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Cited by 644Long-Term Effects of COVID-19COVID-19 Clinical Research StudiesCOVID-19 and Mental Health

Female gender is associated with long COVID syndrome: a prospective cohort study

Open access
Bai, Francesca, Tomasoni, Daniele, Falcinella, Camilla, Barbanotti, Diletta, Castoldi, Roberto, Mulè, Giovanni, Augello, Matteo, Mondatore, Debora +16 more·2022·Clinical Microbiology and Infection
DOI 10.1016/j.cmi.2021.11.002PMC PMC8575536
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Abstract

Objective We explored the association between female gender and long COVID syndrome, defined as persistence of physical and/or psychological symptoms for more than 4 weeks after recovery from acute COVID-19 disease. The secondary aim was to identify predictors of long COVID syndrome by multivariable logistic regression analysis. Methods This was a single-centre prospective cohort study conducted at San Paolo Hospital in Milan, Italy. We enrolled adult patients who were evaluated at the post-COVID outpatient service of our Infectious Diseases Unit between 15 April 2020 and 15 December 2020. Participants were individuals who had clinically recovered from COVID-19 and in whom virological clearance had occurred. Previous infection by SARS-CoV-2 was microbiologically documented by positivity using a reverse-transcriptase polymerase chain reaction (RT-PCR) assay of nasopharyngeal swab. All enrolled patients underwent blood tests and a comprehensive medical examination at follow-up. Individuals were interviewed about resolved and persisting symptoms and were asked to fill in two questionnaires to allow assessment of the Hospital Anxiety and Depression symptoms (HADS) score and of the Impact of Event Scale–Revised (IES-R) score. Results A total of 377 patients were enrolled in the study. The median time from symtpom onset to virological clerance was 44 (37–53) days. A diagnosis of long COVID syndrome was made in 260/377 (69%) patients. The most common reported symptoms were fatigue (149/377, 39.5%), exertional dyspnoea (109/377, 28.9%), musculoskeletal pain (80/377, 21.2%) and “brain fog” (76/377, 20.2%). Anxiety symptoms were ascertained in 71/377 (18.8%) individuals, whereas 40/377 (10.6%) patients presented symptoms of depression. Post-traumatic stress disorder (defined by a pathological IES-R score) was diagnosed in one-third of patients (85/275, 31%). Female gender was independently associated with long COVID syndrome at multivariable analysis (AOR 3.3 vs. males, 95% CI 1.8–6.2, p < 0.0001). Advanced age (adjusted (A)OR 1.03 for 10 years older, 95% CI 1.01–1.05, p 0.01) and active smoking (AOR 0.19 for former smokers vs. active smokers, 95% CI 0.06–0.62, p 0.002) were also associated with a higher risk of long COVID, while no association was found between severity of disease and long COVID (AOR 0.67 for continuous positive airway pressure (CPAP)/non-invasive mechanical ventilation (NIMV)/orotracheal intubation (OTI) vs. no 02 therapy, 95% CI 0.29–1.55, p 0.85). Discussion Factors that were found to be associated with a higher risk of developing “long COVID” syndrome were female gender, older age and active smoking, but not severity of the acute disease. Individuals affected by SARS-CoV-2 infection with the aforementioned features should be early identified and involved in follow-up programmes.

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Crossref · 10.1016/j.cmi.2021.11.002

Cites

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Statistics

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Claims the paper makes

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  • Findingown data

    In a multivariable logistic regression model, female sex was linked to an approximately three times greater likelihood of long COVID, even after controlling for age, illness severity, length of stay, comorbidities, smoking, BMI, and time from symptom onset to viral clearance.

    “At multivariable logistic regression analysis, female gender was associated with a threefold higher risk of long COVID, also after adjustment for age, severity of illness, LOS, comorbidities, smoking, BMI and time from symptoms onset to virological clearance”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The follow-up duration used in the study is sufficient to capture long COVID.
  • Findingown data

    Severity of acute disease was not associated with long COVID (AOR 0.67 for CPAP/NIMV/OTI versus no oxygen therapy, 95% CI 0.29-1.55, p = 0.85).

