Development and performance evaluation of a solenoid valve assisted low-cost ventilator on gas exchange and respiratory mechanics in a porcine model.

INTRODUCTION: During the COVID-19 pandemic, ventilator shortages necessitated the development of new, low-cost ventilator designs. The fundamental requirements of a ventilator include precise gas delivery, rapid adjustments, durability, and user-friendliness, often achieved through solenoid valves. However, few solenoid-valve assisted low-cost ventilator (LCV) designs have been published, and gas exchange evaluation during LCV testing is lacking. This study describes the development and performance evaluation of a solenoid-valve assisted low-cost ventilator (SV-LCV) in vitro and in vivo, focusing on gas exchange and respiratory mechanics. METHODS: The SV-LCV, a fully open ventilator device, was developed with comprehensive hardware and design documentation, utilizing solenoid valves for gas delivery regulation. Lung simulator testing calibrated tidal volumes at specified inspiratory and expiratory times, followed by in vivo testing in a porcine model to compare SV-LCV performance with a conventional ventilator. RESULTS: The SV-LCV closely matched the control ventilator's respiratory profile and gas exchange across all test cycles. Lung simulator testing revealed direct effects of compliance and resistance changes on peak pressures and tidal volumes, with no significant changes in respiratory rate. In vivo testing demonstrated comparable gas exchange parameters between SV-LCV and conventional ventilator across all cycles. Specifically, in cycle 1, the SV-LCV showed arterial blood gas (ABG) results of pH 7.54, PCO2 34.5 mmHg, and PO2 91.7 mmHg, compared to the control ventilator's ABG of pH 7.53, PCO2 37.1 mmHg, and PO2 134 mmHg. Cycle 2 exhibited ABG results of pH 7.53, PCO2 33.6 mmHg, and PO2 84.3 mmHg for SV-LCV, and pH 7.5, PCO2 34.2 mmHg, and PO2 93.5 mmHg for the control ventilator. Similarly, cycle 3 showed ABG results of pH 7.53, PCO2 32.1 mmHg, and PO2 127 mmHg for SV-LCV, and pH 7.5, PCO2 35.5 mmHg, and PO2 91.3 mmHg for the control ventilator. CONCLUSION: The SV-LCV provides similar gas exchange and respiratory mechanic profiles compared to a conventional ventilator. With a streamlined design and performance akin to commercially available ventilators, the SV-LCV presents a viable, readily available, and reliable short-term solution for overcoming ventilator supply shortages during crises.

COVID-Specific Long-term Sequelae in Comparison to Common Viral Respiratory Infections: An Analysis of 17 487 Infected Adult Patients.

Background: A better understanding of long-term health effects after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has become one of the health care priorities in the current pandemic. We analyzed a large and diverse patient cohort to study health effects related to SARS-CoV-2 infection occurring >1 month postinfection. Methods: We analyzed 17 487 patients who received diagnoses for SARS-CoV-2 infection in a total of 122 health care facilities in the United States before April 14, 2022. Patients were propensity score-matched with patients diagnosed with the common cold, influenza, or viral pneumonia from March 1, 2020, to April 1, 2021. For each outcome, SARS-CoV-2 was compared with a generic viral respiratory infection (VRI) by predicting diagnoses in the period between 30 and 365 days postinfection. Both coronavirus disease 2019 (COVID-19) and VRI patients were propensity score-matched with patients with no record of COVID-19 or VRI, and the same methodology was applied. Diagnoses where COVID-19 infection was a significant positive predictor in both COVID-19 vs VRI and COVID-19 vs control comparisons were considered COVID-19-specific effects. Results: Compared with common VRIs, SARS-CoV-2 was associated with diagnoses of palpitations, hair loss, fatigue, chest pain, dyspnea, joint pain, and obesity in the postinfectious period. Conclusions: We identify that some diagnoses commonly described as "long COVID" do not appear significantly more frequent post-COVID-19 infection compared with other common VRIs. We also identify sequelae that are specifically associated with a prior SARS-CoV-2 infection.

Effect of Race and Ethnicity on In-Hospital Mortality in Patients with COVID-19.

