SARS-CoV2 Infection Research Articles

Epidemiological, clinical, paraclinical, evolutionary, and therapeutic aspects of hypertensive patients infected by COVID-19: about 702 patients in our city

Abstract Introduction Hypertension (HT) is a major cardiovascular risk factor frequently observed in COVID-19 patients. This study aimed to determine the frequency of hypertensive patients infected with COVID-19 at a national hospital, describe their epidemiological, clinical, paraclinical, and therapeutic profile, their disease progression, and identify factors associated with death. Methodology A retrospective, descriptive, and analytical study was conducted over 24 months and 4 days, from 27 March 2020 to 30 March 2022, at national hospital. Included were hospitalized patients at a hospital with a confirmed COVID-19 diagnosis, known hypertensives, regardless of gender, and with a hospitalization record. COVID-19 diagnosis was based on a positive SARS-CoV-2 RT-PCR or a positive COVID Rapid Diagnostic Test. Data were collected using a survey form, with a p-value less than 0.05 considered statistically significant for bivariate analysis. Results The study enrolled 702 patients, a hospital frequency of 23.95%. The average age was 65.14 ± 12.24 years with a sex ratio of 0.81. Comorbidities were predominantly diabetes (40.5%) and dyslipidemia (4.8%). Common symptoms included cough (65%), dyspnea (42.3%), fever (47.4%), and asthenia (35.9%). Blood pressure was normal in 15.2%, high-normal in 16.8% of patients. HT was Grade I in 12.1%, Grade II in 10%, and Grade III in 6.8% of the population, with blood pressure unmeasurable in 0.3% of known hypertensive patients. SARSCOV2 infection was mild in 34.2% and moderate in 42.8% of cases. CT scans showed extensive (31.8%), severe (25.9%), moderate (25.6%), critical (8.5%), and minimal (7.9%) lung damage. Treatment mainly consisted of ACE inhibitors (29%), ACE inhibitors in combination with another antihypertensive (8.4%), and ARBs in combination with an antihypertensive (). The average hospital stay was 12.85 days with a favorable outcome in 81% and a mortality rate of 15.5%. Factors associated with death included not being vaccinated against COVID-19 (HR: 11.70; 95% CI: 1.324-103.519), critical clinical form (HR: 11.70; 95% CI: 1.324-103.519), pulmonary consolidation (HR: 8.87; 95% CI: 7.539-24.207), high creatinine (HR: 4.69; 95% CI: 1.360-16.181), critical CT thoracic level (HR: 2.42; 95% CI: 1.020-5.745), and not taking ARBs (HR: 6.02; 95% CI: 2.812-12.889). Conclusion HT can be associated with COVID-19, impacting the disease's prognosis with significant mortality. Preventing its incidence and morbidity/mortality is crucial.

Supporting Long Covid Care: a webtool to facilitate help-seeking among people with Long Covid

Abstract Background Long Covid (also known as Post-COVID19 Condition or Post-COVID Syndrome) is characterised by persistent symptoms following SARSCoV2 infection not explained by other pathology. Some evidence suggests that people from marginalised communities are more likely to experience Long Covid but are less likely to be represented in post-covid care in England. Objectives Findings from the STIMULATE-ICP case finding and HI-COVE studies show that some people living with Long Covid struggle to get adequate healthcare and social support. Barriers to obtaining support include a lack of awareness of Long Covid and supports available, uncertainty around the cause and complexity of symptoms, as well as experiences and expectations of stigma. The new Supporting Long Covid Care (SLCC) webtool was developed based on these findings and aimed to both facilitate help-seeking for people with probable Long Covid who are not receiving care and raise awareness among professionals. Extensive engagement with people with lived experience and professionals shaped the webtool. SLCC content was then beta-tested with stakeholders. Results SLCC (long-covid-care.org.uk) was launched in March 2024. One of its features is the acknowledgement that Long Covid can be a stigmatising condition. SLCC includes real-life quotes to connect emotionally with users, highlights the shared experiences of people living with Long Covid and illustrates the difficulties faced when seeking recognition and support. It encourages conversations with professionals, friends, family and others who may be relied on for support and offers resources to facilitate those conversations and inform next steps. SLCC is also an informative tool for healthcare professionals around Long Covid stigma. Conclusions SLCC is open to use by members of the public. Real-world evaluation and translation to other languages are now needed to explore if this webtool is beneficial and contributes towards addressing health inequalities. Key messages • SLCC encourages people with probable Long Covid to seek help and support. • SLCC raises awareness among healthcare professionals about the barriers and stigma people, particularly those from disadvantaged backgrounds, may face when considering reaching out for support.

