Severe Critical Coronavirus Disease 2019 Research Articles

Multiplex PCR in the empirical antibiotic treatment of patients with SARS-CoV-2 and bacterial respiratory superinfection

SummaryBackgroundThe severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic led to overuse of antimicrobials, which increased concerns regarding antimicrobial resistance.ObjectiveTo measure the impact of a multiplex polymerase chain reaction (PCR) pneumonia panel on empirical antibiotic treatment for patients with critical coronavirus disease 2019 (COVID-19) with suspected bacterial respiratory superinfection.MethodsThis descriptive, prospective study was undertaken in a 36-bed intensive care unit from June 2020 to July 2021. Patients with severe COVID-19 who were ventilated and under suspicion of bacterial respiratory superinfection were included in the study. The intervention was a semi-quantitative multiplex PCR alongside concurrent standard cultures. When PCR panel results were expected to be obtained within 3 h of sampling, empirical antibiotic treatment was not administered while awaiting the results. Otherwise, empirical treatment was initiated. Patients classified as ‘avoided empirical treatment’ avoided 48–72 h of empirical antibiotic therapy. For those patients who received empirical treatment, the PCR panel results were used to decide whether treatment should be escalated, de-escalated, maintained or stopped. Positive and negative predictive values, and ‘avoided empirical treatment’ were calculated. Medical conduct and panel results were analysed for patients who received empirical treatment.ResultsEighty-two patients (71% male, 29% female) were included in this study. The mean age was 57.5 years, and the mean APACHE II score was 16. Ninety PCR panels were performed, and the negative and positive predictive values were 99.9% and 66.7%, respectively. Empirical treatment was avoided in 61% of episodes. Of those patients who were receiving antibiotics when the PCR panel was performed, treatment was de-escalated in 71%, escalated in 14%, stopped in 9% and maintained in 6%. A diagnosis of bacterial respiratory superinfection was ruled out in 19% of cases.ConclusionsPCR panels prevented the initiation of empirical antibiotic treatment in two-thirds of patients, and led to de-escalation in more than two-thirds of those who had started empirical antibiotic treatment. The high negative predictive value of the PCR panel allowed the diagnosis of bacterial respiratory superinfection to be ruled out. This tool represents a significant contribution to diagnostic stewardship in order to avoid the unnecessary use of antibiotics.

Inflammatory biomarkers and severity of COVID-19: Cross sectional study among Egyptian patients

The newly emerging coronavirus disease 2019 (COVID-19) is characterized by multisystem inflammatory syndrome. The development of SARS-CoV-2 complications usually starts within few days following infection, and the severity of the disease determines its outcome. Vitamin D insufficiency is associated with risk of lung infections, also cell-based studies reported the ability of vitamin D to control enveloped virus growth. We aimed to investigate the relationship between the most eminent inflammatory biomarkers and the level of vitamin D aiming to provide a tool for early diagnosis and prediction of disease progression. The current study was approved by Research Ethics Committee (REC), Kasr Al-Ainy. After confirmation of being COVID-19 by PCR, the admitted patients were categorized as mild-moderate, and severe-critically ill based on clinical and radiologic data. The total levels of serum 25(OH)D, as well as other pro-inflammatory biomarkers were measured and were analyzed by receiver operating characteristic curve (ROC) analysis for detection of their association with COVID-19 disease severity and to determine their sensitivity and specificity at optimum cutoff points. The area under the curve (AUC) ROC for predicting COVID-19 disease severity was the highest (of 0.97) for vitamin D, inflammatory cytokines, liver enzymes, ferritin, and D-Dimer. In addition, high serum levels of creatinine, and elevated liver enzymes associated with severe-critical COVID-19. The low 25(OH)D was associated with the disease severity.

