Severe COVID-19 Research Articles

Case-control study on risk factors for in-hospital mortality in patients with severe COVID-19.

The purpose of this study was to identify independent risk factors affecting patient survival and explore predictors of severe cases of coronavirus disease 2019 (COVID-19). We conducted a retrospective, observational, case-control study on adult patients with severe COVID-19 who were admitted to affiliated hospitals in Tianjin between December 18, 2022, and January 31, 2023. We used univariate and multifactorial logistic regression analyses to analyze demographic indicators, comorbidity profiles, and laboratory parameters in two groups of patients (deceased and surviving) to identify independent risk factors for death in patients with severe COVID-19. Patients in the deceased group were older than those in the survival group (p = 0.018), and there were more cases of coexisting respiratory insufficiency in the deceased group (p = 0.002). Additionally, laboratory test results for white blood cell count (WBC) and creatine kinase (CK) showed significantly higher values in the deceased group (p = 0.047 and p = 0.029, respectively), while arterial oxygen partial pressure (PAO2) showed significantly lower values compared to the survival group (p = 0.021). Age, respiratory insufficiency, WBCH (highest WBC value), CKH (highest CK value), and PAO2F (first PAO2 value) had area under curve (AUC) values of 0.698, 0.838, 0.721, 0.744, and 0.633, respectively. The main risk factors for mortality in patients with severe COVID-19 that we identified in this study were the advanced age of patients, coexisting respiratory insufficiency, elevated levels of WBC and CK, and decreased levels of PAO2. Elevated WBC and CK laboratory parameters, in particular, demonstrated good predictive value for in-hospital mortality risk.

Role of SARS-CoV-2-specific memory B cells promoting immune protection after booster vaccination in solid organ transplantation.

Solid organ transplant (SOT) recipients display weak seroconversion and neutralizing antibody (NAb) responses after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination and remain at risk of severe coronavirus disease 2019 (COVID-19). While B-cell memory is the hallmark of serological immunity, its role in driving successful vaccine responses and providing immune protection in SOT patients remains unclear. We investigated the function and interplay of SARS-CoV-2-specific memory B cells (mBc), different cytokineproducing T cells, and cross-reactive NAb in driving seroconversion and protection against COVID-19 in two cohorts. First, we studied a large cohort of 148 SOT recipients and 32 immunocompetent individuals who underwent several vaccinations. Subsequently, we assessed 25 SOT patients participating in a randomized controlled trial to compare two different immunosuppressive strategies for allowing successful seroconversion and memory-cell responses after booster vaccination. We corroborate previous findings that B- and T-cell memory responses are weaker and more delayed in SOT patients than in immunocompetent (IC) individuals; however, within the SOT cohort, we found that these responses are relatively stronger and more robust in patients not receiving mycophenolate mofetil (MMF)-based therapies. Anti- spike IgG titers strongly correlated with RBD-specific IgG-producing mBc, with both displaying broad viral cross reactivity. Prebooster SARS-CoV-2-specific mBc and IL-2- producing T cells accurately predicted Nab seroconversion (AUC, 0.828) and protection against severe COVID-19. While switching unresponsive SOT patients from calcineurin inhibitors (CNI)/MMF to a low-exposure CNI/mTOR-i regimen favored wider SARS-CoV-2-specific immune responses after a fourth booster vaccination, preformed RBD-specific mBc predicted NAb seroconversion. Our study adds new insights into the pathobiology of immune memory and highlights the pivotal role of SARS-CoV-2-specific mBc in promoting immune protection inSOT patients.

Forensic assessment of maternal deaths from the COVID-19 during the 2021 pandemic

