Live to die another day: novel insights may explain the pathophysiology behind smoker's paradox in SARS-CoV-2 infection.

The severe acute respiratory coronavirus 2 (SARS-CoV-2) infection demonstrates a highly variable and unpredictable course. Several reports have claimed a smoker's paradox in coronavirus disease 2019 (COVID-19), in line with previous suggestions that smoking is associated with better survival after acute myocardial infarction and appears protective in preeclampsia. Several plausible physiological explanations exist accounting for the paradoxical observation of smoking engendering protection against SARS-CoV-2 infection. In this review, we delineate novel mechanisms whereby smoking habits and smokers' genetic polymorphism status affecting various nitric oxide (NO) pathways (endothelial NO synthase, cytochrome P450 (CYP450), erythropoietin receptor (EPOR); ß-common receptor (ßcR)), along with tobacco smoke modulation of microRNA-155 and aryl-hydrocarbon receptor (AHR) effects, may be important determinators of SARS-CoV-2 infection and COVID-19 course. While transient NO bioavailability increase and beneficial immunoregulatory modulations through the above-mentioned pathways using exogenous, endogenous, genetic and/or therapeutic modalities may have direct and specific, viricidal SARS-CoV-2 effects, employing tobacco smoke inhalation to achieve protection equals self-harm. Tobacco smoking remains the leading cause of death, illness, and impoverishment.

Rapid Replacement of SARS-CoV-2 Variants by Delta and Subsequent Arrival of Omicron, Uganda, 2021.

Genomic surveillance in Uganda showed rapid replacement of severe acute respiratory syndrome coronavirus 2 over time by variants, dominated by Delta. However, detection of the more transmissible Omicron variant among travelers and increasing community transmission highlight the need for near-real-time genomic surveillance and adherence to infection control measures to prevent future pandemic waves.

Comorbidities as Risk Factors for Severe Disease in Hospitalized Elderly COVID-19 Patients by Different Age-Groups in Japan.

INTRODUCTION: Old age is an independent risk factor (RF) for severe COVID-19; evidence for clinico-epidemiological characteristics among elderly COVID-19 patients is scarce. We aimed to analyze clinical and epidemiological characteristics and comorbidities associated with COVID-19 inpatients in age-stratified populations of an elderly COVID-19 cohort. METHODS: We conducted a retrospective cohort study, using nationwide registry data of COVID-19 patients hospitalized before October 31, 2020 (major information entered in the registry as of December 28, 2020). Participants were divided by age according to the Japan Geriatrics Society and the Japan Gerontological Society: pre-old (65-74 years), old (75-89 years), and super-old (≥90 years). Multivariable logistic regression (MLR) analyses were conducted to identify stratified risk and relationships with comorbidities associated with worse outcomes in different age-groups of elderly patients. Demographics and supportive care were evaluated by category. RESULTS: Data of 4,701 patients from 444 hospitals were included. Most patients (79.3%) had at least one comorbidity; the proportion of patients with hypertension was high in all categories. The proportion of patients with dementia, cardiovascular disease, and cerebrovascular disease increased with age. The percentage of patients who underwent invasive mechanical ventilation/extracorporeal membrane oxygenation was lower in the super-old group. In total, 11.5% of patients died (5.3%, pre-old; 15.2%, old; and 22.4%, super-old). MLR showed that the risk of critical illness differed among age-groups. Male sex was a significant RF in all ages. Collagen disease, moderate to severe renal disorder, and dialysis were significant RFs in older patients, while hematological malignancies and metastatic tumors were more important RFs for severe disease in relatively younger patients. Most of the RFs for critical illnesses were associated with death. CONCLUSION: Differences in the epidemiological and clinical characteristics among the different age-groups were found.

SARS-CoV-2 (COVID-19) structural and evolutionary dynamicome: Insights into functional evolution and human genomics.

