Severe Critical Coronavirus Disease 2019 Research Articles

Clinical features of COVID-19 infection in patients with myasthenia gravis: a real-world retrospective study.

We investigated the risk factors associated with severe or critical Coronavirus disease 2019 (COVID-19) infection due to the Omicron variant in patients with myasthenia gravis (MG) and determined the potential effect of COVID-19 on myasthenic exacerbation during the Omicron pandemic. This retrospective study included 287 patients with MG in Tianjin, China. Clinical data of the patients were collected using electronic questionnaires, databases, and clinical records. The overall infection rate was 84.7%. Advanced age, comorbidities, generalized phenotype, and MG instability were drivers of COVID-19 severity, and post-COVID-19 myasthenic exacerbation. The concurrent use of a steroid-sparing agent did not affect COVID-19 susceptibility or severity. It did lower the risk of myasthenic exacerbation after COVID-19 infection. Patients with severe COVID-19 experienced myasthenic exacerbation earlier than patients with non-severe infection (p < 0.001). The severity of COVID-19 (Hazards Ratio = 3.04, 95% CI: 1.41-6.54, p = 0.004) and the clinical phenotype (Hazards Ratio = 3.29, 95% CI: 1.63-6.63, p < 0.001) emerged as independent risk factors for early MG exacerbation. Generally, patients with MG appear to be susceptible to the Omicron strains. Immunotherapy for MG did not increase COVID-19 susceptibility or severity. We do not advocate an immediate cessation of ongoing immunosuppressive treatments once a COVID-19 infection is diagnosed. Instead, a judicious evaluation of the risks and benefits, tailored to each individual, is recommended.

Role of ACE2 and TMPRSS2 polymorphisms on COVID-19 outcome and disease severity in adult patients: A prospective cohort study in a tertiary hospital, Indonesia.

Coronavirus disease 2019 (COVID-19) has led to a significant number of infections and deaths worldwide, yet its pathogenesis and severity remain incompletely understood. Angiotensin-converting enzyme 2 (ACE2) and transmembrane protease, serine 2 (TMPRSS2), play crucial roles as receptors and molecules responsible for the virus's entry into host cells, initiating the infection process. Their polymorphisms have been extensively studied in relation to COVID-19 severity. The aim of this study was to examine the association of ACE2 (rs2074192) and TMPRSS2 (rs12329760) polymorphisms with COVID-19 outcome and severity. A prospective cohort study was conducted in 2022 at Haji Adam Malik Hospital, Medan, Indonesia. We randomly recruited hospitalized adult patients with COVID-19, confirmed by real-time polymerase chain reaction (RT-PCR). The baseline demographic data, disease severity, underlying disease, comorbidities, and COVID-19 vaccination status were collected. The single-nucleotide polymorphism (SNP) was assessed using TaqMan SNP genotyping assay, and the levels of TMPRSS2 and ACE2 proteins were measured using enzyme-linked immunosorbent assay (ELISA). A total of 151 COVID-19 patients were recruited and there were significant associations between age and severity with mortality outcomes. The age, kidney and lung diseases, and vaccination status were associated with severity levels. The results showed the CC genotype of ACE2 had the highest proportion, followed by TT and CT genotypes among patients, while CT was the most prevalent genotype, followed by CC and TT for TMPRSS2. This study did not find a significant association between ACE2 and TMPRSS2 genetic variants with disease severity and outcome but highlighted a specific association of TMPRSS2 SNP with mortality within the group. In addition, ACE2 concentration was significant different between mild-moderate and severe-critical COVID-19 groups (p=0.033).

Twenty-eight-day mortality among patients with severe or critical COVID-19 in Hong Kong during the early stages of the pandemic.

