Clinical effects of traditional Chinese herbal medicine management in patients with COVID-19 sequelae: A hospital-based retrospective cohort study in Taiwan.

Introduction: An estimated 43% of COVID-19 patients showed sequelae, including fatigue, neurocognitive impairment, respiratory symptoms, and smell or taste disorders. These sequelae significantly affect an individual's health, work capacity, healthcare systems, and socioeconomic aspects. Traditional Chinese herbal medicine (TCHM) management showed clinical benefits in treating patients with COVID-19 sequelae. This study aimed to analyze the effects of personalized TCHM management in patients with COVID-19 sequelae. Methods: After the COVID-19 outbreak in Taiwan, we recorded Chronic Obstructive Pulmonary Disease Assessment Tool (CAT), Chalder Fatigue Questionnaire (CFQ-11), and Brief Symptom Rating Scale (BSRS-5) to assess post-COVID respiratory, fatigue, and emotional distress symptoms, respectively. In this study, we retrospectively reviewed the medical records between July 2022 and March 2023. We analyzed the effects of TCHM administration after 14- and 28-days of treatment. Results: 47 patients were included in this study. The results demonstrated that personalized TCHM treatment significantly improved the CAT, CFQ-11, and BSRS-5 scores after 14 and 28 days. TCHM alleviated physical and psychological fatigue. In logistic regression analysis, there was no statistically significant differences in the severity of the baseline symptoms and TCHM administration effects concerning the duration since the initial confirmation of COVID-19, sex, age, or dietary preference (non-vegetarian or vegetarian). Conclusions: Our study suggested that personalized TCHM treatment notably reduced fatigue, respiratory and emotional distress symptoms after 14- and 28-days of treatment in patients with COVID-19 sequelae. We propose that TCHM should be considered as an effective intervention for patients with COVID-19 sequelae.

Addressing psychosocial needs in patients with Long-COVID (PsyLoCo-Study): study protocol of a pilot-study of a specialized modular intervention.

Introduction: After an acute infection with the corona virus 10-20% of those affected suffer from ongoing or new symptoms. A causal therapy for the phenomenon known as Long/Post-COVID is still lacking and specific therapies addressing psychosocial needs of these patients are imperatively needed. The aim of the PsyLoCo-study is developing and piloting a psychotherapeutic manual, which addresses Long/Post-COVID-related psychosocial needs and supports in coping with persistent bodily symptoms as well as depressive or anxiety symptoms. Methods and analysis: This pilot trial implements a multi-centre, 2-arm (N=120; allocation ratio: 1:1), parallel group, randomised controlled design. The pilot trial is designed to test the feasibility and estimate the effect of 1) a 12-session psychotherapeutic intervention compared to 2) a wait-list control condition on psychosocial needs as well as bodily and affective symptoms in patients suffering from Long/Post-COVID. The intervention uses an integrative, manualized, psychotherapeutic approach. The primary study outcome is health-related quality of life. Outcome variables will be assessed at three timepoints, pre-intervention (t1), post-intervention (t2) and three months after completed intervention (t3). To determine the primary outcome, changes from t1 to t2 are examined. The analysis will be used for the planning of the RCT to test the efficacy of the developed intervention. Discussion: The pilot study will evaluate a 12-session treatment manual for Long/Post-COVID sufferers and the therapy components it contains. The analysis will provide insights into the extent to which psychotherapeutic treatment approaches improve the symptoms of Long/Post-COVID sufferers. The treatment manual is designed to be carried out by psychotherapists as well as people with basic training in psychotherapeutic techniques. This approach was chosen to enable a larger number of practitioners to provide therapeutic support for Long/Post-COVID patients. After completion of the pilot study, it is planned to follow up with a randomized controlled study and to develop a treatment guideline for general practitioners and interested specialists. Trial registration: The pilot trial has been registered with the German Clinical Trials Register (Deutsches Register Klinischer Studien; Trial-ID: DRKS00030866; URL: https://drks.de/search/de/trial/DRKS00030866) on March 7, 2023.

Event rates and incidence of post-COVID-19 condition in hospitalised SARS-CoV-2 positive children and young people and controls across different pandemic waves: exposure-stratified prospective cohort study in Moscow (StopCOVID).