    “no association was found between severity of disease and long COVID (AOR 0.67 for continuous positive airway pressure (CPAP)/non-invasive mechanical ventilation (NIMV)/orotracheal intubation (OTI) vs. no 02 therapy, 95% CI 0.29–1.55, p 0.85).”
    Quote in the paperNot a substantial claim
  • Findingown data

    In the cohort, 260 of 377 patients (69%) were observed to have long COVID.

    “Long COVID was observed in 260/377 (69%) patients”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: The follow-up duration used in the study is sufficient to capture long COVID.
  • Findingown data

    Time to viral clearance was not linked to long COVID in univariable or multivariable analysis.

    “Severity of disease, LOS and time to virological clearance were not associated with long COVID at univariable and multivariable analyses”
    Quote in the paperNot a substantial claim
  • Findingown data

    Active smoking was an independent predictor of long COVID.

    “Other independent predictors of long COVID were advanced age and active smoking.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: No prior research had examined the link between smoking and long COVID.
  • Classified as probably not a substantial claim. 46
  • May combine two claims. 18

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

    Findingown data

    The median age of enrolled patients was 57 years (IQR 49-68).

    “Females accounted for 137/377 (36%) of all patients; median age was 57 (IQR 49–68) years.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The most common physical symptoms of long COVID were fatigue (39.5%), exertional dyspnoea (28.9%), musculoskeletal pain (21.2%), and brain fog (20.2%).

    “The most common physical symptoms characterising long COVID were fatigue (149/377, 39.5%), exertional dyspnoea (109/377, 28.9%), musculoskeletal pain (80/377, 21.2%) and “brain fog” (76/377, 20.2%)”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: The tools used to assess dyspnoea and fatigue are adequate for identifying long COVID symptoms.

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

    Findingown data

    Females accounted for 137 of 377 enrolled patients (36%).

    “Females accounted for 137/377 (36%) of all patients; median age was 57 (IQR 49–68) years.”
    Quote in the paperNot a substantial claim

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

    Findingown data

    The follow-up examination was performed at a median of 56 days from virological clearance.

    “The follow-up examination was done at a median of 102 (IQR 86–126) days from acute symptom onset, a median of 79 (IQR 69–102) days from clinical recovery and a median of 56 (IQR 47–74) days from virological clearance.”
    Quote in the paperNot a substantial claim

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

    Findingown data

    Fever was reported in 280 of 377 patients (74%) as an acute symptom.

    “The most frequent acute symptoms were fever (280/377, 74%), cough (198/377, 53%), dyspnoea (161/377, 43%) and fatigue (59/377, 16%).”
    Quote in the paperNot a substantial claim

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

    Findingown data

    Post-traumatic stress disorder, defined by a pathological IES-R score, was diagnosed in 85 of 275 patients (31%).

    “Post-traumatic stress disorder (defined by a pathological IES-R score) was diagnosed in one-third of patients (85/275, 31%).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Anxiety symptoms were the most frequent psychological manifestation, present in 18.8% of patients.

    “manifestations of anxiety were the most frequent (71/377, 18.8%)”
    Quote in the paperNot a substantial claim

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

    Findingown data

    Brain fog was reported by 76 of 377 patients (20.2%).

    “The most common reported symptoms were fatigue (149/377, 39.5%), exertional dyspnoea (109/377, 28.9%), musculoskeletal pain (80/377, 21.2%) and “brain fog” (76/377, 20.2%).”
    Quote in the paperNot a substantial claim

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

    Findingown data

    Anxiety symptoms were ascertained in 71 of 377 patients (18.8%).

    “Anxiety symptoms were ascertained in 71/377 (18.8%) individuals, whereas 40/377 (10.6%) patients presented symptoms of depression.”
    Quote in the paperNot a substantial claim

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

    Findingown data

    Cough was reported in 198 of 377 patients (53%) as an acute symptom.

    “The most frequent acute symptoms were fever (280/377, 74%), cough (198/377, 53%), dyspnoea (161/377, 43%) and fatigue (59/377, 16%).”
    Quote in the paperNot a substantial claim

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

    Findingown data

    CPAP or NIMV was received by 115 of 377 patients (31%) during hospitalization.

