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

Spinicci, Michele; Graziani, Lucia; Tilli, Marta; Nkurunziza, Jerusalem; Vellere, Iacopo; Borchi, Beatrice; Mencarini, Jessica; Campolmi, Irene; Gori, Leonardo; Giovannoni, Lorenzo; Amato, Carla; Livi, Luca; Rasero, Laura; Fattirolli, Francesco; Marcucci, Rossella; Giusti, Betti; Olivotto, Iacopo; Tomassetti, Sara; Lavorini, Federico; Maggi, Laura; Annunziato, Francesco; Marchionni, Niccolò; Zammarchi, Lorenzo; Bartoloni, Alessandro

doi:10.3390/v14112367

Cited by 33 publications

(25 citation statements)

References 37 publications

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“…A second interesting finding is that the variant wave is associated with Long COVID symptoms even with adjustment for timing of vaccination (preinfection, postinfection, or not vaccinated) and number of symptoms during acute infection; more recent variants were associated with lower odds of Long COVID. One prior study suggested that there may be some subtle differences in Long COVID symptoms by variant wave (more dyspnea with ancestral strain, more neuropsychiatric and myalgic symptoms with Alpha, and hair loss with Delta for example) [ 23 , 24 ]. Our findings are consistent with 3 prior studies that suggested that there may be a lower prevalence of Long COVID with the more recent variant waves (Epsilon, Omicron) [ 15 , 25 , 26 ].…”

Section: Discussionmentioning

confidence: 99%

Factors Associated With Long COVID Symptoms in an Online Cohort Study

Durstenfeld

Peluso

Peyser

et al. 2023

Open Forum Infectious Diseases

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Background Few prospective studies of Long COVID risk factors have been conducted. The purpose of this study was to determine whether sociodemographic factors, lifestyle, or medical history preceding COVID-19 or characteristics of acute SARS-CoV-2 infection are associated with Long COVID. Methods The COVID-19 Citizen Science (CCS) study is an online cohort study that began enrolling March 26, 2020, with longitudinal assessment of symptoms before, during, and after SARS-CoV-2 infection. Adult participants who reported a positive SARS-CoV-2 test result prior to April 4, 2022, were surveyed for Long COVID symptoms. The primary outcome was at least 1 prevalent Long COVID symptom greater than 1 month after acute infection. Exposures of interest included age, sex, race/ethnicity, education, employment, socioeconomic status/financial insecurity, self-reported medical history, vaccination status, variant wave, number of acute symptoms, pre-COVID depression, anxiety, alcohol and drug use, sleep, and exercise. Results Of 13,305 participants who reported a SARS-CoV-2 positive test, 1480 (11.1%) responded. Respondents’ mean age was 53 and 1017 (69%) were female. 476 (32.2%) reported Long COVID symptoms at a median 360 days after infection. In multivariable models, number of acute symptoms (OR 1.30 per symptom, 95%CI 1.20-1.40), lower socioeconomic status/financial insecurity (OR 1.62, 95%CI 1.02-2.63), pre-infection depression (OR 1.08, 95%CI 1.01-1.16), and earlier variants (OR 0.37 for Omicron compared to ancestral strain, 95%CI 0.15-0.90) were associated with Long COVID symptoms. Conclusions Variant wave, severity of acute infection, lower socioeconomic status and pre-existing depression are associated with Long COVID symptoms.

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Section: Discussionmentioning

confidence: 99%

Factors Associated With Long COVID Symptoms in an Online Cohort Study

Durstenfeld

Peluso

Peyser

et al. 2023

Open Forum Infectious Diseases

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“…On the other hand, among more than 600 children and adolescents previously hospitalised due to COVID-19 in Argentina, risk factors for long COVID, with headache, cough, and fatigue comprising the most common symptoms, included older age apart from symptomatic infection and comorbidities, including diabetes [37]. In an Italian cohort of 428 patients, assessed 4-12 weeks after hospital discharge, it was found that female sex and severe SARS-CoV-2 infection were the main risk factors for post-COVID manifestations, among which chronic dyspnoea and fatigue were the most common [38]. Finally, a recent Czech study examining healthcare workers at least 12 weeks after the onset of SARS-CoV-2 infection, revealed that female sex and increasing age were the only significant predictors of post-COVID syndrome, with almost half of those patients reporting fatigue interfering with their daily life [39].…”

Section: Discussionmentioning

confidence: 99%

Course of fatigue among patients previously hospitalised due to COVID-19

Mazurkiewicz

Chatys-Bogacka

Słowik

et al. 2023

Neurol Neurochir Pol.

