Tag: post-infectious sequelae

Risk Factors Associated with Development and Persistence of Long COVID: A Cross-Sectional Study

Abstract:

Background: Long coronavirus disease (COVID) has been a social concern. Though patient characteristics associated with the
development of long COVID are partially known, those associated with its persistence have not been identified.

Methods: We conducted a cross-sectional questionnaire survey of patients after COVID-19 recovery who visited the National
Center for Global Health and Medicine between February 2020 and March 2021. Demographic and clinical data and
data regarding the presence and duration of long COVID were obtained. We identified factors associated with the
development and persistence of long COVID using multivariate logistic and linear regression analysis, respectively.

Results: We analyzed 457 of 526 responses (response rate, 86.9%). The median age was 47 years, and 378 patients (84.4%)
had mild disease in the acute phase. The number of patients with any symptoms after 6 and 12 months after onset or
diagnosis were 120 (26.3%) and 40 (8.8%), respectively. Women were at risk for development of fatigue (odds ratio
[OR]: 2.03, 95% confidence interval [CI]: 1.31-3.14), dysosmia (OR: 1.91, 95% CI: 1.24-2.93), dysgeusia (OR: 1.56, 95% CI:
1.02-2.39), and hair loss (OR: 3.00, 95% CI: 1.77-5.09) and for persistence of any symptoms (coefficient: 38.0, 95% CI:
13.3-62.8). Younger age and low body mass index were risk factors for developing dysosmia (OR: 0.96, 95% CI: 0.94-
0.98 and OR: 0.94, 95% CI: 0.89-0.99, respectively) and dysgeusia (OR: 0.98, 95% CI: 0.96-1.00 and OR: 0.93, 95% CI:
0.88-0.98, respectively).

Conclusion: We identified risk factors for the development and persistence of long COVID. Many patients suffer from long-term
residual symptoms, even in mild cases.

Source: Yusuke Miyazato, Shinya Tsuzuki, Shinichiro Morioka, Mari Terda, Satoshi Kutsuna, Sho Saito, Yumiko Shimanishi, Kozue Takahashi, Mio Sanada, Masako Akashi, Chika Kuge, Yasuyo Osanai, Keiko Tanaka, Michiyo Suzuki, Kayoko Hayakawa, Norio Ohmagari. Risk Factors Associated with Development and Persistence of Long COVID: A Cross-Sectional Study.
doi: https://doi.org/10.1101/2021.09.22.21263998 https://www.medrxiv.org/content/10.1101/2021.09.22.21263998v1.full-text (Full text)

Who has long-COVID? A big data approach

Abstract:

Background Post-acute sequelae of SARS-CoV-2 infection (PASC), otherwise known as long-COVID, have severely impacted recovery from the pandemic for patients and society alike. This new disease is characterized by evolving, heterogeneous symptoms, making it challenging to derive an unambiguous long-COVID definition. Electronic health record (EHR) studies are a critical element of the NIH Researching COVID to Enhance Recovery (RECOVER) Initiative, which is addressing the urgent need to understand PASC, accurately identify who has PASC, and identify treatments.

Methods Using the National COVID Cohort Collaborative’s (N3C) EHR repository, we developed XGBoost machine learning (ML) models to identify potential long-COVID patients. We examined demographics, healthcare utilization, diagnoses, and medications for 97,995 adult COVID-19 patients. We used these features and 597 long-COVID clinic patients to train three ML models to identify potential long-COVID patients among (1) all COVID-19 patients, (2) patients hospitalized with COVID-19, and (3) patients who had COVID-19 but were not hospitalized.

Findings Our models identified potential long-COVID patients with high accuracy, achieving areas under the receiver operator characteristic curve of 0.91 (all patients), 0.90 (hospitalized); and 0.85 (non-hospitalized). Important features include rate of healthcare utilization, patient age, dyspnea, and other diagnosis and medication information available within the EHR. Applying the “all patients” model to the larger N3C cohort identified 100,263 potential long-COVID patients.

Interpretation Patients flagged by our models can be interpreted as “patients likely to be referred to or seek care at a long-COVID specialty clinic,” an essential proxy for long-COVID diagnosis in the current absence of a definition. We also achieve the urgent goal of identifying potential long-COVID patients for clinical trials. As more data sources are identified, the models can be retrained and tuned based on study needs.

