Risk factors for rejection following COVID-19 in lung transplant recipients

Introduction/Aim: The prevalence of and risk factors for acute cellular (ACR) and antibody mediated rejection (AMR) in lung transplant (LTx) recipients is unclear. Method(s): We performed a retrospective cohort study of all living LTx recipients between January 2020 and September 2022. Recipients with COVID-19 infection and those diagnosed with and/or treated for ACR or AMR were identified. Baseline demographics are described. A logistic regression univariate analysis was used to identify risk factors for rejection. Result(s): 128/387 (33%) LTx recipients tested positive to SARS-CoV-2 during the study period. 44 (32.3%) patients were investigated for graft dysfunction, with persistent loss of >=10% of FEV 1 at >=90-days in 37 (31.4%), median was 54.5 years (23-76). There was no significant difference between gender, disease severity or presence of chronic lung allograft dysfunction (CLAD) at time of COVID-19 infection. 9(20.5%) recipients experienced rejection, 3 (6.8%) with AMR, 5 (11.4%) ACR, and 1 (2.3%) both. Median time to onset of rejection was 59 days (16-239). Change in FEV 1 post COVID-19 was not significantly different between recipients with and without rejection, with mean volume loss in rejection group 559 mL (SD 678 mL, 22.9%), and 842 mL (SD 824 mL, 42.9%) in non-rejecters. Univariate logistic regression of risk factors demonstrated younger patients were at higher risk of rejection (OR 0.95 [95% CI 0.90-1.00] p = 0.05). Female gender was weakly associated with rejection (OR 0.21 [95% CI 0.04-1.18] p = 0.08). Time post-transplant, severe COVID illness, early COVID-19 treatment did not show association. Conclusion(s): Acute rejection occurs frequently following COVID infection and should be considered a differential in persistent allograft dysfunction. Younger age and female gender were associated with increased risk of rejection. The volume of lung function lost did not differentiate between those who did and did not suffer rejection;we hypothesise due to non-alloimmune inflammatory processes.

Hospitalisation and death in lung transplant recipients following COVID-19 infection

Introduction/Aim: Rates of hospitalisation and death from COVID-19 in lung transplant (LTx) recipients vary internationally. We aimed to assess risk factors for this in an Australian cohort. Method(s): We performed a retrospective cohort study of all LTx recipients between January 2020 and September 2022. LTx recipients with COVID-19 were included. Baseline characteristics and treatments were recorded. Multivariate logistic regression was performed to identify risk factors associated with hospitalisation and death. Result(s): 128/387 (33%) recipients tested positive to SARS-CoV-2 during the study period, 97.6% during the Omicron waves with 40(31.3%) requiring hospitalisation and 10 (7.8%) died. The median (IQR) recipient age was 50.6 (22-77). The cohort was of Caucasian ethnicity 105 (82%), 48% were female with high vaccination rates (98.4%). Chronic lung allograft dysfunction (CLAD) was present in 48 (37.5%). 103 (80.5%) of patients received early SARS-CoV-2 treatment with either Sotrovimab 84(65%), Molnupirivir 50(39%) or combination 31(24%). 25 patients (19.5%) received no early treatment. All hospitalised patients received Remdesivir and Dexamethasone as per local treatment protocols. Regarding risk of hospitalisation, multivariate analysis showed that recipient age (1-unit change OR 1.04 95% CI 1.01-1.07 p = 0.019) was associated with an increased risk, whereas Molnupiravir was protective (OR 0.32 95% CI 0.13-0.80 p = 0.02). In univariable analysis, increasing age (1-unit change, OR 1.07 95% CI 1.02-1.129 p = 0.01) and severe disease (OR 9.95 95% CI 2.58-38.32 p =< 0.001) were associated with an increased risk of death. Male gender, non-Caucasian ethnicity, CLAD, CKD stage 3-5 were correlated with death with weak association. Conclusion(s): Recipient age is a significant risk factor for both hospitalisation and death, and older patients with COVID-19 should be monitored closely during COVID-19 illness. Molnupirivir is protective against hospitalisation, with Sotrovimab having a weak association. Further analysis of the protective effect of pre-exposure prophylaxis with emerging therapies such as Evusheld would be helpful to fully evaluate the currently available early disease therapies in Australia.