BACKGROUND: According to the literature, the mortality rate from SARS-CoV-2 infection among pregnant women is up to 25%. The high-risk group for the development of severe forms of COVID-19 includes pregnant women with extragenital pathology. Obstetric tactics are determined by the severity of the condition of the mother and fetus, as well as the duration of pregnancy. The decision on early delivery is made as a result of an interdisciplinary medical consultation. Delivery in the midst of the disease is associated with an increase in maternal mortality. According to the literature, including our own research, it has been established that the basis for favorable perinatal outcomes in patients with severe and moderate forms of COVID-19 is: an adequate assessment of the condition of the pregnant woman and fetus (especially at the outpatient stage, where the pregnant woman goes first), early hospitalization, early initiation of intensive care and timely delivery before the onset of irreversible organ changes in pregnant women. AIM: The aim of this study was to analyze the tactics of pregnancy management, delivery and perinatal outcomes, assessing the quality of medical care at the outpatient and hospital stages provided to pregnant women who died in a specialized obstetric hospital from the extremely severe new coronavirus infection COVID-19 (based on the data of commission forensic examinations). MATERIALS AND METHODS: This retrospective study of pregnancy outcomes was performed in 11 patients who died from complications of extremely severe COVID-19 in a regional specialized obstetric hospital in Russia based on the data of commission forensic examinations performed in the Bureau of Forensic Medical Examination (Saint Petersburg, Russia) in 2021, at gestation periods of 28–34 weeks (n = 7) and 37–39 weeks (n = 4) in the context of assessing the quality of medical care in the field of obstetrics and gynecology. We confirmed the diagnosis of the new coronavirus infection COVID-19 in 10 (90.9%) patients by SARS-CoV-2 RNA identification using polymerase chain reaction in a nasopharyngeal smear on an average of 4.9 ± 3.6 days from the onset of the disease. In one patient, the clinical diagnosis was confirmed postmortem by the detection of SARS-Cov-2 RNA during autopsy (in the trachea, lungs, and spleen). All patients in the hospital underwent a comprehensive anamnestic, clinical and laboratory examination in the amount regulated by the administrative regulations of the Ministry of Health of the Russian Federation that were relevant at the time of providing medical care. Nine (81.8%) patients sought medical help from a local therapist on 3.1 ± 1.6 days from the onset of the disease and received outpatient treatment for 3.4 ± 1.8 days, two patients not seeing a doctor and receiving outpatient care. The average time before admission to the specialized obstetric hospital was 6.0 ± 2.2 days from the onset of the disease. RESULTS: During the forensic assessment of the medical records of deceased patients, significant defects in the quality of medical care were identified in the framework of this study at the stages of information collection, diagnosis, treatment, and succession. An indirect causal relationship was established between the most significant defects in the quality of medical care and adverse pregnancy outcomes, since the cause of death or critical conditions were individually determined severe complications, rather than defects in medical care, which, nevertheless, does not exclude their significance in the totality of causes of severe maternal outcomes. CONCLUSIONS: The data obtained indicate the need for earlier delivery in pregnant women with the new coronavirus infection COVID-19 before the appearance of irreversible changes in patients with progressive respiratory failure, multiple organ failure syndrome, systemic inflammatory response syndrome, and cytokine storm.

COVID-19 Disease Incidence and Severity in Previously Infected Unvaccinated Compared with Previously Uninfected Vaccinated Persons.

Using the VA COVID-19 National Database, we created matched pairs of previously uninfected vaccinated (≥2 doses of an mRNA vaccine) and previously infected unvaccinated individuals. The incidence rate (per 1000 person-days) of breakthrough infection among vaccinated individuals (0.30, 95% CI 0.29-0.32) was similar to reinfection rate among unvaccinated individuals (0.31, 95% CI 0.30-0.32; p=0.5). The incidence rate of hospitalization/death was higher after reinfection (7.31, 95% CI 6.66-8.03) compared with rate after breakthrough infection (4.69, 95% CI 4.06-5.42; P<0.0001). Conclusion: The incidence of hospitalization/death is significantly higher after reinfection among unvaccinated individuals compared with breakthrough infection after vaccination.

The effect of severe COVID-19 infection on biochemical markers (FBS, HbA1C, FA, INS, C-Pep) in diabetic patients

Background &amp; objective: Several studies have been conducted around the world on the impact of COVID-19 on people with diabetes mellitus (DM). Any acute illness can cause stress and increased inflammatory reactions, which increase sympathetic outflow and produce catecholamines, growth hormones, cortisol, and cytokines, all of which raise the risk and severity of complications from diabetes. Diabetes is a significant risk factor for the severity of COVID-19. We conducted this study to identify whether severe COVID-19 infection has any effect on the biomarkers, including fasting blood sugar (FBS), HbA1C, FA, INS, C-Pep, in individuals with DM. Methodology: This study was simultaneously conducted at Department of Chemistry and Biochemistry, College of Medicine of Al-Nahrain University, and Department of Medicine of Mustansiriyah University College of Medicine, Baghdad, Iraq. During the months of February and March 2022, 50 COVID-19 patients with diabetes and 50 COVID-19 patients without diabetes were included in the study. The control group included 100 healthy, sexually identical people (age 50-80), collected under the supervision of the second supervisor from relatives and students of Mustansiriyah University, College of Medicine. Venous blood samples of 5 mL were taken from all participants and subjected to laboratory tests to detect the levels of the biomarkers. Results: Average FBS level in DM patients was 304.9 mg/dL, (range 132-545.9 mg/dL), which was remarkably higher than in non-DM patient groups (193.3 mg/dL), range (of 66.2–458). The DM patients' group had a significantly higher concentration of HbA1C (median = 6.70 mg/dL, range 5.2-8.1) than the non-DM patient group (median = 5.8, range 4.2–7.6) with a significant difference. Although The group of DM patients had significantly greater FA concentrations than the group of non-DM patients. In contrast, the median and range for insulin and c-peptide Displays non-significant differences for covid-19 patients (DM and non-DM), but it's significant with a control group. Conclusion: According to this study, COVID-19 patients with diabetes had greater biochemical indicator levels than non-diabetic people. Pre- and postprandial hyperglycemia and diabetic ketoacidosis were more common in COVID-19 DM patients than in non-infected DM patients. We found that COVID-19 increased the severity risk for T2DM patients and glucose level is raised and progresses in a vicious cycle exacerbated by insulin resistance (IR) and decreased pancreatic b-cell function. Keywords: COVID-19, Diabetes mellitus, FBS, HbA1C, FA, INS, C-Pep Citation: Yones MS, Al-Wasiti E, Al Qaseer AH, Al-Rubaiawi HK. The effect of severe COVID-19 infection on biochemical markers (FBS, HbA1C, FA, INS, C-Pep) in diabetic patients. Anaesth. pain intensive care 2024;28(5):804−808; DOI: 10.35975/apic.v28i5.2553 Received: June 01, 2024; Reviewed: June 19, 2024; Accepted: June 19, 2024