Remdesivir use in pregnancy during the SARS-CoV-2 pandemic

Objective To ascertain the composite maternal and neonatal outcomes in pregnant individuals with moderate, severe, or critical coronavirus disease 2019 (COVID-19) treated with remdesivir. Materials and methods This is a secondary analysis of the COVID in Pregnancy Registry in Houston, Texas. Women were included if they met the criteria of moderate, severe or critical COVID-19 illness. Composite adverse maternal outcome was defined as any of the following outcomes: placental abruption, pregnancy-related hypertension, chorioamnionitis, stroke, delivery with estimated blood loss >1000 mL, diagnosis of pulmonary embolism or deep venous thromboembolism, or maternal death. Composite adverse neonatal outcome was defined as any of the following: Apgar score ≤3 at 5 min, arterial cord pH <7.0, positive SAR-CoV-2 test, intraventricular hemorrhage, periventricular leukomalacia, stillbirth, or neonatal death. Comparative analyses between participants receiving remdesivir versus those not exposed were performed. Results A total of 994 patients were diagnosed with COVID-19 infection. Of these, 95 (9.6%) met criteria for moderate, severe, or critical disease. Forty-one percent of these patients (n = 39) received remdesivir. Baseline demographic characteristics were not different between groups. No patients reported an allergic reaction with the administration of remdesivir; however, 16.7% of the patients had the medication discontinued due to transaminitis. Patients receiving the drug were more likely to have a longer illness duration on admission, more likely to require oxygen support on arrival and have a longer hospital stay. Conclusions Remdesivir appears to be safe, well tolerated within our cohort with no cases of recorded adverse reaction.

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).

The association between neutrophil to lymphocyte ratio and echocardiographic parameters in hospitalised adults with COVID-19 - a retrospective analysis

Funding AcknowledgementsType of funding sources: None.BackgroundThe neutrophil to lymphocyte ratio (NLR) is an inflammatory biomarker with prognostic value in several cardiovascular conditions. Hyperinflammation contributes to severe coronavirus disease 2019 (COVID-19), which is characterized by a multi-organ dysfunction. Cardiovascular complications of COVID-19 include arrhythmias, myocardial damage, acute heart failure, and acute coronary syndrome. Transthoracic echocardiography (TTE) can be used to assess cardiovascular structure and function non-invasively.PurposeTo investigate the association between NLR at admission and TTE abnormalities in hospitalised adults with COVID-19.MethodsThis single-centre retrospective study was conducted at a COVID-19 referral hospital in Indonesia. All consecutive hospitalised adults with confirmed COVID-19 who underwent TTE assessments between 3 April 2020 to 6 April 2021 were included. Comprehensive data including NLR at admission, demographics, co-morbidities, peak severity of COVID-19, and TTE parameters were extracted from electronic medical records. A receiver operating characteristic (ROC) curve analysis was conducted to determine the optimal NLR cut-off for prediction of severe-critical COVID-19. Patients with high and low NLR were compared using the chi-square test and odds ratios (OR), with a confidence level of 95%.ResultsA total of 487 patients were included in this study. From ROC curve analysis, the area under curve was 0.80 (95% CI: 0.76 – 0.84). The optimal NLR cut-off was determined as 4.42, which predicted severe-critical COVID-19 with a sensitivity of 74.5% and a specificity of 74.6%. Based on this, the low NLR and high NLR groups had 223 and 264 patients, respectively. Male sex, diabetes, and chronic kidney disease occurred more frequently in the high NLR group (P < 0.05). On TTE assessment, the high NLR group had higher odds of left ventricular (LV) systolic dysfunction (OR: 2.49; 95% CI: 1.14 – 5.45), LV wall motion abnormalities (OR: 2.62; 95% CI: 1.41 – 4.87), valve abnormalities (OR: 2.04; 95% CI: 1.35 – 3.07), and right ventricular (RV) dysfunction (OR: 10.55; 95% CI: 2.46 – 45.25).ConclusionsCOVID-19 patients with a high NLR at admission had higher odds of abnormal TTE findings, including LV systolic dysfunction, LV wall motion abnormalities, valve abnormalities, and RV dysfunction. This indicates a possible link between inflammation and cardiovascular dysfunction in COVID-19, which must be confirmed in larger prospective studies. Figure. ROC Curve Analysis Figure. Odds Ratios for TTE Abnormalities

The association between transthoracic echocardiographic parameters and severity of COVID-19 in hospitalised adults - a retrospective analysis

