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Severe pneumonia accounts for 15% of the total severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, and the affected patients require hospitalization and oxygen support. In addition, 5% of patients with severe coronavirus disease 2019 (COVID-19) experience acute respiratory distress syndrome and sepsis, which contributes to the high mortality rate. Moreover, the risk of severe COVID-19 increases with age and is the highest among elderly people over 70 years of age. Notably, these pneumonia cases can be attributed to the reactivation of latent cytomegalovirus (CMV). We hereby report two cases of patients with COVID-19 who required prolonged mechanical ventilation and were later diagnosed with secondary CMV pneumonia. These cases support the theory that in some patients with severe COVID-19, there is a possibility of CMV reactivation, contributing to the disease's severity and pathogenesis. These cases also highlight the risk involved in using steroids for a long time and the requirement of routine evaluation for CMV infection in patients with COVID-19 who require prolonged mechanical ventilation or have difficulty weaning off from the ventilator support., (© Journal of the Association of Physicians of India 2024.)

Background: The aim of the study is to evaluate the mortality risk factors and hospitalization outcomes of adenovirus pneumonia in pediatric patients with congenital heart disease., Methods: In this retrospective multicenter cohort study utilizing the Pediatric Health Information System database, we analyzed congenital heart disease patients with adenovirus pneumonia from January 2004 to September 2018, categorizing them into shunts, obstructive lesions, cyanotic lesions and mixing lesions. Multivariate logistic regression analysis was employed to identify mortality risk factors with 2 distinct models to mitigate collinearity issues and the Mann-Whitney U test was used to compare the hospital length of stay between survivors and nonsurvivors across these variables., Results: Among 381 patients with a mean age of 3.2 years (range: 0-4 years), we observed an overall mortality rate of 12.1%, with the highest mortality of 15.1% noted in patients with shunts. Model 1 identified independent factors associated with increased mortality, including age 0-30 days (OR: 8.13, 95% CI: 2.57-25.67, P < 0.005), sepsis/shock (OR: 3.34, 95% CI: 1.42-7.83, P = 0.006), acute kidney failure (OR: 4.25, 95% CI: 2.05-13.43, P = 0.0005), shunts (OR: 2.95, 95% CI: 1.14-7.67, P = 0.03) and cardiac catheterization (OR: 6.04, 95% CI: 1.46-24.94, P = 0.01), and Model 2, extracorporeal membrane oxygenation (OR: 3.26, 95% CI: 1.35-7.87, P = 0.008). Nonsurvivors had a median hospital stay of 47 days compared to 15 days for survivors., Conclusion: The study revealed a 12.1% mortality rate in adenoviral pneumonia among children with congenital heart disease, attributed to risk factors such as neonates, sepsis, acute kidney failure, shunts, cardiac catheterization, extracorporeal membrane oxygenation use and a 3-fold longer hospital stay for nonsurvivors compared to survivors., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

The distribution of the immune system throughout the body complicates in vitro assessments of coronavirus disease 2019 (COVID-19) immunobiology, often resulting in a lack of reproducibility when extrapolated to the whole organism. Consequently, developing animal models is imperative for a comprehensive understanding of the pathology and immunology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. This review summarizes current progress related to COVID-19 animal models, including non-human primates (NHPs), mice, and hamsters, with a focus on their roles in exploring the mechanisms of immunopathology, immune protection, and long-term effects of SARS-CoV-2 infection, as well as their application in immunoprevention and immunotherapy of SARS-CoV-2 infection. Differences among these animal models and their specific applications are also highlighted, as no single model can fully encapsulate all aspects of COVID-19. To effectively address the challenges posed by COVID-19, it is essential to select appropriate animal models that can accurately replicate both fatal and non-fatal infections with varying courses and severities. Optimizing animal model libraries and associated research tools is key to resolving the global COVID-19 pandemic, serving as a robust resource for future emerging infectious diseases.

Introduction: This descriptive study reviews clinical outcomes of individuals admitted to a northern Canadian, rural intensive care unit (ICU) with severe COVID-19. It reports our site-specific data that is part of an ongoing global effort to gather data and guide therapy; the aims of this study were to describe participants admitted to our ICU with COVID-19 and illuminate challenges faced by rural and remote centres., Methods: This retrospective study examined data from participants admitted to the ICU with COVID-19 pneumonia between 24th November 2020 and 28th February 2022. Using data from electronic and hardcopy health records, data were obtained according to standardised forms developed for the Short Period Incidence Study of Severe Acute Respiratory Infection., Results: Eighty-five adult participants were admitted to our ICU with COVID-19. The median age of participants was 57 years old (range: 23-83 years); 49.4% were males and 50.6% were females. Of our cohort, 58.9% required mechanical ventilation at some point during their stay and the median duration of stay in our ICU was 5 days (range: 1-36 days). Amongst individuals included, 25.9% were discharged alive from our hospital on their index admission, 57.6% were transferred to another facility and 16.5% died in our facility., Conclusion: COVID-19 significantly strained our local ICU resources, necessitating high numbers of patient transfers. However, despite limited resources, patients at our site received contemporary guideline-based care for COVID-19 pneumonia. Future pandemic and surge capacity planning must ensure that rural and remote communities receive adequate additional resources to meet the anticipated needs of their local populations., Introduction: Cette étude descriptive examine les résultats cliniques des personnes admises dans une unité de soins intensifs rurale du nord du Canada avec une COVID-19 sévère. Elle rapporte des données spécifiques à notre site qui font partie d'un effort global en cours pour rassembler des données et guider la thérapie. Les objectifs de cette étude étaient de décrire les participants admis dans notre unité de soins intensifs avec la COVID-19 et d'éclairer les défis auxquels sont confrontés les centres ruraux et éloignés., Mthodes: Cette étude rétrospective a examiné les données des participants admis à l'unité de soins intensifs pour une pneumonie due à la COIVD-19 entre le 24 novembre 2020 et le 28 février 2022. Les données ont été obtenues à partir de dossiers médicaux électroniques et papier, selon des formulaires standardisés développés pour l'étude d'incidence à court terme des infections respiratoires aiguës sévères (SPRINT-SARI)., Rsultats: 85 participants adultes ont été admis dans notre unité de soins intensifs avec la COVID-19. L'âge médian des participants était de 57 ans (intervalle: 23-83 ans); 49,4% étaient des hommes et 50,6% des femmes. Dans notre cohorte, 58,9% ont eu besoin d'une ventilation mécanique à un moment ou à un autre de leur séjour et la durée médiane du séjour dans notre unité de soins intensifs était de 5 jours (intervalle: 1-36 jours). Parmi les personnes incluses, 25,9% sont sorties vivantes de notre hôpital lors de leur admission initiale, 57,6% ont été transférées dans un autre établissement et 16,5% sont décédées dans notre établissement., Conclusion: La COVID-19 a mis à rude épreuve les ressources de notre unité locale de soins intensifs, nécessitant un grand nombre de transferts de patients. Cependant, malgré des ressources limitées, les patients de notre site ont reçu des soins fondés sur des lignes directrices contemporaines pour la pneumonie due à la COVID-19. À l'avenir, la planification de la pandémie et de la capacité de pointe doit garantir que les communautés rurales et éloignées reçoivent des ressources supplémentaires adéquates pour répondre aux besoins anticipés de leurs populations locales., (Copyright © 2024 Copyright: © 2024 Society of Rural Physicians of Canada.)

Background: Acute kidney injury (AKI) is common among hospitalized patients with COVID-19 and associated with worse prognosis. The Spanish Society of Nephrology created the AKI- COVID Registry to characterize the population admitted for COVID-19 that developed AKI in Spanish hospitals. The need of renal replacement therapy (RRT) therapeutic modalities, and mortality in these patients were assessed MATERIAL AND METHOD: In a retrospective study, we analyzed data from the AKI-COVID Registry, which included patients hospitalized in 30 Spanish hospitals from May 2020 to November 2021. Clinical and demographic variables, factors related to the severity of COVID-19 and AKI, and survival data were recorded. A multivariate regression analysis was performed to study factors related to RRT and mortality., Results: Data from 730 patients were recorded. A total of 71.9% were men, with a mean age of 70 years (60-78), 70.1% were hypertensive, 32.9% diabetic, 33.3% with cardiovascular disease and 23.9% had some degree of chronic kidney disease (CKD). Pneumonia was diagnosed in 94.6%, requiring ventilatory support in 54.2% and admission to the ICU in 44.1% of cases. The median time from the onset of COVID-19 symptoms to the appearance of AKI (37.1% KDIGO I, 18.3% KDIGO II, 44.6% KDIGO III) was 6 days (4-10). A total of 235 (33.9%) patients required RRT: 155 patients with continuous renal replacement therapy, 89 alternate-day dialysis, 36 daily dialysis, 24 extended hemodialysis and 17 patients with hemodiafiltration. Smoking habit (OR 3.41), ventilatory support (OR 20.2), maximum creatinine value (OR 2.41), and time to AKI onset (OR 1.13) were predictors of the need for RRT; age was a protective factor (0.95). The group without RRT was characterized by older age, less severe AKI, and shorter kidney injury onset and recovery time (p < 0.05). 38.6% of patients died during hospitalization; serious AKI and RRT were more frequent in the death group. In the multivariate analysis, age (OR 1.03), previous chronic kidney disease (OR 2.21), development of pneumonia (OR 2.89), ventilatory support (OR 3.34) and RRT (OR 2.28) were predictors of mortality while chronic treatment with ARBs was identified as a protective factor (OR 0.55)., Conclusions: Patients with AKI during hospitalization for COVID-19 had a high mean age, comorbidities and severe infection. We defined two different clinical patterns: an AKI of early onset, in older patients that resolves in a few days without the need for RRT; and another more severe pattern, with greater need for RRT, and late onset, which was related to greater severity of the infectious disease. The severity of the infection, age and the presence of CKD prior to admission were identified as a risk factors for mortality in these patients. In addition chronic treatment with ARBs was identified as a protective factor for mortality., (Copyright © 2023 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.)

