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. 2021 Dec 29;101:93–135. doi: 10.1016/j.bbi.2021.12.020

Table 2.

Characteristics and results of studies (n = 81) examining individuals with confirmed COVID-19 12 or more weeks following diagnosis.

Study Country Study Design Sample Source Sample Characteristics Follow-up Duration Ascertainment of COVID-19 Ascertainment of Outcomes Results Factors Associated with persistent symptoms
Abdallah et al., 2021 Canada Prospective Cohort The Ottawa Hospital N = 63 (including 25 previously hospitalized cases and 38 previously non-hospitalized cases)
  • ●

    Age Range: ≥18

  • ●

    Mean Age*:59.1 ± 13.5

  • ●

    Mean Age**: 42.2 ± 12.9

  • ●

    Sex (%F/%M)*: 36.0/64.0

  • ●

    Sex (%F/%M)**: 47.4/52.6

*pertains to hospitalized cohort**pertains to non-hospitalized cohort		 Mean 119.9 ± 16.2 days following first positive test for hospitalized patients, and mean 129 ± 16.5 days for non-hospitalized patients RT-PCR Subjective self-report via clinical follow-up
  • ●

    71.4% (45/63) reported fatigue (72% [18/25] hospitalized and 71.1% [27/38] non-hospitalized)
Amin-Chowdhury et al., 2021a England Prospective Cohort Public Health England (ESCAPE study) N = 140 (clinical and non-clinical healthcare workers)
  • ●

    Age Range: ≥20

  • ●

    Median Age*: 41(31–52)

  • ●

    Sex* (%F/%M): 71.3/28.7

 Median 7.5 (7.1–7.8) months following COVID-19 diagnosis Serologyand RT-PCR Subjective self-report via online questionnaire
  • ●

    39.3% (55/140) of cases reported fatigue/tiredness after exertion

  • ●

    35.0% (49/140) of cases reported forgetfulness

  • ●

    27.9% (39/140) of cases reported confusion/brain fog/trouble focusing attention

  • ●

    20.7% (29/140) of cases reported short-term memory loss

  • ●

    15.7% (22/140) of cases reported trouble trying to form words
  • ●

    Female sex was associated with unusual fatigue and forgetfulness

  • ●

    Having underlying comorbidities was associated with unusual fatigue and confusion
Arnold et al., 2020 United Kingdom Prospective Cohort Diagnostic and Severity markers of COVID-19 to Enable Rapid triage (DISCOVER) study (Bristol) N = 110 (all previously hospitalized cases)
  • ●

    Age Range: ≥18

  • ●

    Median Age*: 47 (32–61)

  • ●

    Median Age**: 57 (48–67)

  • ●

    Median Age***: 62 (54–71)

  • ●

    Sex*(%F/%M): 38.2/61.8

*mild cases**moderate cases***severe cases		 Median 90 (80–97) days following onset of symptoms RT-PCR or clinico-radiological diagnosis Objective assessment via laboratory testing (inflammatory parameters), SF-36 (quality of life), as well as subjective self-report via questionnaire
  • ●

    39% (43/110) reported fatigue

  • ●

    SF-36 scores demonstrated a reduction in reported health status across all domains as compared with age-matched population norms

  • ●

    1.8% (2/110) exhibited CRP levels > 10 mg/L
  • ●

    Physical SF-36 scores were significantly lower in patients with severe COVID-19 compared with mild/moderate
Augustin et al., 2021 Germany Prospective Cohort University Hospital Cologne (recruited through public media) N = 353
  • ●

    Age Range: age* ≥18

  • ●

    Median Age*: 43 (31–54)

  • ●

    Sex* (%F/%M): 53.5/46.5

*pertains to initial cohort of 958 COVID-19 convalescent individuals, which were not all followed up		 Median 6.8 (6–8) months following onset of symptoms RT-PCR Subjective self-report via systematic questionnaires and evaluation by physician
  • ●

    14.7% (52/353) of individuals reported fatigue
  • ●

    Anosmia and diarrhea during acute COVID-19, as well as a lower baseline level of SARS-CoV-2 IgG, were associated with higher risk of developing long-term symptoms

  • ●

    Male sex was associated with a lower risk of post-COVID syndrome

  • ●

    Female patients and individuals with a prior diagnosis of depression or anxiety had a higher risk of suffering from fatigue
Breton et al., 2021 USA Retrospective Cohort Residents of greater New York City Tristate Region N = 41 cases (including 8 previously hospitalized)
  • ●

    Age Range: 24–73

  • ●

    Median Age: 45

  • ●

    Sex (%F/%M): 36.6/63.4

 Mean 6.1 months following COVID-19 infection RT-PCR Objective assessment via laboratory testing (flow cytometry; intracellular cytokine staining)
  • ●

    Antigen-specific CD4 + T cells expressing IL-2, IFN-γ, and TNF-α were markedly increased in COVID-19–recovered individuals as compared with healthy donors
Buonsenso et al., 2021 Italy Cross-sectional Fondazione Policlinico Universitario Agostino Gemelli (part of ISARIC) N = 68 children (including 6 previously hospitalized and 3 in pediatric ICU)
  • ●

    Age Range: ≤18

  • ●

    Mean Age: 11 ± 4.4

  • ●

    Sex (%F/%M): 48.1 /51.9

 Mean 162.5 ± 113.7 days following diagnosis RT-PCR Subjective self-report via phone interview or outpatient assessment
  • ●

    13.2% (9/68) of individuals reported more fatigue compared to before COVID-19 diagnosis

  • ●

    11.8% (8/68) of individuals reported lack of concentration
Cirulli et al., 2020a USA Prospective Cohort Helix DNA Discovery Project and the Healthy NevadaProject N = 357 (including 9 previously hospitalized cases)
  • ●

    Age Range*: ≥18

  • ●

    Median Age*: 56

  • ●

    Sex* (%F/%M): 64.1/35.9

*pertains to entire cohort, including both COVID-19 positive and negative		 90 days following onset of symptoms Laboratory test Subjective self-report via online questionnaires
  • ●

    7.96% (9/113) reported fatigue

  • ●

    7.50% (9/120) reported decreased alertness

  • ●

    8.20% (10/122) reported memory loss

  • ●

    12.61% (15/119) reported difficulty concentrating
  • ●

    Initial dyspnea and a large number of initial symptoms were associated with long COVID symptoms after 30 days

  • ●

    Individuals who were more ill at the onset of symptoms are at higher risk of long-term symptoms

  • ●

    There was an association of between anxiety disorders and autoimmune/rheumatologic disorders and long-term symptoms

  • ●

    Female patients were more likely to have long-term symptoms
Darley et al., 2021a Australia Prospective Cohort St. Vincent’s Hospital Sydney (ADAPT study) N = 99
  • ●

    Age Range: ≥18

  • ●

    Median Age: 47 (35–58)

  • ●

    Sex (%F/%M): 39/61

 Median 240 (227–256) days following infection RT-PCR Objective assessment via SPHERE-34 (fatigue, cognitive function)
  • ●

    23% (15/65) reported fatigue

  • ●

    27% (26/97) reported poor memory a good part of, or most of the time

  • ●

    33% (32/97) patients reported poor concentration a good part of, or most of the time

  • ●

    18% (17/97) patients reported feeling lost for words a good part of, or most of the time
  • ●

    Female sex and hospitalization for acute COVID-19 were independently associated with persistent symptoms at 8-months
Elkan et al., 2021a Israel Retrospective Case-control Shamir (Assaf Harofeh) Medical Center N = 66 (all previously hospitalized cases)
  • ●

    Age Range: ≥18

  • ●

    Median Age: 58.5 (49.8–68.3)

  • ●

    Sex (%F/%M): 56.1/43.9

 Median 9 (6–9) months following discharge RT-PCR Objective assessment via RAND-36 (quality of life), as well as subjective self-report
  • ●

    50% (33/66) reported fatigue

  • ●

    ∼17% reported memory impairment and concentration impairment (exact proportion not provided)

  • ●

    RAND-36 emotional role median score: 100 (0–100)

  • ●

    RAND-36 social functioning median score: 87.5 (50–100)

  • ●

    RAND-36 vitality median score: 57.5 (30–76.2)
  • ●

    A greater proportion of patients with more severe acute disease reported persistent symptoms
Evans et al., 2021a United Kingdom Prospective Cohort 53 National Health Service hospitals (PHOSP-COVID study) N = 1077 (all previously hospitalized cases)
  • ●

    Age Range: ≥18

  • ●

    Mean Age: 58 ± 13

  • ●

    Sex (%F/%M): 35.7/64.3

 Median 159 (120–189) days following discharge RT-PCR or clinician-diagnosed Objective assessment via FACIT (fatigue), MoCA (cognitive function), EQ-5D-5L, WG-SS (quality of life and functioning), laboratory testing (serology), and subjective self-report via research visit and clinical follow-up questionnaire
  • ●

    56.2% (429/763), reported significantly worse fatigue compared to pre-COVID-19 (mean FACIT score 16.8 ± 13.2)

  • ●

    16.9% (150/888) reported cognitive impairment, operationalized as a MoCA score < 23

  • ●

    11.2% (90/804) exhibited persistent systemic inflammation (CRP > 10 mg/L)

  • ●

    13.1% (97/738) exhibited elevated D-dimer levels (≥500 ng/ml)

  • ●

    19.3% (124/641) experienced a health-related change in their occupational status

  • ●

    Mean EQ5D-5L VAS changed from 81 ± 17 (pre-COVID-19) to 72 ± 20 (post-COVID-19)

  • ●

    1/5 of the population reached the threshold for a new disability with at least one domain coded as “a lot of difficulty” or “cannot do it all” on the WG-SS
  • ●

    Female sex, middle-age, white ethnicity, two or more comorbidities, and more severe acute illness were associated with failure to recover (persistent symptoms)
Evlice et al., 2021 Turkey Retrospective Cohort Hospital in Turkey N = 266 (all previously hospitalized cases, including 11 in ICU)
  • ●

    Age Range: ≥18

  • ●

    Mean Age: 56.96 ± 16.62

  • ●

    Sex (%F/%M): 51.5/48.5

 Mean 99.80 ± 26.16 days following discharge RT-PCR or CT Subjective self-report via telephone survey
  • ●