Funding AcknowledgementsType of funding sources: None.BackgroundThe coronavirus disease 2019 (COVID-19) is an ongoing global pandemic with more than 220 million cases and 4.5 million deaths reported worldwide. Its clinical spectrum varies widely, and non-invasive prognostic markers are valuable as they can guide efficient resource allocation. Cardiovascular complications of COVID-19 include myocardial injury, acute heart failure, and arrhythmias. Both de novo cardiovascular complications and pre-existing cardiovascular co-morbidities are associated with a poor prognosis. Transthoracic echocardiography (TTE) can be used to assess cardiovascular structure and function non-invasively.PurposeTo investigate the association between TTE parameters and severity of disease in hospitalised adults with confirmed COVID-19MethodsThis single-centre retrospective analysis was conducted at a COVID-19 referral hospital in Indonesia. All consecutive adults hospitalised with confirmed COVID-19 who underwent TTE assessment between 3 April 2020 to 6 April 2021 were included. Comprehensive data including demographics, peak COVID-19 severity, pre-existing co-morbidities, and TTE findings were extracted from electronic medical records. Patients with mild-moderate and severe-critical disease were compared using the chi-square test and odds ratios (OR), with a confidence level of 95%.ResultsA total of 488 patients were included in this study; 202 with mild-moderate disease and 286 with severe-critical disease. Frequency of old age (>60 years), obesity, diabetes, chronic kidney disease, and congestive heart failure were higher in the severe-critical group (P < 0.05). On TTE assessment, Patients with severe-critical disease had higher odds of left ventricular hypertrophy (LVH) (OR: 2.20; CI: 1.49 – 3.24), LV wall motion abnormality (OR: 3.33; CI: 1.68 – 6.60), diastolic dysfunction (OR: 1.46; CI: 1.02 – 2.11), valve abnormality (OR: 1.93; CI: 1.27 – 2.92), and right ventricular (RV) dysfunction (OR: 5.53; CI: 1.63 – 18.73). After matching for age, obesity, and diabetes, patients with severe-critical COVID-19 continued to have higher odds of LVH (OR: 1.91; CI: 1.21 – 3.02), LV wall motion abnormality (OR: 2.76; CI: 1.28 – 5.96), diastolic dysfunction (OR: 1.55; CI: 1.00 – 2.38), and RV dysfunction (OR: 3.86; CI: 1.06 – 14.08).ConclusionsThe presence of LVH, LV wall motion abnormality, diastolic dysfunction, and RV dysfunction on TTE assessment were associated with severe-critical disease in hospitalised adults with COVID-19. These findings must be validated in a larger prospective study. Figure. Odds Ratios for the Entire Cohort Figure. Odds Ratios for the Matched Cohort

Gastrointestinal manifestations of COVID-19 in a single center in the Eastern Province of Saudi Arabia.

Background:Several gastrointestinal (GI) symptoms have been associated with novel coronavirus disease-2019 (COVID-19). Their prevalence and relation to the severity and hospital outcome of COVID-19 have not been well reported in the Middle East and Saudi Arabia. We aimed to examine the GI manifestations of COVID-19 and their association with the severity and hospital outcome of COVID-19 infection.Methods:We conducted a retrospective observational study of hospitalized COVID-19 patients who had a positive SARS-COV2 PCR test and were admitted at a university hospital in Saudi Arabia, from March to September 2020. The primary objective of the study was to describe the GI manifestations of COVID-19. The secondary objective was to investigate the association of GI manifestations with severity and outcome of COVID-19 infection.Results:We included 390 patients, of which 111 (28.5%) presented with GI manifestations. The most common presentation was diarrhea followed by nausea, vomiting, and abdominal pain. Patients without GI manifestations had a higher risk of severe-critical COVID-19 infection evident by the development of lung infiltration in more than 50% of lung fields within 24–48 h, acute respiratory distress syndrome, altered mental status, multiorgan failure, and cytokine storm syndrome (P < 0.05). These patients had a higher mortality rate compared to patients with GI manifestations (P = 0.01). A lower odds of death was seen among patients with GI symptoms (AOR 0.36; 95% CI, 0.158–0.82; P = 0.01).Conclusion:COVID-19 infection presents commonly with GI manifestations. Patients with GI manifestations have less severe COVID-19 disease and lower mortality rates.

New life after near death: Surviving critical COVID-19 infection.

