Direct bilirubin and the neutrophil-to-monocyte ratio timely predict intensive care unit admission in patients with severe acute respiratory syndrome coronavirus-2 infection (COVID-19)

Objective: Intensive care units (ICUs) collapsed under the global wave of coronavirus disease 2019 (COVID-19). Thus, we designed a clinical decision-making model that can help predict at hospital admission what patients with COVID-19 are at higher risk of requiring critical care. Method(s): This was a cross-sectional study in 119 patients that met hospitalization criteria for COVID-19 including less than 30 breaths per minute, peripheral oxygen saturation < 93%, and/or >= 50% lung involvement on imaging. Depending on the need for critical care, patients were retrospectively assigned to ICU and non-ICU groups. Demographic, clinical, and laboratory parameters were collected at admission and analyzed by classification and regression tree (CRT). Result(s): Forty-five patients were admitted to ICU and 80% of them were men older than 57.13 +/- 12.80 years on average. The leading comorbidity in ICU patients was hypertension. The CRT revealed that direct bilirubin (DB) > 0.315 mg/dl together with the neutrophil-to-monocyte ratio (NMR) > 15.90 predicted up to correctly in 92% of the patients the requirement of intensive care management, with sensitivity of 93.2%. Preexisting comorbidities did not influence on the tree growing. Conclusion(s): At hospital admission, DB and NMR can help identify nine in 10 patients with COVID-19 at higher risk of ICU admission.Copyright © 2022 Sociedad Medica del Hospital General de Mexico.

Liver biomarkers for prognosis in COVID-19

The novel coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2).Mortality attributable to COVID-19 remains considerably high, with case fatality rates as high as 8-11%. Early medical intervention in patients who are seriously and critically ill with COVID-19 reduces fatal outcomes. Thus, there is an urgent need to identify biomarkers that could help clinicians determine which patients with SARS-CoV-2 infection are at a higher risk of developing the most adverse outcomes, which include intensive care unit (ICU) admission, invasive ventilation, and death. In COVID-19 patients experiencing the most severe form of the disease, tests of liver function are frequently abnormal and liver enzymes are found to be elevated. For this reason, we examine the most promising liver biomarkers for COVID-19 prognosis in an effort to help clinicians predict the risk of ARDS, ICU admission, and death at hospital admission. In patients meeting hospitalization criteria for COVID-19, serum albumin < 36 g/L is an independent risk factor for ICU admission, with an AUC of 0.989, whereas lactate dehydrogenase (LDH) values > 365 U/L accurately predict death with an AUC of 0.943.The clinical scores COVID-GRAM and SOFA that include measures of liver function such as albumin, LDH, and total bilirubin are also good predictors of pneumonia development, ICU admission, and death, with AUC values ranging from 0.88 to 0.978.Thus, serum albumin and LDH, together with clinical risk scores such as COVID-GRAM and SOFA, are the most accurate biomarkers in the prognosis of COVID-19.Copyright © 2021 Sociedad Medica del Hospital General de Mexico. Published by Permanyer.

T-cell immune response to SARS-CoV-2 in HIV patients.

Objective. To assess the T-cell immune status against SARS-CoV-2 in HIV patients with or without antiretroviral therapy. Patients and methods. The study included 21 HIV patients who had laboratory-confirmed COVID-19 between September and December 2021 without previous immunization against SARS-CoV-2. The characteristics of HIV infection (CD4-lymphocytes count, HIV viral load in blood plasma, the presence of antiretroviral therapy) and COVID-19 (the severity degree and duration of the disease) were analyzed, the T-cell immune response to SARS-CoV-2 was assessed using the ELISPOT method 1 month after COVID-19. Statistical analysis was carried out by non-parametric methods (Mann-Whitney U test, Spearman's rank correlation coefficient) using the IBM SPSS Statistics 22 software package. Results. The study showed a more favorable course of COVID-19 in HIV-infected persons who achieved HIV suppression in the blood: a mild form of the disease was significantly more common, and the virus was eliminated faster. T-cell immune response to SARS-CoV-2 was recorded more frequently in these patients. Significant correlation of T-cell immune status with the CD4-lymphocytes count and HIV suppression in the blood was revealed. Conclusion. Thus, T-cell immune response to SARS-CoV-2 as assessed using the ELISPOT method was registered significantl.Copyright © 2023, Dynasty Publishing House. All rights reserved.

The impact of deprivation on Respiratory Support Unit outcomes in COVID-19 patients, and highlights from wave 2 data in Portsmouth