    “One-third of patients received CPAP or NIMV (115/377, 31%) during hospitalization, whereas only 30/377 (8%) patients underwent OTI.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Compared with men, women showed greater frequencies of nearly all physical symptoms and every psychological symptom.

    “women were characterized by a higher proportion of most physical symptoms and all psychological symptoms than men”
    Quote in the paperSubstantial claim

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

    Findingown data

    Depression symptoms were present in 40 of 377 patients (10.6%).

    “Anxiety symptoms were ascertained in 71/377 (18.8%) individuals, whereas 40/377 (10.6%) patients presented symptoms of depression.”
    Quote in the paperNot a substantial claim

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

    Findingown data

    Fatigue was reported in 59 of 377 patients (16%) as an acute symptom.

    “The most frequent acute symptoms were fever (280/377, 74%), cough (198/377, 53%), dyspnoea (161/377, 43%) and fatigue (59/377, 16%).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Among long COVID patients, 55% reported only ongoing physical symptoms, 38% reported both physical and psychological symptoms, and 7% reported only psychological distress.

    “142/260, 55%) reported ongoing physical symptoms only, 100/260 (38%) complained both physical and psychological symptoms, while 18/260 (7%) presented psychological distress solely at follow-up”
    Quote in the paperNot a substantial claim

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

    Findingown data

    Interstitial pneumonia was present in 346 of 377 patients (92%) at chest X-ray or CT scan at hospital admission.

    “In total, 346/377 (92%) presented interstitial pneumonia at chest X-ray or CT scan at the time of hospital admission.”
    Quote in the paperNot a substantial claim

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

    Findingown data

    Musculoskeletal pain was reported by 80 of 377 patients (21.2%).

    “The most common reported symptoms were fatigue (149/377, 39.5%), exertional dyspnoea (109/377, 28.9%), musculoskeletal pain (80/377, 21.2%) and “brain fog” (76/377, 20.2%).”
    Quote in the paperNot a substantial claim

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

    Findingown data

    Dyspnoea was reported in 161 of 377 patients (43%) as an acute symptom.

    “The most frequent acute symptoms were fever (280/377, 74%), cough (198/377, 53%), dyspnoea (161/377, 43%) and fatigue (59/377, 16%).”
    Quote in the paperNot a substantial claim

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

    Findingown data

    In all 28 patients with elevated D-dimer at follow-up, levels were lower than in the acute phase of illness.

    “In all 28 patients with elevated D-dimer at follow-up, levels were lower than the acute phase of illness; however, two of these patients presented persisting dyspnoea and therefore underwent chest CT scan with contrast medium that excluded pulmonary thromboembolism.”
    Quote in the paperNot a substantial claim

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

    Findingown data

    Two of the 28 patients with elevated D-dimer had persisting dyspnoea and chest CT with contrast excluded pulmonary thromboembolism.

    “In all 28 patients with elevated D-dimer at follow-up, levels were lower than the acute phase of illness; however, two of these patients presented persisting dyspnoea and therefore underwent chest CT scan with contrast medium that excluded pulmonary thromboembolism.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    IES-R was available in 275 of 377 patients (73%), and 85 of 275 (31%) had a pathological IES-R score.

    “IES-R was available in an unselected sub-group of patients (275/377, 73% patients): in one-third (85/275, 31%) of cases the IES-R score resulted pathological”
    Quote in the paperNot a substantial claim

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

    Findingown data

    D-dimer was out of range in 28 of 377 patients (7.4%) without correlation with organ dysfunction.

    “Blood tests at follow-up showed no significant alterations: C-reactive protein (CRP) and complete blood count (CBC) were normal for all patients, while D-dimer was still out of range in 28/377 (7.4%) patients without however any correlation with organ dysfunction”
    Quote in the paperNot a substantial claim

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

    Findingown data

    The median time from symptom onset to virological clearance was 44 days (IQR 37-53).

    “The median time from symtpom onset to virological clerance was 44 (37–53) days.”
    Quote in the paperNot a substantial claim

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

    Findingown data

    Women were less frequently active smokers than men.

    “Women were less frequently active smokers than men.”
    Quote in the paperNot a substantial claim

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

    Findingown data

    Depression symptoms were present in 10.6% of patients.

