness of breath (median, 36.0%; IQR, 27.6%-50.0%; 26 studies), fatigue/exhaustion (median, 40.0%; IQR, 31.0%-57.0%; 25 studies), cough (median, 16.9%; IQR, 14.4%-25.1% excluding one outlier), atypical chest pain (median, 13.1%; IQR, 10.8%-18.0%), and fever (median, 1.0%; IQR, 0%-3.0%).
  • Depression was reported in 10 studies (median, 14.9%; IQR, 11.0%-18.0%), anxiety in 10 studies (median, 22.1%; IQR, 10.0%-29.6%), cognitive deficits in 6 studies (median, 17.6%; IQR, 15.0%-21.6%), and memory loss in 5 studies (median, 28.3%; IQR, 18.6%-35.8%).
  • Adjusted persistent anosmia had a median frequency of 23.6% (IQR, 12.4%-40.7%) if present during acute illness, and adjusted persistent ageusia/dysgeusia had a median frequency of 15.6% (IQR, 10.1%-23.9%).

Methods

  • Systematic review following MOOSE; searched PubMed and Web of Science for articles published January 1, 2020, to March 11, 2021; included English-language cohort studies with defined follow-up (≥2 months from symptom onset, diagnosis, or hospitalization, or ≥1 month from recovery or discharge) and excluded case reports/case series.
  • Included 45 studies with 9751 participants reporting 84 clinical signs or symptoms; two authors independently extracted data and assessed quality using 6 NIH-based criteria, without excluding studies based on quality.
  • Used a descriptive synthesis because of heterogeneity; reported median and IQR for outcomes with 5 or more estimates and individual values for outcomes with 4 or fewer; baseline disease severity was calculated as a weighted mean.

Limitations

  • Stated: design limitations prevented addressing duration of persistent symptoms, the percentage ultimately resolved, and long-term trajectory of quality of life and function; limited data existed on persistence by initial severity, especially among outpatients; nonstandard symptom definitions/instruments made comparisons difficult; few studies assessed baseline symptom prevalence or included a contemporaneous non-COVID comparison group.
  • Stated: retention exceeded 80% in only 15 of 45 studies (33.3%), indicating quality was no better than moderate based on retention alone; outcomes were measured more than once in only 6 studies.
  • Evident from the text: most included patients were previously hospitalized (33 studies recruited only inpatients, 10 included mixed inpatients/outpatients, and 2 included only outpatients), and time-zero definitions and follow-up periods varied substantially, limiting combinability of estimates.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1001/jamanetworkopen.2021.11417

Cites

56 of 56 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 21 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    Only 15 of 45 studies (33.3%) exceeded 80% retention.

    “Among studies that reported retention, the median was 74.0% (IQR, 60.0%-83.6%), with only 15 studies9,10,15,17,20,22,24,30,31,34,36,43,46,47,50 (33.3%) exceeding 80% retention and 6 studies10,24,36,43,46,47 (13.3%) exceeding 90% retention (Table 1).”
    Quote in the paperNot a substantial claim
  • Findingown data

    Attrition was the variable most representative of low study quality, reported in 36 of 45 studies (80.0%).

    “The variable that was most representative of low study quality was attrition, which was reported in 36 of 45 studies9,10,11,12,13,14,15,17,18,20,21,22,23,24,26,27,28,29,30,31,33,34,36,39,40,41,42,43,45,46,47,48,49,50,51,52 (80.0%).”
    Quote in the paperNot a substantial claim
  • Findingown data

    Almost all included studies were of moderate or low quality based only on retention, standardization, and representativeness criteria.

    “Although we did not create a composite quality score because of the different implications of these dimensions for risk of bias, almost all studies were of moderate or low quality based only on retention, standardization, and representativeness criteria.”
    Quote in the paperSubstantial claim
  • Findingcitation

    The finding of symptom persistence was consistent even among studies that followed up patients for almost 6 months.

