After COVID-19 infection, about 30% of people have clinically persisting symptoms, characterized as Post COVID-19 Condition (PCC). One of the most reported symptoms in PCC is cognitive dysfunction, yet there are only a few studies investigating long-term effects on different domains of cognitive function. A total of 107 young adults, university students aged 18-34 years, participated. In total, 68.2% had contracted SARS-CoV-2; 21.9% showed PCC. Three groups were compared: no-C19 (COVID-19-negative controls), C19 (COVID-19-recovered without PCC) and PCC. Attention and executive function were measured with the Vienna Test System (Schuhfried®, Mödling, Austria). In verbal working memory, the PCC group had a significantly lower performance with a moderate effect. The rate of below-average performance was higher in PCC (56.2%) compared to no-C19 (20.6%) and C19 (15.8%). In divided attention and response inhibition, PCC also showed lower performance, 62.5% and 37.5%, respectively, than no-C19 and C19. The co-occurrence of decreased cognitive functions was pronounced in PCC. The present study revealed significant long-lasting cognitive dysfunction in PCC in young adults, two years after COVID-19 infection. Verbal working memory was significantly impaired, and a lower performance was found in divided attention and response inhibition. In addition, there was an increased reaction time in most cognitive tasks, demonstrating cognitive slowing in young people with PCC.

Bufei huoxue capsules (BFHX), manufactured products of traditional Chinese medicine, have demonstrated anti-inflammatory properties and efficacy against chronic pulmonary diseases and COVID-19. This study was designed to further determine the clinical efficacy of BFHX in diverse patient subgroups during the convalescent phase of COVID-19, extending upon previously reported findings from a multicenter randomized controlled trial. Patients who had clinically recovered from COVID-19 were blindly assigned to BFHX or placebo groups. All enrolled patients underwent chest computed tomography (CT) imaging, 6-min walking distance (6MWD) test, and fatigue assessment inventory (FAI) at monthly follow-up for 3 months. A post hoc subgroup reanalysis was performed on subgroups of sex, age, severity of acute illness, and positive/negative IgG antibody against S antigen variants. A total of 129 patients were enrolled in BFHX (N = 64) and placebo groups (N = 65). The 6MWD and FAI scores were more significantly improved in females and mild patients than in males and severe patients after BFHX treatment. Lung CT image evaluated by the change in whole lung volume and mean CT value showed that the patients below 60 years gained more therapeutic effects after 3 months of BFHX treatment (p = 0.0008; p = 0.017; p = 0.0313, respectively). The subgroup reanalysis implies that the therapeutic effectiveness of BFHX in managing COVID-19 convalescence could potentially be influenced by factors including gender, age, and disease severity. Trial registration: This study was registered with the China Clinical Trial Registration Center (registration number: ChiCTR2000032573).

IntroductionThe first aim of this study was to compare synchronous and asynchronous telerehabilitation programs in COVID-19 survivors with classes 4-6 and determine the more appropriate telerehabilitation approach.MethodsThirty-six COVID-19 survivors with class 4-6 severity were randomly divided into two groups. Telerehabilitation programs were an 8-week exercise program that comprised pulmonary, aerobic, and strengthening exercises. Patients were assessed at the baseline, post-treatment, and follow-up for the incremental shuttle walk test (ISWT), short physical performance battery (SPPB), health-related quality of life (HRQoL) and hospital anxiety and depression scale (HADS)ResultsThe overall mean age of the study population was 54.06 (SD 10.50), and 15 (46.8%) were male. There were no significant differences between the two groups in any of the demographics and clinical characteristics at the baseline (p > 0.05), except for physical function (p < 0.05). There was a significant improvement in exercise capacity (p < 0.001) and lower extremity function (p < 0.01) within both groups in the short term and long term. There was a significant improvement in some subparameters of quality of life in both groups. As the synchronous group's short-term and long-term psychological status improved significantly, the asynchronous group's short-term psychological status improved significantly (p < 0.05). Telerehabilitation programs had similar effects, and only synchronous telerehabilitation outperformed asynchronous telerehabilitation in terms of physical function, role-emotional, and long-term anxiety.DiscussionAsynchronous telerehabilitation was as effective as synchronous telerehabilitation in developing clinical and functional parameters when properly planned and implemented.

Although post-COVID major depressive disorder (MDD) is frequent, the physiological mechanisms associated with it remain unclear. This study aimed to assess the association between 10 residual blood markers of inflammation and the presence of MDD 4 months after the acute phase of COVID-19.

This is a cross-sectional study of the COMEBAC cohort that followed patients 4 months after hospitalization for COVID-19 at Bicêtre Hospital. Patients with lingering symptoms or who had been in critical care (n = 177) were invited to a day hospital for assessment of MDD and peripheral inflammation. Ten peripheral inflammatory markers were examined: plasmatic C-reactive protein; leukocyte, monocyte, neutrophil, and lymphocyte counts; the neutrophil to lymphocyte ratio; the systemic inflammatory index (i.e., the (platelet x neutrophil) to lymphocyte ratio); cortisol, ferritin, and hemoglobin levels. Current MDD was assessed through structured interviews with a psychiatrist, depressive symptoms through self-questionnaires. Peripheral inflammatory markers were compared between patients with post-COVID MDD and patients without a lifetime history of psychiatric disorders (controls).

Out of 177 patients, 24 (13.6%) had MDD. No significant differences in peripheral inflammatory markers were observed between patients with post-COVID MDD and controls. Furthermore, peripheral inflammatory markers were not correlated with symptoms of depression.

We found no association between post-COVID MDD and 10 peripheral inflammatory markers 4 months after COVID-19 infection. Other potential mechanisms warrant investigation.

The length of hospital stays for severe COVID-19 cases significantly impacts the overall burden on the health system. Current COVID-19 vaccines have proven effective at reducing severe cases. However, the influence of vaccination status on the progression of COVID-19 after hospitalization is not well understood. Here, we estimated the impact of vaccination on the length of stay of hospitalized COVID-19 cases in Brazil.