    “depression symptoms were present in 40/377, 10.6% of patients”
    Quote in the paperNot a substantial claim

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

    Findingown data

    Fatigue was reported by 149 of 377 patients (39.5%).

    “The most common reported symptoms were fatigue (149/377, 39.5%), exertional dyspnoea (109/377, 28.9%), musculoskeletal pain (80/377, 21.2%) and “brain fog” (76/377, 20.2%).”
    Quote in the paperNot a substantial claim

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

    Findingown data

    The follow-up examination was performed at a median of 79 days from clinical recovery.

    “The follow-up examination was done at a median of 102 (IQR 86–126) days from acute symptom onset, a median of 79 (IQR 69–102) days from clinical recovery and a median of 56 (IQR 47–74) days from virological clearance.”
    Quote in the paperNot a substantial claim

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

    Findingown data

    Physical and psychological manifestations were similarly represented in both genders.

    “Physical and psychological manifestations were similarly represented in both genders”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Blood tests at follow-up showed no significant alterations: CRP and complete blood count were normal for all patients.

    “Blood tests at follow-up showed no significant alterations: C-reactive protein (CRP) and complete blood count (CBC) were normal for all patients, while D-dimer was still out of range in 28/377 (7.4%) patients without however any correlation with organ dysfunction”
    Quote in the paperNot a substantial claim

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

    Findingown data

    Exertional dyspnoea was reported by 109 of 377 patients (28.9%).

    “The most common reported symptoms were fatigue (149/377, 39.5%), exertional dyspnoea (109/377, 28.9%), musculoskeletal pain (80/377, 21.2%) and “brain fog” (76/377, 20.2%).”
    Quote in the paperNot a substantial claim

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

    Findingown data

    The follow-up examination was performed at a median of 102 days from acute symptom onset.

    “The follow-up examination was done at a median of 102 (IQR 86–126) days from acute symptom onset, a median of 79 (IQR 69–102) days from clinical recovery and a median of 56 (IQR 47–74) days from virological clearance.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Among patients with long COVID, 37.3% had one persisting symptom, 32.3% had two, and 30.4% had three or more.

    “Within long COVID patients, 97/260 (37.3%) participants had only one persisting symptom, 84/260 (32.3%) had two persisting symptoms and 79/260 (30.4%) had three or more persisting symptoms.”
    Quote in the paperNot a substantial claim

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

    Findingown data

    OTI was undergone by 30 of 377 patients (8%) during hospitalization.

    “One-third of patients received CPAP or NIMV (115/377, 31%) during hospitalization, whereas only 30/377 (8%) patients underwent OTI.”
    Quote in the paperNot a substantial claim

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

    Study design and conductnone given

    p values were adjusted by Bonferroni's correction.

    “p values have been adjusted by Bonferroni's correction.”
    Quote in the paperNot a substantial claim

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

    Premisecitation

    Factors found to correlate with long COVID so far were increased length of acute illness, longer time from symptom onset to virological clearance, and comorbidities.

    “Previous studies have not distinctly identified predictors of long COVID syndrome; factors found to have a correlation with long COVID so far were increased length of acute illness, longer time from symptom onset to virological clearance and comorbidities [11,16].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [11] Carvalho-Schneider, 2020, Follow-up of adults with noncritical COVID-19 two months after symptom onset, Clin Microbiol Infect source

      Not checked in the free run.

    • cites [16] Xiong, 2021, Clinical sequelae of COVID-19 survivors in Wuhan, China: a single-centre longitudinal study, Clin Microbiol Infect source

      Not checked in the free run.

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

    Study design and conductown data

    The study included 377 of 492 patients (77%) who were given an appointment.

    “In total 115/492 (23%) patients missed their visit, thus the study includes a total of 377/492 individuals, namely 77% of those who were given an appointment.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductown data

    The association between female gender and long COVID was analysed by multivariable logistic regression adjusting for age, severity of disease, length of hospital stay, comorbidities, BMI, smoking, and time to virological clearance.

