Supplemental Oxygen Requirement Research Articles

Early Oxygen Requirement in Patients with Mild-to-Moderate COVID-19 Who Received Regdanvimab after Delta-Variant Outbreak.

BackgroundRegdanvimab is a monoclonal antibody targeted against the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and a treatment option for patients with mild-to moderate coronavirus disease 2019 (COVID-19). However, there has been limited information on the clinical effectiveness of regdanvimab in the Delta variant of SARS-CoV-2. Therefore, we aimed to investigate the effectiveness of regdanvimab after the Delta variant was dominant using chronological analysis of regdanvimab use in a real-world setting.Materials and MethodsThe electrical medical records of patients infected with mild-to-moderate COVID-19 who received regdanvimab within 7 days of symptom onset were reviewed before (February – June 2021) and after (August – November 2021) the Delta variant became predominant in Korea. Clinical outcomes were assessed by the need for oxygen supplementation, time from symptom onset to oxygen requirement, in-hospital mortality, and length of hospitalization. To match the difference between the basic characteristics of the two groups, the clinical outcomes were compared again after 1 : 1 propensity score matching.ResultsPatients treated with regdanvimab in the Delta-predominant group were more likely to require oxygen supplementation (17.5% vs. 6.0%, P = 0.019) and had shorter times from symptom onset to supplemental oxygen use (mean ± standard deviation [SD]: 5.8 ± 2.8 vs. 10.0 ± 3.7, P = 0.007) than those in the control group. After propensity score matching, the percentage of patient requiring oxygen supplementation was higher (15.2% vs. 6.1%, P = 0.156), while the time from symptom onset to oxygen supplementation was significantly shorter in the Delta-predominant group (mean ± SD: 4.9 ± 2.1 vs. 10.0 ± 3.7, P = 0.007) than that in the control group.ConclusionConsidering that high proportion of vaccinated patients in the Delta-predominant group, this finding suggests the uncertainty whether the effect of regdanvimab is maintained even during the Delta-predominant period. It is hence necessary to continuously monitor the effectiveness of regdanvimab as new SARS-CoV-2 variants emerge.

Effectiveness of Regdanvimab at Preventing the Need for Oxygen Therapy in Patients with Mild-to-Moderate COVID-19: A Retrospective Cohort Study

BackgroundMonoclonal antibodies are a treatment option for patients with mild-to-moderate coronavirus disease (COVID-19). We investigated the effectiveness of regdanvimab, an anti-severe acute respiratory syndrome coronavirus-2 monoclonal antibody approved in Korea, in the treatment of patients with mild-to-moderate COVID-19.Materials and MethodsMedical records of patients who were admitted to a COVID-19 designated hospital during the study period of February 1 to June 31 and met the indications for administration of regdanvimab were reviewed to assess baseline characteristics and clinical outcomes such as supplemental oxygen requirements, mortality, and length of hospitalization. Multivariable logistic regression analysis was conducted to identify factors associated with requiring supplemental oxygen. Subgroup analysis was performed according to the presence of pneumonia confirmed on a chest X-ray.ResultsThree hundred ninety-eight COVID-19 patients were included in the study, and 65 (16.3%) of them were administered regdanvimab. The proportion of patients requiring supplemental oxygen was significantly lower in the regdanvimab group than in the control group (6.2% vs. 20.1%, P = 0.007). There was no significant difference in mortality (0% vs. 1.5%, P >0.999) and the length of hospitalization (median: 10 days vs. 10 days, P = 0.267) between two groups. The multivariable analysis demonstrated that administration of regdanvimab was independently associated with lower oxygen supplement [odds ratio (OR): 0.20, 95% confidence interval (CI): 0.06 - 0.55, P = 0.004] after adjustment of potential risk factors related to supplemental oxygen including age, sex, chest X-ray abnormality, and underlying chronic kidney disease. Among the patients with pneumonia radiologically, administration of regdanvimab was also associated with lower risk of oxygen supplement (OR: 0.13, 95% CI: 0.02 - 0.46, P = 0.007).ConclusionRegdanvimab use was related to lower need for supplemental oxygen in patients with mild-to-moderate COVID-19 for the indications for administration of regdanvimab.

Markers for severe disease and long-term sequelae in pediatric patients with severe acute respiratory syndrome coronavirus 2 infection.