    “This finding was common, with a median frequency of 72.5% (IQR, 55.0%-80.0%), and consistent, even among studies that followed up patients for almost 6 months (eg, 76% of patients in the Huang et al22 study and 84% of patients in the Taboada et al43 study) (eTable 6 in the Supplement).”
    Quote in the paperSubstantial claim
  • Findingown data

    In this systematic review of 45 studies including 9751 participants with COVID-19, the median proportion of individuals who experienced at least 1 persistent symptom was 73%.

    “In this systematic review of 45 studies including 9751 participants with COVID-19, the median proportion of individuals who experienced at least 1 persistent symptom was 73%”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The search strategy identified all relevant studies on persistent COVID-19 symptoms.
    • Rests on an assumption: The included studies' reported symptom frequencies are valid measures of persistent symptoms.
  • May combine two claims. 35
  • Classified as probably not a substantial claim. 17

  • May combine two claims.

    Findingown data

    Most included studies measured outcomes at a single follow-up time and reported the percentage of the study population that continued to experience the outcome at the end of follow-up.

    “Most studies8,9,10,12,13,14,15,16,17,18,19,20,21,22,25,26,27,28,30,31,32,33,34,35,36,37,38,39,41,42,43,44,45,46,48,49,50,51,52 measured outcomes at a single follow-up time and reported the percentage of the study population that continued to experience the outcome at the end of follow-up.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    Thirty-five included studies used standardized scales to measure some or all included outcomes.

    “Thirty-five studies9,10,11,12,13,15,16,17,18,20,21,22,23,24,25,26,27,28,29,30,31,36,37,39,40,41,42,43,44,45,46,47,48,49,50 used standardized scales to measure some or all included outcomes.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The remaining 22 studies did not specify how fatigue was defined; the median frequency of fatigue in these studies was 39.8% (IQR, 31.4%-59.0%).

    “The remaining 22 studies9,10,11,15,16,18,20,21,22,26,27,28,31,35,36,38,42,43,44,48,51,52 did not specify how fatigue was defined; the median frequency of fatigue in these studies was 39.8% (IQR, 31.4%-59.0%).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Thirty-three studies recruited only inpatients; 10 studies included a combination of outpatients and inpatients; and 2 studies included only outpatients.

    “Thirty-three studies recruited only inpatients; 10 studies11,13,29,34,35,40,41,45,47,48 included a combination of outpatients and inpatients, with the proportion of inpatients ranging from 23.0% to 80.0% (Table 1), and 2 studies24,33 included only outpatients.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    Baseline illness severity was reported in 23 studies.

    “Other variables associated with study quality were the frequency of outcome measurements (with outcomes measured more than once in only 6 studies11,23,24,29,40,47) and the reporting of baseline illness severity (23 studies8,9,11,12,13,15,19,20,22,23,24,26,27,28,31,34,35,36,40,41,43,49,51).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    Among 9751 total participants, 5266 (54.0%) were male.

    “Among 9751 total participants, 5266 (54.0%) were male”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Fatigue or exhaustion was examined by 25 studies and was frequently experienced by participants (median frequency, 40.0%; IQR, 31.0%-57.0%).

    “Fatigue or exhaustion was examined by 25 studies9,10,11,15,16,18,20,21,22,23,26,27,28,31,35,36,37,38,42,43,44,45,48,51,52 and was frequently experienced by participants (median frequency, 40.0%; IQR, 31.0%-57.0%).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The symptoms occurring most frequently were shortness of breath or dyspnea, fatigue or exhaustion, and sleep disorders or insomnia.

    “symptoms occurring most frequently included shortness of breath or dyspnea, fatigue or exhaustion, and sleep disorders or insomnia.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The included studies' reported symptom frequencies are valid measures of persistent symptoms.

  • May combine two claims.

    Findingown data

    The most commonly reported comorbidities were diabetes (median frequency, 16.6%; IQR, 10.0%-23.0%) and hypertension (median frequency, 35.0%; IQR, 21.8%-41.0%).