Background: The second wave of the COVID-19 pandemic caused significant demand for beds capable of delivering enhanced respiratory support. NHS England recommended the use of CPAP for patients with COVID-19 respiratory failure, a treatment which can be offered outside of a critical care facility, and on a Respiratory High Care/ Support Unit (RSU). The enhancement of Portsmouth's RSU provided CPAP and NIV for patients with COVID-19 respiratory failure. With our intensive care facilities at 300% their normal capacity, this greatly alleviated bed pressures on critical care. Varied levels of deprivation exist in Portsmouth's dense population. Deprivation has an impact on overall health, however the effect of postcode on outcomes for people going onto support for COVID-19 respiratory failure, is unknown. Method(s): Retrospective cohort analysis of consecutive patients admitted to Respiratory Support Unit during the second wave of the COVID-19 pandemic, from 02/11/2020 to 31/01/2021. 227 patients were included in the study with 8 removed due to incomplete data, all of the patients received respiratory support in the form of CPAP or NIV. We collected multivariate data including biochemical markers, demographics, oxygenation status, co-morbidities and outcomes. Outcomes measured were: 1) Death in RSU, 2) Discharge from RSU or 3) Intubation and Ventilation. To measure deprivation, we linked a persons postcode to an area called an LSOA (Lower-layer Super Output Area). These are small areas of similar population size, each of which has a deprivation score (ie. top 10%, to the lowest 10% areas of deprivation in the UK). This is measured using an 'index of multiple deprivation'. An individual's outcome from the RSU was then analysed in relation to the deprivation score allocated to their postcode. Result(s): We observed a significant number of patients discharged from RSU, without needing invasive mechanical ventilation. 80/219 were discharged directly. 45/219 died in RSU, and 94 were eventually admitted to ITU. The average stay on CPAP or NIV before needing admission to ITU was 3 days. Some biochemical markers which stood out in relation to the outcomes described were as follows: average LDH, D-dimer and Troponin levels were higher in those who were admitted to intensive care. In patients who died, the PCT was significantly higher on average when compared to the other two groups. In the group who were discharged, mean lymphocyte count was >1, in the other two groups this was <1. From our observations in Portsmouth, there is a negative correlation between deprivation and lower aged individuals admitted for COVID-19 related respiratory support. Overall, we also saw disproportionate representation of those from the most deprived 50% of the UK in our respiratory support unit. Conclusion(s): CPAP and NIV can effectively be used in an RSU during a spike of COVID-19, to safely minimise demand on critical care services. Deprivation may have an impact on outcomes in patients needing respiratory support related to COVID-19. Deprivation levels may help predict risk of needing enhanced respiratory support in certain age groups. Multiple biochemical markers may be of prognostic value in COVID-19.

Postnatal SARSCOV2 Infection in Neonates, Characteristics and Outcomes: An Observational Study

Background: Many aspects of the severe acute respiratory syndrome coronavirus 2 (SARSCoV2) pandemic in 2019 have been unclear, especially in newborns, and reports of neonatal diseases are usually associated with perinatal infection. Objective(s): The purpose of this study was to evaluate clinical and para-clinical manifestations in newborns that contracted the infection after birth. Method(s): This observational research was conducted from October 2020 to March 2022 to examine postnatal SARSCoV2 infection in infants admitted to the NICU or neonatal ward at the Children's Medical Center in Tehran, Iran. Inclusion in the study was open to neonates who had positive RT-PCR results postnatally. Result(s): In total, 55 newborns were confirmed to have postnatal SARSCOV2. Fever was the most frequently observed symptom, with 35 (61%). Necrotizing enterocolitis was seen in 18% of neonates, and 30% of them were preterm. Neutropenia was seen in 34% of cases, with five cases having severe neutropenia. All neonates had a normal platelet count. Twenty percent of patients showed C-reactive protein higher than 6 mg/L. Two newborns had co-existing bacterial urinary tract infections. Our neonates didn't require antiviral, anticoagulant, or corticosteroid medications, and they recovered while receiving only supportive care. Everyone in the group of newborns was discharged without complications, and there were no deaths. Conclusion(s): The high rate of fever, high C-reactive protein, and neutropenia in SARSCoV2 neonates suggests that more observational research is needed to compare these symptoms to bacterial sepsis to avoid the overuse of antibiotics in these patients.Copyright © 2023, Author(s).

Primary immunodeficiency associated with a SAMD9L mutation

Background: SAMD9L is a tumor suppressor involved in regulating the proliferation and maturation of cells, particularly those derived from the bone marrow, and appears to play an important role in cerebellar function. It can be activated in hematopoietic stem cells by type I and type II interferons. It has been hypothesized to act as a critical antiviral gatekeeper regulating interferon dependent demand driven hematopoiesis. Gain of function mutations can present with an immunodeficiency due to transient severe cytopenias during viral infection. Case presentation: We report a 3-year-old boy born full term with a history of severe thrombocytopenia requiring transfusions, developmental delay, ataxia, seizure disorder, and recurrent severe respiratory viral infections. His infectious history was significant for respiratory syncytial virus with shock requiring extracorporeal membrane oxygenation complicated by cerebral infarction and a group A streptococcus empyema, osteomyelitis requiring a left below the knee amputation, and infections with rhinovirus, COVID-19, and parainfluenza requiring hospitalizations for respiratory support. Initial immunologic evaluation was done during his hospitalization for parainfluenza. His full T cell subsets was significant for lymphopenia across all cell lines with CD3 934/microL, CD4 653/microL, CD8 227/microL, CD19 76/microL, and CD1656 61/microL. His mitogen stimulation assay to phytohemagglutinin and pokeweed was normal. Immunoglobulin panel showed a mildly decreased IgM of 25 mg/dL, but normal IgA and IgG. Vaccine titers demonstrated protective titers to 12/22 pneumococcus serotypes, varicella, diphtheria, mumps, rubella, and rubeola. Repeat full T cell subsets 6 weeks later revealed marked improvement in lymphocyte counts with CD3 3083/microL, CD4 2101/microL, CD8 839/microL, CD19 225/microL, and CD1656/microL. A primary immunodeficiency genetic panel was ordered and positive for a heterozygous SAMD9L c.1549T>C (p.Trp517Arg) mutation classified as a variant of unknown significance. Discussion(s): This patient's history of severe viral infections, ataxia, thrombocytopenia, and severe transient lymphopenia during infection is suggestive of a SAM9DL gain of function mutation. Protein modeling done by the laboratory suggests this missense mutation would affect protein structure. The mutation found has been observed in individuals with thrombocytopenia. This case highlights the importance of immunophenotyping both during acute illness and once recovered.Copyright © 2023 Elsevier Inc.

