One-Year Mental and Physical Health Assessment in Survivors After ECMO for COVID-19-related ARDS.

RATIONAL: Long-term outcomes of patients with COVID-19-related acute respiratory distress syndrome (ARDS) treated with extracorporeal membrane oxygenation (ECMO) are unknown. METHODS: Multicenter, prospective study in patients who received ECMO for COVID-19 ARDS from March to June 2020 and survived hospital discharge. Physical examination, pulmonary function tests, anxiety, depression, post-traumatic stress disorders (PTSD), and quality of life (QoL) were assessed at 6 and 12 months after ECMO onset. RESULTS: Of 80 eligible patients, 62 were enrolled in 7 French Intensive Care Units (ICU). ECMO and invasive mechanical ventilation duration were 18 (11-25) and 36 (27-62) days, respectively. All were alive but only 19/50 (38%) returned to work and 13/42 (31%) had recovered a normal sex drive at one year. Pulmonary function tests were almost normal at 6 months except for diffusing capacity for carbon monoxide which was still impaired at 12 months. Mental health, role-emotional, and role-physical were the most impaired domain compared to non-COVID ECMO patients. One year after ICU admission, 19/43 (44%) patients had significant anxiety, 18/43 (42%) had depression symptoms and 21/50 (42%) were at risk for PTSD. CONCLUSIONS: Despite the partial recovery of the lung function tests at one year, the physical and psychological function of this population remains impaired. Based on the comparison with long-term follow-up of non-COVID ECMO patients, poor mental and physical health may be more related to COVID-19 than to ECMO in itself, although this needs confirmation This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Comparative outcomes of extracorporeal membrane oxygenation for COVID-19 delivered in experienced European centres during successive SARS-CoV-2 variant outbreaks (ECMO-SURGES): an international, multicentre, retrospective cohort study.

BACKGROUND: To inform future research and practice, we aimed to investigate the outcomes of patients who received extracorporeal membrane oxygenation (ECMO) for acute respiratory distress syndrome (ARDS) due to different variants of SARS-CoV-2. METHODS: This retrospective study included consecutive adult patients with laboratory-confirmed SARS-CoV-2 infection who received ECMO for ARDS in 21 experienced ECMO centres in eight European countries (Austria, Belgium, England, France, Germany, Italy, Portugal, and Spain) between Jan 1, 2020, and Sept 30, 2021. We collected data on patient characteristics, clinical status, and management before and after the initiation of ECMO. Participants were grouped according to SARS-CoV-2 variant (wild type, alpha, delta, or other) and period of the pandemic (first [Jan 1-June 30] and second [July 1-Dec 31] semesters of 2020, and first [Jan 1-June 30] and second [July 1-Sept 30] semesters of 2021). Descriptive statistics and Kaplan-Meier survival curves were used to analyse evolving characteristics, management, and patient outcomes over the first 2 years of the pandemic, and independent risk factors of mortality were determined using multivariable Cox regression models. The primary outcome was mortality 90 days after the initiation of ECMO, with follow-up to Dec 30, 2021. FINDINGS: ECMO was initiated in 1345 patients. Patient characteristics and management were similar for the groups of patients infected with different variants, except that those with the delta variant had a younger median age and less hypertension and diabetes. 90-day mortality was 42% (569 of 1345 patients died) overall, and 43% (297/686) in patients infected with wild-type SARS-CoV-2, 39% (152/391) in those with the alpha variant, 40% (78/195) in those with the delta variant, and 58% (42/73) in patients infected with other variants (mainly beta and gamma). Mortality was 10% higher (50%) in the second semester of 2020, when the wild-type variant was still prevailing, than in other semesters (40%). Independent predictors of mortality were age, immunocompromised status, a longer time from intensive care unit admission to intubation, need for renal replacement therapy, and higher Sequential Organ Failure Assessment haemodynamic component score, partial pressure of arterial carbon dioxide, and lactate concentration before ECMO. After adjusting for these variables, mortality was significantly higher with the delta variant than with the other variants, the wild-type strain being the reference. INTERPRETATION: Although crude mortality did not differ between variants, adjusted risk of death was highest for patients treated with ECMO infected with the delta variant of SARS-CoV-2. The higher virulence and poorer outcomes associated with the delta strain might relate to higher viral load and increased inflammatory response syndrome in infected patients, reinforcing the need for a higher rate of vaccination in the population and updated selection criteria for ECMO, should a new and highly virulent strain of SARS-CoV-2 emerge in the future. Mortality was noticeably lower than in other large, multicentre series of patients who received ECMO for COVID-19, highlighting the need to concentrate resources at experienced centres. FUNDING: None.