BackgroundCoronavirus disease 2019 (COVID‐19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) and has resulted in substantial global morbidity and mortality since late 2019. Children can be infected but the disease predominantly affects adults, and research into the acute and chronic sequelae mostly pertains to this population. This study determines the clinical and demographic parameters associated with severe acute disease and chronic complications from COVID‐19 in the pediatric population.MethodsA retrospective chart review was undertaken of all patients between birth and 21 years of age who were positive for SARS‐CoV‐2 by polymerase chain reaction (PCR) and were admitted to two tertiary care hospitals between March 1, 2020, and January 21, 2021. Markers for severe disease were defined as supplemental oxygen requirement, positive pressure ventilation, and acute chest radiograph abnormality at presentation. Chronic disease was defined as symptoms persisting >4 weeks.ResultsReview of 101 patients with positive SARS‐CoV2 testing found 67 presentations consistent with acute symptomatic infection. Age distribution was bimodal, with predominance in infancy and adolescence. Most (75%) had an extrapulmonary comorbidity, and fewer patients (33%) had pre‐existing lung disease. A history of pulmonary comorbidity and obesity was significantly associated with markers for severe disease. Long‐term chronic complications were associated with history of underlying lung disease and acute severe COVID‐19.ConclusionsDemographic and clinical markers were associated with severe COVID‐19 in children. Moreover, both the presence of pulmonary comorbidity and severe acute COVID‐19 are associated with long‐term sequelae.

Clinical profile of patients infected with suspected SARS-CoV-2 Omicron variant of concern, Tamil Nadu, India, December 2021-January 2022.

Background & objectives:COVID-19 cases have been rising rapidly in countries where the SARS-CoV-2 variant of concern (VOC), Omicron (B.1.1.529) has been reported. We conducted a study to describe the epidemiological and clinical characteristics and outcomes of COVID-19 patients with ‘S’ gene target failure (SGTF, suspected Omicron). Furthermore, their clinical outcomes with COVID-19 patients with non-SGTF (non-Omicron) were also compared.Methods:This study was conducted in Tamil Nadu, India, between December 14, 2021 and January 7, 2022 among patients who underwent reverse transcription-PCR testing for SARS-CoV-2 in four laboratories with facilities for S gene screening. Consecutively selected COVID-19 patients with SGTF were telephonically contacted, seven and 14 days respectively after their date of positive result to collect information on the socio-demographic characteristics, previous history of COVID-19, vaccination status and clinical course of illness along with treatment details. To compare their outcomes with non-SGTF patients, one randomly suspected non-Omicron case for every two suspected Omicron cases from the line-list were selected, matching for the date of sample collection and the testing laboratory.Results:A total of 1175 SGTF COVID-19 patients were enrolled for this study. Almost 6 per cent (n=72) reported a history of previous infection. 141 (13.5%) suspected Omicron cases were non-vaccinated, while 148 (14.2%) and 703 (67.4%) had received valid one and two doses of COVID-19 vaccines, respectively. Predominant symptoms reported included fever (n=508, 43.2%), body pain (n=275, 23.4%), running nose (n=261, 22.2%) and cough (n=249, 21.2%). Five (0.4%) of the 1175 suspected Omicron cases required oxygen supplementation as compared to ten (1.6%) of the 634 suspected non-Omicron cases. No deaths were reported among omicron suspects, whereas there were four deaths among suspected non-Omicron cases.Interpretation & conclusions:Majority of the suspected Omicron cases had a mild course of illness. The overall severity of these cases was less compared to the suspected non-Omicron cases.

Multi‐disciplinary collaborative consensus guidance statement on the assessment and treatment of breathing discomfort and respiratory sequelae in patients with post‐acute sequelae of SARS‐CoV‐2 infection (PASC)

<scp>Multi‐disciplinary</scp> collaborative consensus guidance statement on the assessment and treatment of breathing discomfort and respiratory sequelae in patients with <scp>post‐acute</scp> sequelae of <scp>SARS‐CoV</scp>‐2 infection (<scp>PASC</scp>)

MELD-Na score, Acute Physiologic and Chronic Health Evaluation II score, and SOFA score and their association with mortality in critically ill COVID-19 patients with liver injury: A retrospective single-center study.

The Acute Physiologic and Chronic Health Evaluation II (APACHE-II), Sequential Organ Failure Assessment (SOFA), and Model for End-Stage Liver Disease modified for Sodium concentration (MELD-Na) scores are validated to predict disease mortality. We studied the prognostic utility of these scoring systems in critically ill coronavirus disease 2019 (COVID-19) patients with liver injury. This was a retrospective study of 291 confirmed COVID-19 and liver injury patients requiring intensive care unit level of care. These patients required supplemental oxygen requirement with fraction of inspired oxygen >55% and/or the use of vasopressor. MELD-Na, SOFA, and APACHE-II scores were adjusted. Outcomes were mortality and length of stay (LOS). SOFA (odds ratio: 0.78, 95% confidence interval: 0.63-0.98, P < 0.05) was associated with decreased odds for mortality. APACHE-II and MELD-Na were not associated with mortality or LOS. We suggest that the novel nature of COVID-19 necessitates new scoring systems to predict outcomes in critically ill COVID-19 patients with liver injury.

