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Purpose: We aimed to investigate risk factors for COVID-19 pneumonia in patients with hematological malignancies (HM) after Omicron infection., Methods: Data from a registered multi-center, prospective, observational study (ChiCTR2300071830) during the latest Omicron BA.5.2 wave in Chongqing, China was used for analysis., Results: A total of 475 HM patients enrolled in this study. COVID-19 pneumonia was observed in 15.8% (75/475) of patients, with a median age of 58 years (interquartile range [IQR], 48-69 years) and males accounting for 61.3%. Risk factors associated with COVID-19 pneumonia included: 1) Active disease status of HM at infection, with an odds ratio (OR) of 3.42 (95% confidence interval [CI]: 1.59-7.37, P=0.002) compared to complete remission (CR); 2) Incomplete COVID-19 vaccination, 1-2 doses of the vaccine (OR=2.55, 95% CI: 1.28-5.10, P=0.008) or no vaccination (OR=4.81, 95% CI: 2.45-9.43, P<0.001), as opposed to 3 doses (booster); 3) chemotherapy prior to infection, <6 months (OR=2.58, 95% CI: 1.12-5.96, P=0.027) or ≥ 6 months (OR=2.93, 95% CI: 1.31-6.53, P=0.009) compared to no chemotherapy history; 4) NK-cell reduction (< 150/μL) (OR=2.19, 95% CI: 1.27-3.79, P=0.005) versus a normal range of NK cells. During the 6-week follow-up period, 12 patients (2.5%) died, accounting for 16% of COVID-19 pneumonia patients., Conclusions: Our study investigated risk factors for COVID-19 pneumonia in HM patients after Omicron BA.5.2 infection. Highlights that HM patients with these risk factors may be susceptible to lung involvement after Omicron BA.5.2 infection and need to be taken seriously in clinical practice., Clinical Trial Registration: https://www.chictr.org.cn/bin/project/edit?pid=195998, identifier ChiCTR2300071830., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Li, Chen, Cao, Liu, Zhang, Wei, Liu, Yang, Liu, Zhou, Xu, Chen, Ding, Lei, Liu, Yang, Chen, Zhang, Tang, Fu, He, Xiao, Xie, Li, Nan, Li, Chen and Liu.)

Coronavirus disease 2019 (COVID-19) pneumonia has had catastrophic effects worldwide. Radiology, in particular computed tomography (CT) imaging, has proven to be valuable in the diagnosis, prognostication, and longitudinal assessment of those diagnosed with COVID-19 pneumonia. This article will review acute and chronic pulmonary radiologic manifestations of COVID-19 pneumonia with an emphasis on CT and also highlighting histopathology, relevant clinical details, and some notable challenges when interpreting the literature., Competing Interests: Disclosure Nothing to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

COVID-19 pneumonia severity assessment is of great clinical importance, and lung ultrasound (LUS) plays a crucial role in aiding the severity assessment of COVID-19 pneumonia due to its safety and portability. However, its reliance on qualitative and subjective observations by clinicians is a limitation. Moreover, LUS images often exhibit significant heterogeneity, emphasizing the need for more quantitative assessment methods. In this paper, we propose a knowledge fused latent representation framework tailored for COVID-19 pneumonia severity assessment using LUS examinations. The framework transforms the LUS examination into latent representation and extracts knowledge from regions labeled by clinicians to improve accuracy. To fuse the knowledge into the latent representation, we employ a knowledge fusion with latent representation (KFLR) model. This model significantly reduces errors compared to approaches that lack prior knowledge integration. Experimental results demonstrate the effectiveness of our method, achieving high accuracy of 96.4 % and 87.4 % for binary-level and four-level COVID-19 pneumonia severity assessments, respectively. It is worth noting that only a limited number of studies have reported accuracy for clinically valuable exam level assessments, and our method surpass existing methods in this context. These findings highlight the potential of the proposed framework for monitoring disease progression and patient stratification in COVID-19 pneumonia cases., 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 © 2024 Elsevier B.V. All rights reserved.)

Objective: This retrospective cohort study aimed to assess the clinical features, treatment outcomes, and short-term prognosis in kidney transplant recipients (KTRs) with concurrent coronavirus disease 2019 (COVID-19) pneumonia., Methods: KTRs with COVID-19 pneumonia who were admitted to our hospital from December 28, 2022, to March 28, 2023 were included in the study. Their clinical symptoms, responses to antiviral medications, and short-term prognosis were analyzed., Results: A total of 64 KTRs with initial diagnosis of COVID-19 pneumonia were included in this study. The primary symptoms were fever, cough, and myalgia, with an incidence of 79.7%, 89.1%, and 46.9%, respectively. The administration of antiviral drugs (paxlovid or molnupiravir) within 1-5 days and for over 5 days demonstrated a statistically significant reduction in viral shedding time compared to the group without antiviral medication (P=0.002). Both the paxlovid and molnupiravir treatment groups exhibited a significantly shorter duration of viral shedding time in comparison to the group without antiviral drugs (P=0.002). After 6 months of recovery, there was no significantly negative impact on transplant kidney function (P=0.294)., Conclusion: Fever, cough, and myalgia remain common initial symptoms of concurrent COVID-19 pneumonia in KTRs. Early use of antiviral drugs (paxlovid or molnupiravir) is associated with better therapeutic outcomes. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had a limited impact on the short-term renal function of the KTRs with concurrent moderate or severe COVID-19 pneumonia., Competing Interests: Author XY was employed by Hugobiotech Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Xu, Chen, Yang, Chen, Yang, Yuan, Chen, Wang, Jiang, Xu and Wang.)

Pulmonary infections contribute substantially to emergency department (ED) visits, posing a considerable health burden. Lower respiratory tract infections are prevalent, particularly among the elderly, constituting a significant percentage of infectious disease-related ED visits. Timely recognition and treatment are crucial to mitigate morbidity and mortality. Imaging studies, primarily chest radiographs and less frequently CT chests, play a pivotal role in diagnosis. This article aims to elucidate the imaging patterns of both common and rare pulmonary infections (bacterial and viral) in the post COVID-19 era, emphasizing the importance of recognizing distinct radiological manifestations. The integration of clinical and microbiological evidence aids in achieving accurate diagnoses, and guiding optimal therapeutic interventions. Despite potential overlapping manifestations, a nuanced understanding of radiological patterns, coupled with comprehensive clinical and microbiological information, enhances diagnostic precision in majority cases., (© 2024. The Author(s), under exclusive licence to American Society of Emergency Radiology (ASER).)