We utilized nationwide data from hospital stays due to COVID-19 and the vaccination status of over 1.6 million individuals who tested positive for COVID-19 between January 17, 2021, and January 31, 2022. A competing-risk survival analysis was conducted to assess the COVID-19 in-hospital progression. We considered the hospital pathway according to four states: ward, ICU, discharge and death and measuring the length of stay accordingly.

Over half of hospital patients were unvaccinated. For patients aged 50-69-year-olds, the average length of stay for those discharged directly from the hospital ward (ward-to-discharge) ranged from 12.51 days (95 % CI, 12.39-12.63) in the unvaccinated to 11.02 days (95 % CI, 10.98-11.07) in booster recipients. Similar results were observed in the 20-49 and 70 or + age groups. For all age groups, the average time between hospital admission and ICU entrance was shorter in the unvaccinated. In the 50-69 age group, the average interval between ICU and discharge was 19.29 days (95 % CI, 18.95-19.64) in the unvaccinated and 16.92 days (95 % CI, 16.78-17.07) in the booster recipients, with a similar trend in other age groups. A higher discharge probability was observed among vaccinated individuals including hospital-to-discharge and ICU-to-discharge pathways.

Vaccination reduced hospital admissions and length-of-stay across the hospital-to-discharge and ICU-to-discharge pathways, contributing to a reduced health system burden. Our results demonstrate that even when vaccines do not prevent severe cases leading to hospitalizations, they significantly shorten the duration of hospital stays.

Fundação Oswaldo Cruz (FIOCRUZ), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Fundação de Amparo a Pesquisa do Estado do Rio de Janeiro (FAPERJ), Pan American Health Organization (PAHO), Departamento de Ciência e Tecnologia da Secretaria de Ciência, Tecnologia, Inovação e Insumos Estratégicos em Saúde do Ministério da Saúde do Brasil (DECIT/SCTIE/MS).

Fatigue has been characterized as a post COVID-19 condition known to persist months after SARS-CoV-2 infection. COVID-19 has been reported to be associated with impaired cognitive function, including disorders in attention, memory, information processing, and executive functions. The objective of this study was to determine if post-COVID fatigue, manifested as tiredness while performing low-intensity physical activity, has a detrimental effect on neuropsychological performance, to achieve this, we randomly selected 20 participants with post-COVID fatigue and 20 SARS-CoV-2 negative age-matched controls from a database of 360 residents of Tijuana, Baja California in a cross-sectional study design. All 40 participants responded to a health survey, along with a neuropsychological assessment test via telephone call. Statistical analysis was performed using a multiple linear regression model including the following independent variables: study condition (post-COVID fatigue or negative control), sex, age, years of education, hypertension, asthma, administration of supplemental oxygen during COVID-19 recovery, and the hour at which the evaluation started. Significant regression analysis was obtained for all global parameters of the assessment, including BANFE-2 score (p = 0.021, R2 Adj. = 0.263), NEUROPSI score (p = 0.008, R2 Adj. = 0.319), and total errors (p = 0.021, R2 Adj. = 0.263), with significant regression coefficients for study condition on two global parameters, BANFE-2 score (p = 0.028, β = - 0.371) and NEUROPSI score (p = 0.010, β = -0.428). These findings suggest that the presence of post-COVID fatigue is a factor associated with a decrease in neuropsychological performance.

Background & objectives Evidence suggests that individuals who have been hospitalised due to COVID-19 are more susceptible to future mortality and readmission, thereby imposing a substantial strain on their quality of life. The available data on intensive care unit (ICU) survivors, particularly in terms of long-term outcomes, is notably insufficient. This study focused on the long-term outcomes for ICU survivors of COVID-19, specifically readmission and mortality, as well as possible risk factors that could lead to their need for readmission. Methods We conducted a prospective observational study of 505 individuals admitted to the ICU of a tertiary care hospital between March 2020 and March 2021. Follow up concluded in January 2024. We evaluated the need for hospital and ICU readmissions, examining potential risk factors, including patient comorbidities, clinical situation at the time of the previous hospital and ICU admission, and evolution and treatment in the ICU. As a secondary objective, we determined the prevalence of long-term mortality. Results Among 341 ICU survivors, 75 (22%) required hospital readmission, with a median time to readmission of 415 days (IQR: 166-797). The most frequent cause of readmission was respiratory conditions (29.3%). The median hospital stay during readmission was six days. Independent risk factors for hospital readmission included age, elevated creatinine levels at ICU admission, and length of stay in the ICU. Of the 75 readmitted to the hospital, 19 required ICU readmission. Ten individuals died following hospital discharge. Interpretation & conclusions Patients requiring ICU admission due to COVID-19 have a significant risk of hospital readmission, particularly those with advanced age, elevated creatinine levels at ICU admission, and longer ICU stays.

This systematic review and meta-analysis aimed to investigate the objective, functional recovery of patients more than 3 months after acute coronavirus disease 2019 (COVID-19) infection.

Comprehensive database searches of EMBASE, PubMed/MEDLINE, Cochrane COVID-19 Study Register, CINAHL, and Google Scholar in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement were carried out until October 19, 2022. Data were extracted and agreed in duplicate. Data were narratively synthesized, and a series of meta-analyses were performed using the random-effects inverse variance method.

One-hundred six papers covering 20,063 patients, who were either hospitalized or not hospitalized with acute COVID-19 and were followed-up between 3 and 24 months, were included. Percentage predicted 6-minute walk distance at 3 months to <5 months was 84.3% (95% CI = 79.2-89.3; n = 21; I2 = 98.3%) and 92.5% (95% CI = 89.8-95.3; n = 9; I2 = 94.5%) at ≥11 months. Cardiopulmonary exercise testing revealed the percentage predicted peak oxygen consumption rate ($peak\dot{\mathsf{V}}{\mathsf{o}}_{\mathsf{2}}$) at 3 months to <5 months was 77.3% (95% CI = 71.0-83.7; n = 6; I2 = 92.3%) and 95.4% (95% CI = 87.1-103.6; n = 2; I2 = 77.3%) at ≥11 months. Mean handgrip strength was greatest at ≥11 months at 31.16 kg (95% CI = 19.89-42.43; n = 2; I2 = 98.3%) of all time points. All analyses showed marked heterogeneity.