In 2020, patients with critical coronavirus disease 2019 (COVID-19) had a 28-day mortality rate of 30% to 50% worldwide; outcomes among such patients in Hong Kong were unknown. This study investigated 28-day mortality and corresponding risk factors among patients with severe or critical COVID-19 in Hong Kong. This retrospective cohort study included adult patients with severe or critical COVID-19 who were admitted to three public hospitals in Hong Kong from 22 January to 30 September 2020. Demographics, comorbidities, symptoms, treatment, and outcomes were examined. Among 125 patients with severe or critical COVID-19, 15 (12.0%) died within 28 days. Overall, the median patient age was 64 years; 48.0% and 54.4% of patients had hypertension and obesity, respectively. Respiratory samples were confirmed severe acute respiratory syndrome coronavirus 2 RNA-positive after a median of 3 days. The most common presenting symptom was fever (80.0% of patients); 45.6% and 32.8% of patients received care in intensive care unit and required mechanical ventilation, respectively. In logistic regression analysis comparing 28-day survivors and non-survivors, factors associated with greater 28-day mortality were older age (odds ratio [OR] per 1-year increase in age=1.12, 95% confidence interval [CI]=1.04-1.21; P=0.002), history of stroke (OR=15.96, 95% CI=1.65-154.66; P=0.017), use of renal replacement therapy (OR=15.32, 95% CI=2.67-87.83; P=0.002), and shorter duration of lopinavir-ritonavir treatment (OR per 1-day increase=0.82, 95% CI=0.68-0.98; P=0.034). The 28-day mortality rate among patients with severe or critical COVID-19 in Hong Kong was 12.0%. Older age, history of stroke, use of renal replacement therapy, and shorter duration of lopinavir-ritonavir treatment were independent predictors of 28-day mortality.

Risk Factors for Severe-Critical COVID-19 in Pregnant Women.

Risk factors associated with severe-critical COVID-19 (coronavirus disease 2019) are based on findings in the general population. Pregnant women are at increased risk of severe-critical infection, and few reports are based on these women. A multicentric case-control study was conducted at the Mexican Institute of Social Security, State of Mexico, during the COVID-19 pandemic. We included pregnant women who were consecutively admitted to respiratory care units and were followed until 30 days after the resolution of pregnancy. A total of 758 pregnant women with a positive RT-PCR test for SARS-CoV-2 were enrolled from June 2020 to July 2021. We defined groups using the World Health Organization Severity Classification; cases were pregnant women with severe-critical COVID-19 (n = 123), and controls were subjects with non-severe COVID-19 (n = 635). Data was gathered from clinical files. A multivariate logistic regression analysis was used to adjust odds ratios and their 95% confidence intervals of factors associated with severe-critical COVID-19. Risk factors associated with severe-critical COVID-19 in pregnancy were non-vaccination (OR 10.18), blood type other than O (OR 6.29), maternal age > 35 years (OR 5.76), history of chronic hypertension (OR 5.12), gestational age at infection ≥ 31 weeks (OR 3.28), and multiparity (OR 2.80).

Relative Bradycardia and Tachycardia and Their Associations with Adverse Outcomes in Hospitalized COVID-19 Patients.

Relative-tachycardia (RT), a phenomenon of unproportionately high heart-rate elevation in response to fever, has been previously attributed to unfavourable outcomes in severe-inflammatory-response-syndrome (SIRS). Relative heart-rate to body-temperature ratio (RHR) and its prognostic associations in patients with severe and critical coronavirus disease 2019 (COVID-19) have not been investigated. We retrospectively analyzed heart-rate and body-temperature data at admission in patients who were hospitalized due to COVID-19 at a tertiary center from March 2020 to June 2021. After excluding patients with known heart rate affecting medications (beta-blockers and other antiarrhythmics) and atrial fibrillation, a total of 3490 patients were analyzed. Patients were divided into quartiles based on RHR on admission, with patients belonging to the 1st quartile designated as having relative-bradycardia (RB) and patients belonging to 4th quartile designated as having RT. Comparisons with baseline clinical characteristics and the course of treatment were done. There were 57.5% male patients. Median age was 69 years. Most patients had severe or critical COVID-19 at admission. Median heart-rate at the time of hospital admission was 90/min, median body-temperature was 38 °C, and median RHR was 2.36 with interquartile-range 2.07-2.65. RB in comparison to middle-range RHR was significantly associated with older age, higher comorbidity burden, less severe COVID-19 and less pronounced inflammatory profile, and in comparison to RT additionally with higher frequency of hyperlipoproteinemia but lower frequency of obesity. RT in comparison to middle-range RHR was significantly associated with younger age, more severe COVID-19, lower comorbidity burden, lower frequency of arterial hypertension, higher frequency of diabetes mellitus, and more pronounced inflammatory profile. In multivariate analyses adjusted for clinically meaningful parameters, RB patients experienced more favorable survival compared to RT, whereas RT patients experienced higher mortality in comparison to RB and middle-range RHR patients, independently of older age, male sex, higher comorbidity burden and higher COVID-19 severity. Heart rate and axillary temperature are an indispensable part of a clinical exam, easy to measure, at effectively no cost. RT at admission, as a sign of excessive activation of the sympathetic nervous system, is independently associated with fatal outcomes in COVID-19 patients.

