Fatigue is a common symptom in those presenting with symptomatic COVID-19 infection. However, it is unknown if COVID-19 results in persistent fatigue in those recovered from acute infection. We examined the prevalence of fatigue in individuals recovered from the acute phase of COVID-19 illness using the Chalder Fatigue Score (CFQ-11). We further examined potential predictors of fatigue following COVID-19 infection, evaluating indicators of COVID-19 severity, markers of peripheral immune activation and circulating pro-inflammatory cytokines. Of 128 participants (49.5 ± 15 years; 54% female), more than half reported persistent fatigue (67/128; 52.3%) at median of 10 weeks after initial COVID-19 symptoms. There was no association between COVID-19 severity (need for inpatient admission, supplemental oxygen or critical care) and fatigue following COVID-19. Additionally, there was no association between routine laboratory markers of inflammation and cell turnover (leukocyte, neutrophil or lymphocyte counts, neutrophil-to-lymphocyte ratio, lactate dehydrogenase, C-reactive protein) or pro-inflammatory molecules (IL-6 or sCD25) and fatigue post COVID-19. Female gender and those with a pre-existing diagnosis of depression/anxiety were over-represented in those with fatigue. Our findings demonstrate a significant burden of post-viral fatigue in individuals with previous SARS-CoV-2 infection after the acute phase of COVID-19 illness. This study highlights the importance of assessing those recovering from COVID-19 for symptoms of severe fatigue, irrespective of severity of initial illness, and may identify a group worthy of further study and early intervention.

Fatigue is a common symptom in those presenting with symptomatic COVID-19 infection. However, it is unknown if COVID-19 results in persistent fatigue in those recovered from acute infection. We examined the prevalence of fatigue in individuals recovered from the acute phase of COVID-19 illness using the Chalder Fatigue Score (CFQ-11). We further examined potential predictors of fatigue following COVID-19 infection, evaluating indicators of COVID-19 severity, markers of peripheral immune activation and circulating pro-inflammatory cytokines. Of 128 participants (49.5 ± 15 years; 54% female), more than half reported persistent fatigue (52.3%; 45/128) at 10 weeks (median) after initial COVID-19 symptoms. There was no association between COVID-19 severity (need for inpatient admission, supplemental oxygen or critical care) and fatigue following COVID-19. Additionally, there was no association between routine laboratory markers of inflammation and cell turnover (leukocyte, neutrophil or lymphocyte counts, neutrophil-to-lymphocyte ratio, lactate dehydrogenase, C-reactive protein) or pro-inflammatory molecules (IL-6 or sCD25) and fatigue post COVID-19. Female gender and those with a pre-existing diagnosis of depression/anxiety were over-represented in those with fatigue. Our findings demonstrate a significant burden of post-viral fatigue in individuals with previous SARS-CoV-2 infection after the acute phase of COVID-19 illness. This study highlights the importance of assessing those recovering from COVID-19 for symptoms of severe fatigue, irrespective of severity of initial illness, and may identify a group worthy of further study and early intervention.

Natural killer (NK) cells are circulating cytotoxic lymphocytes that exert potent and nonredundant antiviral activity and antitumoral activity in the mouse; however, their function in host defense in humans remains unclear. Here, we investigated 6 related patients with autosomal recessive growth retardation, adrenal insufficiency, and a selective NK cell deficiency characterized by a lack of the CD56 dim NK subset. Using linkage analysis and fine mapping, we identified the disease-causing gene, MCM4, which encodes a component of the MCM2-7 helicase complex required for DNA replication. A splice-site mutation in the patients produced a frameshift, but the mutation was hypomorphic due to the creation of two new translation initiation methionine codons downstream of the premature termination codon. The patients' fibroblasts exhibited genomic instability, which was rescued by expression of WT MCM4. These data indicate that the patients' growth retardation and adrenal insufficiency likely reflect the ubiquitous but heterogeneous impact of the MCM4 mutation in various tissues. In addition, the specific loss of the NK CD56 dim subset in patients was associated with a lower rate of NK CD56 bright cell proliferation, and the maturation of NK CD56 bright cells toward an NK CD56 dim phenotype was tightly dependent on MCM4-dependent cell division. Thus, partial MCM4 deficiency results in a genetic syndrome of growth retardation with adrenal insufficiency and selective NK deficiency.