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has challenged the speed at which laboratories can discover the viral composition and study health outcomes. The small ∼30-kb ssRNA genome of coronaviruses makes them adept at cross-species spread while enabling a robust understanding of all of the proteins the viral genome encodes. We have employed protein modeling, molecular dynamics simulations, evolutionary mapping, and 3D printing to gain a full proteome- and dynamicome-level understanding of SARS-CoV-2. We established the Viral Integrated Structural Evolution Dynamic Database (VIStEDD at RRID:SCR_018793) to facilitate future discoveries and educational use. Here, we highlight the use of VIStEDD for nsp6, nucleocapsid (N), and spike (S) surface glycoprotein. For both nsp6 and N, we found highly conserved surface amino acids that likely drive protein-protein interactions. In characterizing viral S protein, we developed a quantitative dynamics cross-correlation matrix to gain insights into its interactions with the angiotensin I-converting enzyme 2 (ACE2)-solute carrier family 6 member 19 (SLC6A19) dimer. Using this quantitative matrix, we elucidated 47 potential functional missense variants from genomic databases within ACE2/SLC6A19/transmembrane serine protease 2 (TMPRSS2), warranting genomic enrichment analyses in SARS-CoV-2 patients. These variants had ultralow frequency but existed in males hemizygous for ACE2. Two ACE2 noncoding variants (rs4646118 and rs143185769) present in ∼9% of individuals of African descent may regulate ACE2 expression and may be associated with increased susceptibility of African Americans to SARS-CoV-2. We propose that this SARS-CoV-2 database may aid research into the ongoing pandemic.

Bloodstream Infection Risk, Incidence, and Deaths for Hospitalized Patients during Coronavirus Disease Pandemic.

Hospital-acquired infections are emerging major concurrent conditions during the coronavirus disease (COVID-19) pandemic. We conducted a retrospective review of hospitalizations during March‒October 2020 of adults tested by reverse transcription PCR for severe acute respiratory syndrome coronavirus 2. We evaluated associations of COVID-19 diagnosis with risk for laboratory-confirmed bloodstream infections (LCBIs, primary outcome), time to LCBI, and risk for death by using logistic and competing risks regression with adjustment for relevant covariates. A total of 10,848 patients were included in the analysis: 918 (8.5%) were given a diagnosis of COVID-19, and 232 (2.1%) had LCBIs during their hospitalization. Of these patients, 58 (25%) were classified as having central line‒associated bloodstream infections. After adjusting for covariates, COVID-19‒positive status was associated with higher risk for LCBI and death. Reinforcement of infection control practices should be implemented in COVID-19 wards, and review of superiority and inferiority ranking methods by National Healthcare Safety Network criteria might be needed.

Chest CT in the Emergency Department for Diagnosis of COVID-19 Pneumonia: Dutch Experience.

Background Clinicians need to rapidly and reliably diagnose coronavirus disease 2019 (COVID-19) for proper risk stratification, isolation strategies, and treatment decisions. Purpose To assess the real-life performance of radiologist emergency department chest CT interpretation for diagnosing COVID-19 during the acute phase of the pandemic, using the COVID-19 Reporting and Data System (CO-RADS). Materials and Methods This retrospective multicenter study included consecutive patients who presented to emergency departments in six medical centers between March and April 2020 with moderate to severe upper respiratory symptoms suspicious for COVID-19. As part of clinical practice, chest CT scans were obtained for primary work-up and scored using the five-point CO-RADS scheme for suspicion of COVID-19. CT was compared with severe acute respiratory syndrome coronavirus 2 reverse-transcription polymerase chain reaction (RT-PCR) assay and a clinical reference standard established by a multidisciplinary group of clinicians based on RT-PCR, COVID-19 contact history, oxygen therapy, timing of RT-PCR testing, and likely alternative diagnosis. Performance of CT was estimated using area under the receiver operating characteristic curve (AUC) analysis and diagnostic odds ratios against both reference standards. Subgroup analysis was performed on the basis of symptom duration grouped presentations of less than 48 hours, 48 hours through 7 days, and more than 7 days. Results A total of 1070 patients (median age, 66 years; interquartile range, 54-75 years; 626 men) were included, of whom 536 (50%) had a positive RT-PCR result and 137 (13%) of whom were considered to have a possible or probable COVID-19 diagnosis based on the clinical reference standard. Chest CT yielded an AUC of 0.87 (95% CI: 0.84, 0.89) compared with RT-PCR and 0.87 (95% CI: 0.85, 0.89) compared with the clinical reference standard. A CO-RADS score of 4 or greater yielded an odds ratio of 25.9 (95% CI: 18.7, 35.9) for a COVID-19 diagnosis with RT-PCR and an odds ratio of 30.6 (95% CI: 21.1, 44.4) with the clinical reference standard. For symptom duration of less than 48 hours, the AUC fell to 0.71 (95% CI: 0.62, 0.80; P < .001). Conclusion Chest CT analysis using the coronavirus disease 2019 (COVID-19) Reporting and Data System enables rapid and reliable diagnosis of COVID-19, particularly when symptom duration is greater than 48 hours. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Elicker in this issue.

