Post-COVID Syndrome

Abstract:

Background: As defined by the WHO, the term post-COVID syndrome (PCS) embraces a group of symptoms that can occur following the acute phase of a SARS-CoV-2 infection and as a consequence thereof. PCS is found mainly in adults, less frequently in children and adolescents. It can develop both in patients who initially had only mild symptoms or none at all and in those who had a severe course of coronavirus disease 2019 (COVID-19).

Methods: The data presented here were derived from a systematic literature review.

Results: PCS occurs in up to 15% of unvaccinated adults infected with SARS-CoV-2. The prevalence has decreased in the most recent phase of the pandemic and is lower after vaccination. The pathogenesis of PCS has not yet been fully elucidated. Virus triggered inflammation, autoimmunity, endothelial damage (to blood vessels), and persistence of virus are thought to be causative. Owing to the broad viral tropism, different organs are involved and the symptoms vary. To date, there are hardly any evidence-based recommendations for definitive diagnosis of PCS or its treatment.

Conclusion: The gaps in our knowledge mean that better documentation of the prevalence of PCS is necessary to compile the data on which early detection, diagnosis, and treatment can be based. To ensure the best possible care of patients with PCS, regional PCS centers and networks embracing existing structures from all healthcare system sectors and providers should be set up and structured diagnosis and treatment algorithms should be established. Given the sometimes serious consequences of PCS for those affected, it seems advisable to keep the number of SARS-CoV-2 infections low by protective measures tailored to the prevailing pandemic situation.

Source: Hallek M, Adorjan K, Behrends U, Ertl G, Suttorp N, Lehmann C. Post-COVID Syndrome. Dtsch Arztebl Int. 2023 Jan 27;120(4):48-55. doi: 10.3238/arztebl.m2022.0409. PMID: 36633452; PMCID: PMC10060997. https://www.aerzteblatt.de/int/archive/article/229208 (Full text)

Risk Factors Associated With Post−COVID-19 Condition A Systematic Review and Meta-analysis

Abstract:

Importance  Post−COVID-19 condition (PCC) is a complex heterogeneous disorder that has affected the lives of millions of people globally. Identification of potential risk factors to better understand who is at risk of developing PCC is important because it would allow for early and appropriate clinical support.

Objective  To evaluate the demographic characteristics and comorbidities that have been found to be associated with an increased risk of developing PCC.

Data sources  Medline and Embase databases were systematically searched from inception to December 5, 2022.

Study Selection  The meta-analysis included all published studies that investigated the risk factors and/or predictors of PCC in adult (≥18 years) patients.

Data Extraction and Synthesis  Odds ratios (ORs) for each risk factor were pooled from the selected studies. For each potential risk factor, the random-effects model was used to compare the risk of developing PCC between individuals with and without the risk factor. Data analyses were performed from December 5, 2022, to February 10, 2023.

Main Outcomes and Measures  The risk factors for PCC included patient age; sex; body mass index, calculated as weight in kilograms divided by height in meters squared; smoking status; comorbidities, including anxiety and/or depression, asthma, chronic kidney disease, chronic obstructive pulmonary disease, diabetes, immunosuppression, and ischemic heart disease; previous hospitalization or ICU (intensive care unit) admission with COVID-19; and previous vaccination against COVID-19.

Results  The initial search yielded 5334 records of which 255 articles underwent full-text evaluation, which identified 41 articles and a total of 860 783 patients that were included. The findings of the meta-analysis showed that female sex (OR, 1.56; 95% CI, 1.41-1.73), age (OR, 1.21; 95% CI, 1.11-1.33), high BMI (OR, 1.15; 95% CI, 1.08-1.23), and smoking (OR, 1.10; 95% CI, 1.07-1.13) were associated with an increased risk of developing PCC. In addition, the presence of comorbidities and previous hospitalization or ICU admission were found to be associated with high risk of PCC (OR, 2.48; 95% CI, 1.97-3.13 and OR, 2.37; 95% CI, 2.18-2.56, respectively). Patients who had been vaccinated against COVID-19 with 2 doses had a significantly lower risk of developing PCC compared with patients who were not vaccinated (OR, 0.57; 95% CI, 0.43-0.76).

Conclusions and Relevance  This systematic review and meta-analysis demonstrated that certain demographic characteristics (eg, age and sex), comorbidities, and severe COVID-19 were associated with an increased risk of PCC, whereas vaccination had a protective role against developing PCC sequelae. These findings may enable a better understanding of who may develop PCC and provide additional evidence for the benefits of vaccination.

