Genetic Association between ACE2 (rs2285666 and rs2074192) and TMPRSS2 (rs12329760 and rs2070788) Polymorphisms with Post-COVID Symptoms in Previously Hospitalized COVID-19 Survivors.

The aim of the study was to identify the association between four selected COVID-19 polymorphisms of ACE2 and TMPRSS2 receptors genes with the presence of long-COVID symptomatology in COVID-19 survivors. These genes were selected as they associate with the entry of the SARS-CoV-2 virus into the cells, so polymorphisms could be important for the prognoses of long-COVID symptoms. Two hundred and ninety-three (n = 293, 49.5% female, mean age: 55.6 ± 12.9 years) individuals who had been previously hospitalized due to COVID-19 were included. Three potential genotypes of the following single nucleotide polymorphisms (SNPs) were obtained from non-stimulated saliva samples of participants: ACE2 (rs2285666), ACE2 (rs2074192), TMPRSS2 (rs12329760), TMPRSS2 (rs2070788). Participants were asked to self-report the presence of any post-COVID defined as a symptom that started no later than one month after SARS-CoV-2 acute infection and whether the symptom persisted at the time of the study. At the time of the study (mean: 17.8, SD: 5.2 months after hospital discharge), 87.7% patients reported at least one symptom. Fatigue (62.8%), pain (39.9%) or memory loss (32.1%) were the most prevalent post-COVID symptoms. Overall, no differences in long-COVID symptoms were dependent on ACE2 rs2285666, ACE2 rs2074192, TMPRSS2 rs12329760, or TMPRSS2 rs2070788 genotypes. The four SNPs assessed, albeit previously associated with COVID-19 severity, do not predispose for developing long-COVID symptoms in people who were previously hospitalized due to COVID-19 during the first wave of the pandemic.

Post-COVID Pain Is Not Associated with Inflammatory Polymorphisms in People Who Had Been Hospitalized by COVID-19.

Our aim was to assess the association between four inflammatory polymorphisms with the development of post-COVID pain and to associate these polymorphisms with the clinical pain phenotype in individuals who had been hospitalized by COVID-19. Three potential genotypes of IL-6 (rs1800796), IL-10 (rs1800896), TNF-α (rs1800629), and IFITM3 (rs12252) single nucleotide polymorphisms (SNPs) were obtained from no-stimulated saliva samples from 293 (49.5% female, mean age: 55.6 ± 12.9 years) previously hospitalized COVID-19 survivors by polymerase chain reactions. Pain phenotyping consisted of the evaluation of pain features, sensitization-associated symptoms, anxiety levels, depressive levels, sleep quality, catastrophizing, and kinesiophobia levels in patients with post-COVID pain. Analyses were conducted to associate clinical features with genotypes. One hundred and seventeen (39.9%) patients experienced post-COVID pain 17.8 ± 5.2 months after hospital discharge. No significant differences in the distribution of the genotype variants of any SNPs were identified between COVID-19 survivors with and without post-COVID pain (all, p > 0.47). Similarly, the clinical pain phenotype was not significantly different between patients with and without post-COVID pain since no differences in any variable were observed for any SNPs. In conclusion, four SNPs associated with inflammatory and immune responses did not appear to be associated with post-COVID pain in previously hospitalized COVID-19 survivors. Further, neither of the SNPs were involved in the phenotyping features of post-COVID pain.

Psychometric Properties of the Functional Impairment Checklist (FIC) as a Disease-Specific Patient-Reported Outcome Measure (PROM) in Previously Hospitalized COVID-19 Survivors with Long-COVID.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus is associated with a plethora of long-lasting symptoms (long-COVID). The presence of long-COVID symptoms causes decreased functionality. This study described the psychometric properties of the Functional Impairment Checklist (FIC), a disease-specific patient-reported outcome measure (PROM) used for evaluating the functional consequences of SARS in previously hospitalized COVID-19 survivors with long-COVID symptoms. The LONG-COVID-EXP-CM is a multicenter cohort study including patients hospitalized with COVID-19 during the first wave of the pandemic in five hospitals in Madrid. A total of 1969 (age: 61 ± 16 years, 46.4% women) COVID-19 survivors with long-COVID completed the FIC at a long-term follow-up after hospitalization (mean: 8.4 ± 1.5 months). Internal consistency (Cronbach alpha value), reliability (item-internal consistency, item-discriminant validity), construct validity (exploratory factor analysis), floor effect and ceiling effect were calculated. The mean time for fulfilling the FIC was 62 ± 11 s. The Cronbach's alpha values reflecting the internal consistency reliability were 0.864 for FIC-symptoms and 0.845 for FIC-disability. The correlation coefficient between the FIC-symptoms and FIC-disability scale was good (r: 0.676). The ceiling effect ranged from 2.29% to 9.02%, whereas the floor effect ranged from 38.56% to 80.19%. The exploratory factor analysis showed factor loadings from 0.514 to 0.866, supporting good construct validity. Women exhibited greater limitations in all physical symptoms and disability-related domains of the FIC compared with men (all, p < 0.001). Further, younger patients (those aged <45 years) self-reported lower physical symptoms and disability-related domains than older patients. In conclusion, this study indicates that the FIC has good psychometric properties to be used as a specific-disease PROM to measure function and disability in COVID-19 survivors with long-COVID.

