Tag: long covid symptoms

Mid-term Follow-Up chest CT findings in recovered COVID-19 patients with residual symptoms

Abstract:

Objectives: More than a year has passed since the initial outbreak of SARS-CoV-2, which caused many hospitalizations worldwide due to COVID-19 pneumonia and its complications. However, there is still a lack of information detailing short- and long-term outcomes of previously hospitalized patients. The purpose of this study is to analyze the most frequent lung CT findings in recovered COVID-19 patients at mid-term follow-ups.

Methods: A total of 407 consecutive COVID-19 patients who were admitted to the XXXX and discharged between February 27, 2020, and June 26, 2020 were recruited into this study. Out of these patients, a subset of 108 patients who presented with residual asthenia and dyspnea at discharge, altered spirometric data, positive lung ultrasound and positive chest X-ray was subsequently selected, and was scheduled to undergo a mid-term chest computer tomography study, which was evaluated for specific lung alterations and morphological patterns.

Results: The most frequently observed lung CT alterations, in order of frequency, were ground glass opacities (81%), linear opacities (74%), bronchiolectases (64,81%), and reticular opacities (63,88%). The most common morphological pattern was the nonspecific interstitial pneumonia pattern (63,88%). Features consistent with pulmonary fibrosis were observed in 32 patients (29,62%).

Conclusions: Our work showed that recovered COVID-19 patients that were hospitalized and that exhibited residual symptoms after discharge had a slow radiological recovery with persistent residual lung alterations.

Advances in knowledge: This slow recovery process should be kept in mind when determining the follow-up phases in order to improve the long-term management of patients affected by COVID-19.

Source: Marchetti F, Izzi N, Donatelli A, Valentini A, Muzic SI, Dore R, Di Sabatino A, Perrone T, Falaschi F, Sabatini U, Ballesio A, Meloni F, Lettieri S, Mojoli F, Perlini S, Novati S, Pagani E, Klersy C, Bruno R, Preda L. Mid-term Follow-Up chest CT findings in recovered COVID-19 patients with residual symptoms. Br J Radiol. 2022 Nov 25:20220012. doi: 10.1259/bjr.20220012. Epub ahead of print. PMID: 36427055.  https://pubmed.ncbi.nlm.nih.gov/36427055/

Recommendations for Successful Implementation of the Use of Vocal Biomarkers for Remote Monitoring of COVID-19 and Long COVID in Clinical Practice and Research

Abstract:

The COVID-19 pandemic accelerated the use of remote patient monitoring in clinical practice or research for safety and emergency reasons, justifying the need for innovative digital health solutions to monitor key parameters or symptoms related to COVID-19 or Long COVID. The use of voice-based technologies, and in particular vocal biomarkers, is a promising approach, voice being a rich, easy-to-collect medium with numerous potential applications for health care, from diagnosis to monitoring.

In this viewpoint, we provide an overview of the potential benefits and limitations of using voice to monitor COVID-19, Long COVID, and related symptoms. We then describe an optimal pipeline to bring a vocal biomarker candidate from research to clinical practice and discuss recommendations to achieve such a clinical implementation successfully.

Source: Fischer A, Elbeji A, Aguayo G, Fagherazzi G. Recommendations for Successful Implementation of the Use of Vocal Biomarkers for Remote Monitoring of COVID-19 and Long COVID in Clinical Practice and Research. Interact J Med Res. 2022 Nov 15;11(2):e40655. doi: 10.2196/40655. PMID: 36378504; PMCID: PMC9668331. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9668331/ (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)

Role of neuroinflammation mediated potential alterations in adult neurogenesis as a factor for neuropsychiatric symptoms in Post-Acute COVID-19 syndrome-A narrative review

Abstract:

Persistence of symptoms beyond the initial 3 to 4 weeks after infection is defined as post-acute COVID-19 syndrome (PACS). A wide range of neuropsychiatric symptoms like anxiety, depression, post-traumatic stress disorder, sleep disorders and cognitive disturbances have been observed in PACS. The review was conducted based on PRISMA-S guidelines for literature search strategy for systematic reviews.