COVID pneumonitis, a risk factor for persistent lung allograft dysfunction

Introduction/Aim: There is a paucity of data regarding the impact of COVID-19 on allograft function in lung transplant (LTx) recipients. Method(s): We performed a retrospective cohort study of all living LTx recipients in our service between January 2020 and September 2022. Patients with COVID-19 were identified and baseline characteristics recorded. Pre- and post-COVID-19 spirometry was used to identify persistent decline in allograft function (>=10% of FEV 1 decline at 90 days after infection and failure to return to baseline during the study period). Multivariable logistic regression was performed to identify risk factors associated with persistent allograft decline. Result(s): 128/387 (33%) LTx recipients tested positive to SARS-CoV-2 during the study period. The majority, 125 (97%) during the Omicron waves. In those with COVID-19, the median (IQR) recipient age was 50.6 (22-77) with median time post-transplant of 1522 (17-9842) days. The cohort was of Caucasian ethnicity, 105 (82%), with vaccination rates (98.4%) and 48% female. Chronic lung allograft dysfunction (CLAD) was present at time of infection in 48 (37.5%). Severe disease (oxygen requirement) was present in 40 (31%) patients and 10 (7.8%) died. Recipients were followed for median of 172 days (range 90-339) post infection. Persistent FEV 1 decline occurred in 37 (31.4%). Multivariate analysis showed severe disease was independently associated with an increased risk of persistent FEV 1 decline (OR 5.55 [95% CI 2.28-13.48] p =< 0.001). Non-Caucasian ethnicity (OR 2.83, [95% CI 0.92-8.65], p = 0.07) and the presence of CLAD (OR 2.39, [95% CI 0.94-6.08], p = 0.06), were positively correlated, with weak association. No significant association between recipient age, gender, time post-transplant, early COVID therapy, SARS-CoV-2 variant with persistent FEV 1 decline was seen. Conclusion(s): Persistent decline in lung allograft function is common post COVID-19 infection. Severe disease is strongly associated with this outcome and these patients should be monitored for poor long-term allograft recovery. Further investigation into pathological mechanisms responsible for persistent allograft decline is required.

Olfactory Performance in Post Mild-to-Moderate Acute Covid-19 across 2 Years

Background: Previous longitudinal studies (n=6) of objective olfaction performance post-acute COVID-19 have a maximum follow-up of 6-month and do not often test biomarkers. Although olfactory dysfunction appears to improve within two months of symptom onset, 4/6 longitudinal studies show persistent olfactory impairment. Method(s): PCR-confirmed COVID-19 patients in the prospective ADAPT cohort (Sydney, Australia) were assessed across 18 acute symptoms and hospitalization status: 40% mild, 50% moderate, 10% severe/hospitalised - none deceased). Blood samples were taken 2 (N=179), 4 (N=148) and 12-month (N=118) post-diagnosis. The NIH Odor Identification Test (OIT) and the Cogstate brief cognitive battery were performed. 58 also had an olfaction test at 24-month. The OIT raw data were transformed into demographically-corrected T-scores. OIT's attrition was completely random and only initial age (40+/-15 versus 47+/-15) differed between patients lost to follow-up and those in the study at 24-month. We tested peripheral neurobiomarkers (NFL, GFAP, S100B, GM-CSF) and immune markers (Interleukin-IL panel: 1-beta, 1Ralpha, 4, 5, 6, 8, 10, 12p40, 12p70, 13, and MCP-1, TNF-alpha and INF-gamma), analyzed as Log transformed and elevated/normal range using published references. Our previous analyses had shown no relationship with the kynurenine pathway, but an association of impaired olfaction and impaired cognition at 2-month only. Linear mixed effect regressions with time effect (months) tested olfaction trajectories (random subject effect) and their association with the biomarkers (main and time interaction). Result(s): At 2 months post-diagnosis 30% had impaired olfaction and those who had acute severe disease were more likely to be impaired (54% versus 26%, p=.009). 21%, 31% and 37% had impaired olfaction at 4, 12 and 24-months. Olfactory performance declined over time (p< .0001), which was dependent on the initial performance (Fig 1). Neurobiomarkers were within the normal range. IFN-gamma, IL-1Ralpha, IL-13 and TNF-alpha increased across time, p< .03-p< .0005. TNF-alpha and IFN-gamma showed a time covariance with poorer olfaction performance. Conclusion(s): Post-acute mild to moderate COVID-19 is associated with a declining olfactory performance up to 2-yr post-diagnosis, especially when initially impaired with the provisio of attrition although random. Olfactory performance decline may be mediated by upregulated immune parameters which are distinct from those driving cognitive changes. (Figure Presented).