Background Few studies have explored the illness perceptions, experiences or attitudes towards the future of survivors of critical coronavirus disease 2019 (COVID-19). Through in-depth qualitative interviews, we aimed to enrich our understanding of participants’ perspectives, with the hope of offering more holistic and appropriate care to future patients. Methods Participants who had survived critical COVID-19 illness (defined as a laboratory or clinical diagnosis of COVID-19, with hypoxia requiring high-flow nasal oxygen (HFNO) or mechanical ventilation) were invited to participate. After informed consent procedures, clinic-demographic details were documented and individual interviews conducted using a topic guide, and were audio-recorded, translated, transcribed and coded into NVivo software where themes were extracted. Results Of 21 participants (13 female, 8 male), the mean age was 51.8 years (range 34 - 68), and mean duration of COVID symptoms was 21.7 days (range 17 - 37). Eighteen participants had been on HFNO, and 5 required mechanical ventilation. The major themes were: distressing experience; faith-based beliefs sustaining them; gratitude to healthcare workers (HCWs); better understanding of COVID and how dangerous it is; optimism for the future; and a resolve to implement lifestyle changes. Conclusion Qualitative interviews revealed our participants’ experience of severe COVID-19 as a difficult and terrifying ordeal, mitigated by faith-based beliefs, and the presence and care of HCWs. These experiences were reported by the participants as life changing, and all were inspired to focus on future self-care, and invest in fulfilling relationships. These insights call for future interventions to improve patient-centred care, including follow-up debriefing sessions, and support for lifestyle changes.

342. Secondary Infections following Tocilizumab for Treatment of COVID-19 Pneumonia

BackgroundGuidelines recommend use of tocilizumab (TCZ), an inhibitor of pro-inflammatory IL-6 signaling, for hospitalized patients with progressive severe or critical Coronavirus disease 2019 (COVID-19). The incidence of infectious complications following the use of TCZ for COVID-19 has not been well-described.MethodsWe conducted a retrospective, observational matched cohort study of severely ill, hospitalized adult patients with confirmed COVID-19 who were treated with TCZ between 2/24/2021 and 6/1/2021. The intervention group, comprised of patients who received a single dose of TCZ, was matched based on c-reactive protein (CRP) and fraction of inspired oxygen (FiO2) with a control group who did not receive TCZ, and were hospitalized between 10/12/2020 and 3/6/2021. The primary outcome of the study was diagnosis of a bacterial or fungal infection after day 3 of the index hospitalization. Secondary outcomes included all-cause mortality during the study period and length of stay. Results75 patients who received TCZ were identified during the study period, and matched 1:1 with 75 control patients. Baseline CRP and FiO2 were similar between groups, while the median age in the TCZ group was younger (61 versus 71 years), reflecting the epidemiology of the outbreak during the TCZ and control study periods. 15 bacterial and fungal infections were identified in the TCZ group (20.0%) and 4 (5.3%) infections in the control group (p = 0.012). The majority of infections in both groups were bacterial, with a disproportionate number of bloodstream infections in the TCZ group [7 (9.3%) vs 2(2.6%); p = 0.166]. 28 patients (37.3%) died in the TCZ group compared to 39 (52.0%) in the matched control (p = 0.068). Median time to discharge was similar between TCZ and control patients (11 versus 12 days; 95% CI -2,2).ConclusionSecondary infections in adult patients with severe and critical COVID-19 were more common in patients who had received TCZ. Prospective studies are needed to confirm and further describe this association.Disclosures All Authors: No reported disclosures

The efficacy of probiotics in patients with severe COVID-19.

To examine the incidence of diarrhea in severe and critical coronavirus disease 2019 (COVID-19) patients, and to observe the efficacy and prognosis of probiotic use in such patients. A retrospective study was conducted to investigate the symptoms and incidence of diarrhea in 156 cases of COVID-19 confirmed by the First Affiliated Hospital of Zhengzhou University and the Xinyang Fifth People's Hospital, China. A total of 58 cases of severe and critical COVID-19 were identified and divided into the treatment group or the control group. The control group was given standard treatment according to the Protocols for Diagnosis and Treatment of COVID-19: Prevention, Control, Diagnosis and Management. Patients in the treatment group were administered oral probiotics as well as the standard treatment. The 2 groups were compared in terms of nutritional status (serum albumin), improvement of diarrhea symptoms, changes in inflammatory condition [procalcitonin (PCT) and C-reactive protein (CRP)], the time taken to register a negative result for respiratory tract pathogens on the nucleic acid test, and changes to white blood cell and lymphocyte cell counts. In this study cohort, diarrhea was detected in 15.38% (24/156) of COVID-19 patients. The incidence of diarrhea in patients with mild and moderate COVID-19 was approximately 8.16% (8/98), and the incidence of diarrhea in severe and critically ill patients was approximately 27.59% (16/58). In patients with severe and critical COVID-19, probiotic treatment obviously shortened the duration of diarrhea. Furthermore, compared with the control group, patients treated with probiotics showed a significantly reduced time to achieving a negative nucleic acid test and the inflammation indexes including PCT and CRP were significantly reduced (P<0.05). The incidence of diarrhea in severe and critically ill COVID-19 patients was significantly higher than that in patients with mild and moderate COVID-19. Probiotics may have a good supporting role in the treatment of patients with COVID-19 and its early application is recommended.