Bleeding and thrombotic events in patients with severe COVID-19 supported with extracorporeal membrane oxygenation: a nationwide cohort study.

PURPOSE: To describe bleeding and thrombotic events and their risk factors in patients receiving extracorporeal membrane oxygenation (ECMO) for severe coronavirus disease 2019 (COVID-19) and to evaluate their impact on in-hospital mortality. METHODS: The ECMOSARS registry included COVID-19 patients supported by ECMO in France. We analyzed all patients included up to March 31, 2022 without missing data regarding bleeding and thrombotic events. The association of bleeding and thrombotic events with in-hospital mortality and pre-ECMO variables was assessed using multivariable logistic regression models. RESULTS: Among 620 patients supported by ECMO, 29% had only bleeding events, 16% only thrombotic events and 20% both bleeding and thrombosis. Cannulation site (18% of patients), ear nose and throat (12%), pulmonary bleeding (9%) and intracranial hemorrhage (8%) were the most frequent bleeding types. Device-related thrombosis and pulmonary embolism/thrombosis accounted for most of thrombotic events. In-hospital mortality was 55.7%. Bleeding events were associated with in-hospital mortality (adjusted odds ratio (adjOR) = 2.91[1.94-4.4]) but not thrombotic events (adjOR = 1.02[0.68-1.53]). Intracranial hemorrhage was strongly associated with in-hospital mortality (adjOR = 13.5[4.4-41.5]). Ventilation duration before ECMO ≥ 7 days and length of ECMO support were associated with bleeding. Thrombosis-associated factors were fibrinogen ≥ 6 g/L and length of ECMO support. CONCLUSIONS: In a nationwide cohort of COVID-19 patients supported by ECMO, bleeding incidence was high and associated with mortality. Intracranial hemorrhage incidence was higher than reported for non-COVID patients and carried the highest risk of death. Thrombotic events were less frequent and not associated with mortality. Length of ECMO support was associated with a higher risk of both bleeding and thrombosis, supporting the development of strategies to minimize ECMO duration.

Time-Controlled Adaptive Ventilation Does Not Induce Hemodynamic Impairment in a Swine ARDS Model.

Background: The current standard of care during severe acute respiratory distress syndrome (ARDS) is based on low tidal volume (VT) ventilation, at 6 mL/kg of predicted body weight. The time-controlled adaptive ventilation (TCAV) is an alternative strategy, based on specific settings of the airway pressure release ventilation (APRV) mode. Briefly, TCAV reduces lung injury, including: (1) an improvement in alveolar recruitment and homogeneity; (2) reduction in alveolar and alveolar duct micro-strain and stress-risers. TCAV can result in higher intra-thoracic pressures and thus impair hemodynamics resulting from heart-lung interactions. The objective of our study was to compare hemodynamics between TCAV and conventional protective ventilation in a porcine ARDS model. Methods: In 10 pigs (63-73 kg), lung injury was induced by repeated bronchial saline lavages followed by 2 h of injurious ventilation. The animals were then randomized into two groups: (1) Conventional protective ventilation with a VT of 6 mL/kg and PEEP adjusted to a plateau pressure set between 28 and 30 cmH2O; (2) TCAV group with P-high set between 27 and 29 cmH2O, P-low at 0 cmH2O, T-low adjusted to terminate at 75% of the expiratory flow peak, and T-high at 3-4 s, with I:E > 6:1. Results: Both lung elastance and PaO2:FiO2 were consistent with severe ARDS after 2 h of injurious mechanical ventilation. There was no significant difference in systemic arterial blood pressure, pulmonary blood pressure or cardiac output between Conventional protective ventilation and TCAV. Levels of total PEEP were significantly higher in the TCAV group (p < 0.05). Driving pressure and lung elastance were significantly lower in the TCAV group (p < 0.05). Conclusion: No hemodynamic adverse events were observed in the TCAV group compared as to the standard protective ventilation group in this swine ARDS model, and TCAV appeared to be beneficial to the respiratory system.

