Despite the multitude of clinical manifestations of post-acute sequelae of SARS-CoV-2 infection (PASC), studies applying statistical methods to directly investigate patterns of symptom co-occurrence and their biological correlates are scarce.

We assessed 30 symptoms pertaining to different organ systems in 749 adults (age = 55 ± 14 years; 47% female) during in-person visits conducted at 6–11 months after hospitalization due to coronavirus disease 2019 (COVID-19), including six psychiatric and cognitive manifestations. Symptom co-occurrence was initially investigated using exploratory factor analysis (EFA), and latent variable modeling was then conducted using Item Response Theory (IRT). We investigated associations of latent variable severity with objective indices of persistent physical disability, pulmonary and kidney dysfunction, and C-reactive protein and D-dimer blood levels, measured at the same follow-up assessment.

The EFA extracted one factor, explaining 64.8% of variance; loadings were positive for all symptoms, and above 0.35 for 16 of them. The latent trait generated using IRT placed fatigue, psychiatric, and cognitive manifestations as the most discriminative symptoms (coefficients > 1.5, p < 0.001). Latent trait severity was associated with decreased body weight and poorer physical performance (coefficients > 0.240; p ⩽ 0.003), and elevated blood levels of C-reactive protein (coefficient = 0.378; 95% CI 0.215–0.541; p < 0.001) and D-dimer (coefficient = 0.412; 95% CI 0.123–0.702; p = 0.005). Results were similar after excluding subjects with pro-inflammatory comorbidities.

Different symptoms that persist for several months after moderate or severe COVID-19 may unite within one latent trait of PASC. This trait is dominated by fatigue and psychiatric symptoms, and is associated with objective signs of physical disability and persistent systemic inflammation.

White-matter hyperintensities have been associated with both schizophrenia and mood disorders, particularly bipolar disorder, but results are inconsistent across studies

To examine whether white-matter hyperintensities are a vulnerability marker for psychosis or are specifically associated with bipolar disorder

T2-weighted magnetic resonance imaging data were acquired in 129 individuals with first-episode psychosis (either affective or non-affective psychoses) and 102 controls who were randomly selected from the same geographical areas. Visual white-matter hyperintensity ratings were used for group and subgroup comparisons

There were no statistically significant between-group differences in white-matter hyperintensity frequency or severity scores. No significant correlations were found between white-matter hyperintensity scores and duration of illness, duration of untreated psychosis, or severity of psychotic, manic or depressive symptoms

White-matter hyperintensities are not associated with vulnerability to psychosis in general, or specifically with affective psychoses. Further, first-episode psychosis investigations using more quantitative methods are warranted to confirm these findings

In low-and middle-income countries people with schizophrenia are reported to experience better outcomes than those in high-income countries

To examine structural brain differences in people with first-episode psychosis and controls in Brazil

Magnetic resonance imaging using voxel-based morphometry was performed on 122 people with first-episode psychosis and 94 controls

There were significant decreases in grey matter in the left superior temporal and inferior prefrontal cortices, insula bilaterally and the right hippocampal region in first-episode psychosis (P<0.05, corrected for multiple comparisons). The subgroup of people with schizophrenia (n=62) exhibited a similar pattern of decrease in grey matter relative to controls

Structural abnormalities reported in psychosis in high-income countries are also present in first-episode psychosis in Brazil

Little is known about the incidence of first-episode psychosis in urban centres of low- or middle-income countries

To estimate the incidence of psychosis in São Paulo, a large metropolis of Brazil

Prospective survey of first-episode psychosis among residents aged 18–64 years resident in a defined area of São Paulo, over a 30-month period (July 2002- December 2004). Assessments were carried out with the SCID–I, and diagnoses given according to DSM – IV criteria. Population at risk was drawn from the 2000 Census data

There were 367 first-episode cases identified (51% women), and almost 40% fulfilled criteria for schizophrenia or schizophreniform disorder. The incidence rate for any psychosis was 15.8/100 000 person-years at risk (95% CI 14.3–17.6). Incidence of non-affective psychoses was higher among younger males

Incidence of psychosis in São Paulo was lower than expected for a large metropolis

5-HT2A receptor antagonism may be crucial to the action of atypical antipsychotics. Previous work has related 5-HT2A receptor blockade to clinical efficacy and protection from extrapyramidal side-effects.

We developed a SPET imaging protocol for assessing 5-HT2A receptor binding using the selective ligand 1231-5-1-R91150. Six healthy volunteers, five clozapine- and five risperidone-treated subjects with DSM–IV schizophrenia were studied. Multi-slice SPET was performed on each subject.

Cortex: cerebellum ratios were significantly lower in both clozapine-and risperidone-treated subjects compared with the healthy volunteers in all cortical regions. There was no difference in occupancy between the two drug-treated groups. No correlation was found between the percentage change in the Global Assessment Scale (GAS) and 5-HT2A receptor binding indices in the drug-treated groups.

Clozapine and risperidone potently block 5-HT2A receptors in vivo. The lack of relationship between receptor binding indices and change in GAS suggests that 5-HT2A receptor blockade may be unrelated to clinical improvement. Future studies will substantiate this finding by studying 5-HT2A receptor binding in large groups of patients treated with both typical and novel atypical antipsychotics.

We tested whether cortical and subcortical regional cerebral blood flow (rCBF) differs between patients with obsessive-compulsive disorder (OCD) and healthy controls. We then explored the relationship between rCBF and OCD mental state.

Thirty out-patients from the Maudsley Hospital with OCD as defined in DSM–III–R were scanned at rest using brain-dedicated, high-resolution, single photon emission tomography. RCBF was measured as uptake of 99mTc-HMPAO in 15 regions of interest and compared with rCBF data in 30 healthy people matched for age, sex and handedness. Symptom ratings were obtained using standard measures on the scanning day. Principal components factor analysis identified two distinct clinical dimensions: obsessive–compulsive (OC) and anxious–avoidant (AA). These were correlated with patients' rCBF measurements, using Spearman's rank correlation coefficient, and multiple regression coefficients calculated.

We found significant reductions in rCBF measurements of OCD patients compared with resting, healthy controls (F = 1.92, P = 0.04) in seven brain regions: the right and left superior frontal cortex, right inferior frontal cortex, left temporal cortex, left parietal cortex, right caudate nucleus and right thalamus. Regional differences were not secondary to generalised reduction in patients' brain perfusion. Reduced blood flow to the right inferior frontal cortex correlated significantly with illness severity (r = 0.37, P = 0.02). There was no relationship with age, age-of-onset, sex, handedness, depression or medication status. OC clinical dimension, concerning obsessions, compulsions and low mood, was significantly negatively correlated with left inferior frontal, medial frontal and right parietal rCBF. AA dimension, concerning anxiety and avoidance, was significantly positively associated with left and right superior frontal, right inferior frontal, medial frontal cortical, and right and left caudate and thalamic rCBF.

rCBF differs significantly between resting OCD patients and healthy controls, and separate clinical dimensions are associated with functionally distinct rCBF patterns.