[Reuse process of positive pressure powered air-filter protective hoods].

OBJECTIVE: To establish reuse process of positive pressure powered air-filter protective hoods during coronavirus disease 2019 (COVID-19) epidemic. METHODS: The procedure of pretreatment, storage, recovery, cleaning, disinfection and sterilization process of positive pressure powered air-filter protective hoods, which were used in the treatment of COVID-19 infection patients was established in Central Sterile Supply Department of the hospital. The cleaning and disinfection effects of the protective hoods after treatment were examined by magnifying glass method, residual protein detection method, real-time PCR, and agar pour plate method. RESULTS: Twenty five used protective hoods underwent totally 135 times of washing, disinfecting and sterilizing procedures. After washing, all the protein residue tests and COVID-19 nucleic acid tests showed negative results. After sterilizing, all the protective hoods met sterility requirement. All the tested protective hoods were undamaged after reprocessing. CONCLUSIONS: The established reuse procedures for used positive pressure powered air-filter protective hoods are safe.

The influence of the type of face mask used by healthcare providers during the SARS-CoV-2 pandemic on the report of pain: a cross-sectional study in a pediatric emergency department.

Background: During 4 months of the severe acute respiratory coronavirus 2 (SARS-CoV-2) pandemic, nurses in a pediatric emergency department (ED) used surgical and clear face masks in triage. This study aimed to find out if the type of face mask influenced children's reports of pain. Methods: A retrospective cross-sectional analysis of the pain scores of all patients aged 3-15 years who visited the ED during the 4-month period was performed. Multivariate regression was used to control for the potential confounders of demographics, diagnosis (medical, trauma), nurse experience, ED time of arrival, and triage acuity level. Self-reports of pain ≥1/10 and pain ≥4/10 were the dependent variables. Results: Overall, 3,069 children attended the ED during the study period. Triage nurses wore surgical and clear face masks in 2,337 and 732 nurse-patient encounters, respectively. The two types of face masks were used in similar proportions of nurse-patient encounters. Compared with the clear face mask, wearing a surgical face mask was associated with a lower likelihood of reporting pain ≥1/10, and a lower likelihood of reporting pain ≥4/10; [adjusted odds ratio (aOR) =0.68; 95% confidence interval (CI): 0.56-0.82], and (aOR =0.71; 95% CI: 0.58-0.86), respectively. Conclusions: The findings suggest that the type of face mask used by the nurse influenced the report of pain. This study provides preliminary evidence that covered face masks worn by healthcare providers might have a negative impact on the child's report of pain.

Beauty and the beast: host microRNA-155 versus SARS-CoV-2.

Severe acute respiratory coronavirus 2 (SARS-CoV-2) infection in the young and healthy usually results in an asymptomatic or mild viral syndrome, possibly through an erythropoietin (EPO)-dependent, protective evolutionary landscape. In the old and in the presence of co-morbidities, however, a potentially lethal coronavirus disease 2019 (COVID-19) cytokine storm, through unrestrained renin-angiotensin aldosterone system (RAAS) hyperactivity, has been described. Multifunctional microRNA-155 (miR-155) elevation in malaria, dengue virus (DENV), the thalassemias, and SARS-CoV-1/2, plays critical antiviral and cardiovascular roles through its targeted translational repression of over 140 genes. In the present review, we propose a plausible miR-155-dependent mechanism whereby the translational repression of AGRT1, Arginase-2 and Ets-1, reshapes RAAS towards Angiotensin II (Ang II) type 2 (AT2R)-mediated balanced, tolerable, and SARS-CoV-2-protective cardiovascular phenotypes. In addition, it enhances EPO secretion and endothelial nitric oxide synthase activation and substrate availability, and negates proinflammatory Ang II effects. Disrupted miR-155 repression of AT1R + 1166C-allele, significantly associated with adverse cardiovascular and COVID-19 outcomes, manifests its decisive role in RAAS modulation. BACH1 and SOCS1 repression creates an anti-inflammatory and cytoprotective milieu, robustly inducing antiviral interferons. MiR-155 dysregulation in the elderly, and in comorbidities, allows unimpeded RAAS hyperactivity to progress towards a particularly aggressive COVID-19 course. Elevated miR-155 in thalassemia plausibly engenders a favorable cardiovascular profile and protection against malaria, DENV, and SARS-CoV-2. MiR-155 modulating pharmaceutical approaches could offer novel therapeutic options in COVID-19.