BACKGROUND: Long-term health outcomes in children and young people (CYP) after COVID-19 infection are not well understood and studies with control groups exposed to other infections are lacking. This study aimed to investigate the incidence of post-COVID-19 condition (PCC) and incomplete recovery in CYP after hospital discharge and compare outcomes between different SARS-CoV-2 variants and non-SARS-CoV-2 infections. METHODS: A prospective exposure-stratified cohort study of individuals under 18 years old in Moscow, Russia. Exposed cohorts were paediatric patients admitted with laboratory-confirmed COVID-19 infection between April 2 and December 11, 2020 (Wuhan variant cohort) and between January 12 and February 19, 2022 (Omicron variant cohort). CYP admitted with respiratory and intestinal infections, but negative lateral flow rapid diagnostic test and PCR-test results for SARS-CoV-2, between January 12 and February 19, 2022, served as unexposed reference cohort. Comparison between the 'exposed cohorts' and 'reference cohort' was conducted using 1:1 matching by age and sex. Follow-up data were collected via telephone interviews with parents, utilising the long COVID paediatric protocol and survey developed by the International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC). The WHO case definition was used to categorise PCC. RESULTS: Of 2595 CYP with confirmed COVID-19, 1707 (65.7%) participated in follow-up interviews, with 1183/1707 (69%) included in the final 'matched' analysis. The median follow-up time post-discharge was 6.7 months. The incidence of PCC was significantly higher in the Wuhan variant cohort (89.7 cases per 1000 person-months, 95% CI 64.3-120.3) compared to post-infection sequalae in the reference cohort (12.2 cases per 1000 person-months, 95% CI 4.9-21.9), whereas the difference with the Omicron variant cohort and reference cohort was not significant. The Wuhan cohort had higher incidence rates of dermatological, fatigue, gastrointestinal, sensory, and sleep manifestations, as well as behavioural and emotional problems than the reference cohort. The only significant difference between Omicron variant cohort and reference cohort was decreased school attendance. When comparing the Wuhan and Omicron variant cohorts, higher incidence of PCC and event rates of fatigue, decreased physical activity, and deterioration of relationships was observed. The rate of incomplete recovery was also significantly higher in the Wuhan variant cohort than in both the reference and the Omicron variant cohorts. CONCLUSIONS: Wuhan variant exhibited a propensity for inducing a broad spectrum of physical symptoms and emotional behavioural changes, suggesting a pronounced impact on long-term health outcomes. Conversely, the Omicron variant resulted in fewer post-infection effects no different from common seasonal viral illnesses. This may mean that the Omicron variant and subsequent variants might not lead to the same level of long-term health consequences as earlier variants.

Exploring the Use of Mobile Health for the Rehabilitation of Long COVID Patients: A Scoping Review.

The COVID-19 pandemic has led to a substantial revolution in the incorporation of digital solutions in healthcare. This systematic review investigates the enduring physical and psychological consequences individuals experience up to two years post-recovery. Additionally, it focuses on examining the influence of mHealth interventions on these effects. Significantly, 41.7% of survivors experience lingering symptoms that have not been addressed, while 14.1% encounter difficulties in returning to work. The presence of anxiety, compromised respiratory functioning, and persistent symptoms highlight the immediate requirement for specific therapies. Telehealth, particularly telerehabilitation, presents itself as a possible way to address these difficulties. The study thoroughly examines 10 studies encompassing 749 COVID-19 patients, investigating the efficacy of telerehabilitation therapies in addressing various health markers. Telerehabilitation-based breathing exercises yield substantial enhancements in functional performance, dyspnea, and overall well-being. The results emphasize the potential of telerehabilitation to have a favorable effect on patient outcomes; however, more research is needed to strengthen the existing evidence base, as one of the most important limitations is the limited number of trials and the evaluation of varied therapies. This analysis highlights the significance of digital solutions in post-COVID care and calls for ongoing research to improve the comprehension and implementation of telehealth interventions in a swiftly changing healthcare environment.

MicroRNA-guided drug discovery for mitigating persistent pulmonary complications in critical COVID-19 survivors: A longitudinal pilot study.

