Prolonged Fatigue and Mental Health Challenges in Critical COVID-19 Survivors.

Background: The aim of this study was to investigate the development of fatigue and mental illness between 3 and 12 months after critical COVID-19 and explore risk factors for long-lasting symptoms. Study Design and Methods: A prospective, multicenter COVID-19 study in southern Sweden, including adult patients (≥18 years) with rtPCR-confirmed COVID-19 requiring intensive care. Survivors were invited to a follow-up at 3 and 12 months, where patient-reported symptoms were assessed using the Modified Fatigue Impact Scale (MFIS), the Hospital Anxiety and Depression Scale (HADS) and the Posttraumatic Stress Disorder Checklist version 5 (PCL-5). The development between 3 and 12 months was described by changes in relation to statistical significance and suggested values for a minimally important difference (MID). Potential risk factors for long-lasting symptoms were analyzed by multivariable logistic regression. Results: At the 3-month follow-up, 262 survivors (87%) participated, 215 (72%) returned at 12 months. Fatigue was reported by 50% versus 40%, with a significant improvement at 12 months (MFIS; median 38 vs. 33, P < .001, MID ≥4). There were no significant differences in symptoms of mental illness between 3 and 12 months, with anxiety present in 33% versus 28%, depression in 30% versus 22%, and posttraumatic stress disorder in 17% versus 13%. A worse functional outcome and less sleep compared to before COVID-19 were risk factors for fatigue and mental illness at 12 months. Conclusions: Fatigue improved between 3 and 12 months but was still common. Symptoms of mental illness remained unchanged with anxiety being the most reported. A worse functional outcome and less sleep compared to before COVID-19 were identified as risk factors for reporting long-lasting symptoms.

Successful use of tocilizumab and casirivimab/imdevimab in a twin pregnancy with critical COVID-19 - A case report.

COVID-19 in pregnancy is associated with increased maternal morbidity and mortality as well as higher risk for hospitalization in intensive care unit and mechanical ventilation. We present a 38-year-old 21+5week pregnant unvaccinated woman with twins and critical COVID-19 pneumonia caused by Delta SARS-CoV-2 strain. Because of rapid worsening of respiratory condition despite standard of care treatment with steroids, she received a combination of casirivimab/imdevimab and tocilizumab. After therapy we noticed respiratory improvement and after 10 days she was extubated. Due to selective fetal growth restriction of one of the twins, a planned caesarean section was performed at 34+6 weeks. Presented case indicates favorable outcome and safe use of casirivimab/imdevimab and tocilizumab in critical COVID-19, as no severe or minor signs or symptoms in the case presentation were observed neither in the mother nor in infants during the time of observation.

The National Early Warning Score 2 with Age and Body Mass Index (NEWS2 Plus) to Determine Patients with Severe COVID-19 Pneumonia.

(1) Background: Early identification of severe coronavirus disease 2019 (COVID-19) pneumonia at the initial phase of hospitalization is very crucial. To address this, we validated and updated the National Early Warning Score 2 (NEWS2) for this purpose. (2) Methods: We conducted a study on adult patients with COVID-19 infection in Chiang Mai, Thailand, between May 2021 and October 2021. (3) Results: From a total of 725 COVID-19 adult patients, 350 (48.3%) patients suffered severe COVID-19 pneumonia. In determining severe COVID-19 pneumonia, NEWS2 and NEWS2 + Age + BMI (NEWS2 Plus) showed the C-statistic values of 0.798 (95% CI, 0.767-0.830) and 0.821 (95% CI, 0.791-0.850), respectively. The C-statistic values of NEWS2 Plus were significantly improved compared to those of NEWS2 alone (p = 0.012). Utilizing a cut-off point of five, NEWS2 Plus exhibited better sensitivity and negative predictive value than the traditional NEWS2, with values of 99.7% vs. 83.7% and 98.9% vs. 80.7%, respectively. (4) Conclusions: The incorporation of age and BMI into the traditional NEWS2 score enhanced the efficacy of determining severe COVID-19 pneumonia. Physicians can rely on NEWS2 Plus (NEWS2 + Age + BMI) as a more effective decision-making tool for triaging COVID-19 patients during early hospitalization.