Complement lectin pathway activation is associated with COVID-19 disease severity, independent of MBL2 genotype subgroups.

Introduction: While complement is a contributor to disease severity in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, all three complement pathways might be activated by the virus. Lectin pathway activation occurs through different pattern recognition molecules, including mannan binding lectin (MBL), a protein shown to interact with SARS-CoV-2 proteins. However, the exact role of lectin pathway activation and its key pattern recognition molecule MBL in COVID-19 is still not fully understood. Methods: We therefore investigated activation of the lectin pathway in two independent cohorts of SARS-CoV-2 infected patients, while also analysing MBL protein levels and potential effects of the six major single nucleotide polymorphisms (SNPs) found in the MBL2 gene on COVID-19 severity and outcome. Results: We show that the lectin pathway is activated in acute COVID-19, indicated by the correlation between complement activation product levels of the MASP-1/C1-INH complex (p=0.0011) and C4d (p<0.0001) and COVID-19 severity. Despite this, genetic variations in MBL2 are not associated with susceptibility to SARS-CoV-2 infection or disease outcomes such as mortality and the development of Long COVID. Conclusion: In conclusion, activation of the MBL-LP only plays a minor role in COVID-19 pathogenesis, since no clinically meaningful, consistent associations with disease outcomes were noted.

Multicenter study evaluating novel multi-specimen pooling assay for the detection of SARS-CoV-2: High sensitivity and high throughput testing.

BACKGROUND/PURPOSE: Mass screening for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is important to prevent the spread of coronavirus disease 2019 (COVID-19). Pooling samples can increase the number of tests processed. LabTurbo AIO 48 is an automated platform that allows ribonucleic acid extraction and sample analysis on the same instrument. We created a novel pooling assay on this platform for SARS-CoV-2 detection and demonstrated that the pooling strategy increases testing capacity without affecting accuracy and sensitivity. METHODS: Comparative limit of detection (LoD) assessment was performed on the LabTurbo AIO 48 platform and the current standard detection system based on real-time reverse transcription polymerase chain reaction (rRT-PCR) using 55 clinically positive samples. An additional 330 primary clinical samples were assessed. RESULTS: Six samples pooled into one reaction tube were detected in approximately 2.5 h using the World Health Organization rRT-PCR protocol. LabTurbo AIO 48 also demonstrated a higher throughput than our reference rRT-PCR assay, with an LoD of 1000 copies/mL. The overall percentage agreement between the methods for the 330 samples was 100%. CONCLUSION: We created a novel multi-specimen pooling assay using LabTurbo AIO 48 for the robust detection of SARS-CoV-2, allowing high-throughput results; this assay will aid in better control and prevention of COVID-19. The diagnostic assay was cost-effective and time-efficient; thus, the pooling strategy is a practical and effective method for diagnosing large quantities of specimens without compromising precision.

Factors Associated with Severity of Acute Kidney Injury and Adverse Outcomes in Critically Ill Patients with COVID-19.