Objective: To identify differences in short-term outcomes of patients with coronavirus disease 2019 (COVID-19) according to various racial/ethnic groups. Design: Analysis of Cerner de-identified COVID-19 dataset. Setting: A total of 62 health care facilities. Participants: The cohort included 49,277 adult COVID-19 patients who were hospitalized from December 1, 2019 to November 13, 2020. Main Outcome Measures: The primary outcome of interest was in-hospital mortality. The secondary outcome was non-routine discharge (discharge to destinations other than home, such as short-term hospitals or other facilities including intermediate care and skilled nursing homes). Methods: We compared patients' age, gender, individual components of Charlson and Elixhauser comorbidities, medical complications, use of do-not-resuscitate, use of palliative care, and socioeconomic status between various racial and/or ethnic groups. We further compared the rates of in-hospital mortality and non-routine discharges between various racial and/or ethnic groups. Results: Compared with White patients, in-hospital mortality was significantly higher among African American (OR 1.5; 95%CI:1.3-1.6, P<.001), Hispanic (OR1.4; 95%CI:1.3-1.6, P<.001), and Asian or Pacific Islander (OR 1.5; 95%CI: 1.1-1.9, P=.002) patients after adjustment for age and gender, Elixhauser comorbidities, do-not-resuscitate status, palliative care use, and socioeconomic status. Conclusions: Our study found that, among hospitalized patients with COVID-2019, African American, Hispanic, and Asian or Pacific Islander patients had increased mortality compared with White patients after adjusting for sociodemographic factors, comorbidities, and do-not-resuscitate/palliative care status. Our findings add additional perspective to other recent studies.

Subarachnoid Hemorrhage and COVID-19: An Analysis of 282,718 Patients.

BACKGROUND: Intracranial hemorrhage (including subarachnoid hemorrhage [SAH]) has been reported in 0.3%-1.2% of patients with coronavirus disease 2019 (COVID-19). However, no study has evaluated the risk of SAH in patients with COVID-19. METHODS: We analyzed data from 62 health care facilities using the Cerner de-identified COVID-19 dataset. RESULTS: There were 86 (0.1%) and 376 (0.2%) patients with SAH among 85,645 patients with COVID-19 and 197,073 patients without COVID-19, respectively. In the multivariate model, there was a lower risk of SAH in patients with COVID-19 (odds ratio 0.5, 95% confidence interval 0.4-0.7, P < 0.0001) after adjusting for sex, age strata, race/ethnicity, hypertension, and nicotine dependence/tobacco use. The proportions of patients who developed pneumonia (58.1% vs. 21.3%, P < 0.0001), acute kidney injury (43% vs. 27.7%, P = 0.0005), septic shock (44.2% vs. 20.7%, P < 0.0001), and respiratory failure (64.0% vs. 39.1%, P < 0.0001) were significantly higher among patients with SAH and COVID-19 compared with patients without COVID-19. The in-hospital mortality among patients with SAH and COVID-19 was significantly higher compared with patients without COVID-19 (31.4% vs. 12.2%, P < 0.0001). CONCLUSIONS: The risk of SAH was not increased in patients with COVID-19. The higher mortality in patients with SAH and COVID-19 compared with patients without COVID-19 is likely mediated by higher frequency of systemic comorbidities.

Acute Ischemic Stroke and COVID-19: An Analysis of 27 676 Patients.

BACKGROUND AND PURPOSE: Acute ischemic stroke may occur in patients with coronavirus disease 2019 (COVID-19), but risk factors, in-hospital events, and outcomes are not well studied in large cohorts. We identified risk factors, comorbidities, and outcomes in patients with COVID-19 with or without acute ischemic stroke and compared with patients without COVID-19 and acute ischemic stroke. METHODS: We analyzed the data from 54 health care facilities using the Cerner deidentified COVID-19 dataset. The dataset included patients with an emergency department or inpatient encounter with discharge diagnoses codes that could be associated to suspicion of or exposure to COVID-19 or confirmed COVID-19. RESULTS: A total of 103 (1.3%) patients developed acute ischemic stroke among 8163 patients with COVID-19. Among all patients with COVID-19, the proportion of patients with hypertension, diabetes, hyperlipidemia, atrial fibrillation, and congestive heart failure was significantly higher among those with acute ischemic stroke. Acute ischemic stroke was associated with discharge to destination other than home or death (relative risk, 2.1 [95% CI, 1.6-2.4]; P<0.0001) after adjusting for potential confounders. A total of 199 (1.0%) patients developed acute ischemic stroke among 19 513 patients without COVID-19. Among all ischemic stroke patients, COVID-19 was associated with discharge to destination other than home or death (relative risk, 1.2 [95% CI, 1.0-1.3]; P=0.03) after adjusting for potential confounders. CONCLUSIONS: Acute ischemic stroke was infrequent in patients with COVID-19 and usually occurs in the presence of other cardiovascular risk factors. The risk of discharge to destination other than home or death increased 2-fold with occurrence of acute ischemic stroke in patients with COVID-19.

