Muscle abnormalities worsen after post-exertional malaise in long COVID

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Jan. 4, 2024

A subgroup of patients infected with SARS-CoV-2 remain symptomatic over three months after infection. distinctive symptom long COVID is post-exertional malaise, which associated a worsening fatigue- and pain-related symptoms acute mental or physical exercise, but its underlying pathophysiology unclear. With this longitudinal case-control study (NCT05225688), we provide new insights into the malaise in COVID. We show that skeletal muscle structure lower exercise capacity patients, local systemic metabolic disturbances, severe exercise-induced myopathy tissue infiltration amyloid-containing deposits muscles worsen induction malaise. This highlights novel pathways help to understand suffering from other post-infectious diseases.

Language: Английский

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Autonomic cardiac function in children and adolescents with long COVID: a case-controlled study

European Journal of Pediatrics, Journal Year: 2024, Volume and Issue: 183(5), P. 2375 - 2382

Published: March 6, 2024

Although the mechanisms underlying pathophysiology of long COVID condition are still debated, there is growing evidence that autonomic dysfunction may play a role in long-term complications or persisting symptoms observed significant proportion patients after SARS-CoV-2 infection. However, studies focused on have primarily been conducted adults, while function has not yet investigated pediatric subjects. In this study, for first time, we assessed whether with present abnormalities cardiac function. Fifty-six (mean age 10.3 ± 3.8 y) and 27 age-, sex-, body surface area-matched healthy controls 10.4 4.5y) underwent standard 12-lead electrocardiography (ECG) 24-h ECG Holter monitoring. Autonomic was by time-domain frequency-domain heart rate variability parameters. A comprehensive echocardiographic study also obtained two-dimensional echocardiography tissue Doppler imaging. Data analysis showed had changes HRV variables compared to controls: significantly lower r-MSSD (root mean square successive RR interval differences, 47.4 16.9 versus 60.4 29.1, p = 0.02), higher values VLF (very low frequency, 2077.8 1023.3 494.3 1015.5 ms, 0.000), LF (low 1340.3 635.6 354.6 816.8 HF (high 895.7 575.8 278.9 616.7 0.000). No differences were between two groups both systolic diastolic parameters echocardiography. Conclusion: These findings suggest an imbalance toward relative predominance parasympathetic tone, as already reported adult COVID. Further needed clarify clinical significance demonstrate its pathophysiological mechanism COVID, paving way effective therapeutic preventive strategies. What Known: • Long Covid children described globally, but mostly collecting temporal evolution symptoms. New: Cardiac tone children, adults.

Language: Английский

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Cardiopulmonary Exercise Testing in Children With Long COVID: A Case-controlled Study

The Pediatric Infectious Disease Journal, Journal Year: 2024, Volume and Issue: 43(8), P. 795 - 802

Published: May 7, 2024

Background: Cardiopulmonary exercise testing (CPET) is a noninvasive and nonexpensive diagnostic tool, that provides comprehensive evaluation of the pulmonary, cardiovascular, skeletal muscle systems’ integrated reactions to exercise. CPET has been extensively used in adults with Long COVID (LC), while evidence about its role children this condition scarce. Methods: Prospective, case-controlled observational study. Children LC control group healthy underwent CPET. findings were compared within 2 groups, groups according main clusters persisting symptoms. Results: Sixty-one 29 controls included. Overall, 90.2% patients (55 61) had pathologic test vs 10.3% (3/29) control. presented statistically significant higher probability having abnormal values peak VO2 ( P = 0.001), AT% pred <0.001), VO2/HR % 0.03), work slope 0.002), VE/VCO2 0.01). The mean was 30.17 (±6.85) 34.37 (±6.55) 0.007). Conclusions: Compared controls, have objective impaired functional capacity (expressed by low peak), signs deconditioning cardiogenic inefficiency when assessed As such, should be routinely clinical practice objectify phenotype limitations LC, follow-up them.

