Severe Forms Of Coronavirus Disease 2019 Research Articles

Predictive significance of hypertension in the incidence of complications in critically ill patients with COVID‑19: A retrospective cohort study.

The association between hypertension as a pre-existing comorbidity and the severe form of coronavirus disease 2019 (COVID-19) remains unclear due to the contradictory results of previously published studies. The present study evaluated the predictive significance of hypertension in the incidence of complications among critically ill patients with COVID-19. The present study included 372 critically ill adults with COVID-19 pneumonia, hospitalized between January 1 and December 31, 2021. The study cohort was divided into the hypertension group (HTA group), which included 245 patients with a history of hypertension, or a non-HTA group (control group), which included 127 patients without hypertension. The incidence of complications was retrospectively extracted from medical records and compared between groups. Multivariate regression analysis (adjusted for potential confounders) and receiver operating characteristic (ROC) curve analysis determined the predictive significance of hypertension on the incidence of complications. The patients in the HTA group were more likely to receive invasive mechanical ventilation [odds ratio (OR), 1.696; P<0.02], develop sepsis (OR, 1.807; P<0.01) and develop complications (OR, 3.101; P<0.001). Hypertension was an independent positive predictor for invasive mechanical ventilation [area under the curve (AUC), 0.67; positive predictive value (PPV), 71.7%; P<0.05], sepsis (AUC, 0.69; PPV, 77.5%; P<0.026) and total complications per patient (AUC, 0.71; PPV, 81.4%; P<0.001). On the whole, the data of the present study indicate that a history of hypertension should be considered as an independent clinical predictor of a higher incidence of complications in critically ill patients with COVID-19. Patients with pre-existing hypertension and a diagnosis of COVID-19 require timely identification, additional attention and treatment to avoid a critical course and help improve outcomes.

Outcomes of COVID-19 in 24 hospitalized liver transplant recipients: an observational study

BackgroundAlthough liver transplant (LT) recipients are considered a population at risk of severe features of coronavirus disease 2019 (COVID-19), data in this regard are scarce and controversial. In this study, we reported the outcome of 24 cases of LT recipients who were hospitalized due to COVID-19 and investigated the role-playing factors in the severity of the disease.MethodsIn this single-center, analytic case-series study, eligible patients were among LT recipients who were hospitalized due to the diagnosis of COVID-19 based on positive results of polymerase chain reaction. Participants were categorized as severe COVID-19 if they were admitted to the intensive care unit, experienced respiratory failure demanding mechanical ventilation, or eventually died. Demographic and clinical data, COVID-19 symptoms and specific treatments, laboratory biomarkers, and immunosuppressive regimens and their alteration during the admission were recorded. Analysis was done using SPSS software.ResultsTwenty-four hospitalized LT patients were included, of which nine had severe and fifteen had non-severe COVID-19. Out of 9 patients with severe COVID-19, four sadly died. The analysis and comparison between the two groups revealed longer hospital stays (P = 0.02), lower lymphocyte counts (P = 0.002), and higher levels of C-reactive protein (CRP) (P = 0.006) in patients with severe COVID-19. Patients with non-severe COVID-19 had higher doses of tacrolimus and mycophenolate in their baseline immunosuppressive regimen (both P = 0.02).ConclusionLymphopenia and high CRP levels are associated with more severe forms of COVID-19 in LT patients. Mycophenolate may have protective properties against severe COVID-19. The role of severity indicators in LT patients with COVID-19 needs to be systematically recognized.

Complement system activation: bridging physiology, pathophysiology, and therapy.

The complement system is a set of over 50 proteins that constitutes an essential part of the innate immune system. Complement system activation involves an organized proteolytic cascade. Overactivation of complement system activation is the main pathogenic mechanism of several diseases and contributes to the manifestations of many other conditions. This review describes the normal complement system and the role for complement dysregulation in critical illnesses, notably sepsis and acute respiratory distress syndrome. Complement activation is involved in the immune system response to pathogens but, when excessive, can contribute to tissue damage, runaway inflammation, and capillary leakage syndrome. Complement overactivation may play a key role in severe forms of coronavirus disease 2019 (COVID-19). Two diseases whose manifestations are mainly caused by complement overactivation, namely, atypical hemolytic and uremic syndrome (aHUS) and myasthenia gravis, are discussed. A diagnostic algorithm for aHUS is provided. Early complement-inhibiting therapy has been proven effective. When renal transplantation is required, complement-inhibiting drugs can be used prophylactically to prevent aHUS recurrence. Similarly, acetylcholine-receptor autoantibody-positive generalized myasthenia gravis involves complement system overactivation and responds to complement inhibition. The two main complement inhibitors used in to date routine are eculizumab and ravulizumab. The main adverse event is Neisseria infection, which is rare and preventable, but can be fatal. The complement system is crucial to health but, when overactivated, can cause or contribute to disease. Effective complement inhibitors are now available, although additional data are required to determine optimal regimens. Further research is also needed to better understand the complement system, develop advanced diagnostic tools, and identify markers that allow the personalization of treatment strategies.