Relationship Between Myocardial Injury During Index Hospitalization for SARS-CoV-2 Infection and Longer-Term Outcomes.

BackgroundMyocardial injury in patients with COVID‐19 is associated with increased mortality during index hospitalization; however, the relationship to long‐term sequelae of SARS‐CoV‐2 is unknown. This study assessed the relationship between myocardial injury (high‐sensitivity cardiac troponin T level) during index hospitalization for COVID‐19 and longer‐term outcomes.Methods and ResultsThis is a prospective cohort of patients who were hospitalized at a single center between March and May 2020 with SARS‐CoV‐2. Cardiac biomarkers were systematically collected. Outcomes were adjudicated and stratified on the basis of myocardial injury. The study cohort includes 483 patients who had high‐sensitivity cardiac troponin T data during their index hospitalization. During index hospitalization, 91 (18.8%) died, 70 (14.4%) had thrombotic complications, and 126 (25.6%) had cardiovascular complications. By 12 months, 107 (22.2%) died. During index hospitalization, 301 (62.3%) had cardiac injury (high‐sensitivity cardiac troponin T≧14 ng/L); these patients had 28.6%, 32.2%, and 33.2% mortality during index hospitalization, at 6 months, and at 12 months, respectively, compared with 4.1%, 4.9%, and 4.9% mortality for those with low‐level positive troponin and 0%, 0%, and 0% for those with undetectable troponin. Of 392 (81.2%) patients who survived the index hospitalization, 94 (24%) had at least 1 readmission within 12 months, of whom 61 (65%) had myocardial injury during the index hospitalization. Of 377 (96%) patients who were alive and had follow‐up after the index hospitalization, 211 (56%) patients had a documented, detailed clinical assessment at 6 months. A total of 78 of 211 (37.0%) had ongoing COVID‐19–related symptoms; 34 of 211 (16.1%) had neurocognitive decline, 8 of 211 (3.8%) had increased supplemental oxygen requirements, and 42 of 211 (19.9%) had worsening functional status.ConclusionsMyocardial injury during index hospitalization for COVID‐19 was associated with increased mortality and may predict who are more likely to have postacute sequelae of COVID‐19. Among patients who survived their index hospitalization, the incremental mortality through 12 months was low, even among troponin‐positive patients.

Decreased severity of disease during the first global omicron variant covid-19 outbreak in a large hospital in tshwane, south africa

INTRODUCTIONThe coronavirus disease 2019 (COVID-19) first reported in Wuhan, China in December 2019 is a global pandemic that is threatening the health and wellbeing of people worldwide. To date there have been more than 274 million reported cases and 5.3 million deaths. The Omicron variant first documented in the City of Tshwane, Gauteng Province, South Africa on 9 November 2021 led to exponential increases in cases and a sharp rise in hospital admissions. The clinical profile of patients admitted at a large hospital in Tshwane is compared with previous waves.METHODS466 hospital COVID-19 admissions since 14 November 2021 were compared to 3962 admissions since 4 May 2020, prior to the Omicron outbreak. Ninety-eight patient records at peak bed occupancy during the outbreak were reviewed for primary indication for admission, clinical severity, oxygen supplementation level, vaccination and prior COVID-19 infection. Provincial and city-wide daily cases and reported deaths, hospital admissions and excess deaths data were sourced from the National Institute for Communicable Diseases, the National Department of Health and the South African Medical Research Council.RESULTSFor the Omicron and previous waves, deaths and ICU admissions were 4.5% vs 21.3% (p<0.00001), and 1% vs 4.3% (p<0.00001) respectively; length of stay was 4.0 days vs 8.8 days; and mean age was 39 years vs 49,8 years.Admissions in the Omicron wave peaked and declined rapidly with peak bed occupancy at 51% of the highest previous peak during the Delta wave.Sixty two (63%) patients in COVID-19 wards had incidental COVID-19 following a positive SARS-CoV-2 PCR test . Only one third (36) had COVID-19 pneumonia, of which 72% had mild to moderate disease. The remaining 28% required high care or ICU admission. Fewer than half (45%) of patients in COVID-19 wards required oxygen supplementation compared to 99.5% in the first wave. The death rate in the face of an exponential increase in cases during the Omicron wave at the city and provincial levels shows a decoupling of cases and deathscompared to previous waves, corroborating the clinical findings of decreased severity of disease seen in patients admitted to the Steve Biko Academic Hospital.CONCLUSIONThere was decreased severity of COVID-19 disease in the Omicron-driven fourth wave in the City of Tshwane, its first global epicentre.

Post-COVID-19 syndrome in patients with primary Sjögren's syndrome after acute SARS-CoV-2 infection.