Language: Английский

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Cardiopulmonary Exercise Testing in Patients With Long COVID

CHEST Pulmonary, Journal Year: 2024, Volume and Issue: 2(2), P. 100036 - 100036

Published: Jan. 24, 2024

BackgroundAfter COVID-19, some patients present with ongoing symptoms (eg, breathlessness, exercise limitations), even after mild acute infection.Research QuestionWhat is the capacity of diagnosed long COVID and does it change from baseline to 1-year follow-up?Study Design MethodsThis retrospective case series included persistent a confirmed diagnosis COVID-19. Exercise was examined by cardiopulmonary testing (CPET), parameters related performance, ventilation, circulation, gas exchange were compared predicted values. A subgroup retested 1 year baseline, self-reported physical fitness assessed at follow-up.ResultsIn total, 169 completed CPET 41 follow-up. Mean maximum workload 172 W (95% CI, 161-182), 19% not achieving least 84% workload. peak oxygen uptake 24.4 mL/kg/min 23.1-25.7), 36% had value below % predicted. Oxygen uptake/workload slope normal threshold 8.4 mL/min/W observed in 54% patients. The follow-up results showed no statistically significant changes any parameters, which correspond lack improvement fitness.InterpretationPatients demonstrated lowered uptake, slope, and/or ventilatory equivalent for carbon dioxide, but different patients, illustrating heterogeneous study population. No improvements found After infection. What follow-up? This In fitness. Patients Take-Home PointStudy Question: follow-up?Results: follow-up.Interpretations: values across various population over time. Study Results: Interpretations: caused SARS-CoV-2 infection, associated multiple organ involvement.1Dennis A. Wamil M. Alberts J. et al.Multiorgan impairment low-risk individuals post-COVID-19 syndrome: prospective, community-based study.BMJ Open. 2021; 11e048391Crossref Scopus (296) Google Scholar Although most recover within few weeks, approximately 80% those infected experience or remain asymptomatic during phase.2World Health OrganizationClinical management severe respiratory infection (SARI) when COVID-19 disease suspected: interim guidance. World Organization, 2020Crossref (80) However, fatigue, muscle weakness, chest pain, cognitive dysfunction) are common among subset both hospitalized nonhospitalized patients.3Bosworth M.P.P. Ayoubkhani D. Prevalence following coronavirus (COVID-19) UK: 2 February 2023.https://www.ons.gov.uk/peoplepopulationandcommunity/healthandsocialcare/conditionsanddiseases/bulletins/prevalenceofongoingsymptomsfollowingcoronaviruscovid19infectionintheuk/2february2023Date accessed: 3, 2023Google Scholar, 4Carfì Bernabei R. Landi F. Persistent COVID-19.JAMA. 2020; 324: 603-605Crossref PubMed (2652) 5Clavario P. De Marzo V. Lotti al.Cardiopulmonary 3 months follow-up.Int J Cardiol. 340: 113-118Abstract Full Text PDF (65) 6Raman B. Cassar M.P. Tunnicliffe E.M. al.Medium-term effects on vital organs, capacity, cognition, quality life mental health, post-hospital discharge.EClinicalMedicine. 31100683Abstract (358) 7Malik Patel K. Pinto C. al.Post-acute syndrome (PCS) health-related (HRQoL)-a systematic review meta-analysis.J Med Virol. 