Trial Registration  PROSPERO Identifier: CRD42022381002

Source: Tsampasian V, Elghazaly H, Chattopadhyay R, et al. Risk Factors Associated With Post−COVID-19 ConditionA Systematic Review and Meta-analysisJAMA Intern Med. Published online March 23, 2023. doi:10.1001/jamainternmed.2023.0750 https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2802877 (Full text)

Objective sleep measures in chronic fatigue syndrome patients: A systematic review and meta-analysis

Abstract:

Patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) often report disrupted and unrefreshing sleep in association with worsened fatigue symptoms. However, the nature and magnitude of sleep architecture alteration in ME/CFS is not known, with studies using objective sleep measures in ME/CFS generating contradictory results.

The current manuscript aimed to review and meta-analyse of case-control studies with objective sleep measures in ME/CSF. A search was conducted in PubMed, Scopus, Medline, Google Scholar, and Psychoinfo databases.

After review, 24 studies were included in the meta-analysis, including 20 studies with 801 adults (ME/CFS = 426; controls = 375), and 4 studies with 477 adolescents (ME/CFS = 242; controls = 235), who underwent objective measurement of sleep.

Adult ME/CFS patients spend longer time in bed, longer sleep onset latency, longer awake time after sleep onset, decreased sleep efficiency, decreased stage 2 sleep, increased Stage 3, and longer rapid eye movement sleep latency.

However, adolescent ME/CFS patients had longer time in bed, longer total sleep time, longer sleep onset latency, and reduced sleep efficiency.

The meta-analysis results demonstrate that sleep is altered in ME/CFS, with changes seeming to differ between adolescent and adults, and suggesting sympathetic and parasympathetic nervous system alterations in ME/CFS.

Source: Abdalla Z. Mohamed, Thu Andersen, Sanja Radovic, Peter Del Fante, Richard Kwiatek, Vince Calhoun, Sandeep Bhuta, Daniel F. Hermens, Jim Lagopoulos, Zack Shan. Objective sleep measures in chronic fatigue syndrome patients: A systematic review and meta-analysis. Sleep Medicine Reviews, 2023, 101771.  https://www.sciencedirect.com/science/article/abs/pii/S1087079223000278

Nursing Diagnoses of Individuals with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Research Protocol for a Qualitative Synthesis

Abstract:

Although previously developed qualitative studies have explored the experience of illness of individuals with myalgic encephalomyelitis/chronic fatigue syndrome, these findings have not been undertaken for the purpose of enabling the identification of nursing care needs in such patients. This study aims to identify NANDA-I nursing diagnoses of adults with myalgic encephalomyelitis/chronic fatigue syndrome based on a qualitative literature review of their experience of illness.

The protocol includes: searches in the electronic databases Medline, Embase, CINAHL, PsycINFO, SCI-EXPANDED, SSCI, SciELO, LILACS, and Cuiden; and manual searches in specialised journals and the references of the included studies. The authors will systematically search qualitative research studies published in databases from 1994 to 2021. Searches are limited to studies in Spanish and English. All stages of the review process will be carried out independently by two reviewers. Any disagreements shall be resolved through joint discussions, involving a third reviewer if necessary.

The findings will be synthesised into a thematic analysis informed by the Domains and Classes of the NANDA-I Classification of Nursing Diagnoses, which will then serve to identify nursing diagnoses. This review will enable nursing professionals to identify the care needs of individuals with myalgic encephalomyelitis/chronic fatigue syndrome by taking into consideration their experience of illness in its entirety.

Source: Oter-Quintana C, Esteban-Hernández J, Cuéllar-Pompa L, Gil-Carballo MC, Brito-Brito PR, Martín-García A, Alcolea-Cosín MT, Martínez-Marcos M, Alameda-Cuesta A. Nursing Diagnoses of Individuals with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Research Protocol for a Qualitative Synthesis. Healthcare (Basel). 2022 Dec 10;10(12):2506. doi: 10.3390/healthcare10122506. PMID: 36554030; PMCID: PMC9777975. https://www.mdpi.com/2227-9032/10/12/2506 (Full text)

COVID-19 disease severity to predict persistent symptoms: a systematic review and meta-analysis

Abstract:

Background: It is unclear, whether the initial disease severity may help to predict which COVID-19 patients at risk of developing persistent symptoms.

Aim: The aim of this study was to examine whether the initial disease severity affects the risk of persistent symptoms in post-acute COVID-19 syndrome and long COVID.

Methods: A systematic search was conducted using PUBMED, Google Scholar, EMBASE, and ProQuest databases to identify eligible articles published after January 2020 up to and including 30 August 2021. Pooled odds ratio (OR) and confidence intervals (CIs) were calculated using random effects meta-analysis.

Findings: After searching a total of 7733 articles, 20 relevant observational studies with a total of 7840 patients were selected for meta-analysis. The pooled OR for persistent dyspnea in COVID-19 survivors with a severe versus nonsevere initial disease was 2.17 [95%CI 1.62 to 2.90], and it was 1.33 [95%CI 0.75 to 2.33] for persistent cough, 1.30 [95%CI 1.06 to 1.58] for persistent fatigue, 1.02 [95%CI 0.73 to 1.40] for persistent anosmia, 1.22 [95%CI 0.69 to 2.16] for persistent chest pain, and 1.30 [95%CI 0.93 to 1.81] for persistent palpitation.