Extracorporeal Photopheresis as a Possible Therapeutic Approach for Adults with Severe and Critical COVID-19 Non-Responsive to Standard Treatment: A Pilot Investigational Study.

Background: The optimal approach for adult patients hospitalized with severe and critical coronavirus disease 2019 (COVID-19), non-responsive to antiviral and immunomodulatory drugs, is not well established. Our aim was to evaluate feasibility and safety of extracorporeal photopheresis (ECP) in this setting. Methods: A prospective, single-center investigational study was performed between 2021 and 2022 at a tertiary referral center for COVID-19. Patients diagnosed with COVID-19 were screened, and cases with severe or critical disease fulfilling pre-defined clinical and biochemical criteria of non-response for >5 days, despite remdesivir, dexamethasone and immunomodulation (tocilizumab, baricitinib, ruxolitinib), were consecutively enrolled. After patient inclusion, two ECP sessions on two consecutive days per week for 2 weeks were applied. Patients were followed-up per protocol from study inclusion, and clinical, virological and radiological outcomes were assessed at the end of treatment (EOT) +28 days. Results: A total of seven patients were enrolled. At inclusion, four out of seven (57.1%) were admitted to the ICU, all patients had ongoing cytokine storm. Additionally, 3/7 (42.9%) had radiological progression on chest CT. At EOT+28 days, 2/7 (28.6%) patients died due to non-ECP-related causes. Among the survivors, no additional requirement for intensive care unit admission or radiological progression was observed, and invasive mechanical ventilation could be weaned off in 1/5 (20.0%). All patients achieved whole-blood SARS-CoV-2 RNAemia clearance, while 3/7 (42.9%) no longer showed detectable respiratory SARS-CoV-2 RNA. According to immune biomarker profiling, ECP mainly facilitated a decrease in plasma IL-6 and IL-17A levels, as well as the physiological regeneration of peripheral blood immunocyte subpopulations, notably CD8+/CD45RO+ memory T-cells. No safety signals were identified. Conclusions: ECP appears to be a safe and feasible option for adults hospitalized with severe or critical COVID-19 who do not respond to pharmacological interventions. Further trial data are warranted to assess its optimal use. Trial registration: ClinicalTrials.gov NCT05882331 (retrospectively registered).

Autoantibodies Neutralizing Type III Interferons Are Uncommon in Patients with Severe Coronavirus Disease 2019 Pneumonia.

Autoantibodies (AABs) neutralizing type I interferons (IFN) underlie about 15% of cases of critical coronavirus disease 2019 (COVID-19) pneumonia. The impact of autoimmunity toward type III IFNs remains unexplored. We included samples from 1,002 patients with COVID-19 (50% with severe disease) and 1,489 SARS-CoV-2-naive individuals. We studied the prevalence and neutralizing capacity of AABs toward IFNλ and IFNα. Luciferase-based immunoprecipitation method was applied using pooled IFNα (subtypes 1, 2, 8, and 21) or pooled IFNλ1-IFNλ3 as antigens, followed by reporter cell-based neutralization assay. In the SARS-CoV-2-naive cohort, IFNλ AABs were more common (8.5%) than those targeting IFNα2 (2.9%) and were related with older age. In the COVID-19 cohort the presence of autoreactivity to IFNλ did not associate with severe disease [odds ratio (OR) 0.84; 95% confidence interval (CI) 0.40-1.73], unlike to IFNα (OR 4.88; 95% CI 2.40-11.06; P < 0.001). Most IFNλ AAB-positive COVID-19 samples (67%) did not neutralize any of the 3 IFNλ subtypes. Pan-IFNλ neutralization occurred in 5 patients (0.50%), who all suffered from severe COVID-19 pneumonia, and 4 of them neutralized IFNα2 in addition to IFNλ. Overall, AABs to type III IFNs are rarely neutralizing, and do not seem to predispose to severe COVID-19 pneumonia on their own.