    4.9% (13/266) reported fatigue
  • ●

    Persistent symptoms were observed at a higher rate in cases with comorbidity

  • ●

    Statistically significant relationship between high admission CRP level and presence of persistent symptoms
Fernández-de-Las-Peñas (1) et al., 2021 Spain Retrospective Cohort Four public hospitals in Madrid N = 1142 (all previously hospitalized cases)
  • ●

    Age Range: N/A

  • ●

    Mean Age: 61 ± 17

  • ●

    Sex (%F/%M): 47.5/52.5

 Mean 7.0 ± 0.6 months following discharge RT-PCR Subjective self-report via systematic telephone interview conducted by trained researchers
  • ●

    60.8% (695/1142) reported fatigue

  • ●

    19.0% (217/1142) reported memory loss

  • ●

    9.6% (110/1142) reported brain fog

  • ●

    8.1% (93/1142) reported attention disorders
  • ●

    Women reported fatigue more frequently than men

  • ●

    Female sex, number of days at hospital, previous comorbidities, and number of symptoms at hospital admission were associated with more long COVID symptoms
Fernández-de-Las-Peñas (2) et al., 2021 Spain Retrospective Cohort Three public hospitals in Madrid N = 1950 (all previously hospitalized cases, including 129 in the ICU)
  • ●

    Age Range: N/A

  • ●

    Mean Age: 61 ± 16

  • ●

    Sex (%F/%M): 46.9/53.1

 Mean 11.2 ± 0.5 months after hospital discharge RT-PCR and radiological findings Self-report via systematic telephone interview conducted by trained healthcare professionals
  • ●

    61.4% (1206/1950) reported fatigue

  • ●

    16% (6/38) reported no longer being able to participate in a sport or recreational activity because of their ongoing symptoms
Ferrucci et al., 2021 Italy Prospective Cohort Non-intensive COVID units of the ASST Santi Paolo e Carlo hospitals N = 38 (all previously hospitalized cases in non-intensive wards)
  • ●

    Age Range: 22–74

  • ●

    Mean Age: 53.45 ± 12.64

  • ●

    Sex (%F/%M): 28.9/71.1

 Mean 4.43 ± 1.22 months following discharge RT-PCR Objectively assessed via MoCA (cognitive function), BRB-NT (neurological battery of tests for cognition), SSD (fatigue)
  • ●

    50% (15/30) reported a moderate to severe increase in fatigability

  • ●

    60.5% (23/38) obtained scores below Italian normative cut-offs in at least one task of the BRB-NT [exhibited cognitive abnormalities]

  • ●

    42% (16/38) demonstrated slowing of cognitive processing speed, as evidenced by low SDMT scores

  • ●

    20% (8/38) demonstrated long-term verbal and spatial memory dysfunctions

  • ●

    26.7% (8/30) reported a moderate to severe increase in forgetfulness and lack of concentration

  • ●

    23.3% (7/30) reported a moderate to severe increase in time needed to perform tasks such as reading/writing documents

  • ●

    20% (6/30) reported moderate to severe difficulties in learning new skills or procedures
  • ●

    Females more frequently reported a subjective decline in cognitive performance following hospitalization

  • ●

    Participants aged ≥ 55 obtained lower scores in all measures of verbal memory, when compared to those aged < 55

  • ●

    ARDS at hospitalization was associated with worse verbal memory performance and worse delayed verbal recall performance
Fortini et al., 2021 Italy Prospective Cohort San Giovanni di Dio Hospital N = 59 (all previously hospitalized cases in non-intensive ward)
  • ●

    Age Range: N/A

  • ●

    Mean Age: 68.2 ± 12.8

  • ●

    Sex (%F/%M): 47.5/52.5

 Median 123 (116–145) days following discharge RT-PCR Objective assessment via laboratory testing (inflammatory parameters), as well as subjective self-report via self-administered questionnaire
  • ●

    42.4% (25/59) reported fatigue

  • ●

    13.6% (8/59) reported confusion

  • ●

    32.2% (19/59) exhibited elevated D-dimer levels

  • ●

    32.2% (19.59) exhibited elevated IL-6 levels
  • ●

    No significant correlation between the values of inflammatory parameters and patient-reported symptoms was detected by the multivariable logistic regression analysis
Froidure et al., 2021 Belgium Prospective Cohort Hospital in Belgium N = 126 patients (all previously hospitalized and/or ICU cases)
  • ●

    Age Range: N/A

  • ●

    Median Age: 60 (53–68)

  • ●

    Sex (%F/%M): 59/41

 Median 95 (86–107) days following infection RT-PCR and lung HRTC or chest X-ray Subjective self-report via clinical assessment
  • ●

    25% (32/126) reported ongoing fatigue
Frontera et al., 2021 USA Prospective Cohort Four NYC area hospitals N = 382 (all previously hospitalized cases including 196 neurologic cases, 67 of which were admitted to the ICU, and 186 cases without neurological disorders during hospitalization, 54 of which were admitted to the ICU)
  • ●

    Age Range*: ≥18

  • ●

    Median Age*: 68 (55–77)

  • ●

    Sex* (%F/%M): 65/35

  • ●

    Age Range**: ≥18

  • ●

    Median Age**: 69 (57–78)

  • ●

    Sex** (%F/%M): 65/35

*neurologic COVID-19 cohort**non-neurologic COVID-19 cohort		 Median 6.7 (6.5–6.8) months following onset of symptoms RT-PCR Objective assessment via MoCA (cognitive function), Barthel index (functional impairment), as well as subjective self-report via telephone questionnaire
  • ●

    36.0% (98/272) reported worse than average fatigue, operationalized as T-score > 50

  • ●

    49.3% (106/215) exhibited cognitive impairment, operationalized as MoCA score < 18

  • ●

    52.6% (81/154) of those who were working premorbidly were able to return to work

  • ●

    44.11% (134/304) could not independently perform some basic activities of daily living, operationalized as Barthel index < 100
  • ●

    Patients diagnosed with new neurological complications during hospitalization for COVID-19 had a 2-fold increased odds of worse 6-month functional outcome (as measured by the modified Rankin Score)
García-Abellán et al., 2021a Spain Prospective Cohort Hospital General Universitario de Elche N = 116 (all previously hospitalized cases, including 15 previously admitted to ICU)
  • ●

    Age Range: N/A

  • ●

    Median Age*: 66 (57–76)

  • ●

    Sex* (%F/%M): 50/50

*pertains to patients reporting symptoms at 6-month follow-up		 6 months following discharge RT-PCR and serology Objective assessment via laboratory testing (immunological parameters), and subjective self-report via CSQ (fatigue) during clinical visit
  • ●

    10.3% (12/116) reported fatigue

  • ●

    Median serum IL-6: 3 (1.8–5.1) pg/mL

  • ●

    Median serum CRP: 1 (0.4–5.1) mg/L

  • ●

    Median serum D-dimer: 0.4 (0.2–0.7) mcg/mL
  • ●

    Patients with the highest CSQ scores showed lower CRP levels on admission and weaker initial antibody response

  • ●

    Female sex predicted persistent symptoms

  • ●

    Post-COVID syndrome was associated with additional distinctive innate and adaptive immune traits, consisting of a weaker initial inflammatory response, evidenced by lower baseline levels of CRP and ferritin

  • ●

    Patients with mid-term lasting symptoms [follow up at 2 months] showed persistent residual inflammation
Garrigues et al., 2020 France Retrospective Cohort Beaujon Hospital, COVID-19 Unit N = 120 (all previously hospitalized cases, including 24 in ICU that underwent mechanical ventilation)
  • ●

    Age Range: N/A

  • ●

    Mean Age: 63.2 ± 15.7

  • ●

    Sex (%F/%M): 37.5/62.5

 Mean 110.9 days ± 11.1 following hospital admission RT-PCR and/or chest CT Objective assessment via EQ-5D-5L (quality of life), as well as subjective self-report via telephone questionnaire conducted by trained physicians
  • ●

    55.0% (66/120) reported fatigue

  • ●

    34.2% (41/120) reported loss of memory

  • ●

    26.7% (32/120) reported attention disorders

  • ●

    67.9% (38/56) of those who worked before hospitalization returned to work

  • ●

    71.8 % (28/39) of those who practiced sport regularly before hospitalization resumed sport

  • ●

    EQ-VAS mean score of 70.3 ± 21.5, and EQ-5D index mean score of 0.86 ± 0.20
Ghosn et al., 2021 France Prospective Cohort Institut National de la Santé Et de la Recherche Médicale N = 1137 (all previously hospitalized cases, including 288 in ICU)
  • ●

    Age Range: N/A

  • ●

    Median Age: 61 (51–71)

  • ●

    Sex (%F/%M): 37/63

 3 and 6 (median 194 [188–205] days) months following hospital admission RT-PCR Subjective self-report via physician visit
  • ●

    57% (538/944) reported fatigue at month 3

  • ●

    38% (404/1063) reported fatigue at month 6

  • ●

    29% (125/431) of those who had a professional occupation had not returned to work at 6 months
  • ●

    Presence of 3 + symptoms at 6-month follow-up was associated with female sex and having 3 + symptoms at admission
González et al., 2021 Spain Prospective Cohort Hospital Universitary Arnau de Vilanova N = 62 (all previously ICU cases)
  • ●

    Age Range: ≥18

  • ●

    Median Age: 60 (48–65)

  • ●

    Sex (%F/%M): 25.8/74.2

 3 months following discharge RT-PCR Objective assessment via SF-12 (quality of life), as well as subjective self-report
  • ●

    29.5% (16/62) reported muscular fatigue

  • ●

    SF-12 Physical score median: 45.9 (36.1–54.4)

  • ●

    SF-12 Mental score median: 55.8 (40.6–58.0)

  • ●

    SF-12 showed mean scores that were substantially lower than those of healthy people, those with other chronic diseases, and healthy Spanish people
González-Hermosillo et al., 2021 Mexico Prospective Cohort Instituto Nacional de Cardiología Ignacio Chávez N = 130 (all previously hospitalized cases)
  • ●

    Age Range: ≥18

  • ●

    Mean Age: 51 ± 14

  • ●

    Sex (%F/%M): 36.4/63.6

 3 and 6 (mean 270 ± 32 days) months following discharge RT-PCR Subjective self-report via telephone questionnaire based on ME/CFS International Consensus Criteria
  • ●