BACKGROUND AND PURPOSE: The post-acute sequelae of SARS-CoV-2 infection pose a significant global challenge, with nearly 50% of critical COVID-19 survivors manifesting persistent lung abnormalities. The lack of understanding about the molecular mechanisms and effective treatments hampers their management. Here, we employed microRNA (miRNA) profiling to decipher the systemic molecular underpinnings of the persistent pulmonary complications. EXPERIMENTAL APPROACH: We conducted a longitudinal investigation including 119 critical COVID-19 survivors. A comprehensive pulmonary evaluation was performed in the short-term (median = 94.0 days after hospital discharge) and long-term (median = 358 days after hospital discharge). Plasma miRNAs were quantified at the short-term evaluation using the gold-standard technique, RT-qPCR. The analyses combined machine learning feature selection techniques with bioinformatic investigations. Two additional datasets were incorporated for validation. KEY RESULTS: In the short-term, 84% of the survivors exhibited impaired lung diffusion (DLCO  < 80% of predicted). One year post-discharge, 54.4% of this patient subgroup still presented abnormal DLCO . Four feature selection methods identified two specific miRNAs, miR-9-5p and miR-486-5p, linked to persistent lung dysfunction. The downstream experimentally validated targetome included 1473 genes, with heterogeneous enriched pathways associated with inflammation, angiogenesis and cell senescence. Validation studies using RNA-sequencing and proteomic datasets emphasized the pivotal roles of cell migration and tissue repair in persistent lung dysfunction. The repositioning potential of the miRNA targets was limited. CONCLUSION AND IMPLICATIONS: Our study reveals early mechanistic pathways contributing to persistent lung dysfunction in critical COVID-19 survivors, offering a promising approach for the development of targeted disease-modifying agents.

Long-term health consequences of COVID-19 in survivors hospitalised at a tertiary care hospital and their correlation with acute COVID-19 severity and associated risk factors.

OBJECTIVES: To determine post-COVID syndromes in the Indian population, correlating a wide spectrum of post-COVID manifestations with acute disease severity and associated risk factors. BACKGROUND: Post-COVID Syndrome (PCS) is defined as signs and symptoms that develop during or after acute COVID-19 infection. DESIGN OF STUDY: This is a prospective observational cohort with repetitive measurements. METHODS: The study followed RT-PCR confirmed COVID-19-positive survivors discharged from HAHC Hospital, New Delhi, for a period of 12 weeks. The patients were interviewed over the phone at 4 weeks and 12 weeks from the onset of symptoms for evaluation of clinical symptoms and health-related quality of life parameters. RESULTS: A total of 200 patients completed the study. At the baseline, 50% of the patients were categorised as severe based on their acute infection assessment. At 12 weeks after symptom onset, fatigue (23.5%), hair loss (12.5%) and dyspnea (9%) were the main persistent symptoms. The incidence of hair loss (12.5%), memory loss (4.5%) and brain fog (5%) were found to be increased as compared to the acute infection period. Severity of the acute COVID infection behaved as an independent predictor for the development of PCS, with high odds of experiencing persistent cough (OR = 13.1), memory loss (OR = 5.2) and fatigue (OR = 3.3). Further, 30% of subjects in the severe group experienced statistically significant fatigue at 12 weeks (p < .05). CONCLUSION: From the results of our study, it can be concluded that there is a huge disease burden of post-COVID Syndrome (PCS). The PCS comprised multisystem symptoms ranging from serious complaints of dyspnea, memory loss and brain fog to non-serious complaints of fatigue and hair loss. Severity of the acute COVID infection behaved as an independent predictor for the development of PCS. Our findings strongly recommend vaccination against COVID-19, for protection from disease severity as well as prevention of PCS. RELEVANCE TO CLINICAL PRACTICE: The findings of our study support the multidisciplinary approach required for the management of PCS with a team comprising of physicians, nurses, physiotherapists and psychiatrists working in close coordination for the rehabilitation of these patients. As nurses are considered the most trusted professionals in the community and the class of health workers associated with rehabilitation, focus should be given to educating them on PCS, which would prove to be an important strategy for efficient monitoring and long-term management of COVID-19 survivors.

Prevalence and risk factors for persistent symptoms after COVID-19: a systematic review and meta-analysis.