To analyse the frequency and characteristics of post-COVID-19 syndrome in patients with primary Sjögren's syndrome (pSS) affected by acute SARS-CoV-2 infection. By the first week of April 2021, all centres included in the Big Data Sjögren Consortium were contacted asking for patients included in the Registry diagnosed with SARSCoV-2 infection according to the ECDC guidelines. According to the NICE definitions, symptoms related to COVID-19 were classified as acute COVID-19 (signs and symptoms for up to 4 weeks), ongoing symptomatic COVID-19 (presence of signs and symptoms from 4 to 12 weeks) and post-COVID-19 syndrome (signs and symptoms that continue for > 12 weeks not explained by an alternative diagnosis after a protocolized study). We identified 132 patients who were followed a mean follow-up of 137.8 days (ranging from 5 days to 388 days) after being diagnosed with COVID-19. In the last visit, 75 (57%) patients remained symptomatic: 68 (52%) remained symptomatic for more than 4 weeks fulfilling the NICE definition for ongoing symptomatic post-COVID-19, and 38 (29%) remained symptomatic for more than 12 weeks fulfilling the definition of post-COVID-19 syndrome. More than 40% of pSS patients reported the persistence of four symptoms or more, including anxiety/depression (59%), arthralgias (56%), sleep disorder (44%), fatigue (40%), anosmia (34%) and myalgias (32%). Age-sex adjusted multivariate analysis identified raised LDH levels (OR 10.36), raised CRP levels (OR 7.33), use of hydroxychloroquine (OR 3.51) and antiviral agents (OR 3.38), hospital admission (OR 8.29), mean length of hospital admission (OR 1.1) and requirement of supplemental oxygen (OR 6.94) as factors associated with a higher risk of developing post-COVID-19 syndrome. A sensitivity analysis including hospital admission in the adjusted model confirmed raised CRP levels (OR 8.6, 95% CI 1.33-104.44) and use of hydroxychloroquine (OR 2.52, 95% CI 1.00-6.47) as the key independent factors associated with an enhanced risk of developing post-COVID-19 syndrome. This is the first study that analyses the frequency and characteristics of post-COVID-19 syndrome in patients affected by a systemic autoimmune disease. We found that 57% of patients with pSS affected by COVID-19 remain symptomatic after a mean follow-up of 5 months. The risk of developing post-COVID-19 syndrome in patients who required hospitalisation was 8-times higher than in non-hospitalised patients, with baseline raised CRP levels and the use of hydroxychloroquine being independent risk factors for post-COVID-19.

559. A Nationwide Survey of COVID-19 Management in the Dominican Republic Over the Course of the Pandemic

BackgroundCOVID-19 was declared a global Public Health Emergency by the WHO in January 2020. Limited treatment options existed early in the pandemic. As COVID-19 spread across the globe and new therapeutics emerged, different interpretations of the literature grew, and major societies relayed conflictive recommendations. There is a paucity of data on COVID-19 management in low- and middle-income countries. As a result, we performed a nationwide survey of local treatment practices in the Dominican Republic (DR).MethodsWe performed an anonymous survey of infectious diseases specialists in the DR and US. The survey collected hospital characteristics and COVID-19 management protocols during different quarters of 2020-21. Management was categorized by drug and disease severity based on supplemental oxygen requirements. A convenience sample in the US representing community and academic sites was surveyed for point comparison between the US and DR.ResultsThe survey was completed by physicians from a total of 11 sites located in 4 cities of the DR: Santo Domingo (3), Santiago (4), La Vega (2) and San Francisco (2). These cities were representative of all regions in the country. The survey included 7 (64%) hospitals with < 200 beds, 3 (27%) with 201-300 beds, and 1 (9%) with >400 beds. Seven (47%) were private, 2 (13%) public, and 6 (40%) were teaching hospitals. In the US, 2 academic hospitals with >400 beds and 2 community hospitals with < 200 beds in a major city were surveyed. Management of COVID-19 at sites in the DR and US throughout the pandemic is plotted in Figure 1. Remdesivir use by disease severity is plotted in Figure 2.Figure 1. Management of COVID-19 at sites in the US and DR throughout the COVID-19 pandemic FIgure 2. Remdesivir use by disease severity at sites in the US and DR throughout the COVID-19 pandemic ConclusionThroughout the pandemic, as therapeutic options evolved, hospitals and physicians had to adapt to changing guidelines and availability of novel drugs. Variability between countries and sites emerged. The use of hydroxychloroquine and convalescent plasma waned more rapidly in the US. Dexamethasone was widely used at all sites. Tocilizumab and remdesivir were used more liberally in the DR. Antimicrobial stewardship limited these agents at US sites to more narrow therapeutic windows which could explain the discrepancies seen between the US and DR. Uncertainty of benefit in certain disease states, limited availability, and cost may also play a role.Disclosures All Authors: No reported disclosures