    53% (69/130) reported fatigue that did not exist before COVID-19 at 3-month follow-up (40.5% [28/130] females reported fatigue compared to 27.8% [17/130] without fatigue)

  • ●

    46.9% (61/130) reported fatigue that did not exist before COVID-19 at 6-month follow-up

  • ●

    23% (30/130) reported concentration impairment that did not exist before COVID-19 at 3-month follow-up

  • ●

    45.4% (59/130) reported short-term memory loss that did not exist before COVID-19 at 3-month follow-up
  • ●

    Patients with fatigue at 3-month follow-up were older compared with those without fatigue, and had a longer length of hospital stay

  • ●

    Age 40–50 years old was associated with fatigue

  • ●

    There was a significantly higher prevalence of persisting symptoms in those with fatigue
Havervall et al., 2021 Sweden Prospective Cohort Danderyd Hospital N = 1395 health care professionals (mild cases, hospitalization status not specified)
  • ●

    Age Range: ≥18

  • ●

    Median Age: 43 (33–52)

  • ●

    Sex (%F/%M): 83/17

 8 months following onset of symptoms Serology Objective assessment via Sheehan Disability Scale (functional outcomes), as well as subjective self-report via smartphone app questionnaire
  • ●

    6.8% (22/323) reported fatigue after 4 months, and 4.0% (13/323) reported fatigue after 8 months

  • ●

    1.9% (6/323) reported concentration impairment after 4 months, and 0.6% (2/323) reported concentration impairment after 8 months

  • ●

    1.2% (4/323) reported memory impairment after 4 months, and 0.3% (1/323) reported memory impairment after 8 months

  • ●

    8% reported that long-term symptoms moderately to markedly disrupted work life

  • ●

    15% reported that long-term symptoms moderately to markedly disrupted social life

  • ●

    12% long-term symptoms moderately to markedly disrupted home life

  • ●

    11% long-term symptoms moderately to markedly disruption in any Sheehan Disability Scale category
Huang et al., 2021 China Ambidirectional Cohort Jin Yin-tan Hospital N = 1733 patients (all previously hospitalized cases, including 76 previously admitted to ICU)
  • ●

    Age Range: ≥18

  • ●

    Median Age: 57.0 (47.0–65.0)

  • ●

    Sex (%F/%M): 48/52

 Median 186 (175–199) days following onset of symptoms Laboratory testing Objective assessment viaEQ-5D-3L (quality of life), as well as subjective self-report via questionnaire
  • ●

    63% (1038/1655) reported fatigue/muscle weakness

  • ●

    Median quality of life score was 80/100 (70–90), with 7% (113/1622) reporting mobility problems, 1% (11/1622) reporting personal care problems, 2% (25/1611) reporting problems with usual activity, and 27% (431/1616) reporting pain or discomfort
  • ●

    Increased age and severity of acute disease were positively associated with fatigue and muscle weakness

  • ●

    Women reported a higher percentage of symptoms at follow-up
Jacobson et al., 2021 USA Prospective Cohort Patients from enrolled clinical trials at Stanford University N = 118 participants (including 22 previously hospitalized cases, of which 11 were previously admitted to ICU)
  • ●

    Age Range: N/A

  • ●

    Mean Age: 43.3 ± 14.4

  • ●

    Sex (%F/%M): 46.6/53.4

 Mean 119.3 ± 33.0 days following diagnosis RT-PCR Objective assessment via WPAI (functional outcomes), as well as subjective self-report via questionnaire
  • ●

    30.5% (36/118) reported fatigue overall, including 36.4% (8/22) of previously hospitalized patients and 29.2% (28/96) of non-hospitalized patients

  • ●

    17.0% (20/118) reported memory problems overall, including 22.7% (5/22) of previously hospitalized patients and 15.6% (15/96) of non-hospitalized patients

  • ●

    68.47% (80/117) overall reported being employed, including 72.7% (16/22) of previously hospitalized patients and 67.4% (64/95) of non-hospitalized patients

  • ●

    11.5% (9/78) overall reported missed work due to health, including 13.3% (2/15) of previously hospitalized patients and 11.1% (7/63) of non-hospitalized patients

  • ●

    38.9% (28/72) overall reported any work impairment due to health, including 58.3% (7/12) of previously hospitalized patients and 35.0% (21/60) of non-hospitalized patients

  • ●

    50.9% (54/106) overall reported any activity impairment due to health, including 73.7% (14/19) of previously hospitalized patients and 46.0% (40/87) of non-hospitalized patients
  • ●

    Older age and hospitalization were associated with higher odds of any activity impairment

  • ●

    Presence of fatigue was associated with long-term activity impairment (in multivariate analysis)
Johnsen et al., 2021 Denmark Cross-sectional Copenhagen University Hospital at Bispebjerg N = 57 (34 previously hospitalized cases and 34 non-hospitalized cases)
  • ●

    Age Range: N/A

  • ●

    Mean Age: 51 ± 13

  • ●

    Sex (%F/%M): 51/49

 3 months following discharge/resolution of acute disease RT-PCR Objective assessment via WPAI, PCFS (functional outcomes), EQ-5D-5L (quality of life), and CFQ, SCIP-D, and TMT-B (cognitive function)
  • ●

    58% (26/45) demonstrated clinically significant cognitive impairment (66% [19/29] of previously hospitalized, 44% [8/19] non-hospitalized)

  • ●

    Median EQ-VAS: 70 (55,81)

  • ●

    Percent work time missed due to health: 0 (0,24)

  • ●

    Percent impairment while working due to health: 20 (9, 45)

  • ●

    Percent overall work impairment due to health: 23 (6, 66)

  • ●

    Percent activity impairment due to health: 30 (10,60)
Kashif et al., 2021a Pakistan Prospective Cohort Hameed Latif Hospital N = 242 (including hospitalized cases and non-hospitalized cases who sought healthcare at hospital)
  • ●

    Age Range: 18–65

  • ●

    Mean Age: 35.64 ± 12.57

  • ●

    Sex (%F/%M): 30.6/69.4

 3 months following discharge or onset of symptoms RT-PCR Subjective self-report via telephone interview
  • ●

    41.7% (101/242) reported fatigue
  • ●

    Prolonged symptoms months after recovery from mild COVID-19 were associated with female sex
Klein et al., 2021 Israel Retrospective Cohort Israeli residents recruited through social media and word of mouth N = 103 (all mild symptomatic cases; asymptomatic excluded, hospitalization status not specified)
  • ●

    Age Range: ≥18

  • ●

    Mean Age: 35 ± 12

  • ●

    Sex (%F/%M): 40/60

 6 months following onset of symptoms RT-PCR Subjective self-report via telephone questionnaire
  • ●

    22% (23/103) reported fatigue

  • ●

    6% (6/103) reported memory disorders

  • ●

    1% (1/103) reported concentration disorders
Latronico et al., 2021a Italy Prospective Cohort 3 ICUs of the Spedali Civili University Hospital N = 55 (all cases which were previously admitted to ICU with ARDS)
  • ●

    Age Range: ≥18

  • ●

    Median Age: 59 (54–64)

  • ●

    Sex*(%F/%M): 17/83

*pertains to a larger cohort of 163 admitted to ICU, which were not all followed up		 3 and 6 months following discharge RT-PCR Objective assessment via FSS (fatigue), PICS, MoCA (cognitive function), SF-36 (quality of life), Barthel Index (functional outcomes)
  • ●

    36% (20/55) reported severe fatigue, operationalized as FSS score 36 + at 3 months

  • ●

    36% (16/45) reported severe fatigue, operationalized as FSS score 36 + at 6 months

  • ●

    22% (12/55) exhibited mild-severe cognitive impairment according to MoCA at 3 months

  • ●

    26% (10/38) exhibited mild cognitive impairment according to MoCA at 6 months

  • ●

    33% (18/55) of patients exhibited mild role limitations according to SF-36

  • ●

    65% (36/55) had returned to work with the same pre-COVID-19 employment status, 5% (3/55) with worsening employment status (fewer hours worked per week), and 32% (18/55) had not returned to work

  • ●

    5% (3/55) reported significant derangement in social function, operationalized as > 2 SD on SF-36 domain at 3 months, and 3% (1/36) at 6 months
Leth et al., 2021 Denmark Prospective Cohort Department of Infectious Diseases, Aarhus University Hospital N = 49 (all previously hospitalized cases, including 6 previously admitted to ICU)
  • ●

    Age Range: ≥18

  • ●

    Median Age: 58 (48–73)

  • ●

    Sex (%F/%M): 57/43

 Median 128 (98–148) days following discharge RT-PCR Objective assessment via OMC (cognitive function), as well as subjective self-report via in person or telephonequestionnaire
  • ●

    63% (31/49) reported fatigue

  • ●

    45% (22/49) reported difficulty concentrating

  • ●

    11% (4/38) demonstrated impaired cognitive function, operationalized as an OMC score of ≤ 24
  • ●

    Significantly reduced OR of challenged concentration if the patient was a current or previous smoker
Liang et al., 2020 China Prospective Cohort Wuhan Union Hospital N = 76 (all previously hospitalized, including 65 healthcare worker cases, and 7 previously admitted to ICU)
  • ●

    Age Range: 24–76

  • ●

    Mean Age: 41.3 ± 13.8

  • ●

    Sex (%F/%M): 72.4/27.6

 3 months following discharge RT-PCR Subjective self-report via questionnaire
  • ●

    59% (45/76) reported fatigue
  • ●

    Serum troponin-I levels during acute illness showed high correlation with fatigue after hospital discharge
Liyanage-Don et al., 2021 USA Prospective Cohort 2 Columbia University Hospitals N = 153 (all previously hospitalized cases)
  • ●

    Age Range: ≥18

  • ●

    Mean Age: 54.5 ± 16.7

  • ●

    Sex (%F/%M): 39.9/60.1

 Median 3.7 (2.6–5.7) months following discharge RT-PCR Subjective self-report via online or telephone questionnaire
  • ●

    20.3% (31/153) reported fatigue
  • ●

    Patients with PTSD and/or depression were more likely to report fatigue
Logue et al., 2021 USA Prospective Cohort University of Washington N = 177 (145 previously outpatient cases, 16 previously hospitalized)
  • ●