Purpose: Antibodies against SARS-CoV-2 spike (anti-S) may confer protection against symptomatic COVID-19. Whether their level predicts progression among those with COVID-19 pneumonia remains unclear., Methods: We conducted a retrospective cohort study to assess predictors of anti-S levels and whether anti-S titer is associated with death or mechanical ventilation (MV). Adults hospitalized for COVID-19 pneumonia between July 2021 and July 2022 were enrolled if anti-S had been measured within 72 h of admission. Predictors of anti-S level were explored using multivariable quantile regression. The association between anti-S levels and 30-day death/MV was investigated via multivariable logistic regression. Analyses were stratified by vaccine status., Results: The median anti-S level was 1370 BAU/ml in 328 vaccinated and 15.5 BAU/ml in 206 unvaccinated individuals. Among the vaccinated, shorter symptom duration (p = 0.001), hematological malignancies (p = 0.002), and immunosuppressive therapy (p = 0.004) were associated with lower anti-S levels. In the unvaccinated group, symptom duration was the only predictor of anti-S levels (p < 0.001). After 30 days, 134 patients experienced death or MV. Among vaccinated individuals, higher anti-S levels correlated significantly with lower death/MV risk (per log 2 increase, OR 0.88, 95%CI 0.81-0.97), irrespective of age and solid malignancies. Among unvaccinated, a marginally protective effect was observed (OR 0.86, 95%CI 0.73-1.01), independent of age, immunosuppressive therapy, and diabetes. Adjustment for monoclonal antibody treatment strengthened the association (OR 0.81, 95%CI 0.68-0.96)., Conclusion: This study suggests that levels of anti-S antibodies can predict critical or fatal outcomes in COVID-19 pneumonia patients, regardless of vaccination. Whether anti-S Ab could guide risk assessment and vaccination boosting merits further evaluation., (© 2024. The Author(s).)

Purpose: It has been shown that lower Barthel's index (BI) at admission is associated with a higher in-hospital mortality. There is a lack of evidence regarding the association between the change in BI during hospitalization and mortality after discharge. Our purpose was to determine whether the BI change during hospitalization is associated with all-cause mortality in older adults with COVID-19 pneumonia., Patients and Methods: We conducted a retrospective cohort study of 330 participants at Peking University Third Hospital during the COVID-19 pandemic period. In order to analyze the time to death data, a Kaplan-Meier survival curve was used. We used restricted cubic splines to analyze the association between BI change and all-cause mortality among COVID-19 pneumonia patients aged over 80 years old. Threshold effect analysis was used to assess the ability of BI change score to predict all-cause mortality., Results: Our study included 330 patients aged over 80 years with COVID-19 pneumonia. The Kaplan-Meier curve for mortality showed significantly worst survival with reduced BI among three groups (χ 2 = 6.896, P < 0.05). There was a non-linear association between the BI change and all-cause mortality ( P for all over <0.001). The effect sizes on the left and right sides of the inflection point were 0.958 (HR: 0.958, 95% CI 0.932-0.958, P < 0.05) and 1.013 (HR: 1.013, 95% CI 0.967-1.062, P > 0.05), respectively., Conclusion: Reduced BI during hospitalization was associated with the highest mortality risk. It is crucial to monitor BI change among COVID-19 pneumonia patients aged over 80 years old., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Hao et al.)

Introduction: Infection with SARS-CoV-2 virus may result in long COVID, a syndrome characterized by symptoms such as dyspnea, cardiac abnormalities, cognitive impairment, and fatigue. One potential explanation for these symptoms is hypocortisolism., Objective: To evaluate the prevalence of hypocortisolism in patients with a history of COVID-19 pneumonia., Methods: Cross-sectional study of patients who were aged ≥18 years and had a 3-month history of radiography-confirmed COVID-19 pneumonia. Exclusion criteria included current or previous treatment with glucocorticoids and use of an oral contraceptive. Adrenal function was evaluated using a low dose (1ug) corticotropin stimulation test (CST). Serum cortisol levels were measured at 0, 30, and 60 minutes, and baseline plasma ACTH was also measured., Results: Of the 41 patients enrolled, the median age was 62 years, 17 (42%) were female, and all 41 (100%) had severe pneumonia at baseline. Eleven patients (27%) had hypocortisolism, as evidenced by peak cortisol of less than 402.81 nmol/l after low dose (1 µg) CST. Of these 11 patients, 10 (91%) had secondary hypocortisolism (median ACTH 6.27 pmol/L, range 4.98-9.95 pmol/L) and one had primary hypocortisolism (mean ACTH 32.78 pmol/L). Six of the 11 patients with hypocortisolism (54.5%) reported symptoms of persistent fatigue and 5 (45.5%) required regular glucocorticoid replacement., Conclusions: Our results suggest that hypocortisolism, predominantly caused by pituitary disruption, may emerge after SARS-CoV-2 infection and should be considered in patients with a history of COVID-19 pneumonia with or without clinical hypocortisolism., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Porntharukchareon, Dechates, Sirisreetreerux, Therawit and Tawinprai.)