1327. Human Rhinovirus Infection in Multiple Myeloma Patients: Effect on Morbidity and Mortality

BackgroundHuman Rhinovirus (hRV) causes mild, primarily upper respiratory tract symptoms in immunocompetent hosts. However, in immunocompromised patients, it often progresses to a lower respiratory tract infection. Multiple myeloma (MM) patients are immunocompromised due to inherent immunodeficiency and exposure to biologic and chemotherapeutic agents. The complications of hRV infection in MM patients are not well known. In this study, we aim to identify the morbidity and mortality associated with hRV in MM participants.MethodsThis was a retrospective study, using Arkansas Clinical Registry Database, which identified all MM patients diagnosed with hRV infection by nasopharyngeal multiplex polymerase chain reaction (PCR) in January-December 2019. Duplicates within 30 days were excluded. Patients were followed for 30 days after diagnosis. We assessed the need for hospitalization, intensive care unit (ICU) admission, oxygen administration, mechanical ventilation, and death. We collected their absolute neutrophil (ANC) and lymphocyte count (ALC) within three days of diagnosis and compared values using Mann-Whitney U test.ResultsWe identified 217 MM patients with hRV. Ninety (41%) had prior autologous stem cell transplant, 148 (68%) had received chemotherapy within 30 days. Ninety (41%) had chest imaging, with 11 (12%) having infiltrates. Out of the 217, 69 (31.9%) were admitted, with a mean length of stay of 3 days. 13% of the admitted patients were transferred to the ICU. 65.5% of the admitted patients needed oxygen, and two required mechanical ventilation. The mean ANC and ALC for the admitted group was 3.88 cells/µL and 1.22 cells/µL respectively, compared to 3.57 cells/µL and 1.07 cells/µL in the outpatient group, p=0.6 and 1. Five participants died.ConclusionHuman Rhinovirus infection in MM patients was associated with significant morbidity, including hospitalization, ICU care, supplemental oxygen requirement, and even mechanical ventilation in 2 patients. Death was observed within 30 days, although rarely. The mean ALC and ANC were not predictive of the severity of the disease. Recognizing hRV effects on morbidity and mortality could lead to earlier recognition and management of complications in MM patients.Disclosures All Authors: No reported disclosures

448. COVID-19 Acute Care at Home: A Substitution for Hospitalization in Patients with Mild Symptoms

BackgroundConstraints on resources require healthcare systems to implement alternative and innovative means for delivering care. The COVID-19 pandemic amplified this issue throughout the world, leading to shortages of ventilators, hospital beds, and healthcare personnel. We report the results of an Acute Care at Home Program (ACHP) response to COVID-19, providing in-home hospital-level care to patients with mild symptoms, preserving in-hospital beds for more serious illness.MethodsPatients with COVID-19 were selected for ACHP after undergoing risk stratification for severe disease, including oxygen evaluation, time course of illness, and evaluation of comorbidities. Patients admitted to ACH met inpatient criteria, required oxygen supplementation of ≤4 liters, and received insurance approval. Services were provided consistent with best practice of inpatient care, including 24/7 provider availability via TeleMedicine, bedside care provided by paramedics and nurses, respiratory therapy, radiology and laboratory services, pulse oximetry monitoring, and administration of medications. Protocols existed for patient transfer to hospital in the event of clinical deterioration.ResultsOur initial cohort included 62 patients enrolled October 1, 2020 – May 31, 2021. Of these, 57 patients were discharged successfully from ACHP. Patients presented with initial oxygen requirements of 0-4 liters. Average length-of-stay in ACHP was 5.4 days. Five patients required hospitalization after enrollment in ACHP; one subsequently expired, two were discharged home, one returned to ACHP after inpatient hospitalization, and one remains hospitalized. One additional patient that was successfully discharged home from ACHP was later readmitted and expired in a subsequent hospitalization. The patients that expired had significant immunocompromising conditions that may have contributed to their outcomes.ConclusionACHP can provide care equivalent to hospitalization for select COVID-19 patients. Immunocompromised hosts with COVID-19 may represent a subset of patients in which in-house hospitalization must be carefully considered, even with mild oxygen requirements. Health systems should consider ACHP as a substitution for hospitalization for COVID-19 patients with mild symptoms.Disclosures All Authors: No reported disclosures

556. Ruxolitinib for the Management of Severe Pneumonia Caused by SARS-CoV-2. Exploring the Combination with dexamethasone