BACKGROUND: Acute kidney injury (AKI) is a well-recognized complication of coronavirus disease 2019 (COVID-19). The short and long-term outcomes of patients who develop AKI have not been well characterized. METHODS: In this multicenter retrospective cohort study, we describe the clinical characteristics and outcomes of critically ill adults with severe COVID-19 and AKI. Patient-level variables were extracted from the electronic medical record. Using nadir-to-peak serum creatinine, AKI was defined using the KDIGO definition. Multivariable logistic regression analyses examined factors associated with development of moderate-to-severe (stage 2-3) AKI, severe (stage-3) AKI, and the composite of renal replacement therapy (RRT) or in-hospital death. RESULTS: Among 459 critically ill adults with COVID-19, 371 (80.1%) developed AKI, with 179 (37.9%) developing stage-3 AKI. Male gender, black and Asian/Native American race, lower baseline estimated glomerular filtration rate (eGFR), higher body mass index (BMI), and higher Acute Physiology and Chronic Health Evaluation (APACHE) IV score were more prevalent among patients with severe AKI, as were systemic markers of inflammation. On multivariable analysis, male gender, black and Asian/Native American race, higher APACHE IV score, lower baseline eGFR, and higher BMI (mainly the highest BMI stratum ≥35 kg/m2) were independently associated with higher stages of AKI severity. Male gender, lower baseline eGFR, and higher APACHE IV score were also independently associated with the composite of RRT or in-hospital death. Moderate-to-severe AKI and severe AKI were independently associated with in-hospital death, and there was a significant interaction between BMI and moderate-to-severe AKI for the outcome of in-hospital death. Among 83 (18.1%) patients who required RRT, 27 (32.5%) survived, and 12 (44.4%) remained dialysis-dependent at discharge. At 3 and 6 months, 5 (41.7%) and 4 (33.3%) remained dialysis-dependent, respectively. CONCLUSIONS: AKI is common in critically ill adults with COVID-19. Several patient-level risk factors are associated with higher stages of AKI severity. BMI might be an effect modifier of AKI severity for in-hospital death. Among AKI survivors, there is a high rate of short- and long-term dialysis dependence.

Surgical coronary revascularization in patients with COVID-19; complications and outcomes: A retrospective cohort study.

Background and Aims: Coronary artery disease is high-risk comorbidity of COVID-19 infection. Nonelective coronary artery revascularization in COVID-19 patients carries substantial risk. Therefore, it is essential to understand the risk factors and outcomes fully. This study aims to evaluate the prognosis of coronary artery bypass grafting (CABG) surgery in patients with COVID-19. Methods: This retrospective cohort study assesses 171 patients who underwent urgent and emergent CABG in Tehran Heart Center from March 2020 to September 2021. The patients were allocated to cases and controls based on COVID-19 infection status. Demographic and clinical features, alongside the complications and outcomes, were compared between the two groups. Results: According to diagnostic criteria, 62 patients were diagnosed with COVID-19 (Case) and 109 patients had no COVID diagnosis (Control). Regarding the demographics and risk factors, hypertension was more prevalent among patients with COVID-19 (64.5% compared to 43.1% p= 0.007). Length of hospital stay, ventilation time, and intensive care unit (ICU) stay time were significantly higher in patients infected with COVID-19. Postoperative complications, including stroke, atrial fibrillation, pleural effusion, blood transfusion, and Inotrope use, were significantly higher in the case group. Mortality rates were also higher in COVID-19 patients with an odds ratio of 1.53; however, this difference is not statistically significant (p: 0.44, 95% CI = 0.50-4.01). Conclusion: COVID-19 is associated with a significantly higher hospital stay, ventilation time, and ICU stay. Mortality rates are also higher, albeit insignificantly. Various postoperative complications are also higher with COVID-19.

Comparison of diagnostic performances of different serological tests for SARS-CoV-2 antibody detection in cats and dogs.

Serosurveillance among animals, including pets, plays an important role in the current coronavirus disease 2019 (COVID-19) pandemic, because severe acute respiratory coronavirus 2 (SARS-CoV-2) infections in animal populations could result in the establishment of new virus reservoirs. Serological assays that offer the required sensitivity and specificity are essential. In this study, we evaluated the diagnostic performance of three different commercially available immunoassays for the detection of SARS-CoV-2 antibodies in pets, namely two ELISA tests for the detection of antibodies against SARS-CoV-2 nucleocapsid [ID Screen SARS CoV-2 double antigen multispecies (Double antigen) and ID Screen® SARS-CoV-2-N IgG indirect ELISA (Indirect)] and one test for the detection of neutralizing antibodies against SARS-CoV-2 receptor-binding-domain [surrogate virus neutralization test (sVNT)]. The obtained results were compared with those of conventional virus neutralization test (VNT), which was regarded as reference method. A total of 191 serum samples were analysed. Thirteen (6.8%) samples showed VNT-positive results. The overall sensitivity was higher for sVNT (100%) compared to nucleocapsid-based ELISA assays (23% for Double antigen and 60% for Indirect). The specificity was 100% for Indirect ELISA and sVNT, when a higher cut-off (>30%) was used compared to the one previously defined by the manufacturer (>20%), whereas the other test showed lower value (99%). The sVNT test showed the highest accuracy and agreement with VNT, with a perfect agreement when the higher cut-off was applied. The agreement between each nucleocapsid-based ELISA test and VNT was 96% for Indirect and 94% for Double antigen. Our findings showed that some commercially available serological tests may lead to a high rate of false-negative results, highlighting the importance of assays validation for the detection of SARS-CoV-2 antibodies in domestic animals.