Genetic signatures of AKT1 variants associated with worse COVID-19 outcomes - a multicentric observational study.

The COVID-19, triggered by the SARS-CoV-2 virus, has varied clinical manifestations, ranging from mild cases to severe forms such as fatal pneumonia and acute respiratory distress syndrome (ARDS). Disease severity is influenced by an exacerbated immune response, characterized by high pro-inflammatory cytokine levels. Inhibition of AKT can potentially suppress pathological inflammation, cytokine storm and platelet activation associated with COVID-19. In this study, we aimed to investigate the rs2494746 and rs1130214 variants in the AKT1 gene associated with severe COVID-19 outcomes. Peripheral blood samples and sociodemographic data from 508 individuals with COVID-19, measuring plasma cytokine concentrations using ELISA and genotyped the AKT1 variants. The rs2494746-C allele was associated with severity, ICU admission, and death from COVID-19. The C allele at rs1130214 was linked to increased TNF and D-dimer levels. Moreover, both variants exhibited an increased cumulative risk of disease severity, ICU admission, and mortality caused by COVID-19. In the predictive analysis, the rs2494746 obtained an accuracy of 71%, suggesting a high probability of the test determining the severity of the disease. Our findings contribute to understanding the influence of the AKT1 gene variants on the immunological damage in individuals infected with SARS-CoV-2.

Children with sickle cell disease: are they protected from serious COVID-19?

COVID-19, the pandemic that hit the world in 2020, resulted in millions of deaths, with the elderly and adults succumbing to the disease more often than children. However, the presence of underlying morbidities increased the risk of death. Sickle cell disease (SCD) was previously classified as a major risk factor for severe COVID-19 disease. However, presently, there are only a limited number of studies that identify the clinical course of children with SCD and COVID-19. We conducted a retrospective observational study on children with SCD admitted due to COVID-19 at three different institutions in Saudi Arabia between March 2020 and March 2022. We studied the demographic and clinical characteristics of patients admitted to the hospital. Seventy-six patients with SCD had PCR-confirmed SARS-CoV-2 during the study period; 50.0% of our patient population were children (6-12 years old). Gender was evenly distributed, with 53.9% girls and 46.1% boys. Symptoms more commonly related to the COVID-19 infection included fever, cough, malaise, and vomiting. Chest x-ray findings revealed mild and non-specific symptoms only in approximately one-third (28) of the included children. The most common symptoms associated with SCD were vaso-occlusive crisis (47.4%) and abdominal pain (11.8%). The overall general appearance of most of the patients was reassuring. The median length of hospital stay was 4.2 ± 2.7 days. The mean white blood cell count was 11.4 ± 5.2 × 109/L, and the mean hemoglobin level was 8.3 ± 1.5 g/dl. Despite the fact that higher levels of mean D-dimer, lactate dehydrogenase, and ferritin were reported in these patients, the clinical outcome was not affected. All recruited patients received hydroxyurea as maintenance therapy. The outcome of our study was reassuring, with no significant morbidity or mortality observed among the recruited patients. Despite SCD being a chronic disease with known specific complications, there has been a claim that COVID-19 infection adds further risk. The results of this study suggest that the overall outcome of COVID-19 was favorable, with no reported mortality. Further research is needed to understand the factors that contributed to this favorable outcome. In children with SCD, it is still questionable whether hydroxyurea is one of the protective factors against severe COVID-19. Validation through large-scale research is recommended.

When Chinese patients with plasma cell disorders encountered the nationwide Omicron outbreak (December 2022): a real-world multicenter and multiregional study.