Impaired Pharmacokinetics of Amiodarone under Veno-Venous Extracorporeal Membrane Oxygenation: From Bench to Bedside.

BACKGROUND: Adjusting drug therapy under veno-venous extracorporeal membrane oxygenation (VV ECMO) is challenging. Although impaired pharmacokinetics (PK) under VV ECMO have been reported for sedative drugs and antibiotics, data about amiodarone are lacking. We evaluated the pharmacokinetics of amiodarone under VV ECMO both in vitro and in vivo. METHODS: In vitro: Amiodarone concentration decays were compared between closed-loop ECMO and control stirring containers over a 24 h period. In vivo: Potassium-induced cardiac arrest in 10 pigs with ARDS, assigned to either control or VV ECMO groups, was treated with 300 mg amiodarone injection under continuous cardiopulmonary resuscitation. Pharmacokinetic parameters Cmax, Tmax AUC and F were determined from both direct amiodarone plasma concentrations observation and non-linear mixed effects modeling estimation. RESULTS: An in vitro study revealed a rapid and significant decrease in amiodarone concentrations in the closed-loop ECMO circuitry whereas it remained stable in control experiment. In vivo study revealed a 32% decrease in the AUC and a significant 42% drop of Cmax in the VV ECMO group as compared to controls. No difference in Tmax was observed. VV ECMO significantly modified both central distribution volume and amiodarone clearance. Monte Carlo simulations predicted that a 600 mg bolus of amiodarone under VV ECMO would achieve the amiodarone bioavailability observed in the control group. CONCLUSIONS: This is the first study to report decreased amiodarone bioavailability under VV ECMO. Higher doses of amiodarone should be considered for effective amiodarone exposure under VV ECMO.

Extracorporeal Membrane Oxygenation for Respiratory Failure Related to COVID-19: A Nationwide Cohort Study.

BACKGROUND: Despite expanding use, knowledge on extracorporeal membrane oxygenation support during the COVID-19 pandemic remains limited. The objective was to report characteristics, management, and outcomes of patients receiving extracorporeal membrane oxygenation with a diagnosis of COVID-19 in France and to identify pre-extracorporeal membrane oxygenation factors associated with in-hospital mortality. A hypothesis of similar mortality rates and risk factors for COVID-19 and non-COVID-19 patients on venovenous extracorporeal membrane oxygenation was made. METHODS: The Extracorporeal Membrane Oxygenation for Respiratory Failure and/or Heart failure related to Severe Acute Respiratory Syndrome-Coronavirus 2 (ECMOSARS) registry included COVID-19 patients supported by extracorporeal membrane oxygenation in France. This study analyzed patients included in this registry up to October 25, 2020, and supported by venovenous extracorporeal membrane oxygenation for respiratory failure with a minimum follow-up of 28 days after cannulation. The primary outcome was in-hospital mortality. Risk factors for in-hospital mortality were analyzed. RESULTS: Among 494 extracorporeal membrane oxygenation patients included in the registry, 429 were initially supported by venovenous extracorporeal membrane oxygenation and followed for at least 28 days. The median (interquartile range) age was 54 yr (46 to 60 yr), and 338 of 429 (79%) were men. Management before extracorporeal membrane oxygenation cannulation included prone positioning for 411 of 429 (96%), neuromuscular blockage for 419 of 427 (98%), and NO for 161 of 401 (40%). A total of 192 of 429 (45%) patients were cannulated by a mobile extracorporeal membrane oxygenation unit. In-hospital mortality was 219 of 429 (51%), with a median follow-up of 49 days (33 to 70 days). Among pre-extracorporeal membrane oxygenation modifiable exposure variables, neuromuscular blockage use (hazard ratio, 0.286; 95% CI, 0.101 to 0.81) and duration of ventilation (more than 7 days compared to less than 2 days; hazard ratio, 1.74; 95% CI, 1.07 to 2.83) were independently associated with in-hospital mortality. Both age (per 10-yr increase; hazard ratio, 1.27; 95% CI, 1.07 to 1.50) and total bilirubin at cannulation (6.0 mg/dl or more compared to less than 1.2 mg/dl; hazard ratio, 2.65; 95% CI, 1.09 to 6.5) were confounders significantly associated with in-hospital mortality. CONCLUSIONS: In-hospital mortality was higher than recently reported, but nearly half of the patients survived. A high proportion of patients were cannulated by a mobile extracorporeal membrane oxygenation unit. Several factors associated with mortality were identified. Venovenous extracorporeal membrane oxygenation support should be considered early within the first week of mechanical ventilation initiation.

