Exploring the recovery curve for long-term post-COVID dyspnea and fatigue

Fernández‐de‐las‐Peñas, César; Martín-Guerrero, José D.; Cancela-Cilleruelo, Ignacio; Moro-López-Menchero, Paloma; Pellicer-Valero, Óscar J.

doi:10.1016/j.ejim.2022.03.036

Cited by 15 publications

(21 citation statements)

References 12 publications

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“…Although dyspnea has been reported as a prevalent post–COVID-19 symptom in previous studies, 9 , 10 an analysis of the exponential recovery curve revealed that dyspnea decreased in the years after SARS-CoV-2 infection, 29 supporting the lower prevalence rates seen in our study. On the contrary, fatigue did not decrease in the same way as dyspnea, 29 which could explain the high prevalence of fatigue 2 years after COVID-19. These findings support theories suggesting that fatigue probably represents the most prevalent and the most long-lasting post–COVID-19 symptom.…”

Section: Discussionsupporting

confidence: 86%

Post–COVID-19 Symptoms 2 Years After SARS-CoV-2 Infection Among Hospitalized vs Nonhospitalized Patients

Fernández‐de‐las‐Peñas

Rodríguez‐Jiménez

Cancela-Cilleruelo

et al. 2022

JAMA Netw Open

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ImportanceIdentification of long-term post–COVID-19 symptoms among hospitalized and nonhospitalized patients is needed.ObjectiveTo compare the presence of post–COVID-19 symptoms 2 years after acute SARS-CoV-2 infection between hospitalized and nonhospitalized patients.Design, Setting, and ParticipantsA cross-sectional cohort study was conducted at 2 urban hospitals and general practitioner centers from March 20 to April 30, 2020, among 360 hospitalized patients and 308 nonhospitalized patients with acute SARS-CoV-2 infection during the first wave of the pandemic. Follow-up was conducted 2 years later.Main Outcomes and MeasuresParticipants were scheduled for a telephone interview 2 years after acute infection. The presence of post–COVID-19 symptoms was systematically assessed, with particular attention to symptoms starting after infection. Hospitalization and clinical data were collected from medical records. Between-group comparisons and multivariate logistic regressions were conducted.ResultsA total of 360 hospitalized patients (162 women [45.0%]; mean [SD] age, 60.7 [16.1] years) and 308 nonhospitalized patients (183 women [59.4%]; mean [SD] age, 56.7 [14.7] years) were included. Dyspnea was more prevalent at the onset of illness among hospitalized than among nonhospitalized patients (112 [31.1%] vs 36 [11.7%]; P &lt; .001), whereas anosmia was more prevalent among nonhospitalized than among hospitalized patients (66 [21.4%] vs 36 [10.0%]; P = .003). Hospitalized patients were assessed at a mean (SD) of 23.8 (0.6) months after hospital discharge, and nonhospitalized patients were assessed at a mean (SD) of 23.4 (0.7) months after the onset of symptoms. The number of patients who exhibited at least 1 post–COVID-19 symptom 2 years after infection was 215 (59.7%) among hospitalized patients and 208 (67.5%) among nonhospitalized patients (P = .01). Among hospitalized and nonhospitalized patients, fatigue (161 [44.7%] vs 147 [47.7%]), pain (129 [35.8%] vs 92 [29.9%]), and memory loss (72 [20.0%] vs 49 [15.9%]) were the most prevalent post–COVID-19 symptoms 2 years after SARS-CoV-2 infection. No significant differences in post–COVID-19 symptoms were observed between hospitalized and nonhospitalized patients. The number of preexisting medical comorbidities was associated with post–COVID-19 fatigue (odds ratio [OR], 1.93; 95% CI, 1.09-3.42; P = .02) and dyspnea (OR, 1.91; 95% CI, 1.04-3.48; P = .03) among hospitalized patients. The number of preexisting medical comorbidities (OR, 3.75; 95% CI, 1.67-8.42; P = .001) and the number of symptoms at the onset of illness (OR, 3.84; 95% CI, 1.33-11.05; P = .01) were associated with post–COVID-19 fatigue among nonhospitalized patients.Conclusions and RelevanceThis cross-sectional study suggested the presence of at least 1 post–COVID-19 symptom in 59.7% of hospitalized patients and 67.5% of nonhospitalized patients 2 years after infection. Small differences in symptoms at onset of COVID-19 were identified between hospitalized and nonhospitalized patients. Post–COVID-19 symptoms were similar between hospitalized and nonhospitalized patients; however, lack of inclusion of uninfected controls limits the ability to assess the association of SARS-CoV-2 infection with overall and specific post–COVID-19 symptoms 2 years after acute infection. Future studies should include uninfected control populations.