This study aims to assess the impact of the nationwide Omicron outbreak in December 2022 on Chinese patients with plasma cell disorders (PCD), focusing on the clinical characteristics of PCD patients with COVID-19 and the risk factors contributing to adverse clinical courses (severity and hospitalization) and outcomes. A multicenter retrospective study was performed from December 1, 2022, to January 19, 2023. The study population includes 404 PCD patients, divided into a COVID-19 group (n = 342) and an uninfected group (n = 62). The frequency of COVID-19 infection was 84.7% (342/404), and 16.4% (56/342) were severe COVID-19. Among the 277 patients with complete follow-up, 2 deaths (0.7%) were reported, while 231 (83.4%) recovered from COVID-19. Age > 65 (P = 0.02) and prior anti-CD38 monoclonal antibody (mAb) treatment within six months (P = 0.03) were independent risk factors for severe infection. Additionally, previous chimeric antigen receptor T-cell (CAR-T) therapy within six months was correlated with a higher risk of hospitalization (P = 0.04) and prolonged recovery time (P = 0.03). No significant protective effect of vaccination on infection or severe infection was observed (P > 0.05). The latest Omicron outbreak results in higher rates of severe infection and mortality in PCD patients compared with the general population in China, highlighting the need to protect this vulnerable population during the pandemic. Recent use of anti-CD38 mAb and CAR-T therapy are associated with poorer clinical courses and outcomes of PCD patients with COVID-19.

Impact of chronic kidney disease on the course and outcome of COVID-19

COVID-19 is primarily a respiratory disease. However, patients with COVID-19 are at high risk for acute kidney injury or exacerbation of preexisting kidney disease, especially those with comorbidities such as hypertension, coronary artery disease, chronic liver disease, chronic kidney disease, and malignancies. We reviewed studies that assessed the association between chronic kidney disease and SARS-CoV-2 coronavirus infection and infection outcomes, including hospitalization, severe COVID-19, need for intensive care, COVID-19 progression, and death. The studies showed varied and often contradictory results, as the baseline data differ in many parameters, such as the period of the pandemic, quality and size of the sample, and degree of comorbidity. Nevertheless, the studies consistently revealed that chronic kidney disease is an unfavorable factor with regard to SARS-CoV-2 infection. Furthermore, concomitant chronic kidney disease predisposes patients with COVID-19 to severe COVID-19, viral pneumonia, development of acute respiratory distress syndrome, acute kidney injury, and other complications, which in turn are negative prognostic factors for mortality. Patients with chronic kidney disease who survived COVID-19 are more likely to develop post-COVID syndromes with various persistent or recurrent symptoms than convalescents without renal comorbidity. These patients require long-term monitoring and optimization of therapy and are priority for vaccination.

Quantitative susceptibility mapping at 7 T in COVID-19: brainstem effects and outcome associations.

Post-mortem studies have shown that patients dying from severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection frequently have pathological changes in their CNS, particularly in the brainstem. Many of these changes are proposed to result from para-infectious and/or post-infection immune responses. Clinical symptoms such as fatigue, breathlessness, and chest pain are frequently reported in post-hospitalized coronavirus disease 2019 (COVID-19) patients. We propose that these symptoms are in part due to damage to key neuromodulatory brainstem nuclei. While brainstem involvement has been demonstrated in the acute phase of the illness, the evidence of long-term brainstem change on MRI is inconclusive. We therefore used ultra-high field (7 T) quantitative susceptibility mapping (QSM) to test the hypothesis that brainstem abnormalities persist in post-COVID patients and that these are associated with persistence of key symptoms. We used 7 T QSM data from 30 patients, scanned 93-548 days after hospital admission for COVID-19 and compared them to 51 age-matched controls without prior history of COVID-19 infection. We correlated the patients' QSM signals with disease severity (duration of hospital admission and COVID-19 severity scale), inflammatory response during the acute illness (C-reactive protein, D-dimer and platelet levels), functional recovery (modified Rankin scale), depression (Patient Health Questionnaire-9) and anxiety (Generalized Anxiety Disorder-7). In COVID-19 survivors, the MR susceptibility increased in the medulla, pons and midbrain regions of the brainstem. Specifically, there was increased susceptibility in the inferior medullary reticular formation and the raphe pallidus and obscurus. In these regions, patients with higher tissue susceptibility had worse acute disease severity, higher acute inflammatory markers, and significantly worse functional recovery. This study contributes to understanding the long-term effects of COVID-19 and recovery. Using non-invasive ultra-high field 7 T MRI, we show evidence of brainstem pathophysiological changes associated with inflammatory processes in post-hospitalized COVID-19 survivors.

Rehabilitation and functional outcomes of COVID-19 patients in a rehabilitation hospital in Qatar.