Psychometric Properties of the Hospital Anxiety and Depression Scale (HADS) in Previously Hospitalized COVID-19 Patients.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus is associated with psychological/emotional disturbances. This study aimed to assess internal consistency, reliability, and construct validity of the Hospital Anxiety and Depressive Scale (HADS), as a patient-reported outcome measure (PROM) for evaluating emotional consequences of SARS-CoV-2 in hospitalized COVID-19 survivors with long COVID. The LONG-COVID-EXP-CM is a multicenter cohort study including patients hospitalized by COVID-19 during the first wave of the pandemic in five hospitals in Madrid. A total of 1969 (age: 61 ± 16 years, 46.5% women) COVID-19 survivors experiencing post-COVID symptoms a mean of 8.4 ± 1.5 months after hospital discharge completed HADS. Internal consistency (Cronbach α), reliability (item-internal consistency, item-discriminant validity), construct validity (confirmatory factor analysis), and floor effect and ceiling effect were calculated. The mean time for fulfilling HADS was 65 ± 12 s. A ceiling effect ranging from 1.99% to 13.74% and a floor effect ranging from 43.05% to 77.77% was observed. Based on the item-scale correlation coefficients, the Cronbach's alpha values reflecting the internal consistency reliability were 0.890 for the anxiety scale (HADS-A) and 0.856 for the depressive scale (HADS-D) The correlation coefficient between HADS-A and HADS-D scores was excellent (r: 0.878). The confirmatory factor analysis revealed that five out of the seven fitness indexes were excellent: CFI = 0.969, NNFI = 0.963; TLI = 0.963; AGFI = 0.951; GFI = 0.972), supporting good construct validity. In conclusion, this study indicates that both anxiety and depressive symptoms scales of HADS had overall good psychometric properties to be used for assessing psychological and emotional stress in COVID-19 survivors with long COVID.

Are Pain Polymorphisms Associated with the Risk and Phenotype of Post-COVID Pain in Previously Hospitalized COVID-19 Survivors?

OBJECTIVE: To investigate the association of different, selected pain polymorphisms with the presence of de novo long-COVID pain symptoms and to analyze the association between these polymorphisms with clinical, sensory-related, cognitive and psychological variables in COVID-19 survivors. METHODS: Two hundred and ninety-three (n =293, 49.5% female, mean age: 55.6 ± 12.9 years) previously hospitalized COVID-19 survivors participated. Three genotypes of the following single nucleotide polymorphisms (SNPs) were obtained from non-stimulated saliva: OPRM1 (rs1799971), COMT (rs4680), BDNF (rs6265), and HTR1B (rs6296) by polymerase chain reactions in all participants. Further, clinical (intensity/duration of pain), sensory-related (sensitization-associated symptoms, neuropathic pain features), psychological (anxiety or depressive levels, sleep quality), and cognitive (catastrophizing, kinesiophobia) variables were collected in those COVID-19 survivors suffering from post-COVID pain. Analyses were carried out to associate clinical features with genotype. RESULTS: Participants were assessed 17.8 ± 5.2 months after hospitalization. One hundred and seventeen (39.9%) experienced post-COVID pain (particularly of musculoskeletal origin). The distributions of the genotype variants of any SNP were not significantly different between COVID-19 survivors with and without long-term post-COVID pain (all, p >0.178). No differences in sensitization-associated symptoms, neuropathic pain features, catastrophizing, kinesiophobia levels, anxiety and depressive levels or sleep quality according to the genotype variant in any SNPs were found. No effect of gender was identified. CONCLUSION: The four SNPs generally associated with pain did not appear to predispose to the development of de novo long-COVID pain symptoms in previously hospitalized COVID-19 survivors. The SNPs were not involved in the phenotypic features of post-COVID pain either.