    Age Range: 18–94

  • ●

    Mean Age: 48.0

  • ●

    Sex (%F/%M): 57.1/42.9

 Median 169 (range 31–300) days following onset of acute COVID-19 RT-PCR Subjective self-report via electronic questionnaire
  • ●

    13.6% (24/177) reported fatigue

  • ●

    2.3% (4/177) reported brain fog

  • ●

    29.9% (53/177) reported worsened health-related quality of life compared with baseline measurements
Mattioli et al., 2021 Italy Prospective Cohort Unit of Occupational Health, General University Hospital of Brescia N = 150 (120 healthcare workers cases, including 2 with previous respiratory failure requiring hospitalization) and 30 healthcare worker healthy controls)
  • ●

    Age Range: N/A

  • ●

    Median Age*: 47.86 (26–65)

  • ●

    Sex* (%F/%M): 75/25

*pertains to cases		 4 months following first COVID-19 diagnosis RT-PCR Objective assessment via MMSE (cognitive function), as well as subjective self-report via clinical diagnostic assessment (including questionnaire)
  • ●

    15% (18/120) reported fatigue

  • ●

    11.6% (14/120) reported attention difficulties

  • ●

    6.6% (8/120) reported memory difficulties

  • ●

    MMSE results were normal in both cases (median 29; 27–30), and controls (median 29; 28–30), operationalized as MMSE scores 24+
Mazza et al., 2021 Italy Prospective Cohort IRCCS San Raffaele Hospital N = 226 (including 177 hospitalized cases and 49 cases treated at home)
  • ●

    Age Range: 26–87

  • ●

    Mean Age: 58.5 ± 12.8

  • ●

    Sex (%F/%M): 34/66

 Mean 90.1 ± 13.4 days following discharge RT-PCR Objective assessment via BACS (cognitive function), as well as subjective self-report via questionnaire
  • ●

    8% (11/130) scored poorly in the domain of verbal memory (10% [7/70] males; 9% [4/44] females)

  • ●

    30% (39/130) scored poorly in the domain of verbal fluency (32% [22/130] males; 33% [17/130] females)

  • ●

    24% (30/126) scored poorly in the domain of working memory (15% [11/73] males; 37% [19/51] females)

  • ●

    33% (43/130) scored poorly in the domain of attention and Information processing (38% [29/76] males; 27% [14/52] females)

  • ●

    55% (72/130) scored poorly in the domain of psychomotor coordination (59% [43/73] males; 56% [29/52] females)

  • ●

    46% (60/130) scored poorly in the domain of executive functions (46% [32/70] males; 56% [28/50] females)
  • ●

    Baseline systemic inflammation predicted cognitive impairment at follow-up
Mei et al., 2021 China Prospective Cohort Wuhan No.1 Hospital, Wuchang Hospital, Zhongshang Hospital, and Hubei Province Hospital N = 3,677 (all previously hospitalized cases)
  • ●

    Age Range: 10–98

  • ●

    Median Age: 59 (47–68)

  • ●

    Sex (%F/%M): 54.1/45.9

 Median 144 (135–157) days following discharge RT-PCR Subjective self-report during clinical follow-up
  • ●

    1.5% (55/3677) reported fatigue

  • ●

    1.7% (64/3677) reported reduction in physical strength

  • ●

    1.3% (49/3677) reported headache/ dizziness/poor memory

  • ●

    0.03% (1/3677) reported confusion
  • ●

    The majority of deaths during follow-up were male

  • ●

    The risk of the development of physical abnormalities was independent of age and sex

  • ●

    The incidence of post-COVID-19 sequelae of elderly COVID-19 survivors (age ≥ 60 years) was slightly increased compared to that of young survivors (age < 60)
Menges et al., 2021a Switzerland Cross-sectional General Population of Zurich (Zurich SARS-CoV-2 Cohort Study) N = 431 (including 81 previously hospitalized cases, of which 10 were in ICU, and 350 non-hospitalized cases)
  • ●

    Age Range: ≥18

  • ●

    Median Age: 47 (33–58)

  • ●

    Sex (%F/%M): 49.7/50.3

 Median 220 (181–232) days following diagnosis RT-PCR Objective assessment via FAS (fatigue), EQ-5D-5L (quality of life), as well as subjective self-report via online survey conducted via REDcap
  • ●

    54.7% (233/426) reported fatigue measured by FAS (59.2% [125/211] of females and 50.2% [108/215] males; 55.9% [195/349] non-hospitalized and 49.4% [38/77] hospitalized)

  • ●

    Median FAS score: 22 (19–25)

  • ●

    53% (225/431) reported problems in at least one EQ-5D-5L dimension

  • ●

    0.5% (2/430) reported problems with self-care

  • ●

    10.5% (45/230) reported problems with daily activity

  • ●

    Median EQ-5D-5L: 0.89 (0.85–1.00)
  • ●

    Younger individuals and females more frequently reported symptoms of fatigue

  • ●

    A higher proportion of female participants and initially hospitalized individuals reported not having fully recovered

  • ●

    Severe to very severe acute symptoms and the presence of co-morbidities were associated with non-recovery
Miskowiak et al., 2021 Denmark Prospective Cohort Bispebjerg Hospital (IMPACT-COVID study) N = 129 (29 previously hospitalized cases, and 100 matched healthy controls)
  • ●

    Age Range: N/A

  • ●

    Mean Age (SD): 56.2 ± 10.6

  • ●

    Sex (%F/%M): 41/59

 3–4 months following hospital discharge RT-PCR and serology Objective assessment via SCIP-D, TMT-B, and CFQ (cognitive function), and EQ-5D-5L (quality of life), as well as subjective self-report via questionnaire
  • ●

    65% (19/29) of patients exhibited clinically-significant cognitive impairment, operationalized as SCIP total scores ≥ 0.5 SD below the demographically adjusted predicted scores

  • ●

    83% (19/23) of patients reported subjective cognitive difficulties in daily life, operationalized as CFQ scores ≥ 43, and subjective cognitive complaints (CFQ Total scores) correlated significantly with objectively measured global cognitive impairments

  • ●

    0% reported work time missed due to health (absenteeism)

  • ●

    10% reported impairment while working due to health (presenteeism)

  • ●

    10% reported overall work impairment due to health

  • ●

    20% reported activity impairment due to health
  • ●

    More global cognitive impairment and executive dysfunction both correlated with greater disability within EQ-5D ‘usual activity’ and ‘anxiety and depression

  • ●

    Greater objective cognitive impairments were associated with more subjective cognitive difficulties, absenteeism, and poorer quality of life

  • ●

    Poorer pulmonary function and more respiratory symptoms after recovery were associated with more cognitive impairments
Miyazato et al., 2021 Japan Cross-sectional Disease Control and Prevention Center and National Center for Global Health and Medicine N = 63 (all previously hospitalized cases)
  • ●

    Age Range: N/A

  • ●

    Mean Age: 48.1 ± 18.5

  • ●

    Sex (%F/%M): 33.3/66.7

 Mean 129 ± 21 days following onset of symptoms RT-PCR Subjective self-report via structured telephone interview conducted by the investigators
  • ●

    9.5% (6/63) reported fatigue which was not chronic before onset of COVID-19
Morin et al., 2021 France Prospective Cohort Bicêtre Hospital (Paris-Saclay University hospitals) N = 478 (all previously hospitalized cases, including 142 previously admitted to ICU)
  • ●

    Age Range: ≥18

  • ●

    Mean Age: 60.9 ± 16

  • ●

    Sex (%F/%M): 42.1/57.9

 Median 113 (94–128) days following discharge RT-PCR and/or CT scan Objective assessment via Q3PC, MoCA, d-2R (cognitive function), MFI (fatigue) during in-clinic/ ambulatory assessment, as well as subjective self-report via telephone questionnaire
  • ●

    31.1% (134/431) reported fatigue

  • ●

    17.5% (73/416) reported memory difficulties

  • ●

    10.1% (42/415) reported mental slowness

  • ●

    10.0% (41/412) reported concentration problems

  • ●

    20.7% (86/416) reported at least 1 cognitive symptom

  • ●

    During ambulatory assessment, 49.7% (79/159) reported a cognitive complaint (impaired McNair score), and 38.4% (61/159) reported cognitive impairment (impaired MoCA or d-2R scores)
Munblit et al., 2021a Russia Prospective Cohort Sechenov University Hospital Network N = 2649 (all previously hospitalized cases)
  • ●

    Age Range: ≥18

  • ●

    Median Age: 56 (46–66)

  • ●

    Sex (%F/%M): 51.1/49.9

 Median 217.5 (200.4–235.5) days following discharge RT-PCR or clinically diagnosed Objective assessment via EQ-5D-5L (quality of life), as well as subjective self-report via telephone interview performed by medical students using
  • ●

    21.2% (551/2599) reported fatigue

  • ●

    9.1% (237/2597) reported forgetfulness

  • ●

    Participants reported lower scores (poorer health state) at follow up (median 80 [65–90]) compared to pre-COVID (median 85 [70–95]), p < 0.001)

  • ●

    Significant worsening of health was found across all symptom categories, whereas no statistically significant reduction in health state was found among patients reporting no symptoms
  • ●

    Female sex was associated with chronic fatigue
O’Keefe et al., 2021a USA Cross-sectional Emory Healthcare’s Virtual Outpatient Management Clinic (VOMC) N = 198 participants discharged from outpatient telemedicine program for COVID-19(including 35 previously hospitalized cases)
  • ●

    Age Range: 18–84

  • ●

    Median Age: 44 ± 14

  • ●

    Sex (%F/%M): 74.2/25.8

 Median 119 (range 26–220) days following diagnosis RT-PCR Subjective self-report via e-mail survey
  • ●

    21.2% (42/198) reported fatigue 90–220 days after the acute COVID-19 phase

  • ●

    13.6% (27/198) reported mental fog 90–220 days after the acute COVID-19 phase
  • ●

    Moderate to severe acute COVID-19, female sex, and middle age were highly associated with persistent symptoms
Ong et al., 2021 Singapore Prospective Cohort 4 public hospitals in Singapore
  • ●

    N = 199 (175 prior cases, all of which were previously hospitalized, and 24 healthy controls)