Patients have reduced physical function more than 3 months after COVID-19 infection. Better physical function in multiple physical domains is found after a longer recovery time.

Physical function as measured by the 6-minute walk test, hand grip strength, and cardiopulmonary exercise testing is reduced at 3 months after COVID-19 infection and can remain over 11 months of follow-up. This protracted recovery following acute COVID-19 infection supports the need to assess physical function at any clinical follow-up, and further research into rehabilitation programs and intervention for patients who have not recovered.

Long COVID patients are prone to bronchial hyperresponsiveness and respiratory symptoms like coughing and breathing difficulties, often with positive bronchial provocation test (BPT) results.

This study aims to evaluate the diagnostic value of various lung function tests in patients with long-term COVID-19, explicitly focusing on positive BPT outcomes.

Our study analyzed the BPT outcomes and various pulmonary function parameters of all 9,406 COVID-19 patients who met the inclusion criteria and visited our hospital between February 24, 2022, and April 28, 2024. Key indicators included forced vital capacity (FVC), forced expiratory volume in one second (FEV1), peak expiratory flow (PEF), and single-breath diffusing capacity for carbon monoxide (DLCOc SB). A logistic regression model was employed to identify factors influencing positive BPT results, while the receiver operating characteristic (ROC) curve was used to assess the diagnostic efficacy of these indicators.

A total of 4211 valid samples were analyzed, with 3388 patients (80.46%) testing positive for BPT. Significant differences were observed between positive and negative groups regarding age, gender, smoking status (all P < 0.05), and specific lung function indicators, including FVC, FEV1/FVC ratio, maximum of vital capacity (VC max), and DLCOc SB (all P < 0.001). Logistic regression identified age, MEF50, and DLCOc SB as independent factors influencing positive BPT results. The area under the ROC curve for all assessed factors was <0.700, indicating limited diagnostic value.

Age, the small airway function indicator MEF50, and the pulmonary diffusion function indicator DLCOc SB are independent influencing factors for BPT positivity in long-term COVID patients. However, baseline data and lung function indicators have limited utility for diagnosing positive BPT in this population, highlighting the complex nature of post-COVID respiratory symptoms.

Pulmonary fibrosis (PF) post-COVID-19 has been identified as an important complication of Long-COVID, especially in patients with severe respiratory symptoms. High-resolution computed tomography (HRCT) is the main tool for detecting fibrotic lesions in patients with PF post-COVID-19.

We conducted a systematic review with the following objectives: (1) to summarize the incidence and disease burden of post‑COVID‑19 pulmonary fibrosis, (2) to provide information on available therapies and drugs for its management, (3) to comprehensively evaluate the initial treatment efficacy of these drugs, and (4) to identify the limitations and challenges associated with current treatment approaches.

Cutting-edge treatments for PF post-COVID-19 are focused on the complex and multifactorial nature of the disease progreession during Long COVID, which involves chronic inflammation, fibroblast activation, and excessive extracellular matrix deposition leading to stiffening and fibrosis of lung tissue. While traditional antifibrotic drugs with nintedanid and pirfenidone are being used, novel therapies with anti-interleukines, mesenchymal stem cells, and Rho-kinase inhibitors promise the new treatment approaches for patients with PF post-COVID-19. Further research and clinical trials are needed to determine the most effective strategies for managing this complex condition, with the goal of improving patient outcomes and quality of life.

The role of home oxygen therapy for patients recovering from Coronavirus Disease 2019 (COVID-19) pneumonia, characterized by impaired gas exchange, is not well-defined.

To compare the characteristics, duration, odds of receiving, and continuing to receive home oxygen prescriptions between patients discharged home after COVID-19 pneumonia hospitalization and those discharged after non-COVID-19 pneumonia.

From April 2020 to March 2021, 52,951 patients with COVID-19 pneumonia (53.6 % women, 64 % White) were identified, and from January 2019 to December 2019, 26,701 patients with non-COVID pneumonia (53.9 % women, 76.7 % White) were identified, using the Optum Clinformatics Data Mart Database. New oxygen prescriptions were identified through Healthcare Common Procedure Coding Systems codes. Propensity score matching adjusted for confounders, and Cox regression analysis was conducted to compare post-discharge oxygen use.

Following hospitalization, oxygen was prescribed to 52,951 patients with COVID-19 pneumonia and 26,701 patients with non-COVID pneumonia in the United States. The COVID-19 pneumonia group were four times more likely to be prescribed supplemental oxygen compared to the non-COVID-19 pneumonia group (OR 4.22; 95 % confidence interval [CI] 3.76-4.74). This trend persisted in sensitivity analyses: ICU patients (OR 4.05; 95 % CI 3.36-4.88) and those who received both ICU admission and mechanical ventilation (OR 3.84; 95 % CI 2.32-6.37). Hispanic patients had the highest likelihood of receiving a supplemental oxygen prescription after discharge (OR 6.75; 95 % CI 5.03-9.05).

Post-hospitalization, one in five patients with COVID-19 received prescriptions for supplemental oxygen, which was significantly higher than the proportion of patients with non-COVID-19 pneumonia.

Long-term recovery following critical COVID-19 has not been sufficiently studied.

The primary objective was to describe changes in functional outcome and Health-Related Quality of Life (HRQoL) between 3 and 12 months in critically ill COVID-19 survivors. The secondary objective was to investigate factors associated with good functional outcome and HRQoL at 12 months.