2022; 94: 253-262Crossref (229) 8Heightman Prashar Hillman T.E. al.Post-COVID-19 assessment specialist clinical service: 12-month, single-centre, prospective 1325 individuals.BMJ Open Respir Res. 8Google These cause impaired function, reduced life, compromised often persisting years recovery infection.9Dennis Cuthbertson D.J. Wootton al.Multi-organ COVID: longitudinal cohort study.J R Soc Med. 2023; 116: 97-112Crossref (23) line Organization recommendations, onset referred as COVID.10Soriano J.B. Murthy S. Marshall J.C. Relan Diaz J.V. definition condition Delphi consensus.Lancet Infect Dis. Multiple studies have aimed understand etiology pathophysiology COVID, its impact function capacity. Often, assessments pulmonary cardiac performance rest revealed abnormalities.11Wood G. Kirkevang T.S. Agergaard al.Cardiac SARS-CoV-2.Front Cardiovasc 9871603Crossref (4) 12Beaudry R.I. Brotto A.R. Varughese R.A. al.Persistent dyspnea impairment; cross-sectional persistently dyspneic non-dyspneic controls.Front Physiol. 13917886Crossref (11) 13Singh I. Joseph Heerdt P.M. exertional intolerance COVID-19: insights invasive testing.Chest. 161: 54-63Abstract (154) Cardiopulmonary (CPET) has emerged preferred method quantify degree facilitate differential diagnosis.14Herdy A.H. Ritt L.E. Stein test: background, applicability interpretation.Arq Bras 2016; 107: 467-481PubMed Scholar,15Mezzani testing: basics methodology measurements.Ann Am Thorac Soc. 2017; 14: S3-S11Crossref (159) Therefore, utilization optimal evaluating providing important cardiovascular, respiratory, muscular, metabolic limitations activity.12Beaudry Scholar,16Mancini D.M. Brunjes D.L. Lala Trivieri M.G. Contreras J.P. Natelson B.H. Use stress unexplained post-coronavirus disease.JACC Heart Fail. 9: 927-937Crossref (103) 17Skjørten Ankerstjerne O.A.W. Trebinjac hospitalisation.Eur 58Crossref (107) 18Evers Schulze A.B. Osiaevi al.Sustained single center experience.Can 20222466789Crossref 19Sakellaropoulos S.G. Ali Papadis Mohammed Mitsis Zivzivadze Z. Is transient mitochondriopathy newly discovered: implications CPET.Cardiol 13: 264-267Crossref this study, we investigate determine minimum determined positive polymerase chain reaction antibody test SARS-CoV-2. evaluated clinic, Department Infectious Diseases, Aarhus University Hospital, Denmark, referral their general practitioner. exhibiting dyspnea, pain weakness) Physiotherapy Occupational Therapy CPET. tested between April 2021 May 2023, performed until 2023. Sociodemographic data collected through hospital medical records, electronic questionnaires, visits. managed using REDCap tool hosted University, secure web-based software platform building managing online databases surveys.20Barbagelata L. Masson W. Iglesias syndrome.Med Clin (Barc). Scholar,21Baratto Caravita Faini al.Impact pathophysiology: combined echocardiographic Appl Physiol (1985). 130: 1470-1478Crossref (88) cycle ergometer (Lode Corival CPET; Lode BV) continuous breath-by-breath analysis Vyaire Vyntus CPX SentrySuite v3.10 (CareFusion). system calibrated prior each test. 2-min resting phase preexercise measurements, incremental bicycle started an initial 20 40 increased 10 25 minute participants reached exhaustion. protocol selected based goal reaching exhaustion 8 12 min. ECG, saturation, BP measured Data averaged every 15 s. tests stopped reasons. (V̇o2)/workload (Vo2peak), body weight-indexed Vo2peak (Vo2peak/kg) considered abnormal if ≤ predicted, heart rate (HR) 90% pulse predicted.22van Voorthuizen E.L. van Helvoort H.A.C. Peters den Heuvel M.M. Borst perceived critical role breathing dysregulation?.Phys Ther. 102Crossref (10) V̇o2/workload third (after min) second-to-last step. Values < abnormal.23von Gruenewaldt Nylander E. Hedman Classification