Clinical and laboratory markers of severity of the new coronavirus infection (COVID-19).

The aim of the research. To study clinical and laboratory features of the new coronavirus infection (COVID-19) in order to develop a model that would allow, taking the publicly available research methods into account, to carry out early diagnosis of severe community-acquired pneumonia against the background of the new coronavirus infection. Material and methods. A total of 82 COVID-19 patients who complied with inclusion and exclusion criteria were enrolled. Depending on the clinical severity, three study groups were formed: group 1 included 13 patients with uncomplicated COVID-19, group 2 consisted of 39 patients with non-severe forms of pneumonia that developed against COVID-19 and group 3 was comprised of 30 patients with COVID-19 complicated by severe pneumonia. The groups were comparable in age and gender. All patients underwent general clinical examination, laboratory tests, including general and biochemical blood analysis, as well as chest computed tomography. Results. The clinical picture in COVID-19 patients differed depending on the disease severity. Coughing and shortness of breath were more often observed in patients with severe pneumonia;sore throat, on the contrary, was more often noted in patients with uncomplicated COVID-19. On admission to the inpatient facility, patients with severe pneumonia had higher body temperature and respiratory rate, with simultaneous decrease in blood oxygen saturation. One half of the patients with severe pneumonia had hypertensive disease in medical history, and one third had ischaemic heart disease. As a rule, uncomplicated COVID-19 patients did not have ischaemic heart disease. It was found through laboratory analysis of blood that groups of patients significantly differed in the levels of neutrophils, lymphocytes, monocytes, basophils and eosinophils. Conclusion. The use of such clinical and laboratory data as acute respiratory failure, fever, the levels of neutrophils, monocytes, lymphocytes, eosinophils and basophils makes it possible to identify patients with more severe pneumonia against the background of COVID-19 even before chest computed tomography. Key words:.Copyright © 2022, Krasnoyarsk State Medical University. All rights reserved.

The Association of COVID-19 Severity with Laboratory Parameters, Radiologic Findings, Maternal and Neonatal Outcomes in Pregnant Women: A Multicenter Study in Indonesia

Objectives: Severe acute respiratory syndrome-coronavirus 2/COVID-19 infection is still a global concern, with pregnant women are considered as vulnerable population. Until now, the characteristics of pregnant women in Indonesia who are infected with COVID-19, as well as pregnancy and neonatal outcomes, are still unknown. This study aims to obtain national data, which are expected to be useful for the prevention and management of COVID-19 in pregnant women in Indonesia. Method(s): There were 1,427 patients recruited in this retrospective multicenter study. This study involved 11 hospitals in 10 provinces in Indonesia and was carried out using secondary patient data from April 2020 to July 2021. COVID-19 severity was differentiated into asymptomatic-to-mild symptoms and moderate-to-severe symptoms. The collected data include maternal characteristics, laboratory examinations, imaging, pregnancy outcomes, and neonatal outcomes. Result(s): Leukocyte, platelets, basophil, neutrophils segment, lymphocytes, monocytes, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, alanine aminotransferase (ALT), aspartate aminotransferase (AST), C-reactive protein (CRP), urea, and creatinine were found to be significantly associated with severity differences (p < 0.05). Moderate-severe symptoms of COVID-19 also shown to have suggestive pneumonia findings on chest X-ray findings. Patients with asymptomatic-to-mild symptoms had significantly (p < 0.001) higher recovery rate, shorter hospital stay, less intensive care unit (ICU) admission, and had more vaginal delivery. Neonates from mother with mild symptoms also had significantly (p < 0.001) higher survival rate, higher birth weight, and higher APGAR score. Conclusion(s): Several laboratory and radiology components, as well as maternal and neonatal outcomes are related to the severity of COVID-19 in pregnant women in Indonesia.Copyright © The Author(s). 2023.

Development of warm autoimmune hemolytic anemia after initiation of Ruxolitinib in a patient with STAT1 gain-of-function mutation