A cytokine storm in COVID-19 may cause a breach in the blood brain barrier leading to cytokine and SARS-CoV-2 entry into the brain. This triggers an immune response in the brain by activating microglia, astrocytes, and other immune cells leading to neuroinflammation. Various inflammatory biomarkers like inflammatory cytokines, chemokines, acute phase proteins and adhesion molecules have been implicated in psychiatric disorders and play a major role in the precipitation of neuropsychiatric symptoms. Impaired adult neurogenesis has been linked with a variety of disorders like depression, anxiety, cognitive decline, and dementia.

Persistence of neuroinflammation was observed in COVID-19 survivors 3 months after recovery. Chronic neuroinflammation alters adult neurogenesis with pro-inflammatory cytokines supressing anti-inflammatory cytokines and chemokines favouring adult neurogenesis. Based on the prevalence of neuropsychiatric symptoms/disorders in PACS, there is more possibility for a potential impairment in adult neurogenesis in COVID-19 survivors. This narrative review aims to discuss the various neuroinflammatory processes during PACS and its effect on adult neurogenesis.

Source: Saikarthik J, Saraswathi I, Alarifi A, Al-Atram AA, Mickeymaray S, Paramasivam A, Shaikh S, Jeraud M, Alothaim AS. Role of neuroinflammation mediated potential alterations in adult neurogenesis as a factor for neuropsychiatric symptoms in Post-Acute COVID-19 syndrome-A narrative review. PeerJ. 2022 Nov 4;10:e14227. doi: 10.7717/peerj.14227. PMID: 36353605; PMCID: PMC9639419. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9639419/ (Full text)

Characterization of autonomic symptom burden in long COVID: A global survey of 2,314 adults

Abstract:

Background: Autonomic dysfunction is a known complication of post-acute sequelae of SARS-CoV-2 (PASC)/long COVID, however prevalence and severity are unknown.

Objective: To assess the frequency, severity, and risk factors of autonomic dysfunction in PASC, and to determine whether severity of acute SARS-CoV-2 infection is associated with severity of autonomic dysfunction.

Design: Cross-sectional online survey of adults with PASC recruited through long COVID support groups between October 2020 and August 2021.

Participants: 2,413 adults ages 18-64 years with PASC including patients who had a confirmed positive test for COVID-19 (test-confirmed) and participants who were diagnosed with COVID-19 based on clinical symptoms alone.

Main measures: The main outcome measure was the Composite Autonomic Symptom 31 (COMPASS-31) total score, used to assess global autonomic dysfunction. Test-confirmed hospitalized vs. test-confirmed non-hospitalized participants were compared to determine if the severity of acute SARS-CoV-2 infection was associated with the severity autonomic dysfunction.

Key results: Sixty-six percent of PASC patients had a COMPASS-31 score >20, suggestive of moderate to severe autonomic dysfunction. COMPASS-31 scores did not differ between test-confirmed hospitalized and test-confirmed non-hospitalized participants [28.95 (15.62, 46.60) vs. 26.4 (13.75, 42.10); p = 0.06].

Conclusions: Evidence of moderate to severe autonomic dysfunction was seen in 66% of PASC patients in our study, independent of hospitalization status, suggesting that autonomic dysfunction is highly prevalent in the PASC population and independent of the severity of acute COVID-19 illness.

Source: Larsen NW, Stiles LE, Shaik R, Schneider L, Muppidi S, Tsui CT, Geng LN, Bonilla H, Miglis MG. Characterization of autonomic symptom burden in long COVID: A global survey of 2,314 adults. Front Neurol. 2022 Oct 19;13:1012668. doi: 10.3389/fneur.2022.1012668. PMID: 36353127; PMCID: PMC9639503. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9639503/ (Full text)

Central hypersomnia and chronic insomnia: expanding the spectrum of sleep disorders in long COVID syndrome – a prospective cohort study

Abstract:

Introduction: Long-onset COVID syndrome has been described in patients with COVID-19 infection with persistence of symptoms or development of sequelae beyond 4 weeks after the onset of acute symptoms, a medium- and long-term consequence of COVID-19. This syndrome can affect up to 32% of affected individuals, with symptoms of fatigue, dyspnea, chest pain, cognitive disorders, insomnia, and psychiatric disorders. The present study aimed to characterize and evaluate the prevalence of sleep symptoms in patients with long COVID syndrome.