BACKGROUND: Long-term physical and mental persistent symptoms after COVID-19 represent a growing global public health concern. However, there remains a substantial knowledge gap regarding their prevalence and risk factors. OBJECTIVES: To estimate the prevalence and risk factors for persistent symptoms after COVID-19. METHODS OF DATA SYNTHESIS: We used a random-effects model to pool persistent symptom prevalence and risk ratios comparing COVID-19 patients with non-COVID-19 individuals. DATA SOURCES: Electronic databases were searched for studies published from December 2019 to January 2023. STUDY ELIGIBILITY CRITERIA: Eligible studies that reported the prevalence and risk factors for persistent symptoms after COVID-19 were included. PARTICIPANTS: Patients who recovered from COVID-19. ASSESSMENT OF RISK OF BIAS: The Joanna Briggs Institute critical appraisal tool was used to assess the risk of bias in prevalence studies, whereas the risk of bias in cohort studies was evaluated with the Newcastle-Ottawa Scale. RESULTS: After screening 4359 studies, a total of 211 eligible studies were included, covering a population of 13 368 074 individuals. Fatigue, dyspnoea, post-traumatic stress disorder, anxiety, and depression were the most frequently reported persistent symptoms after COVID-19. Subgroup analyses revealed that individuals with more severe illness in the acute phase or from Europe exhibited a higher prevalence of certain symptoms, whereas children demonstrated a lower prevalence. Furthermore, COVID-19 patients had a significantly higher prevalence of most persistent symptoms compared with non-COVID-19 individuals. Factors frequently associated with a higher prevalence of persistent symptoms included female gender, advanced age, severe illness during the acute phase of COVID-19, multiple comorbidities, an extended duration of hospital stay, and a high body mass index. CONCLUSION: This meta-analysis provides a thorough review of the prevalence and risk factors for persistent symptoms following COVID-19. The findings underscore the importance of long-term monitoring and support for individuals recovering from COVID-19.

Blood microbial analyses reveal long-term effects of SARS-CoV-2 infection on patients who recovered from COVID-19.

OBJECTIVE: Few symptoms persist for a long time after patients recover from COVID-19, called "long COVID". We explored the potential microbial risk factors for COVID-19 for a deeper understanding and assistance in the follow-up treatment of these sequelae. METHODS: Microbiome re-annotation was performed using whole blood RNA-Seq data collected from recovered COVID-19 patients and healthy controls at multiple time points. Subsequently, a series of downstream analyses were conducted to reveal the microbial characteristics of patients who recovered from SARS-CoV-2 infection. RESULTS: The blood microbiome at 12 weeks post-infection was most evidently disturbed, including an increasing ratio of Bacillota/Bacteroidota and a higher microbial alpha diversity. In addition, a group of pathogenic microbes at 12 weeks post-infection were identified, including Staphylococcus aureus, Klebsiella pneumoniae, Streptococcus pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa, which were positively associated with host genes involved in immune regulatory and olfactory transduction pathways. Several microbes, such as Streptococcus pneumoniae were associated with infiltrating immune cells, such as M2 macrophages. CONCLUSION: This study provides insights into the relationship between the blood microbiome and COVID-19 sequelae. Several pathogenic microbes were enriched in recovered COVID-19 patients and thus affected host genes participating in the immune and olfactory transduction pathways, which play critical roles in COVID-19 sequelae.

Association of Sedentary Lifestyle with Risk of Acute and Post-Acute COVID-19 Sequelae: A Retrospective Cohort Study.

BACKGROUND: Evidence suggests that coronavirus disease 2019 (COVID-19) survivors could experience COVID-19 sequelae. Although various risk factors for COVID-19 sequelae have been identified, little is known about whether a sedentary lifestyle is an independent risk factor. METHODS: In this retrospective cohort study, 4850 participants self-reported their COVID-19 sequelae symptoms between June and August 2022. A sedentary lifestyle included physical inactivity (<150 min/week of moderate-to-vigorous intensity physical activity) and prolonged sedentary behavior (≥10 h/day) before the fifth COVID-19 wave was recorded. Logistic regression analysis was performed to determine the relationships between sedentary lifestyle and risk of acute and post-acute (lasting ≥2 months) COVID-19 sequelae. RESULTS: A total of 1443 COVID-19 survivors and 2962 non-COVID-19 controls were included. Of the COVID-19 survivors, >80% and >40% self-reported acute and post-acute COVID-19 sequelae, respectively. In the post-acute phase, COVID-19 survivors who were physically inactive had a 37% lower risk of insomnia, whereas those with prolonged sedentary behavior had 25%, 67%, and 117% higher risks of at least one symptom, dizziness, and "pins and needles" sensation, respectively. For the acute phase, prolonged sedentary behavior was associated with a higher risk of fatigue, "brain fog," dyspnea, muscle pain, joint pain, dizziness, and "pins and needles" sensation. Notably, sedentary behavior, rather than physical inactivity, was correlated with a higher risk of severe post-COVID-19 sequelae in both acute and post-acute phases. CONCLUSIONS: Prolonged sedentary behavior was independently associated with a higher risk of both acute and post-acute COVID-19 sequelae, whereas physical inactivity played contradictory roles in COVID-19 sequelae.