    “The association between female gender and long COVID was analysed by fitting a multivariable logistic regression analysis, adjusting for possible confounders (age, severity of disease, length of hospital stay [LOS], comorbidities, body mass index [BMI], smoking and time to virological clearance).”
    Quote in the paperSubstantial claim

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

    Premisecitation

    Over half of individuals affected by COVID-19 report persisting symptoms after recovery from acute illness.

    “Over half of individuals affected by COVID-19 report persisting symptoms after recovery from acute illness.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Increased COVID-19 severity and female gender as predicting factors are not equivocal findings.

    “Increased COVID-19 severity and female gender as predicting factors are instead not equivocal findings [1,4,5,8,13,[17], [18], [19], [20]].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [1,4,5,8,13,[17], [18], [19], [20]]

      Not checked in the free run.

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

    Study design and conductnone given

    Missing data were handled by the missing-indicator method.

    “Missing data were handled by the missing-indicator method.”
    Quote in the paperNot a substantial claim

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

    Premisecitation

    These symptoms can endure up to 6-7 months and even longer.

    “These symptoms can endure up to 6–7 months and even longer [[1], [2], [3], [4], [5]].”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [1] Huang, 2021, 6-month consequences of COVID-19 in patients discharged from hospital: a cohort study, Lancet source

      Not checked in the free run.

    • cites [2] 2020, Editorial Long COVID: let patients help define long-lasting COVID symptoms, Nature source

      Not checked in the free run.

    • cites [3] Davis, 2021, Characterizing long COVID in an international cohort: 7 months of symptoms and their impact, EClinicalMedicine source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    Female patients overall had a milder form of disease, estimated as a lower proportion of OTI and a shorter length of hospital stay.

    “Furthermore, overall patients of female gender presented a milder form of disease, estimated as a lower proportion of OTI and a shorter LOS (Table 2 ).”
    Quote in the paperNot a substantial claim

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

    Study design and conductown data

    115 of 492 patients (23%) missed their follow-up visit.

    “In total 115/492 (23%) patients missed their visit, thus the study includes a total of 377/492 individuals, namely 77% of those who were given an appointment.”
    Quote in the paperNot a substantial claim

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

    Premisecitation

    Long COVID negatively impacts quality of life and patient work ability and social relationships.

    “Nevertheless, what emerges from preliminary data is the negative impact of long COVID on quality of life and its effects on patient work ability and social relationships [1,4,19].”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [1] Huang, 2021, 6-month consequences of COVID-19 in patients discharged from hospital: a cohort study, Lancet source

      Not checked in the free run.

    • cites [4] Carfì, 2020, Gemelli against COVID-19 post-acute care study group. Persistent symptoms in patients after acute COVID-19, JAMA source

      Not checked in the free run.

    • cites [19] Chopra, 2020, Sixty-day outcomes among patients hospitalized with COVID-19, Ann Intern Med source

      Not checked in the free run.

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

    Interpretationcitation

    The proportion of patients with long COVID in this study matched figures from earlier reports.

    “The high incidence of long COVID within our cohort was similar to that previously reported: more than half of patients reported symptoms lasting more than 2 months after symptom onset [4,5,16,18,19].”
    Quote in the paperNot a substantial claim0 of 5 sources checked
    • cites [4] Carfì, 2020, Gemelli against COVID-19 post-acute care study group. Persistent symptoms in patients after acute COVID-19, JAMA source

      Not checked in the free run.

    • cites [5] Venturelli, 2021, Surviving COVID-19 in Bergamo Province: a post-acute outpatient re-evaluation, Epidemiol Infect

      Not checked in the free run.

    • cites [16] Xiong, 2021, Clinical sequelae of COVID-19 survivors in Wuhan, China: a single-centre longitudinal study, Clin Microbiol Infect source

      Not checked in the free run.

    • cites [18] Moreno-Pérez, 2021, Post-acute COVID-19 Syndrome. Incidence and risk factors: a Mediterranean cohort study, J Infect

      Not checked in the free run.

    • cites [19] Chopra, 2020, Sixty-day outcomes among patients hospitalized with COVID-19, Ann Intern Med source

      Not checked in the free run.

    • Rests on an assumption: The follow-up duration used in the study is sufficient to capture long COVID.