Use of Intravenous Immunoglobulin in the Treatment of Severe COVID-19 Disease – A Case Series

Objective: To study and document the outcomes of adjuvant use of high dose intravenous immunoglobulin (IVIg) therapy in patients with severe or critical corona virus disease 2019 (COVID-19). We report in a case series of five patients who were admitted with severe and critical COVID-19 disease and were treated with adjuvant IVIG along-with the institute's standard of care (SOC) treatment. Methods: It is a retrospective observational study. We retrospectively collected data on all patients with COVID-19 disease who were hospitalized in author’s unit. The severe and critical disease patients who received IVIg were shortlisted and are discussed. Results: Data from 101 patients were analyzed. Of them 5 patients were treated with IVIG along with institution’s SOC. 4 patients were male and 1 was female. Except one patient (P2) all were above 60 years of age and all had one or more co morbidities with Diabetes mellitus (DM) and Hypertension (HT) present all of them. 3 patients had past history of pulmonary tuberculosis (P1, P4 and P5). P2 had chronic kidney disease (CKD) and P4 had coronary artery disease (CAD) with cardiac resynchronization therapy (CRT) device in situ. Median length of stay was 13 days and 4 of them were discharged. Conclusions: This small case series demonstrates that administration of IVIg in patients with severe COVID-19 disease, who did not respond to usual standard of care treatment, could improve clinical outcome and reduce mortality rate. It should be especially considered in cases with severe critical COVID-19 disease along with evidence of hyper inflammation /cytokine storm. Clinical efficacy is possibly driven by its anti-cytokine effects, reduction of inflammation by inhibition of complement activation, and down-regulation of B and T cells’ functions. Among the various inflammatory markers IVIg reduced CRP and D Dimer levels. It did not show relevant effect on other inflammation markers. However, multicenter studies with large sample size are needed to substantiate these observations.

Susceptibility of β-Thalassemia Heterozygotes to COVID-19

Background: β-Thalassemia is the most prevalent single gene blood disorder, while the assessment of its susceptibility to coronavirus disease 2019 (COVID-19) warrants it a pressing biomedical priority. Methods: We studied 255 positive COVID-19 participants unvaccinated against severe acute respiratory syndrome–coronavirus 2 (SARS-CoV-2), consecutively recruited during the last trimester of 2020. Patient characteristics including age, sex, current smoking status, atrial fibrillation, chronic respiratory disease, coronary disease, diabetes, neoplasia, hyperlipidemia, hypertension, and β-thalassemia heterozygosity were assessed for COVID-19 severity, length of hospitalization, intensive care unit (ICU) admission and mortality from COVID-19. Results: We assessed patient characteristics associated with clinical symptoms, ICU admission, and mortality from COVID-19. In multivariate analysis, severe-critical COVID-19 was strongly associated with male sex (p = 0.023), increased age (p < 0.001), and β-thalassemia heterozygosity (p = 0.002, OR = 2.89). Regarding the requirement for ICU care, in multivariate analysis there was a statistically significant association with hypertension (p = 0.001, OR = 5.12), while β-thalassemia heterozygosity had no effect (p = 0.508, OR = 1.33). Mortality was linked to male sex (p = 0.036, OR = 2.09), increased age (p < 0.001) and β-thalassemia heterozygosity (p = 0.010, OR = 2.79) in multivariate analysis. It is worth noting that hyperlipidemia reduced mortality from COVID-19 (p = 0.008, OR = 0.38). No statistically significant association of current smoking status with patient characteristics studied was observed. Conclusions: Our pilot observations indicate enhanced mortality of β-thalassemia heterozygotes from COVID-19.