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The COVID-19 pandemic has had an unprecedented impact on population health and hospital operations. Over 7 million patients have been hospitalized for COVID-19 thus far in the United States alone. Mortality rates for hospitalized patients during the first wave of the pandemic were > 30%, but as we enter the fifth year of the pandemic hospitalizations have fallen and mortality rates for hospitalized patients with COVID-19 have plummeted to 5% or less. These gains reflect lessons learned about how to optimize respiratory support for different kinds of patients, targeted use of therapeutics for patients with different manifestations of COVID-19 including immunosuppressants and antivirals as appropriate, and high levels of population immunity acquired through vaccines and natural infections. At the same time, the pandemic has helped highlight some longstanding sources of harm for hospitalized patients including hospital-acquired pneumonia, ventilator-associated events (VAEs), and hospital-acquired respiratory viral infections. We are, thankfully, on the leeside of the pandemic at present; but the large increases in ventilator-associated pneumonia (VAP), VAEs, bacterial superinfections, and nosocomial respiratory viral infections associated with the pandemic beg the question of how best to prevent these complications moving forward. This paper reviews the burden of hospitalization for COVID-19, the intersection between COVID-19 and both VAP and VAEs, the frequency and impact of hospital-acquired respiratory viral infections, new recommendations on how best to prevent VAP and VAEs, and current insights into effective strategies to prevent nosocomial spread of respiratory viruses., Competing Interests: Dr Klompas discloses relationships with Centers for Disease Control and Prevention, AHRQ, and UpToDate., (Copyright © 2024 by Daedalus Enterprises.)

Background: Infective endocarditis (IE) is a rare cardiovascular complication in patients with coronavirus disease 2019 (COVID-19). IE after COVID-19 can also be complicated by acute respiratory distress syndrome (ARDS); however, the guidelines for the treatment of such cases are not clear. Here, we report a case of perioperative management of post-COVID-19 IE with ARDS using veno-venous extracorporeal membrane oxygenation (V-V ECMO)., Case Presentation: The patient was a 40-year-old woman who was admitted on day 18 of COVID-19 onset and was administered oxygen therapy, remdesivir, and dexamethasone. The patient's condition improved; however, on day 24 of hospitalization, the patient developed hypoxemia and was admitted to the intensive care unit (ICU) due to respiratory failure. Blood culture revealed Corynebacterium striatum, and transesophageal echocardiography revealed vegetation on the aortic and mitral valves. Valve destruction was mild, and the cause of respiratory failure was thought to be ARDS. Despite continued antimicrobial therapy, ARDS did not improve the patient's condition, and valve destruction progressed; therefore, surgical treatment was scheduled on day 13 of ICU admission. After preoperative consultation with the team, a decision was made to initiate V-V ECMO after the patient was weaned from CPB, with concerns about further worsening of her respiratory status after surgery. The patient returned to the ICU with transition to V-V ECMO, and her circulation remained stable. The patient was weaned off V-V ECMO on postoperative day 33 and discharged from the ICU on postoperative day 47., Conclusions: ARDS may occur in patients with IE after COVID-19. Owing to concerns about further exacerbation of pulmonary damage, the timing of surgery should be comprehensively considered. Preoperatively, clinicians should discuss perioperative ECMO introduction and configuration., (© 2024. The Author(s).)

Reactivation and infection with cytomegalovirus (CMV) are frequently observed in recipients of solid organ transplants, bone marrow transplants, and individuals with HIV infection. This presents an increasing risk of allograft rejection, opportunistic infection, graft failure, and patient mortality. Among immunocompromised hosts, interstitial pneumonia is the most critical clinical manifestation of CMV infection. Recent studies have demonstrated the potential therapeutic benefits of exosomes derived from mesenchymal stem cells (MSC-exos) in preclinical models of acute lung injury, including pneumonia, ARDS, and sepsis. However, the role of MSC-exos in the pathogenesis of infectious viral diseases, such as CMV pneumonia, remains unclear. In a mouse model of murine CMV-induced pneumonia, we observed that intravenous administration of mouse MSC (mMSC)-exos reduced lung damage, decreased the hyperinflammatory response, and shifted macrophage polarization from the M1 to the M2 phenotype. Treatment with mMSC-exos also significantly reduced the infiltration of inflammatory cells and pulmonary fibrosis. Furthermore, in vitro studies revealed that mMSC-exos reversed the hyperinflammatory phenotype of bone marrow-derived macrophages infected with murine CMV. Mechanistically, mMSC-exos treatment decreased activation of the NF-κB/NLRP3 signaling pathway both in vivo and in vitro. In summary, our findings indicate that mMSC-exo treatment is effective in severe CMV pneumonia by reducing lung inflammation and fibrosis through the NF-κB/NLRP3 signaling pathway, thus providing promising therapeutic potential for clinical CMV infection.

Objectives: To explore the traits and risk factors of pregnant women admitted to intensive care units (ICUs) with COVID-19. Moreover, the study classifies outcomes based on differing levels of required respiratory support during their intensive care stay., Methods: This retrospective and descriptive study included all pregnant women with COVID-19 admitted to the adult critical care unit at a specialized tertiary hospital in Riyadh, Saudi Arabia. Between January 2020 and December 2022. A total of 38 pregnant women were identified and were eligible for our study., Results: The mean age of the patients was 32.9 (19-45) years, and the average Acute Physiology and Chronic Health Evaluation IV (APACHI IV) score was 49.9 (21-106). Approximately 60.5% of the patients suffered from superimposed infections during their ICU stay. Approximately 81.6% patients were delivered by C-section, 33 of the newborns survived, and 5 died. The crude mortality rate among pregnant women in our cohort was 15.8%. Patients treated with high-flow nasal cannula (HFNC) were mostly discharged or delivered normally, while the mechanical ventilation (MV) and extracorporeal membrane oxygenation groups mostly underwent C-sections. Most of the surviving newborns were on HFNC and MV. Patients with multiple infections had the longest ICU stay and had the highest risk of death., Conclusion: The results of this study highlight the characteristics of pregnant women admitted to the ICU at a specialized tertiary healthcare center in Saudi Arabia. The APACHI IV scores accurately predicted patient's mortality, duration of MV, and length of ICU stay. In our study, we shared our experience of managing severe COVID-19 infections in pregnant patients., (Copyright: © Saudi Medical Journal.)

Respiratory viruses are increasingly recognized as a cause of community-acquired pneumonia (CAP). The implementation of new diagnostic technologies has facilitated their identification, especially in vulnerable population such as immunocompromised and elderly patients and those with severe cases of pneumonia. In terms of severity and outcomes, viral pneumonia caused by influenza viruses appears similar to that caused by non-influenza viruses. Although several respiratory viruses may cause CAP, antiviral therapy is available only in cases of CAP caused by influenza virus or respiratory syncytial virus. Currently, evidence-based supportive care is key to managing severe viral pneumonia. We discuss the evidence surrounding epidemiology, diagnosis, management, treatment, and prevention of viral pneumonia., Competing Interests: None declared., (Thieme. All rights reserved.)

Background: Sphingosine-1-phosphate receptor ligands (SRLs) dampen immunopathologic damages in models of viral pneumonia., Research Question: Is it feasible to administer an SRL therapy, here ozanimod (OZA), to acutely ill patients infected with SARS-CoV-2?, Study Design and Methods: The prospective randomized open-label COVID-19 Ozanimod Intervention (COZI) pilot trial was conducted in three Canadian hospitals. Patients admitted for COVID-19 requiring oxygen were eligible. Randomization was stratified for risk factors of poor outcome and oxygen needs at inclusion. Participants were allocated to standard of care or to standard of care plus OZA. OZA (oral, once daily, incremental dosage) was administered for a maximum of 14 days. Primary end point investigated for size effect and variance over time was the assessment of safety and efficacy, evaluated by the daily score on the World Health Organization-adapted six-point ordinal scale for clinical improvement analyzed under the intention-to-treat principle., Results: Twenty-three patients were randomized to the standard of care arm, and 20 were randomized to the OZA arm from September 2020 to February 2022. Evaluation of efficacy showed nonsignificant reductions of median (interquartile range) duration of respiratory support (6 [3-10] vs 9 [4-12] days; P = .34), median duration of hospitalization (9 [6-12] vs 10 [6-18] days; P = .20), and median time to clinical improvement (4 [3-7] vs 7 [3-11] days; P = .12) for OZA compared with standard of care, respectively. Heart rate was significantly lower with OZA (65 [ 63-67] vs 71 [69-72] beats/min; P < .0001). However, QT and PR intervals were not affected. No severe adverse drug reaction was reported., Interpretation: To our knowledge, SRL utility in severe pneumonia has never been tested in patients. This study shows for the first time that this new pharmacologic agent may safely be administered to patients hospitalized for viral pneumonia, with potential clinical benefits. Bradycardia was frequent but well tolerated., Clinical Trial Registration: ClinicalTrials.gov; No.: NCT04405102; URL: www., Clinicaltrials: gov., Competing Interests: Financial/Nonfinancial Disclosures The authors have reported to CHEST the following: F. L. is a shareholder and administrator of the board of directors of OxyNov for the FreeO(2) device used in a few participants in this study. F. M. has financial participation in OxyNov. None declared (P. B.-L., J.-F. S., P. R., T. N., N. C., D. M.)., (Copyright © 2023 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Influenza and other respiratory viruses are commonly identified in patients with community-acquired pneumonia, hospital-acquired pneumonia, and in immunocompromised patients with pneumonia. Clinically, it is difficult to differentiate viral from bacterial pneumonia. Similarly, the radiological findings of viral infection are in general nonspecific. The advent of polymerase chain reaction testing has enormously facilitated the identification of respiratory viruses, which has important implications for infection control measures and treatment. Currently, treatment options for patients with viral infection are limited but there is ongoing research on the development and clinical testing of new treatment regimens and strategies., Competing Interests: Disclosure R.Cavallazzi: Site investigator for a study that aims to assess the safety of a monoclonal antibody for community-acquired bacterial pneumonia., (Copyright © 2023. Published by Elsevier Inc.)