Coronavirus disease 2019 (COVID-19) pneumonia has had catastrophic effects worldwide. Radiology, in particular computed tomography (CT) imaging, has proven to be valuable in the diagnosis, prognostication, and longitudinal assessment of those diagnosed with COVID-19 pneumonia. This article will review acute and chronic pulmonary radiologic manifestations of COVID-19 pneumonia with an emphasis on CT and also highlighting histopathology, relevant clinical details, and some notable challenges when interpreting the literature., Competing Interests: Disclosure Nothing to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background and Objectives : Amidst the COVID-19 pandemic, concerns about the psychological impact of disease-related anxiety on public health have risen. This study aims to compare general and death anxiety levels between acute coronary artery syndrome and COVID-19 pneumonia patients. Materials and Methods : A cross-sectional study of 132 individuals, including acute myocardial infarction (MI), COVID-19 pneumonia patients, and healthy volunteers from Trakya University Hospital (Turkey), was analyzed. Validated scales like the Beck Anxiety Inventory (BAI), Coronavirus Anxiety Scale Short Form, and Thorson-Powell Death Anxiety Scale (TPDAS) were employed. Demographic data such as age, gender, income levels, employment status, presence of a close relative with COVID-19, and whether participants followed COVID-19-related news were collected and compared across groups with significance level of 0.05 set for all analyses. Results : Among 41 COVID-19, 41 MI, and 50 healthy subjects, the pneumonia group showed highest COVID-19 anxiety ( p = 0.01) and BAI scores ( p = 0.008). Both COVID-19 and MI patients had significantly higher BAI and TPDAS scores compared to healthy controls ( p < 0.001). Factors like female gender ( p = 0.004), low education ( p = 0.003), current employment ( p = 0.008), and low income ( p = 0.002) correlated with higher BAI scores. Low income ( p = 0.001) and COVID-19 news exposure ( p = 0.002) correlated with higher TPDAS scores. Males and married patients had lower anxiety scores ( p = 0.008). High income, education, and employment reduced anxiety levels ( p = 0.008). TPDAS scores decreased with higher income ( p = 0.001), but increased in the MI group ( p = 0.002) with COVID-19 news exposure. The multivariate linear regression analysis found that MI and COVID-19 pneumonia were associated with TPDAS; female gender, university education, and COVID-19 pneumonia with the Beck scale; and COVID-19 pneumonia with anxiety scores on the COVID-19 Anxiety scale. Conclusions : This research showcases differing anxiety patterns between illnesses such as MI and COVID-19 pneumonia amidst the pandemic, emphasizing the amplifying influence of media coverage on death-related anxieties. It underscores the imperative of targeted interventions and socioeconomic considerations in managing psychological consequences and formulating responsive public health strategies.

We systematically reviewed radiological abnormalities in patients with prolonged SARS-CoV-2 infection, defined as persistently positive polymerase chain reaction (PCR) results for SARS-CoV-2 for > 21 days, with either persistent or relapsed symptoms. We extracted data from 24 patients (median age, 54.5 [interquartile range, 44-64 years]) reported in the literature and analyzed their representative CT images based on the timing of the CT scan relative to the initial PCR positivity. Our analysis focused on the patterns and distribution of CT findings, severity scores of lung involvement on a scale of 0-4, and the presence of migration. All patients were immunocompromised, including 62.5% (15/24) with underlying lymphoma and 83.3% (20/24) who had received anti-CD20 therapy within one year. Median duration of infection was 90 days. Most patients exhibited typical CT appearance of coronavirus disease 19 (COVID-19), including ground-glass opacities with or without consolidation, throughout the follow-up period. Notably, CT severity scores were significantly lower during ≤ 21 days than during > 21 days ( P < 0.001). Migration was observed on CT in 22.7% (5/22) of patients at ≤ 21 days and in 68.2% (15/22) to 87.5% (14/16) of patients at > 21 days, with rare instances of parenchymal bands in previously affected areas. Prolonged SARS-CoV-2 infection usually presents as migrating typical COVID-19 pneumonia in immunocompromised patients, especially those with impaired B-cell immunity., Competing Interests: Soon Ho Yoon has stocks and stock options of MEDICAL IP, outside this work. Other authors have no potential conflicts of interest to declare., (Copyright © 2024 The Korean Society of Radiology.)

Background: The antiviral drug Nirmatrelvir was found to be a key drug in controlling the progression of pneumonia during the infectious phase of COVID-19. However, there are very few options for effective treatment for cancer patients who have viral pneumonia. Glucocorticoids is one of the effective means to control pneumonia, but there are many adverse events. EGCG is a natural low toxic compound with anti-inflammatory function. Thus, this study was designed to investigate the safety and efficacy of epigallocatechin-3-gallate (EGCG) aerosol to control COVID-19 pneumonia in cancer populations., Methods: The study was designed as a prospective, single-arm, open-label phase I/II trial at Shandong Cancer Hospital and Institute, between January 5, 2023 to March 31,2023 with viral pneumonia on radiographic signs after confirmed novel coronavirus infection. These patients were treated with EGCG nebulization 10 ml three times daily for at least seven days. EGCG concentrations were increased from 1760-8817umol/L to 4 levels with dose escalation following a standard Phase I design of 3-6 patients per level. Any grade adverse event caused by EGCG was considered a dose-limiting toxicity (DLT). The maximum tolerated dose (MTD) is defined as the highest dose with less than one-third of patients experiencing dose limiting toxicity (DLT) due to EGCG. The primary end points were the toxicity of EGCG and CT findings, and the former was graded by Common Terminology Criteria for Adverse Events (CTCAE) v. 5.0. The secondary end point was the laboratory parameters before and after treatment., Result: A total of 60 patients with high risk factors for severe COVID-19 pneumonia (factors such as old age, smoking and combined complications)were included in this phase I-II study. The 54 patients in the final analysis were pathologically confirmed to have tumor burden and completed the whole course of treatment. A patient with bucking at a level of 1760 umol/L and no acute toxicity associated with EGCG has been reported at the second or third dose gradients. At dose escalation to 8817umol/L, Grade 1 adverse events of nausea and stomach discomfort occurred in two patients, which resolved spontaneously within 1 hour. After one week of treatment, CT showed that the incidence of non-progression of pneumonia was 82% (32/39), and the improvement rate of pneumonia was 56.4% (22/39). There was no significant difference in inflammation-related laboratory parameters (white blood cell count, lymphocyte count, IL-6, ferritin, C-reactive protein and lactate dehydrogenase) before and after treatment., Conclusion: Aerosol inhalation of EGCG is well tolerated, and preliminary investigation in cancer population suggests that EGCG may be effective in COVID-19-induced pneumonia, which can promote the improvement of patients with moderate pneumonia or prevent them from developing into severe pneumonia., Trial Registration: ClinicalTrials.gov Identifier: NCT05758571. Date of registration: 8 February 2023., (© 2024. The Author(s).)

