Using cardiorespiratory fitness assessment to identify pathophysiology in long COVID - Best practice approaches.

Cardio-respiratory fitness (CRF) is well-established in the clinical domains as an integrative measure of the body's physiological capability and capacity to transport and utilise oxygen during controlled bouts of physical exertion. Long COVID is associated with >200 different symptoms and is estimated to affect ∼150 million people worldwide. The most widely reported impact is reduced quality of life and functional status due to highly sensitive and cyclical symptoms that manifest and are augmented following exposure to physical, emotional, orthostatic, and cognitive stimuli, more commonly known as post-exertional symptom exacerbation (PESE) which prevents millions from engaging in routine daily activities. The use of cardiopulmonary exercise testing (CPET) is commonplace in the assessment of integrated physiology; CPET will undoubtedly play an integral role in furthering the pathophysiology and mechanistic knowledge that will inform bespoke Long COVID treatment and management strategies. An inherent risk of previous attempts to utilise CPET protocols in patients with chronic disease is that these are compounded by PESE and have induced a worsening of symptoms for patients that can last for days or weeks. To do this effectively and to meet the global need, the complex multi-system pathophysiology of Long COVID must be considered to ensure the design and implementation of research that is both safe for participants and capable of advancing mechanistic understanding.

Impulse oscillometry assessment of respiratory function in pediatric patients with a history of COVID-19.

OBJECTIVE: While coronavirus disease 2019 (COVID-19) is generally considered to exhibit a less severe clinical course in children than in adults, studies have demonstrated that respiratory symptoms can endure for more than 3 months following infection in at least one-third of pediatric cases. The present study evaluates the respiratory functions of children aged 3-15 years within 3-6 months of their recovery from COVID-19 using impulse oscillometry (IOS) and compares them with the values of healthy children. METHODS: Included in this prospective cross-sectional study were 63 patients (patient group) aged 3-15 years who contracted COVID-19 between December 2021 and May 2022, as well as 57 healthy children as a control group, matched for age and sex. The demographic, clinical, and laboratory data of the patients were recorded, and respiratory function was assessed based on airway resistance (zR5, zR20, R5-20) and reactance (zX5, zX20, reactance area [AX], resonant frequency [Fres]) using an IOS device. RESULTS: There were no significant differences in the age, weight, height, and body weight z score values of the two groups (p > .05). While the zR5 and R5-20 levels of the patient group were higher (p = .008 and p < .001, respectively) than those of the controls, the zR20, AX, and Fres values did not differ significantly between the groups (p > .05). The parameters indicating the reactance, including zX5 and zX20, were significantly lower in the patient group than in the control group (p = .028 and p < .001, respectively). CONCLUSION: Total and peripheral airway resistances were found to be elevated in children who had recovered from COVID-19 in the preceding 3-6 months.

Assessment of thermal and temporal stability of SARS-CoV-2 samples using real-time qRT-PCR.

BACKGROUND: As per the guidelines of the Indian Council of Medical Research, nasopharyngeal and oropharyngeal swabs in viral transport medium (VTM) are to be stored at 4 °C for less than 5 days and for more than 5 days at -70 °C. Samples are not transported or stored as per prescribed conditions because of the limitations, resulting in an apprehensive diagnosis. The aim of the study was to test the stability of the SARS-CoV-2 sample stored in VTM at different temperatures. METHODS: In this study, the stability of 21 positive and 9 negative samples for SARS-CoV-2 was evaluated in commercial VTM at different temperatures (-80 °C, -20 °C, 4 °C, and 25 to 30 °C). Stability was checked for up to 50 days in the above storage conditions at different intervals. PathoDetect™ and Hi-PCR® kits were used for the detection of the four genes of SARS-CoV-2. The Cycle Threshold (Ct) value for determining the positivity of samples for PathoDetect™ was < 40 and for Hi-PCR® was < 38. RESULTS: The SARS-CoV-2 confirmatory genes (RdRp and E genes) and the internal housekeeping gene remained detectable even on the 50th day of the study. The Ct of the RdRp and E genes were found to increase with storage duration, but all positive samples remained positive till the end of the study, or the Ct value remained below the cut-off level. The negative samples gave consistent results until the end of the study. When the differences in Ct values were compared between the days in a set of experiments, they were not significantly different except in a few samples. CONCLUSION: The SARS-CoV-2 genetic materials in commercial VTM were stable at room temperature to -80 °C for 50 days.

Sexual dimorphism in COVID-19: potential clinical and public health implications.