COVID-Associated Pulmonary Aspergillosis and Its Related Outcomes: A Single-Center Prospective Observational Study

Background and objectiveInvasive pulmonary aspergillosis (IPA) is a frequent complication among neutropenic patients. It is increasingly being reported in critical coronavirus disease 2019 (COVID-19) patients requiring ICU admission and invasive mechanical ventilation (IMV) and is known as COVID-associated pulmonary aspergillosis (CAPA). We conducted this large prospective observational study to determine the frequency of CAPA and its outcomes in the ICU population.MethodologyThis was a prospective observational study. We recruited 307 reverse transcription-polymerase chain reaction (RT-PCR)-confirmed cases of severe COVID-19 pneumonia requiring IMV. We excluded those who did not require IMV or had been transferred out to other hospitals. The Chi-square test was applied to find the association between categorical variables. A p-value of <0.05 was considered statistically significant.ResultsOut of the 307 cases of mechanically ventilated COVID-19 pneumonia, 61 had probable CAPA. The median age was 60 years. Malignancy and cirrhosis were significant risk factors associated with CAPA (p=<0.001, 0.001, respectively). Aspergillus fumigatus was detected in 78.7% of the cases. The median length of ICU stay was 11 days [interquartile range (IQR): 4-14]. Among CAPA cases, 70.5% developed septic shock and required ionotropic support. Among 61 probable cases of CAPA, 91.8% did not survive and there was a strong correlation between CAPA and ICU mortality (p=0.001).ConclusionWe concluded that CAPA is a fatal complication of severe COVID-19 pneumonia and is associated with increased mortality.

The role of angiopoietin-2 and surfactant protein-D levels in SARS-CoV-2-related lung injury: A prospective, observational, cohort study.

IntroductionCoronavirus disease‐2019 (COVID‐19) is a respiratory disease whose clinical manifestation ranges from asymptomatic to severe respiratory failure. The purpose of this study was to investigate the place of serum surfactant‐D (SP‐D) and angiopoetin‐2 (Ang‐2) levels in predicting severity of disease in patients diagnosed with COVID‐19.MethodsSixty‐four patients diagnosed with COVID‐19 between September 2020 and February 2021, 50 patients diagnosed with community‐acquired pneumonia and a 50‐member healthy control group were included in the study. Plasma samples and clinical data were collected within 72 h after admission, during hospital stay. Serum SP‐D and Ang‐2 concentrations were measured using the enzyme‐linked immunosorbent assay.ResultsSP‐D and Ang‐2 levels were significantly higher in the mild–moderate pneumonia and severe/critical patient groups compared to the asymptomatic and noncomplicated COVID‐19 patients (p < 0.001 for all groups). Serum SP‐D and Ang‐2 levels of severe‐critical COVID‐19 patients were significantly higher than CAP patients (p < 0.001). Powerful correlation was present between clinical severity of COVID‐19 and SP‐D and Ang‐2 levels (r = 0.885 p < 0.001 and r = 0.913 p < 0.001, respectively). Cut‐off values of 37.7 ng/ml (AUC = 0.763, p < 0.001, 95% confidence interval [CI] = 0.667–0.860) for SP‐D and 4208.3 pg/ml (AUC = 0.659, p = 0.004, 95% CI = 0.554–0.763) for Ang‐2 were identified as predictors of COVID‐19 disease at receiver operating characteristic curve analysis.ConclusionSP‐D and Ang‐2 are predictive factors in differentiating COVID‐19 patients and determining severity of disease. These data may be important for the initiation of treatment in the early stage of the disease in patients with COVID‐19.

National Early Warning Score 2 (NEWS2) better predicts critical Coronavirus Disease 2019 (COVID-19) illness than COVID-GRAM, a multi-centre study

PurposeClinical scores to rapidly assess the severity illness of Coronavirus Disease 2019 (COVID-19) could be considered of help for clinicians. Recently, a specific score (named COVID-GRAM) for severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection, based on a nationwide Chinese cohort, has been proposed. We routinely applied the National Early Warning Score 2 (NEWS2) to predict critical COVID-19. Aim of this study is to compare NEWS2 and COVID-GRAM score.MethodsWe retrospectively analysed data of 121 COVID-19 patients admitted in two Clinics of Infectious Diseases in the Umbria region, Italy. The primary outcome was critical COVID-19 illness defined as admission to the intensive care unit, invasive ventilation, or death. Accuracy of the scores was evaluated with the area under the receiver-operating characteristic curve (AUROC). Differences between scores were confirmed used Hanley–McNeil test.ResultsThe NEWS2 AUROC curve measured 0.87 (standard error, SE 0.03; 95% CI 0.80–0.93; p < 0.0001). The COVID-GRAM score AUROC curve measured 0.77 (SE 0.04; 95% CI 0.68–0.85; p < 0.0001). Hanley–McNeil test showed that NEWS2 better predicted severe COVID-19 (Z = 2.03).ConclusionsThe NEWS2 showed superior accuracy to COVID-GRAM score for prediction of critical COVID-19 illness.