6.X.1. Disentangling Long-COVID: prevalence, risk factors and impact

Abstract Background Prolonged symptoms after the acute SARS-COV2 infection significantly alter daily functioning and work ability for substantial number of people. Application of different long COVID definitions result in variable prevalence estimations, while aetiology of long COVID as well as its impact is insufficiently understood. Our workshop is set to discuss the public health impact of long COVID in the general population, to identify risk factors of developing long COVID, and stimulate dialog to advance adequate health care and public health actions aimed to reduce the impact of this condition. Objectives and Key Questions The overall objective is to discuss the public health impact as well as geographic variations across Europe in long COVID prevalence, major risk factors for long COVID and impact on work capacity, accounting for different population-based and hospital study settings. Specifically, the workshop will address the following key questions: 1) what are the challenges in estimating prevalence of long COVID? 2) what are the risk factors of long COVID and some of the most vulnerable population groups? 3) what is a distribution of long COVID in Europe? 4) what is the impact of long COVID on work ability? Brief Overview The workshop will include 3 presentations (in combined total duration of 12 min) on challenges for research and practice attributable to variability in defining long COVID, prevalence of long COVID across several European countries, risks factors of long COVID and impact on work ability. Active discussion of 13 min will conclude the session. Key messages • Standardized definitions, such as WHO-PCC definition with severity thresholds would facilitate surveillance of long COVID and advance knowledge on the risk factors related to this condition. • Understanding better the risk factors and impact of long COVID will inform more adequate screening and therapeutic strategies, and possibly anticipate effects of potential new infectious threats.

Kidney Health Consequences of Patients with Glomerulonephritis; Before and After SARS-COV2 Infection

Objective: The virus that causes severe acute respiratory syndrome (SARS-CoV-2) was first identified in Wuhan, China, in December 2019. Recent studies have proven that SARS-CoV-2 is also a nephrotrophic virus. Methods: Our study aimed to evaluate kidney function and general kidney health of patients with previously diagnosed glomerular diseases and follow-up after SARS-CoV-2 infection. For this purpose, the data of 36 patients who were diagnosed with and routinely followed up for glomerulonephritis and had SARS-CoV-2 infection at the Kocaeli University Faculty of Medicine Hospital nephrology outpatient clinics between January 2020 and January 2022 were examined before and after the infection. Results: No significant differences were observed in serum creatinine, estimated glomerular filtration rate, and 24-hour urine protein values after infection. There was an increase in platelet and albumin levels following the SARS-CoV-2 infection. A significant decrease was detected in 24-hour urine creatinine values. Conclusion: The results of the study showed that kidney function and general kidney health of patients with SARS-CoV-2 infection diagnosed with glomerulonephritis were not different when compared to their condition before SARS-CoV-2 infection.

Potential hypothesis for the increased risk of Parkinson´s disease following COVID-19.

Patients with severe COVID-19 may be more likely to develop PD as a result of shared biological pathways including a great expansion of MDSCs and an imbalance in Th17/Tregs ratio. We think that these shared pathogenic features may mechanistically explain the COVID-19 - PD axis. Thus, we assume that patients who recovered from critical COVID-19 should be selected based upon a potential higher risk of developing PD. Further studies are needed to better define the possible relationship between COVID-19 and neuroinflammation and identify whether some people are more likely to develop PD after contracting COVID-19 than others with special emphasis to ascertain possible vulnerable genetic backgrounds or epigenetic factors acting on brain which may promote PD during SARS COV-2 infection. Finally, we think that regular physical activity should be performed and encouraged in patients with PD.

A pooled analysis of the incidence and mortality risk of atrial fibrillation in patients with COVID-19.

There exist serious cardiovascular complications subsequent to SARS-Cov2 infection (COVID-19); however, the association between COVID-19 and atrial fibrillation (AF) remains to be elucidated. We aimed to assess the prevalence of AF among COVID-19 patients and its associated risk of death. The present systematic review was performed in accordance with the PRISMA guidelines. The protocol was registered with CRD42022306523. A comprehensive literature search was performed across PubMed, Embase, and Cochrane databases to identify studies reporting on the prevalence of pre-existing or new-onset fibrillation (AF), and/or the associated clinical outcomes in patients with COVID-19 from January 2020 to December 2023. The random-effect model was used to estimate the prevalence of AF and its related mortality. A total of 80 studies, including 39,062,868 COVID-19 patients, were identified in the present investigation. The prevalence rates of pre-existing AF or new-onset AF were 10.5% (95% CI [9.3-11.7%]) or 10.3% (95% CI [6.2-14.5%]), respectively. Subgroup analysis revealed a two fold higher incidence of AF in older patients (≥65 years) compared to younger patients (<65 years) (14.4% vs. 6.4%). The highest rate of AF was observed in Europeans (10.7%, 95% CI [10.2-11.2%]), followed by Northern Americans (10.0%, 95% CI [8.2-11.7%]), while Asians demonstrated a lower prevalence (2.7%, 95% CI [2.2-3.3%]). Notably, severe COVID-19 patients displayed a significantly elevated prevalence of AF at 14.l% (95% CI [13.3-14.9%]), which was approximately 2.5-fold higher than that in non-severe patients (5.2%, 95% CI [4.8-5.5%]). Both pre-existing (HR: 1.83, 95% CI [1.49-2.17]) and new-onset AF (HR: 3.47, 95% CI [2.26-5.33]) were associated with an increased mortality risk among COVID-19 patients. Furthermore, the effect on mortality risk was more significant in Asians (HR: 5.33, 95% CI [1.62-9.04]), compared to Europeans (HR: 1.68, 95% CI [1.24-2.13]) and North Americans (HR: 2.01, 95% CI [1.18-2.83]). This study comprehensively investigated the association between AF and COVID-19 in a real-world setting. Notably, a high prevalence of AF was observed among older individuals, severe COVID-19 patients, and in Europe and Northern America. Moreover, co-existing AF was found to be associated with an increased risk for mortality. Further investigations are warranted to improve the management and outcomes of COVID-19 patients with AF.