Methodology: A total of 207 patients with post-COVID symptoms were evaluated through clinical evaluation with a neurologist and specific exams in the subgroup complaining of excessive sleepiness.

Results: Among 189 patients included in the long COVID sample, 48 (25.3%) had sleep-related symptoms. Insomnia was reported by 42 patients (22.2%), and excessive sleepiness (ES) was reported by 6 patients (3.17%). Four patients with ES were evaluated with polysomnography and test, multiple sleep latencies test, and actigraphic data. Two patients had a diagnosis of central hypersomnia, and one had narcolepsy. A history of steroid use was related to sleep complaints (insomnia and excessive sleepiness), whereas depression was related to excessive sleepiness. We observed a high prevalence of cognitive complaints in these patients.

Conclusion: Complaints related to sleep, such as insomnia and excessive sleepiness, seem to be part of the clinical post-acute syndrome (long COVID syndrome), composing part of its clinical spectrum, relating to some clinical data.

Source: Moura AEF, Oliveira DN, Torres DM, Tavares-Júnior JWL, Nóbrega PR, Braga-Neto P, Sobreira-Neto MA. Central hypersomnia and chronic insomnia: expanding the spectrum of sleep disorders in long COVID syndrome – a prospective cohort study. BMC Neurol. 2022 Nov 9;22(1):417. doi: 10.1186/s12883-022-02940-7. PMID: 36352367; PMCID: PMC9643986. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9643986/ (Full text)

Post COVID and Apheresis – Where are we Standing?

Abstract:

A continual increase in cases of Long/Post COVID constitutes a medical and socioeconomic challenge to health systems around the globe. While the true extent of this problem cannot yet be fully evaluated, recent data suggest that up to 20% of people with confirmed SARS-CoV-2 suffer from clinically relevant symptoms of Long/Post COVID several weeks to months after the acute phase. The clinical presentation is highly variable with the main symptoms being chronic fatigue, dyspnea, and cognitive symptoms. Extracorporeal apheresis has been suggested to alleviate symptoms of Post/COVID. Thus, numerous patients are currently treated with apheresis.

However, at present there is no data from randomized controlled trials available to confirm the efficacy. Therefore, physicians rely on the experience of practitioners and centers performing this treatment. Here, we summarize clinical experience on extracorporeal apheresis in patients with Post/COVID from centers across Germany.

Source: Steenblock C, Walther R, Tselmin S, Jarzebska N, Voit-Bak K, Toepfner N, Siepmann T, Passauer J, Hugo C, Wintermann G, Julius U, Barbir M, Khan TZ, Puhan MA, Straube R, Hohenstein B, Bornstein SR, Rodionov RN. Post COVID and Apheresis – Where are we Standing? Horm Metab Res. 2022 Nov;54(11):715-720. doi: 10.1055/a-1945-9694. Epub 2022 Sep 16. PMID: 36113501. https://www.thieme-connect.de/products/ejournals/html/10.1055/a-1945-9694 (Full text)

Post-acute symptoms 3-15 months after COVID-19 among unvaccinated and vaccinated individuals with a breakthrough infection

Abstract:

Objectives: We aimed to describe post-acute sequelae of SARS-CoV-2 infection (PASC) related symptoms 3-15 months after a positive test in SARS-CoV-2 unvaccinated and vaccinated participants with a breakthrough infection.

Methods: Participants of the Norwegian COVID-19 Cohort, without a positive SARS-CoV-2 test, filled in a questionnaire asking about PASC-related symptoms between November 2020 and January 2021. About a year later, a second questionnaire (which also included the Everyday Memory Questionnaire 13 (EMQ-13)) was filled in by the same participants, most still without a positive SARS-CoV-2 test, but also by unvaccinated and vaccinated participants with a positive test 3-15 months before the questionnaire. Laboratory-confirmed SARS-CoV-2 status (positive or negative swab test determined by reverse transcriptase quantitative polymerase chain reaction) at the time of completing questionnaires was ascertained from the Mandatory Norwegian Surveillance System for Communicable Diseases.