Mortality in patients with interstitial lung diseases hospitalized by severe or critical COVID-19.

BACKGROUND: Since the first case of severe COVID-19, its effect on patients with previous interstitial lung disease (ILD) has been uncertain. We aimed to describe baseline clinical characteristics in ILD patients hospitalized by critical COVID and compare mortality during hospitalization. METHODS: We studied patients with ILD with COVID-19 and a control group matched by age, 1:2 ratio with COVID-19 without previous lung disease. On admission, laboratory tests and sociodemographic variables were evaluated. We evaluated patients critically ill and compared baseline characteristics and mortality in each group. Additionally, we performed a sub-analysis of ILD patients who died versus survivors. RESULTS: Forty-one patients and 82 controls were analyzed. In the group of ILD with COVID-19 there was a predominance of women (65 versus 33%: p < 0.001); lower leukocytes (9 ± 6 versus 11 ± 7, p = 0.01) and neutrophils (8 ± 5 versus 10 ± 6, p = 0.02). The most common ILD was secondary to autoimmune diseases. Patients with ILD and critical COVID-19 showed a significantly higher mortality compared with those without previous ILD (63 versus 33%, p = 0.007). Patients who died in this group had higher BMI (28 ± 6 versus 25 ± 4 kg/m2, p = 0.05), less extended hospital stay (20 ± 17 versus 36 ± 27 days, p = 0.01), and fewer days of evolution (9 ± 7 versus 16 ± 16, p = 0.05). CONCLUSIONS: We found higher mortality in patients with ILD with critical COVID-19. Higher BMI and comorbidities were present in the non-survivors.

Predictive Factors of Mortality in Patients with Severe COVID-19 Treated in the Intensive Care Unit: A Single-Center Study in Vietnam.

INTRODUCTION: The fourth outbreak of COVID-19 with the delta variant in Vietnam was very fierce due to the limited availability of vaccines and the lack of healthcare resources. During that period, the high mortality of patients with severe and critical COVID-19 caused many concerns for the health system, especially the intensive care units. This study aimed to analyze the predictive factors of death and survival in patients with severe and critical COVID-19. METHODS: We conducted a cross-sectional and descriptive study on 151 patients with severe and critical COVID-19 hospitalized in the Intensive Care Unit of Binh Duong General Hospital. RESULTS: Common clinical symptoms of severe and critical COVID-19 included shortness of breath (97.4%), fatigue (89.4%), cough (76.8%), chest pain (47.7%), loss of smell (48.3%), loss of taste (39.1%), and headache (21.2%). The abnormal biochemical features were leukopenia (2.1%), anemia, thrombocytopenia (18%), hypoxia with low PaO2 (34.6%), hypocapnia with reduced PaCO2 (29.6%), and blood acidosis (18.4%). Common complications during hospitalization were septic shock (15.2%), cardiogenic shock (5.3%), and embolism (2.6%). The predictive factors of death were being female, age > 65 years, cardiovascular comorbidity, thrombocytopenia (< 137.109/l), and hypoxia at inclusion or after the first week or blood acidosis (pH < 7.28). The use of a high dose of corticosteroids reduced the mortality during the first 3 weeks of hospitalization but significantly increased risk of death after 3 and 4 weeks. CONCLUSIONS: Common clinical symptoms, laboratory features, and death-related complications of critical and severe COVID-19 patients were found in Vietnamese patients during the fourth wave of the COVID-19 pandemic. The results of this study provide new insight into the predictive factors of mortality for patients with severe and critical COVID-19.

Adverse outcomes and maternal complications in pregnant women with severe-critical COVID-19: a tertiary center experience.