Neurological Complications and Outcomes in Critically Ill Patients With COVID-19: Results From International Neurological Study Group From the COVID-19 Critical Care Consortium

Background In this COVID-19 Critical Care Consortium (CCCC) sub-study, we qualified neurological complications associated with SARS-CoV2 infection. Methods The CCCC is an international, multicenter study. Eligible patients were COVID-19 patients admitted to intensive care units (ICU) across 23 centers between 1/7/2020 to 6/23/2022. Incidence of neurological complications was estimated as number of events per hospital days and per admission using Poisson regression. Associations between neurological complications and risk factors were assessed using multivariable Poisson regression. Results 713 patients were included. Median age = 56 years (interquartile range (IQR) = 45-65). Neurological complications reported in 61/480 patients (12.7%) with the majority being ischemic stroke (2.9%), intracranial hemorrhage (ICH) (2.8%), and seizures (2.6%). Multivariable analysis for neurological complications per admitted days showed comorbid neurological conditions (incidence rate ratio (IRR) = 6.35, 2.57-15.7) were an independent risk factor for ischemic stroke. Extracorporeal membrane oxygenation (IRR = 5.32, 1.52-18.6), low-middle income countries (LMIC) vs high income countries (HIC) (IRR = 4.70, 1.62-13.7), and age &gt;55 (IRR = 3.66, 1.23-10.9) were independent risk factors for ICH. Co-morbid neurological conditions (IRR = 3.43, 1.11-10.6), LMIC vs HIC (IRR = 8.69, 2.15-35.2), July-December 2020 vs January-June 2020 (IRR = 0.17, 0.04-0.69) and age &gt;55 (IRR = 4.05, 1.15-14.3) were independent risk factors for seizure. Conclusions Decision-making should incorporate salient risk factors to inform management of SARS-CoV2 infection and avoid neurological complications.

In silico investigation of therapeutic potential of phytosteroids against SARS-CoV2 infection via inhibition of viral multiplication and attenuation of host cytokine storm

SARS-CoV2 infection overcomes host cell membrane barrier, followed by utilization of host cellular processes for viral multiplication. Simultaneously, it triggers a cytokine storm within and around infected cells and tissues. Anti-inflammatory agents that can potentially inhibit viral penetration and multiplication within the host cells may be ideal drug candidates against COVID-19. Dietary phytosteroids have significant anti-inflammatory potential. Hence, the present study intends to investigate anti-viral potential of three dietary phytosteroids, namely, brassinolide, 28-homocastasterone and 24-epibrassinolide against SARS-CoV2 proteins, S1 spike protein, nucleocapsid protein and main protease enzyme, in addition to host pro-inflammatory proteins, interleukin-1, tumour necrosis factor-α, cyclooxygenase-2 and prostaglandin synthase, as drug targets. Molecular docking studies by AutoDock version 4.0 was performed. Brassinolide, 28-homocastasterone and 24-epibrassinolide exhibits high docking score against all the seven proteins, as compared to hydroxychloroquine. Brassinolide and 28- homocastasterone has maximum binding affinity for pro-inflammatory proteins and SARS-CoV2 proteins.Dietary phytosteroids may potentially attenuate cytokine storm with simultaneous inhibition of host entry and multiplication of SARS-CoV2. In-vitro and in-vivo anti-viral studies of plant steroids may provide a clear path for the identification and development of novel drug candidates against COVID-19, that also provides evidence for the concept of reverse pharmacognosy.

Outcomes of Patients Undergoing Elective Cancer Surgery After SARS-CoV-2 Infection: An Observational Cohort Study.

