Long COVID in Young Patients: Impact on Lung Volume Evaluated Using Multidetector CT

Abstract:

Purpose: To evaluate using quantitative analysis on chest CT images a possible lung volume reduction in Long COVID patients who complain mild respiratory symptoms, with chest CT negative for inflammatory findings.
Materials and Methods: CT images of patients from 18 to 40 years old who underwent chest CT scan at our institution were analyzed retrospectively, using AwServer Thoracic VCAR software for a quantitative study. Exclusion criteria were inflammatory findings at CT, previous lung surgery, lung cancer, and breath artifacts that invalidate the quality of images. Patients were divided into two groups: in the first one (“post-COVID”) were patients who had previous SARS-CoV-2 infection, confirmed by an RT-PCR, who underwent chest CT from 3 to 6 months after their negativization for long COVID symptoms; in the control group (“non-COVID”), were enrolled patients who underwent a chest CT scan from January 2018 to December 2019, before the spread of COVID in Italy.
Results: Our final population included 154 TC, 77 post-COVID patients (mean age 33 ± 6) and 77 non-COVID patients (mean age 33 ± 4.9). Non statistical significative differences were obtained between groups in terms of age, sex, and other characteristics that affect total lung capacity such as obesity, thoracic malformations, and smoking habit. Mean values of the total lung volume (TV), right-lung volume (RV), and left-lung volume (LV) in the post-COVID group compared with non-COVID group were, respectively: 5.25 ± 0.25 L vs. 5.72 ± 0.26 L (p = 0.01); 2.76 ± 0.14 L vs. 3 ± 0.14 L (p = 0.01); 2.48 ± 0.12 L vs. 2.72 ± 0.12 L (p = 0.01).
Conclusion: In patients with symptoms suggesting Long COVID and negative chest CT macroscopic findings, quantitative volume analysis demonstrated a mean value of reduction in lung volume of 10% compared to patients of the same age who never had COVID. A chest CT negative for inflammatory findings may induce clinicians to attribute Long COVID mild respiratory symptoms to anxiety, especially in young patients. Our study brings us beyond appearances and beyond the classic radiological signs, introducing a quantitative evaluation of lung volumes in these patients. It is hard to establish to what extent this finding may contribute to Long COVID symptoms, but this is another step to gain a wider knowledge of the potential long-term effects caused by this new virus.
Source: Bellini D, Capodiferro P, Vicini S, Rengo M, Carbone I. Long COVID in Young Patients: Impact on Lung Volume Evaluated Using Multidetector CT. Tomography. 2023; 9(4):1276-1285. https://doi.org/10.3390/tomography9040101 https://www.mdpi.com/2379-139X/9/4/101 (Full text)
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A Pilot Study of Short-Course Oral Vitamin A and Aerosolised Diffuser Olfactory Training for the Treatment of Smell Loss in Long COVID

Abstract:

Background: Olfactory dysfunction (OD) is a common neurosensory manifestation in long COVID. An effective and safe treatment against COVID-19-related OD is needed.
Methods: This pilot trial recruited long COVID patients with persistent OD. Participants were randomly assigned to receive short-course (14 days) oral vitamin A (VitA; 25,000 IU per day) and aerosolised diffuser olfactory training (OT) thrice daily (combination), OT alone (standard care), or observation (control) for 4 weeks. The primary outcome was differences in olfactory function by butanol threshold tests (BTT) between baseline and end-of-treatment. Secondary outcomes included smell identification tests (SIT), structural MRI brain, and serial seed-based functional connectivity (FC) analyses in the olfactory cortical network by resting-state functional MRI (rs–fMRI).
Results: A total of 24 participants were randomly assigned to receive either combination treatment (n = 10), standard care (n = 9), or control (n = 5). Median OD duration was 157 days (IQR 127–175). Mean baseline BTT score was 2.3 (SD 1.1). At end-of-treatment, mean BTT scores were significantly higher for the combination group than control (p < 0.001, MD = 4.4, 95% CI 1.7 to 7.2) and standard care (p = 0.009) groups. Interval SIT scores increased significantly (p = 0.009) in the combination group. rs–fMRI showed significantly higher FC in the combination group when compared to other groups. At end-of-treatment, positive correlations were found in the increased FC at left inferior frontal gyrus and clinically significant improvements in measured BTT (r = 0.858, p < 0.001) and SIT (r = 0.548, p = 0.042) scores for the combination group.
Conclusions: Short-course oral VitA and aerosolised diffuser OT was effective as a combination treatment for persistent OD in long COVID.
Source: Chung TW-H, Zhang H, Wong FK-C, Sridhar S, Lee TM-C, Leung GK-K, Chan K-H, Lau K-K, Tam AR, Ho DT-Y, et al. A Pilot Study of Short-Course Oral Vitamin A and Aerosolised Diffuser Olfactory Training for the Treatment of Smell Loss in Long COVID. Brain Sciences. 2023; 13(7):1014. https://doi.org/10.3390/brainsci13071014 https://www.mdpi.com/2076-3425/13/7/1014 (Full text)