OBJECTIVES: This study aimed to present perinatal outcomes, clinical challenges, and basic ICU management in pregnant women with severe-critical COVID-19 at our tertiary referral center. METHODS: In this prospective cohort study, patients were divided into two groups, whether they survived or not. Clinical characteristics, obstetric and neonatal outcomes, initial laboratory test results and radiologic imaging findings, arterial blood gas parameters at ICU admission, and ICU complications and interventions were compared between groups. RESULTS: 157 of the patients survived, and 34 of the patients died. Asthma was the leading health problem among the non-survivors. Fifty-eight patients were intubated, and 24 of them were weaned off and discharged healthfully. Of the 10 patients who underwent ECMO, only 1 survived (p<0.001). Preterm labor was the most common pregnancy complication. Maternal deterioration was the most common indication for a cesarean section. Higher neutrophil-to-lymphocyte-ratio (NLR) values, the need for prone positioning, and the occurrence of an ICU complication were important parameters that influenced maternal mortality (p<0.05). CONCLUSIONS: Overweight pregnant women and pregnant women with comorbidities, especially asthma, may have a higher risk of mortality related to COVID-19. A worsening maternal health condition can lead to increased rates of cesarean delivery and iatrogenic prematurity.

Different degree of cytokinemia and T-cell activation according to serum IL-6 levels in critical COVID-19.

Introduction: Tocilizumab, a humanized anti-interleukin-6 receptor (IL-6R) antibody, is recommended for the treatment of severe to critical coronavirus diseases 2019 (COVID-19). However, there were conflicting results on the efficacy of tocilizumab. Therefore, we hypothesized that the differences in tocilizumab efficacy may stem from the different immune responses of critical COVID-19 patients. In this study, we described two groups of immunologically distinct COVID-19 patients, based on their IL-6 response. Methods: We prospectively enrolled critical COVID-19 patients, requiring oxygen support with a high flow nasal cannula or a mechanical ventilator, and analyzed their serial samples. An enzyme-linked immunosorbent assay and flow cytometry were used to evaluate the cytokine kinetics and cellular immune responses, respectively. Results: A total of nine patients with critical COVID-19 were included. The high (n = 5) and low IL-6 (n = 4) groups were distinguished by their peak serum IL-6 levels, using 400 pg/mL as the cut-off value. Although the difference of flow cytometric data did not reach the level of statistical significance, the levels of pro-inflammatory cytokines and the frequencies of intermediate monocytes (CD14+CD16+), IFN-γ+ CD4+ or CD8+ T cells, and HLA-DR+PD-1+ CD4+ T cells were higher in the high IL-6 group than in the low IL-6 group. Conclusion: There were distinctive two groups of critical COVID-19 according to serum IL-6 levels having different degrees of cytokinemia and T-cell responses. Our results indicate that the use of immune modulators should be more tailored in patients with critical COVID-19.

Th-1, Th-2, Th-9, Th-17, Th-22 type cytokine concentrations of critical COVID-19 patients after treatment with Remdesivir.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) rapidly spread around the world causing a pandemic known as coronavirus disease 2019 (COVID-19). Cytokine storm was directly correlated with severity of COVID-19 syndromes. We evaluated the levels of 13 cytokines in ICU hospitalized COVID-19 patients (n = 29) before, and after treatment with Remdesivir as well as in healthy controls (n = 29). Blood samples were obtained from ICU patients during ICU admission (before treatment) and 5 days after treatment with Remdesivir. A group of 29 age- and gender-matched healthy controls was also studied. Cytokine levels were evaluated by multiplex immunoassay method using a fluorescence labeled cytokine panel. In comparison to cytokine levels measured at ICU admission, serum levels were reduced of IL-6 (134.75 pg/mL vs. 20.73 pg/mL, P < 0.0001), TNF-α (121.67 pg/mL vs. 10.15 pg/mL, P < 0.0001) and IFN-γ (29.69 pg/mL vs. 22.27 pg/mL, P = 0.005), whereas serum level was increased of IL-4 (8.47 pg/mL vs. 12.44 pg/mL, P = 0.002) within 5 days after Remdesivir treatment. Comparing with before treatment, Remdesivir significantly reduced the levels of inflammatory (258.98 pg/mL vs. 37.43 pg/mL, P < 0.0001), Th1-type (31.24 pg/mL vs. 24.46 pg/mL, P = 0.007), and Th17-type (36.79 pg/mL vs. 26.22 pg/mL, P < 0.0001) cytokines in critical COVID-19 patients. However, after Remdesivir treatment, the concentrations of Th2-type cytokines were significantly higher than before treatment (52.69 pg/mL vs. 37.09 pg/mL, P < 0.0001). In conclusion, Remdesivir led to decrease levels of Th1-type and Th17-type cytokines and increase Th2-type cytokines in critical COVID-19 patients 5 days after treatment.