Introduction: STAT1 gain-of-function (GOF) disease is associated with chronic mucocutaneous candidiasis (CMC) and a broad spectrum of infectious, inflammatory, and vascular manifestations. The Janus Kinase inhibitor ruxolitinib has been used successfully for CMC and autoimmune phenomena. We describe a case of warm autoimmune hemolytic anemia (WAIHA) in a patient with STAT1 GOF disease after initiating ruxolitinib. Case report: A 36-year-old man with STAT1 c.850G>A (p.Glu284Lys) mutation presented with CMC as well as recurrent viral and bacterial infections, lymphadenopathy, enteritis, nodular regenerative hyperplasia (NRH) and splenomegaly. Immune workup confirmed a combined immunodeficiency with hypogammaglobulinemia and T-cell lymphopenia. Ruxolitinib was initiated at 5 mg twice daily (due to pre-existing thrombocytopenia) with up titration over 3 months to 20 mg twice daily. He improved with weight gain, increased energy, resolution of chronic anemia, and improved lymphadenopathy and splenomegaly on imaging. Serum CXCL9 only minimally decreased from 4660 pg/ml to 3990 pg/ml. Soon after reaching ruxolitinib 20 mg twice daily, he developed JC viremia, prompting dose reduction to 15 mg BID. Within two weeks, he developed a non-COVID upper respiratory tract infection followed by fatigue, shortness of breath with ambulation, and dark urine. Emergency evaluation revealed warm antibody positive hemolytic anemia with a hemoglobin of 5 g/dL, and worsened thrombocytopenia. He was treated with blood transfusions, pulse steroids, and high-dose IVIG with stabilization but continued hemolysis. Due to the JC viremia, there was concern to give rituximab with increased PML risk. Bone marrow showed trilineage hematopoiesis, a mild increase in megakaryocytes and RBC precursors, and a loss of B-cell progenitors with retention of mature B cells. His B and T lymphocyte numbers had increased since prior to ruxolitinib, with a predominance of Tfh1-cells (58.7% of total Tfh-cells). He was started on sirolimus with a slow taper of prednisone with continued stable hemoglobin and platelets, and resolution of hemolysis after 3 months. Conclusion(s): To our knowledge, this is the first case of a STAT1 GOF patient developing WAIHA while receiving ruxolitinib therapy. Treatment choices were complicated by the risks of PML. Sirolimus combined with ruxolitinib allowed wean of corticosteroid and subsequent resolution of hemolysis.Copyright © 2023 Elsevier Inc.

Diagnostic Role of Platelet to Lymphocyte Ratio and Platelet Parameters in COVID-19 Disease

Backgrounds: This study aimed to analyze the applicability of platelet parameters in assessing the severity of COVID-19 disease. Material(s) and Method(s): Patients with RT-PCR confirmed COVID-19 in the Pathology department of a tertiary care hospital in south India from June to December 2020 were included in this study. Clinical details and laboratory parameters of these patients were obtained. The difference between the studied variables in two groups was assessed using independent t-test. The optimum cut-off value of platelet to lymphocyte ratio (PLR) to differentiate between the tested groups was estimated using ROC (receiver operator curve) analysis. Finding(s): This study was conducted on 218 COVID-19 patients, of whom 17.9% showed thrombocytopenia at the time of admission. Among the hematological parameters, PLR, absolute lymphocyte count (ALC), platelet distribution width (PDW), D-dimer, and erythrocyte sedimentation rate (ESR) were significantly different between the ICU (intensive care unit) and non-ICU groups. Increased PLR values were associated with the disease severity. Conclusion(s): PLR could be used as an additional biomarker in assessing the severity of COVID-19 disease, and a cut-off value of 210.27 is optimal to differentiate severe COVID-19 disease from its mild and moderate forms with 79% specificity.Copyright © 2023, TMU Press.

Successful ECMO course in an Acquired Immune Deficiency Syndrome (AIDS) patient with ARDS complicated by pneumocystis jirovecii pneumonia and COVID-19: A unique case

Objectives: Reviewing current literature and case reports of patients placed on Venous-Venous ECMO support for HIV and AIDS, with confection with Pneumocystis pneumonia and covid-19 pneumonia. The use of extracorporeal membrane oxygenation (ECMO) in patients who have acute respiratory distress syndrome has been shown to have very good outcomes. However, there is limited data to support the initiation of ECMO in patients who have human immunodeficiency virus infection with or without acquired immune deficiency syndrome. Method(s): We present a unique and challenging case of a 30 year old male, with no known past medical history, unvaccinated against covid-19, who presented with one week of progressive shortness of breath. On admission he was found with moderate bilateral infiltrates and was diagnosed with covid-19 pneumonia. Despite appropriate medical therapy, patient developed worsening hypoxic respiratory failure. Found to have elevated (1- 3)-7beta;-d-glucan and tested positive for HIV. CD4 count 11, HIV viral load 70,000. The patient remained severely hypoxemic despite mechanical ventilation, sedation, paralytics and proning. Venous venous extracorporeal membrane oxygenation was initiated. Considering his non improvement with variety of antivirals and antibiotics and with elevated (1-3)-7beta;-d-glucan in the setting of AIDS he was treated for presumed Pneumocystis pneumonia. The patient tolerated proning while on VV ECMO and his course was complicated with bilateral pneumothorax necessitating chest tube placement. Result(s): The patient successfully completed 64 days on VV ECMO, where he was treated for PCP pneumonia, covid pneumonia, CMV viremia and tolerated initiation of anti-retroviral therapy. Patient was successfully decannulated, and ultimately discharged from the hospital. Conclusion(s): VV-ECMO can be a beneficial intervention with successful outcomes in severely immunocomprimised patients with AIDS. This case highlights the importance of minimizing sedation and early mobilization on ECMO support. (Figure Presented).

Analyses of kidney biomarkers in patients with sars-cov-2 (Covid-19)

The new coronavirus was first reported in China and caused a widespread global outbreak of pneumonia that spread rapidly across this country and many other countries. Acute kidney injury is one of the important complications of COVID-19, which has been shown in some cases. Exploring the diagnostic features of biomarkers of kidney function in COVID-19 patients may lead to better patient management. We collected laboratory data from 206 people with confirmed COVID-19 disease and evaluated their renal biomarkers, Blood Urea Nitrogen (BUN), and creatinine. The age range of the patients was almost 62 years old. The mean age in the dead patients and recovered patients was 71 and 54 years old, respectively. The average LDH value was 755 U/L, and creatine phosphokinase (CPK) was 267 U/L in the patients. The average BUN was 59.1 U/L, and creatinine was 1.5 U/L in COVID-2019 patients. Among all 193 patients, laboratory results revealed that 163 (85.4%) patients had an elevated BUN level. Based on creatinine levels for total patients, laboratory results revealed that 49 (25.4%) patients had an elevated value. The average BUN value in dead patients was 85 mg/dL, while in recovered patients was 40.5 mg/dL (P<0.0001). Also, the average creatinine level in dead patients was 1.86 mg/dL, while in recovered patients was 1.24 mg/dL (P=0.0004). Inflammation following COVID-19 disease causes kidney damage and elevated urea and creatinine levels, which may increase the risk of death in these patients.Copyright © 2023 Tehran University of Medical Sciences.