We evaluated the impact of preoperative SARS-CoV-2 infections on postoperative outcomes among patients undergoing elective cancer surgery. This ambidirectional (retrospective and prospective) study was conducted among patients undergoing elective cancer surgery between December 2022 and March 2023. Patients with different time intervals between SARS-CoV-2 infection and surgery (0-6 weeks and ≥7 weeks) were compared with those without SARS-CoV-2 infection. The primary outcome was 30-day postoperative pulmonary complications (PPCs). Secondary outcomes included 30-day postoperative mortality, major adverse cardiovascular events (MACE), and other postoperative adverse outcomes. Of the 830 patients analyzed, 239 (28.8%) had SARS-CoV-2 infection 0-6 weeks before cancer surgery, and they had a higher incidence of PPCs (4.6% in no SARS-CoV-2 infection, 12.1% in 0-6 weeks, and 5.1% in ≥7 weeks, p = 0.001). The logistic regression model revealed that, compared with patients without SARS-CoV-2 infection, surgery performed 0-6 weeks after SARSCoV-2 infection was associated with a higher risk of PPCs (adjusted odds ratio [aOR] 2.83; 95% confidence interval [CI] 1.34-5.98), and surgery performed ≥7 weeks after SARSCoV-2 infection was associated with a similar risk of PPCs (aOR 1.19; 95% CI 0.54-2.64). However, preoperative SARS-CoV-2 infection was not associated with a risk of 30-day postoperative mortality, MACE, or other adverse postoperative outcomes. In patients with preoperative Omicron variant infection, nonemergency cancer surgery can be scheduled ≥7 weeks after the infection to decrease the risk of PPCs, but it can be advanced if the risk of delay exceeds the risk of proceeding with the surgery.

A computational biology approach for the identification of potential SARS-CoV-2 main protease inhibitors from natural essential oil compounds.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has fomented a climate of fear worldwide due to its rapidly spreading nature, and high mortality rate. The World Health Organization (WHO) declared it as a global pandemic on 11th March, 2020. Many endeavors have been made to find appropriate medications to restrain the SARS CoV-2 infection from spreading but there is no specific antiviral therapy to date. However, a computer-aided drug design approach can be an alternative to identify probable drug candidates within a short time. SARS-CoV-2 main protease is a proven drug target, and it plays a pivotal role in viral replication and transcription. Methods: In this study, we identified a total of 114 essential oil compounds as a feasible anti-SARS-CoV-2 agent from several online reservoirs. These compounds were screened by incorporating ADMET profiling, molecular docking, and 50 ns of molecular dynamics simulation to identify potential drug candidates against the SARS-CoV-2 main protease. The crystallized SARS-CoV-2 main protease structure was collected from the RCSB PDB database (PDB ID 6LU7). Results: According to the results of the ADMET study, none of the compounds have any side effects that could reduce their druglikeness or pharmacokinetic properties. Out of 114 compounds, we selected bisabololoxide B, eremanthin, and leptospermone as our top drug candidates based on their higher binding affinity scores, and strong interaction with the Cys 145-His 41 catalytic dyad. Finally, the molecular dynamics simulation was implemented to evaluate the structural stability of the ligand-receptor complex. MD simulations disclosed that all the hits showed conformational stability compared to the positive control α-ketoamide. Conclusions: Our study showed that the top three hits might work as potential anti-SARS-CoV-2 agents, which can pave the way for discovering new drugs, but for experimental validation, they will require more in vivo trials.

12469 Impact Of Covid-19 Infection On Diabetic Ketoacidosis Severity And Outcomes In Adult Population- A Retrospective Observational Study

Abstract Disclosure: E.M. Niedzialkowska: None. K. Childers: None. L. Qu: None. L. Misra: None. M.R. Brennan: Consulting Fee; Self; Insulet Corporation, Bayer, Inc., Novo Nordisk. Background: Diabetic ketoacidosis (DKA) is a life-threatening complication of diabetes mellitus (DM) that can be precipitated by SARS-CoV2 infection. We analyzed clinical and demographic characteristics of patients admitted with DKA to investigate if SARS-CoV2 infection affects DKA severity on admission and outcomes. Methods: We conducted a retrospective cohort study that included adult patients admitted with a diagnosis of DKA between March 1, 2020, and March 1, 2023. Patients' demographic data including age, sex, race, ethnicity, laboratory test results on admission, ICU admissions and length of hospital stay (LOS) were compared. Patient characteristics and outcomes of interest were stratified by COVID-19 test results and compared using the Kruskal-Wallis test for continuous variables and Fisher’s exact test for categorical variables. DKA severity was classified based on HCO3 values: mild 15-18 mEq/L, moderate 10-14 mEq/L, severe &amp;lt;10 mEq/L. Results: The study included 902 patients, of which 734 tested negative (COVID-) and 168 tested positive (COVID+) for SARS-CoV2. The mean age was significantly higher (54.09) in COVID-19+ group compared to COVID-19- group (48.25) (p&amp;lt;0.001). The cohort included 49.1% females, 51.7% Whites, 43.3% Blacks, 89.8% Non-Hispanic/Latino, 2.7% Hispanic/Latino. We did not find statistically significant differences in sex (p= 0.608), race (p =0.277), ethnicity (p=0.072) anion gap (p=0.783), glucose (p=0.140), hemoglobin a1c (ha1c) values on admission (p=0.876) and ICU admissions (p=0.266) between both groups. The majority (55.3%) of the patients presented with severe DKA, followed by moderate DKA in 26.6% and mild disease in 18.1% of patients without statistically significant differences between groups (p= 0.128). The mean LOS in COVID + group (11.94 days) was longer than COVID- (6.85) group (p&amp;lt;0.001). Mean venous pH was significantly lower in COVID-19- (7.14) compared to COVID+ (7.17) group (p= 0.016). Betahydroxybutyrate (BHB) levels on admission were higher in COVID- group (7.98 mmol/L, N 0.02-0.27 mmol/L) compared to COVID + (7.10mmol/L) cohort. Conclusion: Patients diagnosed with COVID-19 and DKA on admission did not present with more severe disease compared to patients that tested negative. COVID+ patients were older (54.09 vs 48.2) and had significantly longer LOS (11.94 vs 6.85 days). We did not identify statistically significant differences between race, ethnicity, sex, glucose, anion gap, Ha1c on admission and ICU admission rate. BHB levels on admission were higher in patients that tested negative. Interestingly, mean pH was higher in COVID-19 positive group possibly due to respiratory disorders. Presentation: 6/1/2024