    “The most commonly reported comorbidities were diabetes (34 studies8,10,13,14,15,16,17,18,19,20,22,23,24,25,26,27,28,30,31,33,35,37,38,39,40,41,42,43,47,48,49,50,51,52; median frequency, 16.6%; IQR, 10.0%-23.0%) and hypertension (32 studies9,10,13,14,16,17,18,19,20,21,22,23,24,25,26,27,28,30,31,33,35,37,38,39,40,41,42,43,48,49,51,52; median frequency, 35.0%; IQR, 21.8%-41.0%)”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingcitation

    Weerahandi et al reported the highest dyspnea frequency at 74.3%; however, 30.9% of the study population reported experiencing dyspnea before COVID-19 infection, although that subgroup reported substantial worsening of their baseline symptoms.

    “Weerahandi et al49 reported the highest dyspnea frequency at 74.3%; however, 30.9% of the study population reported experiencing dyspnea before COVID-19 infection, although that subgroup reported substantial worsening of their baseline symptoms.49”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Weerahandi et al49

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    Three studies measured fatigue using validated instruments.

    “Three studies23,37,45 measured fatigue using validated instruments.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Quality of life measures were most commonly assessed using questionnaires, including the EuroQol 5-dimension 5-level questionnaire in 10 studies and the 36-Item Short Form Survey in 5 studies.

    “Quality of life measures were most commonly assessed using questionnaires, including the EuroQol 5-dimension 5-level questionnaire54 (10 studies10,16,18,21,22,25,31,42,43,50) and the 36-Item Short Form Survey55 (5 studies9,12,36,37,48).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingcitation

    Zhao et al reported a low frequency of 16.4%, but fatigue was determined retroactively using patients' medical records.

    “Zhao et al52 reported a low frequency of 16.4%, but fatigue was determined retroactively using patients’ medical records.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Zhao et al52

      Not checked in the free run.

  • May combine two claims.

    Findingown data

    The included studies reported 84 signs or symptoms and 19 laboratory or imaging measurements.

    “The included studies reported 84 signs or symptoms and 19 laboratory or imaging measurements.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    Fatigue or exhaustion was examined in 25 studies.

    “fatigue or exhaustion (25 studies9,10,11,15,16,18,20,21,22,23,26,27,28,31,35,36,37,38,42,43,44,45,48,51,52)”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingcitation

    Twenty-four studies reported the baseline severity of COVID-19 illness, which varied substantially, even among hospitalized patients.

    “Twenty-four studies9,11,12,13,15,19,20,22,23,24,26,27,28,31,34,35,36,40,41,43,48,49,51,52 reported the baseline severity of COVID-19 illness, which varied substantially, even among hospitalized patients.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingcitation

    Carvalho-Schneider et al and Garrigues et al reported dyspnea frequencies of 30.0% and 41.7%, respectively, based on self-report and frequencies of 7.7% and 29.0% based on a modified Medical Research Council Dyspnea Scale score of 2 or higher.

    “Carvalho-Schneider et al11 and Garrigues et al18 reported dyspnea frequencies of 30.0% and 41.7%, respectively, based on self-report and frequencies of 7.7% and 29.0% based on a modified Medical Research Council Dyspnea Scale score of 2 or higher.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Carvalho-Schneider et al11

      Not checked in the free run.

    • cites Garrigues et al18

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Findingown data

    Other outcomes measured by standardized questionnaires included fatigue, dyspnea, and anxiety and/or depression, with variation in the instruments used across studies.

    “Other outcomes measured by standardized questionnaires included fatigue, dyspnea, and anxiety and/or depression, with variation in the instruments used across studies (Table 1).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    Cough was examined in 19 studies.

    “cough (19 studies9,14,15,16,18,20,21,23,26,28,31,36,38,39,40,42,43,50,51)”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Findingnone given

    Most patients reported thus far were previously hospitalized.

    “Most patients reported thus far were previously hospitalized.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingcitation

    Arnold et al and Chen et al measured these outcomes using the 36-Item Short Form Survey and reported comparable composite scores, with mean scores of 40.2 and 55.9 for physical health and 44.8 and 48.9 for mental health, respectively.