Prospective multicentre cohort study including critically ill COVID-19 patients admitted to six intensive care units in Sweden between May 2020 and May 2021. Surviving patients were invited to face-to-face follow-ups at 3 and 12 months. Functional outcome was assessed using the Glasgow Outcome Scale Extended (GOSE), ranging from 1 to 8. Physical and mental HRQoL was assessed by the physical component summary (PCS) and mental component summary (MCS) scores of the Short form health survey version 2 (SF-36v2®). Multivariable logistic regression models were used to identify factors associated with good functional outcome (GOSE ≥7) and good physical and mental HRQoL (PCS and MCS ≥45) at 12 months.

The percentage of participants with a good functional outcome increased from 35% to 64% between 3 and 12 months (p < .001). Mean PCS improved from 40 to 44 between 3 and 12 months (p < .001), while the mean MCS was within the normal range at 3 months, with no change at 12 months (46 vs. 48, p = .05). Increasing age was associated with a good functional outcome. Lower clinical frailty and absence of diabetes mellitus were associated with a good PCS. A shorter duration of mechanical ventilation was associated with a good outcome for all three outcome measures.

Survivors of critical COVID-19 showed improved functional outcome and physical HRQoL from 3 to 12 months post-ICU. A shorter duration of mechanical ventilation is associated with good functional outcome and good HRQoL, while older age is associated with good functional outcome. Younger patients and those with comorbidities or higher frailty may require targeted follow-up and rehabilitation. Study registration ClinicalTrials.gov Identifier: NCT04974775, registered April 28, 2020.

Since it first appeared, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has had a significant and lasting negative impact on the health and economies of millions of individuals all over the globe. At the level of individual health too, many patients are not recovering fully and experiencing a long-term condition now commonly termed 'long-COVID'. Long-COVID is a collection of symptoms which must last more than 12 weeks following initial COVID infection, and which cannot be adequately explained by alternate diagnoses. The neurological and psychosocial impact of long-COVID is itself now a global health crisis and therefore preventing, diagnosing, and managing these patients is of paramount importance. This review focuses primarily on: neurological functioning deficits; mental health impacts; long-term mood problems; and associated psychosocial issues, among patients suffering from long-COVID with an eye towards the neurological basis of these symptoms. A concise account of the clinical relevance of the neurological and psychosocial impacts of long-COVID, the effects on long-term morbidity, and varied approaches in managing patients with significant chronic neurological symptoms and conditions was extracted from the literature, analysed and reported. A comprehensive account of plausible pathophysiological mechanisms involved in the development of long-COVID, its management, and future research needs have been discussed.

Millions of Americans endure post-COVID conditions (PCC), yet research often lacks pre-illness measurements, relying primarily on follow-up assessments for analysis. The study aims to examine the prevalence of PCC, including cognitive impairment, functional limitation, and depressive symptoms, along with relevant risk factors, while controlling for individuals' pre-illness status measured in 2018. A cross-sectional retrospective study utilized the 2018 and 2020 Health and Retirement Study surveys. Sample included individuals with COVID-19 (n = 409; average age 64) and individuals without COVID-19 (n = 8689; average age 59). COVID-19 positive: Individuals with positive tests, physician diagnoses, emergency room visits, or hospitalizations for COVID-19 between 2019-2020. Cognition was assessed using immediate and delayed word-recall tests, serial seven subtractions, and backward counting. Functional status was measured using limitations in activities of daily living (ADLs) and instrumental ADLs. Depressive symptoms were measured using the modified Center for Epidemiology Studies Depression scale. Participants' perception of experiencing PCC was collected. Logistic regression and propensity score matching were employed for these analyses. Among 409 COVID-19-positive respondents (14% hospitalized), 24% exhibited new impairments after COVID-19 infection. Noteworthy increases in functional limitation (OR [95% CI]: 2.18 [0.95, 0.97], p < 0.001) and a marginal rise in cognitive impairment (1.79 [0.99, 3.32], p = 0.053) following COVID-19 infection were observed in comparison to their pre-COVID-19 baseline. Compared to 8689 non-COVID-19 cases, the 409 COVID-19 positives showed increased functional decline (1.78 [1.26, 2.51], p = 0.001) and depressive symptoms (1.41 [1.04, 1.91], p = 0.03). Factors associated with PCC included pre-existing impairments, lower education, female gender, prior hospitalization, higher comorbidity, lower wealth, and mild COVID-19. A notable number of respondents, especially older individuals with fewer pre-existing health conditions, experienced PCC without awareness. Compared to an individual's pre-illness baseline and uninfected individuals, being positive for COVID-19 raised the risk of functional limitation, depressive symptoms, and cognitive impairment. Additionally, addressing PCC through both subjective and objective approaches is essential to alleviate individual and societal burdens.

Usual clinical testing rarely reveals cardiac abnormalities persisting after hospitalization for COVID. Such testing may overlook residual changes causing increased adverse cardiac events post-discharge. To clarify status post-hospitalization, we related exercise stress echocardiography (ESE) in 15 recovering patients (RP) age 30-63 without myocarditis to matching published data from healthy subjects (HS). RP exercise, average duration 8.2 ± 2.2 SD, was halted by dyspnea or fatigue. RP baselines matched HS except for higher heart rate. At peak stress, RP had significantly lower mean left ventricular (LV) ejection fraction (67% ± 7 vs. 73% ± 5, p < 0.0017) and higher peak early mitral inflow velocity/early mitral annular velocity (E/e', 9.1 ± 2.5 vs. 6.6 ± 2.5, p < 0.006) compared with HS performing equal exercise (8.5 ± 2.6 min). Thus, when stressed, patients without known cardiac impairment showed diminished systolic contractile function and diastolic LV compliance vs. HS. RP peak heart rate was significantly higher (172 ± 18 vs. 153 ± 20); peak systolic blood pressure trended higher (192 ± 31 vs. 178 ± 19). Pulmonary artery systolic pressures among RP remained normal. ESE uniquely identified residual abnormality in cardiac contractile function not evident unstressed, exposing previously unrecognized residual influence of COVID-19. This may reflect autonomic dysfunction, microvascular disease, or diffuse interstitial changes; these results may have implications for clinical management and later prognosis.