A baby girl with TBX1 haploinsufficiency who died after elective cardiac repair surgery due to suspected enteroviral meningitis

Introduction: TBX1 haploinsufficiency is an inborn error of immunity with the phenotype of DiGeorge Syndrome. DiGeorge Syndrome has variable immunodeficiency associated with grade of thymic hypoplasia ranging from mild with no infections to severe requiring thymus implant. Enterovirus is an example of an opportunistic infection that can be fatal in these patients. Case Presentation: A 1 year old girl with TBX1 haploinsufficiency complicated by Tetralogy of Fallot, pulmonary atresia, high arched palate, and vesicovaginal fistula presented for elective cardiac repair surgery from another country due to failure to thrive and cyanosis. She had no prior infectious history but was on sulfamethoxazole-trimethoprim for prophylaxis. She was asymptomatic with a negative COVID test but no other infectious studies performed. Immediately postoperatively, she was febrile and nasal respiratory viral panel was positive for rhinovirus/enterovirus with increased procalcitonin and leukocytosis with left shift. She decompensated with multi-organ failure and cardiac arrest on postoperative day two. She was cannulated to veno-arterial extracorporeal membrane oxygenation (ECMO). Pre-operatively, she had a normal absolute lymphocyte count. No thymus tissue was observed in surgery. She had profound CD3 lymphopenia to 130 cells/cmm when critically ill. Enteroviral meningitis was suspected as no infectious, cardiac, or other pathology could be identified causing decompensation. Enteroviral serum polymerase chain reaction (PCR) test was negative while lumbar puncture deferred due to clinical status. She was treated with immunoglobulin. Offlabel investigational drug pocapavir was considered but deferred to patient's irreversible neurological status. The patient was disconnected from ECMO and expired. Discussion(s): Though we cannot confirm that this patient had enteroviral meningitis, invasive enteroviral infections are associated with elevated transaminases, coagulopathy, and seizures all present in our patient. There has also been reported negative serum enteroviral PCR but positive CSF enteroviral PCR in an immunodeficient patient. Additionally, this case highlights the importance of immunologic evaluation in patients with DiGeorge Syndrome and questions if asymptomatic viral screening for viruses like enterovirus should be considered pre-operatively in patients with inborn errors of immunity. This case highlights potential treatment options for invasive enteroviral infections in patients with inborn errors of immunity: high dose immunoglobulin, fluoxetine, and pocapavir.Copyright © 2023 Elsevier Inc.

Persistent lymphocyte reduction and interleukin-6 levels are independently associated with death in patients with COVID-19.