    “Arnold et al9 and Chen et al12 measured these outcomes using the 36-Item Short Form Survey, in which a score of 100 represents the best possible health status. These 2 studies reported comparable composite scores, with mean scores of 40.2 and 55.9 for physical health and 44.8 and 48.9 for mental health, respectively.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Arnold et al9

      Not checked in the free run.

    • cites Chen et al12

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    Puntmann et al reported that 78% of patients with COVID-19 had heart abnormalities, suggesting frequent myocardial inflammation.

    “Puntmann et al35 reported that 78% of patients with COVID-19 had heart abnormalities, suggesting frequent myocardial inflammation.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Puntmann et al35

      Not checked in the free run.

  • May combine two claims.

    Findingown data

    For the remaining studies, the median adjusted frequency was 23.6% (IQR, 12.4%-40.7%) for anosmia if this symptom occurred during the acute phase and 15.6% (IQR, 10.1%-23.9%) for persistent ageusia or dysgeusia.

    “For the remaining studies, we recalculated frequencies to examine the probability of symptoms persisting if they had appeared during acute illness, as no study reported new loss of smell or taste after recovery. The median adjusted frequency was 23.6% (IQR, 12.4%-40.7%) for anosmia if this symptom occurred during the acute phase and 15.6% (IQR, 10.1%-23.9%) for persistent ageusia or dysgeusia.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Although most studies did not stratify outcomes by age, 30 of the 45 studies with age information reported mean or median ages younger than 60 years; in 14 studies, mean or median ages were 50 years or younger.

    “Although most studies did not stratify outcomes by age, 30 of the 45 studies with age information reported mean or median ages younger than 60 years; in 14 studies, mean or median ages were 50 years or younger.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingcitation

    Weerahandi et al reported a mean (SD) of 43.8 (9.3) points for physical health and 47.3 (9.3) points for mental health, and Gonzalez et al reported a median of 45.9 points (IQR, 36.1-54.4 points) for physical health and 55.5 points (IQR, 40.6-58.0 points) for mental health; these scores were comparable to those reported by Arnold et al and Chen et al.

    “Weerahandi et al49 reported a mean (SD) of 43.8 (9.3) points for physical health and 47.3 (9.3) points for mental health, and Gonzalez et al20 reported a median of 45.9 points (IQR, 36.1-54.4 points) for physical health and 55.5 points (IQR, 40.6-58.0 points) for mental health; these scores were comparable to those reported by Arnold et al9 and Chen et al.12”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Weerahandi et al49

      Not checked in the free run.

    • cites Gonzalez et al20

      Not checked in the free run.

    • cites Arnold et al9

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    Xiong et al reported the lowest frequency of depression (4.3%); however, this study did not use a questionnaire or psychometric scale, and queries were limited to individuals who were willing and able to describe their symptoms.

    “Xiong et al51 reported the lowest frequency of depression (4.3%); however, this study did not use a questionnaire or psychometric scale, and queries were limited to individuals who were willing and able to describe their symptoms.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Xiong et al51

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    Inability to concentrate, informally described as brain fog, was only examined in 4 studies and was experienced by approximately 1 in 4 patients.

    “Inability to concentrate, informally described as brain fog, was only examined in 4 studies8,18,21,42 and was experienced by approximately 1 in 4 patients.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Fever was examined by 10 studies, and reported frequencies were relatively consistent (median frequency, 1.0%; IQR, 0% to 3.0%).

    “Fever was examined by 10 studies.9,11,16,20,23,26,31,40,42,44 Reported frequencies were relatively consistent across studies (median frequency, 1.0%; IQR: 0% to 3.0%).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Reported frequencies of cognitive outcomes were relatively consistent across studies; 6 studies reported cognitive deficits (median frequency, 17.6%; IQR, 15.0%-21.6%), 5 studies reported loss of memory (median frequency, 28.3%; IQR, 18.6%-35.8%), and 4 studies reported difficulty concentrating (frequency, 22.0%, 25.4%, 25.6%, and 28.0%).