Current evidence suggests that severity and mortality of COVID-19 is higher in men than in women, whereas women might be at increased risk of COVID-19 reinfection and development of long COVID. Differences between sexes have been observed in other infectious diseases and in the response to vaccines. Sex-specific expression patterns of proteins mediating virus binding and entry, and divergent reactions of the immune and endocrine system, in particular the hypothalamic-pituitary-adrenal axis, in response to acute stress might explain the higher severity of COVID-19 in men. In this Personal View, we discuss how sex hormones, comorbidities, and the sex chromosome complement influence these mechanisms in the context of COVID-19. Due to its role in the severity and progression of SARS-CoV-2 infections, we argue that sexual dimorphism has potential implications for disease treatment, public health measures, and follow-up of patients predisposed to the development of long COVID. We suggest that sex differences could be considered in future pandemic surveillance and treatment of patients with COVID-19 to help to achieve better disease stratification and improved outcomes.

Early assessment of the clinical severity of the SARS-CoV-2 omicron variant in South Africa: a data linkage study.

BACKGROUND: The SARS-CoV-2 omicron variant of concern was identified in South Africa in November, 2021, and was associated with an increase in COVID-19 cases. We aimed to assess the clinical severity of infections with the omicron variant using S gene target failure (SGTF) on the Thermo Fisher Scientific TaqPath COVID-19 PCR test as a proxy. METHODS: We did data linkages for national, South African COVID-19 case data, SARS-CoV-2 laboratory test data, SARS-CoV-2 genome data, and COVID-19 hospital admissions data. For individuals diagnosed with COVID-19 via TaqPath PCR tests, infections were designated as either SGTF or non-SGTF. The delta variant was identified by genome sequencing. Using multivariable logistic regression models, we assessed disease severity and hospitalisations by comparing individuals with SGTF versus non-SGTF infections diagnosed between Oct 1 and Nov 30, 2021, and we further assessed disease severity by comparing SGTF-infected individuals diagnosed between Oct 1 and Nov 30, 2021, with delta variant-infected individuals diagnosed between April 1 and Nov 9, 2021. FINDINGS: From Oct 1 (week 39), 2021, to Dec 6 (week 49), 2021, 161 328 cases of COVID-19 were reported in South Africa. 38 282 people were diagnosed via TaqPath PCR tests and 29 721 SGTF infections and 1412 non-SGTF infections were identified. The proportion of SGTF infections increased from two (3·2%) of 63 in week 39 to 21 978 (97·9%) of 22 455 in week 48. After controlling for factors associated with hospitalisation, individuals with SGTF infections had significantly lower odds of admission than did those with non-SGTF infections (256 [2·4%] of 10 547 vs 121 [12·8%] of 948; adjusted odds ratio [aOR] 0·2, 95% CI 0·1-0·3). After controlling for factors associated with disease severity, the odds of severe disease were similar between hospitalised individuals with SGTF versus non-SGTF infections (42 [21%] of 204 vs 45 [40%] of 113; aOR 0·7, 95% CI 0·3-1·4). Compared with individuals with earlier delta variant infections, SGTF-infected individuals had a significantly lower odds of severe disease (496 [62·5%] of 793 vs 57 [23·4%] of 244; aOR 0·3, 95% CI 0·2-0·5), after controlling for factors associated with disease severity. INTERPRETATION: Our early analyses suggest a significantly reduced odds of hospitalisation among individuals with SGTF versus non-SGTF infections diagnosed during the same time period. SGTF-infected individuals had a significantly reduced odds of severe disease compared with individuals infected earlier with the delta variant. Some of this reduced severity is probably a result of previous immunity. FUNDING: The South African Medical Research Council, the South African National Department of Health, US Centers for Disease Control and Prevention, the African Society of Laboratory Medicine, Africa Centers for Disease Control and Prevention, the Bill & Melinda Gates Foundation, the Wellcome Trust, and the Fleming Fund.

Post-acute COVID-19 Syndrome Negatively Impacts Physical Function, Cognitive Function, Health-Related Quality of Life, and Participation.

OBJECTIVE: This report describes persistent symptoms associated with post-acute COVID-19 syndrome (PACS) and the impact of these symptoms on physical function, cognitive function, health-related quality of life, and participation. DESIGN: This study used a cross-sectional observational study design. Patients attending Mount Sinai's post-acute COVID-19 syndrome clinic completed surveys containing patient-reported outcomes. RESULTS: A total of 156 patients completed the survey, at a median (range) time of 351 days (82-457 days) after COVID-19 infection. All patients were prevaccination. The most common persistent symptoms reported were fatigue (n = 128, 82%), brain fog (n = 105, 67%), and headache (n = 94, 60%). The most common triggers of symptom exacerbation were physical exertion (n = 134, 86%), stress (n = 107, 69%), and dehydration (n = 77, 49%). Increased levels of fatigue (Fatigue Severity Scale) and dyspnea (Medical Research Council) were reported, alongside reductions in levels of regularly completed physical activity. Ninety-eight patients (63%) scored for at least mild cognitive impairment (Neuro-Qol), and the domain of the EuroQol: 5 dimension, 5 level most impacted was Self-care, Anxiety/Depression and Usual Activities. CONCLUSIONS: Persistent symptoms associated with post-acute COVID-19 syndrome seem to impact physical and cognitive function, health-related quality of life, and participation in society. More research is needed to further clarify the relationship between COVID-19 infection and post-acute COVID-19 syndrome symptoms, the underlying mechanisms, and treatment options.