Prevalence of Hospital-Acquired Pneumonia Among Patients With Severe to Critical COVID-19 Pneumonia Given Tocilizumab.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has challenged healthcare systems worldwide since late 2019. The interleukin-6 inhibitor tocilizumab is one of the most studied agents with a proven benefit for patients with severe and critical coronavirus disease 2019 (COVID-19) pneumonia. Known adverse effects of this agent include upper respiratory tract infections, headache, hypertension, and transaminitis. The risk of secondary bacterial complications among patients who were given tocilizumab remains unclear. A descriptive study was done that included all laboratory-confirmed COVID-19 patients with a severe or critical severity for the year 2021 who received at least one dose of tocilizumab. Of the 1220 laboratory-confirmed COVID-19 patients admitted to Manila Doctors Hospital in the year 2021, a total of 139 patients fulfilled the inclusion criteria and were included in the study. Twenty-one patients, or 15% of the study population, were diagnosed with hospital-acquired pneumonia. This value was similar to previous studies showing the prevalence of secondary bacterial infections among patients who were given tocilizumab. These values could potentially aid clinicians when deciding whether or not to give one or two doses of tocilizumab to patients with severe or critical COVID-19 pneumonia. Given that many patients who are admitted with severe or critical COVID-19 pneumonia often have multiple decompensated comorbidities, the decision to give tocilizumab to manage severe COVID-19 should be weighed against the risk of hospital-acquired pneumonia.

Vaccination increased host antiviral gene expression and reduced COVID-19 severity during the Omicron variant outbreak in Fuyang City, China

BackgroundThe differences in host antiviral gene expression and disease severity between vaccinated and non-vaccinated coronavirus disease 2019 (COVID-19) patients are not well characterized. We sought to compare the clinical characteristics and host antiviral gene expression patterns of vaccinated and non-vaccinated cohorts at the Second People's Hospital of Fuyang City. MethodsIn this case-control study, we retrospectively analyzed 113 vaccinated patients with a COVID-19 Omicron variant infection, 46 non-vaccinated COVID-19 patients, and 24 healthy subjects (no history of COVID-19) recruited from the Second People's Hospital of Fuyang City. Blood samples were collected from each study participant for RNA extraction and PCR. We compared host antiviral gene expression profiles between healthy controls and COVID-19 patients who were either vaccinated or non-vaccinated at the time of infection. ResultsIn the vaccinated group, most patients were asymptomatic, with only 42.9 % of patients developing fever. Notably, no patients had extrapulmonary organ damage. In contrast, 21.4 % of patients in the non-vaccinated group developed severe/critical (SC) disease and 78.6 % had mild/moderate (MM) disease, with fever occurring in 74.2 % patients. We found that Omicron infection in COVID-19 vaccinated patients was associated with significantly increased expression of several important host antiviral genes including IL12B, IL13, CXCL11, CXCL9, IFNA2, IFNA1, IFNγ, and TNFα. ConclusionVaccinated patients infected with the Omicron variant were mostly asymptomatic. In contrast, non-vaccinated patients frequently developed SC or MM disease. Older patients with SC COVID-19 also had a higher occurrence of mild liver dysfunction. Omicron infection in COVID-19 vaccinated patients was associated with the activation of key host antiviral genes and thus may play a role in reducing disease severity.

The utility of systemic immune-inflammation index and systemic immune-response index in the prediction of adverse outcomes in pregnant women with coronavirus disease 2019: Analysis of 2649 cases.

To investigate the association of systemic immune-inflammation index (SII) and systemic immune-response index (SIRI) with adverse perinatal outcomes in pregnant women with coronavirus disease 2019 (COVID-19). The cases were divided into (1) the Mild-moderate COVID-19 group (n= 2437) and (2) the Severe-critical COVID-19 group (n= 212). Clinical characteristics, perinatal outcomes, SII (neutrophilXplatelet/lymphocyte), and SIRI (neutrophilXmonocyte/lymphocyte) were compared between the groups. Afterward, SII and SIRI values were compared between subgroups based on pregnancy complications, neonatal intensive care unit (NICU) admission, and maternal mortality. A receiver operator characteristic analysis was performed for the determination of optimal cutoff values for SII and SIRI in the prediction of COVID-19 severity, pregnancy complications, NICU admission, and maternal mortality. Both SII and SIRI were significantly higher in complicated cases (p< 0.05). Cutoff values in the prediction of severe-critical COVID-19 were 1309.8 for SII, and 2.3 for SIRI. For pregnancy complications, optimal cutoff values were 973.2 and 1.6. Cutoff values of 1045.4 and 1.8 were calculated for the prediction of NICU admission. Finally, cut-off values of 1224.2 and 2.4 were found in the prediction of maternal mortality. SII and SIRI might be used in combination with other clinical findings in the prediction of poor perinatal outcomes.