Identifying patterns of reported findings on long-term cardiac complications of COVID-19: a systematic review and meta-analysis.

INTRODUCTION: Prior reviews synthesized findings of studies on long-term cardiac complications of COVID-19. However, the reporting and methodological quality of these studies has not been systematically evaluated. Here, we conducted a systematic review and meta-analysis on long-term cardiac complications of COVID-19 and examined patterns of reported findings by study quality and characteristics. METHODS: We searched for studies examining long-term cardiac complications of COVID-19 that persisted for 4 weeks and over. A customized Newcastle-Ottawa scale (NOS) was used to evaluate the quality of included studies. Meta-analysis was performed to generate prevalence estimates of long-term cardiac complications across studies. Stratified analyses were further conducted to examine the prevalence of each complication by study quality and characteristics. The GRADE approach was used to determine the level of evidence for complications included in the meta-analysis. RESULTS: A total number of 150 studies describing 57 long-term cardiac complications were included in this review, and 137 studies reporting 17 complications were included in the meta-analysis. Only 25.3% (n = 38) of studies were of high quality based on the NOS quality assessment. Chest pain and arrhythmia were the most widely examined long-term complications. When disregarding study quality and characteristics, summary prevalence estimates for chest and arrhythmia were 9.79% (95% CI 7.24-13.11) and 8.22% (95% CI 6.46-10.40), respectively. However, stratified analyses showed that studies with low-quality scores, small sample sizes, unsystematic sampling methods, and cross-sectional design were more likely to report a higher prevalence of complications. For example, the prevalence of chest pain was 22.17% (95% CI 14.40-32.55), 11.08% (95% CI 8.65-14.09), and 3.89% (95% CI 2.49-6.03) in studies of low, medium, and high quality, respectively. Similar patterns were observed for arrhythmia and other less examined long-term cardiac complications. CONCLUSION: There is a wide spectrum of long-term cardiac complications of COVID-19. Reported findings from previous studies are strongly related to study quality, sample sizes, sampling methods, and designs, underscoring the need for high-quality epidemiologic studies to characterize these complications and understand their etiology.

The incidence and risk factors of selected drug prescriptions and outpatient care after SARS-CoV-2 infection in low-risk subjects: a multicenter population-based cohort study.

Background: Knowledge about the dynamics of transmission of SARS-CoV-2 and the clinical aspects of COVID-19 has steadily increased over time, although evidence of the determinants of disease severity and duration is still limited and mainly focused on older adult and fragile populations. Methods: The present study was conceived and carried out in the Emilia-Romagna (E-R) and Veneto Regions, Italy, within the context of the EU's Horizon 2020 research project called ORCHESTRA (Connecting European Cohorts to increase common and effective response to SARS-CoV-2 pandemic) (www.orchestra-cohort.eu). The study has a multicenter retrospective population-based cohort design and aimed to investigate the incidence and risk factors of access to specific healthcare services (outpatient visits and diagnostics, drug prescriptions) during the post-acute phase from day-31 to day-365 after SARS-CoV-2 infection, in a healthy population at low risk of severe acute COVID-19. The study made use of previously recorded large-scale healthcare data available in the administrative databases of the two Italian Regions. The statistical analysis made use of methods for competing risks. Risk factors were assessed separately in the two Regions and results were pooled using random effects meta-analysis. Results: There were 35,128 subjects in E-R and 88,881 in Veneto who were included in the data analysis. The outcome (access to selected health services) occurred in a high percentage of subjects in the post-acute phase (25% in E-R and 21% in Veneto). Outpatient care was observed more frequently than drug prescriptions (18% vs. 12% in E-R and 15% vs. 10% in Veneto). Risk factors associated with the outcome were female sex, age greater than 40 years, baseline risk of hospitalization and death, moderate to severe acute COVID-19, and acute extrapulmonary complications. Conclusion: The outcome of interest may be considered as a proxy for long-term effects of COVID-19 needing clinical attention. Our data suggest that this outcome occurs in a substantial percentage of cases, even among a previously healthy population with low or mild severity of acute COVID-19. The study results provide useful insights into planning COVID-19-related services.

A Clinical Qualification Protocol Highlights Overlapping Genomic Influences and Neuro-Autonomic Mechanisms in Ehlers-Danlos and Long COVID-19 Syndromes.