Previous Coronavirus Disease-2019 Infection and Lung Mechanics in Surgical Patients: A Hospital Registry Study.

Long-term pulmonary complications have been reported after a coronavirus disease-2019 (COVID-19). We hypothesized that a history of COVID-19 is associated with a measurable decrease in baseline respiratory system compliance in patients undergoing general anesthesia. In this hospital registry study, we included adult patients undergoing general anesthesia between January 2020 and March 2022 at a tertiary health care network in Massachusetts. We excluded patients with an American Society of Anesthesiologists physical status >IV, laryngoscopic surgeries, and patients who arrived intubated. The primary exposure was a history of COVID-19. The primary outcome was baseline respiratory system compliance (mL/cmH 2 O). Effects of severity of infection, surges (Alpha 1 , Alpha 2 , Delta, and Omicron), patient demographics, and time between infection and assessment of compliance were investigated. A total of 19,921 patients were included. Approximately 1386 (7.0%) patients had a history of COVID-19. A history of COVID-19 at any time before surgery was associated with a measurably lower baseline respiratory system compliance (ratio of means adj = 0.96; 95% confidence interval [CI], 0.94-0.97; P < .001; adjusted compliance difference: -1.6 mL/cmH 2 O). The association was more pronounced in patients with a severe form of COVID-19 (ratio of means adj = 0.95; 95% CI, 0.90-0.99; P = .02, adjusted compliance difference: -2 mL/cmH 2 O). Alpha 1 , Alpha 2 , and Delta surges, but not Omicron, led to a lower baseline respiratory system compliance ( P < .001, P = .02, and P < .001). The Delta surge effect was magnified in Hispanic ethnicity ( P -for-interaction = 0.003; ratio of means adj = 0.83; 95% CI, 0.74-0.93; P = .001; adjusted compliance difference: -4.6 mL/cmH 2 O). A history of COVID-19 infection during Alpha 1 , Alpha 2 , and Delta surges was associated with a measurably lower baseline respiratory system compliance.

The development of anticyclic citrullinated peptide (anti-CCP) antibody following severe COVID-19.

The dysregulated immune response is one of the cardinal features of severe coronavirus disease 2019 (COVID-19). This study was conducted to clarify the occurrence of autoantibodies (AABs) associated with systemic autoimmune rheumatic diseases (SARDs) in hospitalized patients with a moderate, severe, and critical form of COVID-19. The serum samples obtained from 176 hospitalized COVID-19 patients were investigated in this study, including patients with moderate (N = 90), severe (N = 50), and critical (N = 36) forms of COVID-19. Also, the serum samples collected from healthy subjects before the COVID-19 pandemic were used as controls (N = 176). The antinuclear antibodies (ANAs), antidouble-stranded DNA (anti-dsDNA), cytoplasmic-anti neutrophil cytoplasmic antibody (c-ANCA), perinuclear ANCA (p-ANCA), antiphospholipid antibodies (aPLs), and anticyclic citrullinated peptide (anti-CCP) occurrence was evaluated using a solid-phase enzyme-linked immunosorbent assay (ELISA). The results showed that the occurrence of ANAs, anti-dsDNA, anti-CCP, c-ANCA, and p-ANCA was significantly higher in the COVID-19 patients compared to serum obtained from healthy subjects (p < .0001, p < .0001, p < .0001, p < .05, and p < .001, respectively). The positive number of anti-CCP tests increased significantly in severe COVID-19 compared to the moderate group (p < .01). Our study further supports the development of autoantibodies related to systemic autoimmune rheumatologic diseases. To the best of our knowledge, this is the first study with a large sample size that reported the occurrence of anti-CCP in a severe form of COVID-19.

