Tag: long covid symptoms

Cytokine deficiencies in patients with Long-COVID

Abstract:

Up to half of individuals who contract SARS-CoV-2 develop symptoms of long-COVID approximately three months after initial infection. These symptoms are highly variable, and the mechanisms inducing them are yet to be understood. We compared plasma cytokine levels from individuals with long-COVID to healthy individuals and found that those with long-COVID had 100% reductions in circulating levels of Interferon Gamma (IFNγ) and Interleukin-8 (IL-8). Additionally, we found significant reductions in levels of IL-6, IL-2, IL-17, IL-13, and IL-4 in individuals with long-COVID.

We propose immune exhaustion as the driver of long-COVID, with the complete absence of IFNγ and IL-8 preventing the lungs and other organs from healing after acute infection, and reducing the ability to fight off subsequent infections, both contributing to the myriad of symptoms suffered by those with long-COVID.

Source: Williams ES, Martins TB, Shah KS, Hill HR, Coiras M, Spivak AM, Planelles V. Cytokine Deficiencies in Patients with Long-COVID. J Clin Cell Immunol. 2022;13(6):672. Epub 2022 Nov 18. PMID: 36742994; PMCID: PMC9894377. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9894377/ (Full text)

Symptom persistence and biomarkers in post-COVID-19/chronic fatigue syndrome – results from a prospective observational cohort

Abstract:

Introduction: Post-COVID-19 syndrome (PCS) is characterized by a wide range of symptoms, predominantly fatigue and exertional intolerance. While disease courses during the first year post infection have been repeatedly described, little is known about long-term health consequences.

Methods: We assessed symptom severity and various biomarkers at three time points post infection (3-8 months (mo), 9-16mo, 17-20mo) in 106 PCS patients with moderate to severe fatigue and exertional intolerance. A subset of patients fulfilled diagnostic criteria of myalgic encephalomyelitis/chronic fatigue syndrome (PCS-ME/CFS) based on the Canadian Consensus Criteria.

Results: While PCS-ME/CFS patients showed persisting symptom severity and disability up to 20mo post infection, PCS patients reported an overall health improvement. Inflammatory biomarkers equally decreased in both groups. Lower hand grip force at onset correlated with symptom persistence especially in PCS-ME/CFS.

Discussion: Debilitating PCS may persist beyond 20mo post infection, particularly in patients fulfilling diagnostic criteria for ME/CFS.

Source: Anna Franziska Legler, Lil Meyer-Arndt, Lukas Moedl, Claudia Kedor, Helma Freitag, Elena Steinle, Uta Hoppmann, Rebekka Rust, Frank Konietschke, Andreas Thiel, Friedemann Paul, Carmen Scheibenbogen, Judith Bellmann-Strobl. Symptom persistence and biomarkers in post-COVID-19/chronic fatigue syndrome – results from a prospective observational cohort.
medRxiv 2023.04.15.23288582; doi: https://doi.org/10.1101/2023.04.15.23288582 (Full text available as PDF file)

The Breadth of the Neutralizing Antibody Response to Original SARS-CoV-2 Infection is Linked to the Presence of Long COVID Symptoms

Abstract:

Background: The associations between longitudinal dynamics and the breadth of SARS-CoV-2 neutralizing antibody response with various Long COVID (LC) phenotypes prior to vaccination are not known. The capacity of antibodies to cross neutralize a variety of viral variants may be associated with ongoing pathology and persistent symptoms.

Methods: We measured longitudinal neutralizing and cross-neutralizing antibody responses to pre- and post-SARS-CoV-2 Omicron variants in participants infected during the early waves of the COVID-19 pandemic, prior to wide-spread rollout of SARS-CoV-2 vaccines. Cross sectional regression models adjusted for various clinical covariates and longitudinal mixed effects models were used to determine the impact of the breadth and rate of decay of neutralizing responses on the development of Long COVID symptoms in general, as well as LC phenotypes.

Results: We identified several novel relationships between SARS-CoV-2 antibody neutralization and the presence of LC symptoms. Specifically, we show that, although neutralizing antibody responses to the original, infecting strain of SARS-CoV-2 were not associated with LC in cross-sectional analyses, cross-neutralization ID50 levels to the Omicron BA.5 variant approximately 4 months following acute infection was independently and significantly associated with greater odds of LC and with persistent gastrointestinal and neurological symptoms. Longitudinal modeling demonstrated significant associations in the overall levels and rates of decay of neutralization capacity with LC phenotypes. A higher proportion of participants had antibodies capable of neutralizing Omicron BA.5 compared with BA.1 or XBB.1.5 variants.