Precision Medicine for More Oxygen (P4O2)—Study Design and First Results of the Long COVID-19 Extension

Abstract:

Introduction: The coronavirus disease 2019 (COVID-19) pandemic has led to the death of almost 7 million people, however, with a cumulative incidence of 0.76 billion, most people survive COVID-19. Several studies indicate that the acute phase of COVID-19 may be followed by persistent symptoms including fatigue, dyspnea, headache, musculoskeletal symptoms, and pulmonary functional-and radiological abnormalities. However, the impact of COVID-19 on long-term health outcomes remains to be elucidated.
Aims: The Precision Medicine for more Oxygen (P4O2) consortium COVID-19 extension aims to identify long COVID patients that are at risk for developing chronic lung disease and furthermore, to identify treatable traits and innovative personalized therapeutic strategies for prevention and treatment. This study aims to describe the study design and first results of the P4O2 COVID-19 cohort.
Methods: The P4O2 COVID-19 study is a prospective multicenter cohort study that includes nested personalized counseling intervention trial. Patients, aged 40–65 years, were recruited from outpatient post-COVID clinics from five hospitals in The Netherlands. During study visits at 3–6 and 12–18 months post-COVID-19, data from medical records, pulmonary function tests, chest computed tomography scans and biological samples were collected and questionnaires were administered. Furthermore, exposome data was collected at the patient’s home and state-of-the-art imaging techniques as well as multi-omics analyses will be performed on collected data.
Results: 95 long COVID patients were enrolled between May 2021 and September 2022. The current study showed persistence of clinical symptoms and signs of pulmonary function test/radiological abnormalities in post-COVID patients at 3–6 months post-COVID. The most commonly reported symptoms included respiratory symptoms (78.9%), neurological symptoms (68.4%) and fatigue (67.4%). Female sex and infection with the Delta, compared with the Beta, SARS-CoV-2 variant were significantly associated with more persisting symptom categories.
Conclusions: The P4O2 COVID-19 study contributes to our understanding of the long-term health impacts of COVID-19. Furthermore, P4O2 COVID-19 can lead to the identification of different phenotypes of long COVID patients, for example those that are at risk for developing chronic lung disease. Understanding the mechanisms behind the different phenotypes and identifying these patients at an early stage can help to develop and optimize prevention and treatment strategies.
Source: Baalbaki N, Blankestijn JM, Abdel-Aziz MI, de Backer J, Bazdar S, Beekers I, Beijers RJHCG, van den Bergh JP, Bloemsma LD, Bogaard HJ, et al. Precision Medicine for More Oxygen (P4O2)—Study Design and First Results of the Long COVID-19 Extension. Journal of Personalized Medicine. 2023; 13(7):1060. https://doi.org/10.3390/jpm13071060 https://www.mdpi.com/2075-4426/13/7/1060 (Full text)