6721 Short-Term Responses of Serum 25-Hydroxyvitamin D to Weekly Calcifediol or Cholecalciferol in Healthy Subjects

Abstract Disclosure: R.B. Caldeira: None. A.S. Nunes: None. F.Z. Cazzetta: None. M.S. Medeiros: None. L.B. Oliveira: None. M.P. Bandeira: None. F.F. Bandeira: None. Introduction: Recent studies have shown that oral calcifediol (CAL) induces faster serum 25-hydroxyvitamin D (25OHD) increases than cholecalciferol (CHO) as demonstrated in some studies on SARS-Cov2 infection. It is hypothesized that this rapid elevation is due to the unique mode of intestinal absorption of CAL to the portal vein system in comparison with CHO which is absorbed mainly by the lymphatic route. Data on weekly administration of calcifediol are still scarce. The aim of the present study was to compare serum 25OHD responses in the short term (30 days) to weekly doses of CAL or CHO in healthy subjects. Methods and Results: We studied 35 subjects (34% men, mean age 24.6 ± 4.6 years, BMI 22.9 ± 2.9 kg/m², waist circumference 74.7 ± 6.5 cm, SBP 111.1 ± 12.7 mmHg, and DBP 73.1 ± 9.1 mmHg) who were randomized to receive weekly oral CAL 70 mcg (18 subjects) or CHO 350 mcg (14,000 IU, 17 subjects). Doses were chosen based on the 2000 IU/day potency equivalence. Patients were matched for age, gender, BMI, and BP. They were contacted weekly to confirm medication adherence. Serum 25OHD concentrations were measured before administration of both agents and 24 hours after the last dose, using an immunochemiluminescent assay (Abbott Diagnostics, Lake Forest, IL, USA) with a detection range from 4.9 to 151.3 ng/ml. At baseline serum 25OHD was 32.1 ±8.8 vs 33.1 ± 6.6 in CAL and CHO groups respectively (p=0.691). In CAL group 8 subjects had serum 25 OHD &amp;lt; 30 ng/mL (1 subject had 14.7 ng/mL) and in the CHO none had serum 25OHD below 20 ng/mL and 5 subjects had levels between 20 and 30 ng/mL. After 1 month, serum 25OHD levels rose significantly 3.3 times more with CAL than with CHO (+29.61 ± 7.39 ng/mL vs. 9.00 ± 3.50 ng/mL; p &amp;lt; 0.001). In CHO group one subject remained with 25OHD below 30 ng/mL after the intervention. Conclusion: We found a rapid and robust elevation of serum 25OHD levels with CAL compared to CHO at similar potency doses. This may have clinical implications for conditions in which there is a need for immediate availability of 25OHD to peripheral tissues. Presentation: 6/2/2024