Prevalence and risk factors of musculoskeletal pain symptoms as long-term post-COVID sequelae in hospitalized COVID-19 survivors: a multicenter study.

ABSTRACT: This study investigated the prevalence of long-term musculoskeletal post-COVID pain and their risk factors in a large cohort of COVID-19 survivors. A multicenter cohort study including patients hospitalised because of COVID-19 in 5 hospitals of Madrid (Spain) during the first wave of the pandemic was conducted. Hospitalisation and clinical data were collected from medical records. Patients were scheduled for a telephone interview after hospital discharge for collecting data about the musculoskeletal post-COVID pain. Anxiety/depressive levels and sleep quality were likewise assessed. From 2000 patients recruited, a total of 1969 individuals (46.4% women, age: 61 years, SD: 16 years) were assessed on average at 8.4 (SD: 1.5) months after discharge. At the time of the study, 887 (45% women) reported musculoskeletal post-COVID pain. According to the presence of previous pain symptoms, the prevalence of "de novo" (new-onset) musculoskeletal post-COVID pain was 74.9%, whereas 25.1% experienced an increase in previous symptoms (exacerbated COVID-related pain). Female sex (odds ratio [OR]: 1.349, 95% confidence interval [CI]: 1.059-1.720), history of musculoskeletal pain (OR 1.553, 95% CI 1.271-1.898), presence of myalgia (OR 1.546, 95% CI 1.155-2.070) and headache (1.866, 95% CI 1.349-2.580) as COVID-19-associated onset symptoms, and days at hospital (OR 1.013, 95% CI 1.004-1.022) were risk factors associated with musculoskeletal post-COVID pain. In conclusion, musculoskeletal post-COVID pain is present in 45.1% of COVID-19 survivors at 8 months after hospital discharge with most patients developing de novo post-COVID pain. Female sex, history of musculoskeletal pain, presence of myalgia and headache as COVID-19 symptoms at the acute phase, and days at hospital were risk factors associated with musculoskeletal post-COVID pain.

Fatigue and Dyspnoea as Main Persistent Post-COVID-19 Symptoms in Previously Hospitalized Patients: Related Functional Limitations and Disability.

BACKGROUND: Multicentre studies focussing on specific long-term post-COVID-19 symptoms are scarce. OBJECTIVE: The aim of this study was to determine the levels of fatigue and dyspnoea, repercussions on daily life activities, and risk factors associated with fatigue or dyspnoea in COVID-19 survivors at long term after hospital discharge. METHODS: Age, gender, height, weight, symptoms at hospitalization, pre-existing medical comorbidity, intensive care unit admission, and the presence of cardio-respiratory symptoms developed after severe acute respiratory syndrome coronavirus 2 infection were collected from patients who recovered from COVID-19 at 4 hospitals in Madrid (Spain) from March 1 to May 31, 2020 (first COVID-19 wave). The Functional Impairment Checklist was used for evaluating fatigue/dyspnoea levels and functional limitations. RESULTS: A total of 1,142 patients (48% women, age: 61, standard deviation [SD]: 17 years) were assessed 7.0 months (SD 0.6) after hospitalization. Fatigue was present in 61% patients, dyspnoea with activity in 55%, and dyspnoea at rest in 23.5%. Only 355 (31.1%) patients did not exhibit fatigue and/or dyspnoea 7 months after hospitalization. Forty-five per cent reported functional limitations with daily living activities. Risk factors associated with fatigue and dyspnoea included female gender, number of pre-existing comorbidities, and number of symptoms at hospitalization. The number of days at hospital was a risk factor just for dyspnoea. CONCLUSIONS: Fatigue and/or dyspnoea were present in 70% of hospitalized COVID-19 survivors 7 months after discharge. In addition, 45% patients exhibited limitations on daily living activities. Being female, higher number of pre-existing medical comorbidities and number of symptoms at hospitalization were risk factors associated to fatigue/dyspnoea in COVID-19 survivors 7 months after hospitalization.