Trajectory of Post-COVID Self-Reported Fatigue and Dyspnoea in Individuals Who Had Been Hospitalized by COVID-19: The LONG-COVID-EXP Multicenter Study

Abstract:

Fatigue and dyspnoea are common post-COVID symptoms. The aim of this study was to apply Sankey plots and exponential bar plots for visualizing the evolution and trajectory of post-COVID fatigue and dyspnoea symptoms in a cohort of previously hospitalized COVID-19 survivors. A total of 1266 previously hospitalized patients due to COVID-19 participated in this multicentre study. They were assessed at hospital admission (T0), 8.4 months (T1), 13.2 months (T2) and 18.3 months (T3) after hospital discharge and were asked about the presence of self-reported fatigue or dyspnoea symptoms.
Fatigue was defined as a self-perceived feeling of constant tiredness and/or weakness whereas dyspnoea was defined as a self-perceived feeling of shortness of breath at rest. We specifically asked for fatigue and dyspnoea that participants attributed to the infection. Clinical/hospitalization data were collected from hospital medical records.
The prevalence of post-COVID fatigue was 56.94% (n = 721) at T1, 52.31% (n = 662) at T2 and 42.66% (n = 540) at T3. The prevalence of dyspnoea at rest decreased from 28.71% (n = 363) at hospital admission (T0), to 21.29% (n = 270) at T1, to 13.96% (n = 177) at T2 and 12.04% (n = 153) at T3. The Sankey plots revealed that 469 (37.08%) and 153 (12.04%) patients exhibited fatigue and dyspnoea at all follow-up periods.
The recovery exponential curves show a decreased prevalence trend, showing that fatigue and dyspnoea recover the following three years after hospitalization. The regression models revealed that the female sex and experiencing the symptoms (e.g., fatigue, dyspnoea) at T1 were factors associated with the presence of post-COVID fatigue or dyspnoea at T2 and T3.
The use of Sankey plots shows a fluctuating evolution of post-COVID fatigue and dyspnoea during the first two years after infection. In addition, exponential bar plots revealed a decreased prevalence of these symptoms during the first years after. The female sex is a risk factor for the development of post-COVID fatigue and dyspnoea.
Source:Fernández-de-las-Peñas C, Cancela-Cilleruelo I, Rodríguez-Jiménez J, Fuensalida-Novo S, Martín-Guerrero JD, Pellicer-Valero OJ, de-la-Llave-Rincón AI. Trajectory of Post-COVID Self-Reported Fatigue and Dyspnoea in Individuals Who Had Been Hospitalized by COVID-19: The LONG-COVID-EXP Multicenter Study. Biomedicines. 2023; 11(7):1863. https://doi.org/10.3390/biomedicines11071863 https://www.mdpi.com/2227-9059/11/7/1863 (Full text)

The potential role of Rhodiola rosea L. extract WS® 1375 for patients with post-COVID-19 fatigue

Abstract:

Fatigue and physical exhaustion are the dominant symptoms of post-coronavirus (COVID-19) conditions that might even develop after only mild acute disease. Post-acute infection syndromes have been observed after various infections, e.g., Coxiella burnetii, Ebola, Dengue, Polio, severe acute respiratory syndrome (SARS), Chikungunya, West Nile Virus, Borrelia, or Giardina lamblia. The similarities in symptoms and courses suggest a high likelihood of common pathogenetic pathways, including persistent infection, autoimmune reactions, dysregulation of the microbiome, inability to repair tissue damage, or endothelial dysfunction.

Some herbal drugs, so-called adaptogens, exert effects resulting in an increase in the resistance or regulatory potential of organisms against biological, chemical and physical burden or stress. Therefore, it seems possible that adaptogens can be helpful in cases of post-COVID-19 symptoms. One of these adaptogens is Rhodiola rosea L. The proprietary ethanolic extract made from roots and rhizomes of Rhodiola rosea WS® 1375 has been reported to modulate neuroinflammation in response to stress stimuli in preclinical models. Moreover, it activated the synthesis or resynthesis of adenosine triphosphate (ATP) in skeletal muscle mitochondria and counteracted muscle fatigue.