Management of Severe and Critical COVID-19 Infection with Immunotherapies.

Following the reduction in mortality demonstrated by dexamethasone treatment in severe COVID-19, many targeted immunotherapies have been investigated. Thus far, inhibition of IL-6 and JAK pathways have the most robust data and have been granted Emergency Use Authorization for treatment of severe disease. However, it must be noted that critically ill patients comprised a relatively small proportion of most of the trials of COVID-19 therapeutics, despite bearing a disproportionate burden of morbidity and mortality. Furthermore, the rapidity and fluidity with which clinical trials have been conducted in the pandemic setting have contributed to difficulty in extrapolating available trial data to critically ill patients. The exclusion of many patients requiring invasive mechanical ventilation, preponderance of ordinal scale based endpoints, and frequent lack of blinding are particular challenges. More data is needed to identify beneficial treatments in the complex milieu of critical illness from COVID-19 infection.

COVID-19 Palliative and End-of-Life Care Plan: Development and Audit of Outcomes.

Objectives: Palliative care (PC) referral in serious and critical COVID-19 improves decision-making, health resource utilisation, end-of-life symptom management and family support. In this study, we explored developing a systematic decision-making matrix for PC referral in COVID-19 and audited its outcomes. Materials and Methods: A team of interdisciplinary experts developed a hospital COVID-19 PC plan. PC referral and outcomes of PC referral in hospitalised COVID-19 patients were audited. Results: Out of 1575 inpatients, 1066 (67.7%) had mild and 509 (32.3%) had serious and critical COVID-19 illness. Among 50 (3.1%) referred to PC, 5 (0.4%) had mild and 45 (8.8%) had serious and critical COVID-19 illness. Out of 45 serious and critical COVID-19 patients referred to PC, 38 (84%) received end-of-life care (EOLC), 4 (9%) self-discharged against medical advice and 3 (7%) recovered. Forty-seven (94%) were referred for goals-of-care discussion. About 78% received opioids, 70% benzodiazepines and 42% haloperidol for symptom management. Among 45 serious and critical COVID-19 patients referred to PC, foregoing life-sustaining treatment was documented in 43 (96%) but implemented only in 23 (53%). Out of 38 who received EOLC, ICU was the place of death in 31 (82%) and ward in 7 (18%). Conclusion: Despite interdisciplinary experts developing a hospital COVID-19 PC, low referral of serious and critical COVID-19 patients to PC was observed. PC referral enabled access to management of end-of-life symptoms and facilitated limitation of life-sustaining treatment in some COVID-19 patients with serious illness. Educating critical care physicians about the scope of PC in the COVID-19 setting might improve PC referral.

What is the impact of previous cerebrovascular disease on critical COVID-19 patients' mortality? A prospective cohort study.

OBJECTIVES: We aimed to evaluate the effect of previous cerebrovascular disease (CVD) on mortality rates of critically ill COVID-19 patients. MATERIALS & METHODS: A prospective cohort study was performed between May/2020 and May/2021, at a tertiary-care-center. We consecutively included adult patients admitted to intensive care units (ICU) having as primary diagnosis Acute Respiratory Distress Syndrome due to SARS-CoV-2, requiring invasive mechanical ventilation for >48 h. We considered as exposure the diagnosis of previous CVD and as main outcome the in-ICU mortality. RESULTS: The study sample included 178 patients: 74.2% were males, with a mean age of 63 ± 12.4 years-old(yo). Previous CVD was documented in 17 patients (9.6%). During the study period, the mortality rate at ICU was of 33.1% (n = 59). The proportion of mortality at ICU was higher in patients with prior CVD (58.8% vs 30.4%; p = 0.02). Also, older patients (66 ± 11.4 yo vs. 62 ± 12.7 yo, p = 0.04) and those with higher score at SAPSII at ICU admission (47.8 ± 15.4 vs. 40.7 ± 15.9; p = 0.01) had a higher ICU deathrate. Patients with previous CVD had a 2.70 (95%CI = 1.36-5.39) higher likelihood of dying compared to those who had no previous CVD. After adjustment (for gender, age, SAPSII and total length of stay), multivariate Cox analysis revealed that previous CVD remained a strong predictor for in-ICU death in critically ill COVID-19 patients (HR = 2.51; 95%CI = 1.15-5.51). CONCLUSIONS: Previous CVD was significantly associated to higher mortality in critical COVID-19 patients. We suggest that, in patients with previous CVD, prioritization of vaccination strategies should be implemented alongst with higher surveillance when infected with SARS-CoV-2.

