Effect of cardiopulmonary and metabolic rehabilitation in patients with exercise-induced oxyhemoglobin desaturation after hospital discharge from COVID-19: case series / Efeito da reabilitação cardiopulmonar e metabólica em pacientes que apresentaram dessaturação da oxihemoglobina induzida pelo exercício após alta hospitalar pela COVID-19: série de casos

INTRODUÇÃO: A dessaturação da oxihemoglobina induzida pelo exercício em pacientes pós-COVID-19 parece estar associada à redução da difusão e dos volumes pulmonares, à maior dispneia e baixa capacidade funcional, sendo relacionada à maior mortalidade e pior prognóstico. A reabilitação cardiopulmonar e metabólica (RCPM) é relevante, pois visa restaurar a funcionalidade, tolerância ao esforço e a qualidade de vida (QV). OBJETIVO: Verificar os efeitos da RCPM em pacientes que apresentaram dessaturação da oxihemoglobina induzida pelo exercício após alta hospitalar pela COVID-19 e ainda observar a diferença entre os treinamentos contínuo de moderada intensidade (TCMI) e o intervalado de alta intensidade (TIAI) na tolerância ao esforço, nos sintomas e na QV. MÉTODOS: Trata-se do relato de uma série de 4 casos que foram hospitalizados por COVID-19 e que após alta hospitalar apresentaram dessaturação da oxihemoglobina induzida pelo esforço durante o teste do degrau de 6 minutos (TD6). Os pacientes foram avaliados por meio de espirometria de repouso, mensuração da força da musculatura inspiratória, TD6, teste da caminhada de 6 minutos (TC6), teste de repetições máximas do quadríceps e bíceps braquial e responderam ao questionário SF-36 de QV. Submetidos a um protocolo de treinamento contendo treino da musculatura inspiratória e treino resistido para grandes grupos musculares, adicionalmente, 2 pacientes fizeram TCMI (com 60-80% da frequência cárdica de reserva (FCR)) e 2 TIAI (com 40% da FCR na fase off, durante 4 minutos e 80 a 100%, na fase on, durante 2 minutos) em esteira por 30 minutos e, por fim, após 3 meses foram reavaliados. RESULTADOS: Observouse aumento da tolerância ao esforço, da força muscular inspiratória e periférica, além da melhora da QV e redução dos sintomas em todos os pacientes após a RCPM, porém houve incrementos maiores nos pacientes submetidos ao TIAI comparados ao TCMI na distância percorrida em metros (caso 1- 156 (23% de incremento); caso 3 - 168 (40%)) versus (caso 2 e 4 - 60 metros, com incrementos de 9% e 14%, respectivamente) e maior número de degraus (caso 1- 28 (23% de aumento); caso 3- 37 (34%)) versus (caso 2 ­ 2 (2% incremento); caso 4 - 15 (21%)). CONCLUSÃO: A RCPM apresentou efeitos positivos, com incremento da capacidade funcional e melhora da QV, além da redução dos sintomas durante o esforço, particularmente nos pacientes submetidos ao TIAI.