BackgroundMexico is one of the top five countries with a higher mortality rate of hospitalized patients of 30.1%. Since COVID-19 has been associated with immune dysregulation and hyper inflammation, JAK-12 inhibitors have been tested to reduce IL6 production. Studies have shown improvements when using ruxolitinib (rxb) in severely hospitalized patients with COVID-19. These have included patients in combination with corticosteroids such as dexamethasone (dxm). This work aims to test the response of hospitalized patients with severe or critical COVID-19 treated with rxb with or without dxm. MethodsAn experimental, open, prospective study in a single third-level hospital in Mexico was performed. The primary outcome was favorable clinical response defined as withdrawal or decline of supplementary oxygen. Secondary outcomes such as mean hospital stay, improvement in systemic inflammatory response parameters, and mortality were also evaluated. Statistical differences for baseline and final measure and the use and not use of dxm were estimated. The study included adults with SARS-CoV-2 infection confirmed with polymerase chain reaction, radiological pneumonia, and oxygen saturation less than 90%. Rxb was administered 5mg/12hrs/15days, IV dxm 6mg/day/10days. ResultsThe final sample was 108 adults with complete information and informed consent. Sixty-two patients (57%) received only rxb. There were no differences between groups for any parameter at the beginning of treatment, and all patients were receiving supplemental oxygen. After 28-day follow-up, 70% reduce supplemental oxygen requirement (74% rxb and 71% rxb+dxm; p=0.628), 18% remained, and 2% increases support (1% with rxb, and 5% rxb+dxm; p< 0.001); 87% of patients were discharged (89% rxb and 85% rxb+dxm; p=0.603). In both groups, there was a significant reduction of CRP, LDH, and Ferritin on day 15. The mortality rate was 9% (no difference in groups; p=0.453), and a higher proportion died for Pseudomonas aeruginosa superinfection in the rxb+dxm group (p< 0.001). Differences for support oxygen at baseline and discharge Final health outcomes of patients with severe or critical COVID-19 in a third-level hospital in Mexico ConclusionThe use of rxb could be considered as a treatment helping clinical improvement in hospitalized patients with severe COVID-19. Combination with dxm apparently did not add clinical benefits. It should be further evaluated.Disclosures All Authors: No reported disclosures

Impact of three consecutive intravenous doses of tocilizumab in severe COVID-19 pneumonia: a retrospective cohort study

Background. Acute respiratory distress syndrome (ARDS) in severe COVID-19 pneumonia is mostly responsible for high mortality rate. Tocilizumab, an interleukin-6 (IL-6) inhibitors, down-regulates the progression of cytokine storm leading to ARDS. Objectives. The study aimed to assess the clinical outcomes of three consecutive intravenous doses of tocilizumab in patients with severe COVID-19 pneumonia. Methods. This retrospective observational study was conducted on severe COVID-19 pneumonia patients in a single-center who were treated with three intravenous dose of tocilizumab (8 mg/Kg of body weight, max 800 mg per dose × 3) along with intravenous dexamethasone. Three doses of tocilizumab-associated changes in respiratory function, clinical outcomes and mortality rate were analyzed. Results. Seventy-four patients (N) received intravenous tocilizumab therapy. After third intravenous dose of tocilizumab (48-72 h apart from the second dose), SpO2 (blood oxygen saturation) was increased and the requirement of supplemental oxygen (RSO) was decreased more than after the second dose [Median: 96.5% (IQR: 96-98%) and Median: 0 (IQR: 0-1 L), respectively versus Median: 92% (IQR: 91-92%) and Median: 6 L (IQR: 5-7.2 L, respectively] (P &lt;0.05). SpO2 was normalized in 78.4% of patients (P=0.001) treated with three doses of tocilizumab. Further RSO and demand of invasive mechanical ventilation support were increased in 21.6% (58/74 patients) and 14.8% (11/74 patients) of patients, respectively with a 30-day mortality rate of 4% (3/74 patients). Tocilizumab therapy was well tolerated in all patients. Conclusions. An additional third intravenous dose of tocilizumab improved clinical outcomes and reduced mortality rate in patients with severe COVID-19 pneumonia.

Balloon Pulmonary Angioplasty in Patients With Inoperable or Recurrent/Residual Chronic Thromboembolic Pulmonary Hypertension: A Single-Centre Initial Experience

Patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH) are often treated with pulmonary arterial hypertension-specific drugs. However, most of these patients remain symptomatic, despite medical treatment. Balloon pulmonary angioplasty (BPA) is an emerging therapeutic intervention for patients with inoperable CTEPH. This study aimed to report the initial experience of BPA in a tertiary referral centre for CTEPH. A total of 26 consecutive patients, who underwent 91 BPA sessions, were included in the study. All patients underwent a detailed examination, including 6-minute walking distance (6MWD), and right heart catheterisation at baseline and 3 months after the last BPA session. The mean age of the patients was 51±17 years. Fifteen (15) patients had inoperable CTEPH and 11 patients had residual or recurrent CTEPH post pulmonary endarterectomy (PEA). Functional class improved in 17 of 26 (65%) patients. The 6MWD increased from a mean 315±129 to 411±140 m (p<0.001), and NT pro-BNP reduced from a median 456 to 189 pg/mL (p=0.001). The number of patients who required supplemental oxygen decreased from 11 (42.3%) to five (19%) (p=0.031) after BPA treatment. The mean pulmonary artery pressure decreased from a mean 47.5±13.4 to 38±10.9 mmHg (p<0.001), the pulmonary vascular resistance decreased from a mean 9.3±4.7 to 5.8±2.8 Wood units (p<0.001), and the cardiac index increased from a mean 2.4±0.7 to 2.9±0.6 L/min/m2 (p=0.008). Balloon pulmonary angioplasty improved haemodynamics, 6MWD, and functional class, and reduced the requirement for supplemental oxygen, with an acceptable risk-benefit ratio in patients with inoperable CTEPH and with residual/recurrent CTEPH.