occurrence pattern subjects disease.Physiol Rep. 10e15197Crossref divided into subgroups relationship. Ventilatory efficiency estimated dioxide (Ve/Vco2) slope. ≥ 34 abnormal.22van indirect maximal voluntary ventilation (MVV), calculated FEV1 × 40, used estimate reserve (%) follows: (MMV − [Ve])/MVV) 100). Ve close MVV indicates low reserve, 15% (VT) identified point CO2 output exceeded Vo2 V̇o2 VT exercise.22van outpatient registration FEV1. Tests according ERS/ATS guidelines.24Harris P.A. Taylor Thielke Payne Gonzalez N. Conde J.G. Research capture (REDCap)--a metadata-driven workflow process translational research informatics support.J Biomed Inform. 2009; 42: 377-381Crossref (29101) Mental Fatigue Scale questionnaire containing items about affective, cognitive, sensory along duration sleep daytime variation symptom severity. Each item answered score rating 0 (normal function) (maximal symptom), resulting sum 45. cutoff 10.5 indicating fatigue been suggested.25Harris Minor B.L. al.The consortium: international community partners.J 2019; 95103208Crossref (9300) electronically baseline. At follow-up, asked physiotherapist assess activity level, habits, before time Statistical analyses conducted Stata (version 17.0; StataCorp). Continuous variables checked distribution histogram Q-Q plots. Normally distributed presented mean ± SD 95% CIs. Variables nonnormal median interquartile range. multivariable regression model compare outcomes ratio (RER) age, BMI, gender analysis. An unpaired t (mL/kg/min) Vo2/workload younger (˂ 49 age) older (≥ age). categorized three groups BMI: healthy weight (BMI 18.5-24.9 kg/m2), overweight 25.0-29.9 obese 30 kg/m2). CIs reported group, differences BMI categories quantified linear models. paired Student Bland-Altman plot. McNemar binary yielding risk difference. To account tests, Bonferroni-corrected P .0026 (α = 0.05/19 outcomes) applied. decimals, .001 .001. giving written informed consent, approved Danish Protection Agency (No. 1-16-02-655-20). did require approval ethics committee. age 46.7 12.5 years, females (62%). 27.2 5.4 kg/m2, 41% being kg/m2) 28% Pulmonary 64 98% 13%. > 58 (91%). 18.8 5.6. Of 47 invited (87%). Reasons completing work (n 1), sickness willing participate 4). Patient characteristics shown Table 1.Table 1Characteristic Population Baseline (N 169)CharacteristicValueAge, y46.7 12.5Gender Male64 (38) Female105 (62)BMI, kg/m2 Overall27.2 Underweight(< 18.5)3 (2) Healthy weight(18.5-24.9)48 (28) Overweight(25.0-29.9)69 (41) Obesity(≥ 30)47 (28)Time since d359 (233-468)Patients hospitalized12 (7)FEV1, L/min 64)3.39 0.65FEV1, 64)98 13Educational level Low55 (37) Medium64 (43) High30 (20)Work status Working/studying same hours before54 Sick leave75 (54) Unemployed11 (8)Mental score18.8 5.6Data No. (%), SD, (interquartile range). table new tab threshold. Overall, 77 (46%) HR 8.1 7.8-8.4), 91 (54%) having (Table 2).Table 2Baseline Testing Parameters Peak 169)Mean CI)Cutoff Abnormal ValueAbnormal ValuesPerformance Workload (peak), W172 (162-182)…… Workload, predicted125 (119-132)≤ 84%32 (19) Vo2peak, mL/min2,008 (1,908-2,108)…… mL/kg/min24.4 (23.1-25.7)…… Vo2, mL/kg/min, predicted97 (92-101)≤ 84%60 (36)Circulation HR, beats/min155 (152-159)…… predicted90 (88-91)≤ 90%77 (46) peak, mL/bpm12.9 (12.3-13.5)…… pulse, predicted107 (103-112)≤ 80%28 (17) mL/min/W8.1 (7.8-8.4)< mL/min/W91 systolic BP, mm Hg184 (179-190)…… diastolic Hg85.1 (82.9-87.2)……Ventilation Ve, L/min77.9 (73.7-82.2)…… predicted77 (73-81)< 85%115 (68) frequency35 (34-36)≥ 60 breaths/min2 (1) Breathing 65)39 (35-44)< 15%5 (8) RER1.18 (1.17-1.20)< 1.1027 (16)Gas Ve/Vco2 slope29.2 (28.2-30.1)≥ 3426 (15) Lowest Sao2, %99 (98-100)aMedian range).