Infection related catheter complications in patients undergoing prone positioning for acute respiratory distress syndrome: an exposed/unexposed study.

BACKGROUND: Prone positioning (PP) is a standard of care for patients with moderate-severe acute respiratory distress syndrome (ARDS). While adverse events associated with PP are well-documented in the literature, research examining the effect of PP on the risk of infectious complications of intravascular catheters is lacking. METHOD: All consecutive ARDS patients treated with PP were recruited retrospectively over a two-year period and formed the exposed group. Intensive care unit (ICU) patients during the same period without ARDS for whom PP was not conducted but who had an equivalent disease severity were matched 1:1 to the exposed group based on age, sex, centre, length of ICU stay and SAPS II (unexposed group). Infection-related catheter complications were defined by a composite criterion, including catheter tip colonization or intravascular catheter-related infection. RESULTS: A total of 101 exposed patients were included in the study. Most had direct ARDS (pneumonia). The median [Q1-Q3] PP session number was 2 [1-4]. These patients were matched with 101 unexposed patients. The mortality rates of the exposed and unexposed groups were 31 and 30%, respectively. The incidence of the composite criterion was 14.2/1000 in the exposed group compared with 8.2/1000 days in the control group (p = 0.09). Multivariate analysis identified PP as a factor related to catheter colonization or infection (p = 0.04). CONCLUSION: Our data suggest that PP is associated with a higher risk of CVC infectious complications.

Obesity and mortality in critically ill COVID-19 patients with respiratory failure.

BACKGROUND: Patients with obesity are at increased risk of severe COVID-19, requiring mechanical ventilation due to acute respiratory failure. However, conflicting data are obtained for intensive care unit (ICU) mortality. OBJECTIVE: To analyze the relationship between obesity and in-hospital mortality of ICU patients with COVID-19. SUBJECTS/METHODS: Patients admitted to the ICU for COVID-19 acute respiratory distress syndrome (ARDS) were included retrospectively. The following data were collected: comorbidities, body mass index (BMI), the severity of ARDS assessed with PaO2/FiO2 (P/F) ratios, disease severity measured by the Simplified Acute Physiology Score II (SAPS II), management and outcomes. RESULTS: For a total of 222 patients, there were 34 patients (15.3%) with normal BMI, 92 patients (41.4%) who were overweight, 80 patients (36%) with moderate obesity (BMI:30-39.9 kg/m2), and 16 patients (7.2%) with severe obesity (BMI ≥ 40 kg/m2). Overall in-hospital mortality was 20.3%. Patients with moderate obesity had a lower mortality rate (13.8%) than patients with normal weight, overweight or severe obesity (17.6%, 21.7%, and 50%, respectively; P = 0.011. Logistic regression showed that patients with a BMI ≤ 29 kg/m2 (odds ratio [OR] 3.64, 95% CI 1.38-9.60) and those with a BMI > 39 kg/m2 (OR 10.04, 95% CI 2.45-41.09) had a higher risk of mortality than those with a BMI from 29 to 39 kg/m2. The number of comorbidities (≥2), SAPS II score, and P/F < 100 mmHg were also independent predictors for in-hospital mortality. CONCLUSIONS: COVID-19 patients admitted to the ICU with moderate obesity had a lower risk of death than the other patients, suggesting a possible obesity paradox.