Background/purpose: Patients with influenza infection during their period of admission may have worse computed tomography (CT) manifestation according to the clinical status. This study aimed to evaluate the CT findings of in-hospital patients due to clinically significant influenza pneumonia with correlation of clinical presentations., Methods: In this retrospective, single center case series, 144 patients were included. All in-hospital patients were confirmed influenza infection and underwent CT scan. These patients were divided into three groups according to the clinical status of the most significant management: (1) without endotracheal tube and mechanical ventilator (ETTMV) or extracorporeal membrane oxygenation (ECMO); (2) with ETTMV; (3) with ETTMV and ECMO. Pulmonary opacities were scored according to extent. Spearman rank correlation analysis was used to evaluate the correlation between clinical parameters and CT scores., Results: The predominant CT manifestation of influenza infection was mixed ground-glass opacity (GGO) and consolidation with both lung involvement. The CT scores were all reach significant difference among all three groups (8.73 ± 6.29 vs 12.49 ± 6.69 vs 18.94 ± 4.57, p < 0.05). The chest CT score was correlated with age, mortality, and intensive care unit (ICU) days (all p values were less than 0.05). In addition, the CT score was correlated with peak lactate dehydrogenase (LDH) level and peak C-reactive protein (CRP) level (all p values were less than 0.05). Concomitant bacterial infection had higher CT score than primary influenza pneumonia (13.02 ± 7.27 vs 8.95 ± 5.99, p < 0.05)., Conclusion: Thin-section chest CT scores correlated with clinical and laboratory parameters in in-hospital patients with influenza pneumonia., Competing Interests: Declaration of competing interest The authors have no conflicts of interest relevant to this article., (Copyright © 2023. Published by Elsevier B.V.)

One of the most relevant challenges for healthcare providers during the COVID- 19 pandemic has been assuring the continuity of care to patients with complex health needs such as people living with rare diseases (RDs). The COVID-19 pandemic accelerated the healthcare sector's digital transformation agenda. The delivery of telemedicine services instead of many face-to-face procedures has been expanded and, many healthcare services not directly related to COVID-19 treatments shifted online remotely. Many hospitals, specialist centres, patients and families started to use telemedicine because they were forced to. This trend could directly represent a good practice on how care services could be organized and continuity of care could be ensured for patients. If done properly, it could boast improved patient outcomes and become a post COVID-19 major shift in the care paradigm. There is a fragmented stakeholders spectrum, as many questions arise on: how is e-health interacting with 'traditional' healthcare providers; about the role of the European Reference Networks (ERNs); if remote care can retain a human touch and stay patient centric. The manuscript is one of the results of the European Brain Council (EBC) Value of Treatment research project on rare brain disorders focusing on progressive ataxias, dystonia and phenylketonuria with the support of Academic Partners and in collaboration with European Reference Networks (ERNs) experts, applying empirical evidence from different European countries. The main purpose of this work is to investigate the impact of the COVID-19 pandemic on the continuity of care for ataxias, dystonia and phenylketonuria (PKU) in Europe. The analysis carried out makes it possible to highlight the critical points encountered and to learn from the best experiences. Here, we propose a scoping review that investigates this topic, focusing on continuity of care and novel methods (e.g., digital approaches) used to reduce the care disruption. This scoping review was designed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews (PRISMA-ScR) standards. This work showed that the implementation of telemedicine services was the main measure that healthcare providers (HCPs) put in place and adopted for mitigating the effects of disruption or discontinuity of the healthcare services of people with rare neurological diseases and with neurometabolic disorders in Europe., (© 2024. The Author(s).)

Objective To clarify both the histologic changes in primary viral pneumonia other than COVID-19 and whether patients with severe lung injury (SLI) on biopsy specimens progress to severe respiratory insufficiency. Methods Patients with primary viral pneumonia other than COVID-19, who underwent lung tissue biopsy, were retrospectively studied. Patients Forty-three patients (41 living patients and 2 autopsied cases) were included in the study. Results Nine patients had SLI, whereas most of patients who recovered from primary viral pneumonia showed a nonspecific epithelial injury pattern. One patient underwent a biopsy under mechanical ventilation. Two of 8 (25.0%) patients on ambient air or low-flow oxygen therapy progressed to a severe respiratory condition and then to death, while only 1 (3.1%) of 32 patients without SLI progressed to a severe respiratory condition and death (p=0.096). The proportion of patients who required O 2 treatment for ≥2 weeks was higher in patients with SLI than in those without SLI (p=0.033). The 2 autopsy cases showed a typical pattern of diffuse alveolar damage, with both showing hyaline membranes. Non-specific histologic findings were present in 32 patients without SLI. Conclusion Some patients with SLI progressed to severe respiratory insufficiency, whereas those without SLI rarely progressed to severe respiratory insufficiency or death. The frequency of patients progressing to a severe respiratory condition or death did not differ significantly between those with and without SLI. The proportion of patients who required longer O 2 treatment was higher in SLI group than in those without SLI.

Background: Infection with viral pneumonia (PNA) is known to offset the coagulation cascade. Recent studies assessing novel SARS-CoV-2 infection observed a high frequency of systemic thrombotic events resulting in ambiguity if severity of infection or specific viral strain drive thrombosis and worsen clinical outcomes. Furthermore, limited data exists addressing SARS-CoV-2 in underrepresented patient populations., Objectives: Assess clinical outcomes events and death in patients diagnosed with SARS-CoV-2 pneumonia compared to patients with other types of viral pneumonia., Methods: Retrospective cohort study evaluated electronic medical records in adult patients admitted to University of Illinois Hospital and Health Sciences System (UIHHSS) with primary diagnosis of SARS-CoV-2 PNA or other viral (H1N1 or H3N2) PNA between 10/01/2017 and 09/01/2020. Primary composite outcome was the following event incidence rates: death, ICU admission, infection, thrombotic complications, mechanical ventilation, renal replacement therapy, and major bleeding., Results: Of 257 patient records, 199 and 58 patients had SARS-CoV-2 PNA and other viral PNA, respectively. There was no difference in primary composite outcome. Thrombotic events (n = 6, 3%) occurred solely in SARS-CoV-2 PNA patients in the ICU. A significantly higher incidence of renal replacement therapy (8.5% vs 0%, p=0.016) and mortality (15.6% vs 3.4%, p=0.048) occurred in the SARS-CoV-2 PNA group. Multivariable logistic regression analysis revealed age, presence of SARS-CoV-2, and ICU admission, aOR 1.07, 11.37, and 41.95 respectively, was significantly associated with mortality risk during hospitalization; race and ethnicity were not., Conclusion: Low overall incidence of thrombotic events occurred only in the SARS-CoV-2 PNA group. SARS-CoV-2 PNA may lead to higher incidence of clinical events than those observed in H3N2/H1N1 viral pneumonia, and that race/ethnicity does not drive mortality outcomes., Competing Interests: Declaration of Competing Interest Scott Benken (CareDx, Eurofins, VericiDx, Daichii Sankyo, BMS, Velovis); none relevant to this publication; all authors have no conflicts of interest to disclose., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: Prior to the coronavirus disease 2019 (COVID-19) pandemic, influenza was the most frequent cause of viral respiratory pneumonia requiring intensive care unit (ICU) admission. Few studies have compared the characteristics and outcomes of critically ill patients with COVID-19 and influenza., Methods: This was a French nationwide study comparing COVID-19 (March 1, 2020-June 30, 2021) and influenza patients (January 1, 2014-December 31, 2019) admitted to an ICU during pre-vaccination era. Primary outcome was in-hospital death. Secondary outcome was need for mechanical ventilation., Results: 105,979 COVID-19 patients were compared to 18,763 influenza patients. Critically ill patients with COVID-19 were more likely to be men with more comorbidities. Patients with influenza required more invasive mechanical ventilation (47 vs. 34%, p < 0·001), vasopressors (40% vs. 27, p < 0·001) and renal-replacement therapy (22 vs. 7%, p < 0·001). Hospital mortality was 25% and 21% (p < 0·001) in patients with COVID-19 and influenza, respectively. In the subgroup of patients receiving invasive mechanical ventilation, ICU length of stay was significantly longer in patients with COVID-19 (18 [10-32] vs. 15 [8-26] days, p < 0·001). Adjusting for age, gender, comorbidities, and modified SAPS II score, in-hospital death was higher in COVID-19 patients (adjusted sub-distribution hazard ratio [aSHR]=1.69; 95%CI=1.63-1.75) compared with influenza patients. COVID-19 was also associated with less invasive mechanical ventilation (aSHR=0.87; 95%CI=0.85-0.89) and a higher likelihood of death without invasive mechanical ventilation (aSHR=2.40; 95%CI=2.24-2.57)., Conclusion: Despite younger age and lower SAPS II score, critically ill COVID-19 patients had a longer hospital stay and higher mortality than patients with influenza., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Introduction: Selective serotonin reuptake inhibitors are considered the drugs, whose effectiveness in viral pandemics has been studied. The aim of this study was to evaluate of adding fluoxetine to the treatment regimen of patients with COVID-19 pneumonia., Methods: This study was a double-blind randomized placebo controlled clinical trial .36 patients in the fluoxetine and 36 patients in the placebo group were enrolled. Patients in the intervention group were first treated with fluoxetine 10 mg for 4 days and then the dose of 20 mg was continued for 4 weeks. Data analysis was conducted using SPSS V. 22.0., Results: There was no statistically significant difference between the two groups in terms of clinical symptoms at the beginning of the study and also the score of anxiety and depression, oxygen saturation at the time of hospitalization, mid-hospitalization and discharge periods. The need for mechanical ventilator support (p = 1.00), the need for admission in the intensive care unit (ICU) (p = 1.00), rate for mortality (p = 1.00), and discharge with relative recovery (p = 1.00) were not significantly different between the two groups. The distribution of CRP within the study groups showed a significant decrease during different time periods (p = 0.001), and although there was no statistically significant difference between the two groups on the first day (p = 1.00) and at discharge (p = 0.585), mid-hospital CRP showed a significant decrease in the fluoxetine group (p = 0.032)., Conclusion: Fluoxetine resulted in a faster reduction of patients' inflammation without association with depression and anxiety., (© 2023 The Authors. Neuropsychopharmacology Reports published by John Wiley & Sons Australia, Ltd on behalf of The Japanese Society of Neuropsychopharmacology.)