Rationale: Much is known about the acute infective process of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative virus of the coronavirus disease (COVID-19) pandemic. The marked inflammatory response and coagulopathic state in acute SARS-CoV-2 infection may promote pulmonary fibrosis. However, little is known about the incidence and seriousness of post–COVID-19 pulmonary pathology. Objectives: To describe the respiratory recovery and self-reported health after infection at the time of outpatient attendance. Methods: Infection severity was graded into three groups: 1 ) not requiring admission, 2 ) requiring hospital admission, and 3 ) requiring intensive care unit care. Participants underwent chest radiography and a 6-minute walk test (6MWT). Fatigue and subjective return to health were assessed, and concentrations of CRP (C-reactive protein), IL-6 (interleukin-6), sCD25 (soluble CD25), and D-dimer were measured. The associations between initial illness and abnormal chest X-ray findings, 6MWT distance, and perception of maximal exertion were investigated. Results: A total of 487 patients were offered an outpatient appointment, of whom 153 (31%) attended for assessment at a median of 75 days after diagnosis. A total of 74 (48%) had required hospital admission during acute infection. Persistently abnormal chest X-ray findings were seen in 4%. The median 6MWT distance covered was 460 m. A reduced distance covered was associated with frailty and length of inpatient stay. A total of 95 (62%) patients believed that they had not returned to full health, whereas 47% met the case definition for fatigue. Ongoing ill health and fatigue were associated with an increased perception of exertion. None of the measures of persistent respiratory disease were associated with initial disease severity. Conclusions: This study highlights the rates of objective respiratory disease and subjective respiratory symptoms after COVID-19 and the complex multifactorial nature of post–COVID-19 ill health.

assist device (ELAD), was developed by Sussman et al. 6 Cells The objective of this pilot controlled study was to evalderived from a human hepatoblastoma cell line (C3A) are uate the extracorporeal liver assist device (ELAD) in pacultured within the extracapillary space of a dialysis cartients with acute liver failure who were judged to still tridge. Whole blood is used for the perfusion 7 and, unlike the have a significant chance of survival (Ç50%) and in those BAL where plasma perfusion is limited to 6 hours, ELAD who had already fulfilled criteria for transplantation.support can be continued for long periods of time. 8 In early Twenty-four patients were divided into two groups, 17 experimental work in anhepatic dogs, function of the device with a potentially recoverable lesion (group I) and 7 was deduced from the requirement for further anaesthesia, listed for transplantation (group II), and then randomly changes in plasma ammonia level, and length of survival. allocated to ELAD haemoperfusion or control. The meSmall amounts of human albumin were also detected in the dian period of ELAD haemoperfusion was 72 hours circulation which peaked after 7 hours of haemoperfusion. 9 (range 3-168 h). Biocompatibility of the device was good,In further studies performed in a canine model of ALF inwith no acceleration in platelet consumption, and duced by acetaminophen toxicity, 10 80% of treated animals haemodynamic stability was maintained. Two patients survived as compared with none of the controls. 11 In addition were withdrawn from the study because of worsening the extent of liver injury, assessed both histologically and of preexisting disseminated intravascular coagulation from the serum alanine transaminase, appeared to be less in in one case and a hypersensitivity reaction in the other.the haemoperfused animals. 6 An initial case report of the use Deterioration with respect to encephalopathy grade was of the ELAD included one patient who recovered from acute more frequent in the control patients, 7 of 12 (58%), than liver failure secondary to syncytial giant cell hepatitis, 12 and in the ELAD-treated patients, 3 of 12 (25%). In group I in the first clinical series of cases, mental status was imwhere survival for the ELAD cases was 7 of 9 (78%), there proved in 8 of the 11 patients, 4 of whom were transplanted, was a higher than expected survival in the controls, 6although only 1 case survived. 8 of 8 (75%). For group II cases, survival was 1 of 3 (33%)The objective of the present pilot but controlled study was for the ELAD-treated patients, and 1 of 4 (25%) for the to assess use of the ELAD device in two groups of patients, controls. Both of the survivors underwent transplantathose in whom there was judged to be some potential for tion. Assessment of additive function for the device rerecovery and those affected to a greater extent where it is vealed an improvement in galactose elimination capacused as a bridge to transplantation. Particular attention was ity after 6 hours of haemoperfusion. Based on the results d...