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Cited by 1,804COVID-19 and Mental HealthLong-Term Effects of COVID-19COVID-19 Clinical Research Studies

Anxiety and depression in COVID-19 survivors: role of inflammatory and clinical predictors

Open access
Mazza, Mario Gennaro, De Lorenzo, Rebecca, Conte, Caterina, Poletti, Sara, Vai, Benedetta, Bollettini, Irene, Melloni, Elisa Maria Teresa, Furlan, Roberto +3 more·2020·Brain, Behavior, and Immunity
DOI 10.1016/j.bbi.2020.07.037PMC PMC7390748
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Abstract

Highlights • COVID-19, such as other coronaviruses, is associated with psychiatric implication.• 55% of the sample presented a clinical score for at least one mental disorder.• Psychiatric history, setting, and length of hospitalization influenced psychopathology.• Females suffered more than males, scoring higher in all the measures.• There is the need to diagnose and treat psychiatric sequelae in COVID-19 survivors.

Integrity signals

Registry

Crossref · 10.1016/j.bbi.2020.07.037

Cites

55 of 55 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 34 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    Follow-up oxygen saturation level was higher in patients managed at home.

    “Baseline inflammatory markers (CRP, NLR, MLR, and SII) were higher in males and in patients that were treated as inpatients, while follow-up oxygen saturation level was higher in patients that were managed at home (Table 1).”
    Quote in the paperNot a substantial claim
  • Findingown data

    2.9% of patients scored 1 on the BDI suicide item, indicating suicidal ideation.

    “Severity of depression also included suicide ideation and planning, with 2.9% scoring 1 (suicidal ideation) at the BDI suicide item, 0.8% scoring 2 and 0.8% scoring 3 (suicidal planning).”
    Quote in the paperNot a substantial claim
  • Findingown data

    Duration of hospitalization was inversely correlated with PCL-5 scores.

    “Duration of hospitalization inversely correlated with PCL-5 (r = −0.15, p = 0.019), ZSDS (r = −0.16, p = 0.009), BDI-13 (r = −0.13, p = 0.036), STAI-Y state (r = −0.18, p = 0.003), and OCI (r = −0.12, p = 0.044).”
    Quote in the paperNot a substantial claim
  • Findingown data

    A Student's t-test comparison of mean baseline inflammatory markers between patients with and without clinical-range psychopathological scores showed no significant effects.

    “A comparison (Student’s t test) of mean baseline inflammatory markers between patients who showed or not psychopathological scores in the clinical range did not show significant effects.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Baseline inflammatory markers measured at ED reflect the inflammatory processes relevant to later psychopathology.
  • Findingown data

    In COVID-19 survivors assessed about one month after discharge or ED visit, 55.7% scored in the clinical range on at least one psychopathological dimension.

    “A significant proportion of patients self-rated symptoms in the pathological range: overall, 55.7% scored in the clinical range in at least one psychopathological dimension (PTSD according to IES-R and/or PCL-5, depression according to ZSDS and/or BDI-13, anxiety according to STAI-Y state, and OC symptomatology according to OCI), 36.8% in two, 20.6% in three, and 10% in four.”
    Quote in the paperSubstantial claim
  • The quote only partly states this claim. 1
  • May combine two claims. 14
  • Classified as probably not a substantial claim. 17

  • The quote only partly states this claim.

    Findingown data

    Duration of hospitalization was inversely correlated with STAI-state scores.

    “Duration of hospitalization inversely correlated with PCL-5 (r = −0.15, p = 0.019), ZSDS (r = −0.16, p = 0.009), BDI-13 (r = −0.13, p = 0.036), STAI-Y state (r = −0.18, p = 0.003), and OCI (r = −0.12, p = 0.044).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Baseline inflammatory markers and follow-up oxygen saturation levels did not correlate with psychopathological scores, except for a nominal direct correlation between OCI and baseline MLR that did not survive correction for multiple comparisons.

    “Baseline inflammatory marker as well as follow up oxygen saturation levels did not correlate with psychopathological scores except for a nominal direct correlation between OCI and baseline MLR, not surviving correction for multiple comparisons (Table 2 ).”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Baseline inflammatory markers measured at ED reflect the inflammatory processes relevant to later psychopathology.

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

    Findingown data

    0.8% of patients scored 2 on the BDI suicide item.

    “Severity of depression also included suicide ideation and planning, with 2.9% scoring 1 (suicidal ideation) at the BDI suicide item, 0.8% scoring 2 and 0.8% scoring 3 (suicidal planning).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Baseline inflammatory markers (CRP, NLR, MLR, SII) were higher in males and in patients treated as inpatients.

    “Baseline inflammatory markers (CRP, NLR, MLR, and SII) were higher in males and in patients that were treated as inpatients, while follow-up oxygen saturation level was higher in patients that were managed at home (Table 1).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The study sample showed high rates of PTSD, depression, anxiety, insomnia and obsessive-compulsive symptomatology.