Risk Factors for Severe Courses: The CRB-65 score is recommended as a risk predictor, as well as consideration of unstable comorbidities and oxygenation., Grouping of Community-Acquired Pneumonia: Community-acquired pneumonia is divided into 3 groups: mild pneumonia, moderate pneumonia, severe pneumonia. Whether there is a curative vs palliative treatment goal should be determined early., Diagnostic Recommendation: An X-ray chest radiograph is recommended to confirm the diagnosis, also in the outpatient setting if possible. Sonography of the thorax is an alternative, asking for additional imaging if negative. Streptococcus pneumoniae remains the most common bacterial pathogen., Therapy: Community-acquired pneumonia continues to be associated with high morbidity and lethality. Prompt diagnosis and prompt initiation of risk-adapted antimicrobial therapy are essential measures. However, in times of COVID-19, as well as the current influenza and RSV epidemic, purely viral pneumonias must also be expected. At least with COVID-19, antibiotics can often be avoided. Antiviral and anti-inflammatory drugs are used here., Post-Acute Course: Patients after community-acquired pneumonia have increased acute and long-term mortality due to cardiovascular events in particular. The focus of research is on improved pathogen identification, a better understanding of the host response with the potential of developing specific therapeutics, the role of comorbidities, and the long-term consequences of the acute illness., Competing Interests: Prof. Gernot Rohde gibt an, innerhalb der letzten 3 Jahre in einem Beratungsgremium von Astra Zeneca, Atriva, Boehringer Ingelheim, GSK, Insmed, MSD, Sanofi, Novartis, Pfizer tätig gewesen zu sein und Vortragshonorare von Astra Zeneca, Berlin Chemie, BMS, Boehringer Ingelheim, Chiesi, Essex Pharma, Grifols, GSK, Insmed, MSD, Roche, Sanofi, Solvay, Takeda, Novartis, Pfizer, Vertex erhalten zu haben. Dr. Alexander Seeger gibt an, dass keine Interessenkonflikte bestehen., (Thieme. All rights reserved.)

The SARS-CoV-2 pandemic had a tremendous impact on diagnosis and treatment of interstitial lung diseases (ILD). Especially in the early phase of the pandemic, when the delta variant was prevailling, a huge number of viral pneumonias were observed, which worsened pre-existing, triggered de novo occurence or discovery of previously subclincal interstitial lung diseases. The effect of SARS-CoV-2 infection - without or with accompanying viral pneumonia - on the further development of pre-existing ILD as well of new pulmonary inflitrates and consolidiations is difficult to predict and poses a daily challenge to interdisciplinary ILD boards. This position paper of the German Respiratory Society (DGP e.V.) provides answers to the most pressing questions based on current knowledge., Competing Interests: JB erhielt Honorare für Vortragstätigkeit und Beratung von AstraZeneca, Boehringer-Ingelheim, Ferrer, Galapagos, Novartis, Roche und Sanofi/Gemzyme. MPB hat Honorare für Vorträge, Beratung und Kongresssponsoring von Boehringer-Ingelheim und Roche erhalten. TGB erhielt Honorare für Vortragstätigkeit und Beratung von Astra-Zeneca, Boehringer-Ingelheim, Johnson & Johnson, MSD, Pfizer und Roche (ohne Zusammenhang mit dieser Arbeit). FB erhielt Honorare für Vortragstätigkeit und Beratung von Boehringer-Ingelheim, Roche, Sanofi, Fujirebio und Fibrogen. JD erhielt Honorare für Vortragstätigkeit und Beratung von Boehringer-Ingelheim, Parexel und Astrazeneca. SG erhielt Honorare für Vortragstätigkeit und Beratung von Boehringer-Ingelheim, Roche, Berlin Chemie, Novartis, Astra Zeneca. LH erhielt Honorare für Vortragstätigkeit und Beratung für Boehringer-Ingelheim und Roche. NK hat keine Interessenkonflikte. DK erhielt Honorare für Vortragstätigkeit und Beratung sowie finanzielle Unterstützung bei Kongressbesuchen von Boehringer Ingelheim und Roche. AP erhielt Vortragshonorare von Boehringer Ingelheim, Novartis, Roche, Pfizer und Chiesi und Beratungshonorare von Boehringer Ingelheim, Novartis, Amgen, und Astra-Zeneca. Forschungsprojekte am Fraunhofer ITEM bestehen mit Boehringer Ingelheim, Novartis, Chiesi, AdAlta, Alentis und AiThera. ESP erhielt Honorare für Vortragstätigkeit von Boehringer-Ingelheim, Roche und Bristol-Myers-Squibb. HS hat keine Interessenskonflikte. HW hat Beratungs-/Vortragshonorare von Astra Zeneca, Allergopharma, Boehringer Ingelheim, Bioprojet, GSK, Inspire Medical, Jazz Pharma, Novartis, ResMed, Sanofi, VitalAire sowie Vivisol erhalten. MK erhielt Honorare für Vortragstätigkeit und Beratung von Boehringer-Ingelheim, Roche, Ferrer, Galapagos., (Thieme. All rights reserved.)

Purpose: To compare the incidence and nature of secondary infections (SI) between critically ill patients with viral pneumonia due to COVID-19 and seasonal influenza and explore the association between SI and clinical outcomes., Methods: We conducted a historical cohort study of patients admitted to the intensive care unit (ICU) at two tertiary care centers during the first wave of the COVID-19 pandemic and patients admitted with influenza during the 2018-2019 season. The primary outcome was the rate of SI. Secondary outcomes included rates of ICU and in-hospital mortality, organ-support-dependent disease, and length of ICU and hospital stay., Results: Secondary infections developed in 55% of 95 COVID-19 patients and 51% of 47 influenza patients (unadjusted odds ratio [OR], 1.16; 95% confidence interval [CI], 0.57 to 2.33). After adjusting for baseline differences between cohorts, there were no significant differences between the COVID-19 cohort and the influenza cohort (adjusted OR, 1.00; 95% CI, 0.41 to 2.44). COVID-19 patients with SI had longer ICU and hospital stays and duration of mechanical ventilation. The SI incidence was higher in COVID-19 patients treated with steroids than in those not treated with steroids (15/20, 75% vs 37/75, 49%)., Conclusion: Secondary infections were common among critically ill patients with viral pneumonia including COVID-19. We found no difference in the incidence of SI between COVID-19 and influenza in our cohort study, but SI in patients with COVID-19 were associated with worse clinical outcomes and increased healthcare resource use. The small cohort size precludes any causal inferences but may provide a basis for future research., (© 2023. The Author(s).)

Background: Post-infectious bronchiolitis obliterans (PIBO) is the most common sequelae in children with adenovirus pneumonia (ADVP). However, there are few studies on the risk factors for PIBO occurrence. This study aims to investigate the risk factors for PIBO in pediatric patients with severe ADVP, especially after invasive mechanical ventilation (IMV), as well as to build a nomogram prediction model., Methods: The clinical data, laboratory and imaging features, and treatment of 863 children with ADVP under 3 years old who were admitted to our hospital from January to December 2019 were retrospectively analyzed. Among them, 66 children with severe ADVP received IMV treatment. The situation and the influencing factors of PIBO in children with severe ADVP were explored, and a nomogram prediction model was constructed., Results: Among the 863 cases of ADVP, 46 cases (5.33%) developed PIBO. Duration of fever, IMV, complications, and neutrophil percentage were independent risk factors for PIBO in children with ADVP. Among the 66 patients with ADVP who underwent IMV, 33 patients (50.0%) developed PIBO. Gender, duration of fever, adenovirus (ADV) load, and mixed fungal coinfections were independent risk factors for PIBO. In the nomogram prediction model analysis, the area under the curve (AUC) was 0.857; in addition, Hosmer‒Lemeshow (H-L) detection reflected good alignment (χ2 = 68.75, P < 0.01)., Conclusions: A nomogram prediction model, which can be utilized to predict PIBO occurrence in pediatric patients with ADVP after IMV at an early time period, was successfully built., (© 2023. The Author(s).)