Post-Covid Cognitive Impairment Mri Brain Scan Abnormalities: A Potential Biomarker

Background: Post-acute sequelae of SARS-COV-2 infection (PASC) is associated with cognitive impairment (CI) with unclear pathogenesis though blood brain barrier (BBB) impairment and excitotoxic injury appear significant. Post-acute sequelae of SARS-COV-2 infection (PASC) is associated with cognitive impairment (CI) with unclear pathogenesis though blood brain barrier (BBB) impairment and excitotoxic injury appear significant. We hypothesized that PASC CI patients would have brain inflammation and BBB disruption using advanced MR imaging. Method(s): In this prospective longitudinal study, 14 patients with PASC CI (mild and non-hospitalised) were enrolled (mean age of 45;10 F and 4 M) and 10 sex and age matched healthy controls. 13 had a follow up MR at 9-12 months (mean 10 months). All participants underwent DCE perfusion (an index of BBB integrity with Ktrans as the measurement), Diffusion Tensor Imaging (DTI) and single voxel MR spectroscopy (MRS) of the frontal cortex/white matter and the brainstem in addition to brain anatomical MRI. Between group analyses were used to determine which MRI outcomes were significantly different from controls in patients with PASC CI. Result(s): The PASCI CI group showed significantly increased (ie BBB impairment) Ktrans, and increased region (Frontal white matter and Brain Stem)-specific areas in the brain (p=< 0.005), reduction in NAA (ie neuronal injury) and mild reduction of Glx (ie excitotoxicity) in the frontal white matter and brain stem (p=0.004), and reduction in white matter integrity (increased diffusivity -greater radial and mean diffusivity). Increased Ktrans was correlated with increased both radial and mean diffusivity (r=0.9) in all tested brain regions. Ktrans significantly improved in the follow up MR (p= 002596 Z=-2.794872) with no difference between subjects and controls indicating BBB normalisation (p= 0.442418, z= -0.144841). White matter integrity also improved especially in the fractional anisotropy values in the executive networks (p=< 0.00045). MRS showed significant improvement in the NAA in the frontal white matter but Glx remain high as compared to the controls (p=0.0006). Conclusion(s): PASC CI was characterised by reversible diffuse BBB impairment, neuronal/axonal and excitotoxic injury. BBB impairment was associated with white matter disruption. These are suggestive biomarkers for the presence, severity and prognosis of PASC CI. Such biomarkers could underpin appropriate trial design and timing of intervention.

Prevalence and Risk Factors for Rejection Following COVID-19 in a Single Centre Australian Lung Transplant Cohort

Persistent and irreversible loss of allograft function has been described in lung transplant recipients post COVID-19 illness. The prevalence of and risk factors for acute cellular (ACR) and antibody mediated rejection (AMR) in this cohort is unclear. A retrospective cohort study of all living LTx recipients between Jan-2020 and Sep-2022 was performed. Medical record review identified recipients with COVID-19 infection and those diagnosed with, and/or treated for ACR or AMR. AMR was defined as new or >10% increase in donor specific antibodies with associated loss of lung function. ACR was defined as biopsy proven ISHLT Grade A or B rejection. Baseline demographics are described. A logistic regression univariate analysis was used to identify risk factors for rejection. 128/387 (33%) LTx recipients tested positive to SARS-CoV-2 during the study period. 44 (32.3%) patients were investigated for graft dysfunction, 37 (31.4%) recipients had persistent loss of ≥10% of FEV 1 at ≥90-days. Median age in this cohort is 54.5 years (23-76). There was no significant difference between gender, disease severity or presence of CLAD at COVID-19 infection. Rejection was identified in 9(20.5%) recipients, 3 (6.8%) with AMR, 5 (11.4%) ACR, and 1 (2.3%) both. The median onset of rejection was 59 days (16-239). Volume and percent change in FEV 1 post COVID-19 was not significantly different between recipients with and without rejection. Those with rejection had a mean volume loss of 559 mL (SD 678 mL, 22.9%), while those without rejection had 842 mL (SD 824 mL, 42.9%). Univariate logistic regression analysis demonstrated positive association of younger patients for risk of rejection (OR 0.95, 95% CI 0.90-1.00, p=0.05). Female gender was weakly associated with rejection (OR 0.21, 95% CI 0.04-1.18, p=0.08). There was no significant association with time post-transplant, severe COVID illness, early COVID-19 treatment and rejection. Acute rejection was frequent post COVID infection and should be considered a differential in persistent allograft dysfunction. Younger age and female gender were associated with increased risk of rejection. The volume of lung function lost did not differentiate between those who did and did not suffer rejection. This may be explained by non-alloimmune inflammatory processes resulting in graft dysfunction. [ FROM AUTHOR] Copyright of Journal of Heart & Lung Transplantation is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Risk Factors for Persistent FEV1Decline Following COVID-19 Infection in Lung Transplant Recipients;a Single Australian Transplant Centre Experience