Patients recovering from severe COVID-19 infections have experienced prolonged cognitive, physical, and psychological sequelae, including cardiorespiratory and motor deconditioning, neurological deterioration, anxiety, and depression. The impact of rehabilitation post-acute COVID-19 infection was recognized in the literature, but studies assessing and quantifying specific functional outcomes were lacking. This study aims to describe the characteristics and quantify the changes in functional outcomes of patients admitted to Qatar Rehabilitation Institute (QRI) for inpatient rehabilitation (IPR) post-COVID-19 infection during a 10-month period in 2021. This is a retrospective observational cohort study, which included individuals over 18 years of age with a documented COVID-19-positive diagnosis who were admitted to QRI for IPR due to COVID-19 complications. Data was collected by the investigators from January 1, 2021, until October 30, 2021. A total of 243 patients were included in this study. The changes in functional rehabilitation outcomes were assessed and quantified at both the patient's baseline (on admission to QRI) and after completion of IPR (on discharge). The duration of the IPR program varied based on each patient's baseline assessment. Patients were given a total of 8-12 weeks to achieve their rehabilitation goals and were discharged once those goals were met. Several validated tools were utilized in this study including Functional Independence Measure (FIM), Berg Balance Scale (BBS), Dynamic Gait Index (DGI), Modified Medical Research Council (mMRC) Dyspnea Scale, Mini-Mental State Examination (MMSE), and Right- and left-Hand Grip Strength. In addition, patients' diet, the need for respiratory support, and the presence of a tracheostomy tube before and after IPR were also recorded. In total, 84.4% of the included patients were males (n = 205); with a mean age of 52.44 ± 12.99 years. The most commonly reported comorbidities were type 2 diabetes (62.1%) and hypertension (49.8%) with 83.5% of patients experiencing critical illness neuromyopathy. The average patients' length of stay in QRI was 33.92 ± 27.72 days. A statistically significant improvement in all functional outcome scales was noted following the completion of the IPR program (p = 0.001). The number of patients requiring modification to their diet or feeding via nasogastric tube (NGT) significantly decreased by 35% and 93%, respectively (p = 0.001). Patients requiring respiratory support decreased by 98% (p = 0.001) and the need for a tracheostomy tube among patients was reduced by 95% (p = 0.001). IPR following COVID-19 infection was associated with significant functional, motor, and cardiorespiratory improvement. Dedicating clinics for post-COVID-19 rehabilitation would ensure improved patient outcomes and enhanced recovery.

Elevated serum mtDNA in COVID-19 patients is linked to SARS-CoV-2 envelope protein targeting mitochondrial VDAC1, inducing apoptosis and mtDNA release.

Mitochondria dysfunction is implicated in cell death, inflammation, and autoimmunity. During viral infections, some viruses employ different strategies to disrupt mitochondria-dependent apoptosis, while others, including SARS-CoV-2, induce host cell apoptosis to facilitate replication and immune system modulation. Given mitochondrial DNAs (mtDNA) role as a pro-inflammatory damage-associated molecular pattern in inflammatory diseases, we examined its levels in the serum of COVID-19 patients and found it to be high relative to levels in healthy donors. Furthermore, comparison of serum protein profiles between healthy individuals and SARS-CoV-2-infected patients revealed unique bands in the COVID-19 patients. Using mass spectroscopy, we identified over 15 proteins, whose levels in the serum of COVID-19 patients were 4- to 780-fold higher. As mtDNA release from the mitochondria is mediated by the oligomeric form of the mitochondrial-gatekeeper-the voltage-dependent anion-selective channel 1 (VDAC1)-we investigated whether SARS-CoV-2 protein alters VDAC1 expression. Among the three selected SARS-CoV-2 proteins, small envelope (E), nucleocapsid (N), and accessory 3b proteins, the E-protein induced VDAC1 overexpression, VDAC1 oligomerization, cell death, and mtDNA release. Additionally, this protein led to mitochondrial dysfunction, as evidenced by increased mitochondrial ROS production and cytosolic Ca2+ levels. These findings suggest that SARS-CoV-2 E-protein induces mitochondrial dysfunction, apoptosis, and mtDNA release via VDAC1 modulation. mtDNA that accumulates in the blood activates the cGAS-STING pathway, triggering inflammatory cytokine and chemokine expression that contribute to the cytokine storm and tissue damage seen in cases of severe COVID-19.

Impact of COVID-19 infection on genitourinary cancer management. SOGUG-COVID-19: A spanish, multicenter, observational study.