Pulmonary function tests in extremely low gestational age infants at one year of age.

Identifying neonatal and post-discharge exposures among extremely low gestational age newborns (ELGANs) that drive increased pulmonary morbidity and abnormal lung function at 1 year of age proves challenging. The NIH-sponsored Prematurity and Respiratory Outcomes Program (PROP), evaluated infant pulmonary function tests (iPFTs) at 1 year corrected age to determine which demographic and clinical factors are associated with abnormal lung function. iPFTs were performed on a PROP subcohort of 135 participants following Institutional Review Board (IRB)-approved written consent. Demographic data, Neonatal Intensive Care Unit (NICU) clinical care, and post-NICU exposures were analyzed for association with iPFTs. A significant decrease in forced expiratory volume at 0.5 s (FEV0.5 ) and/or forced expiratory flows at 75% of forced vital capacity (FEF75 ), were associated with male sex and African American race. Clinical factors including longer duration of ventilatory support, exposure to systemic steroids, and weight less than the 10th percentile at 36 weeks postmenstrual age were also associated with airflow obstruction, whereas supplemental oxygen requirement and bronchopulmonary dysplasia were not. Additionally, the need for respiratory medications, technology, or hospitalizations during the first year, ascertained by a quarterly survey, were the only post-NICU factors associated with decreased FEV0.5 and FEF75 . Only 7% of infants had reversible airflow obstruction. Neonatal demographic factors, respiratory support in the NICU, and a history of greater post-NICU medical utilization for respiratory disease had the strongest association with lower lung function at 1 year in ELGANs.

Virological and serological kinetics of SARS-CoV-2 Delta variant vaccine breakthrough infections: a multicentre cohort study

ObjectivesHighly effective vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been developed but variants of concerns are worrisome, especially B.1.617.2 (Delta) which has rapidly spread across the world. We aim to study if vaccination alters virological and serological kinetics in breakthrough infections. MethodsWe conducted a multicentre retrospective cohort study of patients in Singapore who had received a licensed mRNA vaccine and been admitted to hospital with B.1.617.2 SARS-CoV-2 infection. We compared clinical features, virological and serological kinetics (anti-nucleocapsid, anti-spike and surrogate virus neutralization titres) between fully vaccinated and unvaccinated individuals. ResultsOut of 218 individuals with B.1.617.2 infection, 84 received an mRNA vaccine of which 71 were fully vaccinated, 130 were unvaccinated and four received a non-mRNA vaccine. Despite significantly older age in the vaccine breakthrough group, only 2.8% (2/71) developed severe COVID-19 requiring oxygen supplementation compared with 53.1% (69/130) in the unvaccinated group (p < 0.001). Odds of severe COVID-19 following vaccination were significantly lower (adjusted odds ratio 0.07 95% CI 0.015–0.335, p 0.001). PCR cycle threshold values were similar between vaccinated and unvaccinated groups at diagnosis, but viral loads decreased faster in vaccinated individuals. Early, robust boosting of anti-spike protein antibodies was observed in vaccinated patients; however, these titres were significantly lower against B.1.617.2 than the wildtype vaccine strain. DiscussionThe mRNA vaccines are highly effective at preventing symptomatic and severe COVID-19 associated with B.1.617.2 infection. Vaccination is associated with faster decline in viral RNA load and a robust serological response. Vaccination remains a key strategy for control of the COVID-19 pandemic.

Lung Ultrasound Findings Associated With COVID-19 ARDS, ICU Admission, and All-Cause Mortality.