Conclusions: Contrary to expectations, we did not observe an association between the initial COVID-19 disease severity and common persistent symptoms except for dyspnea and fatigue. In addition, it was found that being in the acute or prolonged post-COVID phase did not affect the risk of symptoms. Primary care providers should be alert to potential most prevalent persistent symptoms in all COVID-19 survivors, which are not limited to patients with critical-severe initial disease.

Source: Dirican E, Bal T. COVID-19 disease severity to predict persistent symptoms: a systematic review and meta-analysis. Prim Health Care Res Dev. 2022 Nov 10;23:e69. doi: 10.1017/S1463423622000585. PMID: 36352492.  https://www.cambridge.org/core/journals/primary-health-care-research-and-development/article/covid19-disease-severity-to-predict-persistent-symptoms-a-systematic-review-and-metaanalysis/479FC1E900E22673895FDAC1CF5C12B2 (Full text)

Fibromyalgia and Chronic Fatigue Syndromes: A systematic review and meta-analysis of cardiorespiratory fitness and neuromuscular function compared with healthy individuals

Abstract:

Objective: To determine cardiorespiratory fitness and neuromuscular function of people with CFS and FMS compared to healthy individuals.

Design: Systematic review and meta-analysis.

Data sources: PubMed, Medline, CINAHL, AMED, Cochrane Central Register of Controlled Trials (CENTRAL), and PEDro from inception to June 2022.

Eligible criteria for selecting studies: Studies were included if presenting baseline data on cardiorespiratory fitness and/or neuromuscular function from observational or interventional studies of patients diagnosed with FMS or CFS. Participants were aged 18 years or older, with results also provided for healthy controls. Risk of bias assessment was conducted using the Quality Assessment Tool for Quantitative Studies (EPHPP).

Results: 99 studies including 9853 participants (5808 patients; 4405 healthy controls) met our eligibility criteria. Random effects meta-analysis showed lower cardiorespiratory fitness (VO2max, anaerobic threshold, peak lactate) and neuromuscular function (MVC, fatigability, voluntary activation, muscle volume, muscle mass, rate of perceived exertion) in CFS and FMS compared to controls: all with moderate to high effect sizes.

Discussion: Our results demonstrate lower cardiorespiratory fitness and muscle function in those living with FMS or CFS when compared to controls. There were indications of dysregulated neuro-muscular interactions including heightened perceptions of effort, reduced ability to activate the available musculature during exercise and reduced tolerance of exercise.

Source: Zambolin F, Duro-Ocana P, Faisal A, Bagley L, Gregory WJ, Jones AW, McPhee JS. Fibromyalgia and Chronic Fatigue Syndromes: A systematic review and meta-analysis of cardiorespiratory fitness and neuromuscular function compared with healthy individuals. PLoS One. 2022 Oct 20;17(10):e0276009. doi: 10.1371/journal.pone.0276009. PMID: 36264901; PMCID: PMC9584387. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9584387/ (Full text)

Chinese herbal medicine for the treatment of chronic fatigue syndrome: A systematic review and meta-analysis

Abstract:

Objectives: This meta-analysis aimed to assess the effectiveness and safety of Chinese herbal medicine (CHM) in treating chronic fatigue syndrome (CFS).

Methods: Nine electronic databases were searched from inception to May 2022. Two reviewers screened studies, extracted the data, and assessed the risk of bias independently. The meta-analysis was performed using the Stata 12.0 software.

Results: Eighty-four RCTs that explored the efficacy of 69 kinds of Chinese herbal formulas with various dosage forms (decoction, granule, oral liquid, pill, ointment, capsule, and herbal porridge), involving 6,944 participants were identified. This meta-analysis showed that the application of CHM for CFS can decrease Fatigue Scale scores (WMD: –1.77; 95%CI: –1.96 to –1.57; p < 0.001), Fatigue Assessment Instrument scores (WMD: –15.75; 95%CI: –26.89 to –4.61; p < 0.01), Self-Rating Scale of mental state scores (WMD: –9.72; 95%CI:–12.26 to –7.18; p < 0.001), Self-Rating Anxiety Scale scores (WMD: –7.07; 95%CI: –9.96 to –4.19; p < 0.001), Self-Rating Depression Scale scores (WMD: –5.45; 95%CI: –6.82 to –4.08; p < 0.001), and clinical symptom scores (WMD: –5.37; 95%CI: –6.13 to –4.60; p < 0.001) and improve IGA (WMD: 0.30; 95%CI: 0.20–0.41; p < 0.001), IGG (WMD: 1.74; 95%CI: 0.87–2.62; p < 0.001), IGM (WMD: 0.21; 95%CI: 0.14–0.29; p < 0.001), and the effective rate (RR = 1.41; 95%CI: 1.33–1.49; p < 0.001). However, natural killer cell levels did not change significantly. The included studies did not report any serious adverse events. In addition, the methodology quality of the included RCTs was generally not high.