Conclusions: Our findings suggest that relationships between various immune responses and LC are likely complex but may involve the breadth of antibody neutralization responses.

Source: Buck AM, Deitchman AN, Takahashi S, Lu S, Goldberg SA, Hoh R, Williams MC, Kerbleski M, Deveau TM, Munter SE, Lombardo J, Wrin T, Petropoulos CJ, Durstenfeld MS, Hsue PY, Kelly JD, Greenhouse B, Martin JN, Deeks SG, Peluso MJ, Henrich TJ. The Breadth of the Neutralizing Antibody Response to Original SARS-CoV-2 Infection is Linked to the Presence of Long COVID Symptoms. medRxiv [Preprint]. 2023 Mar 31:2023.03.30.23287923. doi: 10.1101/2023.03.30.23287923. PMID: 37034660; PMCID: PMC10081395. https://www.medrxiv.org/content/10.1101/2023.03.30.23287923v1.full-text (Full text)

Risk factors for psychiatric symptoms in patients with long COVID: A systematic review

Abstract:

Prolonged symptoms of COVID-19 have been found in many patients, often known as Long COVID. Psychiatric symptoms are commonly seen in Long COVID patients and could last for weeks, even months, after recovery. However, the symptoms and risk factors associated with it remain unclear.

In the current systematic review, we provide an overview of psychiatric symptoms in Long COVID patients and risk factors associated with the development of those symptoms. Articles were systematically searched on SCOPUS, PubMed, and EMBASE up to October 2021. Studies involving adults and geriatric participants with a confirmed previous COVID-19 diagnosis and reported psychiatric symptoms that persist for more than four weeks after the initial infection were included. The risk of bias was assessed using the Newcastle-Ottawa Scale (NOS) for observational studies. Prevalence rates and risk factors associated with psychiatric symptoms were collected. This present study was registered at PROSPERO (CRD42021240776). In total, 23 studies were included.

Several limitations in this review were the heterogeneity of studies’ outcomes and designs, studies limited to articles published in English, and the psychiatric symptoms mainly were assessed using self-report questionnaires. The most prevalent  reported psychiatric symptoms, from the most to the least reported, were anxiety, depression, post-traumatic stress disorder (PTSD), poor sleep qualities, somatic symptoms, and cognitive deficits. Being female and having previous psychiatric diagnoses were risk factors for the development of the reported symptoms.

Source: Zakia H, Pradana K, Iskandar S. Risk factors for psychiatric symptoms in patients with long COVID: A systematic review. PLoS One. 2023 Apr 7;18(4):e0284075. doi: 10.1371/journal.pone.0284075. PMID: 37027455; PMCID: PMC10081737. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10081737/ (Full text)

Five cluster classifications of long COVID and their background factors: A cross-sectional study in Japan

Abstract:

Purpose: The long-term symptoms of coronavirus disease 2019 (COVID-19), i.e., long COVID, have drawn research attention. Evaluating its subjective symptoms is difficult, and no established pathophysiology or treatment exists. Although there are several reports of long COVID classifications, there are no reports comparing classifications that include patient characteristics, such as autonomic dysfunction and work status. We aimed to classify patients into clusters based on their subjective symptoms during their first outpatient visit and evaluate their background for these clusters.

Methods: Included patients visited our outpatient clinic between January 18, 2021, and May 30, 2022. They were aged ≥ 15 years and confirmed to have SARS-CoV-2 infection and residual symptoms lasting at least 2 months post-infection. Patients were evaluated using a 3-point scale for 23 symptoms and classified into five clusters (1. fatigue only; 2. fatigue, dyspnea, chest pain, palpitations, and forgetfulness; 3. fatigue, headache, insomnia, anxiety, motivation loss, low mood, and forgetfulness; 4. hair loss; and 5. taste and smell disorders) using CLUSTER. For continuous variables, each cluster was compared using the Kruskal–Wallis test. Multiple comparison tests were performed using the Dunn’s test for significant results. For nominal variables, a Chi-square test was performed; for significant results, a residual analysis was conducted with the adjusted residuals.