Background: COVID-19 pneumonia causes hyperinflammatory response that culminates in acute respiratory syndrome (ARDS) related to increased multiorgan dysfunction and mortality risk. Antiviral-neutralizing immunoglobulins production reflect the host humoral status and illness severity, and thus, immunoglobulin (Ig) circulating levels could be evidence of COVID-19 prognosis., Methods: The relationship among circulating immunoglobulins (IgA, IgG, IgM) and COVID-19 pneumonia was evaluated using clinical information and blood samples in a COVID-19 cohort composed by 320 individuals recruited during the acute phase and followed up to 4 to 8 weeks (n = 252) from the Spanish first to fourth waves., Results: COVID-19 pneumonia development depended on baseline Ig concentrations. Circulating IgA levels together with clinical features at acute phase was highly associated with COVID-19 pneumonia development. IgM was positively correlated with obesity (ρb = 0.156, P = 0.020), dyslipemia (ρb = 0.140, P = 0.029), COPD (ρb = 0.133, P = 0.037), cancer (ρb = 0.173, P = 0.007) and hypertension (ρb = 0.148, P = 0.020). Ig concentrations at recovery phase were related to COVID-19 treatments., Conclusions: Our results provide valuable information on the dynamics of immunoglobulins upon SARS-CoV-2 infection or other similar viruses., (© 2024. The Author(s).)

The aim was to study the relationship between eye tracking (ET) parameters and cerebral tissue oxygen saturation (SctO 2 ) values in the acute period of moderate COVID-19 pneumonia., Materials and Methods: A single-centre, non-randomised study included 92 patients in the acute period of SARS-CoV-2 moderate pneumonia (Delta variant). The mean time from admission was 1.5 ± 0.9 days. M:49, W:43. The mean age was 34.7 ± 3.9 years. The eye vergence reactivity index (VRx) was determined using a mobile ET. The cerebral oximetry was performed using Fore-Sight 2030 and included the detection of the SctO 2 level in the frontal lobe (FLP) region. Statistical analysis was carried out using the methods of parametric statistics., Results: The calculated vertical VRx was 0.781 ± 0.118. The calculated horizontal VRx was 0.821 ± 0.107. SctO 2 in the FLP varied within the range from 61% to 73%. The average SctO2 values were 65.4 ± 5.2% over the left FLP and 66.2 ± 6.3% over the right FLP (p = 0.872). The regression analysis showed that HVRx and VVRx were correlated with SctO 2 levels in both FLPs (p = 0.035 and p = 0.034, respectively, and p = 0.040 and p = 0.049, respectively)., Conclusions: Cerebral oxygen saturation in moderate pneumonia caused by the SARS-CoV-2 coronavirus has a significant destabilising effect on the oculomotor synergy (VVRx and HVRx) (p < 0.05)., (© 2024. Oxygen Transport to Tissue International.)

Introduction: COVID-19 is considered a respiratory virosis in its classic form, although it may present with heterogeneous symptoms. Thoracic complications occur in a small percentage of patients. Our objective was to evaluate existing experience with this disease and its thoracic manifestations and to determine the real-world status of care of these patients., Methods: This study is a retrospective, single-institution analysis of a group of patients hospitalized with acute and post-acute COVID-19 pneumonia at Thomayer Hospital in Prague in the period from December 2020 to March 2022 and indicated for a thoracic surgical procedure., Results: During the peak of COVID-19 pandemic, a thoracic intervention was performed in 46 admitted patients. Thoracic drainage (due to pneumothorax in 18 cases, fluidothorax in 3 cases, CT-guided lung abscess drainage in 2 cases, and CT-guided pneumatocele drainage in 2 cases) were the most common thoracic surgical procedures. Pleurectomy/decortication surgery was done in 10 cases. Additionally, 12 lung parenchyma-sparing resections were performed, while lobectomy was required in 2 cases. Resection of postintubation tracheal stenosis due to a severe course of COVID-19 pneumonia was indicated in 2 patients., Conclusion: Even mild COVID-19 may cause a considerable morphological a functional alteration of the respiratory system. The most common complications of COVID-19 pneumonia that require a thoracic surgical intervention include pathologies associated with an air leak and accumulation of air (pneumothorax, pneumomediastinum and subcutaneous emphysema). The development of pulmonary necrosis, symptomatic bronchiectasis, pneumatocele, and bullous-fibrotic formations may result in pneumothorax, hemothorax or thoracic empyema in sporadic cases. An early thoracic surgical intervention to treat thoracic complications of COVID-19 pneumonia can improve the survival of COVID-19 patients.