There is a paucity of data regarding the impact of COVID-19 on allograft function in LTx recipients We performed a retrospective cohort study of all living LTx recipients between Jan 2020 and Sep 2022. Patients with COVID-19 were identified by medical record review. Baseline characteristics at time of COVID-19 infection were recorded. Pre- and post-COVID-19 spirometry were used to identify persistent decline in graft function (≥10% of FEV 1 decline at 90 days after infection). Multivariable logistic regression was performed to identify risk factors associated with >10% decline in lung function which persisted at 90-days. 128/387 (33%) LTx recipients tested positive to SARS-CoV-2 during the study period;125 (97%) during the Omicron wave. In those with COVID-19, median (IQR) recipient age was 50.6 (22-77) with median time post-transplant 1522 (17 - 9842) days. The cohort was of Caucasian ethnicity 105 (82%), 48% were female and had high vaccination rates (98.4%). CLAD was present at time of infection in 48 (37.5%). Mortality rate was 10 (7.8%) with 40 (31%) requiring hospitalisation. 10 patients were excluded from further analyses (incomplete follow up data or duration post infection <90-days). Patients were followed for a median of 172 days (range 90-339) post infection. Mean FEV 1 across the whole cohort reduced by 10.2%. Persistent FEV 1 loss occurred in 37 (31.4%) patients. Multivariate analysis showed severe disease was independently associated with an increased risk of persistent FEV 1 decline (OR 5.55 [95%CI 2.28-13.48] p=<0.001). Non-Caucasian ethnicity (OR 2.83, [95%CI 0.92-8.65], p=0.07) and CLAD (OR 2.39, [95%CI 0.94-6.08], p=0.06), were weakly associated but positively correlated with persistent graft decline. There was no significant association between recipient age, gender, time post-transplant, early COVID therapy, SARS-CoV-2 variant or CKD with persistent FEV 1 decline. Persistent decline in allograft function at ≥90 days is common post SARS-CoV-2 infection in lung transplant recipients. Severe COVID-19 disease is strongly associated with this outcome and these patients should be monitored for risk of poor long-term graft recovery. Further investigation into the pathological mechanism responsible for persistent FEV 1 decline post SARS-CoV-2 infection is required. [ABSTRACT FROM AUTHOR] Copyright of Journal of Heart & Lung Transplantation is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Risk Factors for Death and Hospitalisation in COVID-19 Infection in Lung Transplant Recipients;a Single Australian Centre Experience