    “Reported frequencies were relatively consistent across studies; 6 studies15,16,17,42,44,48 reported cognitive deficits (median frequency, 17.6%; IQR, 15.0%-21.6%), 5 studies8,18,21,27,42 reported loss of memory (median frequency, 28.3%; IQR, 18.6%-35.8%), and 4 studies8,18,21,42 reported difficulty concentrating (frequency, 22.0%, 25.4%, 25.6%, and 28.0%).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Including all studies, without adjustment, the median frequency for anosmia was 11% (IQR, 5.7%-14.3%) and for ageusia or dysgeusia was 9% (IQR, 3.0%-11.2%).

    “Including all studies, without adjustment, the corresponding median numbers for anosmia were 11% (IQR, 5.7%- 14.3%) and for ageusia or dysgeusia, 9% (IQR, 3.0%-11.2%).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingcitation

    Liang et al reported a cough frequency of 60%, but the remaining 18 studies reported a median frequency of 16.9% (IQR, 14.4%-25.1%).

    “Liang et al26 reported a frequency of 60%, but the remaining 18 studies reported a median frequency of 16.9% (IQR, 14.4%-25.1%).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Liang et al26

      Not checked in the free run.

  • May combine two claims.

    Findingown data

    Anosmia was reported by 19 studies, and ageusia or dysgeusia was reported by 13 studies.

    “Anosmia (loss of smell) was reported by 19 studies,9,13,16,18,19,20,22,23,24,27,33,34,38,40,42,43,44,46,47 and ageusia or dysgeusia (loss or distortion of taste) was reported by 13 studies.16,18,19,20,22,23,27,33,34,38,42,44,47”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Anxiety and/or depression was reported by 16 studies; of those, 10 studies reported depression (median frequency, 14.9%; IQR, 11.0%-18.0%), and 10 studies reported anxiety (median frequency, 22.1%; IQR, 10.0%-29.6%).

    “Anxiety and/or depression was reported by 16 studies8,15,17,20,21,22,27,28,29,30,37,42,44,48,50,51; of those, 10 studies15,17,20,28,29,30,37,44,48,51 reported depression (median frequency, 14.9%; IQR, 11.0%-18.0%), and 10 studies15,17,20,29,30,37,42,44,48,51 reported anxiety (median frequency, 22.1%; IQR, 10.0%-29.6%).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Atypical chest pain was reported by 11 studies, and the reported frequencies were relatively consistent (median, 13.1%; IQR, 10.8%-18.0%).

    “Atypical chest pain was reported by 11 studies,9,10,11,16,17,18,22,35,42,43,51 and the reported frequencies were relatively consistent (median, 13.1%; IQR, 10.8%-18.0%).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    This systematic review found that persistent COVID-19 symptoms were common, with 72.5% of patients reporting at least 1 symptom at 60 days or more after diagnosis, symptom onset, or hospitalization or at 30 days or more after recovery from acute illness or hospital discharge.

    “This systematic review found that persistent COVID-19 symptoms were common, with 72.5% of patients reporting at least 1 symptom at 60 days or more after diagnosis, symptom onset, or hospitalization or at 30 days or more after recovery from acute illness or hospital discharge.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Findingnone given

    Other neurocognitive deficits had similar frequencies.

    “Other neurocognitive deficits had similar frequencies.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingcitation

    Raman et al reported tissue abnormalities in the lungs (60%), kidneys (29%), heart (26%), and liver (10%).

    “Raman et al37 reported tissue abnormalities in the lungs (60%), kidneys (29%), heart (26%), and liver (10%).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Raman et al37

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    Two authors independently extracted data from each article.

    “Two authors (T.N. and M.H.) independently extracted data from each article.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductnone given

    Study quality was assessed, but studies were not excluded based on quality criteria.

    “Study quality was assessed, but studies were not excluded based on quality criteria.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    This study followed the relevant sections of the MOOSE reporting guideline for systematic reviews.

    “This study followed the relevant sections of the Meta-analysis of Observational Studies in Epidemiology (MOOSE) reporting guideline for systematic reviews.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductcitation

    Six quality criteria based on the National Institutes of Health Quality Assessment Tool for Observational and Cohort Studies were used to assess study design or features most likely to bias frequency estimates.