Results: No differences were found in the self-reported PASC-symptoms dyspnea, fatigue, smell/taste changes or concentration problems, or the EMQ-13 score between unvaccinated and vaccinated participants 3-15 months after the positive test. Less memory problems were reported among vaccinated than unvaccinated participants.

Conclusions: SARS-CoV-2 vaccines offer minor protection against PASC-symptoms, although less memory problems were reported among the vaccinated than the unvaccinated participants.

Source: Brunvoll SH, Nygaard AB, Fagerland MW, Holland P, Ellingjord-Dale M, Dahl JA, Søraas A. Post-acute symptoms 3-15 months after COVID-19 among unvaccinated and vaccinated individuals with a breakthrough infection. Int J Infect Dis. 2022 Nov 11;126:10–3. doi: 10.1016/j.ijid.2022.11.009. Epub ahead of print. PMID: 36375693; PMCID: PMC9651990. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9651990/ (Full text)

Infection with SARS-CoV-2 Variants Is Associated with Different Long COVID Phenotypes

Abstract:

COVID-19 has been associated with a broad range of long-term sequelae, commonly referred to as “long-COVID” or “post-COVID-19” syndrome. Despite an increasing body of literature, long COVID remains poorly characterized. We retrospectively analysed data from electronic medical records of patients admitted to the post-COVID-19 outpatient service of the Infectious and Tropical Diseases Unit, Careggi University Hospital, Florence, Italy, between June 2020 and June 2021, 4-12 weeks after hospital discharge.

A total of 428 patients, 41% women, median age 64 years, underwent a follow-up visit a median 53 days after hospital discharge. Overall, 76% patients reported at least one persistent symptom, including dyspnoea (37%), chronic fatigue (36%), insomnia (16%), visual disorders (13%) and brain fog (13%). Increasing oxygen support (OR 1.4, 95% CI 1.1-1.8), use of immunosuppressants (OR 6.4, 95% CI 1.5-28) and female sex (OR 1.8, 95% CI 1.1-2.9) were associated with a higher risk of long COVID symptoms.

Comparison between symptomatic patients infected in the period March-December 2020 (prevalent circulation of wild-type SARS-CoV-2) with those infected in the period January-April 2021 (prevalent circulation of B.1.1.7 Alpha variant) showed a significant modification in the pattern of symptoms belonging to the neurological and cognitive/emotional categories.

Our findings confirmed shortness of breath and chronic fatigue as the most frequent long COVID manifestations, while female sex and severe COVID-19 course were the main risk factors for developing lingering symptoms. SARS-CoV-2 variants may induce different long COVID phenotypes, possibly due to changes in cell tropism and differences in viral-host interaction.

Source: Spinicci M, Graziani L, Tilli M, Nkurunziza J, Vellere I, Borchi B, Mencarini J, Campolmi I, Gori L, Giovannoni L, Amato C, Livi L, Rasero L, Fattirolli F, Marcucci R, Giusti B, Olivotto I, Tomassetti S, Lavorini F, Maggi L, Annunziato F, Marchionni N, Zammarchi L, Bartoloni A. Infection with SARS-CoV-2 Variants Is Associated with Different Long COVID Phenotypes. Viruses. 2022 Oct 27;14(11):2367. doi: 10.3390/v14112367. PMID: 36366465; PMCID: PMC9698829. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9698829/ (Full text)

The Prevalence, Severity, and Impact of Post-COVID Persistent Fatigue, Post-Exertional Malaise, and Chronic Fatigue Syndrome

Background: Fatigue is common after viral infections, including SARS-CoV-2.1 Our purpose was to report the prevalence and impact of persistent fatigue 6 months after SARS-CoV-2 infection, considering post-exertional malaise2 and criteria for chronic fatigue syndrome.3

Methods: Since March 2020, individuals tested for SARS-CoV-2 at the Geneva University Hospitals outpatient testing center benefit from remote ambulatory follow-up (COVICARE). This study included all individuals tested between March 2020 and December 2020 and whose follow-up was at 6 months or more after their test date.