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

    Study design and conductnone given

    Validated instruments for evaluating dyspnoea and fatigue were not available.

    “the lack in validated tools to assess dyspnoea and fatigue”
    Quote in the paperNot a substantial claim

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

    Premisecitation

    Previous reports have documented long COVID in patients who were not hospitalised and had mild, self-limiting illness.

    “long COVID has been previously described also in not hospitalised patients diagnosed with a mild, self-limiting disease [6,[16], [17], [18],24].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [6,[16], [17], [18],24]

      Not checked in the free run.

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

    Premisecitation

    The US CDC and the UK NICE have recognized symptoms that may last for weeks or months following recovery from COVID-19.

    “The American Center for Disease Control (CDC) and the British NICE have identified symptoms that could persist for weeks or even months after recovery from COVID-19.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [6], [7], [8],17

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S1 (asserted), S2 (checkable), S3 (load-bearing). May combine two claims.

    Premisecitation

    The duration of these symptoms, potential risk factors for their persistence, and patient characteristics that predispose to them remain to be clarified.

    “How long these symptoms could endure for, possible risk factors for their persistence and the predisposing patient features are all aspects to be further elucidated [[6], [7], [8],17].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [6], [7], [8],17

      Not checked in the free run.

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

    Premisecitation

    Certain long COVID symptoms also occur in other viral infections, and both physical and psychological after-effects have been documented in MERS and SARS.

    “Some symptoms are also commonly seen in other viral illnesses and both psychical and psychological sequelae have been described in MERS and SARS [12,[23], [24], [25], [26], [27], [28], [29]].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [12,[23], [24], [25], [26], [27], [28], [29]]

      Not checked in the free run.

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

    Premisecitation

    Obesity is known to involve heightened inflammation, impaired adaptive immunity, endothelial dysfunction, and coagulation abnormalities, which could account for the observed association between high BMI and long COVID.

    “Increased inflammation, defective adaptative immune responses, endothelial dysfunction and coagulation-related disorders are all phenomena that have been well described in obesity and might represent a plausible explanation to the link we observed between high BMI and long COVID [33].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [33] Drucker, 2021, Diabetes, obesity, metabolism, and SARS-CoV-2 infection: the end of the beginning, Cell Metab source

      Not checked in the free run.

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

    Premisecitation

    Older age has been linked to persistent fatigue, musculoskeletal pain, and reduced pulmonary function.

    “Advanced age was associated with ongoing fatigue and musculoskeletal pain, or impairment in pulmonary functions, reflecting a decline in organ function and a slower ability to recover [1,16].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [1] Huang, 2021, 6-month consequences of COVID-19 in patients discharged from hospital: a cohort study, Lancet source

      Not checked in the free run.

    • cites [16] Xiong, 2021, Clinical sequelae of COVID-19 survivors in Wuhan, China: a single-centre longitudinal study, Clin Microbiol Infect source

      Not checked in the free run.

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

    Premisecitation

    Published findings on the link between female sex and long COVID are mixed: some studies report higher rates of fatigue or other symptoms in women, whereas others find no association with gender.

    “Literature data are not equivocal about the association between females and long COVID: some preliminary studies have shown an increased prevalence of fatigue [24] or other symptoms among women [1,5,13,16], while in other studies no gender association was found [4,[18], [19], [20]].”
    Quote in the paperNot a substantial claim0 of 6 sources checked
    • cites [24] Townsend, 2020, Persistent fatigue following SARS-CoV-2 infection is common and independent of severity of initial infection, PLoS One source

      Not checked in the free run.

    • cites [1] Huang, 2021, 6-month consequences of COVID-19 in patients discharged from hospital: a cohort study, Lancet source

      Not checked in the free run.

    • cites [5] Venturelli, 2021, Surviving COVID-19 in Bergamo Province: a post-acute outpatient re-evaluation, Epidemiol Infect

      Not checked in the free run.

    • cites [13] Mazza, 2020, Anxiety and depression in COVID-19 survivors: role of inflammatory and clinical predictors, Brain Behav Immun source

      Not checked in the free run.