    “We used 6 quality criteria based on the National Institutes of Health Quality Assessment Tool for Observational and Cohort Studies53 to assess study design or features most likely to bias frequency estimates.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [53] National Heart, Lung, and Blood Institute. Study quality assessment tools. National Heart, Lung, and Blood Institute, National Institutes of Health. Accessed February 1, 2021. https://www.nhlbi.nih.gov/health-topics/study-quality-assessment-tools

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S2 (checkable).

    Interpretationown data

    The finding of common persistent symptoms suggests that inclusion of the prolonged burden of morbidity is warranted for future research on the overall health implications of the pandemic.

    “This finding suggests that inclusion of the prolonged burden of morbidity is warranted for future research on the overall health implications of the pandemic.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Interpretationnone given

    If the definition of time zero varies substantially among studies, particularly in combination with other time dimensions, then the final estimates cannot be combined to increase precision.

    “For example, if the definition of time zero varies substantially among studies, particularly in combination with other time dimensions, then the final estimates cannot be combined to increase precision.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Study design and conductnone given

    Few of the studies examined past history or baseline prevalence of similar symptoms or assessed prevalence in a contemporaneous group that did not have COVID-19, making it difficult to assess the fraction or severity of persistent symptoms that could be associated with COVID-19 infection.

    “Few of the studies examined past history or baseline prevalence of similar symptoms or assessed prevalence in a contemporaneous group that did not have COVID-19, making it difficult to assess the fraction or severity of persistent symptoms that could be associated with COVID-19 infection.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing), S4 (based). May combine two claims.

    Interpretationreasoning

    With millions of individuals experiencing COVID-19 infection, persistent symptoms are a burden on individual patients and their families as well as on outpatient care, public health, and the economy.

    “With millions of individuals experiencing COVID-19 infection, persistent symptoms are a burden on individual patients and their families as well as on outpatient care, public health, and the economy.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    The only feature that was unequivocally a measure of quality rather than design was the extent of patient retention, which exceeded 80% in only 15 of 45 studies (33.3%), indicating that quality was no better than moderate based on this measure alone.

    “The only feature that was unequivocally a measure of quality rather than design was the extent of patient retention, which exceeded 80% in only 15 of 45 studies (33.3%), indicating that quality was no better than moderate (ie, retention was >80%) based on this measure alone.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S2 (checkable).

    Interpretationreasoning

    This heterogeneity of design features and quality emphasizes the importance of improving and standardizing methods used in future studies.

    “This heterogeneity of design features and quality emphasizes the importance of improving and standardizing methods used in future studies.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationcitation

    The finding of symptom persistence was consistent even among studies that followed up patients for almost 6 months, suggesting that symptoms may persist long after recovery among some patients.

    “This finding was consistent even among studies that followed up patients for almost 6 months,22,43 suggesting that symptoms may persist long after recovery among some patients.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Study design and conductreasoning

    Design limitations among the included studies prevented the review from addressing several important issues, including the duration of persistent symptoms, the percentage of symptoms that were ultimately resolved, and the long-term trajectory of global quality of life and function.

    “Design limitations among the included studies prevented us from addressing several important issues, including the duration of persistent symptoms, the percentage of symptoms that were ultimately resolved, and the long-term trajectory of global quality of life and function.”
    Quote in the paperSubstantial claim
49 of 49

  • The paper relies on this without support.

    The search strategy identified all relevant studies on persistent COVID-19 symptoms.

    “We performed a systematic search of PubMed and Web of Science for articles published between January 1, 2020, and March 11, 2021, to identify studies that assessed the prevalence of persistent symptoms among individuals with SARS-CoV-2 infection.”

  • The paper relies on this without support.

    The included studies' reported symptom frequencies are valid measures of persistent symptoms.

    “We used 6 quality criteria based on the National Institutes of Health Quality Assessment Tool for Observational and Cohort Studies53 to assess study design or features most likely to bias frequency estimates.”
2 of 2

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • COVID-associated cognitive impairment ('COVID fog') is characterized by impaired attention, concentration, speed of information processing, memory, and executive function.