IoT-Based Smart Health Monitoring System for COVID-19 Patients.

During the ongoing COVID-19 pandemic, Internet of Things- (IoT-) based health monitoring systems are potentially immensely beneficial for COVID-19 patients. This study presents an IoT-based system that is a real-time health monitoring system utilizing the measured values of body temperature, pulse rate, and oxygen saturation of the patients, which are the most important measurements required for critical care. This system has a liquid crystal display (LCD) that shows the measured temperature, pulse rate, and oxygen saturation level and can be easily synchronized with a mobile application for instant access. The proposed IoT-based method uses an Arduino Uno-based system, and it was tested and verified for five human test subjects. The results obtained from the system were promising: the data acquired from the system are stored very quickly. The results obtained from the system were found to be accurate when compared to other commercially available devices. IoT-based tools may potentially be valuable during the COVID-19 pandemic for saving people's lives.

Assessment of renal function among covid-19 patients admitted to the intensive care unit.

Severe acute respiratory viral infections are frequently associated with multiple organ failure, including acute kidney damage. The present study aimed to investigate the associated influence of COVID-19 on renal function in patients admitted to the intensive care unit in Asir region, Saudi Arabia. Thirty patients infected with COVID-19 who were referred to the intensive care unit during November and October 2020 at Asir central hospital, Asir region, Saudi Arabia were recruited. The age of patients ranged between 30 and 90 years old. Renal function tests exhibited dramatic changes in the renal biomarkers in patients with COVID-19. Blood urea levels in COVID-19 patients were significantly higher than in the control group. In addition, significantly lower albumin levels with abnormally decreased total protein levels were found in COVID-19 patients. Among the different electrolytes analyzed, a significantly lower calcium level was observed in COVID-19 patients' groups than in the controls. Renal function tests for COVID-19-infected ICU patients revealed significant changes, indicating the major impact of COVID-19 on kidney function. Monitoring renal function tests may assist in the early prognosis of COVID-19 patients. It is, therefore, crucial to increase the understanding of renal function tests in COVID-19 patients who were admitted to the hospital before their condition deteriorated.

Small airway dysfunction on impulse oscillometry and pathological signs on lung ultrasound are frequent in post-COVID-19 patients with persistent respiratory symptoms.

BACKGROUND: Thousands of people worldwide are suffering the consequences of coronavirus disease-2019 (COVID-19), and impulse oscillometry (IOS) and lung ultrasound (LUS) might be important tools for the follow-up of this population. Our objective was to prospectively evaluate abnormalities detected using these two methods in a cohort of COVID-19 survivors with respiratory symptoms. METHODS: In this follow-up study, 59 patients underwent clinical evaluations, spirometry, IOS and LUS in the 2nd (M1) and 5th (M2) months after diagnostic confirmation of COVID-19 by real-time reverse transcriptase-polymerase chain reaction. Aeration scores were obtained from the LUS exams based on the following findings: B-lines >2, coalescent B-lines, and subpleural consolidations. RESULTS: Fifty-nine (100%) participants had cough and/or dyspnea at M1, which decreased to 38 (64.4%) at M2 (p = 0.0001). Spirometry was abnormal in 26 (44.1%) and 20 (33.9%) participants at M1 and M2, respectively, although without statistical significance (p = 0.10). Normal examination, restrictive patterns, and obstructive patterns were observed in 33 (55.9%), 18 (30.5%), and 8 (13.6%) participants, respectively, at M1 and in 39 (66.1%), 13 (22%), and 7 (11.9%) participants at M2 (p = 0.14). Regarding IOS, considering changes in resistive and reactive parameters, abnormal exams were detected in 52 (88.1%) and 42 (71.2%) participants at M1 and M2, respectively (p = 0.002). Heterogeneity of resistance between 4 and 20 Hz >20% was observed in 38 (64.4%) and 33 (55.9%) participants at M1 and M2, respectively (p = 0.30). Abnormal LUS was observed in 46 (78%) and 36 (61%) participants at M1 and M2, respectively (p = 0.002), with a reduction in aeration scores between M1 and M2 [5 (2-8) vs. 3 (0-6) points, p<0.0001]. CONCLUSIONS: IOS and LUS abnormalities are frequent in the first 5 months post-COVID-19 infection; however, when prospectively evaluated, significant improvement is evident in the parameters measured by these two methods.