As lung ultrasound (LUS) has emerged as a diagnostic tool in patients with COVID-19, we sought to investigate the association between LUS findings and the composite in-hospital outcome of ARDS incidence, ICU admission, and all-cause mortality. In this prospective, multi-center, observational study, adults with laboratory-confirmed SARS-CoV-2 infection were enrolled from non-ICU in-patient units. Subjects underwent an LUS evaluating a total of 8 zones. Images were analyzed off-line, blinded to clinical variables and outcomes. A LUS score was developed to integrate LUS findings: ≥ 3 B-lines corresponded to a score of 1, confluent B-lines to a score of 2, and subpleural or lobar consolidation to a score of 3. The total LUS score ranged from 0-24 per subject. Among 215 enrolled subjects, 168 with LUS data and no current signs of ARDS or ICU admission (mean age 59 y, 56% male) were included. One hundred thirty-six (81%) subjects had pathologic LUS findings in ≥ 1 zone (≥ 3 B-lines, confluent B-lines, or consolidations). Markers of disease severity at baseline were higher in subjects with the composite outcome (n = 31, 18%), including higher median C-reactive protein (90 mg/L vs 55, P < .001) and procalcitonin levels (0.35 μg/L vs 0.13, P = .033) and higher supplemental oxygen requirements (median 4 L/min vs 2, P = .001). However, LUS findings and score did not differ significantly between subjects with the composite outcome and those without, and were not associated with outcomes in unadjusted and adjusted logistic regression analyses. Pathologic findings on LUS were common a median of 3 d after admission in this cohort of non-ICU hospitalized subjects with COVID-19 and did not differ among subjects who experienced the composite outcome of incident ARDS, ICU admission, and all-cause mortality compared to subjects who did not. These findings should be confirmed in future investigations. The study is registered at Clinicaltrials.gov (NCT04377035).

Correlates of survival after autoantibody reduction therapy for acute IPF exacerbations.

BackgroundNo medical treatment has proven efficacy for acute exacerbations of idiopathic pulmonary fibrosis (AE-IPF), and this syndrome has a very high mortality. Based on data indicating humoral autoimmune processes are involved in IPF pathogenesis, we treated AE-IPF patients with an autoantibody reduction regimen of therapeutic plasma exchange, rituximab, and intravenous immunoglobulin. This study aimed to identify clinical and autoantibody determinants associated with survival after autoantibody reduction in AE-IPF.MethodsTwenty-four(24) AE-IPF patients received the autoantibody reduction regimen. Plasma anti-epithelial autoantibody titers were determined by HEp-2 indirect immunofluorescence assays in 22 patients.ResultsMean age of the patients was 70 + 7 years old, and 70% were male. Beneficial clinical responses that occurred early during therapy were a favorable prognostic indicator: supplemental O2 flows needed to maintain resting SaO2>92% significantly decreased and/or walk distances increased among all 10 patients who survived for at least one year. Plasma anti-HEp-2 autoantibody titers were ~-three-fold greater in survivors compared to non-survivors (p<0.02). Anti-HEp-2 titers >1:160 were present in 75% of the evaluable one-year survivors, compared to 29% of non-survivors, and 10 of 12 patients (83%) with anti-HEP-2 titers <1:160 died during the observation period (Hazard Ratio = 3.3, 95% Confidence Interval = 1.02–10.6, p = 0.047).ConclusionsAutoantibody reduction therapy is associated with rapid reduction of supplemental oxygen requirements and/or improved ability to ambulate in many AE-IPF patients. Facile anti-epithelial autoantibody assays may help identify those most likely to benefit from these treatments.

Whole-organ transdermal photobiomodulation (PBM) of COVID-19: A 50-patient case study.

A nonrandomized 50‐person case study of COVID‐19‐positive patients was conducted employing (for the first time) a regimen of whole‐organ deep‐tissue transdermal dynamic photobiomodulation (PBM) as a primary (or exclusive) therapeutic modality in the treatment of coronavirus. Therapy sessions comprised algorithmically alternating red (650 nm) and near‐infrared (NIR; 850 nm) LEDs with an average irradiance of 11 mW/cm2 dynamically sequenced at multiple pulse frequencies. Delivered via 3D bendable polymeric pads maintaining orthogonal optical incidence to body contours over 1,000 cm2, a single 84‐minute session concurrently delivered 20 kJ to the sinuses and 15 kJ to each lung at skin temperatures below 42°C. Therapeutic outcomes observed include significant reductions in the duration and severity of disease symptoms. Acute conditions including fever, body aches (BA) and respiratory distress comprising paroxysmal coughing; lung congestion, dyspnea and hypoxia; sinus congestion; acute eye inflammation; and extreme malaise were eliminated in 41/50 patients within 4 days of commencing PBM treatments with 50/50 patients fully recovering within 3 weeks with no supplemental oxygen requirements. SpO2 concentrations improved as much as 9 points (average 2.5 points) across the entire study population. The PBM sessions required to completely resolve COVID‐19 conditions appears monotonically correlated to the time‐to‐treatment (TTTx)—the delay between the onset of a patient's symptoms and commencing PBM therapy. In contrast, acute inflammatory symptoms were resolved within 4 days irrespective of TTTx.