Dramatic improvement in severe-critical COVID-19 patient after tocilizumab administration: a clinical experience

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in coronavirus disease 2019 (COVID-19) involve so many inflammatory cytokines, especially Interleukin-6 (IL-6). The usage of tocilizumab as an anti-IL-6 receptor antibody had been approved as COVID-19 medication.Case Presentation: This article reports a 51-year-old woman diagnosed with severe-critical COVID-19. The patient made significant progress after tocilizumab administration. The patient was hospitalized for 14 days before being discharged.Conclusion: Tocilizumab administration showed a significant improvement in COVID-19 patients. However, further investigations are needed to explain this further.

CLINICAL PROFILES AND OUTCOMES OF PATIENTS ADMITTED WITH MODERATE TO CRITICAL CORONAVIRUS DISEASE 2019 (COVID-19)

Objective: To evaluate various demographic, clinical, radiological and hematological manifestations of moderate to critical coronavirus disease 2019 (COVID-19) and to assess its complications and outcomes in the Pakistani population.&#x0D; Study Design: Retrospective observational study.&#x0D; Place and Duration of Study: Pak Emirates Military Hospital, Rawalpindi, from Apr to Jul 2020.&#x0D; Methodology: Demographic, clinical, radiological and hematological data of 600 consecutive patients were retrieved and analyzed from hospital registry.&#x0D; Results: Overall, 449 (74.8%) patients had at least 1 comorbidity, diabetes mellitus being commonest; 228 (38%) [95% CI, 34.1- 42%]. The most common symptoms were cough; 451 (75.2%), fever; 450 (75%) and shortness of breath; 419 (69.8%). At presentation, 222 (37%) patients had moderate disease, 296 (49.3%) severe and 82 (12.7%) had critical disease. At admission, 277 (46.2%) patients required respiratory support and further 185 (30.8%) patients required treatment escalation later on correlated with disease severity and age (p&lt;0.001). A total of 92 (15.3%) patients died out of which 38 (21.2%) were on noninvasive ventilation and 36 (66.6%) on invasive ventilation, (p&lt;0.001). Overall survival (OS) was 84.7%; log rank &lt;0.001. Mortality was highest in critical disease, 72 (31.3%) (p&lt;0.001). A majority of patients, 440 (73.3%) developed complications, the most commonbeing Cytokine release storm (CRS); 57.5% respiratory failure; 43.8% and Acute respiratory distress syndrome (ARDS); 38.8%. Thrombotic events occurred in 106 (17.6%).Conclusion: Majority of patients with moderate to severe COVID-19 had comorbidities and ended up in variouscomplications.

Value of Bedside Lung Ultrasound in Severe and Critical COVID-19 Pneumonia.

Lung ultrasound (LUS) is an effective imaging modality that can differentiate pathological lung from non-diseased lung. We aimed to explore the value of bedside LUS in patients with severe and critical coronavirus disease 2019 (COVID-19)-associated lung injury. Sixty-three severe and 33 critical hospitalized subjects with COVID-19 were enrolled in this study. Bedside LUS was performed in all subjects; chest computed tomography was performed on the same day as bedside LUS in 23 cases. The LUS protocol consisted of 12 scanning zones. LUS score based on B-lines and lung consolidation was evaluated. The most common abnormality of LUS was the various forms of B-lines, detected in 93 (96.9%) subjects; as the second most frequent abnormality, 80 (83.3%) subjects exhibited lung consolidation, mainly located in the posterior lung region. Twenty-four (25.0%) subjects had pleural line abnormalities, and 16 (16.7%) had pleural effusion; 78 (81.3%) subjects had ≥ 2 abnormal LUS patterns, and 93 (96.9%) had bilateral lung involvement. The proportion of bilateral or unilateral lung consolidation and pleural effusion in the critical COVID-19 group were higher than that in the severe group (P < .05). The lung consolidation of critical subjects showed a marked increase in most lung areas, including bilateral lateral lung, posterior lung, and left anterior-inferior lung area. The median (interquartile range) LUS scores of critical cases were higher than those of severe cases: left: 14 (12-17) vs 7 (5-12); right: 14 (10-16) vs 8 (3-12); bilateral: 28 (23-31) vs 15 (8-22) (P < .001 for all). There was a good correlation between the LUS score and the chest computed tomography score (r = 0.887, P < .001). The most common abnormal LUS pattern in subjects with severe and critical COVID-19 pneumonia was B-lines, followed by lung consolidation. Bedside LUS can provide important information for pulmonary involvement in patients with COVID-19.