Assessment of clinical outcomes in renal transplant recipients with COVID-19.

The coronavirus disease 2019 (COVID-19) has affected more than a hundred million individuals and caused more than three million deaths worldwide. Specific risk groups were defined for increased risk of mortality and morbidity in COVID-19, and renal transplant recipients are at a significantly increased risk regarding outcomes due to their immunosuppressed conditions. This study evaluated the general characteristics of kidney transplant recipients with COVID-19 infection. Among 1257 transplant cases, 56 had COVID-19 infection, and 23 (41%) were hospitalized during the 9-month study period. Among all COVID-19 cases, 58% were male with a mean age of 45.5 (±13.2, 19-71) years, and the most frequent comorbidities were hypertension (70.9%) and diabetes (23.6%). Hospitalized patients were older (p = 0.03) and had higher rates of hypertension (p = 0.008), diabetes (p = 0.002), and ischemic heart disease (p = 0.03). Therapeutic management included antimetabolite withdrawal and prednisolone increase in 71%, calcineurin inhibitor withdrawal in 8% and decrease in 58%, hydroxychloroquine in 17%, tocilizumab in 3%, and antivirals in 67% of patients. Acute kidney injury and respiratory failure developed in 34% and 85%, respectively. The mortality rate was 23%. These results emphasized that the COVID-19 infection in renal transplant recipients significantly increases the risk of morbidity and mortality. Therefore, these patients should be intervened earlier and monitored closely to prevent poor outcomes.

Respiratory function assessment at the time of a new respiratory virus pandemic.

We must be aware that new respiratory virus pandemic can happen frequently. Standard lung function tests should keep their crucial role to assist the clinicians in the decision-making process, but they are at risk for the spread of infection because of the generated droplets. We used opto-electronic plethysmography to investigate the post-COVID-19 syndrome on 12 patients after ICU. We found normal ventilatory pattern at rest, a restrictive pattern located in the ribcage during vital capacity and surgical mask to significantly increase minute ventilation. The attention on unconventional respiratory function tests should be sponsored for the important information they can provide.

An in vitro visual study of fugitive aerosols released during aerosol therapy to an invasively ventilated simulated patient.

COVID-19 can cause serious respiratory complications resulting in the need for invasive ventilatory support and concurrent aerosol therapy. Aerosol therapy is considered a high risk procedure for the transmission of patient derived infectious aerosol droplets. Critical-care workers are considered to be at a high risk of inhaling such infectious droplets. The objective of this work was to use noninvasive optical methods to visualize the potential release of aerosol droplets during aerosol therapy in a model of an invasively ventilated adult patient. The noninvasive Schlieren imaging technique was used to visualize the movement of air and aerosol. Three different aerosol delivery devices: (i) a pressurized metered dose inhaler (pMDI), (ii) a compressed air driven jet nebulizer (JN), and (iii) a vibrating mesh nebulizer (VMN), were used to deliver an aerosolized therapeutic at two different positions: (i) on the inspiratory limb at the wye and (ii) on the patient side of the wye, between the wye and endotracheal tube, to a simulated intubated adult patient. Irrespective of position, there was a significant release of air and aerosol from the ventilator circuit during aerosol delivery with the pMDI and the compressed air driven JN. There was no such release when aerosol therapy was delivered with a closed-circuit VMN. Selection of aerosol delivery device is a major determining factor in the release of infectious patient derived bioaerosol from an invasively mechanically ventilated patient receiving aerosol therapy.

Modeling the survival times of the COVID-19 patients with a new statistical model: A case study from China.

Over the past few months, the spread of the current COVID-19 epidemic has caused tremendous damage worldwide, and unstable many countries economically. Detailed scientific analysis of this event is currently underway to come. However, it is very important to have the right facts and figures to take all possible actions that are needed to avoid COVID-19. In the practice and application of big data sciences, it is always of interest to provide the best description of the data under consideration. The recent studies have shown the potential of statistical distributions in modeling data in applied sciences, especially in medical science. In this article, we continue to carry this area of research, and introduce a new statistical model called the arcsine modified Weibull distribution. The proposed model is introduced using the modified Weibull distribution with the arcsine-X approach which is based on the trigonometric strategy. The maximum likelihood estimators of the parameters of the new model are obtained and the performance these estimators are assessed by conducting a Monte Carlo simulation study. Finally, the effectiveness and utility of the arcsine modified Weibull distribution are demonstrated by modeling COVID-19 patients data. The data set represents the survival times of fifty-three patients taken from a hospital in China. The practical application shows that the proposed model out-classed the competitive models and can be chosen as a good candidate distribution for modeling COVID-19, and other related data sets.