In three clinical trials with subjects suffering from burnout symptoms, prolonged or chronic fatigue symptoms or life-stress symptoms, clinically relevant improvements of fatigue and exhaustion were reported over 4 to 12 weeks of treatment at a very favorable tolerability and safety profile in heterogeneous patient populations. In conclusion, Rhodiola rosea extract WS® 1375 has a promising pharmacological and therapeutic profile for the treatment of fatigue and physical exhaustion associated with post-COVID-19 conditions.

Source: Wegener T, Edwards D, Kasper S. The potential role of Rhodiola rosea L. extract WS® 1375 for patients with post-COVID-19 fatigue. hb TIMES Schw Aerztej. 2023;8(1):56-61. doi:10.36000/hbT.2023.09.001 https://schw-aerztej.healthbooktimes.org/article/74319-the-potential-role-of-rhodiola-rosea-l-extract-ws-1375-for-patients-with-post-covid-19-fatigue (Full text)

The impact of acute SARS-CoV-2 on testicular function including insulin-like factor 3 [INSL3] in men with mild COVID-19: A longitudinal study

Abstract:

Background: SARS-CoV-2 may affect the male reproductive system as it uses angiotensin-converting enzyme [ACE]2, which is expressed in testicular tissue, as an entry point into the cell. Few studies have evaluated the long-term effects of mild COVID-19 on testicular function, and INSL3 levels have not previously been assessed during acute SARS-CoV-2 infection.

Objectives: To assess the impact of acute SARS-CoV-2 infection on testicular function including INSL3 and the presence of SARS-CoV-2 RNA in semen in non-hospitalised men with mild COVID-19.

Materials and methods: This longitudinal study included 36 non-hospitalised SARS-CoV-2-positive men (median age 29 years). Inclusion was within seven days following a positive SARS-CoV-2 RT-PCR test. Reproductive hormone levels, semen parameters, and the presence of SARS-CoV-2 RNA in oropharyngeal and semen samples were assessed during acute SARS-CoV-2 infection (baseline) and at three- and six-month follow-up. Wilcoxon matched-pair signed-rank (two samples) test was used to assess time-related alterations in reproductive hormone levels and semen parameters.

Results: Lower plasma testosterone [T] (total and calculated free [c-fT]) and higher LH concentrations were observed during acute SARS-CoV-2 infection (baseline) compared to three- and six-month follow-up. Consequently, ratios of c-fT/LH were lower at baseline compared to three- and six-month follow-up (P < 0.001 and P = 0.003, respectively). Concomitantly, lower INSL3 concentrations were observed at baseline compared to three-month follow-up (P = 0.01). The total number of motile spermatozoa was also lower at baseline compared to six-month follow-up (P = 0.02). The alterations were detected irrespective of whether the men had experienced SARS-CoV-2-related fever episodes or not. No SARS-CoV-2 RNA was detected in semen at any time point.

Discussion and conclusion: This study showed a reduction in testicular function, which was for the first time confirmed by INSL3, in men mildly affected by SARS-CoV-2 infection. The risk of transmission of SARS-CoV-2 RNA via semen seems to be low. Febrile episodes may impact testicular function, but a direct effect of SARS-CoV-2 cannot be excluded. This article is protected by copyright. All rights reserved.