  • ●

    Age Range: N/A

  • ●

    Median Age: 44

  • ●

    Sex (%F/%M): 24.6/75.4

 Median 181 (103–191) days following discharge RT-PCR Objective assessed via immunoassay (inflammatory parameters), as well as subjective self-report
  • ●

    1.7% (2/120) reported fatigue at 180 days follow-up

  • ●

    0.8% (1/120) reported memory loss at 180 days follow-up

  • ●

    Patients exhibited elevated levels of MIP-1β, SDF-1α, eotaxin, IL-12p70, SCF, IL-1B, IL-17A, BDNF, and VEGF, and had systemic cytokine profiles distinct from healthy controls regardless of severity of initial illness

  • ●

    The levels of inflammation-associated IL-6, IP-10, IL-18, and MCP-1 significantly decreased from day 90 to 180
  • ●

    Age > 65 years, non-Chinese ethnicity, and severity of acute infection were associated with increased likelihood of persistent symptoms

  • ●

    There were no significant differences in the levels of immune mediators between patients with different [acute] disease severity
Orrù et al., 2021 Italy Cross-sectional Individuals living in Italy (recruited through the web) N = 152 (hospitalization status not specified)
  • ●

    Age Range: ≥18

  • ●

    Mean age: N/A

  • ●

    Sex* (%F/%M): 82.05/17.95

*pertains to a larger dataset of 507, which do not all follow our inclusion criteria		 At least 3 months following positive test RT-PCR Objective assessment via EQ-5D-3L (quality of life), as well as subjective self-report via online survey
  • ●

    74.34% (113/152) reported fatigue

  • ●

    48.68% (74/152) reported cognitive impairment

  • ●

    10.53% (16/152) reported moderate-serious problems with self-care

  • ●

    68.42% (104/152) reported moderate-serious problems with daily activities
Osmanov et al., 2021a Russia Prospective Cohort Z.A. Bashlyaeva Children’s Municipal Clinical Hospital N = 518 children (all previously hospitalized cases)
  • ●

    Age Range: ≤18

  • ●

    Median Age: 10.4 (3–15.2)

  • ●

    Sex (%F/%M): 52.1/47.9

 Median 256 (223–271) days following discharge RT-PCR Subjective self-report via telephone surveyconducted by medical students
  • ●

    10.7% (53/518) reported fatigue

  • ●

    scores on wellness scale for children with 2 + persistent symptoms significantly declined when compared to before COVID-19 onset (from 90 [80–95] to 70 ([60–80])

  • ●

    Scores on wellness scale for children with 1 persistent symptom significantly declined when compared to before COVID-19 onset (from 90 [80–100]) to 82.5 [70–93.8])
  • ●

    Older age group and pre-existent allergic disease were associated with persistent symptoms
Peghin et al., 2021 Italy Prospective Cohort Udine Hospital N = 599 (442 outpatient cases, 157 previously hospitalized, including 23 in ICU)
  • ●

    Age Range: 18–94

  • ●

    Mean Age: 53 ± 15.8

  • ●

    Sex (%F/%M): 53.4/46.6

 Median 191 (172–204) days following onset of acute COVID-19 Nucleic acid amplification tests and/or clinical diagnosis Subjective self-report via telephone questionnaire administered by trained nurses
  • ●

    13.1% (78/599) reported fatigue
  • ●

    Female sex, a proportional increase in the number of symptoms at onset of COVID-19, and ICU admission were independent risk factors for post-COVID-19 syndrome

  • ●

    Persistence of fatigue was significantly associated with disease severity at onset
Pereira et al., 2021 United Kingdom Prospective Cohort Hospital in North West London N = 38 hospital staff (35 symptomatic and 3 asymptomatic cases, all not requiring hospitalization)
  • ●

    Age Range: 23–67

  • ●

    Mean Age: 43

  • ●

    Sex (%F/%M): 84/16

 7–8 months following symptom onset RT-PCR Subjective self-report via questionnaire based on NICE guidelines
  • ●

    57% (22/38) reported fatigue

  • ●

    24% (9/38) reported difficulty concentrating

  • ●

    16% (6/38) reported no longer being able to participate in a sport or recreational activity due to their ongoing symptoms
  • ●

    Those who experienced more symptoms during the acute phase were more likely to experience persistent symptoms
Petersen et al., 2021 Faroe Islands Prospective Cohort The Faroese Hospital System N = 180 (all outpatient cases)
  • ●

    Age Range: 0–93

  • ●

    Mean Age: 39.9 ± 19.4

  • ●

    Sex (%F/%M): 54.4/45.6

 Mean 125 ± 17 days following symptom onset RT-PCR Objective assessment via fatigue impact scale (fatigue)
  • ●

    23.9% (43/180) reported fatigue

  • ●

    fatigue impact scale score mean score: 1.2 ± 1.0
  • ●

    Symptoms persisted significantly more frequently in Individuals aged 50–66 years when compared with the youngest group (0–17 years)

  • ●

    Symptoms seemed to be more persistent with increasing age
Pilotto et al., 2021a Italy Prospective Cohort Spedali Civili Brescia Hospital N = 165 (all previously hospitalized non-neurological cases)
  • ●

    Age Range: N/A

  • ●

    Mean Age: 64.8 ± 12.6

  • ●

    Sex (%F/%M): 30.3/69.7

 6 months following hospitalization RT-PCR Objective assessment via MoCA (cognitive function), as well as subjective self-report via clinical follow-up checklist
  • ●

    33.9% (56/165) reported fatigue

  • ●

    31.5% (52/165) reported memory/concentration complaints

  • ●

    16.2% (17/105) exhibited cognitive impairment [assessed via MoCA during neurological examination]
  • ●

    Patients with moderate/severe COVID-19 reported higher number of symptoms at follow-up

  • ●

    Premorbid comorbidities, age at admission, and severity of COVID-19 were predictors of total number of symptoms reported at follow-up
Qu et al., 2021 China Prospective Cohort 6 Hospitals in Anhui Province and Hubei Province N = 540 (all previously hospitalized cases)
  • ●

    Age Range: 10–99

  • ●

    Median Age: 47.5 (37.0–57.0)

  • ●

    Sex (%F/%M): 50/50

 3 months following discharge RT-PCR Objective assessment via SF-36 (quality of life), as well as subjective self-report via electronic survey form
  • ●

    29.4% (159/540) reported fatigue

  • ●

    15.4% (83/540) had poor physical component summary scores

  • ●

    32.6% (176/540) had poor mental component summary scores

  • ●

    except for the general health dimension, scores on all other dimensions of SF-36 were significantly lower than Chinese norm

  • ●

    female patients presented with significantly lower scores of all dimensions of SF-36
  • ●

    Female sex, older age, and the presence of physical symptoms after discharge [including fatigue] were risk factors for health-related quality of life scores

  • ●

    Female patients presented with significantly lower scores of all dimensions of SF-36
Rass et al., 2021 Austria Prospective Cohort Department of Internal Medicine II, Medical University of Innsbruck, Zams, and Muenster N = 135 (31 cases previously admitted to ICU, 72 previously admitted to ward, 32 previously received mild outpatient care)
  • ●

    Age Range: 19–87

  • ●

    Median Age: 56 (48–68)

  • ●

    Sex (%F/%M): 39/61

 Median 102 (91–110) days following onset of symptoms RT-PCR Objective assessment via MoCA (cognitive function), SF-36-v2 (quality of life), GOSE and mRS (functional outcome), as well as subjective self-report via clinical follow-up
  • ●

    27% (35/130) reported persistent fatigue (50% [15/30] ICU, 17% [12/71] with ward COVID-19, and 26% [8/31] with outpatient COVID-19)

  • ●

    25% (30/120) reported forgetfulness, trouble concentrating, or difficulty thinking (26% [7/27] ICU, 24% [16/67] with ward COVID-19, and 29% [7/32] with outpatient COVID-19)

  • ●

    23% (29/126) scored below 26 on the MoCA (29% [8/28] ICU, 20% [20/67] with ward COVID-19, and 3% [1/32] with outpatient COVID-19)

  • ●

    Median MoCA score: 28 (26–29) (28 [25–28]) ICU, 28 [25–29] for ward COVID-19, and 29 [28–30] for outpatient COVID-19)

  • ●

    31% (28/90) exhibited an impaired SF-36 score (43% [9/21] ICU, 31% [16/52] with ward COVID-19, and 17% [3/18] with outpatient COVID-19)

  • ●

    Median GOSE: 8 (7–8)

  • ●

    Median mRS: 1 (0–1)
  • ●

    Fatigue was more frequent in patients with sleep disturbances and in those with newly diagnosed neurological diseases
Rauch et al., 2021a Germany Prospective Cohort Life&Covid Online Cohort Study (Ludwig-Maximilians- Universität) N = 127 (including 116 outpatient cases and 11 inpatients)
  • ●

    Age Range: ≥18

  • ●

    Median Age: N/A

  • ●

    Sex (%F/%M): 68.5/31.5

 6 months following infection RT-PCR or Serology Subjective self-report via e-mail survey
  • ●

    25% (32/127) reported fatigue (28% [24/87] females; 20% [8/40] males)

  • ●

    16% (20/127) reported difficulties in concentration
  • ●

    At least one symptom, exertional dyspnea, and fatigue were reported more often after severe acute illness
Romero-Duarte et al., 2021 Spain Retrospective Cohort Four hospitals in Spain N = 797 (all previously hospitalized cases, including 81 previously admitted to ICU)
  • ●

    Age Range: N/A

  • ●

    Mean Age: 63.0 ± 14.4

  • ●

    Sex (%F/%M): 46.3/53.7

 6 months following discharge RT-PCR Subjective self-report via questionnaire
  • ●

    22.1% (176/797) reported fatigue (18.9% [81/428] males; 25.7% [95/369] females)
Savarraj et al., 2021a USA Prospective Cohort University of Texas Health Science Center N = 48 (all previously hospitalized cases)
  • ●

    Age Range: N/A

  • ●

    Mean Age: 50 ± 17

  • ●

    Sex (%F/%M): 48/52

 3 months following discharge RT-PCR Objective assessment via mRS (functional outcomes), BNST (cognitive function), FSS (fatigue)
  • ●