Results: Compared to patients in other cluster categories, those in cluster categories 2 and 3 had higher proportions of autonomic nervous system disorders and leaves of absence, respectively.

Conclusions: Long COVID cluster classification provided an overall assessment of COVID-19. Different treatment strategies must be used based on physical and psychiatric symptoms and employment factors.

Source: Tsuchida, T., Yoshimura, N., Ishizuka, K. et al. Five cluster classifications of long COVID and their background factors: A cross-sectional study in Japan. Clin Exp Med (2023). https://doi.org/10.1007/s10238-023-01057-6 (Full text)

Data-driven analysis to understand long COVID using electronic health records from the RECOVER initiative

Abstract:

Recent studies have investigated post-acute sequelae of SARS-CoV-2 infection (PASC, or long COVID) using real-world patient data such as electronic health records (EHR). Prior studies have typically been conducted on patient cohorts with specific patient populations which makes their generalizability unclear. This study aims to characterize PASC using the EHR data warehouses from two large Patient-Centered Clinical Research Networks (PCORnet), INSIGHT and OneFlorida+, which include 11 million patients in New York City (NYC) area and 16.8 million patients in Florida respectively.

With a high-throughput screening pipeline based on propensity score and inverse probability of treatment weighting, we identified a broad list of diagnoses and medications which exhibited significantly higher incidence risk for patients 30-180 days after the laboratory-confirmed SARS-CoV-2 infection compared to non-infected patients.

We identified more PASC diagnoses in NYC than in Florida regarding our screening criteria, and conditions including dementia, hair loss, pressure ulcers, pulmonary fibrosis, dyspnea, pulmonary embolism, chest pain, abnormal heartbeat, malaise, and fatigue, were replicated across both cohorts. Our analyses highlight potentially heterogeneous risks of PASC in different populations.

Source: Zang C, Zhang Y, Xu J, Bian J, Morozyuk D, Schenck EJ, Khullar D, Nordvig AS, Shenkman EA, Rothman RL, Block JP, Lyman K, Weiner MG, Carton TW, Wang F, Kaushal R. Data-driven analysis to understand long COVID using electronic health records from the RECOVER initiative. Nat Commun. 2023 Apr 7;14(1):1948. doi: 10.1038/s41467-023-37653-z. PMID: 37029117; PMCID: PMC10080528. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10080528/ (Full text)

Prevalence and Characterization of Long Covid-19 Symptoms in Health Care Professionals- A Need of the Hour

Abstract:

Background: With the global advent of Covid-19, Healthcare workers (HCW) were under a lot of physical and psychological pressure. Information on persistent symptoms post Covid-19 Infection in HCWs is lacking.

Objectives: This Study is aimed at assessing the impact of the post Covid-19 syndrome in HCWs.

Materials and Methods: A Questionnaire was prepared as google form and shared with the HCWs through WhatsApp enquiring regarding the health conditions that are still persistent post recovery from Covid-19 infection.

Results: A total of 328 Health Care Professionals participated in the present survey (18-65 yrs). The gender distribution revealed 67.7% were females and 32.3% were males. 60.3% of the participants were infected with COVID-19 before taking the first dose of vaccination which is reduced to 17.5% after vaccination. The post COVID complications observed from the study were hair loss (35.4%), easy fatigability (25%), mood swings (22.9%), anxiety (18.8%), insomnia/sleeplessness (13.9%), depression (12.5%) and joint pains/arthritis (11.8%). The other complications observed were loss of taste (9%), lightheadedness/postural hypotension (8.3%), amnesia/loss of memory and anosmia/loss of smell (7.6%), gastritis (6.3%), palpitations, hypersomnia and pulmonary complications (5.6%) and chest pain (4.9%). Unpaired t-test and One-Way ANNOVA resulted in a significant value (p values of >0.05).