Rates of hospitalisation and death from COVID-19 in lung transplant recipients vary. We aimed to assess risk factors for hospitalisation and death in an Australian cohort of predominantly vaccinated recipients after COVID-19. A retrospective cohort study of all LTx recipients between Jan 2020-Sep 2022 with COVID-19 was performed. Baseline recipient characteristics and treatments were recorded. Multivariate logistic regression was performed to identify risk factors associated with hospitalisation and death. 128/387 (33%) recipients tested positive to SARS-CoV-2 during the study period, 97.6% during the Omicron waves. 40(31.3%) required hospitalisation and 10 (7.8%) died. The median (IQR) recipient age was 50.6 (22-77) with median time post-transplant 1522 (17 - 9842) days. The cohort had high vaccination rates (98.4%), were Caucasian ethnicity 105 (82%), 48% were female. CLAD was present in 48 (37.5%). 103 (80.5%) received early COVID-19 treatment with Sotrovimab 84(65%), Molnupirivir 50(39%) or in combination 31(24%). 25(19%) received no early treatment. All hospitalised patients received Remdesivir and Dexamethasone as per local treatment protocols. Regarding risk of hospitalisation, multivariate analysis showed recipient age (1-unit change OR 1.04 95%CI 1.01-1.07 p=0.019) was associated with an increased risk, where Molnupiravir was protective (OR 0.32 95%CI 0.13-0.80 p=0.02). There were weak positive associations between non-Caucasian ethnicity and protective associations with Sotrovimab and need for hospitalisation. In univariable analysis increasing age (1-unit change, OR 1.07 95%CI 1.02-1.129 p=0.01) and severe disease (OR 9.95 95%CI 2.58-38.32 p=<0.001) were associated with an increased risk of death. Male gender, non-Caucasian ethnicity, CLAD, CKD stage 3-5 were correlated with death with weak association. Recipient age is a significant risk for both hospitalisation and death. Older patients with COVID-19 should be monitored closely during COVID-19 illness. Molnupirivir is protective against hospitalisation, with Sotrovimab having a weak association. Further analysis of the protective effect of pre-exposure prophylaxis with new therapies such as Evusheld would be helpful to fully evaluate the currently available early disease therapies in Australia. [ABSTRACT FROM AUTHOR] Copyright of Journal of Heart & Lung Transplantation is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

QUINOLINIC ACID IS A BIOMARKER of COVID-19-ASSOCIATED COGNITIVE IMPAIRMENT

Background: COVID-19 infection-associated cognitive and olfaction impairments have an unclear pathogenesis, possibly related to systemic disease severity, hypoxia, or illness-associated anxiety and depression. A biomarker for these neurocognitive changes is lacking. The kynurenine pathway (KP) is an interferon stimulated myeloid cell mediated tryptophan degradation pathway important in immune tolerance, neurotoxicity and vascular injury, that is dysregulated in COVID-19. We hypothesized that neurocognitive impairments were associated with an activated KP. Methods: The current analysis includes COVID-19 patients as part of the ADAPT study, a prospective cohort (St Vincent's Hospital Sydney, Australia). Disease severity was assessed with 18 acute symptoms and hospitalization status. Blood samples were taken 2 months (N=136) and 4 months (N=121) post diagnosis along with cognitive (Cogstate Computerized Battery, CBB;NIH toolbox Odor Identification Test, OIT) and mental health screenings (DMI-10;IESR, SPHERE-34 Psychological subscale grouped into a composite score). KP metabolites (PIC, QUIN, 3HK, 3HAA, AA, KYN, TRP, log for analyses except for TRP) were measured by GC-MS and uHPLC. The CBB and OIT data were demographically-corrected. CBB follow-up data was also corrected for practice effect. Linear mixed effect regression models with time effect (days post diagnosis) tested whether cognition, and olfaction were associated the KP (main and time interaction);while correcting for disease severity, mental health and comorbidities. Results: 136 patients: mean age=46±15;40% females;90% English speaking background;disease severity: 40% mild, 50% moderate, 10% severe/hospitalised;34% treated comorbidities. At 2 months post diagnosis, 16% had cognitive impairment, and 25% had impaired olfaction. Cognitive impairment was more common in those with anosmia (p=.05). At 4 months, 23% had cognition impairment and 20% had impaired olfaction. QUIN (p=.001), 3HAA (p<.0001) increased over the study period, while TRP decreased (p=.02). QUIN level associated with poorer cognitive scores (p=.0007;QUIN (nM) between 800-1000 was most predictive). There was no time∗QUIN interaction. QUIN association to cognition persisted when severe cases were excluded (p<.005). Conclusion: COVID-19 is associated with KP activation, and the latter with cognitive impairment. QUIN was the only biomarker associated with cognitive impairment, and may be useful in monitoring and elucidating COVID-19 neuropathogenesis and treatment.