Continuous Renal Replacement Therapy With oXiris Filter May Not be an Effective Resolution to Alleviate Cytokine Release Syndrome in Non-AKI Patients With Severe and Critical COVID-19.

In this study, we aimed to determine whether continuous renal replacement therapy (CRRT) with oXiris filter may alleviate cytokine release syndrome (CRS) in non-AKI patients with severe and critical coronavirus disease 2019 (COVID-19). A total of 17 non-AKI patients with severe and critical COVID-19 treated between February 14 and March 26, 2020 were included and randomly divided into intervention group and control group according to the random number table. Patients in the intervention group immediately received CRRT with oXiris filter plus conventional treatment, while those in the control group only received conventional treatment. Demographic data were collected and collated at admission. During ICU hospitalization, the concentrations of circulating cytokines and inflammatory chemokines, including IL-2, IL-4, IL-6, IL-10, TNF-α, and IFN-γ, were quantitatively measured daily to reflect the degree of CRS induced by SARS-CoV-2 infection. Clinical data, including the severity of COVID-19 white blood cell count (WBC), neutrophil proportion (NEUT%), lymphocyte count (LYMPH), lymphocyte percentage (LYM%), platelet (PLT), C-reaction protein (CRP), high sensitivity C-reactive protein (hs-CRP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TB), albumin (ALB), serum creatinine (SCr), D-Dimer, fibrinogen (FIB), IL-2, IL-4, IL-6, IL-10, TNF-α, IFN-γ, number of hospital days and sequential organ failure assessment (SOFA) score were obtained and collated from medical records, and then compared between the two groups. Age, and SCr significantly differed between the two groups. Besides the IL-2 concentration that was significantly lower on day 2 than that on day 1 in the intervention group, and the IL-6 concentrations that were significantly higher on day 1, and day 2 in the intervention group compared to the control group, similar to the IL-10 concentration on day 5, there were no significant differences between the two groups. To sum up, CRRT with oXiris filter may not effectively alleviate CRS in non-AKI patients with severe and critical COVID-19. Thus, its application in these patients should be considered with caution to avoid increasing the unnecessary burden on society and individuals and making the already overwhelmed medical system even more strained (IRB number: IRB-AF/SC-04).

Therapeutic plasma exchange followed by convalescent plasma transfusion in severe and critically ill COVID-19 patients: A single centre non-randomized controlled trial.

Therapeutic plasma exchange (TPE) has been proposed as a rescue therapy in critically ill COVID-19 patients. The aim of the present study was to determine whether combining TPE with convalescent plasma (CVP) transfusion early in the intensive care unit (ICU) stay improves survival among this heterogeneous population. The primary endpoint was survival at 30 days. Secondary endpoints included assessing the evolution of biomarkers, such as the partial pressure of arterial oxygen to fractional inspired oxygen ratio, and C reactive protein (CRP), lactate dehydrogenase (LDH) and ferritin levels at the 7-day follow-up. This single centre, prospective, non-randomized controlled trial was conducted in an 8-bed COVID-19 ICU and included patients with severe COVID-19 pneumonia requiring intensive care treatment. A total of 19 patients were treated by performing TPE followed by CVP transfusion, in addition to standard treatment, while for another 19 patients, only standard treatment according to hospital protocols was used. TPE was initiated during the first 24 h after ICU admission, followed immediately by transfusion of CVP. Survival at 30 days was 47.37% in the TPE CVP group and 26.32% in the control group (P=0.002). Patients in the TPE CVP group also showed better oxygenation and a reduction in inflammation, with decreased CRP, LDH and ferritin levels compared with those in the control group. Overall, the study indicated that early initiation of TPE followed by CVP transfusion may be a valid rescue therapy in severe and critically ill COVID-19 patients, with a statistically significant survival benefit, improved oxygenation and a reduction in inflammatory markers. The trial was registered in the ClinicalTrials.gov database (trial registration number: NCT04973488) on July 22, 2021 (retrospectively registered).