< 95%7 VT/Vo2peak, %71 (69-73)≤ 40%0 (0)Data CI), otherwise indicated. rate; RER ratio; Sao2 saturation; ventilation; dioxide; uptake; threshold.a Median Maximum 77% 73-81), 68% 85% five (8%). 29.2 28.2-30.1), 26 (15%) scoring 2). Multivariable 1.10 1.10. 1.10, there reduction 270 mL/min 37-504; .024), decrease beats/min 7-23; .001), 14 (95%). Meanwhile, 5.6 3.1-8.1; .001) 3).Table 3Comparison Between With Vo2/Workload Slope Normal BaselineRER 27)RER 142)Mean Difference, ValueVo2/Workload 91)Vo2/Workload 78)Mean ValuePerformance workload, W138 (111-165)179 (168-190)37 (14 59), .002162 (147-177)184 (171-197)25 (9 42), .003 predicted106 (90-121)129 (122-136)25 (8 41), .004115 (106-123)137 (128-147)23 (11 35), mL/min1,799 (1,526-2,071)2,048 (1,940-2,155)270 (37 504), .0241,794 (1,662-1,927)2,257 (2,123-2,390)463 (305 622), mL/kg/min19.7 (16.7-22.8)25.3 (23.9-26.7)3.0 (−0.0 6.1), .05222.5 (20.9-24.1)26.7 (24.7-28.6)5.9 (3.8 7.9), predicted87 (77-98)99 (94-103)12 (1 24), .03486 (81-91)110 (103-116)24 (16 32), .001Circulation beats/min141 (133-150)158 (155-161)15 (7 23), .001156 (151-160)155 (151-160)3 (−3 9), .279 predicted83 (78-88)91 (89-93)8 (3 13), .00189 (86-91)91 (89-93)2 (−2 5), .271 mL/min/W8.9 (8.1-9.7)7.9 (7.6-8.2)−0.8 (−1.6 0.0), .0526.8 (6.5-7.1)9.6 (9.5-9.8)2.8 (2.5 3.2) .001Ventilation L/min67 (58-76)80 (75-85)14 (4 .00771 (64-77)87 (81-92)15 22), predicted69 (61-78)78 (74-82)10 (0 21), .04370 (65-75)85 (80-90)14 65)43 (30-56)39 (34-44)−3 (−16 .58346 (39-52)31 (26-35)−14 (−23 −6), frequency33 (30-36)36 (34-37)3 .58334 (32-36)36 (35-38)2 (−0 .085 RER1.0 (1.0-1.1)1.2 (1.2-1.2)0.2 (0.1 0.2), .0011.2 (1.2-1.2)1.2 (1.1-1.2)−0.0 (−0.1 .125Gas slope34.0 (30.6-37.4)28.2 (27.4-29.1)−5.6 (−8.1 −3.1), .00129.5 (28.1-30.8)28.8 (27.5-30.1)−1.3 (−3.2 0.6), .176 %77 (70-83)70 (68-72)−5 (−10 .08372 (70-75)70 (67-73)4 8), .043Data CI) Similarly, 8. 8.4, 463 305-622; 8-22; .001). difference two (−0.0; −0.1 0.0; .125) 3). overlap illustrated Figure 1. End-tidal end-tidal rest, VT, (e-Table 1). (< 7.5% −16.2 1.2; .09), lowest 93% 87-98). 7.9 7.5-8.3) 8.3 7.9-8.7; .11) 101.3 91.9-110.8), 6.2% −16.6 4.2; .24) lower who 7.1% −18.5 4.3; .22) 7.5-8.4), 7.8 7.2-8.3) overweight, 8.8 8.3-9.2) obese. CPET, 4).Table 4Cardiopulmonary Exercise: 1-Year Follow-up 41)Baseline1-y Follow-upMean Work load, W199 (176-222)202 (178-227)3.3 (−4.5 11.1), .399 predicted128 (114-141)131 (118-145)3.7 (−2.0 9.5), .199 mL/min2,309 (2,070-2,549)2,322 (2,092-2,552)12.8 (−117.7 143.2), .844 mL/kg/min27.7 (24.7-30.8)27.6 (24.7-30.5)−0.1 (−1.8 1.5), .870 predicted102 (92-112)103 (94-111)0.9 (−4.9 6.6), .759Circulation beats/min157 (151-164)156 (149-163)−1.4 (−8.4 5.5), .679 predicted89 (86-93)92 (87-97)2.8 (−2.8 8.3), .323 mL/bpm14.7 (13.3-16.1)14.9 (13.4-16.4)0.2 (−0.7 1.1), .641 mL/bpm, predicted112 (101-122)115 (106-124)3.0 (−4.4 10.6), .409 mL/min/W8.4 (7.7-9.0)8.2 (7.5-8.8)−0.2 (−0.9 .606Ventilation L/min87 (77-98)87 (77-98)0.0 (−6.5 6.7), .988 predicted74 (67-82)81 (73-90)7.1 15.9), .107 frequency36 (33-38)37 (34-39)0.7 3.4), .613 27)36 (28-45)38 (31-46)1.9 6.8), RER1.2 (1.1-1.2)1.2 (1.2-1.2)0.0 (0.0 0.1), .018 .759 %97 (96-98)aMedian range).98 (96-99)aMedian range).0.3 (−0.6 1.2), .558Gas slope28.5 (26.4-30.7)27.0 (25.9-28.1)−1.5 (−3.5 0.5), .128 %70 (66-75)71 (65-76)0 (−5 .764Data considerable decline ba