Major severe acute respiratory coronavirus-2 (SARS-CoV-2) vaccine-associated adverse effects; benefits outweigh the risks.

INTRODUCTION: Since its emergence, there have been huge efforts to design vaccines against coronavirus disease 2019 (COVID-19) to inhibit its interpersonal spread. Global vaccine development is the most promising cost-effective method for overcoming the epidemic. However, following reports of post-vaccination thromboembolic adverse effects, there have been raising concerns about the safety profile of the COVID-19 vaccine. AREAS COVERED: We aimed to review the recent Food and Drug Administration (FDA)-approved vaccines and identify the organ-based major complications of COVID-19 vaccines based on reliable published studies. To find high-quality and large-scale observational, clinical trial, and cohort studies, PubMED, Scholar, Embase, and Web of Science were searched using keywords: COVID-19, SARS-CoV-2, vaccine, Pfizer (BNT162b2), Johnson and Johnson (Ad26.COV2), Moderna (mRNA-1273), Oxford AstraZeneca (ChAdOx1nCoV19), Coronavac (Sinovac), BBIBP-CorV (Sinopharm), adverse effect, and complication. To include all relevant articles, backward searching was also done on similar article citations. Case reports, studies including less than 10 participants, and biased articles were excluded. EXPERT OPINION: Based on data from high-quality and population-based studies, major adverse effects are divided into four major organ-specific groups, including cardiovascular, neurologic, hematologic, and immune-allergic side effects. The incidence of most of these side effects is not different between vaccinated and normal populations, and currently, the benefits of vaccination against COVID-19 are greater than the mortality and morbidity risks of COVID-19 infection. However, further studies, specifically systematic review and meta-analysis, are still indicated to investigate further unknown side effects of these vaccines and the existence of causality between the vaccine and reported adverse events.

Messenger ribonucleic acid vaccine-associated immune thrombocytopenia: A rare complication of vaccine.

Coronavirus disease-2019 continues to have a serious impact in countries with the effect of new variant viruses emerging with mutations. While the effectiveness and protection of the vaccine have been determined all over the world, some vaccine-related side effects can be detected in the form of cases. In our case, the patient was admitted to the emergency department of our hospital with complaints of weakness and progressive rash on his legs. Diffuse petechiae purpura on the legs of the patient was observed and complete blood count revealed thrombocytopenia. Peripheral blood smear supported the blood count test results with thrombocytopenia, secondary causes of thrombocytopenia were excluded, and the patient was diagnosed with vaccine-induced immune thrombocytopenia.

Assessment of respiratory support decision and the outcome of invasive mechanical ventilation in severe COVID-19 with ARDS.