INTRODUCTION: Exercise-induced oxyhemoglobin desaturation in post-COVID-19 patients appears to be associated with reduced diffusion and lung volumes, greater dyspnea and low functional capacity, being related to higher mortality and worse prognosis. Cardiopulmonary and metabolic rehabilitation (CPMR) is relevant, as it aims to restore functionality, exercise tolerance and quality of life (QoL). OBJECTIVE: To verify the effects of CPMR in patients who presented exercise-induced oxyhemoglobin desaturation after hospital discharge due to COVID-19 and also to observe the difference between moderate-intensity continuous training (MICT) and high intensity interval training (HIIT) on effort tolerance, symptoms and QoL. METHODS: This is the report of a series of 4 cases who were hospitalized for COVID-19 and who, after hospital discharge, presented exertion-induced oxyhemoglobin desaturation during the 6-minute step test (6MST). Patients were assessed using spirometry at rest, measurement of inspiratory muscle strength, 6MST, 6-minute walk test (6MWT), quadriceps and biceps brachii maximum repetitions test, and answered the SF-36 QoL questionnaire. Submitted to a training protocol containing training of the inspiratory muscles and resistance training for large muscle groups, additionally, 2 patients underwent CMIT (with 60-80% of heart rate reserve) and 2 HIIT (with 40% of HR reserve in the off, for 4 minutes and 80 to 100%, in the on phase, for 2 minutes) on a treadmill for 30 minutes, finally, after 3 months, they were reassessed. RESULTS: There was an increase in effort tolerance, inspiratory and peripheral muscle strength, in addition to an improvement in QoL and a reduction in symptoms in all patients after CPMR, but there were greater increments in patients submitted to HIIT compared to CMIT in the distance covered in meters (case 1 - 156 (23% increment); case 3 - 168 (40%)) versus (case 2 and 4 - 60 meters, with increments of 9% and 14%, respectively) and greater number of steps (case 1 - 28 (23% increase); case 3- 37 (34%)) versus (case 2 ­ 2 (2% increment); case 4 - 15 (21%)). CONCLUSION: CPMR had positive effects, with an increase in functional capacity and improvement in QoL, in addition to a reduction in symptoms during exertion, particularly in patients undergoing HIIT.

Electrical stimulation to regain lower extremity muscle perfusion and endurance in patients with post-acute sequelae of SARS CoV-2: A randomized controlled trial.

Muscle deconditioning and impaired vascular function in the lower extremities (LE) are among the long-term symptoms experienced by COVID-19 patients with a history of severe illness. These symptoms are part of the post-acute sequelae of Sars-CoV-2 (PASC) and currently lack evidence-based treatment. To investigate the efficacy of lower extremity electrical stimulation (E-Stim) in addressing PASC-related muscle deconditioning, we conducted a double-blinded randomized controlled trial. Eighteen (n = 18) patients with LE muscle deconditioning were randomly assigned to either the intervention (IG) or the control (CG) group, resulting in 36 LE being assessed. Both groups received daily 1 h E-Stim on both gastrocnemius muscles for 4 weeks, with the device functional in the IG and nonfunctional in the CG. Changes in plantar oxyhemoglobin (OxyHb) and gastrocnemius muscle endurance (GNMe) in response to 4 weeks of daily 1 h E-Stim were assessed. At each study visit, outcomes were measured at onset (t0 ), 60 min (t60 ), and 10 min after E-Stim therapy (t70 ) by recording ΔOxyHb with near-infrared spectroscopy. ΔGNMe was measured with surface electromyography at two time intervals: 0-5 min (Intv1 ) and: 55-60 min (Intv2 ). Baseline OxyHb decreased in both groups at t60 (IG: p = 0.046; CG: p = 0.026) and t70 (IG = p = 0.021; CG: p = 0.060) from t0 . At 4 weeks, the IG's OxyHb increased from t60 to t70 (p < 0.001), while the CG's decreased (p = 0.003). The IG had higher ΔOxyHb values than the CG at t70 (p = 0.004). Baseline GNMe did not increase in either group from Intv1 to Intv2 . At 4 weeks, the IG's GNMe increased (p = 0.031), whereas the CG did not change. There was a significant association between ΔOxyHb and ΔGNMe (r = 0.628, p = 0.003) at 4 weeks in the IG. In conclusion, E-Stim can improve muscle perfusion and muscle endurance in individuals with PASC experiencing LE muscle deconditioning.

Multispectral optoacoustic tomography to differentiate between lymph node metastases and coronavirus-19 vaccine-associated lymphadenopathy.