X-Linked TLR7 Deficiency Underlies Critical COVID-19 Pneumonia in a Male Patient with Ataxia-Telangiectasia.

BACKGROUND: Coronavirus disease 2019 (COVID-19) exhibits a wide spectrum of clinical manifestations, ranging from asymptomatic to critical conditions. Understanding the mechanism underlying life-threatening COVID-19 is instrumental for disease prevention and treatment in individuals with a high risk. OBJECTIVES: We aimed to identify the genetic cause for critical COVID-19 pneumonia in a patient with a preexisting inborn error of immunity (IEI). METHODS: Serum levels of specific antibodies against the virus and autoantibodies against type I interferons (IFNs) were measured. Whole exome sequencing was performed, and the impacts of candidate gene variants were investigated. We also evaluated 247 ataxia-telangiectasia (A-T) patients in the Iranian IEI registry. RESULTS: We report a 7-year-old Iranian boy with a preexisting hyper IgM syndrome who developed critical COVID-19 pneumonia. IgM only specific COVID-19 immune response was detected but no autoantibodies against type I IFN were observed. A homozygous deleterious mutation in the ATM gene was identified, which together with his antibody deficiency, radiosensitivity, and neurological signs, established a diagnosis of A-T. Among the 247 A-T patients evaluated, 36 had SARS-CoV-2 infection, but all had mild symptoms or were asymptomatic except the index patient. A hemizygous deleterious mutation in the TLR7 gene was subsequently identified in the patient. CONCLUSIONS: We report a unique IEI patient with combined ATM and TLR7 deficiencies. The two genetic defects underlie A-T and critical COVID-19 in this patient, respectively.

The Role of High Flow Nasal Cannula in COVID-19 Associated Pneumomediastinum and Pneumothorax.

BACKGROUND: Pneumomediastinum, subcutaneous emphysema and pneumothorax are not rarely observed during the COVID-19 pandemic. Such complications can worsen gas exchange and the overall prognosis in critical patients. The aim of this study is to investigate what predisposing factors are related to pneumomediastinum and pneumothorax in SARS-CoV2-Acute Respiratory Distress Syndrome (ARDS), what symptoms may predict a severe and potentially fatal complication and what therapeutical approach may provide a better outcome. METHODS: In this single center cohort study, we recorded data from 45 critically ill COVID-19 patients who developed one or more complicating events among pneumomediastinum, subcutaneous emphysema and pneumothorax. All patients showed ARDS and underwent non-invasive ventilation (NIV) at baseline. Patients with mild to moderate ARDS and pneumomediastinum/pneumothorax (n = 25) received High Flow Nasal Cannula (HFNC), while patients with severe ARDS and pneumomediastinum/pneumothorax underwent HFNC (n = 10) or invasive mechanical ventilation (IMV) (n = 10). RESULTS: Pneumomediastinum/pneumothorax developed in 10.5% of subjects affected by SARS-coV2-ARDS. Dyspnea affected 40% and cough affected 37% of subjects. High resolution computed tomography of the chest showed bilateral diffuse ground glass opacities (GGO) in 100% of subjects. Traction bronchiolectasis, reticulation, crazy paving and distortion were observed in 64%. Furthermore, 36% showed subcutaneous emphysema. Non-severe ARDS cases received HFNC, and 76% patients recovered from pneumomediastinum/pneumothorax over a median follow up of 5 days. Among severe ARDS cases the recovery rate of pneumomediastinum/pneumothorax was 70% with the HFNC approach, and 10% with IMV. CONCLUSION: HFNC is a safe and effective ventilatory approach for critical COVID-19 and has a positive role in associated complications such as pneumomediastinum and pneumothorax.

Decreased Low-Density Lipoprotein Cholesterol Level Indicates Poor Prognosis of Severe and Critical COVID-19 Patients: A Retrospective, Single-Center Study.