Rationale and Objectives: The Omicron variant of COVID-19 is less severe than the ancestral strain, leading to the potential for deaths in patients infected with the virus but who die of other causes. This study evaluated the difference in rates of pneumonia among patients who died with SARS-CoV-2 infection in the ancestral vs Omicron eras., Materials and Methods: We identified patients who died within 30days of a positive SARS-CoV-2 test, from March 2020 through December 2022; variants were assigned based on the prevalent variant in the US at that time. We also obtained a control group from patients who died within 30days of a negative SARS-CoV-2 test in January 2022. The first CT after the test was reviewed in a blinded fashion and assigned a category from the RSNA Consensus Reporting Guidelines. The primary outcome was the difference in rates of positive (typical or indeterminate) COVID-19 findings in the ancestral vs Omicron eras., Results: A total of 598 patients died during the ancestral era and 400 during the Omicron era, and 347 decedents comprised the control group. The rate of positive COVID-19 findings was 67/81 (83%) in the ancestral era and 43/81 (53%) in the Omicron era (P < .001), an absolute difference of 30% (95% CI 16%-43%). The rate of positive findings in the control group was 23/76 (30%)., Conclusion: During the Omicron era, 30% fewer SARS-CoV-2-associated deaths were associated with COVID-19 pneumonia and were caused either by nonpulmonary effects of the infection or were unrelated to the infection., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Mark Hammer reports a relationship with Radiological Society of North America that includes: board membership. Mark Hammer reports a relationship with National Cancer Institute that includes: funding grants., (Copyright © 2023 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Reduced diffusion capacity (DLCO) after COVID 19 pneumonia was reported in hospitalised patients after discharge. Here, we studied the restoration of DLCO over a 24 months period in COVID-19 pneumonia survivors ( n = 317), who were categorised into "moderate" cases (no oxygen supply; no need for hospitalisation), "severe" cases (respiratory frequency > 30/min and/or peripheral oxygen SpO2 < 93%), and "critical" cases (respiratory failure and admission into the intensive care unit). COVID-19 pneumonia survivors with a decreased DLCO (<80%) at 3 months ( n = 133) were invited for 6- and 24-months follow-up. At 3 months, impairment of DLCO was more severe in critical case ( p < .01). Over time, the subgroups showed a similar level of improvement; and, there was no difference in recovery over time between the subgroups. At 24 months, the DLCO did not differ between the subgroups, with a mean DLCO of 73% for all patients. At 24 months, 65% of patients still had a DLCO < 80%, and in 40% of patients DLCO was <70% of predicted. Regardless the initial disease severity, all COVID-19 survivors showed improvement in DLCO during follow-up; however, DLCO had not normalised in the majority of patients with a DLCO <80% 3 months after hospital discharge., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: To evaluate the implementation of an antibiotic stewardship program in critically ill COVID-19 patients and to establish risk factors for coinfection. Secondary objective was to analyze the evolution of the etiology of respiratory nosocomial infections., Methods: Single-center observational cohort study of consecutive patients admitted to ICU due to COVID-19 pneumonia from March 2020 to October 2022. An antibiotic stewardship program was implemented at the end of the second wave., Results: A total of 878 patients were included during 6 pandemic waves. Empirical antibiotic consumption decreased from the 96% of the patients during the first pandemic wave, mainly in combination (90%) to the 30% of the patients in the 6th pandemic wave most in monotherapy (90%). There were not differences in ICU and Hospital mortality between the different pandemic periods. In multivariate analysis, SOFA at admission was the only independent risk factor for coinfection in critically ill COVID-19 patients (OR 1,23 95%CI 1,14 to 1,35). Differences in bacterial etiology of first nosocomial respiratory infection were observed. There was a progressive reduction in Enterobacteriaceae and non- fermentative Gram Negative Bacilli as responsible pathogens, while methicillin-sensitive Staphylococcus aureus increased during pandemic waves. In the last wave, however, a trend to increase of potentially resistant pathogens was observed., Conclusions: Implementation of an antibiotic stewardship program was safe and not associated with worse clinical outcomes, being severity at admission the main risk factor for bacterial coinfection in covid-19 patients. A decline in potentially resistant pathogens was documented throughout the pandemic., (Copyright © 2023. Published by Elsevier B.V.)

Background: Persistence of breathlessness after recovery from SARS-CoV-2 pneumonia is frequent. Recovery from acute respiratory failure (ARF) is usually determined by normalized arterial blood gases (ABGs), but the prevalence of persistent exercise-induced desaturation (EID) and dyspnea is still unknown., Methods: We investigated the prevalence of EID in 70 patients with normal arterial oxygen at rest after recovery from ARF due to COVID-19 pneumonia. Patients underwent a 6-min walking test (6MWT) before discharge from hospital. We recorded dyspnea score and heart rate during 6MWT. We also investigated the possible role of lung ultrasound (LU) in predicting EID. Patients underwent a LU scan and scores for each explored area were summed to give a total LU score., Results: In 30 patients (43%), oxygen desaturation was >4% during 6MWT. These patients had significantly higher dyspnea and heart rate compared to non-desaturators. LU score >8.5 was significantly able to discriminate patients with EID., Conclusion: In SARS-CoV-2 pneumonia, ABGs at discharge cannot predict the persistence of EID, which is frequent. LU may be useful to identify patients at risk who could benefit from a rehabilitation program., Competing Interests: Conflicts of 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 © 2021 Sociedade Portuguesa de Pneumologia. Published by Elsevier España, S.L.U. All rights reserved.)

Background: Chest radiography (CXR) is an adjunct tool in treatment planning and monitoring of the disease course of COVID-19 pneumonia. The purpose of the study was to describe the radiographic patterns and severity scores of abnormal CXR findings in children diagnosed with COVID-19 pneumonia., Methods: This retrospective study included children with confirmed COVID-19 by reverse transcriptase-polymerase chain reaction test who underwent CXR at the arrival. The CXR findings were reviewed, and modified radiographic scoring was assessed., Results: The number of abnormal CXR findings was 106 of 976 (10.9%). Ground-glass opacity (GGO) was commonly found in children aged > 9 years (19/26, 73.1%), whereas peribronchial thickening was predominantly found in children aged < 5 years (25/54, 46.3%). Overall, the most common radiographic finding was peribronchial thickening (54/106, 51%). The lower lung zone (56/106, 52.8%) was the most common affected area, and there was neither peripheral nor perihilar predominance (84/106, 79.2%). Regarding the severity of COVID-19 pneumonia based on abnormal CXR findings, 81 of 106 cases (76.4%) had mild lung abnormalities. Moderate and severe lung abnormalities were found in 21 (19.8%) and 4 (3.8%) cases, respectively. While there were no significant differences in the radiographic severity scores among the various pediatric age groups, there were significant disparities in severity scores in the initial CXR and medical treatments., Conclusions: This study clarified the age distribution of radiographic features across the pediatric population. GGO was commonly found in children aged > 9 years, whereas peribronchial thickening was predominant in children aged < 5 years. The lower lung zone was the most common affected area, and the high severity lung scores required more medical treatments and oxygen support., (© 2023. The Author(s).)