Source: Pfaff ER, Girvin AT, Bennett TD, Bhatia A, Brooks IM, Deer RR, Dekermanjian JP, Jolley SE, Kahn MG, Kostka K, McMurry JA, Moffitt R, Walden A, Chute CG, Haendel MA, The N3C Consortium. (2021). Who has long-COVID? A big data approach [preprint]. UMass Center for Clinical and Translational Science Supported Publications. https://doi.org/10.1101/2021.10.18.21265168. Retrieved from https://escholarship.umassmed.edu/umccts_pubs/253

Viral diseases and the brain: Long COVID puts the spotlight on how viral infections affect the brain

Abstract:

Various viruses can affect the brain directly or indirectly. The specter of Long COVID has focused research on how respiratory viruses can cause infection and inflammation of brain cells.

Source: Hunter P. Viral diseases and the brain: Long COVID puts the spotlight on how viral infections affect the brain. EMBO Rep. 2021 Nov 29:e54342. doi: 10.15252/embr.202154342. Epub ahead of print. PMID: 34842325. https://pubmed.ncbi.nlm.nih.gov/34842325/

Long COVID from rheumatology perspective – a narrative review

Abstract:

Long-term sequel of acute COVID-19, commonly referred to as long COVID, has affected millions of patients worldwide. Long COVID patients display persistent or relapsing and remitting symptoms that include fatigue, breathlessness, cough, myalgia, arthralgia, sleep disturbance, cognitive impairment and skin rashes. Due to the shared clinical features, laboratory and imaging findings, long COVID could mimic rheumatic disease posing a diagnostic challenge. Our comprehensive literature review will help rheumatologist to be aware of long COVID manifestations and differentiating features from rheumatic diseases to ensure a timely and correct diagnosis is reached.

Source: Sapkota HR, Nune A. Long COVID from rheumatology perspective – a narrative review. Clin Rheumatol. 2021 Nov 30:1–12. doi: 10.1007/s10067-021-06001-1. Epub ahead of print. PMID: 34845562; PMCID: PMC8629735. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8629735/ (Full text)

Proposed subtypes of post-COVID-19 syndrome (or long-COVID) and their respective potential therapies

Abstract:

The effects of coronavirus disease 2019 (COVID-19), a highly transmissible infectious respiratory disease that has initiated an ongoing pandemic since early 2020, do not always end in the acute phase. Depending on the study referred, about 10%-30% (or more) of COVID-19 survivors may develop long-COVID or post-COVID-19 syndrome (PCS), characterised by persistent symptoms (most commonly fatigue, dyspnoea, and cognitive impairments) lasting for 3 months or more after acute COVID-19. While the pathophysiological mechanisms of PCS have been extensively described elsewhere, the subtypes of PCS have not. Owing to its highly multifaceted nature, this review proposes and characterises six subtypes of PCS based on the existing literature.

The subtypes are non-severe COVID-19 multi-organ sequelae (NSC-MOS), pulmonary fibrosis sequelae (PFS), myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS), postural orthostatic tachycardia syndrome (POTS), post-intensive care syndrome (PICS) and medical or clinical sequelae (MCS). Original studies supporting each of these subtypes are documented in this review, as well as their respective symptoms and potential interventions. Ultimately, the subtyping proposed herein aims to provide better clarity on the current understanding of PCS.

Source: Yong SJ, Liu S. Proposed subtypes of post-COVID-19 syndrome (or long-COVID) and their respective potential therapies. Rev Med Virol. 2021 Dec 9:e2315. doi: 10.1002/rmv.2315. Epub ahead of print. PMID: 34888989. https://pubmed.ncbi.nlm.nih.gov/34888989/

Skeletal muscle alterations in patients with acute Covid-19 and post-acute sequelae of Covid-19

Abstract:

Background and methods: Skeletal muscle-related symptoms are common in both acute Covid-19 and Post-Acute Sequelae of Covid-19 (PASC). In this narrative review, we discuss cellular and molecular pathways that are affected, and consider these in regard to skeletal muscle involvement in other conditions, such as acute respiratory distress syndrome, critical illness myopathy and post-viral fatigue syndrome.
Results: Patients with severe Covid-19 and PASC suffer from skeletal muscle weakness and exercise intolerance. Histological sections present muscle fiber atrophy, metabolic alterations, and immune cell infiltration. Contributing factors to weakness and fatigue in patients with severe Covid-19 include systemic inflammation, disuse, hypoxemia, and malnutrition. These factors also contribute to post-ICU syndrome and ICU-acquired weakness, and likely explain a substantial part of Covid-19-acquired weakness. The skeletal muscle weakness and exercise intolerance associated with PASC are more obscure and different factors likely contribute. Direct SARS-CoV-2 viral infiltration into skeletal muscle or an aberrant immune system likely contribute. Similarities between skeletal muscle alterations in PASC and chronic fatigue syndrome deserve further study.
Conclusion: Both SARS-CoV-2 specific factors and generic consequences of acute disease likely underlie the observed skeletal muscle alterations in both acute Covid 19 and PASC.
Source: Soares, M., Eggelbusch, M., Naddaf, E., Gerrits, K., van der Schaaf, M., van den Borst, B., Wiersinga, W. J., et al. Skeletal muscle alterations in patients with acute Covid-19 and post-acute sequelae of Covid-19. Journal of Cachexia, Sarcopenia and Muscle. https://doi.org/10.17863/CAM.78509 https://www.repository.cam.ac.uk/handle/1810/331064

Fatigue in post-acute sequelae of SARS-CoV2 (PASC) treated with oxygen-ozone autohemotherapy – preliminary results on 100 patients

Abstract:

Objective: Post-acute sequelae of SARS-CoV2 infection (PASC) are a novel terminology used to describe post-COVID persistent symptoms, mimicking somehow the previously described chronic fatigue syndrome (CFS). In this manuscript, we evaluated a therapeutical approach to address PASC-derived fatigue in a cohort of past-COVID-19 positive patients.

Patients and methods: A number of 100 patients, previously diagnosed as COVID-19 positive subjects and meeting our eligibility criteria, was diagnosed having PASC-related fatigue. They were recruited in the study and treated with oxygen-ozone autohemotherapy (O2-O3-AHT), according to the SIOOT protocol. Patients’ response to O2-O3-AHT and changes in fatigue were measured with the 7-scoring Fatigue Severity Scale (FSS), according to previously published protocols.

Results: Statistics assessed that the effects of O2-O3-AHT on fatigue reduced PASC symptoms by 67%, as a mean, in all the investigated cohort of patients (H = 148.4786 p < 0.0001) (Figure 1). Patients following O2-O3-AHT therapy, quite completely recovered for PASC-associated fatigue, a quote amounting to about two fifths (around 40%) of the whole cohort undergoing ozone treatment and despite most of patients were female subjects, the effect was not influenced by sex distribution (H = 0.7353, p = 0.39117).

Conclusions: Ozone therapy is able to recover normal functionality and to relief pain and discomfort in the form of PASC-associated fatigue in at least 67% of patients suffering from post-COVID sequelae, aside from sex and age distribution.

Source: Tirelli U, Franzini M, Valdenassi L, Pisconti S, Taibi R, Torrisi C, Pandolfi S, Chirumbolo S. Fatigue in post-acute sequelae of SARS-CoV2 (PASC) treated with oxygen-ozone autohemotherapy – preliminary results on 100 patients. Eur Rev Med Pharmacol Sci. 2021 Sep;25(18):5871-5875. doi: 10.26355/eurrev_202109_26809. PMID: 34604980. https://pubmed.ncbi.nlm.nih.gov/34604980/

Evolving phenotypes of non-hospitalized patients that indicate long COVID

Abstract:

Background: For some SARS-CoV-2 survivors, recovery from the acute phase of the infection has been grueling with lingering effects. Many of the symptoms characterized as the post-acute sequelae of COVID-19 (PASC) could have multiple causes or are similarly seen in non-COVID patients. Accurate identification of PASC phenotypes will be important to guide future research and help the healthcare system focus its efforts and resources on adequately controlled age- and gender-specific sequelae of a COVID-19 infection.

Methods: In this retrospective electronic health record (EHR) cohort study, we applied a computational framework for knowledge discovery from clinical data, MLHO, to identify phenotypes that positively associate with a past positive reverse transcription-polymerase chain reaction (RT-PCR) test for COVID-19. We evaluated the post-test phenotypes in two temporal windows at 3-6 and 6-9 months after the test and by age and gender. Data from longitudinal diagnosis records stored in EHRs from Mass General Brigham in the Boston Metropolitan Area was used for the analyses. Statistical analyses were performed on data from March 2020 to June 2021. Study participants included over 96 thousand patients who had tested positive or negative for COVID-19 and were not hospitalized.