Wedge Resection and Optimal Solutions for Invasive Pulmonary Fungal Infection and Long COVID Syndrome—A Case Report and Brief Literature Review

A rise in fungal infections has been observed worldwide among patients with extended hospital stays because of the severe infection caused by the new coronavirus pandemic. A 62-year-old female patient was admitted with a severe form of Coronavirus disease 2019 (COVID-19) and spent four weeks in the intensive care unit (ICU) requiring mechanical ventilation support before being moved to a tertiary hospital for further testing. Aspergillus fumigatus filamentous fungus, Candida spp., and positive bacteriology for multidrug-resistant Klebsiella pneumoniae and Proteus mirabilis were identified by bronchial aspirate cultures. The patient’s progress was gradually encouraging while receiving oral antifungal and broad-spectrum antibiotic therapy along with respiratory physical therapy; but ultimately, thoracic surgery was necessary. Long-lasting tissue damage and severe, persistent inflammatory syndrome were the two main pathophysiological mechanisms that led to significant outcomes regarding lung lesions that were rapidly colonized by fungi and resistant flora, cardiac damage with sinus tachycardia at the slightest effort, and chronic inflammatory syndrome, which was characterized by marked asthenia, myalgias, and exercise intolerance.

Impact of the SARS-CoV-2 Spike Protein on the Innate Immune System: A Review.

The Spike protein enables the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection by binding to multiple receptors, including the angiotensin-converting enzyme 2 (ACE2). Scientific studies also indicate that Spike is involved in severe forms of coronavirus disease 2019 (COVID-19), "long-haul COVID diseases" - also known as "long COVID syndromes" or "post-acute sequelae of SARS-CoV-2 infection" (PACS) - or, recently, in adverse reactions to lipid nanoparticle-messenger ribonucleic acid (mRNA) vaccines or other anti-COVID19 products. Numerous mutations, notably within the subunit 1 of Spike (S1), prevent neutralization by antibodies, but more generally, the virus has developed numerous strategies to avoid immune system surveillance, especially type-I interferons (IFN-I). Meanwhile, a "hyperinflammatory" state, named "cytokine storm,"sets in. However, what role does the Spike protein play in the immune escape mechanisms? Can its inflammatory activities affect IFN-I? Does Spike block IFN-I or hijack them for the virus benefits? What are the other potential consequences? This article was written to provide an up-to-date and more general overview of the impact of the Spike protein on the innate immune system and its effectors at the molecular level.

Association of Polymorphisms of the IL-17A and IL-17F Genes with Increased Risk of Hypertension and Obesity in Mexican Patients with COVID-19.

Coronavirus disease 2019 (COVID-19) is caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV2). COVID-19 can cause a cytokine release syndrome in which cytokines, including interleukin 17 (IL-17), are massively secreted in response to a specific stimulus. This can contribute to mortality and severe forms of COVID-19. The study aimed to determine the association of SARS-CoV2 infection with the IL-17A rs2275913 and IL-17F rs763780 variants, as well as with the associated comorbidities in COVID-19-positive Mexican patients. The study included 178 patients positive to COVID-19 and 177 COVID-19 negative subjects. For genotyping, the samples were amplified with a TaqMan® probe. There was no association between the AA genotype and A allele of IL-17A variant or the IL-17F C allele with the presence of COVID-19. In regard to comorbidities, a statistically significant association was found between IL-17A rs2275913 AA genotype and hypertension, as well as with the presence of obesity (P = 0.003, OR 23, 95% CI: 2.97-178.092 and P = 0.025, OR 28, 95% CI: 1.52-178.029, respectively) in patients with COVID-19. In conclusion, rs2275913 IL-17A polymorphism in COVID-19 patients seems to confer a higher susceptibility to the presence of hypertension and obesity, increasing the risk of premature cardiovascular disease in this population. However, more studies should be conducted for a better understanding of their relation.

Chest Computed Tomography Characteristics of Critically Ill COVID-19 Patients with Auto-antibodies Against Type I Interferons