Introduction: Persisting respiratory symptoms in COVID-19 survivors may be related to development of pulmonary fibrosis. We assessed the proportion of chest CT scans and pulmonary function tests consistent with parenchymal lung disease in the follow-up of people hospitalised with COVID-19 and viral pneumonitis., Methods: Systematic review and random effects meta-analysis of proportions using studies of adults hospitalised with SARS-CoV-2, SARS-CoV, MERS-CoV or influenza pneumonia and followed up within 12 months. Searches performed in MEDLINE and Embase. Primary outcomes were proportion of radiological sequelae on CT scans; restrictive impairment; impaired gas transfer. Heterogeneity was explored in meta-regression., Results: Ninety-five studies (98.9% observational) were included in qualitative synthesis, 70 were suitable for meta-analysis including 60 SARS-CoV-2 studies with a median follow-up of 3 months. In SARS-CoV-2, the overall estimated proportion of inflammatory sequelae was 50% during follow-up (0.50; 95% CI 0.41 to 0.58; I 2 =95%), fibrotic sequelae were estimated in 29% (0.29; 95% CI 0.22 to 0.37; I 2 =94.1%). Follow-up time was significantly associated with estimates of inflammatory sequelae (-0.036; 95% CI -0.068 to -0.004; p=0.029), associations with fibrotic sequelae did not reach significance (-0.021; 95% CI -0.051 to 0.009; p=0.176). Impaired gas transfer was estimated at 38% of lung function tests (0.38 95% CI 0.32 to 0.44; I 2 =92.1%), which was greater than restrictive impairment (0.17; 95% CI 0.13 to 0.23; I 2 =92.5%), neither were associated with follow-up time (p=0.207; p=0.864)., Discussion: Sequelae consistent with parenchymal lung disease were observed following COVID-19 and other viral pneumonitis. Estimates should be interpreted with caution due to high heterogeneity, differences in study casemix and initial severity., Prospero Registration Number: CRD42020183139., Competing Interests: Competing interests: GJ reports NIHR BRC salaries, studentships, professorship (RP-2017-08-ST2-014)., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Severe adenovirus (Adv.) pneumonia can cause significant mortality in young children. There has been no worldwide consensus on the impact of extracorporeal membrane oxygenation (ECMO) in immunocompetent children with severe Adv. pneumonia. This study aimed to assess the impact of ECMO in immunocompetent children with severe Adv. pneumonia., Methods: This study evaluated the medical records of 168 hospitalized children with severe Adv. pneumonia at the Guangzhou Women and Children's Medical Center between 2019 and 2020.Nineteen patients in the ECMO group and 149 patients in the non-ECMO group were enrolled., Results: Between these two groups, there were no differences in host factors such as sex, age (all P > 0.05). Significant differences were observed in shortness of breath/increased work of breathing; cyanosis; seizures; tachycardia; the partial pressure of oxygen in arterial blood (PO 2 ); the ratio of PaO 2 to the fraction concentration of oxygen in inspired air (FiO 2 ; P/F); white blood cell, lymphocyte, monocytes, lactate dehydrogenase (LDH), serum albumin, and procalcitonin levels; and, pulmonary consolidation (all P < 0.05). There were significant differences in the parameters of mechanical ventilation (MV) therapy and complications such as respiratory failure, acute respiratory distress syndrome, septic shock, length of hospitalization, and death (all P < 0.05). The maximum axillary temperatures, respiratory rates, heart rates and LDH levels after receiving ECMO were significantly lower than those before ECMO (all P < 0.05). Additionally, SPO 2 , PO 2 , and P/F were significantly higher than those before ECMO (all P < 0.05). In MV therapy, FiO 2 , PIP, and PEEP were significantly lower than those before ECMO (all P < 0.05)., Conclusions: In our study, the clinical conditions of the patients in the ECMO group were much more severe than those in the non-ECMO group. Our study showed that ECMO might be beneficial for the patients with severe Adv. pneumonia., (© 2023. The Author(s).)

Coronavirus disease 2019 (COVID-19) treatments are still urgently needed for critically and severely ill patients. Human umbilical cord-mesenchymal stem cells (hUC-MSCs) infusion has therapeutic benefits in COVID-19 patients; however, uncertain therapeutic efficacy has been reported in severe patients. In this study, we selected an appropriate cytokine, IL-18, based on the special cytokine expression profile in severe pneumonia of mice induced by H1N1virus to prime hUC-MSCs in vitro and improve the therapeutic effect of hUC-MSCs in vivo. In vitro, we demonstrated that IL-18-primed hUC-MSCs (IL18-hUCMSC) have higher proliferative ability than non-primed hUC-MSCs (hUCMSCcon). In addition, VCAM-1, MMP-1, TGF-β1, and some chemokines (CCL2 and CXCL12 cytokines) are more highly expressed in IL18-hUCMSCs. We found that IL18-hUCMSC significantly enhanced the immunosuppressive effect on CD3 + T-cells. In vivo, we demonstrated that IL18-hUCMSC infusion could reduce the body weight loss caused by a viral infection and significantly improve the survival rate. Of note, IL18-hUCMSC can also significantly attenuate certain clinical symptoms, including reduced activity, ruffled fur, hunched backs, and lung injuries. Pathologically, IL18-hUCMSC transplantation significantly enhanced the inhibition of inflammation, viral load, fibrosis, and cell apoptosis in acute lung injuries. Notably, IL18-hUCMSC treatment has a superior inhibitory effect on T-cell exudation and proinflammatory cytokine secretion in bronchoalveolar lavage fluid (BALF). Altogether, IL-18 is a promising cytokine that can prime hUC-MSCs to improve the efficacy of precision therapy against viral-induced pneumonia, such as COVID-19., (© 2023. The Author(s).)

Background: A radiological finding of a cavitary pulmonary lesion in a patient acutely infected with severe acute respiratory syndrome coronavirus-2 early during the coronavirus disease 2019 pandemic created a diagnostic and treatment dilemma, as invasive procedures with bronchoscopy and percutaneous needle lung biopsy posed an infection hazard to healthcare workers due to the associated risk of viral aerosolization. Available guidelines recommended delay of non-emergent procedures, but timely proceeding with those deemed urgent provided appropriate personal protective equipment and negative pressure isolation were available and exposure risk was not excessive. Thoughtful consideration by clinicians was required to avoid delay in diagnosis of a potential new malignancy and prevent unnecessary healthcare worker exposure to the virus. Additionally, acute severe acute respiratory syndrome coronavirus-2 infection in patients with malignancy complicated timing of oncologic treatment., Case Presentation: A 26-year-old otherwise healthy Caucasian male initially presented with an enlarging right upper lobe cavitary pulmonary lesion despite antimicrobial therapy. During his hospitalization and evaluation, the patient was found to be acutely infected with severe acute respiratory syndrome coronavirus-2 without hypoxia or viral pneumonia. Bronchoscopy was deemed too high risk for viral aerosolization and healthcare worker infection. He underwent computed-tomography-guided percutaneous needle biopsy of the lesion by interventional radiology while on mechanical ventilation after elective intubation by anesthesiology. Biopsy revealed classic Hodgkin lymphoma consistent with primary pulmonary Hodgkin lymphoma. After collaboration with oncology, his treatment with combined chemotherapy and immunotherapy was delayed for 3 weeks following diagnosis to allow for viral clearance., Conclusion: A careful multidisciplinary strategy is required to expeditiously diagnose and treat aggressive cancers of the respiratory tract in patients acutely infected with severe acute respiratory syndrome coronavirus-2 while observing practices to prevent healthcare worker infection during the ongoing coronavirus disease 2019 pandemic., (© 2023. The Author(s).)

Background: The presence of treatment limitations in patients with frailty at intensive care unit (ICU) admission is unknown. We aimed to evaluate the presence and predictors of treatment limitations in patients with and without COVID-19 pneumonitis in those admitted to Australian and New Zealand ICUs., Methods: This registry-based multicenter, retrospective cohort study included all frail adults (≥16 years) with documented clinical frailty scale (CFS) scores, admitted to ICUs with admission diagnostic codes for viral pneumonia or acute respiratory distress syndrome (ARDS) over 2 years between January 01, 2020 and December 31, 2021. Frail patients (CFS ≥5) coded as having viral pneumonitis or ARDS due to COVID-19 were compared to those with other causes of viral pneumonitis or ARDS for documented treatment limitations., Results: 884 frail patients were included in the final analysis from 129 public and private ICUs. 369 patients (41.7%) had confirmed COVID-19. There were more male patients in COVID-19 (55.3% vs 47.0%; p = 0.015). There were no differences in age or APACHE-III scores between the two groups. Overall, 36.0% (318/884) had treatment limitations, but similar between the two groups (35.8% [132/369] vs 36.1% [186/515]; p = 0.92). After adjusting for confounders, increasing frailty (OR = 1.72; 95%-CI 1.39-2.14), age (OR = 1.05; 95%-CI 1.04-1.06), and presence of chronic respiratory condition (OR = 1.58; 95%-CI 1.10-2.27) increased the likelihood of instituting treatment limitations. However, the presence of COVID-19 by itself did not influence treatment limitations (odds ratio [OR] = 1.39; 95%-CI 0.98-1.96)., Conclusions: The proportion of treatment limitations was similar in patients with frailty with or without COVID-19 pneumonitis at ICU admission., (© 2022 The Authors. Journal of the American Geriatrics Society published by Wiley Periodicals LLC on behalf of The American Geriatrics Society.)