To investigate the value of the peripheral blood lymphocyte count (LYM) combined with interleukin-6 (IL-6) in predicting disease severity and prognosis in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia. This was a prospective observational cohort study. A total of 109 patients with SARS-CoV-2 pneumonia who were admitted to Nanjing First Hospital from December 2022 to January 2023 were enrolled. The patients were divided into two groups based on disease severity: severe (46 patients) and critically ill (63 patients). The clinical data of all patients were collected. The clinical characteristics, sequential organ failure assessment (SOFA) score, peripheral blood lymphocyte count, IL-6 level and other laboratory test results were compared between the two groups. A receiver operating characteristic (ROC) curve was plotted to evaluate the predictive value of each index for SARS-CoV-2 pneumonia severity; patients were regrouped using the optimal cut-off value of the ROC curve, and the relationship between different LYM and IL-6 levels and the prognosis of patients was analysed. Kaplan‒Meier survival curve analysis was performed; in the different LYM and IL-6 groups, the patients were regrouped based on whether thymosin was used, and the effect of thymosin on patient prognosis was compared between the groups. Patients in the critically ill group were significantly older than patients in the severe group (age: 78 ± 8 vs. 71 ± 17, t = 2.982, P < 0.05), and the proportion of patients with hypertension, diabetes and cerebrovascular disease was significantly higher in the critically ill group than in the severe group (69.8% vs. 45.7%, 38.1% vs. 17.4%, 36.5% vs. 13.0%; χ2 values, 6.462, 5.495, 7.496, respectively, all P < 0.05). Compared with the severe group, the critically ill group had a higher SOFA score on admission (score: 5.4 ± 3.0 vs. 1.9 ± 1.5, t = 24.269, P < 0.05); IL-6 and procalcitonin (PCT) in the critically ill group were significantly higher than those in the severe group on the first day of admission [288.4 (191.4, 412.9) vs. 513.0 (288.2, 857.4), 0.4 (0.1, 3.2) vs. 0.1 (0.05, 0.2); Z values, 4.000, 4.456, both P < 0.05]. The lymphocyte count continued to decline, and the lymphocyte count on the 5th day (LYM-5d) was still low (0.6 ± 0.4 vs. 1.0 ± 0.4, t = 4.515, both P < 0.05), with statistically significant differences between the two groups. ROC curve analysis indicated that LYM-5d, IL-6 and LYM-5d + IL-6 all had value for predicting SARS-CoV-2 pneumonia severity; the areas under the curve (AUCs) were 0.766, 0.725, and 0.817, respectively, and the 95% confidence intervals (95% CI) were 0.676-0.856, 0.631-0.819, and 0.737-0.897, respectively. The optimal cut-off values for LYM-5d and IL-6 were 0.7 × 109/L and 416.4 pg/ml, respectively. LYM-5d + IL-6 had the greatest value in predicting disease severity, and LYM-5d had higher sensitivity and specificity in predicting SARS-CoV-2 pneumonia severity. Regrouping was performed based on the optimal cut-off values for LYM-5d and IL-6. Comparing the IL-6 ≥ 416.4 pg/ml and LYM-5d < 0.7 × 109/L group with the other group, i.e., patients in the non-low-LYM-5d and high-IL-6 group, patients in the low-LYM-5d and high-IL-6 group had a higher 28-day mortality rate (71.9% vs. 29.9%, χ2 value 16.352, P < 0.05) and a longer hospital stay, intensive care unit (ICU) stay and mechanical ventilation time (days: 13.7 ± 6.3 vs. 8.4 ± 4.3, 9.0 (7.0, 11.5) vs. 7.5 (4.0, 9.5), 8.0 (6.0, 10.0) vs. 6.0 (3.3, 8.5); t/Z values, 11.657, 2.113, 2.553, respectively, all P < 0.05), as well as a higher incidence of secondary bacterial infection during the disease course (75.0% vs. 41.6%, χ2 value 10.120, P < 0.05). Kaplan‒Meier survival analysis indicated that the median survival time of patients in the low LYM-5d and high-IL-6 group was significantly shorter than that of patients in the non-low LYM-5d and high-IL-6 group (14.5 ± 1.8 d vs. 22.2 ± 1.1 d, Z value 18.086, P < 0.05). There was no significant difference in the curative effect between the thymosin group and the nonthymosin group. LYM and IL-6 levels are closely related to SARS-CoV-2 pneumonia severity. The prognosis for patients with IL-6 ≥ 416.4 pg/ml at admission and a lymphocyte count < 0.7 × 10 9/L on the 5th day is poor.

Acute liver injury in COVID-19 patients in Cohort Ward, Somdejphrachaotaksin Maharaj Hospital

Objective: To study the prevalence and risk factors for acute liver injury in COVID-19 patients and to assess the clinical outcome of COVID-19 in patients with acute liver injury in cohort ward, Somdejphrachaotaksin Maharaj Hospital. Method(s): A cross-sectional study was done in moderate-to-severe COVID-19 patients who hospitalized in cohort ward, Somdejphrachaotaksin Maharaj Hospital. Demographic data, laboratory results and clinical data were collected during 1st April to 31st October 2021. Result(s): From total of 93 COVID-19 patients, the prevalence of acute liver injury (ALI) were 28% (95%CI 18.6-37.2). Factor associated with acute liver injury was male (p<0.05). Mean absolute lymphocyte count of ALI patients and non-ALI patients were 1154.77 and 1530.02 respectively (p = 0.063). There was no difference in vasopressor support, ventilator support, length of stay and dead of COVID-19 patients between ALI group and non-ALI group. Conclusion(s): The prevalence of acute liver injury among COVID-19 patients was high. Factor associated with acute liver injury were male and tendency of lower absolute lymphocyte count. There were differences in clinical outcome of COVID-19 patients between acute liver injury and non-acute liver injury.

Single-centre review of rapid antiretroviral therapy initiation during the COVID-19 pandemic

Background: BHIVA released interim guidance on first line anti-retroviral therapy (ART) initiation during the COVID-19 pandemic, when investigations/follow-up was restricted. Our HIV service didn't restrict follow-up but suspended in-house resistance testing (RT) due to laboratory capacity. Having prescribed 'rapid ART' based on the Northern Algorithm 01/08/2020-01/01/2022 we wanted to evaluate our prescribing during the pandemic. Method(s): All new HIV diagnoses 01/08/2020-31/12/2021 were identified via our HARS dataset. Retrospective casenote review identified ART prescribed, and switches that occurred upon baseline RT availability, to more suitable and/or cost-effective regimes. Result(s): 32 new diagnoses: 11 female, 21 male, median age 41 years (17-81), 10 MSM, 22 Heterosexuals, White British 14, African 9, other 7. Median time to ART initiation 10 days (0-210). Median CD4 count 359 (2-1251), 8 had CD4<200. 7/32 had Primary HIV infection, 5 initiating ART at 1st visit. 30/32 started ART within our service, 1 relocated, 1 initiated abroad. 28/30 started algorithm compliant rapid ART. Of the 2 that delayed, 1 had significant resistance, the other patient choice. 8/30 (27%) 'rapid ART' initiations switched post RT availability. Conclusion(s): All patients initiating ART in our service during the pandemic were algorithm compliant and fulfilled BHIVA recommendations. 7/10 starting Darunavir/ r-based therapy switched to Delstrigo post RT, a more cost-effective STR. Zero patients on Biktarvy switched post RT;implying it's difficult to switch patients from small INSTI-based-STRs. Future work includes comparing our results with other centres and reviewing ART switches post HIV National Prescribing Guide implementation. (Table Presented).