    “Colloquially known as “COVID fog,” this syndrome of COVID-associated cognitive impairment is characterized by impaired attention, concentration, speed of information processing, memory, and executive function (Becker et al., 2021; Nasserie et al., 2021).”

    From Mild respiratory COVID can cause multi-lineage neural cell and myelin dysregulation (2022) · cites this paper as Nasserie et al., 2021

  • Persistent cognitive impairment affects approximately one in four COVID survivors.

    “Neurological symptoms are emerging as relatively common sequelae, with persistent cognitive impairment affecting approximately one in four COVID survivors (Nasserie et al., 2021).”

    From Mild respiratory COVID can cause multi-lineage neural cell and myelin dysregulation (2022) · cites this paper as Nasserie et al., 2021

  • Even individuals with mild symptoms in the acute phase of COVID may experience lasting cognitive dysfunction.

    “While more common in individuals who had experienced severe COVID requiring hospitalization, even those with mild symptoms in the acute phase may experience lasting cognitive dysfunction (Becker et al., 2021; Nasserie et al., 2021).”

    From Mild respiratory COVID can cause multi-lineage neural cell and myelin dysregulation (2022) · cites this paper as Nasserie et al., 2021

  • The neurological sequelae of SARS-CoV-2 infection are proving to be both common and debilitating.

    “It is thus not surprising that the neurological sequelae of SARS-CoV-2 infection are proving to be both common and debilitating (Nasserie et al., 2021; Mazza et al., 2021; Qureshi et al., 2022; Becker et al., 2021; Tabacof et al., 2022).”

    From Mild respiratory COVID can cause multi-lineage neural cell and myelin dysregulation (2022) · cites this paper as Nasserie et al., 2021

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Xiong et al is assigned to Italy but listed in China

    Minor

    The country breakdown cites study 51 as an Italian study, while Table 1 lists Xiong et al, study 51, in China.

  • Conflicting counts of studies reporting baseline severity

    Minor

    The patient-characteristics section says 24 studies reported baseline illness severity, whereas the study-quality section says 23. Their cited study lists also differ.

  • Xiong age median falls below its reported interquartile range

    Minor

    The reported median age is 52 years, but the reported interquartile range begins at 95 years. A median cannot be below the first quartile.

  • Qu et al is assigned to Spain but listed in China

    Minor

    The country breakdown cites study 36 as a Spanish study, while Table 1 lists Qu et al, study 36, in China.

4 of 4

Cites

1 retracted

Flagged first, then by citations

Cited by

Sorted by citations

Related

Authors
Nasserie, T., Hittle, M., & Goodman, S. N.
Affiliations
Stanford University (US)
Corresponding author
Goodman, Steven N.
ORCID
Venue
JAMA Network Open
Publisher
American Medical Association (AMA)
Published
2021-05-26
Volume
4
Issue
5
Pages
e2111417
ISSN
2574-3805 (ISSN-L)
DOI
10.1001/jamanetworkopen.2021.11417
PMC
PMC8155823
OpenAlex
W3165456356
Cited by
702
References
56
Citations by year
2026: 34 · 2025: 71 · 2024: 153 · 2023: 185 · 2022: 205 · 2021: 53 · 2013: 1
FWCI
19.14
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • JAMA Network Open (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
National Heart, Lung, and Blood Institute (T32HL151323)
Topics
  • Health Sciences › Medicine › Neurology › Long-Term Effects of COVID-19
  • Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
  • Social Sciences › Psychology › Clinical Psychology › COVID-19 and Mental Health
Keywords
COVID-19 pandemic, SARS-CoV-2, long COVID, persistent symptoms, long-term morbidity, dyspnea, fatigue, post-COVID-19 neurological symptoms, symptom prevalence, symptom severity
MeSH terms
COVID-19, SARS-CoV-2, Dyspnea, Fatigue, Hospitalization, Humans, Sleep Wake Disorders, Survivors, Pandemics

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-10.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-10.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

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