Background: To date, there has been little agreement on what drug is the "best" drug for treating severe COVID-19 patients. This study aimed to assess the efficacy and safety of different medications available at present for severe COVID-19., Methods: We searched databases for randomized controlled trials (RCTs) published up to February 28, 2022, with no language restrictions, of medications recommended for patients (aged 16 years or older) with severe COVID-19 infection. We extracted data on trials and patient characteristics, and the following primary outcomes: all-cause mortality (ACM), and treatment-emergent adverse events (TEAEs)., Results: We identified 4021 abstracts and of these included 48 RCTs comprising 9147 participants through database searches and other sources. For decrease in ACM, we found that ivermectin/doxycycline, C-IVIG (i.e., a hyperimmune anti-COVID-19 intravenous immunoglobulin), methylprednisolone, interferon-beta/standard-of-care (SOC), interferon-beta-1b, convalescent plasma, remdesivir, lopinavir/ritonavir, immunoglobulin gamma, high dosage sarilumab (HS), auxora, and imatinib were effective when compared with placebo or SOC group. We found that colchicine and interferon-beta/SOC were only associated with the TEAEs of severe COVID-19 patients., Conclusion: This study suggested that ivermectin/doxycycline, C-IVIG, methylprednisolone, interferon-beta/SOC, interferon-beta-1b, convalescent plasma (CP), remdesivir, lopinavir/ritonavir, immunoglobulin gamma, HS, auxora, and imatinib were efficacious for treating severe COVID-19 patients. We found that most medications were safe in treating severe COVID-19. More large-scale RCTs are still needed to confirm the results of this study., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: It is unclear if the impact of frailty on mortality differs between patients with viral pneumonitis due to COVID-19 or other causes. We aimed to determine if a difference exists between patients with and without COVID-19 pneumonitis., Methods: This multicentre, retrospective, cohort study using the Australian and New Zealand Intensive Care Society Adult Patient Database included patients aged ≥ 16 years admitted to 153 ICUs between 01/012020 and 12/31/2021 with admission diagnostic codes for viral pneumonia or acute respiratory distress syndrome, and Clinical Frailty Scale (CFS). The primary outcome was hospital mortality., Results: A total of 4620 patients were studied, and 3077 (66.6%) had COVID-19. The patients with COVID-19 were younger (median [IQR] 57.0 [44.7-68.3] vs. 66.1 [52.0-76.2]; p < 0.001) and less frail (median [IQR] CFS 3 [2-4] vs. 4 [3-5]; p < 0.001) than non-COVID-19 patients. The overall hospital mortality was similar between the patients with and without COVID-19 (14.7% vs. 14.9%; p = 0.82). Frailty alone as a predictor of mortality showed only moderate discrimination in differentiating survivors from those who died but was similar between patients with and without COVID-19 (AUROC 0.68 vs. 0.66; p = 0.42). Increasing frailty scores were associated with hospital mortality, after adjusting for Australian and New Zealand Risk of Death score and sex. However, the effect of frailty was similar in patients with and without COVID-19 (OR = 1.29; 95% CI: 1.19-1.41 vs. OR = 1.24; 95% CI: 1.11-1.37)., Conclusion: The presence of frailty was an independent risk factor for mortality. However, the impact of frailty on outcomes was similar in COVID-19 patients compared to other causes of viral pneumonitis., (© 2022. The Author(s).)

Infection with the novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), may cause viral pneumonia and acute respiratory distress syndrome (ARDS). Treatment of ARDS often requires mechanical ventilation and may take weeks for resolution. In areas with a large outbreaks, there may be shortages of ventilators available. While rudimentary methods for ventilator splitting have been described, given the range of independent ventilatory settings required for each patient, this solution is suboptimal. Here, we describe a device that can split a ventilator among up to four patients while allowing for individualized settings. The device has been validated in vitro and in vivo ., Competing Interests: Disclosure: The authors have no conflicts of interest to report., (Copyright © ASAIO 2022.)

Background: Human adenovirus type B7 (HAdV-B7) has been reported to cause pneumonia. However, there are limited data about the epidemiological and clinical features of HAdV-B7 pneumonia in young adults., Methods: This retrospective observational study included 52 patients diagnosed of human adenovirus B7 pneumonia in Nanjing, China from February 7, 2016, to February 20, 2016. We retrospectively collected and analyzed clinical, laboratory, and radiologic features, treatments and outcomes., Results: The median age of the 52 patients was 19.5 years (IQR 18.0-21.0). The most common symptoms were fever (50, 96.2%), cough (49, 94.2%), and expectoration (48, 92.3%). Most of the routine hematology and blood chemistry parameters were within the normal range. The predominant abnormal patterns seen on chest CT were unilateral (33, 66%), multifocal (36, 72%), and ground-glass opacity (27, 54%), mainly involving the left lower lobes (41 [36.0%] of 114 affected segments). As the disease progressed in the second week after symptom onset, consolidation and mixed patterns became more common, while the ground glass opacity pattern decreased. The single-agent ribavirin therapy group had a significantly shorter duration of nonrespiratory symptoms, and no statistically significant difference was observed between the single-agent methylprednisolone group and the nonglucocorticoid group., Conclusions: The main symptoms in immunocompetent patients with adenovirus type 7 are fever, cough and sputum, with no significant abnormalities in laboratory tests. Chest CT scan mostly shows a ground-glass opacity at the beginning of the disease, which subsequently changes to a mixed pattern. Ribavirin and glucocorticoids did not shorten the course of disease., (Copyright © 2022. Published by Elsevier B.V.)

Background: The study aimed to explore risk factors for bronchial mucus plugs (BMP) formation in children with adenovirus (AdV) pneumonia., Methods: A retrospective study was conducted on children with AdV pneumonia who underwent bronchoscopy from January 2019 to December 2019. Children were divided into the BMP group and the control group, depending on whether BMP was formed or not. The clinical information and treatment proposals of the two groups of children were counted and analyzed via multiple logistic regression analysis, ROC curve analysis, and correlation analysis., Results: Among 453 patients with AdV pneumonia, 185 (40.84%) were in the BMP group. Among all the cases, there were 188 patients with a single AdV infection, including 64 (34.04%) in the BMP group and 124 (65.96%) in the control group. The incidence of dyspnea, poor spirits, mixed infections, and other symptoms in the BMP group was higher than in the control group. Children in the BMP group had a longer heat range. C-reactive protein (CRP), lactate dehydrogenase (LDH), D-dimer (DD), and AdV load levels were higher in the MBP group. AdV load, Mycoplasma coinfection, DD, heat range, and LDH were independent risk factors for BMP, among which AdV load was the most significant (AUC = 0.819). AdV load was positively correlated with other risk factors, respectively. AdV load and heat range were independent risk factors for BMP patients with a single AdV infection., Conclusion: AdV load might have important clinical value in predicting BMP development in AdV pneumonia., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Li Peng et al.)

Background: Convalescent plasma containing high levels of SARS-CoV-2 antibodies has been studied as a possible treatment for COVID-19. Better understanding of predictors of high antibody levels is needed for improving supply of high-quality therapeutic plasma., Aims: We have evaluated demographic and clinical factors associated with the probability of a convalescent plasma donor having high SARS-CoV-2 IgG antibody levels., Methods: A total of 29,585 convalescent plasma donors employed during the first and second waves of the COVID-19 pandemic in England were included in this study. All had been tested for SARS-CoV-2 IgG antibodies by EUROimmun ELISA. A multivariable logistic regression model was used to quantify the association of the demographic and clinical factors with high (EUROimmun S/Co>6.0) SARS-CoV-2 IgG antibody level., Results: Most of the donors were male (23,024; 78%), with white ethnic background (24,598;83%) and had not been tested for SARS-CoV-2 (15,266; 52%).Overall, less than 20% of convalescent plasma donors with confirmed or suspected SARS-CoV-2 infection harboured high SARS-CoV-2 antibody levels (n = 4,978). We found that older male donors who had been hospitalised with COVID-19 were most likely to harbour high levels of antibodies. White donors were less likely to have high SARS-CoV-2 antibody levels than donors with Asian orblack ethnic backgrounds residing in affluent areas likely reflecting ethnic inequality previously associated with SARS-CoV-2 infection., Discussion: In a time of great uncertainty, and predicted new waves associated with newly emerging SARS-CoV-2 variants, these results will help us to target future convalescent plasma collections., (© 2022 British Blood Transfusion Society.)

The Coronavirus 2019 (COVID-19) pandemic, caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) virus, has resulted in unprecedented morbidity and mortality worldwide. While COVID-19 typically presents as viral pneumonia, cardiovascular manifestations such as acute coronary syndromes, arterial and venous thrombosis, acutely decompensated heart failure (HF), and arrhythmia are frequently observed. Many of these complications are associated with poorer outcomes, including death. Herein we review the relationship between cardiovascular risk factors and outcomes among patients with COVID-19, cardiovascular manifestations of COVID-19, and cardiovascular complications associated with COVID-19 vaccination., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2022 Elsevier Inc. All rights reserved.)

As the coronavirus disease (COVID-19) pandemic led to a global health crisis, there were limited treatment options and no prophylactic therapies for those exposed to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Convalescent plasma is quick to implement, potentially provides benefits, and has a good safety profile. The therapeutic potential of COVID-19 convalescent plasma (CCP) is likely mediated by antibodies through direct viral neutralization and Fc-dependent functions such as a phagocytosis, complement activation, and antibody-dependent cellular cytotoxicity. In the United States, CCP became one of the most common treatments with more than a half million units transfused despite limited efficacy data. More than a dozen randomized trials now demonstrate that CCP does not provide benefit for those hospitalized with moderate to severe disease. However, similar to other passive antibody therapies, CCP is beneficial for early disease when provided to elderly outpatients within 72 hours after symptom onset. Only high-titer CCP should be transfused. CCP should also be considered for immunosuppressed patients with COVID-19. CCP collected in proximity, by time and location, to the patient may be more beneficial because of SARS-CoV-2 variants. Additional randomized trial data are still accruing and should be incorporated with other trial data to optimize CCP indications., (© 2022 by The American Society of Hematology.)