8524 Pituitary Hormone Dysregulation In Symptomatic Long COVID: A Multi-Center Observational Study

Abstract Disclosure: S.L. Sims: None. A. Labadzhyan: None. Z. Chen: None. S. Kim: None. J. Brathwaite: None. L. Cullen: None. M. Koga: None. U. Cheliadinova: None. V. Hwe: None. D. Gomez: None. C. Andriakos: None. T. Melnik: None. E. Puig-Wong: None. S. Whelan: None. S. Cheng: None. S. Joung: None. Z. Abelev: None. C. Le: None. R. Zabner: None. Y. Kawakami: None. T. Araki: Consulting Fee; Self; Chiesi. Objective: Pituitary hormone dysregulation has been reported in symptomatic long COVID, but it has not been rigorously studied. We conducted a multicenter observational cross-sectional study to assess pituitary hormone levels in long COVID patients and a longitudinal study to follow patients with abnormal results. Methods: Male and female adults with confirmed symptomatic long COVID were recruited from post COVID clinics at Mount Sinai in New York, Cedars-Sinai in Los Angeles, and the University of Minnesota, as well as nationwide physician referrals. Pituitary hormone levels were measured, and because fatigue is common in long COVID, patients completed the QoL-AGHDA survey. Those who exceeded pre-determined survey cutoffs or demonstrated any hormone abnormality were invited to the longitudinal study to repeat surveys and blood work every 3 months. A separate cohort with banked serum samples from before and 3, 6, and 9 months after subacute COVID was used as a comparator. Correlation analysis examined associations between QoL-AGHDA scores and pituitary hormone levels. Results: 246 patients were enrolled in the cross-sectional study after a median of 17.0 months (range, 1-39) since the most recent SARS-CoV2 infection prior to the onset of long COVID symptoms. 56% were enrolled in the longitudinal study due to a high questionnaire score and/or pituitary hormone abnormalities. Current mean follow-up period is 7.95 ± 3.2 months. Mildly elevated prolactin levels were most frequent, observed in 12.7% of patients (males 14.0%, females 12.2%). These patients presented post-COVID with galactorrhea, irregular menses, erectile dysfunction, and nonspecific symptoms of hyperprolactinemia. On follow-up, mild hyperprolactinemia tended to persist. Mildly low IGF1 levels (Z-score &amp;lt;-1.0) were observed in 9.0% of patients (males 6.3%, females 10.0%); on follow-up, IGF1 levels recovered in only 15% of these patients. 2.0% of the entire cohort showed transiently elevated IGF1 levels (Z-score &amp;gt;2.0). Low morning cortisol (&amp;lt;5.0 µg/dL) was observed in 3.3% of patients, but response to cosyntropin stimulation was normal. Mild secondary hypothyroidism was observed in 3.7% of all patients, and mild hypogonadism was observed in 7.8% of males. There was no correlation between QoL-AGHDA score and level of each pituitary hormone. After excluding pre-COVID hormone abnormalities in the post subacute COVID cohort, the rate of hyperprolactinemia was lower than that seen in the long COVID cohort (1% vs 12.7%). The rate of low IGF1 levels was higher in the subacute COVID cohort (22% vs 9.0), but unlike with long COVID, low IGF1 levels after subacute COVID recovered in 3-6 months. Conclusion: Abnormalities in pituitary hormone levels in symptomatic long COVID are frequent, with persistent hyperprolactinemia in &amp;gt;10%. Pituitary hormone screening may be important in patients with prolonged symptomatic long COVID. Presentation: 6/3/2024

B-217 Effective Diagnostic Platform and Method to Differentiate the Infectious From Non-Infectious Viruses With Nucleic Acid Detection Workflow

Abstract Background While qPCR has demonstrated high sensitivity, specificity, and ability to deliver reliable quantitative data in clinical samples, such results do not differentiate between infectious and non-infectious viral particles. In view of the principle of the qPCR method itself, the amplification detects the nucleic acid (DNA/RNA) of the virus, not the virus itself. In many cases, it is still possible to detect DNA/RNA fragments from dead viruses in recovered patients, while they are not infectious anymore. This will lead to prolonged quarantine period or treatment for the patients, which could cause great psychological pressure to the patients and increased healthcare burden. Therefore, an effective detection method that can discriminate viable and inviable pathogens is of great significance. Methods SARS-CoV2 viral RNA, SARS-CoV-2 viruses, or clinical samples with SARS-CoV2 infection were diluted in Delta MTM (Molecular Transport Media) to the respective testing concentrations. The samples were incubated with intercalating dye (PMAxx 100nM) with or without Triton X-100 for 10 min. The mixture was then exposed to the photo-activation device for 5-15 min (@ temperature below 37° C). The samples were then subjected to the standard nucleic acid extraction &amp; purification steps with Qiagen viral RNA extraction kit. The extracted RNA was subjected to amplification with SARS-CoV2 Resolute 2.0 &amp; Fortunate 2.1 assays on BioRAD CFX96. Results The viability PCR (vPCR) efficiency was almost 100% for all SARS-CoV2 RNA input tested suggesting that without viral membrane protection, PMAxx dye effectively bound to the naked RNA after photoactivation process, and the bound RNA was not able to be amplified. The vPCR efficiency was further enhanced with addition of surfactant Triton X-100 suggesting the improved permeability of dye through the viral envelope facilitated the PMAxx binding to the nucleic acid. COVID19 positive clinical samples with viral load ≈ Ct 30 treated with or without PMAxx and photo-activation procedures showed distinctive ΔCt value ranging from 9.27±0.18 to 15.01±0.14. The Ct after dye treatment were all non-numeric (non-detectable) if cut-off Ct sets @ 42.0, indicating the complete inhibition after vPCR pretreatment. Since the clinical samples were undergone heat-inactivation pre-treatment, the result shown here indicating that all samples were non-infectious, which was consistent with the samples tested. Conclusions We developed an effective viability PCR detection method and proprietary vPCR device, which was specifically designed for effective dye photo-activation. In addition, the method takes less than 15 min and could be integrated into the existing standard nucleic acid extraction and amplification workflow. Comparing to the standard PCR test result, this method could provide the information not only on the positivity of the tested pathogen, but also its viability, which could be very essential information for public surveillance and diagnostic decisions for healthcare providers.