Source: Lauritsen MP, Kristensen TL, Bo Hansen C, Schneider UV, Talbot AL, Skytte AB, Petersen JH, Johannsen TH, Zedeler A, Albrethsen J, Juul A, Priskorn L, Jørgensen N, Westh H, Freiesleben NC, Nielsen HS. The impact of acute SARS-CoV-2 on testicular function including insulin-like factor 3 [INSL3] in men with mild COVID-19: A longitudinal study. Andrology. 2023 Jul 8. doi: 10.1111/andr.13494. Epub ahead of print. PMID: 37421657. https://pubmed.ncbi.nlm.nih.gov/37421657/

Post-COVID-19 Syndrome in Non-Hospitalized Individuals: Healthcare Situation 2 Years after SARS-CoV-2 Infection

Abstract:

Although “post-COVID-19 syndrome” (PCS) is reported to be common even in non-hospitalized individuals, long-term information on symptom burden, healthcare needs, utilization, and satisfaction with healthcare is scarce. The objectives of this study were to describe symptom burden, healthcare utilization and experiences with the healthcare offered for PCS in a German sample of non-hospitalized persons 2 years after SARS-CoV-2 infection.

Individuals with past COVID-19 confirmed by positive polymerase chain reaction testing were examined at the University Hospital of Augsburg from 4 November 2020 to 26 May 2021 and completed a postal questionnaire between 14 June 2022 and 1 November 2022. Participants who self-reported the presence of fatigue, dyspnea on exertion, memory problems or concentration problems were classified as having PCS.

Of the 304 non-hospitalized participants (58.2% female, median age 53.5), 210 (69.1%) had a PCS. Among these, 18.8% had slight to moderate functional limitations. Participants with PCS showed a significantly higher utilization of healthcare and a large proportion complained about lacking information on persistent COVID-19 symptoms and problems finding competent healthcare providers.

The results indicate the need to optimize patient information on PCS, facilitate access to specialized healthcare providers, provide treatment options in the primary care setting and improve the education of healthcare providers.

Source: Kirchberger I, Meisinger C, Warm TD, Hyhlik-Dürr A, Linseisen J, Goßlau Y. Post-COVID-19 Syndrome in Non-Hospitalized Individuals: Healthcare Situation 2 Years after SARS-CoV-2 Infection. Viruses. 2023 Jun 5;15(6):1326. doi: 10.3390/v15061326. PMID: 37376625; PMCID: PMC10303962. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10303962/ (Full text)

Unsuspected Subclinical Left Ventricular Dysfunction in Post-COVID Patients: A Real-world Observation

Abstract:

Background: Subclinical myocardial dysfunction may exist in post-COVID-19 patients and may carry significance in long term.

Methodology: Subjects of long-COVID-19 with historically and radiologically significant pulmonary involvement (without documented cardiac involvement) were evaluated on outpatient follow-up echocardiographically when they had disproportionate shortness of breath (SOB), fatigue, or high pulse rate as perceived by the physicians. The common acute-phase symptoms were noted and scored retrospectively. The assessment included spirometry and measurement of chronic obstructive pulmonary disease (COPD) assessment test (CAT) score with measurement of the left ventricular (LV) and right ventricular (RV) free wall global longitudinal strain as an adjunct to routine two-dimensional and Doppler echocardiography and spirometry. The results were evaluated statistically with respect to the history of hospitalization.

Results: The hospitalized (n = 15) and nonhospitalized (n = 10) patients were demographically similar. However, the nonhospitalized patients had higher total symptom score (p = 0.03), anosmia (p = 0.017), and ageusia (p = 0.0019). At follow-up (&gt;3 months of acute illness), the nonhospitalized patients had a better CAT score (p = 0.04), higher change in max pulse rate (p = 0.03), and higher forced expiratory volume in 1 second (FEV1) (p = 0.002), tricuspid annular plane systolic excursion (TAPSE) (p = 0.02), and left ventricular global longitudinal strain (LVGLS) (-17.15 ± 1.19 vs -13.11 ± 1.91) (p = 0.0001). Overall, the two groups formed distinct clusters. The LVGLS and the maximum pulse rate difference in the two chair test (2CT) seem to contribute maximally to the variance between the two groups in multivariate analysis.

Conclusion: The subclinical myocardial dysfunction persisting in post-COVID patients (without suspected cardiac affection and lower neuroinflammatory symptoms in the acute phase) with significant pulmonary affection needs further evaluation. They demonstrate a higher max pulse rate difference in the 2CT. This real-world observation demands further investigations.