A substantial fraction of the 15% with double-jointedness or hypermobility have the traditionally ascertained joint-skeletal, cutaneous, and cardiovascular symptoms of connective tissue dysplasia and its particular manifestation as Ehlers-Danlos syndrome (EDS). The holistic ascertainment of 120 findings in 1261 EDS patients added neuro-autonomic symptoms like headaches, muscle weakness, brain fog, chronic fatigue, dyspnea, and bowel irregularity to those of arthralgia and skin laxity, 15 of these symptoms shared with those of post-infectious SARS-CoV-2 (long COVID-19). Underlying articulo-autonomic mechanisms guided a clinical qualification protocol that qualified DNA variants in 317 genes as having diagnostic utility for EDS, six of them identical (F2-LIFR-NLRP3-STAT1-T1CAM1-TNFRSF13B) and eighteen similar to those modifying COVID-19 severity/EDS, including ADAMTS13/ADAMTS2-C3/C1R-IKBKG/IKBKAP-PIK3C3/PIK3R1-POLD4/POLG-TMPRSS2/TMPRSS6-WNT3/WNT10A. Also, contributing to EDS and COVID-19 severity were forty and three genes, respectively, impacting mitochondrial functions as well as parts of an overlapping gene network, or entome, that are hypothesized to mediate the cognitive-behavioral, neuro-autonomic, and immune-inflammatory alterations of connective tissue in these conditions. The further characterization of long COVID-19 natural history and genetic predisposition will be necessary before these parallels to EDS can be carefully delineated and translated into therapies.

Prophylactic rivaroxaban in the early post-discharge period reduces the rates of hospitalization for atrial fibrillation and incidence of sudden cardiac death during long-term follow-up in hospitalized COVID-19 survivors.

Introduction: While acute Coronavirus disease 2019 (COVID-19) affects the cardiovascular (CV) system according to recent data, an increased CV risk has been reported also during long-term follow-up (FU). In addition to other CV pathologies in COVID-19 survivors, an enhanced risk for arrhythmic events and sudden cardiac death (SCD) has been observed. While recommendations on post-discharge thromboprophylaxis are conflicting in this population, prophylactic short-term rivaroxaban therapy after hospital discharge showed promising results. However, the impact of this regimen on the incidence of cardiac arrhythmias has not been evaluated to date. Methods: To investigate the efficacy of this therapy, we conducted a single center, retrospective analysis of 1804 consecutive, hospitalized COVID-19 survivors between April and December 2020. Patients received either a 30-day post-discharge thromboprophylaxis treatment regimen using rivaroxaban 10 mg every day (QD) (Rivaroxaban group (Riva); n = 996) or no thromboprophylaxis (Control group (Ctrl); n = 808). Hospitalization for new atrial fibrillation (AF), new higher-degree Atrioventricular-block (AVB) as well as incidence of SCD were investigated in 12-month FU [FU: 347 (310/449) days]. Results: No differences in baseline characteristics (Ctrl vs Riva: age: 59.0 (48.9/66.8) vs 57 (46.5/64.9) years, p = n.s.; male: 41.5% vs 43.7%, p = n.s.) and in the history of relevant CV-disease were observed between the two groups. While hospitalizations for AVB were not reported in either group, relevant rates of hospitalizations for new AF (0.99%, n = 8/808) as well as a high rate of SCD events (2.35%, n = 19/808) were seen in the Ctrl. These cardiac events were attenuated by early post-discharge prophylactic rivaroxaban therapy (AF: n = 2/996, 0.20%, p = 0.026 and SCD: n = 3/996, 0.30%, p < 0.001) which was also observed after applying a logistic regression model for propensity score matching (AF: χ 2-statistics = 6.45, p = 0.013 and SCD: χ 2-statistics = 9.33, p = 0.002). Of note, no major bleeding complications were observed in either group. Conclusion: Atrial arrhythmic and SCD events are present during the first 12 months after hospitalization for COVID-19. Extended prophylactic Rivaroxaban therapy after hospital discharge could reduce new onset of AF and SCD in hospitalized COVID-19 survivors.

COVID-19 Oral Sequelae: Persistent Gustatory and Saliva Secretory Dysfunctions after Recovery from COVID-19.