This study aims to analyze the difference in clinical features and prognosis of severe adenovirus pneumonia (SAP) in children of different ages and analyze the risk factors for poor prognosis in children with SAP. A retrospective observational study was performed to describe the clinical features and analyze the risk factors for death and postinfectious bronchiolitis obliterans (PIBO) in 303 children hospitalized with SAP from January 2015 through to January 2020. The participants were divided into four age groups: <6 months (n = 25, 8.3%); 6-12 months (n = 98, 32.3%); 12-36 months (n = 118, 38.9%); and >36 months (n = 62, 20.5%). Fever rate, peak, and duration were the lowest in the <6 months group, while no significant difference was found among other age groups. Serum levels of lactate dehydrogenase and a load of adenovirus were the lowest in the <6 months group, and the highest in the 6-12 and 12-36 months groups, respectively. A total of 80.9% of patients recovered, 3.3% of patients died, and 15.8% of patients were diagnosed with PIBO. The mortality rate showed no significance between age groups. The >36 months group had the highest recovery rate and the lowest incidence of PIBO, while the 6-12 months group had the lowest recovery rate and the highest incidence of PIBO. Independent risk factors for PIBO among all participants from the four groups were invasive mechanical ventilation, administration of intravenous steroids, duration of fever, and male gender. Independent risk factors for death among all participants from the four groups were hypercapnia, low albumin levels, and invasive mechanical ventilation. Risk factor analysis of different ages was not possible due to the limited sample size. The morbidity, clinical features, and prognosis of SAP are affected by children's ages. Pediatric patients with a longer duration of fever, hypercapnia, low serum albumin levels, invasive mechanical ventilation, and intravenous steroids use are more likely to develop a poor prognosis in SAP, especially if the patient is male., (© 2022 Wiley Periodicals LLC.)

The COVID-19 pandemic has drawn considerable attention to viral pneumonia from clinicians, public health authorities, and the general public. With dozens of viruses able to cause pneumonia in humans, differentiating viral from bacterial pneumonia can be very challenging in clinical practice using traditional diagnostic methods. Precision medicine is a medical model in which decisions, practices, interventions, and therapies are adapted to the individual patient on the basis of their predicted response or risk of disease. Precision medicine approaches hold promise as a way to improve outcomes for patients with viral pneumonia. This review describes the latest advances in the use of precision medicine for diagnosing and treating viral pneumonia in adults and discusses areas where further research is warranted., (© 2022. The Author(s).)

Objective: To investigate the curative efficacy and application value of convalescent plasma (CP) in severe and critical coronavirus disease 2019 (COVID-19) caused by Delta variant., Methods: The treatment process and results of CP therapy for a patient with critical COVID-19 caused by Delta variant were reported. The clinical application value of CP for COVID-19 caused by Delta variant was analyzed along with the literature review., Results: Our case was a 50-year-old male, who was imported from abroad and had not been vaccinated against COVID-19. The novel coronavirus nucleic acid test was negative before entry. On the second day after entry, fever occurred, novel coronavirus nucleic acid test was positive. Chest CT images showed bilateral multiple mottling and ground-glass opacity with symptoms of nausea, headache, loss of appetite, diarrhea, but no running nose, nasal obstruction, dyspnea, abnormal smell and taste. The infection rapidly developed from medium to critical. On the basis of standard treatment, Delta variant CP was intravenous dripped on the 10th day of hospital admission (the 6th day after becoming severe). The patient's condition improved rapidly., Conclusions: The curative efficacy evaluation of this patient proved that CP therapy is of great value in the treatment of severe and critical COVID-19.

Objective: To evaluate whether pregnancy is an independent risk factor for in-hospital mortality among patients of reproductive age hospitalized with coronavirus disease 2019 (COVID-19) viral pneumonia., Methods: We conducted a retrospective cohort study (April 2020-May 2021) of 23,574 female inpatients aged 15-45 years with an International Classification of Diseases, Tenth Revision, Clinical Modification diagnosis code for COVID-19 discharged from 749 U.S. hospitals in the Premier Healthcare Database. We used a viral pneumonia diagnosis to select for patients with symptomatic COVID-19. The associations between pregnancy and in-hospital mortality, intensive care unit (ICU) admission, and mechanical ventilation were analyzed using propensity score-matched conditional logistic regression. Models were matched for age, marital status, race and ethnicity, Elixhauser comorbidity score, payer, hospital number of beds, season of discharge, hospital region, obesity, hypertension, diabetes mellitus, chronic pulmonary disease, deficiency anemias, depression, hypothyroidism, and liver disease., Results: In-hospital mortality occurred in 1.1% of pregnant patients and 3.5% of nonpregnant patients hospitalized with COVID-19 and viral pneumonia (propensity score-matched odds ratio [OR] 0.39, 95% CI 0.25-0.63). The frequency of ICU admission for pregnant and nonpregnant patients was 22.0% and 17.7%, respectively (OR 1.34, 95% CI 1.15-1.55). Mechanical ventilation was used in 8.7% of both pregnant and nonpregnant patients (OR 1.05, 95% CI 0.86-1.29). Among patients who were admitted to an ICU, mortality was lower for pregnant compared with nonpregnant patients (OR 0.33, 95% CI 0.20-0.57), though mechanical ventilation rates were similar (35.7% vs 38.3%, OR 0.90, 95% CI 0.70-1.16). Among patients with mechanical ventilation, pregnant patients had a reduced risk of in-hospital mortality compared with nonpregnant patients (0.26, 95% CI 0.15-0.46)., Conclusion: Despite a higher frequency of ICU admission, in-hospital mortality was lower among pregnant patients compared with nonpregnant patients with COVID-19 viral pneumonia, and these findings persisted after propensity score matching., Competing Interests: Financial Disclosure Jacqueline G Parchem disclosed received funding from the Foundation for SMFM/(AAOGF) (grant) and UTHealth CCTS (Grant). The other authors did not report any potential conflicts of interest., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.)

Among the viruses possibly responsible for hospital-acquired and ventilator-associated pneumonia, herpes simplex virus (HSV) is probably the most often involved: HSV reactivation is frequent in intensive care unit patients, and lung parenchymal infection (HSV bronchopneumonitis) has been well described, either using cytological signs of parenchymal involvement in cells obtained during bronchoalveolar lavage or using HSV virus load in the lower respiratory tract. Although treating patients with HSV bronchopneumonitis may be recommended, based on expert opinion, prophylactic or preemptive treatment of HSV reactivation should be avoided. Ventilator-associated pneumonia due to cytomegalovirus (CMV) is less frequent than HSV bronchopneumonitis, and more difficult to diagnose. No data exists on the impact of antiviral treatment on CMV pneumonia. The involvement of respiratory viruses has been described in patients with healthcare-associated pneumonia and hospital-acquired pneumonia, but their role in ventilator-associated pneumonia is not clear., Competing Interests: None declared., (Thieme. All rights reserved.)

Objectives: Coronavirus disease 2019 has been reported to be a prothrombotic condition; however, multicenter data comparing this with other viral pneumonias in those requiring extracorporeal membrane oxygenation are lacking. We conducted a multicenter study using whole-body CT to examine the prevalence, severity, and nature of vascular complications in coronavirus disease 2019 in comparison with patients with other viral pneumonias., Design: We analyzed whole-body CT scans for the presence of vascular thrombosis (defined as pulmonary artery thrombus, venous thrombus, systemic arterial thrombus, or end-organ infarct). The severity, distribution, and morphology of pulmonary artery thrombus were characterized. Competing risk cumulative incidence analysis was used to compare survival with discharge., Setting: Three centers of the English national extracorporeal membrane oxygenation service., Patients: Consecutive patients admitted with either coronavirus disease 2019 or noncoronavirus disease 2019 viral pneumonia admitted from January 2019., Interventions: None., Measurements and Main Results: One-hundred thirty-six patients (45.2 ± 10.6 yr old, 39/146 [27%] female) requiring extracorporeal membrane oxygenation support underwent whole-body CT scans at admission. Of these, 86 had coronavirus disease 2019 pneumonia, and 50 had noncoronavirus disease 2019 viral pneumonia. Vascular thrombosis was seen more often in patients with coronavirus disease 2019 (odds ratio, 12.9 [95% CI 4.5-36.8]). In those with coronavirus disease 2019, 57 (73%) demonstrated pulmonary artery thrombus or pulmonary perfusion defects. Eighty-two percent of thrombus exhibited emboli-like morphology. The location of pulmonary artery thrombus and parenchymal perfusion defects was only concordant in 30% of cases. The risk of mortality was higher in those with coronavirus disease 2019 compared with noncoronavirus disease 2019 pneumonia (χ2 = 3.94; p = 0.047). Mortality was no different in coronavirus disease 2019 patients with or without vascular thrombosis (χ2 = 0.44; p = 0.51)., Conclusions: In patients who received extracorporeal membrane oxygenation, coronavirus disease 2019 is associated with a higher prevalence of vascular thrombosis compared with noncoronavirus disease viral pneumonias. The pattern of pulmonary vascular changes suggests concurrent embolic disease and small vessel disease. Despite this, vascular thrombosis was not linked to poorer short-term prognosis in those with coronavirus disease 2019., Competing Interests: Dr. Weir-McCall received support for article research from Research Councils UK. Dr. Toshner received funding from Bayer and Actelion/Jansen; he disclosed he is a member of MorphogenIX scientific advisory board. Drs. Toshner and Jacob received funding from GlaxoSmithKline. Dr. Rodrigues received funding from Sanofi. Drs. Rodrigues and Jacob received funding from National Health Service Digital. Dr. Jacob received funding from Boehringer Ingelheim and Roche; he received support for article research from Wellcome Trust/Charity Open Access Fund. Dr. Jacob is supported by a grant 209553/Z/17/Z from the Wellcome Trust and the National Institute for Health Research University of College London Biomedical Research Center. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2022 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Purpose: Severe viral pneumonia is associated with significant morbidity and mortality. Recent COVID-19 pandemic continues to impose significant health burden worldwide, and individual pandemic waves often lead to a large surge in the intensive care unit (ICU) admissions for respiratory support. Comparisons of severe SARS-CoV-2 pneumonia with other seasonal and nonseasonal severe viral infections are rarely studied in an intensive care setting., Methods: A retrospective cohort study comparing patients admitted to ICU with COVID-19 between March and June 2020 and those with viral pneumonias between January and December 2019. We compared patient specific demographic variables, duration of illness, ICU organ supportive measures and outcomes between both groups., Results: Analysis of 93 COVID-19 (Group 1) and 52 other viral pneumonia patients (Group 2) showed an increased proportion of obesity (42% vs. 23%, p = 0.02), non-White ethnicities (41% vs. 6%, p < 0.001) and diabetes mellitus (30% vs. 13%, p = 0.03) in Group 1, with lower prevalence of chronic obstructive pulmonary disease (COPD)/asthma (16% vs. 34%, p = 0.02). In Group 1, the neutrophil to lymphocyte ratio was much lower (6.7 vs. 10, p = 0.006), and invasive mechanical ventilation (58% vs. 26%, p < 0.001) was more common. Length of ICU (8 vs. 4, p < 0.001) and hospital stay (22 vs. 11, p < 0.001) was prolonged in Group 1, with no significant difference in mortality. Influenza A and rhinovirus were the most common pathogens in Group 2 (26% each)., Conclusions: Key differences were identified within demographics (obesity, ethnicity, age, ICU scores, comorbidities) and organ support. Despite these variations, there were no significant differences in mortality between both groups. Further studies with larger sample sizes would allow for further assessment of clinical parameters in these patients., (© 2022 The Authors. The Clinical Respiratory Journal published by John Wiley & Sons Ltd.)