Results: We identified 33 phenotypes among different age/gender cohorts or time windows that were positively associated with past SARS-CoV-2 infection. All identified phenotypes were newly recorded in patients’ medical records 2 months or longer after a COVID-19 RT-PCR test in non-hospitalized patients regardless of the test result. Among these phenotypes, a new diagnosis record for anosmia and dysgeusia (OR 2.60, 95% CI [1.94-3.46]), alopecia (OR 3.09, 95% CI [2.53-3.76]), chest pain (OR 1.27, 95% CI [1.09-1.48]), chronic fatigue syndrome (OR 2.60, 95% CI [1.22-2.10]), shortness of breath (OR 1.41, 95% CI [1.22-1.64]), pneumonia (OR 1.66, 95% CI [1.28-2.16]), and type 2 diabetes mellitus (OR 1.41, 95% CI [1.22-1.64]) is one of the most significant indicators of a past COVID-19 infection. Additionally, more new phenotypes were found with increased confidence among the cohorts who were younger than 65.

Conclusions: The findings of this study confirm many of the post-COVID-19 symptoms and suggest that a variety of new diagnoses, including new diabetes mellitus and neurological disorder diagnoses, are more common among those with a history of COVID-19 than those without the infection. Additionally, more than 63% of PASC phenotypes were observed in patients under 65 years of age, pointing out the importance of vaccination to minimize the risk of debilitating post-acute sequelae of COVID-19 among younger adults.

Source: Estiri H, Strasser ZH, Brat GA, Semenov YR; Consortium for Characterization of COVID-19 by EHR (4CE), Patel CJ, Murphy SN. Evolving phenotypes of non-hospitalized patients that indicate long COVID. BMC Med. 2021 Sep 27;19(1):249. doi: 10.1186/s12916-021-02115-0. PMID: 34565368. https://pubmed.ncbi.nlm.nih.gov/34565368/

Patient perceptions of infectious illnesses preceding Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Abstract:

Objectives: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is often reported to be caused by an infectious agent. However, it is unclear whether one infectious agent might be the cause or whether there might be many different infectious agents. The objective of this study was to identify self-reported infectious illnesses associated with the onset of ME/CFS.

Methods: The present study involved data from multiple sites in several countries. 1773 individuals diagnosed with either ME, CFS or ME/CFS provided qualitative data concerning infectious triggers which were coded and classified for analysis.

Results: 60.3% of patients report a variety of infectious illnesses some time before onset of ME/CFS. The most frequently reported infectious illness was Mononucleosis, which occurred in 30% of infections. However, over 100 other infectious illnesses were mentioned.

Discussion: The findings suggest that many infectious agents might be associated with the onset of ME/CFS.

Source: Jason LA, Yoo S, Bhatia S. Patient perceptions of infectious illnesses preceding Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Chronic Illn. 2021 Sep 20:17423953211043106. doi: 10.1177/17423953211043106. Epub ahead of print. PMID: 34541918. https://pubmed.ncbi.nlm.nih.gov/34541918/

Long COVID: Is it really myalgic encephalomyelitis? Bibliographic review and considerations

Abstract:

Clinical sequelae of a disease as widespread as COVID-19 can be of great importance for primary care due to their prevalence and the morbidity they entail. The definition of long COVID and the establishment of its temporality are various, but some authors consider possible that this syndrome is actually myalgic encephalomyelitis.

Similarities are observed when comparing the International Consensus Criteria for the diagnosis of myalgic encephalomyelitis with the symptoms described for long COVID. Blood tests, pulse oximetry, chest radiography, and thoracic ultrasound are recommended in patients with persistent symptoms after acute infection. Management in both conditions consists of treating the main symptoms. The possibility that COVID-19 can lead to a chronic condition such as myalgic encephalomyelitis makes long-term follow-up of patients who have suffered from this infection essential.

Source: Espinosa Rodríguez, P et al. “COVID persistente: ¿es en realidad una encefalomielitis miálgica? Revisión bibliográfica y consideraciones” [Long COVID: Is it really myalgic encephalomyelitis? Bibliographic review and considerations]. Semergen, S1138-3593(21)00091-5. 13 Sep. 2021, doi:10.1016/j.semerg.2021.03.006 [Abstract in English, Spanish] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8437705/  (Full text)