Treatment of pregnant and early postpartum women with severe and critical COVID-19: experience at a tertiary center

BackgroundThe management of acute respiratory failure during pregnancy is a poorly defined issue in the literature, especially regarding the use of the prone position and the appropriate time for delivery. This study describes our experience in treating pregnant and postpartum women with severe or critical coronavirus disease 2019 (COVID-19).Materials and methodsThis descriptive retrospective study included 25 pregnant and 4 postpartum women admitted to an ICU due to respiratory complications from COVID-19 from June 2020 to August 2021.ResultsThe mean maternal age was 33.6 years, and the median gestational age (GA) at admission was 33 weeks. Obesity was the most common comorbidity. The median time between symptom onset and ICU admission was 10 days, while the median length of ICU stay was 14 days. Invasive mechanical ventilation (IMV) was required in 16 (55.2%) patients for a median time of 16.5 days. Prone positioning (PP) was performed in 68.7% of the patients on IMV, and resulted in an expressive increase in arterial oxygen partial pressure to fractional inspired oxygen (PaO2/FiO2 ratio). Eleven (44%) pregnant women delivered during their ICU stay for obstetric or fetal reasons: of these, 2 (18%) developed postpartum hemorrhagic shock and 1 (9%) developed abdominal wall infection. None of the 25 pregnant women underwent delivery due to acute respiratory failure or in an attempt to avoid intubation. There were 2 fetal deaths, but no maternal or neonatal deaths.ConclusionWe observed favorable outcomes in pregnant and postpartum women with severe and critical COVID-19 admitted to our institution. This finding reinforces the effectiveness of PP in the treatment of hypoxemic respiratory failure secondary to COVID-19 in pregnant women undergoing IMV, and suggests that gestation should only be interrupted in cases of obstetric and fetal complications, provided the patient is stable, or when hypoxemia is refractory to PP.

Clinical, laboratory, and chest radiographic characteristics of COVID-19 associated severe pediatric pneumonia.A retrospective study

To evaluate the demographics, clinical presentation, laboratory data, chest radiographs, and outcomes of pediatric patients with critical coronavirus disease 2019 (COVID-19). This retrospective study included 34 children who were diagnosed with severe COVID-19 pneumonia between August 2020 and July 2021. Severe pneumonia was defined as fever, respiratory distress (tachypnea, chest retractions, and hypoxia [oxygen saturation <90% in room air]), and obvious infiltrations on chest radiography. Ages of the patients ranged from newborns to 12 years old, with a median of 24 months (interquartile range: 12-72 months). Preschool-aged children were the most common age group (44%). Levels of inflammatory markers (C-reactive protein, ferritin, and procalcitonin) were elevated in most patients. A total of 13 patients developed severe acute respiratory distress syndrome (ARDS), while 4 developed multiorgan failure. Despite receiving supportive therapy, 2 (5.9%) patients died due to severe septic shock and multiorgan failure. One deceased patient was born prematurely at 30 weeks, while the other had chronic granulomatous disease. This study described a single-center cohort of pediatric patients with severe COVID-19 pneumonia. In this cohort, children with cardiopulmonary comorbidities and ARDS had a high mortality and long-term morbidity, as observed in other pediatric studies.

The Trend of Arterial Carboxyhemoglobin in Non-smokers as a Prognostic Tool in Severe COVID-19 Patients: A Single-Centre Prospective Study.