Mental health and stress among ICU healthcare professionals in France according to intensity of the COVID-19 epidemic.

BACKGROUND: We investigated the impact of the COVID-19 crisis on mental health of professionals working in the intensive care unit (ICU) according to the intensity of the epidemic in France. METHODS: This cross-sectional survey was conducted in 77 French hospitals from April 22 to May 13 2020. All ICU frontline healthcare workers were eligible. The primary endpoint was the mental health, assessed using the 12-item General Health Questionnaire. Sources of stress during the crisis were assessed using the Perceived Stressors in Intensive Care Units (PS-ICU) scale. Epidemic intensity was defined as high or low for each region based on publicly available data from Santé Publique France. Effects were assessed using linear mixed models, moderation and mediation analyses. RESULTS: In total, 2643 health professionals participated; 64.36% in high-intensity zones. Professionals in areas with greater epidemic intensity were at higher risk of mental health issues (p < 0.001), and higher levels of overall perceived stress (p < 0.001), compared to low-intensity zones. Factors associated with higher overall perceived stress were female sex (B = 0.13; 95% confidence interval [CI] = 0.08-0.17), having a relative at risk of COVID-19 (B = 0.14; 95%-CI = 0.09-0.18) and working in high-intensity zones (B = 0.11; 95%-CI = 0.02-0.20). Perceived stress mediated the impact of the crisis context on mental health (B = 0.23, 95%-CI = 0.05, 0.41) and the impact of stress on mental health was moderated by positive thinking, b = - 0.32, 95% CI = - 0.54, - 0.11. CONCLUSION: COVID-19 negatively impacted the mental health of ICU professionals. Professionals working in zones where the epidemic was of high intensity were significantly more affected, with higher levels of perceived stress. This study is supported by a grant from the French Ministry of Health (PHRC-COVID 2020).

The Fundamentals of Respiratory Physiology to Manage the COVID-19 Pandemic: An Overview.

The growing coronavirus disease (COVID-19) crisis has stressed worldwide healthcare systems probably as never before, requiring a tremendous increase of the capacity of intensive care units to handle the sharp rise of patients in critical situation. Since the dominant respiratory feature of COVID-19 is worsening arterial hypoxemia, eventually leading to acute respiratory distress syndrome (ARDS) promptly needing mechanical ventilation, a systematic recourse to intubation of every hypoxemic patient may be difficult to sustain in such peculiar context and may not be deemed appropriate for all patients. Then, it is essential that caregivers have a solid knowledge of physiological principles to properly interpret arterial oxygenation, to intubate at the satisfactory moment, to adequately manage mechanical ventilation, and, finally, to initiate ventilator weaning, as safely and as expeditiously as possible, in order to make it available for the next patient. Through the expected mechanisms of COVID-19-induced hypoxemia, as well as the notion of silent hypoxemia often evoked in COVID-19 lung injury and its potential parallelism with high altitude pulmonary edema, from the description of hemoglobin oxygen affinity in patients with severe COVID-19 to the interest of the prone positioning in order to treat severe ARDS patients, this review aims to help caregivers from any specialty to handle respiratory support following recent knowledge in the pathophysiology of respiratory SARS-CoV-2 infection.

Six-Month Survival After Extracorporeal Membrane Oxygenation for Severe COVID-19.