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Section: Discussionsupporting

confidence: 86%

Post–COVID-19 Symptoms 2 Years After SARS-CoV-2 Infection Among Hospitalized vs Nonhospitalized Patients

Fernández‐de‐las‐Peñas

Rodríguez‐Jiménez

Cancela-Cilleruelo

et al. 2022

JAMA Netw Open

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“…The presence of post-COVID fatigue has been associated with a high burden [ 32 ], and 60% of our sample continued experiencing this symptom 18 months after hospitalization. Way to manage this symptom is crucial, since it seems to be the most prevalent and long-lasting post-COVID symptom and impact sufferers from working as efficiently as before infection [ 33 ]. In fact, some hypotheses propose that post-COVID fatigue shares common features with myalgic encephalomyelitis [ 34 ].…”

Section: Discussionmentioning

confidence: 99%

Genetic Association between ACE2 (rs2285666 and rs2074192) and TMPRSS2 (rs12329760 and rs2070788) Polymorphisms with Post-COVID Symptoms in Previously Hospitalized COVID-19 Survivors

Fernández‐de‐las‐Peñas

Arendt‐Nielsen

Dı́az-Gil

et al. 2022

Genes

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The aim of the study was to identify the association between four selected COVID-19 polymorphisms of ACE2 and TMPRSS2 receptors genes with the presence of long-COVID symptomatology in COVID-19 survivors. These genes were selected as they associate with the entry of the SARS-CoV-2 virus into the cells, so polymorphisms could be important for the prognoses of long-COVID symptoms. Two hundred and ninety-three (n = 293, 49.5% female, mean age: 55.6 ± 12.9 years) individuals who had been previously hospitalized due to COVID-19 were included. Three potential genotypes of the following single nucleotide polymorphisms (SNPs) were obtained from non-stimulated saliva samples of participants: ACE2 (rs2285666), ACE2 (rs2074192), TMPRSS2 (rs12329760), TMPRSS2 (rs2070788). Participants were asked to self-report the presence of any post-COVID defined as a symptom that started no later than one month after SARS-CoV-2 acute infection and whether the symptom persisted at the time of the study. At the time of the study (mean: 17.8, SD: 5.2 months after hospital discharge), 87.7% patients reported at least one symptom. Fatigue (62.8%), pain (39.9%) or memory loss (32.1%) were the most prevalent post-COVID symptoms. Overall, no differences in long-COVID symptoms were dependent on ACE2 rs2285666, ACE2 rs2074192, TMPRSS2 rs12329760, or TMPRSS2 rs2070788 genotypes. The four SNPs assessed, albeit previously associated with COVID-19 severity, do not predispose for developing long-COVID symptoms in people who were previously hospitalized due to COVID-19 during the first wave of the pandemic.

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“…PASC occurs in 3-11.7% of infected individuals and is characterized by symptoms such as fatigue, headache, cognitive dysfunction, altered smell and taste, shortness of breath, and dyspnea, occurring >12 weeks after acute virus infection 4,5 . Of note, among patients with severe disease requiring hospitalization, shortness of breath or dyspnea are reported with a much higher frequency (in up to 49% and 23.3% of cases, respectively) 8-10 months after acute disease 6,7 . The pathomorphological correlates and mechanisms responsible for respiratory PASC are still not fully understood.…”

Section: Introductionmentioning

confidence: 99%

Hamsters are a model for post-COVID-19 alveolar regeneration mechanisms: an opportunity to understand post-acute sequelae of SARS-CoV-2

Heydemann

Ciurkiewicz

Beythien

et al. 2022

Preprint

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A relevant number of coronavirus disease 2019 (COVID-19) survivors suffers from post-acute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (PASC). Current evidence suggests a dysregulated alveolar regeneration in COVID-19 as a possible explanation for respiratory PASC symptoms, a phenomenon which deserves further investigation in a suitable animal model. This study investigates morphologic and transcriptomic features of alveolar regeneration in SARS-CoV-2 infected Syrian golden hamsters. We demonstrate that CK8+ alveolar differentiation intermediate (ADI) cells accumulate following SARS-CoV-2-induced diffuse alveolar damage. A subset of ADI cells shows nuclear accumulation of p53 at 6- and 14-days post infection (dpi), indicating a prolonged block in the ADI state. Transcriptome data shows the expression of gene signatures driving ADI cell senescence, epithelial-mesenchymal transition, and angiogenesis. Moreover, we show that multipotent CK14+ airway basal cell progenitors migrate out of terminal bronchioles, aiding alveolar regeneration. At 14 dpi, persistence of ADI cells, peribronchiolar proliferates, M2-type macrophages, and sub-pleural fibrosis is observed, indicating incomplete alveolar restoration. The results demonstrate that the hamster model reliably phenocopies indicators of a dysregulated alveolar regeneration of COVID-19 patients. The study provides a suitable translational model for future research on the pathomechanims of PASC and testing of prophylactic and therapeutical approaches.

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Exploring the recovery curve for long-term post-COVID dyspnea and fatigue

Cited by 15 publications

References 12 publications

Post–COVID-19 Symptoms 2 Years After SARS-CoV-2 Infection Among Hospitalized vs Nonhospitalized Patients

Post–COVID-19 Symptoms 2 Years After SARS-CoV-2 Infection Among Hospitalized vs Nonhospitalized Patients

Genetic Association between ACE2 (rs2285666 and rs2074192) and TMPRSS2 (rs12329760 and rs2070788) Polymorphisms with Post-COVID Symptoms in Previously Hospitalized COVID-19 Survivors

Hamsters are a model for post-COVID-19 alveolar regeneration mechanisms: an opportunity to understand post-acute sequelae of SARS-CoV-2

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