PurposePatients with auto-antibodies neutralizing type I interferons (anti-IFN auto-Abs) are at risk of severe forms of coronavirus disease 19 (COVID-19). The chest computed tomography (CT) scan characteristics of critically ill COVID-19 patients harboring these auto-Abs have never been reported.MethodsBicentric ancillary study of the ANTICOV study (observational prospective cohort of severe COVID-19 patients admitted to the intensive care unit (ICU) for hypoxemic acute respiratory failure between March 2020 and May 2021) on chest CT scan characteristics (severity score, parenchymal, pleural, vascular patterns). Anti-IFN auto-Abs were detected using a luciferase neutralization reporting assay. Imaging data were collected through independent blinded reading of two thoracic radiologists of chest CT studies performed at ICU admission (± 72 h). The primary outcome measure was the evaluation of severity by the total severity score (TSS) and the CT severity score (CTSS) according to the presence or absence of anti-IFN auto-Abs.ResultsTwo hundred thirty-one critically ill COVID-19 patients were included in the study (mean age 59.5 ± 12.7 years; males 74.6%). Day 90 mortality was 29.5% (n = 72/244). There was a trend towards more severe radiological lesions in patients with anti-IFN auto-Abs than in others, not reaching statistical significance (median CTSS 27.5 (21.0–34.8) versus 24.0 (19.0–30.0), p = 0.052; median TSS 14.5 (10.2–17.0) versus 12.0 (9.0–15.0), p = 0.070). The extra-parenchymal evaluation found no difference in the proportion of patients with pleural effusion, mediastinal lymphadenopathy, or thymal abnormalities in the two populations. The prevalence of pulmonary embolism was not significantly different between groups (8.7% versus 5.3%, p = 0.623, n = 175).ConclusionThere was no significant difference in disease severity as evaluated by chest CT in severe COVID-19 patients admitted to the ICU for hypoxemic acute respiratory failure with or without anti-IFN auto-Abs.

Clinical Outcomes of COVID-19 Infection among Patients with Chronic Obstructive Pulmonary Disease: Findings from the Philippine CORONA Study.

The global pandemic caused by the coronavirus disease 2019 (COVID-19) resulted in many deaths from fulminant respiratory failure. Chronic obstructive pulmonary disease (COPD) is the leading cause of morbidity and mortality worldwide. There has been great concern regarding the impact of COPD on the COVID-19 illness. Data from the Philippine CORONA study were analyzed to determine the association of COPD and COVID-19 in terms of mortality, disease severity, respiratory failure, mechanical ventilation, and lengths of stay in the intensive care unit (ICU) and hospital. A total of 10,881 patients were included in this study, and 156 (1.4%) patients had been diagnosed with COPD. A majority of COVID-19 patients with COPD had other existing comorbidities: hypertension, diabetes mellitus, chronic cardiac disease, and chronic kidney disease. COPD patients were 2.0× more likely to present with severe to critical COVID-19 disease. COVID-19 patients with COPD in our study have a 1.7× increased mortality, 1.6× increased respiratory failure, and 2.0× increased risk for ICU admission. Smokers with COVID-19 were 1.8× more likely to present with more severe disease and have a 1.9× increased mortality. Our study supports the growing evidence that COPD among COVID-19 patients is a risk factor for higher mortality, more severe form of COVID-19, higher ICU admission, and higher respiratory failure needing ventilatory support.

MTOR gene variants are associated with severe COVID-19 outcomes: A multicenter study

BackgroundThe worst outcomes linked to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have been attributed to the cytokine storm, which contributes significantly to the immunopathogenesis of the disease. The mammalian target of rapamycin (mTOR) pathway is essential for orchestrating innate immune cell defense including cytokine production and is dysregulated in severe Coronavirus Disease 2019 (COVID-19) individuals. The individual genetic background might play a role in the exacerbated immune response. ObjectiveIn this study, we aimed to investigate the association between MTOR genetic variants and COVID-19 outcomes. MethodsThis study enrolled groups of individuals with severe (n = 285) and mild (n = 207) COVID-19 from Brazilian states. The MTOR variants, rs1057079 and rs2536, were genotyped. A logistic regression analysis and Kaplan–Meier survival curves were performed. We applied a genotyping risk score to estimate the cumulative contribution of the risk alleles. Tumor necrosis factor (TNF) and interleukin-6 (IL-6) plasma levels were also measured. ResultsThe T allele of the MTOR rs1057079 variant was associated with a higher likelihood of developing the most severe form of COVID-19. In addition, higher levels of IL-6 and COVID-19 death was linked to the T allele of the rs2536 variant. These variants exhibited a cumulative risk when inherited collectively. ConclusionsThese results show a potential pathogenetic role of MTOR gene variants and may be useful for predicting severe outcomes following COVID-19 infection, resulting in a more effective allocation of health resources.