    • cites [16] Xiong, 2021, Clinical sequelae of COVID-19 survivors in Wuhan, China: a single-centre longitudinal study, Clin Microbiol Infect source

      Not checked in the free run.

    • cites [4,[18], [19], [20]]

      Not checked in the free run.

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

    Study design and conductnone given

    Losses to follow-up may have introduced selection bias.

    “a possible selection bias due to losses to follow-up”
    Quote in the paperNot a substantial claim

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

    Study design and conductnone given

    Information on whether symptoms existed prior to acute infection was missing.

    “and in information about the presence of the symptoms before the onset of acute infection”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Study design and conductnone given

    The sample size was small for patients with severe disease and for females.

    “the limited sample size for patients with severe disease and females”
    Quote in the paperNot a substantial claim
56 of 56

  • The paper relies on this without support.

    The tools used to assess dyspnoea and fatigue are adequate for identifying long COVID symptoms.

    “the lack in validated tools to assess dyspnoea and fatigue”

  • The paper relies on this without support.

    The follow-up duration used in the study is sufficient to capture long COVID.

    “The evaluation of our patients at six months still needs to be completed”

  • The paper relies on this without support.

    No prior research had examined the link between smoking and long COVID.

    “the relationship between smoking and long COVID has not been previously explored”
3 of 3

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.

  • Pooled GOT median exceeds both subgroup medians

    Minor

    The reported overall median is 27, although the medians of the two groups comprising the population are 25 and 26. A pooled median cannot exceed both subgroup medians.

  • Antiviral-treatment percentage uses the wrong denominator

    Minor

    The table reports 92 patients receiving antivirals out of a study population of 377. That is 24.4%, not 22.4%.

    Reported 22.4 · recomputed 24.403183

  • BMI odds ratio falls outside its confidence interval

    Minor

    For BMI below 30, the unadjusted odds ratio is 0.55, but its stated 95% confidence interval runs from 2.27 to 5.06 and does not contain the estimate.

  • Adjusted BMI-unknown estimate falls outside its confidence interval

    Minor

    The adjusted odds ratio for unknown BMI is 0.13, below the stated confidence interval's lower bound of 0.30.

  • Pooled GPT median exceeds both subgroup medians

    Minor

    The reported overall median is 21, while each of the two constituent groups has a median of 20. The overall median cannot be higher than both.

5 of 5

Cites

1 retracted

Flagged first, then by citations

Cited by

Sorted by citations

Related

Authors
Bai, F., Tomasoni, D., Falcinella, C., Barbanotti, D., Castoldi, R., Mulè, G., Augello, M., Mondatore, D., Allegrini, M., Cona, A., Tesoro, D., Tagliaferri, G., Viganò, O., Suardi, E., Tincati, C., Beringheli, T., Varisco, B., Battistini, C. L., Piscopo, K., Vegni, E., Tavelli, A., Terzoni, S., Marchetti, G., & Monforte, A. D.
Affiliations
University of Milan (IT)
Corresponding author
Bai, Francesca
ORCID
Venue
Clinical Microbiology and Infection
Publisher
Elsevier BV
Published
2022-04
Volume
28
Issue
4
Pages
611.e9-611.e16
ISSN
1198-743X (ISSN-L)
DOI
10.1016/j.cmi.2021.11.002
PMC
PMC8575536
OpenAlex
W3213374156
Semantic Scholar
2259751868b43bde80c15a6bb28194b9e5077efe
Cited by
644
References
33
Citations by year
2026: 56 · 2025: 138 · 2024: 206 · 2023: 148 · 2022: 95 · 2013: 1
FWCI
54.37
Type
journal article
Language
en
Open access
Licence
Locations
  • Clinical Microbiology and Infection (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
Gilead Sciences
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
long COVID, female gender, sex differences, COVID-19 pandemic, post-traumatic stress disorder, anxiety, depression, fatigue, brain fog, exertional dyspnea, musculoskeletal pain, sex hormones
MeSH terms
COVID-19, SARS-CoV-2, Post-Acute COVID-19 Syndrome, Adult, Female, Humans, Male, Prospective Studies, Respiration, Artificial

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 2026-10-06.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-06.

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.

What counts as a claim ›How we measure confidence ›How we check this ›

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