Discussion: Despite the fact that females experienced more post-Covid-19 symptoms (15 out of 17), males experienced more chest pain and anxiety symptoms. According to our findings, 57 of 100 Covid-19 health care workers have post-Covid complications. The participants presented with non-specific symptoms such as easy fatigability, mood swings, light headedness, anxiety but most of the participants quoted more specific symptoms such as depression, pulmonary complications, hair loss, joint pains, gastritis, chest pain, palpitations, loss of taste, amnesia, hyperglycemia, insomnia, hypersomnia and anosmia. However, non-specific symptoms such as fatigue, mood swings, lightheadedness, and anxiety were also mentioned. The symptoms of post-acute COVID-19 syndrome vary greatly. Early detection requires a unified definition of long COVID and characterization of its manifestation. Furthermore, more research should be conducted to identify risk factors and the precise mechanisms that lead to the development of long COVID syndrome. Such knowledge may aid future research aimed at preventing such a complication.

Source: Mote Srinath, Syeda Fakiha Mehreen, Surya Prem Kumar et al. Prevalence and Characterization of Long Covid-19 Symptoms in Health Care Professionals- A Need of the Hour, 05 April 2023, PREPRINT (Version 1) available at Research Square. https://doi.org/10.21203/rs.3.rs-2764197/v1 (Full text)

Gut Microbiota Dysbiosis Correlates With Long COVID-19 at One-Year After Discharge

Abstract:

Background: Long coronavirus disease 2019 (COVID-19) in recovered patients (RPs) is gradually recognized by more people. However, how long it will last and the underlining mechanism remains unclear.
Methods: We conducted a prospective follow-up study to evaluate the long-term symptoms and clinical indices of RPs at one-year after discharge from Union Hospital, Wuhan, China between December 2020 to May 2021. We also performed the 16S rRNA sequencing of stool samples from RPs and healthy controls (HCs) and analyzed the correlation between the gut microbiota and long COVID-19.
Results: In total, 187 RPs were enrolled, among them, 84 (44.9%) RPs reported long COVID-19 symptoms at one-year after discharge. The most common long-term symptoms were cardiopulmonary symptoms, including chest tightness after activity (39/187, 20.9%), palpitations on exercise (27/187, 14.4%), sputum (21/187, 11.2%), cough (15/187, 8.0%) and chest pain (13/187, 7.0%), followed by systemic symptoms including fatigue (34/187, 18.2%) and myalgia (20/187, 10.7%), and digestive symptoms including constipation (14/187, 7.5%), anorexia (13/187, 7.0%), and diarrhea (8/187, 4.3%). Sixty-six (35.9%) RPs presented either anxiety or depression (42/187 [22.8%] and 53/187 [28.8%] respectively), and the proportion of anxiety or depression in the long symptomatic group was significantly higher than that in the asymptomatic group (41/187 [50.6%] vs. 25/187 [24.3%]). Compared with the asymptomatic group, scores of all nine 36-Item Short Form General Health Survey domains were lower in the symptomatic group (all P < 0.05).
One hundred thirty RPs and 32 HCs (non-severe acute respiratory syndrome coronavirus 2 infected subjects) performed fecal sample sequencing. Compared with HCs, symptomatic RPs had obvious gut microbiota dysbiosis including significantly reduced bacterial diversities and lower relative abundance of short-chain fatty acids (SCFAs)-producing salutary symbionts such as Eubacterium_hallii_group,  Subdoligranulum,  Ruminococcus, Dorea, Coprococcus, and Eubacterium_ventriosum_group. Meanwhile, the relative abundance of Eubacterium_hallii_group,  Subdoligranulum, and Ruminococcus showed decreasing tendencies between HCs, the asymptomatic group, and the symptomatic group.
Conclusion: This study demonstrated the presence of long COVID-19 which correlates with gut microbiota dysbiosis in RPs at one-year after discharge, indicating gut microbiota may play an important role in long COVID-19.
Source: Zhang D, Zhou Y, Ma Y, Chen P, Tang J, Yang B, Li H, Liang M, Xue Y, Liu Y, Zhang J, Wang X. Gut Microbiota Dysbiosis Correlates With Long COVID-19 at One-Year After Discharge. J Korean Med Sci. 2023;38(15):e120. https://doi.org/10.3346/jkms.2023.38.e120 (Full text)

Fatigue, sleepiness and sleep quality are SARS-CoV-2 variant independent in patients with long COVID symptoms

Abstract:

Acute infections with SARS-CoV-2 variants of concerns (VOCs) differ in clinical presentation. Discrepancies in their long-term sequelae, commonly referred to as long COVID, however, remain to be explored. We retrospectively analyzed data of 287 patients presented at the post-COVID care of the Pulmonology Department, Semmelweis University, Budapest, Hungary, and infected with SARS-CoV-2 during a period of 3 major epidemic waves in Hungary (February-July 2021, VOC: B.1.1.7, Alpha, N = 135; August-December 2021, VOC: B.1.617.2, Delta, N = 89; and January-June 2022, VOC: B.1.1.529, Omicron; N = 63), > 4 weeks after acute COVID-19.