Diabetes related phenotypes and their influence on outcomes of patients with corona virus disease 2019 (COVID-19)

IntroductionDiabetes mellitus (DM) is associated with severe forms of COVID-19 but little is known about the diabetes—related phenotype considering pre-admission, on-admission and data covering the entire hospitalization period.MethodsWe analyzed COVID-19 inpatients (n = 3327) aged 61.2(48.2–71.4) years attended from March to September 2020 in a public hospital.ResultsDM group (n = 1218) differed from Non-DM group (n = 2109) by higher age, body mass index (BMI), systolic blood pressure and lower O2 saturation on admission. Gender, ethnicity and COVID-19-related symptoms were similar. Glucose and several markers of inflammation, tissue injury and organ dysfunction were higher among patients with diabetes: troponin, lactate dehydrogenase, creatine phosphokinase (CPK), C-reactive protein (CRP), lactate, brain natriuretic peptide, urea, creatinine, sodium, potassium but lower albumin levels. Hospital (12 × 11 days) and intensive care unit permanence (10 × 9 days) were similar but DM group needed more vasoactive, anticoagulant and anti-platelet drugs, oxygen therapy, endotracheal intubation and dialysis. Lethality was higher in patients with diabetes (39.3% × 30.7%) and increased with glucose levels and age, in male sex and with BMI < 30 kg/m2 in both groups (obesity paradox). It was lower with previous treatment with ACEi/BRA in both groups. Ethnicity and education level did not result in different outcomes between groups. Higher frequency of comorbidities (hypertension, cardiovascular/renal disease, stroke), of inflammatory (higher leucocyte number, RCP, LDH, troponin) and renal markers (urea, creatinine, potassium levels and lower sodium, magnesium) differentiated lethality risk between patients with and without diabetes.ConclusionsComorbidities, inflammatory markers and renal disfunction but not Covid-19-related symptoms, obesity, ethnicity and education level differentiated lethality risk between patients with and without diabetes.

Host mitochondria: more than an organelle in SARS-CoV-2 infection.

Since December 2019, the world has been facing viral pandemic called COVID-19 (Coronavirus disease 2019) caused by a new beta-coronavirus named severe acute respiratory syndrome coronavirus-2, or SARS-CoV-2. COVID-19 patients may present with a wide range of symptoms, from asymptomatic to requiring intensive care support. The severe form of COVID-19 is often marked by an altered immune response and cytokine storm. Advanced age, age-related and underlying diseases, including metabolic syndromes, appear to contribute to increased COVID-19 severity and mortality suggesting a role for mitochondria in disease pathogenesis. Furthermore, since the immune system is associated with mitochondria and its damage-related molecular patterns (mtDAMPs), the host mitochondrial system may play an important role during viral infections. Viruses have evolved to modulate the immune system and mitochondrial function for survival and proliferation, which in turn could lead to cellular stress and contribute to disease progression. Recent studies have focused on the possible roles of mitochondria in SARS-CoV-2 infection. It has been suggested that mitochondrial hijacking by SARS-CoV-2 could be a key factor in COVID-19 pathogenesis. In this review, we discuss the roles of mitochondria in viral infections including SARS-CoV-2 infection based on past and present knowledge. Paying attention to the role of mitochondria in SARS-CoV-2 infection will help to better understand the pathophysiology of COVID-19 and to achieve effective methods of prevention, diagnosis, and treatment.

Pediatric COVID-19 and Diabetes: An Investigation into the Intersection of Two Pandemics.

Coronavirus disease 2019 (COVID-19) is a complex infectious disease caused by the SARS-CoV-2 virus, and it currently represents a worldwide public health emergency. The pediatric population is less prone to develop severe COVID-19 infection, but children presenting underlying medical conditions, such as diabetes mellitus, are thought to be at increased risk of developing more severe forms of COVID-19. Diabetic children face new challenges when infected with SARS-CoV-2. On one hand, the glycemic values become substantially more difficult to manage as COVID-19 is a predisposing factor for hyperglycemia. On the other hand, alongside other risk factors, high glycemic values are incriminated in modulating immune and inflammatory responses, leading to potentially severe COVID-19 cases in the pediatric population. Also, there are hypotheses of SARS-CoV-2 being diabetogenic itself, but this information is still to be confirmed. Furthermore, it is reported that there was a noticeable increase in the number of cases of new-onset type 2 diabetes among the pediatric population, and the complications in these patients with COVID-19 include the risk of developing autoimmune diseases under the influence of stress. Additionally, children with diabetes mellitus are confronted with lifestyle changes dictated by the pandemic, which can potentially lead to the onset or exacerbation of a potential underlying anxiety disorder or depression. Since the literature contains a series of unknowns related to the impact of COVID-19 in both types of diabetes in children, the purpose of our work is to bring together the data obtained so far and to identify potential knowledge gaps and areas for future investigation regarding COVID-19 and the onset of diabetes type 1 or type 2 among the pediatric population.

Evaluation of the Humoral and Cellular Immune Response Post COVID-19 Infection in Kidney Transplant Recipients.