Background: Immune checkpoint inhibitors (ICIs) are commonly used to treat lung cancer patients, but their use can lead to immune-related adverse events (irAEs), which pose a challenge for treatment strategies. The impact of irAEs on the incidence of COVID-19 pneumonia in lung cancer patients during the ongoing COVID-19 pandemic is unclear. This study aims to investigate the association between irAEs and COVID-19 pneumonia in lung cancer patients receiving ICIs., Methods: We conducted a cross-sectional study of lung cancer patients who received ICIs and were infected with COVID-19 due to the Omicron variant between December 2022 and February 2023 in China. We collected data on irAEs and COVID-19 outcomes. Logistic regression analyses were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between irAEs and the incidence of COVID-19 pneumonia., Results: A total of 193 patients were enrolled, with 72 patients (37.30%) in the irAEs group and 121 patients (62.70%) in the non-irAEs group. Twenty-six patients (13.47%) developed COVID-19 pneumonia and 6 patients (3.11%) progressed to severe cases after COVID-19 infection. Multivariate logistic regression showed that the lung cancer patients who experienced irAEs was significantly associated with a higher incidence rate of COVID-19 pneumonia (OR = 9.56, 95%CI: 2.21-41.33; P = 0.0025)., Conclusion: Our study suggests that lung cancer patients receiving ICIs and experiencing irAEs may have a higher risk of developing COVID-19 pneumonia due to the Omicron variant. Therefore, close monitoring of these patients during the COVID-19 pandemic is necessary to mitigate this risk., (© 2023. The Author(s).)

Background and Objectives: Krebs von den Lungen-6 (KL-6), expressed by damaged type II pneumocytes, is useful in the diagnosis and severity assessment of many diffuse interstitial lung diseases. The objective of our study was to determine the prognostic value of the initial KL-6 plasma level in COVID-19 pneumonia., Methods: All patients hospitalized for a suspected COVID-19 pneumonia between March and May 2020 in our Chest department of a French university hospital were included. KL-6 serum concentrations were measured within 72 h of diagnostic suspicion by chemiluminescence enzyme immunoassay Survival analysis was performed using a Cox regression and modeled by a Kaplan-Meier curve., Results: Sixty-six COVID-19 patients (average age = 64 ± 14 years, 71.2 % males) with KL-6 serum measurement were included. Median KL-6 serum concentration was 409 ± 312 U/mL. KL-6 was significantly higher in men (p = 0.003), elders (p = 0.0001) and in patients with greater Charlson's score (p = 0.002). Higher KL-6 concentration was significantly associated with in-hospital mortality (HR: 8.66; 95 % CI:1.1-69.2, p = 0.014), radiological extension of lesions on chest CT scan (p = 0.004) and higher WHO severity score (p = 0.042), but not with admission in intensive care unit. In 9 (14 %) non-surviving COVID-19 patients, KL-6 serum concentration increased whereas it remained stable or decreased in survivors. At 3 months follow-up (n = 48), DLCO was negatively correlated with the initial KL-6 value (r = 0.47, p = 0.001), while FVC, FEV1 and MRC score were not., Conclusion: Initial KL-6 serum concentration is significantly associated with in-hospital mortality, unfavorable outcome, and persistent impairment of DLCO at 3 months. Initial KL-6 plasma determination appears as a prognostic biomarker in COVID-19 pneumonia., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2023 SPLF and Elsevier Masson SAS. All rights reserved.)

Background: Soluble suppressor of tumorigenicity-2 (sST2) is a biomarker for heart failure and pulmonary injury. We hypothesize that sST2 could help predict severity of SARS-CoV-2 infections., Methods: sST2 was analyzed in patients consecutively admitted for SARS-CoV-2 pneumonia. Other prognostic markers were also measured. In-hospital complications were registered, including death, ICU admission, and respiratory support requirements., Results: 495 patients were studied (53% male, age: 57.6±17.6). At admission, median sST2 concentrations was 48.5ng/mL [IQR, 30.6-83.1ng/mL] and correlated with male gender, older age, comorbidities, other severity biomarkers, and respiratory support requirements. sST2 levels were higher in patients who died (n=45, 9.1%) (45.6 [28.0, 75.9]ng/mL vs. 144 [82.6, 319] ng/mL, p<0.001) and those admitted to ICU (n=46, 9.3%) (44.7 [27.5, 71.3] ng/mL vs. 125 [69.0, 262]ng/mL, p<0.001). sST2 levels>210ng/mL were a strong predictor of complicated in-hospital courses, with higher risk of death (OR, 39.3, CI95% 15.9, 103) and death/ICU (OR 38.3, CI95% 16.3-97.5) after adjusting for all other risk factors. The addition of sST2 enhanced the predictive capacity of mortality risk models., Conclusions: sST2 represents a robust severity predictor in COVID-19 and could be an important tool for identifying at-risk patients who may benefit from closer follow-up and specific therapies., (Copyright © 2023 Elsevier España, S.L.U. All rights reserved.)