    42% (19/45) exhibited fatigue symptoms, operationalized as FSS cutoff of ≥ 4

  • ●

    12% (5/43) exhibited cognitive deficits, operationalized as BNST cutoff of ≤ 8

  • ●

    21% (10/48) scored poorly in terms of functional outcome, operationalized as mRS cutoff of ≥ 3
  • ●

    People with long-term symptoms were significantly older

  • ●

    The persistence of long-term symptoms was not associated with the severity of acute COVID-19 symptoms

  • ●

    Subjects with mild course of hospitalization had a high incidence of symptoms, especially fatigue
Say et al., 2021 Australia Prospective Cohort Royal Children's Hospital N = 151 children (including 54 asymptomatic, 91 mostly mild symptomatic cases, and 14 previously hospitalized)
  • ●

    Age Range: ≤18

  • ●

    Median Age: 3 (1–8)

  • ●

    Sex (%F/%M): 47/53

 3–6 months following diagnosis RT-PCR Subjective self-report via follow-up clinic proforma
  • ●

    2% (3/151) reported fatigue
  • ●

    All children that had post-acute COVID-19 symptoms had symptomatic acute COVID-19
Shang et al., 2021 China Prospective Cohort Zhongnan Hospital of Wuhan University, No. 7 Hospital of Wuhan, Leishenshan Hospital N = 796 (all previously hospitalized cases, including 38 in ICU)
  • ●

    Age Range: ≤18

  • ●

    Median Age: 62.0 (51.0–69.0)

  • ●

    Sex (%F/%M): 49.2/50.8

 6 months following discharge RT-PCR Subjective self-report via telephone interview
  • ●

    25.3% (201/796) reported fatigue (21.3% [86/392] males; 29.3% [115/404] females)
  • ●

    Female sex was associated with reporting > 1 persistent symptom
Shendy et al., 2021 Egypt Prospective Cohort Ministry of Health and Population N = 81 (11 previously hospitalized cases, 70 non-hospitalized cases)
  • ●

    Age Range: 25–40

  • ●

    Mean Age: 34.03 ± 4.9

  • ●

    Sex (%F/%M): 68/32

 3–5 months following recovery from COVID-19 RT-PCR Objective assessment via MFIS (fatigue)
  • ●

    64.2% (52/81) exhibited fatigue (72.7% [8/11] hospitalized; 62.9% [44/70] non-hospitalized), operationalized as MFIS total score ≤ 38
Shuwa et al., 2021 United Kingdom Prospective Cohort Coronavirus Immune Response and Clinical Outcomes (CIRCO) study based at 4 hospitals in greater Manchester N = 83 (all previously hospitalized cases)
  • ●

    Age Range: N/A

  • ●

    Median Age: 60 (51.0–66.5)

  • ●

    Sex (%F/%M): 38.6/61.4

 Median 158 (116.5–184.5) days following hospital admission RT-PCR or clinical diagnosis Objective assessment via cell culture and flow cytometry (immune parameters)
  • ●

    Moderate to severe patients demonstrated an elevation in cytokine-producing T cells (except for TNF-α + CD8 + T cells) and increased production of cytokines

  • ●

    No significant differences in the frequency of TNF-α + B cells were observed
  • ●

    No significant increase in IFNγ + CD4 + T cells was seen when stratifying patients for fatigue

  • ●

    Increased production of type 1 cytokines in convalescent patients was associated with COVID-19 disease severity, (apart from for IFNγ + CD4 + T cells)

  • ●

    The convalescent group defined by the highest proportions of CD8 + T cells and type 1 cytokine production was enriched in patients with a poorer outcome at follow-up
Simani et al., 2021 Iran Prospective Cohort University-affiliated hospital of Tehran N = 120 (all previously hospitalized, including 9 in ICU)
  • ●

    Age Range: N/A

  • ●

    Mean Age: 54.62 ± 16.94

  • ●

    Sex (%F/%M): 33.3/66.7

 6 months following COVID-19 infection RT-PCR or CT Objective assessment via previously validated questionnaire based on Fukuda guidelines for CFS/EM (fatigue)
  • ●

    17.5% (21/120) exhibited various fatigue levels

  • ●

    14.2% (17/120) qualified for CFS criteria
  • ●

    Female sex was associated with an increased risk of CFS/ME before adjustment
Skala et al., 2021 Czech Republic Prospective Cohort Hradec Kralove District N = 102 (including 15 previously hospitalized cases and 87 outpatient cases)
  • ●

    Age Range: 10–98

  • ●

    Mean Age: 46.7

  • ●

    Sex (%F/%M): 54/46

 3 months following COVID-19 diagnosis RT-PCR Objective assessment via laboratory testing (inflammatory parameters), as well as subjective self-report via questionnaires administered by physician
  • ●

    21.6% (22/102) reported fatigue

  • ●

    4.9% (5/102) reported memory impairment

  • ●

    10.8% (11/102) exhibited CRP elevation

  • ●

    9.8% (10/102) exhibited D-dimer elevation
Soldati et al., 2021 Brazil Prospective Cohort ICU unit, Complexo Hospitalar de Niterói N = 23 (all previously admitted to ICU)
  • ●

    Age Range: N/A

  • ●

    Mean Age: 53.6 ± 11.7

  • ●

    Sex (%F/%M): 21.8/78.2

 Median 83 (37–115) days following discharge RT-PCR Objective assessment viaTICS (cognitive function), EuroQol (quality of life)
  • ●

    13% (3/23) exhibited cognitive impairment, operationalized as TICS score 21–25

  • ●

    Mean EuroQol score: 71.9 ± 27.5

  • ●

    Patients with mild cognitive impairment had lower EuroQol scores (median 50) compared to patients with ambiguous and with normal cognitive performance (median 85), however this difference was not statistically significant (p = 0.062)
Sonnweber et al., 2021 Austria Prospective Cohort Department of Internal Medicine II, Medical University of Innsbruck, and two additional medical centres in Zams and Münster (CovILD study) N = 134 (including 109 previously hospitalized, of which 29 were previously admitted to ICU)
  • ●

    Age Range: 19–87

  • ●

    Mean Age: 57 ± 14

  • ●

    Sex (%F/%M): 43/57

 Mean 103 ± 21 days following diagnosis RT-PCR Objective assessment via laboratory testing (serology)
  • ●

    12% (16/134) exhibited elevated CRP levels (mean: 0.3 ± 0.6 mg/dL)

  • ●

    6% (8/134) exhibited elevated IL-6 levels (mean: 3.0 ± 2.5 mg/dL)

  • ●

    9% (12/134) exhibited elevated procalcitonin levels (mean: 0.07 ± 0.02)

  • ●

    27% (36/134) exhibited elevated D-dimer (mean: 564 ± 804 µg/L)
  • ●

    Severity of acute COVID-19, age, sex, cardiovascular diseases, pulmonary diseases, diabetes mellitus type 2 and malignancy were related to patient recovery
Soraas et al., 2021a Norway Prospective Cohort Conducted online in Norway N = 588 (all previously non-hospitalized cases)
  • ●

    Age Range: ≥18

  • ●

    Mean Age: 48

  • ●

    Sex (%F/%M): 57/43

 Mean 248 ± 18 days from baseline (mean 15.9 ± 9 days from testing to baseline) RT-PCR Objective assessment via RAND-36 (quality of life), as well as subjective self-report via online questionnaire
  • ●

    31% (183/588) reported feeling fatigued in the 3 weeks before 8-month follow-up

  • ●

    11.5% (68/588) reported memory problems in the 3 weeks before 8-month follow-up

  • ●

    13% (74/588) reported problems concentrating and thinking in the 3 weeks before 8-month follow-up

  • ●

    42% (246/588) reported worsening of health compared to one year ago

  • ●

    20% (119/588) reported that physical health has limited work or other activities in the past 4 weeks

  • ●

    13% (78/588) reported that pain has limited activities mildly or worse in the past 4 weeks
Stavem et al., 2021 Norway Cross-sectional Akershus University Hospital (Ahus) and Østfold Hospital N = 458 (all non-hospitalized cases)
  • ●

    Age Range: ≥18

  • ●

    Mean Age: 49.5 ± 15.3

  • ●

    Sex (%F/%M): 56/44

 Median 117.5 (105–135) days following first COVID-19 symptom RT-PCR Objective assessment via CFQ-11 and RAND-36 (fatigue) administered via web or post
  • ●

    46% (211/458) reported fatigue

  • ●

    Mean CFQ-11 bimodal score: 3.9 ± 3.7

  • ●

    Mean RAND-36 energy/fatigue scale score: 56.8 ± 23.9
  • ●

    Female sex, previous depression, higher BMI, single/divorced/widowed, short time since symptom debut, high symptom load and, confusion during acute COVID-19 were associated with higher multivariable odds of fatigue
Suárez-Robles et al., 2020 Spain Cross-sectional Hospital Clínico San Carlos N = 134 (all previously hospitalized, including 2 previously admitted to ICU)
  • ●

    Age Range: N/A

  • ●

    Mean Age: 58.53 ± 18.53

  • ●

    Sex (%F/%M): 53.7/46.3

 90 days following discharge RT-PCR Subjective self-report via telephone structured interview
  • ●

    54.5% (73/134) reported fatigue

  • ●

    18.7% (25/134) reported general malaise
Sykes et al., 2021 UK Prospective Cohort Hull University Teaching Hospitals NHS Trust N = 134 (all previously hospitalized, including 27 previously admitted to ICU)
  • ●

    Age Range: 25–89

  • ●

    Mean Age: 59.6 ± 14

  • ●

    Sex (%F/%M): 34.3/65.7

 Median 113 (range 46–167) days following discharge RT-PCR Objective assessment via EQ-5D-5L (quality of life), as well as subjective self-report via standardised clinical assessment by a specialist nurse and/or physiotherapist
  • ●

    39.6% (53/134) reported extreme fatigue (30.7% [27/88] males; 56.5% [26/46] females)

  • ●

    25.4% (34/134) reported an attention deficit (20.5% [18/88] males; 34.8% [16/46] females)

  • ●

    37.3% (50/134) reported memory impairment (27.3% [24/88] males; 56.5% [26/46] females)

  • ●

    9.7% (13/134) reported cognitive impairment (5.7% -[5/88] males; 17.4% [8/46] females)