High rate of persistent symptom 4 months after community-managed COVID-19 infection

Background: The spectrum of recovery following community-managed and hospitalized SARS-CoV-2 infection remains uncertain. The aim of the ADAPT study was to determine prevalence and nature of persistent symptoms after community and hospitalised SARS-CoV-2 infection;and to evaluate lung function;health-related quality of life (HRQOL);and neurocognitive abnormalities. Methods: A prospective observational cohort study was performed at St Vincent's Hospital Sydney Australia. Adult patients with a positive SARS-CoV-2 RNA PCR test between Mar-2020 and Apr-2020 including mild, moderate, and severe acute infection were offered enrollment. The clinical outcomes included symptom prevalence at initial infection and follow-up, HRQOL measures, pulmonary function, neurocognition and COVID-19 antibody responses. Initial study assessments were performed up to 4 months after first detection of SARS-CoV-2. Results: Ninety-six patients were recruited following community-managed mild (39%) and moderate (50%), and hospitalized severe (11%) COVID-19 infection. 39.7% patients had persistent symptoms at median 72 days after diagnosis (IQR 65-87), including those in severe (77.8%), moderate (33.3%), and mild (36.7%) sub-populations. The most common persistent symptoms were fatigue (28%), shortness of breath (25%) and cough (21%). Total lung capacity (TLC) was significantly lower after severe, compared with community-managed, COVID-19, p=0.05. Abnormal diffusion capacity for carbon monoxide values were observed in 16% patients unrelated to acute illness severity. Twenty-four percent patients demonstrated anxiety/depression, as measured by SPHERE-34 item, with the highest proportion in the moderate sub-population (37%). Neurocognitive impairment was low (9%) but associated with abnormal olfaction (p=0.02). A high proportion of patients (77-85%) demonstrated positive antibody responses, on four commercial assays, at follow-up and titres were related to acute illness severity. Conclusion: A considerable proportion of patients experience persistent symptoms at 4 months after SARS-CoV-2 infection including one third of community managed patients. High rates of depression and anxiety were reported across the cohort. Outpatient follow-up to further assess those with persistent symptoms after COVID-19 is important to allow multi-disciplinary input, further investigation, and appropriate management. Data collection on the prevalence of persisting symptoms at 8 month follow-up of the ADAPT study is currently underway.

Cognitive deficits are not a byproduct of Anxio-depressive symptoms in COVID-19

Background: Cognitive deficits and anxio-depressive symptoms have been described in the recovery phase of COVID-19. Their association, or lack thereof, may assist in better understanding the long-term consequences of COVID-19. Methods: Patients underwent neurocognitive and mental health assessment at 2 months after initial SARS-CoV-2 infection as part of the St Vincent's Hospital ADAPT study, a prospective cohort study after COVID-19 disease. Cognition was assessed with the culture fair computerized Cogstate battery. A demographically-corrected composite z-score was created representing global cognitive performance, and then classified as impaired, borderline, and unimpaired. Anxio-depressive symptoms were assessed with the Depression in the Medical Ill scale-10 (DMI-10), the Somatic and Psychological HEalth Report-34 (SHPERE) Psych subscale, and the Impact of Events Scale-Revised (IESR). The scales scores were amenable to a single Principal Component explaining 80% of the variance. Female sex (p<.01) and Non-English-Speaking Background-NESB (p=.02) were associated with greater anxio-depressive symptoms but not age, education. Regression analyses tested sex and NESB unadjusted and adjusted predictions of anxio-depression to cognition. Results: 132 patients (mean age=46±15;40% women, median education=16 years, 10% NESB) were tested after predominantly community-managed COVID-19 (10% hospitalised). 17% had impaired global cognition, and 10% had borderline deficit. 25% had elevated symptoms on the DMI-10 (score>9), 13% on the IESR (score>24) and 35% on the SPHERE Psych scale (score≥2). Anxio-depression was not predictive of cognitive performance (unadjusted p=.43;adjusted p=.98) and of impaired/unimpaired status (unadjusted p=.50;adjusted p=.78). Anxio-depression tended to predict of borderline (vs. unimpaired) performance in unadjusted (p=.08) and adjusted (=.09) analyses. This was explained by the fact that women who had borderline performance tended to report higher anxio-depressive symptoms compared to their peers who were unimpaired (p<.06);further impaired women (vs. unimpaired) tended to report the least anxio-depressive symptoms (p=.09). Conclusion: Cognitive deficits are not a by-product of anxio-depressive symptoms in recovering COVID-19 patients. Women appear to have a higher degree of introspection and reaction to very mild cognitive decline. Cognitive changes appear to be a direct consequence of COVID-19.