Kidney transplantation is a major risk factor for severe forms of coronavirus disease 2019 (COVID-19). The dynamics and the persistence of the immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in this immunocompromised population remain largely unknown. This study aimed to evaluate the persistence of humoral and cellular immune response in kidney transplant recipients (KTRs) and to establish whether immunosuppressive therapy influenced long-term immunity in this population. We report here the analysis of anti-SARS-CoV-2 antibodies and T cell-mediated immune responses in 36 KTRs compared to a control group who recovered from mild COVID-19. After a mean time of 5.22 ± 0.96 months post symptom onset for kidney transplant recipients, 97.22% of patients and 100% of the control group displayed anti-S1 immunoglobulin G SARS-CoV-2 antibodies (p > 0.05). No significant difference was reported in the median of neutralizing antibodies between the groups (97.50 [55.25-99] in KTRs vs. 84 [60-98] in control group, p = 0.35). A significant difference in SARS-CoV-2-specific T cell reactivity was found in the KTRs compared to the healthy controls. The levels of IFNγ release after stimulation by Ag1, Ag2 and Ag3 were higher in the control group compared to the kidney transplant group (p = 0.007, p = 0.025 and p = 0.008, respectively). No statistically significant correlation between humoral and cellular immunity was found in the KTRs. Our findings indicated that humoral immunity persisted similarly for up to 4 to 6 months post symptom onset in both the KTRs and the control group; however, T cell response was significantly higher in the healthy population compared to the immunocompromised patients.

Muscle ultrasonographic changes in critically ill COVID-19 patients

Background: Patients with severe forms of COVID-19 (coronavirus disease 2019) present a systemic inflammatory response and hypermetabolism. The objective of this study was to identify the change in rectus femoris and vastus medialis muscle mass in patients with severe COVID-19 who required invasive mechanical ventilation, and to establish the correlation between the change in muscle size and the amount of calories and proteins administered. Materials &amp; methods: This prospective observational longitudinal study was conducted in the adult intensive care unit in a tertiary care clinic. Muscle mass was measured with ultrasound from admission, at seven-day intervals, until discharge from the unit. Anthropometric and biochemical data as well as the amount of calories and proteins administered were taken into account. Results: A total of 39 patients were included (59.6 ± 11.3 years; 79.5% men) with a median BMI of 27.7 kg/m2 (IQR 24.2–29.7). The size of the rectus femoris and vastus medialis muscles had diminished significantly at seven days of hospitalization: right middle third 0.38 cm (IQR 0.16-0.47), left middle third 0. 29 cm (IQR 0.08-0.54) and right middle third 0.37 cm (IQR 0.11-0.71) left middle third 0.25 cm (IQR 0.09-0.52), respectively. The changes in both muscles were directly correlated with caloric and protein intake during nutritional support. Conclusions: Critically ill patients with COVID-19 were found to lose muscle mass progressively as a result of lower coverage of caloric and protein requirements.

Immunogenicity of Anti-SARS-CoV-2 Vaccination After Kidney Transplantation in Kidney Transplant Recipients Vaccinated Before Transplantation.