Follow-up included questions about the prevalence of symptoms (yes/no) and their severity using a Likert scale (mild, moderate, or severe). Fatigue was assessed using the Eastern Cooperative Oncology Group (ECOG) scale and the Chalder fatigue scale. The Chalder fatigue scale was scored using the 4-item Likert and the bimodal scoring schemes. A score of ≥ 4 on bimodal scoring indicated severe fatigue.

The DePaul brief questionnaire was used to identify post-exertional malaise and criteria for chronic fatigue syndrome.

The Sheehan Disability Scale was used to assess functional impairment. Reduced work capacity was defined as missing days off work or having a reduced productivity on the Sheehan disability scale.

Comorbidities were considered present if pre-existing prior to SARS-CoV-2 infection. Statistical analysis included descriptive comparisons of percentages using chi-square tests and Student’s t test.

Results: Overall, 5515 individuals participated in this study (response rate 70.7%), with 5406 participants at 6 months or more after their test date. A total of 1497 (27.7%) participants had a documented positive SARS-CoV-2 test and were ultimately included in the study. The median time for follow-up was 225 days (interquartile range 207–398). Respectively, fatigue was reported by 17.2%, post-exertional malaise by 8.2%, and the presence of criteria for chronic fatigue syndrome by 1.1% of SARS-CoV-2-positive individuals, compared to 8.9%, 3.5%, and 0.5% of SARS-CoV-2-negative individuals. Characteristics are presented in Table 1.

Out of SARS-CoV-2-positive participants with fatigue (n = 258), 35.3% had moderate to severe limitations on the ECOG scale, and 83.0% had a score ≥ 4 on the Chalder fatigue scale. The Chalder fatigue scale revealed a mean score of 19 out of 33, SD 5.4, and a mean score of 6.7 out of 11, SD 3.3 using bimodal scoring. After adjusting for age and sex, 47.7% of SARS-CoV-2-positive individuals with fatigue at 6 months or more had the frequency and severity criteria for post-exertional malaise, and 6.2% had criteria for chronic fatigue syndrome.

Individuals had a higher prevalence of insomnia, cognitive impairment, headaches, generalized pain, functional impairment, reduced work capacity, and decreased physical activity, after SARS-CoV-2 infection. The prevalence of these sequelae was adjusted for age and sex and was increasingly higher with severe fatigue, with post-exertional malaise, or when criteria for chronic fatigue syndrome were present (Fig. 1).

Discussion: Fatigue is the most common and persistent post-COVID symptom. The spectrum of fatigue severity in post-COVID individuals ranges from feeling tired to having severe fatigue, post-exertional malaise, or criteria for chronic fatigue syndrome with an increasing impact on health, functional capacity, and physical activity.

Almost half of individuals experiencing fatigue at 6 months after the infection had post-exertional malaise, and 6.2% had criteria for chronic fatigue syndrome, prompting physicians to consider pacing as a management option, in the absence of other treatment options at this stage. SARS-CoV-2 infection was positively associated with fatigue and post-exertional malaise.

Results showed that individuals with fatigue were more likely to be vaccinated. This was partially explained by the baseline distribution as older individuals and those with more comorbidities were more likely to get vaccinated.

Results compare to recent reviews showing an overlap between post-COVID condition and chronic fatigue syndrome. Our study graded post-COVID fatigue by severity in correlation with functional capacity, and showed the high prevalence of post-exertional malaise.

Limitations include the self-reported nature of this follow-up with individuals infected in 2020 and follow-up in 2021, lacking comparisons to individuals infected with other variants. Additionally, this study considered having received at least 2 doses as full vaccination, a concept that continues to evolve with time.

Physicians, employers, and insurance companies should address fatigue on a spectrum, accounting for the correlated functional impairment, decreased activity levels, and potentially poorer quality of life.

Source: Nehme M, Chappuis F, Kaiser L, Assal F, Guessous I. The Prevalence, Severity, and Impact of Post-COVID Persistent Fatigue, Post-Exertional Malaise, and Chronic Fatigue Syndrome. J Gen Intern Med. 2022 Nov 10:1–5. doi: 10.1007/s11606-022-07882-x. Epub ahead of print. PMID: 36357723; PMCID: PMC9648889. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9648889/ (Full text)