Coronavirus disease 2019 (COVID-19) has become a global public health crisis. Reduced low-density lipoprotein cholesterol (LDL-C) levels were observed in COVID-19 patients. The present study aimed to explore the relationship between LDL-C levels and the prognosis of severe and critical COVID-19 patients. A total of 211 severe and critical COVID-19 patients were enrolled and divided into four groups according to the LDL-C levels, including 53 patients in Group A (LDL-C ≥ 2.71 mmol/L), 53 patients in Group B (2.28 ≤ LDL-C < 2.71 mmol/L), 53 patients in Group C (1.83 ≤ LDL-C < 2.28 mmol/L) and 52 patients in Group D (LDL-C < 1.83 mmol/L). LDL-C levels were lower in critically ill patients than in severe patients. The main symptoms before admission, characteristics on admission and comorbidities of enrolled patients did not differ among the four groups. Compared with patients with high LDL-C levels, patients with low LDL-C levels were more likely to have immune and inflammation dysfunction, renal dysfunction, liver dysfunction and cardiac dysfunction on admission. The proportions of patients with shock and acute cardiac injury, of those admitted to intensive care unit (ICU) and of those treated with mechanical ventilation were inversely related to LDL-C level. The mortality of COVID-19 patients increased with LDL-C reduction. Serum LDL-C levels of COVID-19 patients was negatively correlated with CRP level, but positively correlated with lymphocyte count, as shown by Pearson correlation analysis. Proportional hazard models showed that low LDL-C levels were associated with increased risk of hospitalization death, cardiac injury and admission to the ICU. Taken together, these results suggest that decreased LDL-C levels indicate poor prognosis of severe and critical COVID-19 patients.

Hyperimmune anti-COVID-19 IVIG (C-IVIG) treatment in severe and critical COVID-19 patients: A phase I/II randomized control trial.

BACKGROUND: Hyperimmune anti-COVID-19 Intravenous Immunoglobulin (C-IVIG) is an unexplored therapy amidst the rapidly evolving spectrum of medical therapies for COVID-19 and is expected to counter the three most life-threatening consequences of COVID-19 including lung injury by the virus, cytokine storm and sepsis. METHODS: A single center, phase I/II, randomized controlled, single-blinded trial was conducted at Dow University of Health Sciences, Karachi, Pakistan. Participants were COVID-19 infected individuals, classified as either severely or critically ill with Acute Respiratory Distress Syndrome (ARDS). Participants were randomized through parallel-group design with sequential assignment in a 4:1 allocation to either intervention group with four C-IVIG dosage arms (0.15, 0.20, 0.25, 0.30 g/kg), or control group receiving standard of care only (n = 10). Primary outcomes were 28-day mortality, patient's clinical status on ordinal scale and Horowitz index (HI), and were analysed in all randomized participants that completed the follow-up period (intention-to-treat population). The trial was registered at clinicaltrials.gov (NCT04521309). FINDINGS: Fifty participants were enrolled in the study from June 19, 2020 to February 3, 2021 with a mean age of 56.54±13.2 years of which 22 patients (44%) had severe and 28 patients (56%) had critical COVID-19. Mortality occurred in ten of 40 participants (25%) in intervention group compared to six of ten (60%) in control group, with relative risk reduction in intervention arm I (RR, 0.333; 95% CI, 0.087-1.272), arm II (RR, 0.5; 95% CI, 0.171-1.463), arm III (RR, 0.167; 95% CI, 0.024-1.145), and arm IV (RR, 0.667; 95% CI, 0.268-1.660). In intervention group, median HI significantly improved to 359 mmHg [interquartile range (IQR) 127-400, P = 0.009)] by outcome day, while the clinical status of intervention group also improved as compared to control group, with around 15 patients (37.5%) being discharged by 7th day with complete recovery. Additionally, resolution of chest X-rays and restoration of biomarkers to normal levels were also seen in intervention groups. No drug-related adverse events were reported during the study. INTERPRETATION: Administration of C-IVIG in severe and critical COVID-19 patients was safe, increased the chance of survival and reduced the risk of disease progression. FUNDING: Higher Education Commission (HEC), Pakistan (Ref no. 20-RRG-134/RGM/R&D/HEC/2020).

Ethical challenges in management of critically ill pregnant patients with coronavirus disease 2019 (COVID-19).