  • ●

    EQ-5D-5L mean: 0.657 (0.30)

  • ●

    CRP levels were within normal range in 84% (54/64) of patients (median: 2.9 (0.2–33) mg/L)
  • ●

    Females were significantly more likely to report residual symptoms including fatigue
Taboada (1) et al., 2020 Spain Prospective Cohort Seven hospitals located in northwestern Spain N = 91 (all cases previously admitted to ICU)
  • ●

    Age Range: N/A

  • ●

    Mean Age: 65.5 ± 10.4

  • ●

    Sex (%F/%M): 35.2/64.8

 6 months following ICU treatment RT-PCR Objectively assessed via EQ-5D-3L (quality of life) and PCFS (functional outcomes), as well as subjective self-report via structured interview conducted by trained research coordinators
  • ●

    37% (34/91) reported asthenia

  • ●

    67% (61/91) exhibited a decrease in the quality of life, including 56% (51/91) experiencing mobility problems, 37% (34/91) experiencing problems with usual activities, and 13% (12/91) experiencing problems with self-care

  • ●

    63% (57/91) reported a decreased functional status; 38% (35/91) had lowered two grades in the PCFS, 45% (41/91) described persistent functional limitations (operationalized as grades 2–4 in the PCFS)
  • ●

    Advanced age, male sex, need for mechanical ventilation during ICU stay, duration of mechanical ventilation, length of ICU stay, and length of hospital stay were associated with a decreased quality of life and/or functional status
Taboada (2) et al., 2021 Spain Cross-sectional University Hospital of Santiago N = 183 (all previously hospitalized cases, including 32 to ICU)
  • ●

    Age Range: N/A

  • ●

    Mean Age*: 65.9 ± 14.1

  • ●

    Sex* (%F/%M): 40.5/59.5

*pertains to all who were admitted to hospital at index, including those who are not included in follow-up		 6 months following hospitalization RT-PCR Objective assessment via PCFS (functional status), as well as subjective self-reportvia surveys conducted by trained study investigators
  • ●

    47.5% (87/183) patients exhibited decreased functional status, operationalized as PCFS grades 2–4
  • ●

    Female sex, age, length of hospital stay, mechanical ventilation, and ICU admission were associated with limitations in functional status
Tawfik et al., 2021 Egypt Retrospective Cohort Ain-Shams University and Ministry of Health and Population hospitals N = 120 healthcare workers (including 18 previously hospitalized)
  • ●

    Age Range: 23–62

  • ●

    Mean Age: 33.7 ± 7.29

  • ●

    Sex (%F/%M): 58/42

 3 months following COVID-19 infection RT-PCR and CT Subjective self-report via questionnaire
  • ●

    35.0% (42/120) reported fatigue

  • ●

    3.3% (4/120) reported memory and attention problems
  • ●

    Age ≥ 35 years was associated with development of persistent symptoms
Todt et al., 2021 Brazil Prospective Cohort Hospital Municipal Dr. Moyses Deutsch N = 251 patients (all previously hospitalized, including 42 in ICU)
  • ●

    Age Range: ≥18

  • ●

    Mean Age: 53.6 ± 14.9

  • ●

    Sex (%F/%M): 40.2/59.8

 3 months following discharge RT-PCR Objective assessment viaEQ-5D-3L (quality of life)
  • ●

    Overall worsening of EQ-5D-3L single summary index compared to before the onset of COVID-19 symptoms (medians: 0.80 [0.74–1.0] vs. 1.0 [0.80–1.0])

  • ●

    7.4% (18/251) reported problems with self-care (EQ-5D-3L levels 2 or 3)

  • ●

    15.6% (38/251) reported problems with usual activities (EQ-5D-3L levels 2 or 3)
  • ●

    Worsening of health status in usual activities was higher among females

  • ●

    Participants with worsening of health status were predominantly female, more frequently had required mechanical ventilation and intensive care, and had longer length of hospital stay than participants without worsening of health status

  • ●

    Poorer health status prior to admission was associated with more significant decline in health status

  • ●

    Factors associated with self-care impairment: age, hypertension, number of comorbidities, intensive care, new onset hemodialysis, and length of hospital stay

  • ●

    Factors associated with impairment in usual activities: age, heart failure, number of comorbidities, new onset hemodialysis, and length of hospital stay
Valiente-De Santis et al., 2020a Spain Prospective Cohort Outpatients’ office of Regional University Hospital of Málaga N = 108 (all outpatient cases; both symptomatic and asymptomatic, including 30 healthcare workers)
  • ●

    Age Range: N/A

  • ●

    Mean Age: 55.4 ± 15.4

  • ●

    Sex (%F/%M): 55.6/44.4

 12 weeks following acute COVID-19 Serology Subjective self-report via telephone survey
  • ●

    44.9% (48/107) reported asthenia

  • ●

    1.9% (2/108) reported loss of memory

  • ●

    1.9% (2/108) reported difficulty concentrating

  • ●

    CRP > 2.9 mg/dL was detected in 24.5% (25/108)

  • ●

    D-dimer > 500 ng/mL was detected in 31.4% (32/108)

  • ●

    IL-6 > 40 pg/mL was detected in 3.9% (4/108)
  • ●

    Being a health-care worker was associated with symptom persistence, while age ≥ 65 years was protective
van den Borst et al., 2020 The Netherlands Prospective Cohort Radboud University Medical Center (POSTCOVER study) N = 124 (all previously hospitalized cases)
  • ●

    Age Range: N/A

  • ●

    Mean Age: 59 ± 14

  • ●

    Sex (%F/%M): 40/60

 Mean 13.0 ± 2.2 weeks following onset of symptoms RT-PCR or clinically diagnosed Objective assessment via laboratory testing (serological parameters), TICS, CFQ (cognitive function), SF-36 and NCSI (quality of life, fatigue)
  • ●

    69% (86/124) reported fatigue

  • ●

    64% (79/124) reported functional impairments in daily life

  • ●

    36% (45/124) exhibited abnormal scores on all mental and cognitive status questionnaires

  • ●

    15% (19/124) exhibited abnormal cognitive status, operationalized as TICS score < 34

  • ●

    17% (21/124) exhibited self-reported cognitive impairment, operationalized as CFQ > 43

  • ●

    scores on all domains of the SF-36 were lowered, especially on the domains functioning, energy/fatigue, and general health.

  • ●

    median CRP (1 (1–3) mg/L) and D-dimer (500 (500–500) ng/ml) were at normal levels in all participants

  • ●

    72% (89/124) reported impaired general quality of life
Van Veenendaal et al., 2021a The Netherlands Prospective Cohort University Medical Center Groningen, ICU (COFICS) N = 60 (all previously admitted cases to ICU) [50 at 6 months]
  • ●

    Age Range: N/A

  • ●

    Median Age: 62.5 (55.3–68.0)

  • ●

    Sex (%F/%M): 32/68

 6 months following ICU discharge RT-PCR Objective assessment via SF-20 (quality of life), FAD-GF6+ (social functioning), as well as subjective self-report via telephone questionnaire conducted by research nurses (at 3 months), and mail questionnaire (at 6 months)
  • ●

    24% (12/50) reported fatigue at 6-month follow-up

  • ●

    14% (7/50) reported cognitive problems

  • ●

    Role activities were impaired in ICU-survivors with a median of 0 (IQR 0–0)

  • ●

    Social functioning scored a median of 80.0 (IQR 60.0–100.0)

  • ●

    33% (10/30) of pre-ICU employed persons were too ill to return to work, and employment rate was decreased for the vast majority of patients; 90% did not reach their pre-ICU employment level
Venturelli et al., 2021 Italy Prospective Cohort Papa Giovanni XXIII Hospital N = 767 (all previously hospitalized cases, including 66 in ICU)
  • ●

    Age Range: 20–92

  • ●

    Mean Age: 63 ± 13.6

  • ●

    Sex (%F/%M): 32.9/67.1

 Median 105 (84–127) days following onset of symptoms RT-PCR or Serology Objective assessment via laboratory testing (serology), MoCA (cognitive function), Barthel index (functional impairment), and Brief Fatigue inventory (fatigue), as well as subjective self-report via questionnaire
  • ●

    70.3% (539/767) reported mild to severe asthenia, according to the Brief Fatigue Inventory

  • ●

    44.1% (334/767) reported new-onset fatigue, according to the Brief Fatigue inventory

  • ●

    24.3% (186/767) self-reported asthenia

  • ●

    0.7% (2/304) exhibited a pathologic MoCA score of 0

  • ●

    22.7% (69/304) reported cognitive impairment symptoms

  • ●

    16% (121/767) were no longer independent, according to the Barthel index scale results

  • ●

    Mean D-dimer: 700 ± 1021 ng/ml (22% [163/743] exhibited 500–999, 12% [89/743] exhibited 1000–1999, 5% [37/743] exhibited >=2000); above upper limit in 38% of cases

  • ●

    Mean CRP: 0.36 ± 0.85 mg/dL (7% [53/759] exhibited values > 1.0)
  • ●

    Women were more symptomatic than men, with fatigue reported almost twice as frequently
Walle-Hansen et al., 2021 Norway Retrospective Cohort Four general hospitals in South-Eastern Norway N = 106 (all previously hospitalized cases, including 28 in ICU)
  • ●

    Age range: 60–96

  • ●

    Mean age: 74.3 ± 8.5

  • ●

    Sex (%F/%M): 43/57

 6 months following hospitalization RT-PCR Objective assessment via MoCA (cognitive function), and EQ 5D-5L (quality of life)
  • ●

    43% (46/106) displayed a negative change in cognitive function, according to MoCA

  • ●

    54% (111/206) reported decrease of 7 + points in quality of life (mean change from baseline: −11.5 ± 14.2)

  • ●

    35% (37/106) reported decline in mobility and ability to perform daily activities

  • ●

    17% (18/106) reported decline in ability to self-care

  • ●

    11% (12/106) reported major change in usual activities
  • ●

    The mean sum scores of MoCA were lower in the oldest age group, indicating lower cognitive and physical function in older compared to younger participants
Wong et al., 2020 Canada Prospective Cohort Post-COVID-19 Respiratory Clinic in Vancouver N = 78 (all previously hospitalized cases)
  • ●