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Introduction. Discrepancies exist regarding the clinical course and prognostic factors for post-COVID fatigue. Therefore, our aim was to assess the timely course of fatigue and its possible predictors in patients previously hospitalised due to SARS-CoV-2 infection. Material and methods.Patients and employees of the University Hospital in Krakow were assessed with the use of a validated neuropsychological questionnaire. Included were participants aged 18 or more, previously hospitalised due to COVID-19, who completed questionnaires only once > 3 months after the onset of infection. Individuals were retrospectively asked about the presence of eight symptoms of chronic fatigue syndrome at four timepoints: before COVID-19, within 0-4 weeks, 4-12 weeks, and > 12 weeks post-infection.Results. We enrolled 204 patients [40.2% women, median age 58 (46-66) years] evaluated after a median of 187 (156-220) days from the first positive nasal swab test for SARS-CoV-2. The most common comorbidities were hypertension (44.61%), obesity (36.27%), smoking (28.43%), and hypercholesterolemia (21.08%); none of the patients required mechanical ventilation during hospitalisation. Before COVID-19, 43.62% of patients reported at least one symptom of chronic fatigue. Within 4, 4-12, and > 12 weeks after COVID-19, the prevalence of chronic fatigue was 76.96%, 75.49%, and 66.17%, respectively (all p < 0.001). The frequency of chronic fatigue symptoms decreased within > 12 weeks following the onset of infection but did not return to baseline values, except for self-reported lymph node enlargement. In a multivariable linear regression model, the number of fatigue symptoms was predicted by female sex [β 0.25 (0.12; 0.39), p < 0.001 and 0.26 (0.13; 0.39), p < 0.001 for weeks 0-12 and > 12, respectively], and age [for < 4 weeks, β -0.12 (-0.28; -0.01), p = 0.029]. Conclusions.Most patients previously hospitalised due to COVID-19 suffer from fatigue > 12 weeks after infection onset. The presence of fatigue is predicted by female sex and -only for the acute phase -age.

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“…Clinical evidence has shown CVD PACS symptoms in patients infected by the Wuhan original strain. For example, Palpitation and tachycardia were reported in patients infected with the Wuhan variant in the cohorts from Spain and Italy [54, 55]. In U.S., long-term CVD sequelae was early reported from a cohort in Michigan (6 March to 1 July 2020) [56] and a cohort of veterans (1 March 2020 to 15 January 2021) [20].…”

Section: Discussionmentioning

confidence: 99%

The SARS-CoV-2 Spike protein induces long-term transcriptional perturbations of mitochondrial metabolic genes, causes cardiac fibrosis, and reduces myocardial contractile in obese mice

Cao

Nguyen

Tsai

et al. 2023

Preprint

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Background: As the pandemic evolves, post-acute sequelae of CoV-2 (PACS) including cardiovascular manifestations have emerged as a new health threat. This study aims to study whether the Spike protein plus obesity can exacerbate PACS-related cardiomyopathy. Methods: A Spike protein-pseudotyped (Spp) virus with the proper surface tropism of SARS-CoV-2 was developed for viral entry assay in vitro and administration into high fat diet (HFD)-fed mice. The systemic viral loads and cardiac transcriptomes were analyzed at 2 and 24 hrs, 3, 6, and 24 weeks post introducing (wpi) Spp using RNA-seq or real time RT-PCR. Echocardiography was used to monitor cardiac functions. Results: Low-density lipoprotein cholesterol enhanced viral uptake in endothelial cells, macrophages, and cardiomyocyte-like H9C2 cells. Selective cardiac and adipose viral depositions were observed in HFD mice but not in normal-chow-fed mice. The cardiac transcriptional signatures in HFD mice at 3, 6, and 24 wpi showed systemic suppression of mitochondria respiratory chain genes including ATP synthases and nicotinamide adenine dinucleotide:ubiquinone oxidoreductase gene members, upregulation of stress pathway-related crucial factors such as nuclear factor-erythroid 2-related factor 1 and signal transducer and activator of transcription 5A, and increases in expression of glucose metabolism-associated genes. As compared with the age-matched HFD control mice, cardiac ejection fraction and fractional shortening were significantly decreased, while left ventricular end-systolic diameter and volume were significantly elevated, and cardiac fibrosis was increased in HFD mice at 24 wpi. Conclusion: Our data demonstrated that the Spike protein could induce long-term transcriptional suppression of mitochondria metabolic genes and cause cardiac fibrosis and myocardial contractile impairment, providing mechanistic insights to PACS-related cardiomyopathy.

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

Cited by 33 publications

References 37 publications

Factors Associated With Long COVID Symptoms in an Online Cohort Study

Factors Associated With Long COVID Symptoms in an Online Cohort Study

Course of fatigue among patients previously hospitalised due to COVID-19

The SARS-CoV-2 Spike protein induces long-term transcriptional perturbations of mitochondrial metabolic genes, causes cardiac fibrosis, and reduces myocardial contractile in obese mice

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