Solid-organ transplant patients, including kidney transplant recipients (KTRs) are at high risk of severe forms of coronavirus disease 2019 (COVID-19) infection1 and fail to mount a robust and sustained humoral response to COVID-19 vaccines,2 despite reinforced schemes (Reference S1, SDC, https://links.lww.com/TP/C770).3 In this context, the use of anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) monoclonal antibodies, because preexposure prophylactic strategy has been dramatically helpful to provide passive protection against COVID-19. However, currently available monoclonal antibodies are no longer effective at neutralizing the most recent Omicron variants of SARS-CoV-2.4,5 Hence, vaccination is the unique remaining prophylactic tool against COVID-19 in vulnerable individuals. Unlike KTRs, patients with chronic kidney disease, including those undergoing long-term dialysis, have shown potent vaccine responses against SARS-Cov-2, reaching antibody levels close to those observed in the general population (Reference S3, SDC, https://links.lww.com/TP/C770). Whether a pretransplant vaccination improves the response to subsequent doses after transplantation has yet to be established. To address this important question, we aimed to investigate the trajectory of the SARS-CoV-2-specific humoral immune response following a booster dose in KTRs who had received at least 2 vaccine shots before the transplantation. This retrospective single-center study (Necker Hospital, Paris, France) enrolled all consecutive patients, transplanted between June and December 2021, following a minimum of 2 vaccine doses before the kidney transplantation (KT), in the absence of concurrent immunosuppressive therapy. Forty-nine patients (25 men [51.0%], median age of 57.2 y, interquartile range 42.9–68.1) were enrolled (Table S1 and Material S1, SDC, https://links.lww.com/TP/C770). At time of KT, most patients (93.6%) displayed a positive SARS-CoV-2 serology and 66% showed an anti-Spike IgG titer >264 binding antibody unit (BAU)/mL (median titer of 809 [128.5–3210.0]). In the 26 KTRs who did not receive an additional vaccine shot after transplantation, antibody titers decreased to 131 BAU/mL at M3 and to 136 BAU/mL (24.5–662.5) at the last follow-up, after a median posttransplant time of 5.0 (3.0–6.9) mo (Table S1, SDC, https://links.lww.com/TP/C770). Twenty-three KTRs (46.9%) received a booster dose of messenger RNA COVID-19 vaccine after KT. The median time between KT and first dose was 13.4 wk (11.1–22.1). Nineteen (82.6%) received only 1 posttransplant dose, while 4 patients (17.4%) received an additional one. Most patients exhibited a strong postvaccinal humoral response after one injection: 20 patients (90.9%) showed a postvaccinal anti-Spike titer > 264 BAU/mL (versus 10 before vaccine) and anti-Spike IgG titers increased significantly from 172.0 (48.0–698.5) to 1220.0 (583.8–3299.5), P = 0.0004 (Figure 1). Compared to responders, the nonresponders (to one posttransplant dose) were significantly older, were given more frequently rituximab at induction, and had received a greater number of vaccine doses before KT (Table S2, SDC, https://links.lww.com/TP/C770). One of the nonresponders after the first dose developed an effective response after the second. Interestingly, a strong recall humoral response also occurred in KTRs treated with belatacept after one vaccine dose (anti-Spike IgG titers increased from 590.5 [118.3–987] to 3641.5 BAU/mL [2898.5–3819]), whereas belatacept was found to dramatically hamper the antibody response to COVID-19 vaccine in patients who were vaccine-naive at the time of transplantation (Reference S1, SDC, https://links.lww.com/TP/C770).2Figure 1.: Evolution of anti-SARS-CoV-2 spike IgG at day 0 postkidney transplantation, before and after 1 injection of anti-SARS-CoV-2 mRNA vaccination in 23 KTRs who received anti-SARS-CoV-2 vaccination before transplantation. BAU, binding antibody unit; KT, kidney transplantation; KTR, kidney transplant recipient; mRNA, messenger RNA; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.Eleven patients (22.4%) experienced COVID-19 after KT, including 2 breakthrough infections following posttransplant dose. All but one cases were infected with the Omicron variants (Delta variant in one case). Three patients were admitted to hospital, two of whom experienced a severe infection requiring intensive care unit and eventually died. These latter were infected with the Omicron variants, displayed a weak anti-spike response and were not administered preventive mAbs before COVID-19. Our study is limited by its retrospective nature, by the relatively small number of patients and the lack of data about neutralizing antibodies (which are a better measure of protection than the commercially available anti-spike antibody assay) and vaccine-specific cellular response. However, it clearly demonstrates that a pretransplant vaccination against COVID-19 before KT significantly improves the response to vaccine after KT. Anti-SARS-CoV-2 vaccination is recommended in dialysis patients, who are exposed to severe forms of COVID-19 (Reference S6, SDC, https://links.lww.com/TP/C770). Our data further stress the importance of vaccination in patients on the waiting list for solid-organ transplantation. Pretransplant priming of vaccine-specific responses can dramatically improve the posttransplant vaccine response through the recall stimulation of a preexisting memory response.

Immunometabolic interference between cancer and COVID-19.

Even though cancer patients are generally considered more susceptible to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, the mechanisms driving their predisposition to severe forms of coronavirus disease 2019 (COVID-19) have not yet been deciphered. Since metabolic disorders are associated with homeostatic frailty, which increases the risk of infection and cancer, we asked whether we could identify immunometabolic pathways intersecting with cancer and SARS-CoV-2 infection. Thanks to a combined flow cytometry and multiomics approach, here we show that the immunometabolic traits of COVID-19 cancer patients encompass alterations in the frequency and activation status of circulating myeloid and lymphoid subsets, and that these changes are associated with i) depletion of tryptophan and its related neuromediator tryptamine, ii) accumulation of immunosuppressive tryptophan metabolites (i.e., kynurenines), and iii) low nicotinamide adenine dinucleotide (NAD+) availability. This metabolic imbalance is accompanied by altered expression of inflammatory cytokines in peripheral blood mononuclear cells (PBMCs), with a distinctive downregulation of IL-6 and upregulation of IFNγ mRNA expression levels. Altogether, our findings indicate that cancer not only attenuates the inflammatory state in COVID-19 patients but also contributes to weakening their precarious metabolic state by interfering with NAD+-dependent immune homeostasis.