The long-term effects of COVID-19 on lung function are not understood, especially for periods extending beyond 1 year after infection. This observational, longitudinal study investigated lung function in Mexican Hispanics who experienced severe COVID-19, focusing on how the length of recovery affects lung function improvements. At a specialized COVID-19 follow-up clinic in Yucatan, Mexico, lung function and symptoms were assessed in patients who had recovered from severe COVID-19. We used z-scores, and Wilcoxon's signed rank test to analyse changes in lung function over time. Lung function was measured twice in 82 patients: the first and second measurements were taken a median of 94 and 362 days after COVID-19 diagnosis, respectively. Initially, 61% of patients exhibited at least one of several pulmonary function abnormalities (lower limit of normal = -1.645), which decreased to 22% of patients by 390 days post-recovery. Considering day-to-day variability in lung function, 68% of patients showed improvement by the final visit, while 30% had unchanged lung function from the initial assessment. Computed tomography (CT) scans revealed ground-glass opacities in 33% of patients. One year after infection, diffusing capacity of the lungs for carbon monoxide z-scores accounted for 30% of the variation in CT fibrosis scores. There was no significant correlation between the length of recovery and improvement in lung function based on z-scores. In conclusion, 22% of patients who recovered from severe COVID-19 continued to show at least one lung function abnormality 1 year after recovery, indicating a prolonged impact of COVID-19 on lung health.

To examine patients' experiences of receiving care on an ICU for COVID-19 and the subsequent rehabilitation process.

An explorative and inductive design was used. Participants were recruited from two university hospitals in Sweden. Patients admitted to the ICU due to COVID-19 from March 2020 to April 2021, who enrolled in the ICU follow-up, and understood and spoke Swedish were invited to participate. In total, 20 participants completed a semi-structured interview, of whom 18 were included in the thematic analysis.

The analysis resulted in two themes: "An isolated world with silver linings" and "Recovery in the wake of the pandemic". Findings show that patients cared for on an ICU for COVID-19 during the pandemic felt safe but experienced a sense of vulnerability. After discharge, physical rehabilitation was a slow process with frustrating day-to-day fluctuations. Mentally, participants felt isolated, fatigued, and emotionally sensitive. Patients reported that love and support from family and friends were crucial for the recovery process.

This study highlights the challenges of recovering from COVID-19, emphasizing the importance of continued support from health care, public services, family and friends. It provides important insights into patients' experiences and can inform future healthcare strategies and policies.

It is unclear whether pre-COVID medical conditions are risk factors for post-COVID major depressive episode (MDE). We aimed to determine which pre-COVID medical conditions are risk factors for post-COVID MDE after a hospitalization for COVID-19.

We conducted a nested retrospective case-cohort study within a cohort of 650 patients evaluated six months after hospitalization for COVID-19 at Bicêtre hospital, France. Nine medical conditions present before COVID-19 (High blood pressure, obesity, type 2 diabetes, cardiac, respiratory and renal disease, immune deficiency, neoplasia and liver disease) were extracted from medical records. MDE was assessed using the Structured Clinical Interview for DSM-5 Disorders-Clinician Version (SCID-5-CV). Bivariate and multivariable analyses were performed to determine which pre-COVID medical conditions are independent risk factors for post-COVID new-onset MDE.

Patients mean age was 62.8 (15.8), 258 (39.7 %) were women; 301 (46.3 %) had high blood pressure, 205 (32.4 %) had obesity, and 186 (28.6 %) had type 2 diabetes. Thirty-six (5.5 %) patients were diagnosed with a new-onset MDE. In contrast to other medical conditions, type 2 diabetes was significantly associated with new-onset MDE (OR = 2.51 [1.19-5.29]).

Unlike other pre-COVID medical conditions, type 2 diabetes is a risk factor for post-COVID MDE. Patients with type 2 diabetes should be screened for MDE after a hospitalization for COVID-19.

Background: The aim of this study was to investigate the development of fatigue and mental illness between 3 and 12 months after critical COVID-19 and explore risk factors for long-lasting symptoms. Study Design and Methods: A prospective, multicenter COVID-19 study in southern Sweden, including adult patients (≥18 years) with rtPCR-confirmed COVID-19 requiring intensive care. Survivors were invited to a follow-up at 3 and 12 months, where patient-reported symptoms were assessed using the Modified Fatigue Impact Scale (MFIS), the Hospital Anxiety and Depression Scale (HADS) and the Posttraumatic Stress Disorder Checklist version 5 (PCL-5). The development between 3 and 12 months was described by changes in relation to statistical significance and suggested values for a minimally important difference (MID). Potential risk factors for long-lasting symptoms were analyzed by multivariable logistic regression. Results: At the 3-month follow-up, 262 survivors (87%) participated, 215 (72%) returned at 12 months. Fatigue was reported by 50% versus 40%, with a significant improvement at 12 months (MFIS; median 38 vs. 33, P < .001, MID ≥4). There were no significant differences in symptoms of mental illness between 3 and 12 months, with anxiety present in 33% versus 28%, depression in 30% versus 22%, and posttraumatic stress disorder in 17% versus 13%. A worse functional outcome and less sleep compared to before COVID-19 were risk factors for fatigue and mental illness at 12 months. Conclusions: Fatigue improved between 3 and 12 months but was still common. Symptoms of mental illness remained unchanged with anxiety being the most reported. A worse functional outcome and less sleep compared to before COVID-19 were identified as risk factors for reporting long-lasting symptoms.