Laboratory Tests for COVID-19: A Review of Peer-Reviewed Publications and Implications for Clinical Use.

Diagnostic tests for the coronavirus infection 2019 (COVID-19) are critical for prompt diagnosis, treatment and isolation to break the cycle of transmission. A positive real-time reverse-transcriptase polymerase chain reaction (RT-PCR), in conjunction with clinical and epidemiologic data, is the current standard for diagnosis, but several challenges still exist. Serological assays help to understand epidemiology better and to evaluate vaccine responses but they are unreliable for diagnosis in the acute phase of illness or assuming protective immunity. Serology is gaining attention, mainly because of convalescent plasma gaining importance as treatment for clinically worsening COVID-19 patients. We provide a narrative review of peer-reviewed research studies on RT-PCR, serology and antigen immune-assays for COVID-19, briefly describe their lab methods and discuss their limitations for clinical practice.

Zoonotic Risk, Pathogenesis, and Transmission of Avian-Origin H3N2 Canine Influenza Virus.

Two subtypes of influenza A virus (IAV), avian-origin canine influenza virus (CIV) H3N2 (CIV-H3N2) and equine-origin CIV H3N8 (CIV-H3N8), are enzootic in the canine population. Dogs have been demonstrated to seroconvert in response to diverse IAVs, and naturally occurring reassortants of CIV-H3N2 and the 2009 H1N1 pandemic virus (pdmH1N1) have been isolated. We conducted a thorough phenotypic evaluation of CIV-H3N2 in order to assess its threat to human health. Using ferret-generated antiserum, we determined that CIV-H3N2 is antigenically distinct from contemporary human H3N2 IAVs, suggesting that there may be minimal herd immunity in humans. We assessed the public health risk of CIV-H3N2 × pandemic H1N1 (pdmH1N1) reassortants by characterizing their in vitro genetic compatibility and in vivo pathogenicity and transmissibility. Using a luciferase minigenome assay, we quantified the polymerase activity of all possible 16 ribonucleoprotein (RNP) complexes (PB2, PB1, PA, NP) between CIV-H3N2 and pdmH1N1, identifying some combinations that were more active than either parental virus complex. Using reverse genetics and fixing the CIV-H3N2 hemagglutinin (HA), we found that 51 of the 127 possible reassortant viruses were viable and able to be rescued. Nineteen of these reassortant viruses had high-growth phenotypes in vitro, and 13 of these replicated in mouse lungs. A single reassortant with the NP and HA gene segments from CIV-H3N2 was selected for characterization in ferrets. The reassortant was efficiently transmitted by contact but not by the airborne route and was pathogenic in ferrets. Our results suggest that CIV-H3N2 reassortants may pose a moderate risk to public health and that the canine host should be monitored for emerging IAVs.IMPORTANCE IAV pandemics are caused by the introduction of novel viruses that are capable of efficient and sustained transmission into a human population with limited herd immunity. Dogs are a a potential mixing vessel for avian and mammalian IAVs and represent a human health concern due to their susceptibility to infection, large global population, and close physical contact with humans. Our results suggest that humans are likely to have limited preexisting immunity to CIV-H3N2 and that CIV-H3N2 × pdmH1N1 reassortants have moderate genetic compatibility and are transmissible by direct contact in ferrets. Our study contributes to the increasing evidence that surveillance of the canine population for IAVs is an important component of pandemic preparedness.

An Integrated Approach to Sequence-Independent Local Alignment of Protein Binding Sites.

Accurate alignment of protein-protein binding sites can aid in protein docking studies and constructing templates for predicting structure of protein complexes, along with in-depth understanding of evolutionary and functional relationships. However, over the past three decades, structural alignment algorithms have focused predominantly on global alignments with little effort on the alignment of local interfaces. In this paper, we introduce the PBSalign (Protein-protein Binding Site alignment) method, which integrates techniques in graph theory, 3D localized shape analysis, geometric scoring, and utilization of physicochemical and geometrical properties. Computational results demonstrate that PBSalign is capable of identifying similar homologous and analogous binding sites accurately and performing alignments with better geometric match measures than existing protein-protein interface comparison tools. The proportion of better alignment quality generated by PBSalign is 46, 56, and 70 percent more than iAlign as judged by the average match index (MI), similarity index (SI), and structural alignment score (SAS), respectively. PBSalign provides the life science community an efficient and accurate solution to binding-site alignment while striking the balance between topological details and computational complexity.