Diverse manifestations have been recognized to last for a long time in patients infected with SARS-CoV-2. However, understanding of oral sequelae after recovery from COVID-19 is relatively poor compared to that of oral symptoms in the acute phase of COVID-19 and other COVID-19 sequelae. The aim of the present study was to characterize persistent gustatory and saliva secretory dysfunctions and to speculate on their pathogenic mechanisms. Articles were retrieved by searching scientific databases with a cutoff date of September 30, 2022. The literature search indicated that ageusia/dysgeusia and xerostomia/dry mouth are reported by 1-45% of COVID-19 survivors at follow-ups of 21-365 days and by 2-40% of COVID-19 survivors at follow-ups of 28-230 days, respectively. The prevalence of gustatory sequelae partly depends on difference in ethnicity, gender, age, and disease severity of subjects. Co-occurring gustatory and saliva secretory sequelae are pathogenically related to either or both of the following: expression of SARS-CoV-2 cellular entry-relevant receptors in taste buds and salivary glands, and SARS-CoV-2 infection-induced deficiency in zinc that is essential for normality of taste perception and saliva secretion. Given the long-term oral sequelae, hospital discharge is not the end of the disease; therefore, careful attention should be continuously paid to oral conditions of post-COVID-19 patients.

SARS-CoV-2 and the nervous system: current perspectives.

SARS-CoV-2 infection frequently causes neurological impairment in both adults and children. Recent publications have described significant aspects of the viral pathophysiology associated with neurological dysfunction. In theory, neurological manifestations following SARS-CoV-2 infection may be caused directly by the effects of the virus infecting the brain or indirectly by the local and systemic immune responses against the virus. Neurological manifestations can occur during the acute phase as well as in the post-acute phase of the infection. In this review, we discuss recent literature describing the association of nervous system disorders with COVID-19.

Bronchoscopy in the post-acute phase of COVID-19: an observational study.

BACKGROUND: Bronchoscopy is a useful technique adopted in the management of patients with COVID-19. 10-40% of COVID-19 survivors experience persistent symptoms. A comprehensive description of the utility and safety of bronchoscopy in the management of patients with COVID-19 sequelae is lacking. The aim of the study was to evaluate the role of bronchoscopy in patients with suspected post-acute sequelae of COVID-19. METHODS: An observational, retrospective study was carried out in Italy. Patients requiring bronchoscopy for suspected COVID-19 sequelae were enrolled. RESULTS: 45 (21, 46.7%, female) patients were recruited. Bronchoscopy was more frequently indicated for patients with a previous critical disease. The most frequent indications were tracheal complications, mostly performed in patients who were hospitalized during the acute phase than treated at home (14, 48.3% VS. 1, 6.3%; p-value: 0.007) and persistent parenchymal infiltrates, more frequent in those treated at home (9, 56.3% VS. 5, 17.2%; p-value: 0.008). 3 (6.6%) patients after the first bronchoscopy required higher oxygen flow. Four patients were diagnosed with lung cancer. CONCLUSION: Bronchoscopy is a useful and safe technique in patients with suspected post-acute sequelae of COVID-19. The severity of acute disease plays a role in the rate and indications of bronchoscopy. Endoscopic procedures were mostly performed for tracheal complications in critical, hospitalized patients and for persistent lung parenchymal infiltrates in mild-moderate infections treated at home.

Post COVID-19 syndrome and new onset diseases: A prospective observational study.

Introduction: The National Institute of Health and Care Excellence (NICE) has defined the terms, 'acute coronavirus disease 2019' (COVID-19), 'ongoing symptomatic COVID-19' and 'post-COVID-19 syndrome', with the latter two described as having persistent symptoms after the onset of COVID-19 symptoms for 4-12 weeks and >12 weeks, respectively. Persistent symptoms can either be due to the after-effects of COVID-19 or new-onset diseases after acute COVID-19. All symptoms observed beyond 4 weeks after the onset of COVID-19 need not be present at the time of onset. Previous studies on persistent post-COVID-19 symptoms have not mentioned new-onset diseases after acute COVID-19, and only a select few studies have discussed such new-onset symptoms. Methods: Ninety-five patients who attended the post-COVID-19 clinic completed the requisite follow-up till 16 weeks after COVID-19 symptom onset. Data was recorded on a predesigned proforma. Necessary investigations were conducted to rule out any other cause of persistent symptoms. Results: Fatigue (62.1%), breathlessness (50.5%) and cough (27.4%) were the most common symptoms present beyond 4 weeks after the onset of COVID-19 symptoms. Forty-nine (51.57%) patients developed post-COVID-19 syndrome - their severity of symptoms (odds ratio [OR] 17.77) and longer duration of hospital stay (OR 1.095) during acute disease were significantly associated with the development of post-COVID-19 syndrome. During follow-up, 25 patients developed new-onset symptoms, such as diabetes mellitus, hypertension and idiopathic tachycardia. Conclusion: Patients can have persistent symptoms, new-onset symptoms and new-onset diseases after recovery from acute COVID-19.