The COVID-19 pandemic is a great burden worldwide, but its impact on patients with genitourinary cancer (GUC) is poorly characterized. This study aimed to characterize the clinical features and evolution of GUC patients affected by COVID-19 in Spain. SOGUG-COVID-19 was an observational ambispective non-interventional study that recruited patients with SARS-CoV-2 infection who had been treated for GUC in 32 Spanish hospitals. Data were collected from patients' medical records in a short period of time, coinciding with the first waves of COVID-19, when the mortality was also higher in the general population. From November 2020 to April 2021, 408 patients were enrolled in the study. The median age was 70years, and 357 patients (87.5%) were male. Most frequent Cancer Origin was: prostate (40.7%), urothelial (31.4%) and kidney (22.1%). Most patients (71.3%) were diagnosed at the metastatic stage, and 33.3% had poorly differentiated histology. Anticancer treatment during the infection was reported in 58.3% of patients, and 21.3% had received immunotherapy prior to or concurrent with the infection. The most frequent COVID-19 symptoms were pyrexia (49.0%), cough (38.2%) and dyspnea (31.9%). Median age was higher for patients with pneumonia (p < 0.001), patchy infiltrates (p = 0.005), ICU admission (p < 0.001) and death (p < 0.001). Tumor stage was associated with complications (p = 0.006). The fatality rate was 19.9% and the 6-month COVID-19-specific survival rate was 79.7%. Patients with genitourinary cancers seem exceptionally vulnerable to COVID-19 regardless of tumor type or anticancer therapy. Age and tumor stage were the only identified risk factors for severe COVID-19.

6479 Acute Estradiol and Progesterone Therapy In Hospitalized Adults With Moderate COVID-19: A Randomized Control Trial

Abstract Disclosure: D. Lovre: Research Investigator; Self; Novo Nordisk, Corcept Therapeutics. K.M. Bateman: None. L.Y. Saltzman,: None. M. Qadir: None. F. Mauvais-Jarvis: None. Background and Objective: COVID-19 outcomes are less severe in women vs men. Experimental studies show that estradiol (E2) and progesterone (P4) produce anti-inflammatory immune responses and immune tolerance and enhance antibody production. The effect of E2 and P4 combination on COVID-19 severity is unknown. The aim of the study was to evaluate the efficacy of a short systemic E2/P4 combination in mitigating COVID-19 severity in hospitalized men and women. Methods: Phase 2, double blind, placebo-equivalent controlled, single center trial of ten participants (men and women) who were hospitalized for COVID-19, with scores 3 to 5 on the 9-point World Health Organization (WHO) ordinal scale for clinical improvement. Participants were randomized into two arms and treated for five days: 1) E2 Cypionate (5 mg IM once) and micronized P4 (200mg, PO daily); and 2) Placebo-equivalent (normal saline (1ml, IM once) and folate (400mcgs, PO daily), in addition to standard of care (SOC). The primary outcome was the proportion of patients improving to scores 1 or 2 on the WHO scale on the day of discharge. Secondary outcomes included length of hospital stay (LOS), days on oxygen therapy (DOT), readmission rates (RR), adverse events (AEs) and change in inflammatory biomarkers assessed by untargeted proteomics. Findings: There were no significant differences between the treatment groups in COVID-19 severity by WHO score, LOS, DOT, RR or AEs. Patients in the E2/P4 arm exhibited a decrease in inflammatory biomarkers of respiratory and gastrointestinal disease (GI) and significant change in immune and inflammatory responses. Conclusions: Use of short-term systemic E2/P4 is associated with decrease in biomarkers of respiratory and GI disease inflammation and change in biomarkers of immune and inflammatory response. Presentation: 6/3/2024

CD151 identifies an NK cell subset that is enriched in COVID-19 patients and correlates with disease severity

Severe coronavirus disease 2019 (COVID-19) often leads to acute respiratory distress syndrome and multi-organ dysfunction, driven by a dysregulated immune response, including a cytokine storm with elevated proinflammatory cytokine levels. Natural killer (NK) cells are part of the innate immune system with a fundamental role in the defense against viral infections. However, during COVID-19 acute infection, they exhibit an altered phenotype and impaired functionality contributing to the immunopathogenesis of the disease. In this work, we have studied a cohort of patients with COVID-19 (ranging from mild to severe) by analyzing IL-15, TGF-β, PlGF and GDF-15 plasma levels and performing multiparametric flow cytometry studies. Our results revealed that severe COVID-19 patients exhibited high levels of IL-15, PlGF and GDF-15, along with an enrichment of anNK cell subset expressing the CD151 tetraspanin, which correlated with IL-15 plasma levels and disease severity. In patients, these CD151+ NK cells displayed a more activated phenotype characterized by an increased expression of HLA-DR, CD38 and granzyme B, a distinct receptor repertoire, with lower levels of CD160 and CD31 and higher levels of CD55 and, remarkably, a higher expression of tissue-resident markers CD103 and the NK cell decidual marker CD9. Last of all, in individuals with severe disease, we identified an expansion of a CD151brightCD9+ NK cell subset, suggesting that these cells play a specific role in COVID-19. Altogether, our findings suggest that CD151+ NK cells may have a relevant role in COVID-19 immunopathogenesis.