Documented radiological and physiological anomalies among coronavirus disease 2019 survivors necessitate prompt recognition of residual pulmonary parenchymal abnormalities for effective management of chronic pulmonary consequences. This study aimed to devise a predictive model to identify patients at risk of such abnormalities post-COVID-19. Our prognostic model was derived from a dual-center retrospective cohort comprising 501 hospitalized COVID-19 cases from July 2022 to March 2023. Of these, 240 patients underwent Chest CT scans three months post-infection. A predictive model was developed using stepwise regression based on the Akaike Information Criterion, incorporating clinical and laboratory parameters. The model was trained and validated on a split dataset, revealing a 33.3% incidence of pulmonary abnormalities. It achieved strong discriminatory power in the training set (area under the curve: 0.885, 95% confidence interval 0.832-0.938), with excellent calibration and decision curve analysis suggesting substantial net benefits across various threshold settings. We have successfully developed a reliable prognostic tool, complemented by a user-friendly nomogram, to estimate the probability of residual pulmonary parenchymal abnormalities three months post-COVID-19 infection. This model, demonstrating high performance, holds promise for guiding clinical interventions and improving the management of COVID-19-related pulmonary sequela.

Patients recovering from COVID-19 often present with impaired health and persisting symptoms such as exercise intolerance ⩾3 months post-infection. Uncertainty remains about long-term recovery. We aimed to review studies examining cardiac function, macro- or microvascular function, blood biomarkers and physical activity in adult patients post-COVID-19 and highlight current knowledge gaps.

Using echocardiography, persistent cardiac involvement of the left ventricle was observed in a fraction of patients both hospitalized and non-hospitalized. Ventricular dysfunction was often subclinical but may partly contribute to exercise intolerance post-COVID-19. Endothelial dysfunction was seen on micro- and macrovascular levels using retinal vessel imaging methods and brachial artery flow-mediated dilation, respectively. Studies reporting blood biomarkers of disease-specific impairment and endothelial dysfunction yielded upregulated inflammation, hypercoagulability, organ and endothelial damage up to several months after infection. Omics' scale lipid profiling studies provide preliminary evidence of alterations in several lipid subspecies, mostly during acute COVID-19, which might contribute to subsequent endothelial and cardiometabolic dysfunction. Yet, more robust evidence is warranted. Physical activity may be reduced up to 6 months post-COVID-19. However, studies measuring physical activity more precisely using accelerometry are sparse. Overall, there is growing evidence for long-term multiple organ dysfunction.

Research combining all the above methods in the search for underlying mechanisms of post-COVID-19 symptoms is mostly missing. Moreover, studies with longer follow-ups (i.e. ⩾18 months) and well-matched control groups are lacking. The findings may aid the development of rehabilitation regimes for post-COVID-19 syndrome.

This review examined cardiac function, vascular function, blood biomarkers and physical activity in patients post-COVID-19. Evidence suggests long-term dysfunction in multiple organ systems and exercise intolerance due to various factors, including endothelial damage and, in some patients, subclinical ventricular dysfunction. We highlight knowledge gaps for further research to aid post-COVID-19 rehabilitation.

Following the Omicron wave in early 2022, an estimated 60-70% of the French population was infected with the SARS-CoV-2 virus. One out of ten infected subjects could have persistent symptoms three months after infection, representing a public health challenge.

The persistent symptoms may be secondary to diverse entities with distinct mechanisms. While organic infection sequelae occur mainly after severe COVID-19, some symptoms appear to be essentially psychological in origin; in addition, many subjects present stereotyped symptoms of fluctuating intensity with no identified anatomical or psychic substratum, often in the aftermath of a benign infection. The most frequent complaints are fatigue, pain, dyspnea and difficulty concentrating.

The hypotheses explored to explain these symptoms include: persistent immune dysfunction, inducted autoimmunity, and microbiome disturbances. Persistent viral antigens may lie at the crossroads of these mechanisms. To date, these different etiological avenues have yet to lead to the development of diagnostic tests or specific therapeutic strategies.

Prolonged symptoms after COVID-19 correspond to heterogeneous nosological entities with poorly understood mechanisms.

To assess the value of serum ferritin and Krebs von den Lungen-6 (KL-6) levels for predicting severe COVID-19 (death or requirement for invasive mechanical ventilation [IMV]/high-flow oxygen).

Data were analyzed on 2495 patients with COVID-19 from February 2020 to November 2022 using data from a nationwide COVID-19 database.

Patients with high KL-6 and low ferritin levels were older with more comorbidities and higher mortality rates, whereas those with high ferritin and low KL-6 levels were younger, predominantly male, and more likely to need IMV. A high level of both markers was strongly associated with critical outcomes (adjusted odds ratio: 13.6, 95% confidence interval: 8.58-21.5). The combination of both markers had higher predictive value than either marker alone (area under the curve: 0.709, 0.745, and 0.781 for KL-6, ferritin, and KL-6 + ferritin, respectively).

The combination of both markers accurately predicted COVID-19 severity.

Although many symptoms of post-COVID syndrome have been described, a comprehensive evaluation of their prevalence is lacking. We aimed to describe symptoms at 16 months from hospitalization for COVID-19.

A telephone assessment was performed one year later in a cohort of COVID-19 survivors hospitalized between March and May 2020 and already evaluated four months after discharge. Patients with relevant symptoms at 16 months, patients who presented symptoms at four months, and all intensive care unit patients were invited for assessment at an outpatient facility. At telephone consultation, respiratory, cognitive, and functional symptoms were assessed. Patients underwent pulmonary function tests, lung CT scans, and psychometric and cognitive tests at the outpatient facility.