OBJECTIVES: The authors evaluated the outcome of adult patients with coronavirus disease 2019 (COVID-19)-related acute respiratory distress syndrome (ARDS) requiring the use of extracorporeal membrane oxygenation (ECMO). DESIGN: Multicenter retrospective, observational study. SETTING: Ten tertiary referral university and community hospitals. PARTICIPANTS: Patients with confirmed severe COVID-19-related ARDS. INTERVENTIONS: Venovenous or venoarterial ECMO. MEASUREMENTS AND MAIN RESULTS: One hundred thirty-two patients (mean age 51.1 ± 9.7 years, female 17.4%) were treated with ECMO for confirmed severe COVID-19-related ARDS. Before ECMO, the mean Sequential Organ Failure Assessment score was 10.1 ± 4.4, mean pH was 7.23 ± 0.09, and mean PaO2/fraction of inspired oxygen ratio was 77 ± 50 mmHg. Venovenous ECMO was adopted in 122 patients (92.4%) and venoarterial ECMO in ten patients (7.6%) (mean duration, 14.6 ± 11.0 days). Sixty-three (47.7%) patients died on ECMO and 70 (53.0%) during the index hospitalization. Six-month all-cause mortality was 53.0%. Advanced age (per year, hazard ratio [HR] 1.026, 95% CI 1.000-1-052) and low arterial pH (per unit, HR 0.006, 95% CI 0.000-0.083) before ECMO were the only baseline variables associated with increased risk of six-month mortality. CONCLUSIONS: The present findings suggested that about half of adult patients with severe COVID-19-related ARDS can be managed successfully with ECMO with sustained results at six months. Decreased arterial pH before ECMO was associated significantly with early mortality. Therefore, the authors hypothesized that initiation of ECMO therapy before severe metabolic derangements subset may improve survival rates significantly in these patients. These results should be viewed in the light of a strict patient selection policy and may not be replicated in patients with advanced age or multiple comorbidities. CLINICAL TRIAL REGISTRATION: identifier, NCT04383678.

Long-term ACE Inhibitor/ARB Use Is Associated With Severe Renal Dysfunction and Acute Kidney Injury in Patients With Severe COVID-19: Results From a Referral Center Cohort in the Northeast of France.

BACKGROUND: In patients with severe coronavirus disease 2019 (COVID-19), data are scarce and conflicting regarding whether chronic use of angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) influences disease outcomes. In patients with severe COVID-19, we assessed the association between chronic ACEI/ARB use and the occurrence of kidney, lung, heart, and liver dysfunctions and the severity of the inflammatory reaction as evaluated by biomarkers kinetics, and their association with disease outcomes. METHODS: We performed a retrospective longitudinal cohort study on consecutive patients with newly diagnosed severe COVID-19. Independent predictors were assessed through receiver operating characteristic analysis, time-series analysis, logistic regression analysis, and multilevel modeling for repeated measures. RESULTS: On the 149 patients included in the study 30% (44/149) were treated with ACEI/ARB. ACEI/ARB use was independently associated with the following biochemical variations: phosphorus >40 mg/L (odds ratio [OR], 3.35, 95% confidence interval [CI], 1.83-6.14), creatinine >10.1 mg/L (OR, 3.22, 2.28-4.54), and urea nitrogen (UN) >0.52 g/L (OR, 2.65, 95% CI, 1.89-3.73). ACEI/ARB use was independently associated with acute kidney injury stage ≥1 (OR, 3.28, 95% CI, 2.17-4.94). The daily dose of ACEI/ARB was independently associated with altered kidney markers with an increased risk of +25 to +31% per each 10 mg increment of lisinopril-dose equivalent. In multivariable multilevel modeling, UN >0.52 g/L was independently associated with the risk of acute respiratory failure (OR, 3.54, 95% CI, 1.05-11.96). CONCLUSIONS: Patients chronically treated with ACEI/ARB who have severe COVID-19 are at increased risk of acute kidney injury. In these patients, the increase in UN associated with ACEI/ARB use could predict the development of acute respiratory failure.

The spectrum of biochemical alterations associated with organ dysfunction and inflammatory status and their association with disease outcomes in severe COVID-19: A longitudinal cohort and time-series design study.