Conclusion: Our study showed that CHM seems to be effective and safe in the treatment of CFS. However, given the poor quality of reports from these studies, the results should be interpreted cautiously. More international multi-centered, double-blinded, well-designed, randomized controlled trials are needed in future research.

Source: Zhang, Jin, Wei, Jin, Xie, Pan and Shen. Chinese herbal medicine for the treatment of chronic fatigue syndrome: A systematic review and meta-analysis. Front. Pharmacol., 29 September 2022. Sec. Ethnopharmacology https://doi.org/10.3389/fphar.2022.958005 https://www.frontiersin.org/articles/10.3389/fphar.2022.958005/full (Full text)

Prevalence and clinical presentation of long COVID in children: a systematic review

Abstract:

A systematic literature review was conducted up to 15th February 2022 to summarize long COVID evidence and to assess prevalence and clinical presentation in children and adolescents. Articles reporting long COVID prevalence and symptoms based on original data in the paediatric population were included. Case series quality was assessed through the JBI Critical Appraisal Checklist. For observational studies, adherence to STROBE checklist was evaluated. Twenty-two articles were included: 19 observational studies (12 cohort/7 cross-sectional) and 3 case series. Nine studies provided a control group. We found a high variability in terms of prevalence (1.6-70%). The most frequently reported symptoms were fatigue (2-87%), headache (3.5-80%), arthro-myalgias (5.4-66%), chest tightness or pain (1.4-51%), and dyspnoea (2-57.1%). Five studies reported limitations in daily function due to long COVID. Alterations at brain imaging were described in one study, transient electrocardiographic abnormalities were described in a minority of children, while most authors did not evidence long-term pulmonary sequelae. Older age, female sex, and previous long-term pathological conditions were more frequently associated with persistent symptoms.

Conclusion: Long COVID evidence in children is limited, heterogeneous, and based on low-quality studies. The lockdown consequences are difficult to distinguish from long COVID symptoms. High-quality studies are required: WHO definition of long COVID should be used, controlled clinical studies should be encouraged, and the impact of new variants on long COVID prevalence should be investigated to ensure an objective analysis of long COVID characteristics in children and a proper allocation of healthcare system resources.

What is known: • Children rarely develop a severe respiratory disease in the acute phase of COVID-19. • A limited number of patients develop a multisystem inflammatory condition that can lead to multiorgan failure and shock.

What is new: • Persistent symptoms after SARS-CoV-2 infection are reported in children and limitations in daily function due to long COVID symptoms affect school attendance. • Functional complaints of post-acute COVID are difficult to be distinguished from those due to social restrictions.

Source: Pellegrino R, Chiappini E, Licari A, Galli L, Marseglia GL. Prevalence and clinical presentation of long COVID in children: a systematic review. Eur J Pediatr. 2022 Sep 15:1–15. doi: 10.1007/s00431-022-04600-x. Epub ahead of print. PMID: 36107254; PMCID: PMC9476461.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9476461/ (Full text)

Long COVID in children and adolescents

Abstract:

Purpose of review: Although acute COVID-19 has been milder in children and young people compared with adults, there is a concern that they may suffer persistent symptoms. There is a need to define the clinical phenotype, determine those most at risk, the natural course of the condition and evaluate preventive and therapeutic strategies for both mental health and physical symptoms.

Recent findings: More recent studies with control groups reported a lower prevalence of persistent symptoms in children and young people exposed to SARS-CoV-2. A systematic review and meta-analysis found that the frequency of the majority of reported persistent symptoms is similar in SARS-CoV-2 positive cases and controls. Children and young people infected with SARS-COV-2 had small but significant increases in persisting cognitive difficulties, headache and loss of smell. Factors associated with persisting, impairing symptoms include increased number of symptoms at the time of testing, female sex, older age, worse self-rated physical and mental health, and feelings of loneliness preinfection.

Summary: This review highlights the importance of a control group in studies following SARS-CoV-2 infection, the need for case definitions and research to understand the outcomes of long COVID in children and young people.

Source: Stephenson T, Shafran R, Ladhani SN. Long COVID in children and adolescents. Curr Opin Infect Dis. 2022 Sep 12. doi: 10.1097/QCO.0000000000000854. Epub ahead of print. PMID: 36094094.  https://journals.lww.com/co-infectiousdiseases/Fulltext/2022/10000/Long_COVID_in_children_and_adolescents.14.aspx (Full text)