Clinical epidemiology of COVID-19 in Black people with HIV in south London, UK

Background: The COVID-19 pandemic disproportionally affected Black communities who were at greater risk of SARS-CoV-2 acquisition, morbidity, and mortality than those of White ethnicity. We describe the clinical epidemiology of COVID-19 in the GEN-AFRICA cohort of Black people with HIV in two South London clinics. Method(s): First reported episodes of COVID-19 up to 12/2021 were ascertained by direct questioning and/or medical records review. The cumulative incidence of COVID-19 and vaccination was determined by Nelson- Aalen methods. Pre-pandemic immunovirological and comorbidity status obtained prior to 01/2020 was used to identify risk factors for COVID-19 using Cox regression. We compared characteristics of participants with mild/ moderate (not requiring hospitalization) and severe (requiring hospitalization or resulting in death) COVID-19. Result(s): COVID-19 status was available for 1184 (95%) of 1289 GEN-AFRICA participants (mean age 49.1 years;55% female;median CD4 565;93% HIV RNA <200), and SARS-CoV-2 vaccination status for 1160;998 (86%) had received at least one vaccine dose (administered to 50% by 16/02/2021). A total of 310 participants (26.2%) reported a first episode of COVID-19 (any severity), with a cumulative incidence of 6%, 14%, 15% and 22% following the initial, alpha, delta, and omicron waves. Women, people of East African ancestry, and those with detectable HIV RNA were more likely to report COVID-19 (Table). CD4 (current/nadir), class of antiretroviral therapy (ART), and comorbidity status were not associated with COVID-19. Findings were similar when restricted to episodes in 2020 (prior to vaccine availability) or testconfirmed COVID-19. Severe COVID-19 cases (N=34) were more often male (p=0.002), of West-African ancestry (p=0.01), with lower CD4 cell counts (p=0.002), and they more often had a history of AIDS, diabetes mellitus, cardiovascular disease, and chronic kidney disease (all p=0.001) compared to mild/moderate cases;they were also more likely to be on protease inhibitor (PI)- containing ART (p=0.01). Conclusion(s): By the end of the second year of the pandemic, 22% of black people with HIV in South London had experienced COVID-19. Immune and comorbidity status were not associated with COVID-19 when all cases were considered but strongly associated with severe COVID-19 disease, as were West-African ancestry and being on a PI. (Table Presented).

Week 48 results of a phase 3 randomized controlled trial of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) vs dolutegravir 1 emtricitabine/tenofovir disoproxil fumarate (DTG 1 F/TDF) as initial treatment in HIV-1/HBV-coinfected adults (ALLIANCE)

Background/Aims: The clinical course of hepatitis B virus (HBV) infection in individuals with HIV-1 coinfection is marked by accelerated disease progression. A tenofovir-containing antiretroviral regimen is recommended in most people with HIV-1/HBV-coinfection, but there have not been randomized studies of tenofovir disoproxil fumarate (TDF) vs tenofovir alafenamide (TAF) in treatment- naive HIV-1/HBV-coinfected individuals. We report primary endpoint results from a Phase 3 study comparing bictegravir/emtricitabine/ TAF (B/F/TAF) vs dolutegravir + emtricitabine/TDF (DTG + F/TDF) at Week (W)48 in participants initiating treatment for both viruses. Method(s): Adults with HIV-1/HBV coinfection were randomized 1:1 to initiate blinded treatment with B/F/TAF or DTG + F/TDF (with placebo). Primary endpoints were the proportion of participants with HIV-1 RNA<50 copies/mL (FDA Snapshot) and plasma HBV DNA<29 IU/mL (missing = failure) at W48. Noninferiority was assessed with 95% CI (12% margin). Secondary and other endpoints included change from baseline cluster of differentiation 4 (CD4) count, proportion with hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) loss/seroconversion, and alanine transaminase (ALT) normalization (AASLD criteria). Result(s): Participants (N = 243) were randomized and treated (B/F/ TAF [n = 121], DTG + F/TDF [n = 122]) from 11 countries in Asia, Europe, North, and Latin America. Baseline characteristics were median age of 32 years, 4.5% female, 88% Asian, 30% HIV-1 RNA>100,000 c/mL, 40% CD4<200 cells/lL, median HBV DNA 8.1 log10 IU/mL, 78% HBeAg+. At W48, B/F/TAF was noninferior to DTG + F/TDF at achieving HIV-1 RNA<50 copies/mL (95% vs 91%, difference 4.1%;95% CI -2.5%-10.8%;P = 0.21), with mean CD4 gains of + 200 and + 175 cells/lL, respectively. B/F/TAF was superior to DTG + F/TDF at achieving HBV DNA<29 IU/mL (63% vs 43%, difference 16.6%;95% CI 5.9%-27.3%;P = 0.0023). Participants treated with B/F/TAF vs DTG + F/TDF had numerically higher HBsAg loss (13% vs 6%;P = 0.059), HBeAg loss (26% vs 14%;P = 0.055), HBeAg seroconversion (23% vs 11%;P = 0.031), and ALT normalization (73% vs 55%;P = 0.066). The most frequent adverse events among participants treated with B/F/TAF vs DTG + F/TDF were upper respiratory tract infection (17% vs 11%), COVID- 19 (13% vs 11%), pyrexia (9% vs 12%), ALT increase (7% vs 11%), and nasopharyngitis (11% vs 4%). ALT flares (elevations at >= 2 consecutive postbaseline visits) occurred in 11 participants (7 B/F/ TAF, 4 DTG + F/TDF), and all resolved. Conclusion(s): Among adults with HIV-1/HBV-coinfection starting antiviral therapy, both B/F/TAF and DTG + F/TDF had high HIV-1 suppression at year 1, with B/F/TAF resulting in superior HBV DNA suppression and significantly more HBeAg seroconversion. Safety findings were similar between groups.