Background: High drive and high effort during spontaneous breathing can generate patient self-inflicted lung injury (P-SILI) due to uncontrolled high transpulmonary and transvascular pressures, with deterioration of respiratory failure. P-SILI has been demonstrated in experimental studies and supported in recent computational models. Different treatment strategies have been proposed according to the phenotype of elastance of the respiratory system (Ers) for patients with COVID-19. This study aimed to investigate the effect of three spontaneous ventilation modes on respiratory drive and muscle effort in clinical practice and their relationship with different phenotypes. This was achieved by obtaining the following respiratory signals: airway pressure (Paw), flow (V´) and volume (V) and calculating muscle pressure (Pmus)., Methods: A physiologic observational study of a series of cases in a university medical-surgical ICU involving 11 mechanically ventilated patients with COVID-19 pneumonia at the initiation of spontaneous breathing was conducted. Three spontaneous ventilation modes were evaluated in each of the patients: pressure support ventilation (PSV), airway pressure release ventilation (APRV), and BiLevel positive airway pressure ventilation (BIPAP). Pmus was calculated through the equation of motion. For this purpose, we acquired the signals of Paw, V´ and V directly from the data transmission protocol of the ventilator (Dräger). The main physiological measurements were calculation of the respiratory drive (P0.1), muscle effort through the ΔPmus, pressure‒time product (PTP/min) and work of breathing of the patient in joules multiplied by respiratory frequency (WOBp, J/min)., Results: Ten mechanically ventilated patients with COVID-19 pneumonia at the initiation of spontaneous breathing were evaluated. Our results showed similar high drive and muscle effort in each of the spontaneous ventilatory modes tested, without significant differences between them: median (IQR): P0.1 6.28 (4.92-7.44) cm H 2 O, ∆Pmus 13.48 (11.09-17.81) cm H 2 O, PTP 166.29 (124.02-253.33) cm H 2 O*sec/min, and WOBp 12.76 (7.46-18.04) J/min. High drive and effort were found in patients even with low Ers. There was a significant relationship between respiratory drive and WOBp and Ers, though the coefficient of variation widely varied., Conclusions: In our study, none of the spontaneous ventilatory methods tested succeeded in reducing high respiratory drive or muscle effort, regardless of the Ers, with subsequent risk of P-SILI., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Cell and cytokine analyses from bronchoalveolar lavage (BAL) in non-critically ill patients with COVID-19 pneumonia are poorly described. This study focused on patients hospitalized in the non-intensive care unit for either suspected COVID-19 pneumonia or persistent respiratory symptoms following proven COVID-19 pneumonia. Overall, 54 patients who underwent BAL between April 2020 and February 2021 for suspected or follow-up of proven COVID-19 pneumonia were included. Based on SARS-CoV-2 polymerase chain reaction test results and clinical follow-up, three pulmonary disease groups were defined: non-COVID-19 (n = 20), acute COVID-19 (n = 13), and post-COVID-19 (n = 24) pneumonia patients. Cytological and cytokine analyses were performed on BAL fluid (IL-1β, IL-6, IL-8, IL-10, TNF-α, IFN-γ, HGF, and TGF-β), with investigators blinded to the patient groups. Lymphocytic alveolitis with plasmocytes was observed in acute COVID-19 pneumonia, returning to normal post-COVID-19. The highest cytokine levels were observed in COVID-19 patients, with significantly increased IFN-γ, IL-10, and HGF levels compared to non-COVID-19 patients, while significantly decreased IL-6, IL-8, IL-10, IFN-γ, TNF-α, and HGF levels were noted in post-COVID-19 patients. In COVID-19 patients, correlations between IL-10, TNF-α and IFN-γ concentrations were found. Lymphocytic alveolitis with plasmacytosis was found in non-critical COVID-19 pneumonia This alveolitis is associated with the presence of IL-6, IL-8, IL-10, TNF-α, IFN-γ and HGF. Alveolitis and cytokines levels decreased in post-COVID-19 pneumonia., (© 2023. The Author(s), under exclusive licence to Società Italiana di Medicina Interna (SIMI).)

Purpose: To assess the efficacy of lung low-dose radiotherapy (LD-RT) in the treatment of patients with COVID-19 pneumonia., Materials and Methods: Ambispective study with two cohorts to compare treatment with standard of care (SoC) plus a single dose of 0.5 Gy to the whole thorax (experimental prospective cohort) with SoC alone (control retrospective cohort) for patients with COVID-19 pneumonia not candidates for admission to the intensive care unit (ICU) for mechanical ventilation., Results: Fifty patients treated with LD-RT were compared with 50 matched controls. Mean age was 85 years in both groups. An increase in arterial oxygen partial pressure (PaO 2 )/fraction of inspired oxygen (PAFI) in the experimental LD-RT-treated group compared to the control group could not be found at 48 h after LD-RT, which was the primary endpoint of the study. However, PAFI values significantly improved after 1 month (473 vs. 302 mm Hg; p < 0.0001). Pulse oxymetric saturation/fraction of inspired oxygen (SAFI) values were also significantly higher in LD-RT-treated patients than in control patients at 1 week (405 vs. 334 mm Hg; p = 0.0157) and 1 month after LD-RT (462 vs. 326 mm Hg; p < 0.0001). All other timepoint measurements of the respiratory parameters were similar across groups. Patients in the experimental group were discharged from the hospital significantly earlier (23 vs. 31 days; p = 0.047). Fifteen and 26 patients died due to COVID-19 pneumonia in the experimental and control cohorts, respectively (30% vs. 48%; p = 0.1). LD-RT was associated with a decreased odds ratio (OR) for 1‑month COVID-19 mortality (OR = 0.302 [0.106-0.859]; p = 0.025) when adjusted for potentially confounding factors. Overall survival was significantly prolonged in the LD-RT group compared to the control group (log-rank p = 0.027). No adverse events related to radiation treatment were observed., Conclusion: Treatment of frail patients with COVID-19 pneumonia with SoC plus single-dose LD-RT of 0.5 Gy improved respiratory parameters, reduced the period of hospitalization, decreased the rate of 1‑month mortality, and prolonged actuarial overall survival compared to SoC alone., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection is silent or benign in most infected individuals, but causes hypoxemic COVID-19 pneumonia in about 10% of cases. We review studies of the human genetics of life-threatening COVID-19 pneumonia, focusing on both rare and common variants. Large-scale genome-wide association studies have identified more than 20 common loci robustly associated with COVID-19 pneumonia with modest effect sizes, some implicating genes expressed in the lungs or leukocytes. The most robust association, on chromosome 3, concerns a haplotype inherited from Neanderthals. Sequencing studies focusing on rare variants with a strong effect have been particularly successful, identifying inborn errors of type I interferon (IFN) immunity in 1-5% of unvaccinated patients with critical pneumonia, and their autoimmune phenocopy, autoantibodies against type I IFN, in another 15-20% of cases. Our growing understanding of the impact of human genetic variation on immunity to SARS-CoV-2 is enabling health systems to improve protection for individuals and populations.