Background: Severe fatal human adenoviral (HAdV) pneumonia is associated with significant mortality and no effective drug is available for clinical therapy. We evaluated the association and safety of high titer neutralizing antibodies (NAbs) plasma in pediatric patients with severe fatal HAdV pneumonia., Methods: A retrospective cohort study was performed between January 2016 to June 2021 in pediatric intensive care unit. Pediatric patients with severe fatal HAdV pneumonia were included and divided into plasma group (conventional treatment plus high titer NAbs plasma treatment) and control group (conventional treatment alone). The primary outcome was mortality in hospital. Secondary outcomes were the duration of fever after adenovirus genotype determined, duration of invasive mechanical ventilation, length of hospital stay. T-test, Mann-Whitney U-test, chi-square test, univariable and multivariable logistic regression analysis, Kaplan-Meier method and log-rank test were adopted to compare differences between two groups., Results: A total of 59 pediatric patients with severe fatal HAdV pneumonia were enrolled. They were divided into plasma group (n = 33) and control group (n = 26). The mortality in hospital was 28.8% (17/ 59). Significantly fewer patients progressed to death in plasma group than control group (18.2% vs 42.3%, p = 0.042). Sequential organ failure assessment (SOFA) score, oxygen index (OI) and high titer NAbs plasma treatment were included in multivariable logistic regression analysis for mortality risk factors. Consequentially, SOFA score (Hazard Ratio [HR] 7.686, 95% Confidence Interval [CI] 1.735-34.054, p = 0.007) and without high titer NAbs plasma treatment (HR 4.298, 95%CI 1.030-17.934, p = 0.045) were significantly associated with mortality. In addition, high titer NAbs plasma treatment were associated with faster temperature recovering in survivors (p = 0.031). No serious adverse effects occurred., Conclusions: Administration of high titer NAbs plasma were associated with a lower hazard for mortality in pediatric patients with severe fatal HAdV pneumonia. For survivors, high titer NAbs plasma treatment shorten the duration of fever., (© 2022. The Author(s).)

Background: To assess the outcome of extracorporeal membrane oxygenation (ECMO) for severe adenovirus (Adv) pneumonia with refractory hypoxic respiratory failure (RHRF) in paediatric patients., Methods: A retrospective observational study was performed in a tertiary paediatric intensive care unit (PICU) in China. Patients with RHRF caused by Adv pneumonia who received ECMO support after mechanical ventilation failed to achieve adequate oxygenation between 2017 and 2020 were included. The outcome variables were the in-hospital survival rate and the effects of ECMO on the survival rate., Results: In total, 18 children with RHRF received ECMO. The median age was 19 (9.5, 39.8) months, and the median ECMO duration was 196 (152, 309) h. The in-hospital survival rate was 72.2% (13/18). Thirteen patients (72.2%) required continuous renal replacement therapy (CRRT) due to fluid imbalance or acute kidney injury (AKI). At ECMO initiation, compared with survivors, nonsurvivors had a lower PaO 2 /FiO 2 ratio [49 (34.5, 62) vs. 63 (56, 71); p = 0.04], higher oxygen index (OI) [41 (34.5, 62) vs. 30 (26.5, 35); p = 0.03], higher vasoactive inotropic score (VIS) [30 (16.3, 80) vs. 100 (60, 142.5); p = 0.04], longer duration from mechanical ventilation to ECMO support [8 (4, 14) vs. 4 (3, 5.5) h, p=0.02], and longer time from confirmed RHRF to ECMO initiation [9 (4.8, 13) vs. 5 (1.3, 5.5) h; p = 0.004]. Patients with PaO 2 /FiO 2 <61 mmHg or an OI >43 and hypoxic respiratory failure for more than 9 days before the initiation of ECMO had worse outcomes., Conclusions: ECMO seemed to be effective, as severe paediatric Adv pneumonia patients with RHRF had a cumulative survival rate of 72.2% in our study. Our study provides insight into ECMO rescue in children with severe Adv pneumonia., (© 2022. The Author(s).)

Background: In a decade, we faced two pandemic viruses, influenza A H1N1pdm09 and SARS CoV-2, whose most serious manifestation is pneumonia., Aim: To compare the clinical, epidemiological and management aspects of pneumonias caused by each pandemic virus in adults requiring hospitalization., Material and Methods: Comparative, observational study carried out at a regional Chilean hospital, including 75 patients with influenza A H1N1pdm09 prospectively studied in 2009 and 142 patients with SARS-CoV-2 studied in 2020., Results: Patients with SARS-CoV-2 pneumonia were older (56 and 39.7 years respectively, p < 0.01) and had significantly more comorbidities. Cough, fever and myalgias were more frequent in influenza. Dyspnea was more frequent in COVID-19. Patients with COVID-19 had more extensive lung involvement and a longer hospitalization (13.6 and 8.6 days respectively, p = 0.01). There was no difference on ICU admission requirements and mortality attributable to pneumonia. Patients with influenza had greater APACHE scores and a higher frequency of a PaO2/FiO2 ratio ≤ 200. During COVID-19pandemic chest sean replaced x-ray examination. Also high-flow nasal cannulas and awake prone position ventilation were added as treatments., Conclusions: COVID-19 patients were older, had fewer classic flu symptoms but more dyspnea and longer hospitalization periods than patients with influenza.

Importance: Little is known about COVID-19 outcomes among children and adolescents in sub-Saharan Africa, where preexisting comorbidities are prevalent., Objective: To assess the clinical outcomes and factors associated with outcomes among children and adolescents hospitalized with COVID-19 in 6 countries in sub-Saharan Africa., Design, Setting, and Participants: This cohort study was a retrospective record review of data from 25 hospitals in the Democratic Republic of the Congo, Ghana, Kenya, Nigeria, South Africa, and Uganda from March 1 to December 31, 2020, and included 469 hospitalized patients aged 0 to 19 years with SARS-CoV-2 infection., Exposures: Age, sex, preexisting comorbidities, and region of residence., Main Outcomes and Measures: An ordinal primary outcome scale was used comprising 5 categories: (1) hospitalization without oxygen supplementation, (2) hospitalization with oxygen supplementation, (3) ICU admission, (4) invasive mechanical ventilation, and (5) death. The secondary outcome was length of hospital stay., Results: Among 469 hospitalized children and adolescents, the median age was 5.9 years (IQR, 1.6-11.1 years); 245 patients (52.4%) were male, and 115 (24.5%) had comorbidities. A total of 39 patients (8.3%) were from central Africa, 172 (36.7%) from eastern Africa, 208 (44.3%) from southern Africa, and 50 (10.7%) from western Africa. Eighteen patients had suspected (n = 6) or confirmed (n = 12) multisystem inflammatory syndrome in children. Thirty-nine patients (8.3%) died, including 22 of 69 patients (31.9%) who required intensive care unit admission and 4 of 18 patients (22.2%) with suspected or confirmed multisystem inflammatory syndrome in children. Among 468 patients, 418 (89.3%) were discharged, and 16 (3.4%) remained hospitalized. The likelihood of outcomes with higher vs lower severity among children younger than 1 year expressed as adjusted odds ratio (aOR) was 4.89 (95% CI, 1.44-16.61) times higher than that of adolescents aged 15 to 19 years. The presence of hypertension (aOR, 5.91; 95% CI, 1.89-18.50), chronic lung disease (aOR, 2.97; 95% CI, 1.65-5.37), or a hematological disorder (aOR, 3.10; 95% CI, 1.04-9.24) was associated with severe outcomes. Age younger than 1 year (adjusted subdistribution hazard ratio [asHR], 0.48; 95% CI, 0.27-0.87), the presence of 1 comorbidity (asHR, 0.54; 95% CI, 0.40-0.72), and the presence of 2 or more comorbidities (asHR, 0.26; 95% CI, 0.18-0.38) were associated with reduced rates of hospital discharge., Conclusions and Relevance: In this cohort study of children and adolescents hospitalized with COVID-19 in sub-Saharan Africa, high rates of morbidity and mortality were observed among infants and patients with noncommunicable disease comorbidities, suggesting that COVID-19 vaccination and therapeutic interventions are needed for young populations in this region.