5164 Long COVID patients with menstrual symptoms: a retrospective study in Japan

Abstract Disclosure: F. Otsuka: None. Y. Sakurada: None. Y. Matsuda: None. T. Hasegawa: None. Y. Otsuka: None. Y. Nakano: None. K. Tokumasu: None. K. Yamamoto: None. N. Sunada: None. H. Honda: None. H. Hagiya: None. K. Ueda: None. It has been recognized that about one third of patients may suffer from prolonged illness after surviving from the acute phase of COVID-19. Various symptoms of the prolonged illness have been evaluated by many institutions including WHO. However, the mechanisms of the prolonged symptoms have yet to be elucidated. Long COVID is a complicated illness that develops after SARS-CoV-2 infection, independent of the severity of COVID-19. Long COVID is defined as symptoms that occur within 3 months after the initial infection and persist for at least 2 months. The major symptoms of long COVID include general fatigue, post-exertional malaise, headache, insomnia, dyspnea, cognitive dysfunction, low-grade fever, and muscle pain. Proposed pathophysiological mechanisms of long COVID include pathogen persistence and viral reactivation, immune dysregulation and autoimmunity, neurological abnormalities, tissue damage due to hypoperfusion and/or microclots, autonomic and endocrine dysfunctions, and dysregulation of microbiomes. In the present study, we aimed to elucidate the impact of long COVID on female reproductive health. In this retrospective study, medical records of patients who visited our long COVID clinic and clinical trends of their menstrual symptoms were evaluated. In our study, of 349 female patients who visited our clinic between Feb 2021 and Mar 2023, 223 patients with long COVID (18-50 years) were included. It was revealed that 44 females (19.7%) had menstrual symptoms associated with long COVID. The patients with menstrual symptoms were significantly older than those without menstrual symptoms (42.5 vs. 38 years). The percentage of patients with menstrual symptoms was higher during the Omicron phase (24%) than during the Preceding (13%) and Delta (12%) phases. Cycle irregularity (63.6%) was the most frequent menstrual symptom, followed by severe pain (25%), heavy bleeding (20.5%), perimenopausal symptoms (18.2%), and premenstrual syndrome (15.9%). Fatigue and depression were the most frequent complications with menstrual complaints. Scores indicating fatigue and QOL were significantly worse in long COVID patients with menstrual symptoms. Endocrine examinations showed significantly increased cortisol levels in patients with menstrual complaints although plasma adrenocorticotropin levels were not altered. Hence, long COVID has an impact on women’s reproductive and mental health. Presentation: 6/1/2024

5164 Long COVID patients with menstrual symptoms: a retrospective study in Japan

Abstract Disclosure: F. Otsuka: None. Y. Sakurada: None. Y. Matsuda: None. T. Hasegawa: None. Y. Otsuka: None. Y. Nakano: None. K. Tokumasu: None. K. Yamamoto: None. N. Sunada: None. H. Honda: None. H. Hagiya: None. K. Ueda: None. It has been recognized that about one third of patients may suffer from prolonged illness after surviving from the acute phase of COVID-19. Various symptoms of the prolonged illness have been evaluated by many institutions including WHO. However, the mechanisms of the prolonged symptoms have yet to be elucidated. Long COVID is a complicated illness that develops after SARS-CoV-2 infection, independent of the severity of COVID-19. Long COVID is defined as symptoms that occur within 3 months after the initial infection and persist for at least 2 months. The major symptoms of long COVID include general fatigue, post-exertional malaise, headache, insomnia, dyspnea, cognitive dysfunction, low-grade fever, and muscle pain. Proposed pathophysiological mechanisms of long COVID include pathogen persistence and viral reactivation, immune dysregulation and autoimmunity, neurological abnormalities, tissue damage due to hypoperfusion and/or microclots, autonomic and endocrine dysfunctions, and dysregulation of microbiomes. In the present study, we aimed to elucidate the impact of long COVID on female reproductive health. In this retrospective study, medical records of patients who visited our long COVID clinic and clinical trends of their menstrual symptoms were evaluated. In our study, of 349 female patients who visited our clinic between Feb 2021 and Mar 2023, 223 patients with long COVID (18-50 years) were included. It was revealed that 44 females (19.7%) had menstrual symptoms associated with long COVID. The patients with menstrual symptoms were significantly older than those without menstrual symptoms (42.5 vs. 38 years). The percentage of patients with menstrual symptoms was higher during the Omicron phase (24%) than during the Preceding (13%) and Delta (12%) phases. Cycle irregularity (63.6%) was the most frequent menstrual symptom, followed by severe pain (25%), heavy bleeding (20.5%), perimenopausal symptoms (18.2%), and premenstrual syndrome (15.9%). Fatigue and depression were the most frequent complications with menstrual complaints. Scores indicating fatigue and QOL were significantly worse in long COVID patients with menstrual symptoms. Endocrine examinations showed significantly increased cortisol levels in patients with menstrual complaints although plasma adrenocorticotropin levels were not altered. Hence, long COVID has an impact on women’s reproductive and mental health. Presentation: 6/1/2024