    “We reported high rates of PTSD, depression, anxiety, insomnia, and OC symptomatology.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In this sample, females and patients with a positive previous psychiatric diagnosis had greater severity across all psychopathological dimensions.

    “With regard to the risk factor related to psychopathology, consistently with previous epidemiological studies, we have found that females, and patients with positive previous psychiatric diagnoses, suffered more in all psychopathological dimensions (Vindegaard and Eriksen Benros, 2020, Ozamiz-Etxebarria et al., 2020, Pappa et al., 2020).”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Vindegaard and Eriksen Benros, 2020 source

      Not checked in the free run.

    • cites Ozamiz-Etxebarria et al., 2020

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    • cites Pappa et al., 2020 source

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  • May combine two claims.

    Findingown data

    OCI scores correlated directly with MLR, and there was a trend toward a direct correlation of OCI with NLR and SII.

    “Interestingly, we also found a direct correlation between OCI and MLR and a trend for a direct correlation between OCI and NLR and SII, suggesting that higher baseline inflammation could be associated whit later OC symptomatology.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Neither oxygen saturation level at follow-up nor baseline inflammatory markers were associated with depression, anxiety, PTSD or insomnia.

    “Neither oxygen saturation level at follow up nor baseline inflammatory markers associated with depression, anxiety, PTSD nor insomnia, suggesting that psychiatric symptomatology was not a manifestation of physical symptoms, with the exception of baseline SII that positively associated with measures of anxiety and depression at follow-up.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Outpatients showed increased anxiety and sleep disturbances.

    “Moreover, outpatients showed increased anxiety and sleep disturbances, while the duration of hospitalization inversely correlated with PTSD, depression, anxiety, and OC symptomatology.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In a multivariate GLM of baseline inflammatory markers (CRP, NLR, MLR, SII) on current psychopathological status, only SII showed a significant effect (Wilks' λ = 0.92; F = 2.12; d.f. 8,185; p = 0.0357); no other marker survived the statistical threshold.

    “A multivariate GLM analysis of the effects of baseline inflammatory markers (CRP, NLR, MLR, and SII) on the current psychopathological status revealed however a significant effect of SII (Wilks’ λ = 0.92; F = 2.12; d.f. 8,185; p = 0.0357), with no effect of the other markers surviving the statistical threshold.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingnone given

    Baseline inflammatory parameters were higher among males and inpatients, who showed less psychopathology at follow-up.

    “Moreover, baseline inflammatory parameters where higher among males and inpatients, who showed less psychopathology at follow-up, corroborating the complexity of the interaction between psychopathology and physical status.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    Coronaviruses could induce psychopathological sequelae through direct viral infection of the CNS or indirectly via an immune response.

    “Coronaviruses could induce psychopathological sequelae through direct viral infection of the central nervous system (CNS) or indirectly via an immune response (Wu et al., 2020).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Wu et al., 2020

      Not checked in the free run.

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

    Premisecitation

    Coronavirus exposure has been implicated in neuropsychiatric diseases during and after SARS and MERS outbreaks.

    “Coronavirus exposure has also been implicated in neuropsychiatric diseases during and after Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS) outbreaks (Rogers et al., 2020).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Rogers et al., 2020 source

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

    Premisecitation

    SARS survivors reported psychiatric symptoms including PTSD, depression, panic disorder, and OCD at 1 to 50 months follow-up.

    “SARS survivors reported psychiatric symptoms, including post-traumatic stress disorder (PTSD), depression, panic disorder, and obsessive-compulsive disorder (OCD) at 1 to 50 months follow up (Wu et al., 2020, Cheng et al., 2004, Lam et al., 2009).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Wu et al., 2020

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    • cites Cheng et al., 2004 source

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    • cites Lam et al., 2009 source

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

    Premisecitation

    Seropositivity for coronaviruses is associated with suicide and psychosis persisting one year after SARS.

    “Moreover, seropositivity for coronaviruses associated with suicide and psychosis persisting one year after SARS (Okusaga et al., 2011).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Okusaga et al., 2011 source

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  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    Preliminary data suggest that patients with COVID-19 might experience delirium, depression, anxiety, and insomnia.

    “Preliminary data suggest that patients with COVID-19 might experience delirium, depression, anxiety, and insomnia (Rogers et al., 2020).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Rogers et al., 2020 source

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  • May combine two claims.

    Premisecitation

    Coronaviruses are potentially neurotropic and can induce neuronal injuries.

    “Clinical, post-mortem, animal, in vitro, and cell culture studies demonstrated that coronaviruses are potentially neurotropic and can induce neuronal injuries (Desforges et al., 2019).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Desforges et al., 2019 source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    Infection-triggered perturbation of the immune system could specifically foster psychopathology.