    Age range: ≥18

  • ●

    Mean age: 62 ± 16

  • ●

    Sex (%F/%M): 36/64

 Median 13 (11–14) weeks following onset of symptoms Laboratory test Objective assessment via EQ-5D-5L (quality of life)
  • ●

    51% (40/78) exhibited quality of life impairment, operationalized as at least a moderate problem in one or more EQ-5D-5L dimensions
Woo et al., 2020 United Kingdom Cross-sectional University Medical Centre Hamburg-Eppendorf N = 28 (11 previously hospitalized cases, 6 previously outpatient cases, 1 case receiving no medical care, and 10 healthy controls)
  • ●

    Age Range: 17–71

  • ●

    Mean Age: 42.2 ± 14.3

  • ●

    Sex (%F/%M): 57.9/42.1

 Median 85 (range 20–105) days following recovery RT-PCR Objective assessment via TICS-M (cognitive function), as well as subjective self-report via questionnaire
  • ●

    16.7% (3/18) reported fatigue

  • ●

    Cases scored median 24.17 (range: 13–40) on the fatigue assessment scale compared to healthy controls median 18.1 (range: 18–19)

  • ●

    50% (9/18) reported attention deficits

  • ●

    44.4% (8/18) reported concentration deficits

  • ●

    44.4% (8/18) reported short-term memory deficits

  • ●

    27.8% (5/18) reported trouble in finding words

  • ●

    5.6% (1/18) reported incoherent thoughts

  • ●

    Cases scored a TICS-M mean of 38.83 (range: 31–46) compared to healthy controls mean of 45.8 (range, 43–50)
  • ●

    Neurocognitive deficits after recovery from COVID-19 were independent from fatigue and mood alterations and may therefore might be different from the classical post-viral syndrome
Xiong et. al., 2020 China Prospective cohort Renmin Hospital of Wuhan University N = 722 (538 previously hospitalized cases, and 184 healthy controls)
  • ●

    Age range: 20–80

  • ●

    Median age: 52 (41–62)

  • ●

    Sex (%F/%M): 30.3/69.7

 Median 97 (95–102) days following discharge COVID-19 diagnosis according to WHO interim guidance Subjective self-report via telephone survey conducted by three experienced clinicians
  • ●

    28.3% (152/538) reported physical decline or fatigue (34% [52/152] males; 66% [100/152] females)
  • ●

    Physical decline/fatigue was more common in female than male subjects, and in those aged 41–60
Zhao et al., 2020 China Retrospective cohort 3 Tertiary Hospitals in Henan Province N = 55 (all previously hospitalized cases)
  • ●

    Age Range: ≥18

  • ●

    Mean Age: 47.74 ± 15.49

  • ●

    Sex (%F/%M): 41.82/58.18

 3 months following discharge RT-PCR Self-report via clinical follow-up
  • ●

    16.4% (9/55) reported fatigue
Zhou et al., 2021 China Cross-sectional 4 Hospitals in Wuhan N = 72 (55 cases, including 16 asymptomatic, and 17 healthy controls)
  • ●

    Age Range*: N/A

  • ●

    Median Age*: 60 (57–64)

  • ●

    Sex* (%F/%M): 57.9/42.1

  • ●

    Age Range**: N/A

  • ●

    Median Age**: 56.50 (52.3–63.0)

  • ●

    Sex** (%F/%M): 75/25

  • ●

    Age Range***: N/A

  • ●

    Median Age***: 57 (52.8–62.0)

  • ●

    Sex*** (%F/%M): 56.2/43.8

*severe cohort**mild cohort***asymptomatic cohort		 Mean 139.79 ± 7.41 days following illness onset for severe cohort, mean 133.75 ± 9.64 days following illness onset for mild cohort RT-PCR or serology Objective assessment via mesoscale-discovery (MSD) multiplexed immunoassay(immunological parameters)
  • ●

    D-dimer median level in severe cohort: 0.34 (0.28–0.51) μg/ml (vs. healthy controls: 0.29 [0.29–0.38] μg/ml])

  • ●

    D-dimer median level in moderate cohort: 0.38 (0.29–0.46) μg/ml (vs. healthy controls: 0.29 [0.29–0.38] μg/ml])

  • ●

    D-dimer median level in asymptomatic cohort: 0.32 (0.25–0.46) μg/ml (vs. healthy controls: 0.29 [0.29–0.38] μg/ml])

  • ●

    CRP median level in severe cohort: 1.30 (0.46–3.74) mg/L (vs. healthy controls: 0.42 [0.11–1.23] mg/L])

  • ●

    CRP median level in moderate cohort: 0.63 (0.29–1.50) mg/L (vs. healthy controls: 0.42 [0.11–1.23] mg/L])

  • ●

    CRP median level in asymptomatic cohort: 1.06 (0.56–1.50) mg/L (vs. healthy controls: 0.42 [0.11–1.23] mg/L])

  • ●

    CRP and D-dimer levels were not significantly elevated compared to healthy control levels (p > 0.05)

  • ●

    Significant increases in SAA, TNF-α, and IL-1RA in severe cohort (class 1,2,3 cytokines upregulated in cases)

  • ●

    Higher than normal levels of IL-17A and IL-17D in severe cohort

  • ●

    No difference across all cohorts in IL-1α and IL-1β

  • ●

    Normal levels of IL-6 and IL-10 across all groups

  • ●

    IL-7 was decreased in severe cohort
  • ●

    Cytokines such as TNF-α were correlated with abnormal clinical features

Proportions are reported as cases/total study sample size. ‘Cases’ refers to previous confirmed COVID-19 cases. Medians are reported as median (interquartile range), if the interquartile range was provided, or unless otherwise specified. Means are reported as mean ± standard deviation, if the standard deviation was provided. ‘Previously hospitalized’/‘admitted to ICU’ refers to COVID-19 treatment. ‘Admission’ and ‘discharge’ refer to COVID-19 inpatient treatment. ‘Infection’ refers to infection with SARS-CoV-2. Ages are given in years. ‘%F/%M’ refers to percentage of study sample which is female/percentage of study sample which is male.

Acronyms: COVID-19: Coronavirus disease 2019, SARS-CoV-2: Severe acute respiratory syndrome coronavirus 2, ICU: Intensive care unit, USA: United States of America, RT-PCR: Reverse transcription polymerase chain reaction, ESCAPE: Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness, DISCOVER: Diagnostic and Severity Markers of COVID-19 to Enable Rapid Triage, ISARIC: International Severe Acute Respiratory and Emerging Infection Consortium, SF-36: 36-Item Short Form Survey, CRP: C-reactive protein, IgG: Immunoglobulin G, CD4+: Cluster of differentiation 4+, CD8+: Cluster of differentiation 8+, IL-2: Interleukin-2, IFN-γ: Interferon gamma, TNF-α: Tumor necrosis factor alpha, ADAPT: Australians’ Drug Use: Adapting to Pandemic Threats, SPHERE-34: 34-Item Somatic and Psychological Health Report, RAND-36: Rand 36-Item Health Survey, PHOSP-COVID: Post-hospitalization COVID-19 study, IQR: Interquartile range, FACIT: Functional Assessment of Chronic Illness Therapy, CFS/ME: Chronic Fatigue Syndrome/Myalgic Encephalomyelitis, MoCA: Montreal Cognitive Assessment, EuroQol: European Quality of Life Scale, EQ-VAS: EuroQol visual analog scale, EQ-5D-5L: EuroQol-5 Dimension-5 levels, EQ-5D-3L: EuroQol-5-Dimension-3 levels, EQ-5D-5L VAS: EuroQol-5 Dimension-5 levels visual analog scale, WG-SS: Washington Group Short Set on Functioning, CT: Computerized tomography, BRB-NT: Brief Repeatable Battery of Neuropsychological Tests, SSD: Subjective Scale of Damage, SDMT: Symbol Digit Modalities Test, ARDS: Acute respiratory distress syndrome, IL-6: Interleukin-6, NYC: New York City, CSQ: COVID-19 Symptom Questionnaire, SF-12: 12-Item Short Form Survey, SF-23: 23-Item Short Form Survey, ME/CFS: Myalgic encephalomyelitis/chronic fatigue syndrome, WPAI: Work Productivity and Activity Impairment Questionnaire, PCFS: Post-COVID-19 Functional Status, CFQ: Cognitive Failures Questionnaire, HRTC: High Resolution Computed Tomography, SCIP-D: Screen for Cognitive Impairment in Psychiatry, TMT-B: Trail Making Test Part B, FSS: Fatigue Severity Scale, PICS: Post-intensive care syndrome, SF-35: 35-Item Short Form Survey, SD: Standard deviation, OMC: Orientation-Memory-Concentration Test, OR: Odds ratio, PTSD: Post-traumatic stress disorder, MMSE: Mini-Mental State Examination, BACS: Brief Assessment of Cognition in Schizophrenia, REDCap: Research Electronic Data Capture, FAS: Fatigue Assessment Scale, Q3PC: questionnaire of cognitive complaints, d-2R: D2 Test of Attention, MFI: Multidimensional fatigue inventory, WHO CRF: World Health Organization’s Post COVID Case Report form, MIP-1β: Macrophage inflammatory protein-1 beta, SDF-1α: Stromal Cell Derived Factor 1 alpha, IL-12p70: Interleukin-12p70, SCF: Stem cell factor, IL-17A: Interleukin-17A, BDNF: Brain-derived neurotrophic factor, VEGF: Vascular endothelial growth factor, IP-10: Interferon-inducible protein 10, IL-18: Interleukin-18, MCP-1: Monocyte chemoattractant protein-1, ELISA: Enzyme-linked immunosorbent assay, GOSE: Glasgow Outcome Scale-Extended, mRS: Modified Rankin Scale, BNST: Brief neurocognitive screening test, MFIS: Modified Fatigue Impact Scale, CIRCO: Coronavirus Immune Response and Clinical Outcome, TICS: Telephone interview for cognitive status, CFQ-11: Chalder Fatigue Scale 11, BMI: Body mass index, POSTCOVER: Post-COVID-19 Recovery Study, SF-20: 20-Item Short Form Survey, FAD-GF6+: McMaster Family Assessment Device-General Functioning subscale, MSD: Mesoscale-discovery multiplexed immunoassay.

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This article is a pre-print as of June 8, 2021.