Background: The coronavirus disease 2019 (COVID-19) is an ongoing pandemic. Invasive mechanical ventilation (IMV) is essential for the management of COVID-19 with acute respiratory distress syndrome (ARDS). We aimed to assess the impact of compliance with a respiratory decision support system on the outcomes of patients with COVID-19-associated ARDS who required IMV. Methods: In this retrospective, single-center, case series study, patients with COVID-19-associated ARDS who required IMV at Zhongnan Hospital of Wuhan University, China, from January 8th, 2020, to March 24th, 2020, with the final follow-up date of April 20th, 2020, were included. Demographic, clinical, laboratory, imaging, and management information were collected and analyzed. Compliance with the respiratory support decision system was documented, and its relationship with 28-day mortality was evaluated. Results: The study included 46 COVID-19-associated ARDS patients who required IMV. The median age of the 46 patients was 68.5 years, and 31 were men. The partial pressure of arterial oxygen (PaO2)/fraction of inspired oxygen (FiO2) ratio at intensive care unit (ICU) admission was 104 mmHg. The median total length of IMV was 12.0 (interquartile range [IQR]: 6.0-27.3) days, and the median respiratory support decision score was 11.0 (IQR: 7.8-16.0). To 28 days after ICU admission, 18 (39.1%) patients died. Survivors had a significantly higher respiratory support decision score than non-survivors (15.0 [10.3-17.0] vs. 8.5 (6.0-10.3), P = 0.001). Using receiver operating characteristic (ROC) curve to assess the discrimination of respiratory support decision score to 28-day mortality, the area under the curve (AUC) was 0.796 (95% confidence interval [CI]: 0.657-0.934, P = 0.001) and the cut-off was 11.5 (sensitivity = 0.679, specificity = 0.889). Patients with a higher score (>11.5) were more likely to survive at 28 days after ICU admission (log-rank test, P < 0.001). Conclusions: For severe COVID-19-associated ARDS with IMV, following the respiratory support decision and assessing completion would improve the progress of ventilation. With a decision score of >11.5, the mortality at 28 days after ICU admission showed an obvious decrease.

Fungal and bacterial co-infections of the respiratory tract among patients with COVID-19 hospitalized in intensive care units.

Backgrounds: The pandemic of COVID-19 has created a global public health crisis. ICU patients with COVID-19 are prone to infections of bacterial and/or fungal origins due to several risk factors. Consequently, the current study was conducted to evaluate the frequency, demographic characteristics, underlying conditions, and etiologic agents of fungal and bacterial co-infections of the respiratory tract among ICU patients with COVID-19 in Iran. Materials and methods: From May to October 2020, sputa and endotracheal aspirates were collected from ICU patients hospitalized with COVID-19 who also were suspected of bacterial and/or fungal co-infections according to inclusion criteria. The etiologic agents of bacterial co-infections were identified using the Vitek 2 identification method. For fungal identification, all samples were analyzed by direct microscopy using KOH 10% and culture. Furthermore, all isolates were subjected to sequencing method. Results: A total of 73 lung specimens were obtained from patients who met the inclusion criteria. Of these, in 15 cases (20.54%) fungal and/or bacterial co-infections were confirmed. Males were more infected (73.33%) and all of them were between 49 and 79 years. Candida albicans (n = 8, 61.53%) and Klebsiella pneumoniae (n = 5, 38.46%) were the most frequent etiologic agents related to fungal and bacterial co-infections, respectively. Pneumonia (n = 15, 100%) and diabetes mellitus (n = 8, 53.33%) were documented as the most prevalent underlying conditions. In the current study, 3 out of 15 patients (20%) died. Conclusion: The frequency of bacterial co-infections of the respiratory tract in ICU patients hospitalized with COVID-19 was relatively high. According to the results, one of the causes of death of these patients could be a secondary infection.

COVID-19 and Plethora of Fungal Infections.

Purpose of Review: Severe-acute respiratory coronavirus 2 (SARS-CoV-2) causing corona virus disease 2019 (COVID-19) has been the single most important pathogen driving health care delivery system for the last one and half years. Now, as the time is passing, many issues related to co-infections/secondary infections/superinfections in COVID-19 patients are emerging. The literature is getting enriched everyday by addition of reports from all over the world for the same. The purpose of this review is to decipher the plethora of fungal infections in COVID-19. Recent Findings: COVID-19 infection along with it brought many risk factors namely lung injury, immunosuppression, need for oxygen therapy, monoclonal antibodies, steroid therapy, etc. which are known predisposing factors for fungal infections. Rather the extent and severity of fungal pathogens has been so much that it has led to new terminologies like CAC (COVID-19-associated Candida), CAPA (COVID-19-associated pulmonary aspergillosis) and CAM (COVID-19-associated mucormycosis). There is increase in invasiveness of Candida, prevalence of aspergillosis in COVID-19 damaged lung and outbreak of mucormycosis in COVID-19 patients resulting in "double trouble," keeping laboratory personnel, clinicians, and intensivists on their toes in managing these patients. Summary: Awareness and understanding regarding these possible complications is necessary to decrease the morbidity and mortality among patients. The COVID-19 and fungal coinfections may bring more insight into ways of pathogenesis of fungal infections, need for better antifungal agents, quick diagnostic modalities, and better management policies in the near future.