Introduction Carboxyhemoglobinemia is characterised by decreased oxygen delivery to tissues. In severe and critical coronavirus disease 2019 (COVID-19) illness withhypoxia, this can herald a grave and protracted course of illness. Patients with COVID-19 experience respiratory impairment, lowering the pace at which carbon monoxide (CO) is eliminated and raising the likelihood of carboxyhemoglobinemia. We set out to exploreearly arterial carboxyhemoglobin (COHb) and COVID-19 patient outcomes in non-smokers andits potential as a predictive tool for mortality. Methods Forty-five patients, non-smokers with severe/critical severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection requiring admission in a North Indian 1200-bedded tertiary care hospital, were recruited prospectively from October 2020 to March 2021. Arterial COHb% was evaluated with arterial blood gases using an analyser, which were taken at the time of admission and then every alternate day for the first 10 days. Carboxyhemoglobinemia was defined as COHb% more than 1%. The primary outcome was defined as the patient's hospital outcome (survivor/non-survivor). Results Of the total 45 subjects, 51.1% (n=23) survived. Patients developed carboxyhemoglobinemia with an incidence of 51% during the course of their hospital stay. The mean ± SD of COHb% on admission was 1.0 ± 0.58 and 1.03 ± 0.8 in non-survivors and survivors, respectively (p=0.870). Maximal individual values of 5.3%and 6.1% were seen in survivors and non-survivors, respectively. On serial COHb measurement, non-survivors had significantly higher COHb% on days 6 and 10. No co-relation of COHb% with inflammatory markers was noted. Conclusion Arterial COHb levels in non-survivors were significantly higher than in survivors on days 6 and 10. Our study did not show a prognostic value of serial COHb measurement inpatients with severe COVID-19. To establish COHb as a predictive marker in severely ill COVID-19 patients, additional research is required.

Netosis and the Formation of Neutrophil Extracellular Traps (NETs) in Patients with Severe and Critical COVID-19 May Contribute to Disease Progression and Thrombosis

Introduction. NETosis and the formation of neutrophil extracellular traps (NETs) are known to be associated with the pathogenesis of various infectious diseases and thrombosis. However, the extent and clinical significance of NETosis and its released plasma markers in patients with a SARS-CoV2 infection resulting in severe and critical coronavirus disease 2019 (COVID-19) are not fully understood. Patients and Methods. COVID-19 patients on admission were prospectively enrolled for the study. Patients were classified according to WHO guidelines into asymptomatic (control), mild-moderate (not requiring oxygenation), severe (requiring oxygenation), and critical (multiple organ failure and/or requiring ventilator). Whole blood anticoagulated with EDTA from each patient was collected. Cells were fixed and stained for flow cytometry analysis following incubation with anti-CitrH3 and anti-MPO, and plasmas were used for assessing the soluble NETs. Results. Seventy-six hospitalized patients with PCR positive SARS-CoV2 were categorized into asymptomatic control (n=11), mild-moderate (n=28), severe (n=22), and critical (n=15) groups. Flow cytometry detected only few CitH3+/MPO+ positive neutrophils (undergoing NETosis) in blood of asymptomatic controls on admission. However, the number of CitH3+/MPO+ neutrophil dramatically increased following a 15-minute stimulation with a bacterial Shigatoxin-2 at 100 ng/mL or polyinosinic-polycytidylic acid [Poly (I:C)], a TLR3 agonist at 5 ug/mL for 3 hours (Fig. 1). The number of the CitH3+/MPO+ positive neutrophils in the samples from severe COVID-19 patients was significantly higher than that in asymptomatic controls (p=0.021). Interestingly, the number of the CitH3+/MPO+ positive neutrophils in critical patients was in fact lower than that in severe patients (p=0.013). Moreover, upon stimulation with Poly (I:C), the number of the CitH3+/MPO+ positive neutrophils in asymptomatic patients were more dramatically increased than those in severe/critical patients, suggesting a decrease in neutrophil reserve that could undergo NETosis and fight for infection. Microfluidic shear-based assay and confocal imaging analysis further demonstrated an increased formation of NETs strings under flow in whole blood samples from severe COVID-19 patients compared with those from asymptomatic controls (p=0.012). The NETs strings were sensitive to digestion by DNase I (Fig. 2), suggesting the therapeutic efficacy of DNase I in severe COVID-19 patients. Finally, plasma levels of cell-free DNA and histone-DNA complexes (the soluble markers of NETs in blood) were also more significantly increased in patients with severe and critical COVID-19 than those in the asymptomatic controls. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Timing of tofacitinib therapy is critical to improving outcomes in severe-critical COVID-19 infection: A retrospective study from a tertiary care hospital.