BACKGROUND: In patients with severe COVID-19, no data are available on the longitudinal evolution of biochemical abnormalities and their ability to predict disease outcomes. METHODS: Using a retrospective, longitudinal cohort study design on consecutive patients with severe COVID-19, we used an extensive biochemical dataset of serial data and time-series design to estimate the occurrence of organ dysfunction and the severity of the inflammatory reaction and their association with acute respiratory failure (ARF) and death. FINDINGS: On the 162 studied patients, 1151 biochemical explorations were carried out for up to 59 biochemical markers, totaling 15,260 biochemical values. The spectrum of biochemical abnormalities and their kinetics were consistent with a multi-organ involvement, including lung, kidney, heart, liver, muscle, and pancreas, along with a severe inflammatory syndrome. The proportion of patients who developed an acute kidney injury (AKI) stage 3, increased significantly during follow-up (0·9%, day 0; 21·4%, day 14; P<0·001). On the 20 more representative biochemical markers (>250 iterations), only CRP >90 mg/L (odds ratio [OR] 6·87, 95% CI, 2·36-20·01) and urea nitrogen >0·36 g/L (OR 3·91, 95% CI, 1·15-13·29) were independently associated with the risk of ARF. Urea nitrogen >0·42 g/L was the only marker associated with the risk of COVID-19 related death. INTERPRETATION: Our results point out the lack of the association between the inflammatory markers and the risk of death but rather highlight a significant association between renal dysfunction and the risk of COVID-19 related acute respiratory failure and death.

Clinical recurrences of COVID-19 symptoms after recovery: Viral relapse, reinfection or inflammatory rebound?

For the first 3 months of COVID-19 pandemic, COVID-19 was expected to be an immunizing non-relapsing disease. We report a national case series of 11 virologically-confirmed COVID-19 patients having experienced a second clinically- and virologically-confirmed acute COVID-19 episode. According to the clinical history, we discuss either re-infection or reactivation hypothesis. Larger studies including further virological, immunological and epidemiologic data are needed to understand the mechanisms of these recurrences.

Coronavirus disease 2019: acute Fanconi syndrome precedes acute kidney injury.

BACKGROUND: Recent data have shown that severe acute respiratory syndrome coronavirus 2 can infect renal proximal tubular cells via Angiotensin Converting Enzyme 2 (ACE2) . Our objective was to determine whether Fanconi syndrome is a frequent clinical feature in coronavirus disease 2019 (COVID-19) patients. METHODS: A retrospective cohort of 42 laboratory-confirmed COVID-19 patients without history of kidney disease hospitalized in University Hospital of Nancy was investigated. Patients were admitted to the intensive care unit (ICU) (n = 28) or the Medical department (n = 14) and were screened at least once for four markers of proximal tubulopathy. RESULTS: The mean (standard deviation) follow-up was 19.7 (±12.2) days. Of the patients, 75% (30/40) showed at least two proximal tubule abnormalities (incomplete Fanconi syndrome). The main disorders were proteinuria (88%, n = 35), renal phosphate leak defined by renal phosphate threshold/glomerular filtration rate (TmPi/GFR) <0.77 (55%, n = 22), hyperuricosuria (43%, n = 17) and normoglycaemic glycosuria (30%, n = 12). At the time of the first renal evaluation, ICU patients presented more frequent (96 versus 62%, P = 0.0095) and more severe (844 ± 343 versus 350 ± 221 mg/g, P = 0.0001) proteinuria, and a trend for an increased number of proximal tubule abnormalities (P = 0.038). During follow-up, they presented a lower nadir of serum phosphate [median (interquartile range) 0.68 (0.43-0.76) versus 0.77 (0.66-1.07) mmol/L, P = 0.044] and Acute kidney Injury (AKI) during the hospitalization (P = 0.045). Fanconi syndrome preceded severe AKI KDIGO Stages 2 and 3 in 88% (7/8) of patients. Proximal tubular abnormalities (such as proteinuria, TmPi/GFR and glycosuria in five, two and two patients, respectively) were not detected anymore in recovering patients before hospital discharge. CONCLUSION: Incomplete Fanconi syndrome is highly frequent in COVID-19 patients and precedes AKI or disappears during the recovery phase.