Prevalence and Associated Factors of Mental Health Problems Among Peripartum Women During the COVID-19 Pandemic

Objective: This study aimed to determine the prevalence and associated factors of probable depression and probable anxiety in early postpartum women during the COVID-19 pandemic. Methods: This cross-sectional study was conducted with early postpartum women who applied to a maternity hospital to give birth in Turkey between March-June 2021. Women aged 19-45 years, with 23–42 weeks of gestation, with a singleton pregnancy, and negative for the SARSCoV-2 polymerase chain reaction test were included in the study. The Hospital Anxiety and Depression Scale (HADS) was used to assess the presence of probable depression (HADS depression score &gt;7) and probable anxiety (HADS anxiety score &gt;10). The associations between women’s sociodemographic and obstetric characteristics and depression and anxiety were evaluated using univariate and multivariate analyses. Results: A total of 450 women were included in the study. Of these, 50.2% (n=226) had probable depression, and 28% (n=126) had probable anxiety. Multivariate analysis revealed that while perceived poor income level increased the odds for the presence of probable depression, unintended pregnancy, anemia, and SARS-CoV2 infection during pregnancy were associated with probable anxiety. Conclusion: The presence of probable depression and probable anxiety were considerably high among women who had given birth during the pandemic. This study identified the most vulnerable groups in terms of mental health problems among women who were in the early postpartum period during the pandemic. It is essential to develop strategies to prevent and control the mental health problems of these risk groups for future emergency health crises.

Asymptomatic SARS-COV2 Infection or COVID-19 vaccination effect for severe multisystem inflammatory syndrome in a 6-year-old girl: case report and review of the literature

BackgroundMultisystem Inflammatory Syndrome in Children (MIS-C) is a rare complication, which develops within 3–6 weeks after SARS-CoV2 infection. The coronavirus disease 2019 (COVID-19) vaccine was firstly introduced in adults and adolescents and later in patients aged 5–11 years old. Although a reduced incidence of MIS-C and with less severe symptoms has been reported in vaccinated adolescents, there is little knowledge in children younger than 12 years of age. In addition, it is not understood whether MIS-C in vaccinated patients can be triggered by Covid19 vaccination or be secondary to a recent asymptomatic Sars-Cov2 infection.Case presentationWe describe the case of a Caucasian 6-year-old girl, one month after double COVID-19 vaccination, who presented fever, acute abdominal pain, rash, pharyngotonsillitis, cheilitis, cervical lymphadenopathy without a prior detected Sars-Cov2 infection. She also had lymphopenia, increase in inflammatory markers, cardiac and pulmonary involvement. Therefore, we dosed both anti Sars-Cov2 Spike and Nucleocapsid antibodies, which were positive and allowed us to confirm the diagnosis of MIS-C. We promptly administered intravenous immunoglobulins and methylprednisone, resulting in the initial regression of fever. During the hospitalization, the child also developed pancreatitis and severe neurological involvement, including irritability, drowsiness, distal tremor, dyskinesia and buccal asymmetry with complete resolution after 2 months. After 3 months from the onset of the symptoms, she reported a transient loss of hair compatible with telogen effluvium. After 12 months of follow-up, she did not show any symptomatic sequelae.ConclusionsThis case raises the question of whether COVID-19 vaccination may be involved in the pathogenesis of MIS-C in children between the ages of 5 and 11 years old.

Relationship between SARS-CoV-2 infection and ICU-acquired candidemia in critically ill medical patients: a multicenter prospective cohort study

BackgroundWhile SARS-CoV2 infection has been shown to be a significant risk-factor for several secondary bacterial, viral and Aspergillus infections, its impact on intensive care unit (ICU)-acquired candidemia (ICAC) remains poorly explored.MethodUsing the REA-REZO network (French surveillance network of ICU-acquired infections), we included all adult patients hospitalized for a medical reason of admission in participating ICUs for at least 48 h from January 2020 to January 2023. To account for confounders, a non-parsimonious propensity score matching was performed. Rates of ICAC according to SARS-CoV2 status were compared in matched patients. Factors associated with ICAC in COVID-19 patients were also assessed using a Fine-Gray model.ResultsA total of 55,268 patients hospitalized at least 48 h for a medical reason in 101 ICUs were included along the study period. Of those, 13,472 were tested positive for a SARS-CoV2 infection while 284 patients developed an ICAC. ICAC rate was higher in COVID-19 patients in both the overall population and the matched patients’ cohort (0.8% (107/13,472) versus 0.4% (173/41,796); p < 0.001 and 0.8% (93/12,241) versus 0.5% (57/12,241); p = 0.004, respectively). ICAC incidence rate was also higher in those patients (incidence rate 0.51 per 1000 patients-days in COVID-19 patients versus 0.32 per 1000 patients-days; incidence rate ratio: 1.58 [95% CI:1.08–2.35]; p = 0.018). Finally, patients with ICAC had a higher ICU mortality rate (49.6% versus 20.2%; p < 0.001).ConclusionIn this large multicenter cohort of ICU patients, although remaining low, the rate of ICAC was higher among COVID-19 patients.