Rituximab and Covid-19 Vaccines, Are They Fit for Purpose?

Background/Aims Since the COVID-19 outbreak the rheumatology community have been concerned about the risk of SARS-CoV-2 infection in patients prescribed immunosuppressing medications. Data suggests that patients receiving Rrtuximab are at increased risk of developing severe outcomes from COVID-19 (1). In our unit all patients receiving rituximab were selected to receive a targeted vaccination and booster programme with all patients receiving at least 2 vaccinations and up to 3 booster vaccinations. We studied the efficacy of the COVID-19 vaccines in rituximab patients, by checking the the Roche Elecsys Anti-SARS-CoV-2-S (Spike) IgG/IgM total antibody levels post vaccination. Our aim was to assess the vaccination response in patients receiving rituximab and to offer advice on continued shielding or alternatively passive immunization with tixagevimab/cilgavimab in those patients who did not mount a response. Methods Taking 39 patients currently on rituximab therapy, we measured Anti- SARS-CoV-2-S (Spike) antibody levels post vaccination. We recorded whether the test was positive or negative, and the numerical result. We recorded rituximab dates of administration and dates of vaccines. We also recorded diagnosis, co-prescribed DMARDs, immunoglobulin levels, white cell and lymphocyte counts. We took record of whether or not the patient subsequently contracted COVID-19, required a hospital admission, ICU or died. Results Of our 39 patients, 21 had Anti-SARS-CoV-2-S (Spike) antibody levels checked. Of these patients, 7 (33%) had a negative spike protein result. Of the patients with a positive result, 8 (38%) had an antibody level between 0-250U/ML, and only 6 (28.6%) had a level >250U/ML (The manufacturer advises that a level above 0.8U/ML is a positive result). Of patients with a negative result, 1 patient had received 3 vaccines, 5 patients had received 4, and 1 patient had 5. All of the patients had received a vaccine >4 weeks prior to receiving the drug. Two patients were co-prescribed Belimumab, 3 were co-prescribed low-dose methotrexate and 2 were not on additional disease modifying agents. The diagnoses of these patients were, 2 patients with SLE, 4 with SPRA, and 1 MPO Vasculitis. There were no significant findings in lymphocyte count, white cell count or immunoglobulin levels. Conclusion These findings suggest that our current COVID-19 vaccination and booster programme may not provide adequate response in patients receiving rituximab therapy. Despite this being a small cohort, these results show that 33% of patients have not mounted a vaccine response and this is concerning. We suggest that vaccine response should be checked in all patients receiving rituximab therapy and those patients who do not mount a vaccine response should be offered passive immunity and advised of possible additional risks regarding COVID-19 exposure.

Prognostic criteria for the development of severe clinical forms of COVID-19 in medical organization workers

Employees of medical organizations are one of the risk groups for infection with a new coronavirus infection (COVID-19), including with the development of severe clinical forms. The aim of the study was to analyze the clinical manifestations of a new coronavirus infection in medical workers with the determination of laboratory markers for the development of severe COVID-19. Material and methods. The study included 186 medical workers who had COVID-19 in 2020. In 67 people (observation group), the disease occurred in the form of pneumonia, in 119 people (comparison group) - acute respiratory infection caused by SARS-CoV-2. In the acute period of the disease, a laboratory examination was carried out: a general clinical blood test, CD-typing of lymphocyte subpopulations, assessment of biochemical parameters, determination of parameters of the hemostasis system and cytokine levels. Using the binary logistic regression method, we have built multifactor models. To determine the threshold values of the indicators, we used ROC analysis. Statistical processing of materials was carried out using Microsoft Office 2016 and IBM SPSS Statistics (version 26). The differences were considered statistically significant at p<0.05. Results and discussion. The most frequent clinical manifestations of COVID-19 were: weakness, fever, myalgia, arthralgia, difficulty in nasal breathing, serous-mucous discharge from the nose, sore throat, cough, feeling of "tightness" in the chest, shortness of breath, headache, pain in the eyeballs, dizziness, anosmia, ageusia and dyspeptic manifestations in the form of diarrhea, nausea or vomiting. Markers associated with the development of severe pneumonia associated with COVID-19 have been identified. Threshold values of laboratory parameters for predicting the severe course of COVID-19 were determined: the number of platelets (less than 239x109/l), lymphocytes (less than 1.955x109/l), cytotoxic T-lymphocytes (less than 0.455x109/l), T-helper cells (less than 0.855x109/l), NK-cells (less than 0.205x109/l), ESR (more than 11.5 mm/h), LDH (more than 196 units/l), total protein (less than 71.55 g/l), D-dimer (more than 0.325 mcg/ml), CRP (more than 4.17 mg/l), IL-6 (more than 3.63 pg/l). Conclusion. The data obtained make it possible to predict the possibility of developing a severe variant of the COVID-19 course.Copyright © 2022 Infectious Diseases: News, Opinions, Training. All rights reserved.