INTRODUCTION: Worldwide mass vaccination for COVID-19 started in late 2020. COVID-19 vaccines cause benign hypermetabolic lymphadenopathies. Clinical stratification between vaccine-associated benign lymphadenopathies and malignant lymphadenopathies through ultrasound, MRI or FDG PET-CT is not feasible. This leads to unnecessary lymph node biopsies, excisions and even radical lymph node dissections. Therefore, to avoid unnecessary surgeries, we assessed whether noninvasive multispectral optoacoustic tomography (MSOT) enables a better differentiation between benign and malignant lymphadenopathies. PATIENTS AND METHODS: All patients were vaccinated for COVID-19. We used MSOT to image deoxy- and oxyhaemoglobin levels in lymph nodes of tumour patients to assess metastatic status. MSOT imaging results were compared with standard ultrasound and pathological lymph node analysis. We also evaluated the influences of gender, age and time between vaccination and MSOT measurement of lymph nodes on the measured deoxy- and oxyhaemoglobin levels in patients with reactive lymph node changes. RESULTS: Multispectral optoacoustic tomography was able to identify cancer-free lymph nodes in vivo without a single false negative (33 total lymph nodes), with 100% sensitivity and 50% specificity. A statistically significant higher deoxyhaemoglobin content was detected in patients with tumour manifestations in the lymph node (p = 0.02). There was no statistically significant difference concerning oxyhaemoglobin (p = 0.65). Age, sex and time between vaccination and MSOT measurement had statistically non-significant impact on deoxy- and oxyhaemoglobin levels in patients with reactive lymph nodes. CONCLUSION: Here, we show that MSOT measurement is an advantageous clinical approach to differentiate between vaccine-associated benign lymphadenopathy and malignant lymph node metastases based on the deoxygenation level in lymph nodes.

The oxyhaemoglobin dissociation curve is generally left-shifted in COVID-19 patients at admission to hospital, and this is associated with lower mortality.

Lung damage caused by SARS-Cov-2 virus results in marked arterial hypoxia, accompanied in many cases by hypocapnia. The literature is inconclusive as to whether these conditions induce alteration of the affinity of haemoglobin for oxygen. We studied the oxyhaemoglobin dissociation curves (ODCs) of 517 patients hospitalized with coronavirus disease 2019 (COVID-19) for whom arterial blood gas analysis (BGA) was performed upon hospitalization (i.e., before treatment). With respect to a conventional normal p50 (pO2 at 50% saturation of haemoglobin) of 27 mmHg, 76% had a lower standardized p50 (p50s) and 85% a lower in vivo p50 (p50i). In a 33-patient subgroup with follow-up BGAs after 3, 6, 9, 12, 15 and 18 days' treatment, p50s and p50i exhibited statistically significant differences between baseline values and values recorded at all these time points. The 30-day Kaplan-Meier survival curves of COVID-19 patients stratified by p50i level show a higher probability of survival among patients who at admission had p50 values below 27 mmHg (p = 0.012). Whether the observed alteration of the affinity of haemoglobin for oxygen in COVID-19 patients is a direct or indirect effect of the virus on haemoglobin is unknown.

Impact of wearing a surgical and cloth mask during cycle exercise.

We sought to determine the impact of wearing cloth or surgical masks on the cardiopulmonary responses to moderate-intensity exercise. Twelve subjects (n = 5 females) completed three, 8-min cycling trials while breathing through a non-rebreathing valve (laboratory control), cloth, or surgical mask. Heart rate (HR), oxyhemoglobin saturation (SpO2), breathing frequency, mouth pressure, partial pressure of end-tidal carbon dioxide (PetCO2) and oxygen (PetO2), dyspnea were measured throughout exercise. A subset of n = 6 subjects completed an additional exercise bout without a mask (ecological control). There were no differences in breathing frequency, HR or SpO2 across conditions (all p > 0.05). Compared with the laboratory control (4.7 ± 0.9 cmH2O [mean ± SD]), mouth pressure swings were smaller with the surgical mask (0.9 ± 0.7; p < 0.0001), but similar with the cloth mask (3.6 ± 4.8 cmH2O; p = 0.66). Wearing a cloth mask decreased PetO2 (-3.5 ± 3.7 mm Hg) and increased PetCO2 (+2.0 ± 1.3 mm Hg) relative to the ecological control (both p < 0.05). There were no differences in end-tidal gases between mask conditions and laboratory control (both p > 0.05). Dyspnea was similar between the control conditions and the surgical mask (p > 0.05) but was greater with the cloth mask compared with laboratory (+0.9 ± 1.2) and ecological (+1.5 ± 1.3) control conditions (both p < 0.05). Wearing a mask during short-term moderate-intensity exercise may increase dyspnea but has minimal impact on the cardiopulmonary response. Novelty: Wearing surgical or cloth masks during exercise has no impact on breathing frequency, tidal volume, oxygenation, and heart rate However, there are some changes in inspired and expired gas fractions that are physiologically irrelevant. In young healthy individuals, wearing surgical or cloth masks during submaximal exercise has few physiological consequences.