Among 478 patients evaluated four months after discharge, 317 (67 %) were assessed at telephone consultation and 124 at ambulatory assessment. At telephone assessment, ≥1 new symptom was reported by 216 patients (68 %), mainly fatigue (53 %), dyspnea (37 %), and memory difficulties (24 %). Seventy-nine patients (25 %) were asymptomatic at four months but declared ≥1 symptom one year later. In patients evaluated twice, the prevalence of cognitive impairment was 45 % at four months and 40 % at 16 months. Depression and post-traumatic symptoms prevalence remained stable, and the prevalence of anxiety significantly decreased. Dysfunctional breathing was detected in 32 % of patients. At 16 months after discharge, lung CT-scan exhibited abnormalities in 30/80 patients (38 %), compared to 52/85 patients (61 %) at four months.

At 16 months after hospitalization for COVID-19, 68 % of patients declared symptoms, including patients whose symptoms appeared between 4 and 16 months.

ClinicalTrials.gov, NCT04704388.

Coronavirus disease (COVID-19) patients treated in an intensive care unit (ICU) are at high risk of developing cognitive impairments of a "post-intensive care syndrome" (PICS). We explored whether critically ill COVID-19 and non-COVID-19 survivors differ in their post-ICU recovery course in terms of severity and affected cognitive domains.

An observational prospective study was conducted in a German post-acute neurological early rehabilitation clinic. Critically ill patients with or without SARS-CoV-2 infection (at least mechanically ventilated for one week) underwent repeated standardized assessments during their subsequent inpatient rehabilitation stay. Cognitive functions (information processing speed, learning, recognition, short-term and working-memory, word fluency, flexibility) assigned to different domains (attention, memory, executive functions) were assessed as primary outcome. Secondary outcomes included mental (depression, anxiety) and physical (Barthel index, modified ranking scale) state.

Out of 92 eligible patients (screened between June 2021 and August 2023), 34 were examined, and 30 were available for analysis (15 per group). Both groups were ventilated for a similar period (COVID-19 vs. Non-COVID-19: median: 48 vs. 53 days). Patients of COVID-19 group spend on average 10 days longer at ICU and developed slightly more complications, but subsequent inpatient rehabilitation was of comparable duration (median: 36.5 vs. 37 days). On the group-level both groups showed similar cognitive dysfunctions with striking impairments (normative T-scores < 41) in information processing speed, word fluency, flexibility, and recognition memory on admission. Significant gains until discharge were only revealed for information processing speed in both groups (main effect visit, mean difference [95%CI] - 7.5 [- 13.1, - 2.0]). Physical and mental state were also similarly affected in both groups on admission, but improved over time, indicating that overall recovery for higher-order cognitive functions is slowest. Interestingly, majority of patients stated correctly being still physically disabled, while a discrepancy was found between subjective and objective evaluation of cognitive health.

Results suggest a substantial overlap of cognitive, mental and physical dysfunction in post-acute recovery of ICU survivors independent of SARS-CoV-2 infection which warrants further monitoring to reduce the risk of long-term burden and enable a return to previous functionality.

Retrospectively registered at https://drks.de/search/de/trial/DRKS00025523 , 21.06.2021.

Symptoms of the Post-COVID-19 Condition are often non-specific making it a challenge to distinguish them from symptoms due to other medical conditions. In this study, we compare the proportion of emergency department patients who developed symptoms consistent with the World Health Organization's Post-COVID-19 Condition clinical case definition between those who tested positive for Severe Acute Respiratory Syndrome Coronavirus-2 infection and time-matched patients who tested negative. Our results show that over one-third of emergency department patients with a proven acute infection meet Post-COVID-19 Condition criteria 3 months post-index visit. However, one in five test-negative patients who claim never having been infected also report symptoms consistent with Post-COVID-19 Condition highlighting the lack of specificity of the clinical case definition. Testing for SARS-CoV-2 during the acute phase of a suspected infection should continue until specific biomarkers of Post-COVID-19 Condition become available for diagnosis and treatment.

The term "Long-COVID" (LC) is characterized by the aftereffects of COVID-19 infection. Various studies have suggested that Epstein-Barr virus (EBV) reactivation is among the significant reported causes of LC. However, there is a lack of in-depth research that could largely explore the pathogenic mechanism and pinpoint the key genes in the EBV and LC context. This study mainly aimed to predict the potential disease-associated common genes between EBV reactivation and LC condition using next-generation sequencing (NGS) data and reported naturally occurring biomolecules as inhibitors. We applied the bulk RNA-Seq from LC and EBV-infected peripheral blood mononuclear cells (PBMCs), identified the differentially expressed genes (DEGs) and the Protein-Protein interaction (PPI) network using the STRING database, identified hub genes using the cytoscape plugins CytoHubba and MCODE, and performed enrichment analysis using ClueGO. The interaction analysis of a hub gene was performed against naturally occurring bioflavonoid molecules using molecular docking and the molecular dynamics (MD) simulation method. Out of 357 common genes, 22 genes (CCL2, CCL20, CDCA2, CEP55, CHI3L1, CKAP2L, DEPDC1, DIAPH3, DLGAP5, E2F8, FGF1, NEK2, PBK, TOP2A, CCL3, CXCL8, DEPDC1, IL6, RETN, MMP2, LCN2, and OLR1) were classified as hub genes, and the remaining ones were classified as neighboring genes. Enrichment analysis showed the role of hub genes in various pathways such as immune-signaling pathways, including JAK-STAT signaling, interleukin signaling, protein kinase signaling, and toll-like receptor pathways associated with the symptoms reported in the LC condition. ZNF and MYBL TF-family were predicted as abundant TFs controlling hub genes' transcriptional machinery. Furthermore, OLR1 (PDB: 7XMP) showed stable interactions with the five shortlisted refined naturally occurring bioflavonoids, i.e., apigenin, amentoflavone, ilexgenin A, myricetin, and orientin compounds. The total binding energy pattern was observed, with amentoflavone being the top docked molecule (with a binding affinity of -8.3 kcal/mol) with the lowest total binding energy of -18.48 kcal/mol. In conclusion, our research has predicted the hub genes, their molecular pathways, and the potential inhibitors between EBV and LC potential pathogenic association. The in vivo or in vitro experimental methods could be utilized to functionally validate our findings, which would be helpful to cure LC or to prevent EBV reactivation.