7725 Could COVID-19 Be the Trigger for Type 1 Diabetes?

Abstract Disclosure: E. Ahsan: None. F.F. Foo: None. A. Ravin: None. M. Akula: None. K. Hu: None. R. Ong: None. S. Holland: None. M. Hossain: None. J. Cheng: None. Introduction: COVID-19 disrupts glucose homeostasis, which may result in hyperglycemia and new-onset diabetes mellitus. It has been hypothesized to be caused by an increased inflammatory response, increased insulin resistance, and a degree of acute viral pancreatic damage. A meta-analysis showed that the incidence of new-onset diabetes was found to be as high as 14.4% (95% CI: [5.9%-25.8%]). Here, we report a case of COVID-19-induced diabetes to spread awareness among healthcare providers and encourage early detection to prevent long-term complications. Clinical Case: A 54-year-old African American female with a past medical history of hyperlipidemia, obesity, and hypothyroidism presented to our endocrinology office for evaluation and management of diabetes mellitus (DM). She presented with symptoms of 66-pound weight loss, polydipsia, polyphagia, and polyuria. Her labs on diagnosis were significant for blood glucose of 550 mg/dl (70-100 mg/dl), hemoglobin A1c &amp;gt;15.5% (&amp;lt;5.7%), and bicarbonate 23 mmol/L (20-31 mmol/L). She started on insulin and then switched to semaglutide after six months. Her fasting glucose on the follow-up visit was 103 mg/dl, the anti-glutamic acid decarboxylase 65 (GAD-65) antibody was 8,558.9 units/ml (&amp;lt;5 units/ml), C peptide was 1.9 ng/ml (0.5-2ng/ml), and Islet Antigen-2 (IA-2) autoantibody was &amp;lt;7.5 U/ml (0-7.49 U/ml). Despite positive antibodies, her C-peptide suggested enough beta-cell function, and she was switched from insulin to semaglutide. The patient was diagnosed with autoimmune diabetes, which may be from the COVID-19 infection, and was educated about regular follow-up and new medications like teplizumab that may help prevent the progression to needing insulin. Clinical Lesson: The exact mechanism of new-onset COVID-19-induced diabetes is still unknown. However, multiple risk factors are theorized to play a role in COVID-induced DM. These include defects in insulin production and glucose clearance, obesity, stress hyperglycemia, insulin resistance, and steroid therapy. Our patient had a history of obesity but no history of diabetes, steroid use, or any personal or family history of autoimmune processes. Compared to COVID-19 patients with normoglycemia or hyperglycemia, patients with preexisting diabetes and newly diagnosed diabetes experienced more severe complications, such as shock, ARDS, acute kidney injury, hypoalbuminemia, and severe COVID-19 complications. Additional research is required to investigate the various pathophysiologies and treatment options, including new medications that may prevent the disease's further progression. Diabetes caused by COVID-19 should be treated cautiously, and prompt diagnosis and care are essential to preventing further complications. Presentation: 6/3/2024

Pulmonary fibrosis followed by severe pneumonia in patients with COVID-19 infection requiring mechanical ventilation: a prospective multicentre study

BackgroundsThe management of lung complications, especially fibrosis, after COVID-19 pneumonia, is an important issue in the COVID-19 post-pandemic era. We aimed to investigate risk factors for pulmonary fibrosis development in...

Exploring the characteristics and antecedents of clinically significant long COVID: A longitudinal cohort study

BackgroundA significant number of coronavirus disease 2019 (COVID-19) survivors are experiencing long COVID, with symptoms lasting beyond three months. While diverse long COVID symptoms are established, there are gaps in understanding its long-term trends, intensity, and risk factors, requiring further investigation. AimsThis study aimed to investigate the long COVID characteristics and associated factors by following COVID-19 survivors for one year post-infection and comparing them with healthy counterparts. Main methodsIn this longitudinal, correlational study, COVID-19 survivors diagnosed between November 2021 and February 2023 were monitored every three months for a year. Participants aged ≥18 years who had reported a positive COVID-19 test were recruited via social media and healthcare provider referrals. Key findingsOut of 182 survivors who initially agreed to participate, 176 completed the study. The mean age was 47.56 years (SD = 16.2), and 51.1 % were female. There was a clinically significant decline in cognitive function and health-related quality of life over time, with symptoms like shortness of breath, reduced physical fitness, and increased health concerns. Those with severe acute COVID-19 symptoms experienced greater cognitive and physical declines and more shortness of breath a year later. Lower financial status was linked to poorer health-related quality of life and increased health concerns. SignificanceA year post-infection, COVID-19's impact on cognitive function and health-related quality of life remains significant, affecting individuals and communities. Survivors with severe initial symptoms and economic disadvantages need more attention. Future research should identify additional predictors of severe long COVID.