The Perspectives of Individuals with Comorbidities Towards COVID-19 Booster Vaccine Shots in Twitter: A Social Media Analysis Using Natural Language Processing, Sentiment Analysis and Topic Modeling

Individuals with comorbidities (i.e., Diabetes Mellitus, hypertension, heart diseases) are more likely to develop a more severe form of coronavirus disease 2019 (COVID-19), thus, they should take necessary precautions to avoid infection with severe acute respiratory syndrome coronavirus–2 (SARS-CoV-2) and its emerging variants and subvariants by getting COVID-19 vaccination and booster doses. In this regard, we used text analytics techniques, specifically Natural Language Processing (NLP), to understand the perception of Twitter users having comorbidities (diabetes, hypertension, and heart diseases) towards the COVID-19 vaccine booster doses. Understanding and identifying Twitter users’ perceptions and perspectives will help the members of medical fraternities, governments, and policymakers to frame and implement a suitable public health policy for promoting the uptake of booster shots by such vulnerable people. A total of 176,540 tweets were identified through the scrapping process to understand the perception of individuals with the mentioned comorbidities regarding the COVID-19 booster dose. From sentiment analysis, it was revealed that 57.6% out of 176,540 tweets expressed negative sentiments about the COVID-19 vaccine booster doses. The reasons for negative expressions have been found using the topic modeling approach (i.e., risk factors, fear of myocardial fibrosis, stroke, or death, and using vaccines as bio-weapons). Of note, enhancing the COVID-19 vaccination drive by administering its booster doses to more and more people is of paramount importance for rendering higher protective immunity under the current threats of recently emerging newer Omicron subvariants which are presently causing a rise in cases in a few countries, such as China and others, and might lead to a feasible new wave of the pandemic with the surge in cases at the global level.

The Outcome of COVID-19 Infection in Patients With Gastrointestinal Diseases: An Experience at a Tertiary Center.

Observing the impact of the coronavirus disease 2019 (COVID-19) pandemic on digestive diseases in hospitalized patients at the Department of Gastroenterology-Hepatology in "Mother Teresa" University Hospital Center (UHC),Tirana. This retrospective study was carried out from June 2020 to December 2021 involving 41 cases of patients >18 years who were positive for COVID-19 infection detected by RT-PCR (Reverse Transcription-Polymerase Chain Reaction) assays of nasopharyngeal swab specimens. The severity of COVID-19 infection was evaluated by hematological/biochemical parameters, blood oxygenation/need for oxygen, radiological data on pulmonary CT imaging. Out of 2527 hospitalized cases, 1.6% (41) were positive for the infection. The average age was 60.05 +/- 15.008 years. The group of age with more patients (48.8%) was 41-60 years. Infected males were higher than females (p<0.001). Out of the total, 21% were vaccinated at the diagnosis. Most patients came from urban areas, more than a half from the capital. Frequency of the digestive diseases was: cirrhosis 31.7%, pancreatitis 21.9%, alcoholic liver disease 21.9%, gastrointestinal hemorrhage 19.5%, digestive cancer 14.6%, biliary diseases 7.3%, inflammatory bowel disease (IBD) 2.4%, other digestive diseases 4.8%. Fever (90%) and fatigue (78.04%) were the dominant clinical signs. Biochemical and hematological parameters showed elevation of average value of aspartate amino transferase (AST), alanine transaminase (ALT) (AST>ALT, p<0.001), and bilirubin in all the patients. Higher levels of creatinine andsignificantly predictive value of systemic inflammation indices NLR (neutrophil to lymphocyte ratio) and MLR (monocyte to lymphocyte ratio) were found in the fatality cases. Patients with cirrhosis had more severe form of COVID-19, lower blood oxygenationand needed treatment by O2-therapy (p<0.046). Death rate was 12%. A strong correlation was found between the need for O2-therapy and deaths (p<0.001) and between characteristic findings for COVID-19 in pulmonary CT imaging and low blood oxygenation (p<0.003). Comorbiditywith chronic diseases, such as liver cirrhosis, has an important impact on the severity and mortality of the patients with COVID-19 infection. Inflammatory indices, such as NLR (neutrophil to lymphocyte ratio) and MLR (monocyte to lymphocyte ratio), are useful tools in predicting the evolution toward severe forms of the disease.