Describe the use of tofacitinib in severe and critical coronavirus disease-2019 (COVID-19), and explore the association of drug initiation time with survival. A retrospective study of inpatients with severe or critical COVID-19 at a tertiary care hospital, who were prescribed generic tofacitinib for at least 48 hours, was conducted. Baseline demographics, comorbidities, illness severity, treatment, adverse effects and outcomes were analyzed. Patients were grouped based on median duration of symptomatic illness prior to tofacitinib administration, as early or late initiation groups. Forty-one patients ([85.4% males], mean age 52.9 ± 12.5 years), were studied. 65.9% (n = 27) had severe COVID-19, while 34.1% (n = 14) were critically ill. Death occurred in 36.6% patients (n = 15). The median time to prescription of tofacitinib was 13 (9.50, 16.0) days of symptom onset. Tofacitinib was initiated early (8-13 days) in 56.1% of patients (n = 23), while the remaining received it beyond day 14 of symptom onset (late initiation group). Multivariate logistic regression adjusted for age, presence of diabetes mellitus and illness duration prior to hospitalization demonstrated higher odds of survival (adjusted odds ratio 19.3, 95% confidence interval 2.57, 145.2) in the early initiation group, compared to the late initiation group. Early initiation of tofacitinib in severe and critical COVID-19 has potential to improve survival odds.

NOTCH and Tumor Necrosis Factor-Alpha Converting Enzyme Levels Could be used in COVID-19 for Risk Stratification

Background: Novel coronavirus disease-2019 (COVID-19) has become a public emergency that is characterized by a dysregulated immune response and hypercoagulable state. The purpose of the present study was to evaluate NOTCH and tumor necrosis factor-alpha converting enzyme (TACE) levels in COVID-19-infected patients and assess their predictive value on the severity of the disease. Methods: A total of 116 severe-critical COVID-19 patients who were interned intensive care were included in the study. The severity of the disease was evaluated according to the WHO classification system. Patients were divided into two groups according to their cTroponin T (cTnT) levels. Patients who had cTnT levels at least five times the upper limit of normal constituted Group 1 (n = 58); patients who had normal cTnT levels constituted Group 2 (n = 58). Besides, 62 age- and sex-matched healthy controls, who applied to cardiology outward clinic were taken as a control group (Group 3). All patients underwent echocardiographic examination. NOTCH and TACE levels were assessed using enzyme-linked immunosorbent assay. Results: The average age of the patients was 59.96 ± 15.46 years, 92 (51.7%) were female and 86 (48.3%) were male. The mean length of hospital stay was 16.35 ± 10.97 days. NOTCH levels were significantly higher in Group 1 patients compared to Group 2 and control group of patients P = 0.001). NOTCH levels of Group 2 were significantly higher compared to the control group (P = 0.002). Similarly, the TACE levels of Group 1 were significantly higher than that of Group 2 and the control group (P = 0.001). Mortality and length of hospital stay were significantly higher in Group 1 patients compared to Group 2 patients (P = 0.002 and P = 0.004, respectively). TACE levels of deceased patients were significantly higher than that of live patients (P = 0.004). There was a positive relationship between the length of hospital stay and NOTCH levels in Group 1 patients (r = 0.527, P = 0.003). TACE and NOTCH levels were positively correlated with troponin levels (r = 0.627 and r = 0.671, respectively P &lt; 0.001 for both). NOTCH value of 0.34 nmol/L and TACE value of 6.53 μg/mL predicted inhospital mortality with a sensitivity of 90.30% and 63.6% and specificity of 91.5% and 78.6%, respectively. Conclusion: Measurement of NOTCH and TACE levels during severe acute respiratory syndrome coronavirus infection could be helpful for risk stratification.

Expert consensus on the diagnosis and treatment of severe and critical coronavirus disease 2019.

Expert consensus on the diagnosis and treatment of severe and critical coronavirus disease 2019.

Comparison of Tocilizumab and Anakinra in the Treatment of COVID-19: A Single-Center Experience

Aim: The aim of this study was to examine whether a difference between endotracheal intubation, non-invasive mechanical ventilation, high flow oxygen therapy requirements and 28-day mortality rate in severe and critical coronavirus disease 2019 (COVID-19) patients receiving anakinra and tocilizumab treatment. Material and Methods: A total of 70 patients infected with COVID-19, who were treated with tocilizumab and anakinra from April 2020 to March 2021 at Karabük Training and Research Hospital, were recruited in this retrospective study. Data on patient demographics, comorbidities, treatments, clinical outcomes of the patients’ and hemogram findings were retrieved from hospital records. Results: The mean age of the patients was 61.34±11.8 years. Of the 70 patients, 12 (17.1%) were female and 58 (82.9%) were male. Severe and critical COVID-19 cases were evident in 48 (68.6%), and 22 (31.4%) patients, respectively. The mortality rate in 28 days was not statistically significantly different between the tocilizumab and anakinra groups (p=0.999). Both the necessity of high flow oxygen therapy and non-invasive mechanical ventilation were lower in the tocilizumab group than in the anakinra group (p&amp;lt;0.001, and p=0.002, respectively), while there was no statistically significant difference in the necessity of intubation between the two groups (p=0.999). The length of stay was also significantly shorter in the tocilizumab group (p=0.027). Conclusion: High flow oxygen therapy, non-invasive mechanical ventilation requirements, and length of stay were significantly lower than anakinra in the tocilizumab group. Excessive inflammatory response with cytokine storm features causes severe disease course and worsens prognosis in COVID-19.