This study aimed to longitudinally follow self-reported symptoms of depression, anxiety, post-traumatic stress disorder, and fatigue during the first year after hospitalization because of COVID-19.

The study was an observational longitudinal study.

Between July 2020, and February 2021, 211 patients aged ≥ 18 years, hospitalized ≥ 5 days at 5 hospitals in Region Västra Götaland, who had COVID-19, and were non-contagious (at study enrolment) were included in the baseline assessment. Of these, 168 (79.6%) patients completed mental health questionnaires at a 3-month follow-up, and 172 (83.1%) at a 12-month follow-up. A total of 120 (56.9%) participants who completed at least 1 questionnaire at both the 3- and 12-month follow-ups were analysed; the majority were male (n = 78, 65.0%).

There was an improvement in all patients from 3 to 12 months on the fatigue subscales "reduced activity" (p = 0.02) and "physical fatigue" (p = 0.04). No other significant mental health improvements were found. At 12 months, 34 (28.4%) were classified as having anxiety symptoms, 29 (24.1%) as having depression symptoms, and 40 (33.3%) had symptoms of probable post-traumatic stress disorder.

Participants in the present study did not report full mental health recovery 1 year after hospitalization for COVID-19.

Survival prospects following SARS-CoV-2 infection may extend beyond the acute phase, influenced by various factors including age, health conditions, and infection severity; however, this topic has not been studied in detail. Therefore, within this study, the mortality risk post-acute COVID-19 in the CRIT-COV-U cohort was investigated.

Survival data from 651 patients that survived an acute phase of COVID-19 were retrieved and the association between urinary peptides and future death was assessed. Data spanning until December 2023 were collected from six countries, comparing mortality trends with age- and sex-matched COVID-19-negative controls. A death prediction classifier was developed and validated using pre-existing urinary peptidomic datasets.

Notably, 13.98% of post-COVID-19 patients succumbed during the follow-up, with mortality rates significantly higher than COVID-19-negative controls, particularly evident in younger individuals (<65 years). These data for the first time demonstrate that SARS-CoV-2 infection highly significantly increases the risk of mortality not only during the acute phase of the disease but also beyond for a period of about one year. In our study, we were further able to identify 201 urinary peptides linked to mortality. These peptides are fragments of albumin, alpha-2-HS-glycoprotein, apolipoprotein A-I, beta-2-microglobulin, CD99 antigen, various collagens, fibrinogen alpha, polymeric immunoglobulin receptor, sodium/potassium-transporting ATPase, and uromodulin and were integrated these into a predictive classifier (DP201). Higher DP201 scores, alongside age and BMI, significantly predicted death.

The peptide-based classifier demonstrated significant predictive value for mortality in post-acute COVID-19 patients, highlighting the utility of urinary peptides in prognosticating post-acute COVID-19 mortality, offering insights for targeted interventions. By utilizing these defined biomarkers in the clinic, risk stratification, monitoring, and personalized interventions can be significantly improved. Our data also suggest that mortality should be considered as one possible symptom or a consequence of post-acute sequelae of SARS-CoV-2 infection, a fact that is currently overlooked.

In the postacute phase of coronavirus disease-2019 (COVID-19), survivors may have persistent symptoms, lung function abnormalities, and sequelae lesions on thoracic computed tomography (CT). This new entity has been defined as post-COVID interstitial lung disease (ILD) or residual disease.

To evaluate the characteristics, risk factors and clinical significance of post-COVID ILD.

Multicenter cross-sectional analysis of data from a randomized clinical study.

In this study, patients with persistent respiratory symptoms 3 months after recovery from COVID-19 were evaluated by two pulmonologists and a radiologist. post-COVID ILD was defined as the presence of respiratory symptoms, hypoxemia, restrictive defect on lung function tests, and interstitial changes on follow-up high-resolution computed tomography (HRCT).

At the three-month follow-up, 375 patients with post-COVID-19 syndrome were evaluated, and 262 patients were found to have post-COVID ILD. The most prevalent complaints were dyspnea (n = 238, 90.8%), exercise intolerance (n = 166, 63.4%), fatigue (n = 142, 54.2%), and cough (n = 136, 52%). The mean Medical Research Council dyspnea score was 2.1 ± 0.9, oxygen saturation was 92.2 ± 5.9%, and 6-minute walking distance was 360 ± 140 meters. The mean diffusing capacity of the lung for carbon monoxide was 58 ± 21, and the forced vital capacity was 70% ± 19%. Ground glass opacities and fibrotic bands were the most common findings on thoracic HRCT. Fibrosis-like lesions such as interlobular septal thickening and traction bronchiectasis were observed in 38.3% and 27.9% of the patients, respectively. No honeycomb cysts were observed. Active smoking [odds ratio (OR), 1.96; 95% confidence interval (CI), 1.44-2.67), intensive care unit admission during the acute phase (OR, 1.46; 95% CI, 1.1-1.95), need for high-flow nasal oxygen (OR, 1.55; 95% CI, 1.42-1.9) or non-invasive ventilation (OR, 1.31; 95% CI, 0.8-2.07), and elevated serum lactate dehydrogenase levels (OR, 1.23; 95% CI 1.18-1.28) were associated with the development of post-COVID ILD. At the 6-month follow-up, the respiratory symptoms and pulmonary functions had improved spontaneously without any specific treatment in 35 patients (13.4%). The radiological interstitial lesions had spontaneously regressed in 54 patients (20.6%).

The co-existence of respiratory symptoms, radiological parenchymal lesions, and pulmonary functional abnormalities which suggest a restrictive ventilatory defect should be defined as post-COVID-19 ILD. However, the term “fibrosis” should be used carefully. Active smoking, severe COVID-19, and elevated lactate dehydrogenase level are the main risk factors of this condition. These post-COVID functional and radiological changes could disappear over time in 20% of the patients.