CANPT Score: A Tool to Predict Severe COVID-19 on Admission.

Background and Aims: Patients with critical coronavirus disease 2019 (COVID-19) have a mortality rate higher than 50%. The purpose of this study was to establish a model for the prediction of the risk of severe disease and/or death in patients with COVID-19 on admission.Materials and Methods: Patients diagnosed with COVID-19 in four hospitals in China from January 22, 2020 to April 15, 2020 were retrospectively enrolled. The demographic, laboratory, and clinical data of the patients with COVID-19 were collected. The independent risk factors related to the severity of and death due to COVID-19 were identified with a multivariate logistic regression; a nomogram and prediction model were established. The area under the receiver operating characteristic curve (AUROC) and predictive accuracy were used to evaluate the model's effectiveness.Results: In total, 582 patients with COVID-19, including 116 patients with severe disease, were enrolled. Their comorbidities, body temperature, neutrophil-to-lymphocyte ratio (NLR), platelet (PLT) count, and levels of total bilirubin (Tbil), creatinine (Cr), creatine kinase (CK), and albumin (Alb) were independent risk factors for severe disease. A nomogram was generated based on these eight variables with a predictive accuracy of 85.9% and an AUROC of 0.858 (95% CI, 0.823–0.893). Based on the nomogram, the CANPT score was established with cut-off values of 12 and 16. The percentages of patients with severe disease in the groups with CANPT scores <12, ≥12, and <16, and ≥16 were 4.15, 27.43, and 69.64%, respectively. Seventeen patients died. NLR, Cr, CK, and Alb were independent risk factors for mortality, and the CAN score was established to predict mortality. With a cut-off value of 15, the predictive accuracy was 97.4%, and the AUROC was 0.903 (95% CI 0.832, 0.974).Conclusions: The CANPT and CAN scores can predict the risk of severe disease and mortality in COVID-19 patients on admission.

Disease Severity and Perinatal Outcomes of Pregnant Patients With Coronavirus Disease 2019 (COVID-19).

To describe coronavirus disease 2019 (COVID-19) severity in pregnant patients and evaluate the association between disease severity and perinatal outcomes. We conducted an observational cohort study of all pregnant patients with a singleton gestation and a positive test result for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) who delivered at 1 of 33 U.S. hospitals in 14 states from March 1 to July 31, 2020. Disease severity was classified by National Institutes of Health criteria. Maternal, fetal, and neonatal outcomes were abstracted by centrally trained and certified perinatal research staff. We evaluated trends in maternal characteristics and outcomes across COVID-19 severity classes and associations between severity and outcomes by multivariable modeling. A total of 1,219 patients were included: 47% asymptomatic, 27% mild, 14% moderate, 8% severe, 4% critical. Overall, 53% were Hispanic; there was no trend in race-ethnicity distribution by disease severity. Those with more severe illness had older mean age, higher median body mass index, and pre-existing medical comorbidities. Four maternal deaths (0.3%) were attributed to COVID-19. Frequency of perinatal death or a positive neonatal SARS-CoV-2 test result did not differ by severity. Adverse perinatal outcomes were more frequent among patients with more severe illness, including 6% (95% CI 2-11%) incidence of venous thromboembolism among those with severe-critical illness compared with 0.2% in mild-moderate and 0% in asymptomatic (P<.001 for trend across severity). In adjusted analyses, severe-critical COVID-19 was associated with increased risk of cesarean birth (59.6% vs 34.0%, adjusted relative risk [aRR] 1.57, 95% CI 1.30-1.90), hypertensive disorders of pregnancy (40.4% vs 18.8%, aRR 1.61, 95% CI 1.18-2.20), and preterm birth (41.8% vs 11.9%, aRR 3.53, 95% CI 2.42-5.14) compared with asymptomatic patients. Mild-moderate COVID-19 was not associated with adverse perinatal outcomes compared with asymptomatic patients. Compared with pregnant patients with SARS-CoV-2 infection without symptoms, those with severe-critical COVID-19, but not those with mild-moderate COVID-19, were at increased risk of perinatal complications.