Oxyhemoglobin concentrations do not support hemoglobinopathy in COVID-19.

Based on computerized modeling studies, it has been postulated that the severe hypoxemia in COVID-19 may result from impaired oxygen carrying capacity on hemoglobin. Standard pulse oximetry may not detect hypoxemia resulting from hemoglobinopathy, therefore hemoglobin co-oximetry is needed to evaluate this divergence. In a clinical data analysis of a multicenter cohort of hospitalized patients with COVID-19, we found a minimal effect, less than 1%, on the correlation between oxyhemoglobin concentration and predicted oxygen saturation in the presence of COVID-19 infection. This effect is unlikely to explain the clinically significant hypoxia in COVID-19 patients.

A left shift in the oxyhaemoglobin dissociation curve in patients with severe coronavirus disease 2019 (COVID-19).

Critically ill patients with coronavirus disease 2019 (COVID-19) present with hypoxaemia and are mechanically ventilated to support gas exchange. We performed a retrospective, observational study of blood gas analyses (n = 3518) obtained from patients with COVID-19 to investigate changes in haemoglobin oxygen (Hb-O2 ) affinity. Calculated oxygen tension at half-saturation (p50 ) was on average (±SD) 3·3 (3·13) mmHg lower than the normal p50 value (23·4 vs. 26·7 mmHg; P < 0·0001). Compared to an unmatched historic control of patients with other causes of severe respiratory failure, patients with COVID-19 had a significantly higher Hb-O2 affinity (mean [SD] p50 23·4 [3·13] vs. 24·6 [5.4] mmHg; P < 0·0001). We hypothesise that, due to the long disease process, acclimatisation to hypoxaemia could play a role.

Non-optimal effectiveness of convalescent plasma transfusion and hydroxychloroquine in treating COVID-19: a case report.

BACKGROUND: Convalescent plasma (CP) transfusion was reported to be effective in treating critically ill patients with COVID-19, and hydroxychloroquine could potently inhibit SARS-CoV-2 in vitro. Herein, we reported a case receiving combination therapy with CP transfusion and hydroxychloroquine for the first time. CASE PRESENTATION: Laboratory findings showed high lactic acid level (2.1 mmol/L) and C-reactive protein (CRP, 48.8 mg/L), and low white blood cell count (1.96 × 109/L) in a 65-year-old Chinese man, who was diagnosed with severe COVID-19. CP was intravenously given twice, and hydroxychloroquine was orally administrated for a week (0.2 g, three times a day). The lactic acid and C-reactive protein levels remained high (2.1 mmol/L and 73.23 mg/L, respectively), while the arterial oxyhemoglobin saturation decreased to 86% with a low oxygenation index (OI, 76 mmHg) on day 4 after CP transfusion. His temperature returned to normal and the OI ascended above 300 on day 11. Moreover, the RNA test remained positive in throat swab, and computed tomography revealed severe pulmonary lesions on day 11 after admission. CONCLUSION: These findings suggested that the effectiveness of combination therapy with CP and hydroxychloroquine may be non-optimal, and specific therapy needs to be explored.