Single-cell RNA sequencing reveals heterogeneity of ALI model and epithelial cell alterations after exposure to electronic cigarette aerosol

Electronic cigarettes (e-cigarettes) have been advertised as a healthier alternative to traditional cigarettes; however, their exact effects on the bronchial epithelium are poorly understood. Air-liquid interface culture human bronchial epithelium (ALI-HBE) contains various cell types, including basal cell, ciliated cell and secretory cell, providing an in vitro model that simulates the biological characteristics of normal bronchial epithelium. Multiplex single-cell RNA sequencing of ALI-HBE was used to reveal previously unrecognized transcriptional heterogeneity within the human bronchial epithelium and cell type–specific responses to acute exposure to e-cigarette aerosol (e-aerosol) containing distinct components (nicotine and/or flavoring). The findings of our study show that nicotine-containing e-aerosol affected gene expression related to transformed basal cells into secretory cells after acute exposure; inhibition of secretory cell function by down-regulating genes related to epithelial cell differentiation, calcium ion binding, extracellular exosomes, and secreted proteins; and enhanced interaction between secretory cells and other cells. On the other hand, flavoring may alter the growth pattern of epithelial cells and make basal cells more susceptible to SARS-CoV infection. Besides, the data also indicate factors that may promote SARS-CoV-2 infection and suggest therapeutic targets for restoring normal bronchial epithelium function after e-cigarette use. In summary, the current study offered fresh perspectives on alterations in the cellular landscape and cell type–specific responses in human bronchial epithelium that are brought about by e-cigarette use.

Can CRP and Lymphocyte Count be Considered as Predictive Factors for the Prognosis of COVID-19 in Intensive Care? An Analytic Study

Introduction: SARS Cov2 infection still represents a real threat whose clinical severity results from an inadequate immuno-inflammatory reaction. The objective of our study was to determine the prognostic interest of the value of CRP and the rate of lymphocytes in the management of patients contaminated by SARS-Cov2. Material And Methods: This is a prospective, descriptive and analytical study of interest to patients with severe COVID-19, admitted to medical intensive care at the Oued Eddahab military hospital, for a period of one year. The biological parameters were analyzed on admission and during the stay in intensive care. The ROC curve was used to determine the sensitivity and specificity of CRP and lymphocytes as well as their optimal predictive threshold values. Results: 32 patients were included in our study. The average age of admissions was 65 years ± 12.38 with a sex ratio of 5.4 in favor of men. The optimal predictive threshold for the severity found was 147mg/l for CRP with a sensitization of 95% and a specificity of 83.3%, and 807/mm3 for lymphocytes with a sensitivity of 91.7% and a specificity of 95%. The odds ratio (OR) found for CRP and lymphocytes was &gt; 1. Conclusion: The CRP and the level of lymphocytes at the threshold defined above are risk factors for the severity of Sars-Cov2 infection.

Rapid progression of CD8 and CD4 T cells to cellular exhaustion and senescence during SARS-CoV2 infection

Abstract Risk factors for the development of severe COVID-19 include several comorbidities, but age was the most striking one since elderly people were disproportionately affected by SARS-CoV-2 infection. Among the reasons for this markedly unfavorable response in the elderly, immunosenescence and inflammaging appear as major drivers of this outcome. A finding that was also notable was that hospitalized patients with severe COVID-19 have an accumulation of senescent T cells, suggesting that immunosenescence may be aggravated by SARS-CoV-2 infection. The present work was designed to examine whether these immunosenescence changes are characteristic of COVID-19 and whether it is dependent on disease severity using cross-sectional and longitudinal studies. Our cross-sectional data show that COVID-19, but not other respiratory infections, rapidly increased cellular senescence and exhaustion in CD4 and CD8 T cells during early infection. In addition, longitudinal analyses with patients from Brazil and Portugal provided evidence of increased frequencies of senescent and exhausted T cells over a 7-d period in patients with mild/moderate and severe COVID-19. Altogether, the study suggests that accelerated immunosenescence in CD4 and especially CD8 T-cell compartments may represent a common and unique outcome of SARS-CoV2 infection.