    “Current insight into inflammation in psychiatry suggests that infection-triggered perturbation of the immune system could specifically foster psychopathology, adding to the psychological stress of enduring a potentially fatal disease, and to stress-associated inflammation (Miller and Raison, 2016).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Miller and Raison, 2016 source

      Not checked in the free run.

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

    Premisecitation

    The systemic immune-inflammation index is an objective marker of the balance between host systemic inflammation and immune response status, combining neutrophil, platelet and lymphocyte counts, each involved in different immune/inflammatory pathways.

    “The SII is an objective marker of the balance between host systemic inflammation and immune response status considering together neutrophil, platelet, and lymphocyte all of them involved in different pathway of immune/inflammatory response (Huang et al., 2019).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Huang et al., 2019 source

      Not checked in the free run.

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

    Premisecitation

    In a single study, higher SII levels were associated with major depressive disorder.

    “In a single study, higher SII levels were associated with major depressive disorder (MDD) (Zhou et al., 2020), suggesting that it could be a marker of the low-grade inflammation observed in mood disorders (Benedetti et al., 2020, Arteaga-Henríquez et al., 2019).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Zhou et al., 2020 source

      Not checked in the free run.

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

    Premisecitation

    Depression is associated with a markedly increased risk of all-cause and cause-specific mortality.

    “Moreover, depression associates with a markedly increased risk of all-cause and cause-specific mortality (Cuijpers et al., 2014).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Cuijpers et al., 2014 source

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  • Classified as probably not a substantial claim.

    Study design and conductnone given

    Psychiatric assessment was performed by well-trained psychiatrists using the best estimation procedure, taking into account charts, medical records, and relative information.

    “An unstructured clinical interview was conducted by well-trained psychiatrists in charge using the best estimation procedure, taking into account available charts, computerized medical records, and, if needed, the information provided by a relative.”
    Quote in the paperSubstantial claim

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

    Interpretationnone given

    This is the first study to investigate psychopathology in a sample of COVID-19 survivors one month after hospital treatment.

    “This is the first study that investigates psychopathology in a sample of COVID-19 survivors at one month follow-up after hospital treatment.”
    Quote in the paperNot a substantial claim

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

    Study design and conductreasoning

    Exclusion criteria were limited to patients under 18 to keep a naturalistic study design.

    “To keep a naturalistic study design, exclusion criteria were limited to patients under 18 years.”
    Quote in the paperNot a substantial claim

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

    Premisecitation

    Higher concentrations of these cytokines appear to indicate a more severe clinical course.

    “Higher concentrations of these cytokines seem to suggest a more severe clinical course (Huang et al., 2020).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Huang et al., 2020 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Less healthcare support may have increased the social isolation and loneliness characteristic of the COVID-19 pandemic, thereby inducing more psychopathology after remission.

    “Also considering the worse severity of COVID-19 in hospitalized patients, this observation suggests that less healthcare support could have increased the social isolation and loneliness typical of COVID-19 pandemics, thus inducing more psychopathology after remission (Ozbay et al., 2007, Leigh-Hunt et al., 2017).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Ozbay et al., 2007

      Not checked in the free run.

    • cites Leigh-Hunt et al., 2017 source

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

    Premisecitation

    Higher SII levels have been associated with worse prognosis in several medical diseases, particularly in oncology.

    “Higher levels have been associated with worse prognosis in several medical diseases, in particular in the field of oncology.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Huang et al., 2019 source

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

    Premisecitation

    The interaction between innate and adaptive immune systems and neurotransmitters emerged as a mechanism underpinning mood disorders, psychosis, and anxiety disorders.

    “The interaction between innate and adaptive immune systems and neurotransmitters emerged as a mechanism underpinning mood disorders, psychosis, and anxiety disorders (Najjar et al., 2013).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Najjar et al., 2013 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationnone given

    Psychiatric consequences of SARS-CoV-2 infection may arise either from the immune response to the virus itself or from psychological stressors such as social isolation, the impact of a novel severe and potentially fatal illness, worry about infecting others, and stigma.

    “Psychiatric consequences to SARS-CoV-2 infection can be caused both, by the immune response to the virus itself, or by psychological stressors such as social isolation, psychological impact of a novel severe and potentially fatal illness, concerns about infecting others, and stigma.”
    Quote in the paperSubstantial claim

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

    Interpretationcitation

    The present findings parallel those of earlier coronavirus outbreak studies, in which post-illness psychiatric morbidity ranged from 10% to 35%.

    “Our findings mirror the results from previous coronaviruses outbreak studies, where the psychiatric morbidities ranged from 10% to 35% in the post-illness stage (Rogers et al., 2020, Sheng et al., 2005).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Rogers et al., 2020 source

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    • cites Sheng et al., 2005 source

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  • The paper relies on this without support.