Despite the overwhelming number of coronavirus disease 2019 (COVID-19) cases worldwide, data regarding the optimal clinical guidance in pregnant patients is not uniform or well established. As a result, clinical decisions to optimize maternal and fetal benefit, particularly in patients with critical COVID-19 in the early preterm period, continue to be a challenge for obstetricians. There is often uncertainty in clinical judgment about fetal monitoring, timing of delivery, and mode of delivery because of the challenge in balancing maternal and fetal interests in reducing morbidity and mortality. The obstetrician and critical care team should empower pregnant patients or their surrogate decision maker to make informed decisions in response to the team's clinical evaluation. A clinically grounded ethical framework, based on the concepts of the moral management of medical uncertainty, beneficence-based obligations, and preventive ethics, should guide the decision-making process.

Correlation of the ratio of IgM/IgG concentration to days after symptom onset (IgM/T or IgG/T) with disease severity and outcome in non-critical COVID-19 patients.

BACKGROUND: Correlation of SARS-CoV-2 serum antibodies with COVID-19 development and outcome has not been fully studied. Due to the time dynamic of antibodies, the antibody concentration of the same patient varies greatly at different times during the course of the disease. Therefore, our study used IgM/T or IgG/T (the ratio of serum antibody concentration to days after symptom onset) to reflect the patient's humoral immune status, and analyzed their correlation with COVID-19 development and outcome. METHODS: Clinical data of 50 non-critical COVID-19 patients were retrospectively analyzed. Time-resolved fluorescence immunochromatography was used to quantitatively detect SARS-CoV-2 IgM and IgG. Correlation analysis was performed. RESULTS: IgM antibody was positive on day 5 of symptom onset, increased within 2 weeks, and then gradually decreased. However, IgG antibody was positive on week 2 of symptom onset and continued to increase since. Additionally, IgM/T, but not IgG/T of recovery period (Spearman ρ=0.17; P=0.283), was negatively correlated with disease course in 2 weeks of symptom onset (Spearman ρ=-0.860; P=0.000). IgG/T of recovery period was positively correlated with clinical classification (Spearman ρ=0.432; P=0.004), number of involved lung lobes (Spearman ρ=0.343; P=0.026), and lung lesions (Spearman ρ=0.472; P=0.002). CONCLUSIONS: Within 2 weeks of symptom onset, higher IgM/T indicates faster recovery and shorter disease course. In recovery period, higher IgG/T suggests more serious disease. IgM/T or IgG/T may predict disease severity and outcome in non-critical COVID-19 patients.

Different characteristics of critical COVID-19 and thinking of treatment strategies in non-elderly and elderly severe adult patients.

BACKGROUND: The differences in the characteristics and main causes of critical COVID-19 infection in non-elderly and elderly severe patients remain unknown. METHODS: We included 273 adult patients with confirmed severe COVID-19 from Tongji Hospital, Wuhan, China from February 10 to March 8, 2020. Clinical characteristics and risk factors for outcomes were compared between the young and middle-aged and the elderly severe patients. RESULTS: Hemoglobin, neutrophil percentage, inflammatory markers, hepatic, renal, and cardiovascularparameters differed between the non-elderly and elderly severe patients. In young and middle-aged patients, critical patients showed higher high-sensitivity C-reactive protein (hsCRP) during hospitalization than severe patients. However, in the elderly patients, critical patients showed decreased hsCRP during hospitalization and higher proBNP values. The hsCRP fluctuation and proBNP were independent risk factors for intensive care unit (ICU) admission in young and middle-aged severe patients (OR=1.068) and elderly severe patients (OR=1.026), respectively. CONCLUSION: The study revealed different potential causes of disease and predictive factors for non-elderly and elderly critical patients and treatment recommendations. Deterioration of inflammatory state was the main cause of ICU admission in young and middle-aged severe COVID-19 patients, while a decline in hsCRP was not associated with better outcomes in elderly severe patients, indicating the need for different treatments for non-elderly and elderly severe patients. Anti-inflammatory therapy with corticosteroids should be considered in the early disease stage among non-elderly severe patients, but cardiovascular protection plays a more important role in elderly severe patients.