Six-month follow-up after recovery of COVID-19 Delta variant survivors via CT-based deep learning.

Purpose: Using computer-aided diagnosis (CAD) methods to analyze the discharge and 6-month follow-up data of COVID-19 Delta variant survivors, evaluate and summarize the recovery and prognosis, and improve people's awareness of this disease. Methods: This study collected clinical data, SGRQ questionnaire results, and lung CT scans (at both discharge and 6-month follow-up) from 41 COVID-19 Delta variant survivors. Two senior radiologists evaluated the CT scans before in-depth analysis. Deep lung parenchyma enhancing (DLPE) method was used to accurately segment conventional lesions and sub-visual lesions in CT images, and then quantitatively analyze lung injury and recovery. Patient recovery was also measured using the SGRQ questionnaire. The follow-up examination results from this study were combined with those of the original COVID-19 for further comparison. Results: The participants include 13 males (31.7%) and 28 females (68.3%), with an average age of 42.2 ± 17.7 years and an average BMI of 25.2 ± 4.4 kg/m2. Compared discharged CT and follow-up CT, 48.8% of survivors had pulmonary fibrosis, mainly including irregular lines (34.1%), punctuate calcification (12.2%) and nodules (12.2%). Compared with discharged CT, the ground-glass opacity basically dissipates at follow-up. The mean SGRQ score was 0.041 (0-0.104). The sequelae of survivors mainly included impaired sleep quality (17.1%), memory decline (26.8%), and anxiety (21.9%). After DLPE process, the lesion volume ratio decreased from 0.0018 (0.0003, 0.0353) at discharge to 0.0004 (0, 0.0032) at follow-up, p < 0.05, and the absorption ratio of lesion was 0.7147 (-1.0303, 0.9945). Conclusion: The ground-glass opacity of survivors had dissipated when they were discharged from hospital, and a little fibrosis was seen in CT after 6-month, mainly manifested as irregular lines, punctuate calcification and nodules. After DLPE and quantitative calculations, we found that the degree of fibrosis in the lungs of most survivors was mild, which basically did not affect lung function. However, there are a small number of patients with unabsorbed or increased fibrosis. Survivors mainly had non-pulmonary sequelae such as impaired sleep quality and memory decline. Pulmonary prognosis of Delta variant patients was better than original COVID-19, with fewer and milder sequelae.

Long-term cardiac symptoms following COVID-19: a systematic review and meta-analysis.

Background: There is growing body of literature on the long-term cardiac symptoms following COVID-19. We conducted a systematic review and meta-analysis to synthesize and evaluate related evidence to inform clinical management and future studies. Methods: We searched two preprint and seven peer-reviewed article databases from January 1, 2020 to January 8, 2022 for studies investigating cardiac symptoms that persisted for at least 4 weeks among individuals who survived COVID-19. A customized Newcastle-Ottawa scale was used to evaluate the quality of included studies. Random-effects meta-analyses were performed to estimate the proportion of symptoms with 95% confidence intervals (CI), and stratified analyses were conducted to quantify the proportion of symptoms by study characteristics and quality. Results: A total of 101 studies describing 49 unique long-term cardiac symptoms met the inclusion criteria. Based on quality assessment, only 15.8% of the studies (n=16) were of high quality, and most studies scored poorly on sampling representativeness. The two most examined symptoms were chest pain and arrhythmia. Meta-analysis showed that the proportion of chest pain was 10.1% (95% CI: 6.4-15.5) and arrhythmia was 9.8% (95% CI: 5.4-17.2). Stratified analyses showed that studies with low-quality score, small sample size, unsystematic sampling method, and cross-sectional design were most likely to report high proportions of symptoms. For example, the proportion of chest pain was 21.3% (95% CI: 10.5-38.5), 9.3% (95% CI: 6.0-14.0), and 4.0% (95% CI: 1.3-12.0) in studies with low, medium, and high-quality scores, respectively. Similar patterns were observed for other cardiac symptoms including hypertension, cardiac abnormalities, myocardial injury, thromboembolism, stroke, heart failure, coronary disease, and myocarditis. Discussion: There is a wide spectrum of long-term cardiac symptoms following COVID-19. Findings of existing studies are strongly related to study quality, size and design, underscoring the need for high-quality epidemiologic studies to characterize these symptoms and understand their etiology.