    The sample of COVID-19 survivors from a single hospital is representative of COVID-19 survivors generally.

    “We screened for psychiatric symptoms 402 patients surviving COVID-19 (265 male, mean age 57.8, age range from 18 to 87 years), from April 6 to June 9, 2020, during an ongoing prospective cohort study at IRCCS San Raffaele Hospital in Milan.”

  • The paper relies on this without support.

    Baseline inflammatory markers measured at ED reflect the inflammatory processes relevant to later psychopathology.

    “Baseline inflammatory markers during acute COVID-19 were extracted from ED charts: C-reactive Protein (CRP), neutrophil/lymphocyte ratio (NLR), monocyte/lymphocyte ratio (MLR), and systemic immune-inflammation index (SII) (SII = platelets X neutrophils/lymphocytes) (Feng et al., 2020).”

  • The paper relies on this without support.

    The cohort of 402 hospitalized COVID-19 patients studied is representative of COVID-19 survivors generally, so that prevalence estimates from it apply to survivors at large.

    “In conclusion, our study hypotheses were supported by the present results based on a cohort of 402 patients.”
    “As predicted, COVID-19 survivors presented a high prevalence of emergent psychiatric sequelae, with 55% of the sample presenting a pathological score for at least one disorder.”
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Claims other papers make about this one

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

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.

  • Male count differs between the methods and Table 1

    Minor

    The methods report 265 male participants, while Table 1 reports 264 for the whole sample. The table's sex-group heading also gives 265 males.

  • MOS completion percentage is incorrect

    Minor

    Of the 402 participants, 328 represent about 81.59%, not the reported 87.6%.

    Reported 87.6 · recomputed 81.59204

  • IES-R sex-comparison chi-square has two values

    Minor

    The results text gives the IES-R sex comparison a chi-square value of 54.98, whereas the corresponding Table 1 row gives 54.06.

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Cites

Flagged first, then by citations

Research works printed but not linked: 2

  1. Benedetti, 2020, Neuroinflammation in bipolar depression, Front. Psychiatry, 11, 71, 10.3389/fpsyt.2020.00071 · DOI
  2. Hill, T., Lewicki, P., 2006. Statistics: methods and applications. A comprehensive reference for science, industry, and data mining. General Linear Models, StatSoft, Tulsa (OK); Chapter 18:245-276.

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Related

Authors
Mazza, M. G., De Lorenzo, R., Conte, C., Poletti, S., Vai, B., Bollettini, I., Melloni, E. M. T., Furlan, R., Ciceri, F., Rovere-Querini, P., & Benedetti, F.
Affiliations
Vita-Salute San Raffaele University (IT)
Corresponding author
Mazza, Mario Gennaro
ORCID
Venue
Brain, Behavior, and Immunity
Publisher
Elsevier BV
Published
2020-10
Volume
89
Pages
594-600
ISSN
0889-1591 (ISSN-L)
DOI
10.1016/j.bbi.2020.07.037
PMC
PMC7390748
OpenAlex
W3045973332
Semantic Scholar
b722f6a287c29c5fe0219e487aaf1f427b3e6209
Cited by
1,804
References
55
Citations by year
2026: 62 · 2025: 148 · 2024: 248 · 2023: 360 · 2022: 524 · 2021: 414 · 2020: 46 · 2019: 1 · 2012: 1
FWCI
133.81
Type
journal article
Language
en
Open access
Licence
Locations
  • Brain Behavior and Immunity (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Archivio Istituzionale della Ricerca - Università Vita-Salute San Raffaele (submittedVersion)
Topics
  • Social Sciences › Psychology › Clinical Psychology › COVID-19 and Mental Health
  • Health Sciences › Medicine › Neurology › Long-Term Effects of COVID-19
  • Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
Keywords
COVID-19 survivors, anxiety, depression, post-traumatic stress disorder, insomnia, obsessive-compulsive symptoms, systemic inflammation, inflammatory markers, systemic immune-inflammation index, sex differences, psychiatric comorbidity
MeSH terms
Betacoronavirus, COVID-19, SARS-CoV-2, Adolescent, Adult, Aged, Aged, 80 and over, Anxiety, Anxiety Disorders, Mental Disorders, C-Reactive Protein, Depression, Major Depressive Disorder, Depressive Disorder, Emergency Service, Hospital, Female, Humans, Inflammation, Sleep Initiation and Maintenance Disorders, Italy, Length of Stay, Leukocyte Count, Male, Middle Aged, Monocytes, Neutrophils, Obsessive-Compulsive Disorder, Pneumonia, Viral, Severity of Illness Index, Sex Factors, Stress Disorders, Post-Traumatic, Survivors, Coronavirus Infections, Lymphocyte Count, Young Adult, Pandemics, Suicidal Ideation

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