Management of COVID-19 in Kidney Transplant Recipients: A Single-Center Case Series.

Background Kidney transplant recipients (KTRs) were reported to be at higher risk of developing severe coronavirus disease-2019 (COVID-19). Despite being one of the most impacted countries, little is known about KTRs with COVID-19 in Indonesia. This report aims to explore the management strategies and short-term clinical outcomes of KTRs with COVID-19 in an Indonesian transplant center. Methods We observed KTRs who were admitted following COVID-19 diagnosis. Anamnesis, physical, laboratory, and radiologic examinations were performed. Demographic and transplant histories were recorded, along with symptoms, vaccination status, and management related to COVID-19. Results Nineteen KTRs were observed and 14 (73.6%) were male. The most common presenting symptoms were fever, cough, and shortness of breath. Nine (47.3%) KTRs had severe-critical COVID-19. The mortality rate was 42.1%. Acute kidney injury (AKI) was present in six (31.6%) of KTRs, five (83.3%) of whom were nonsurvivors. The median D-dimer level was higher in nonsurvivors (5,800 versus 670 μL), while other laboratory parameters were comparable. Seven (36.8%) KTRs were vaccinated. The mortality rates of vaccinated and unvaccinated KTRs were 14.2% and 70%, respectively. Antiviral therapy, anticoagulant, intravenous immunoglobulin, and tocilizumab were prescribed to 89.5%, 89.5%, 15.8%, and 10.5%, respectively. Immunosuppressive therapy (IST) was halted in 68% of KTRs, among which 61.5% passed away. Conclusion The clinical presentation of COVID-19 in KTRs was similar to that in the general population, whereas the mortality rate was higher. Management strategies for KTRs with COVID-19 should include prevention of AKI and hypercoagulation. Vaccination seems to be beneficial for KTRs, while temporary withdrawal of IST does not.

Duration of Replication-Competent Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Shedding Among Patients With Severe or Critical Coronavirus Disease 2019 (COVID-19).

BackgroundPatterns of shedding replication-competent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in severe or critical COVID-19 are not well characterized. We investigated the duration of replication-competent SARS-CoV-2 shedding in upper and lower airway specimens from patients with severe or critical coronavirus disease 2019 (COVID-19).MethodsWe enrolled patients with active or recent severe or critical COVID-19 who were admitted to a tertiary care hospital intensive care unit (ICU) or long-term acute care hospital (LTACH) because of COVID-19. Respiratory specimens were collected at predefined intervals and tested for SARS-CoV-2 using viral culture and reverse transcription–quantitative polymerase chain reaction (RT-qPCR). Clinical and epidemiologic metadata were reviewed.ResultsWe collected 529 respiratory specimens from 78 patients. Replication-competent virus was detected in 4 of 11 (36.3%) immunocompromised patients up to 45 days after symptom onset and in 1 of 67 (1.5%) immunocompetent patients 10 days after symptom onset (P = .001). All culture-positive patients were in the ICU cohort and had persistent or recurrent symptoms of COVID-19. Median time from symptom onset to first specimen collection was 15 days (range, 6–45) for ICU patients and 58.5 days (range, 34–139) for LTACH patients. SARS-CoV-2 RNA was detected in 40 of 50 (80%) ICU patients and 7 of 28 (25%) LTACH patients.ConclusionsImmunocompromise and persistent or recurrent symptoms were associated with shedding of replication-competent SARS-CoV-2, supporting the need for improving respiratory symptoms in addition to time as criteria for discontinuation of transmission-based precautions. Our results suggest that the period of potential infectiousness among immunocompetent patients with severe or critical COVID-19 may be similar to that reported for patients with milder disease.