Source: Bhattacharyya P, Sengupta S, De A, Mukherjee S, Paul M, Dey D. Unsuspected Subclinical Left Ventricular Dysfunction in Post-COVID Patients: A Real-world Observation. J Assoc Physicians India. 2022 Nov;70(11):11-12. doi: 10.5005/japi-11001-0147. PMID: 37355939. https://japi.org/article/files/JAPI0147_p18-22_compressed.pdf (Full text)

Do COVID-19 Vaccinations Affect the Most Common Post-COVID Symptoms? Initial Data from the STOP-COVID Register-12-Month Follow-Up

Abstract:

Around the world, various vaccines have been developed to prevent the SARS-CoV-2 virus infection and consequently the COVID-19 disease. However, many patients continue to report persistent symptoms after the acute phase. Since gathering scientific information on long COVID and post-COVID syndrome has become an urgent issue, we decided to investigate them in relation to the vaccination status of patients from the STOP-COVID registry.

In this retrospective study, we analyzed data from the medical visit after contraction of COVID-19 and follow-up visits in the 3rd and 12th month after the disease. In total, 801 patients were included in the analysis. The most frequent complaints after 12 months included deterioration of exercise tolerance (37.5%), fatigue (36.3%), and memory/concentration difficulties (36.3%). In total, 119 patients declared that they had been diagnosed with at least one new chronic disease since the end of isolation, and 10.6% required hospitalization.

The analysis of individual symptoms revealed that headache (p = 0.001), arthralgia (p = 0.032), and dysregulation of hypertension (p = 0.030) were more common in unvaccinated patients. Considering headache and muscle pain, people vaccinated after the disease manifested these symptoms less frequently. Subsequent research is needed to consider vaccines as a preventive factor for post-COVID syndrome.

Source: Babicki M, Kapusta J, Pieniawska-Śmiech K, Kałuzińska-Kołat Ż, Kołat D, Mastalerz-Migas A, Jankowski P, Chudzik M. Do COVID-19 Vaccinations Affect the Most Common Post-COVID Symptoms? Initial Data from the STOP-COVID Register-12-Month Follow-Up. Viruses. 2023 Jun 13;15(6):1370. doi: 10.3390/v15061370. PMID: 37376668; PMCID: PMC10304551. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10304551/ (Full text)

Microbiome and intestinal pathophysiology in post-acute sequelae of COVID-19

Abstract:

Long COVID, also known for post-acute sequelae of COVID-19, describes the people who have the signs and symptoms that continue or develop after the acute COVID-19 phase. Long COVID patients suffer from an inflammation or host responses towards the virus approximately 4 weeks after initial infection with the SARS CoV-2 virus and continue for an uncharacterized duration.

Anyone infected with COVID-19 before could experience long-COVID conditions, including the patients who were infected with SARS CoV-2 virus confirmed by tests and those who never knew they had an infection early. People with long COVID may experience health problems from different types and combinations of symptoms over time, such as fatigue, dyspnea, cognitive impairments, and gastrointestinal (GI) symptoms (e.g., nausea, vomiting, diarrhea, decreased or loss of appetite, abdominal pain, and dysgeusia). The critical role of the microbiome in these GI symptoms and long COVID were reported in clinical patients and experimental models.

Here, we provide an overall view of the critical role of the GI tract and microbiome in the development of long COVID, including the clinical GI symptoms in patients, dysbiosis, viral-microbiome interactions, barrier function, and inflammatory bowel disease patients with long COVID. We highlight the potential mechanisms and possible treatment based on GI health and microbiome. Finally, we discuss challenges and future direction in the long COVID clinic and research.

Source: Zhang J, Zhang Y, Xia Y, Sun J. Microbiome and intestinal pathophysiology in post-acute sequelae of COVID-19. Genes Dis. 2023 Jun 19. doi: 10.1016/j.gendis.2023.03.034. Epub ahead of print. PMID: 37362775; PMCID: PMC10278891. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10278891/ (Full text)