Overall, the ratio of long COVID symptomatic (LC) and asymptomatic (NS) patients was 2:1. Self-reported questionnaires on fatigue (Fatigue Severity Scale, FSS), sleepiness (Epworth Sleepiness Scale, ESS) and sleep quality (Pittsburgh Sleep Quality Index, PSQI) showed higher scores for LC (4.79 ± 0.12, 7.45 ± 0.33 and 7.46 ± 0.27, respectively) than NS patients (2.85 ± 0.16, 5.23 ± 0.32 and 4.26 ± 0.29, respectively; p < 0.05 for all vs. LC). By comparing data of the three waves, mean FSS and PSQI scores of LC patients, but not ESS scores, exceeded the normal range in all, with no significant inter-wave differences.

Considering FSS ≥ 4 and PSQI > 5 cutoff values, LC patients commonly exhibited problematic fatigue (≥ 70%) and poor sleep quality (> 60%) in all three waves. Comparative analysis of PSQI component scores of LC patients identified no significant differences between the three waves.

Our findings highlight the importance of concerted efforts to manage both fatigue and sleep disturbances in long COVID patient care. This multifaceted approach should be followed in all cases infected with either VOCs of SARS-CoV-2.

Source: Percze AR, Nagy A, Polivka L, Barczi E, Czaller I, Kovats Z, Varga JT, Ballai JH, Muller V, Horvath G. Fatigue, sleepiness and sleep quality are SARS-CoV-2 variant independent in patients with long COVID symptoms. Inflammopharmacology. 2023 Apr 5:1–7. doi: 10.1007/s10787-023-01190-4. Epub ahead of print. PMID: 37020055; PMCID: PMC10075170. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10075170/ (Full text)

Post-COVID-19 condition and persisting symptoms in English schoolchildren: repeated surveys to March 2022

Abstract:

Background: Both post-COVID-19 condition (long COVID) and the presence of persisting symptoms that do not meet formal definitions of post-COVID-19-condition may adversely affect quality of life and function. However, their prevalence among children and young people in England is unclear.

Methods: We used data from repeated surveys in a large cohort of English schoolchildren from the COVID-19 Schools Infection Survey (SIS) for the school year 2021/22 to describe the weighted prevalence of post-COVID-19-condition and compare persisting symptoms between individuals with a positive SARS-CoV-2 test and those with neither a positive test history nor suspected infection.

Results: Among 7797 children from 173 schools, 1.8% of primary school pupils (aged 4 to 11 years), 4.5% of secondary school pupils in years 7-11 (aged 11 to 16 years) and 6.9% of those in years 12-13 (aged 16 to 18 years) met a definition of post-COVID-19 condition in March 2022. Specific persisting symptoms such as anxiety or difficulty concentrating were frequently reported regardless of prior infection status and increased with age: 48.0% of primary school pupils, 52.9% of secondary school pupils in years 7-11 and 79.5% in years 12-13 reporting at least one symptom lasting more than 12 weeks. Persisting loss of smell and taste, cardiovascular and some systemic symptoms were more frequently reported by those with a previous positive test.

Conclusions: We showed that ongoing symptoms were frequently reported by English schoolchildren regardless of SARS-CoV-2 test results and some specific symptoms such as loss of smell and taste were more prevalent in those with a positive test history. Our study emphasises the wide-ranging impacts of the COVID-19 pandemic on the health and wellbeing of children and young people.

Source: Warren-Gash C, Lacey A, Cook S, Stocker D, Toon S, Lelii F, Ford B, Ireland G, Ladhani SN, Stephenson T, Nguipdop-Djomo P, Mangtani P; COVID-19 Schools Infection Survey 2 Study Group. Post-COVID-19 condition and persisting symptoms in English schoolchildren: repeated surveys to March 2022. BMC Infect Dis. 2023 Apr 5;23(1):201. doi: 10.1186/s12879-023-08203-1. PMID: 37020190; PMCID: PMC10075149. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10075149/ (Full text)