Language: Английский

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Characteristics and predictors of Long Covid in children: a 3-year prospective cohort study

EClinicalMedicine, Journal Year: 2024, Volume and Issue: 76, P. 102815 - 102815

Published: Sept. 5, 2024

Language: Английский

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Long-term hypercoagulability, endotheliopathy and inflammation following acute SARS-CoV-2 infection

Expert Review of Hematology, Journal Year: 2023, Volume and Issue: 16(12), P. 1035 - 1048

Published: Nov. 28, 2023

Introduction both symptomatic and asymptomatic SARS-CoV-2 infections – coined Coronavirus disease 2019 (COVID-19) have been linked to a higher risk of cardiovascular events after recovery.

Language: Английский

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A review of post COVID syndrome pathophysiology, clinical presentation and management in children and young people

Paediatric Respiratory Reviews, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 1, 2024

Language: Английский

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Advances in researches on long coronavirus disease in children: a narrative review

Translational Pediatrics, Journal Year: 2024, Volume and Issue: 13(2), P. 318 - 328

Published: Feb. 1, 2024

In the context of global pandemic coronavirus disease 2019 (COVID-19), more than 700 million infections and millions deaths have occurred in countries around world. Currently, two main sequelae this are considered to occur children, namely, multi-system inflammatory syndrome children long COVID. Among these two, incidence COVID is higher its impact on population extensive, which focus us. However, due lack relevant studies limitations most studies, COVID-19 infection lag behind those adults, but they begun attract attention some clinicians researchers. We aim summarize current knowledge helping pediatricians researchers better understand providing guidance research clinical treatment it.

Language: Английский

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Long‐term outcome of a child with postcovid condition: Role of cardiopulmonary exercise testing and 24‐h Holter ECG to monitor treatment response and recovery

Pediatric Pulmonology, Journal Year: 2023, Volume and Issue: 58(10), P. 2944 - 2946

Published: June 28, 2023

Danilo Buonsenso has received grants to study long covid from Pfizer and Roche. The remaining authors declare no conflict of interest. data that support the findings this are available corresponding author upon reasonable request.

Language: Английский

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Susceptibility of SARS-CoV2 infection in children

European Journal of Pediatrics, Journal Year: 2023, Volume and Issue: 182(11), P. 4851 - 4857

Published: Sept. 13, 2023

Abstract Coronavirus disease 2019 in children presents with distinct phenotype comparison to adults. Overall, the pediatric infection a generally milder clinical course of acute compared adults still faces several unknown aspects. Specifically, presence wide range inflammatory manifestations, including multisystem syndrome (MIS-C), myocarditis, and long COVID period after suggests particular susceptibility some upon severe respiratory coronavirus 2 (SARS-CoV-2) infection. Albeit peculiar complications such as covid are less frequent adults, research on relationship between syndromes SARS-CoV-2 is rapidly evolving. Conclusions : new studies findings continue emerge, providing further insights into underlying mechanisms potential therapeutic strategies. In present work, we revised current knowledge main factors accounting for variability over age group. What Known: • COVID19 overall showed during phase Children be susceptible post infectious neuroinflammation, COVID. New: Mechanisms were recently shown pertain host. A specific combination HLA was associated higher MIS-C children.

Language: Английский

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