Background: Coronavirus disease 2019 (COVID-19)-associated mortality is predominantly due to respiratory failure. However, risk factors and predictive models for disease progression in patients with COVID-19 are not consistent across the globe. In this study, we aimed to assess the risk factors associated with intensive care (ICU) admission and mortality in patients with COVID-19 pneumonia., Methods: Information was retrieved from the database of all patients admitted with COVID-19 pneumonia between March 2020 and July 2020 at a tertiary care center in Saudi Arabia. The patients' demographic, clinical, laboratory and radiological characteristics were analyzed., Results: Of 1054 patients admitted with PCR proven COVID-19, 254 patients (24%) with radiological evidence of pneumonia were enrolled. The median age was 55, with 25.6% above 65 years and 55.1% males. The comorbidities included hypertension (45%), diabetes (43%), dyslipidemia (24%), solid organ and bone marrow transplantation (14.5%), malignancy (13.4%), ischemic heart disease (10.6%) and chronic kidney disease (9.4%). The mortality rate was 4.7%, and 22.8% were admitted to the ICU. The risk factors for ICU admission were> 65 years of age (RR: 1.74, CI 95%, 1.10-2.74, p = 0.017), diabetes melitus (RR: 1.66, CI 95% 1.06-2.62, p = 0.028), heart failure (RR: 2.51, CI 95%, 1.28-4.93, p = 0.007), respiratory rate> 25 (RR: 2.75, CI 95%, 1.66-4.55, p < 0.001), upper lobe involvement (RR: 1.68, CI 95%, 1.02-2.77, p = 0.043), and C-reactive protein (CRP)> 140 (RR: 1.89, CI 95%, 1.14-3.13, p = 0.013). The risk factors for mortality were> 65 years of age (RR: 5.82, CI 95%, 1.81-18.68, p = 0.003), upper lobe involvement on chest radiography (RR:4.40, CI 95%, 1.22-15.86, p = 0.016), diffuse chest computed tomography changes (RR: 7.36, CI 95%, 2.31-23.46, p < 0.011), ischemic heart disease (RR: 4.20, CI 95%, 1.36-13.04, p = 0.028), chronic kidney disease (RR: 6.85, CI 95%, 2.35-19.90, p < 0.003), cerebrovascular disease (RR:13.61, CI 95%, 5.01-36.96 p < 0.001), respiratory rate> 25 (RR: 3.94, CI 95%, 1.32-11.78 p = 0.023), oxygen saturation< 90% on admission (RR: 12.19, CI 95%, 3.71-40.01, p < 0.001), thrombocytopenia (RR:4.16, CI 95%, 1.37-12.64, p = 0.013), and elevated troponin (RR: 6.20, CI 95%, 1.73-22.24, p = 0.003)., Conclusions: In this study, nearly a quarter of the patients with COVID-19 pneumonia required intensive care. We identified several risk factors associated with ICU admission and mortality that may be useful for predicting, triaging, and managing COVID-19 pneumonia patients. However, these findings need to be validated prospectively., Competing Interests: Declaration of Competing Interest Authors declare that they have no interest to declare., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

The rate of thrombotic complications in COVID-19 patients is high and could be associated with the risk of unfavourable outcomes. Moreover, pulmonary thrombotic events can occur even in patients already on anticoagulant treatment. We present the case of a patient with severe COVID-19 pneumonia, without traditional risk factors for thrombosis, who developed massive pulmonary thrombosis (PT) despite therapeutic anticoagulation. The diagnosis was challenging, and the case raised concerns about the protective role of conventional anticoagulant treatment in COVID-19 pneumonia. Thus, we searched for literature reports on COVID-19 patients who developed PT despite being under anticoagulation therapy. We identified 13 cohort studies including 4058 patients of which 346 (8.5%) developed PT and nine case reports/series enrolling 14 patients. Four cohorts were further analysed, which reported data on risk factors for thrombosis, outcomes and biological characteristics. We found that there were no differences between patients with and without PT regarding the classical risk factors for thrombosis. PT occurred regardless of the anticoagulation regimen, and the risk factor identified was severe COVID-19 pneumonia and a stay in an intensive care unit (ICU). Pulmonary thrombotic events in patients with COVID-19 are rather inflammation-related than correlated with traditional thromboembolic risk factors, and the therapeutic approach must take into consideration this aspect.

Background: Remdesivir is widely used for treatment of SARS-CoV-2 pneumonia. The aim of this study was to evaluate the characteristics of patients with moderate-to-severe COVID-19 treated with remdesivir, and their outcomes during hospitalization., Methods: This retrospective observational multicenter study included consecutive patients, hospitalized for moderate-to-severe COVID-19 (September 2020-September 2021), who were treated with remdesivir., Results: One thousand four patients were enrolled, all with onset of symptoms occurring less than 10 days before starting remdesivir; 17% of patients had 4 or more concomitant diseases. Remdesivir was well tolerated, adverse drug reactions (ADRs) being reported in 2.3% of patients. In-hospital death occurred in 80 patients (8.0%). The median timing of the first remdesivir dose was 5 days after symptom onset. The following endpoints did not differ according to the time span from the onset of symptoms to the first dose: length of hospitalization, in-hospital death, composite outcome (in-hospital death and/or endotracheal intubation). Advanced age, number of comorbidities ≥ 4, and severity of respiratory failure at admission were associated with poor in-hospital outcomes., Conclusion: In a real-world setting, remdesivir proved to be a safe and well-tolerated treatment for moderate-to-severe COVID-19. In patients receiving remdesivir less than 3 or 5 days from the onset of SARS-CoV-2 symptoms, mortality and the need for mechanical ventilation did not differ from the rest of the sample., (© 2023. The Author(s).)

Background Radiological lung sequelae may explain the persistence of respiratory complaints in post-COVID-19 condition (long-COVID). Purpose To perform a systematic review and meta-analysis of the prevalence and type of COVID-19 residual lung abnormalities at 1-year chest CT. Materials and Methods A literature search of PubMed, Web of Science, Embase, and Medline databases was performed from January 2020 to January 2023. Full-text reports of CT lung sequelae in adults (≥18 years) with confirmed COVID-19 at 1-year follow-up were included. The prevalence of any residual lung abnormality and type (fibrotic or not) was analyzed according to the Fleischner Glossary. The meta-analysis included studies with chest CT data assessable in no less than 80% of individuals. A random-effects model was used to estimate pooled prevalence. Multiple sub-group (country, journal category, methodological quality, study setting, outcomes) and meta-regression analyses were performed to identify potential sources of heterogeneity. I 2 statistics estimated low (25%), moderate (26-50%) and high (>50%) heterogeneity. 95% Prediction Intervals (95% PIs) were computed to describe the expected estimates range. Results Of 22 709 records, 21 studies were reviewed (20 prospective, 9 from China, and 7 in radiology journals). The meta-analysis included 14 studies with chest CT data in 1854 of 2043 individuals (M/F: 1109/934). Estimates of lung sequelae were highly heterogeneous (7.1-96.7%), with a pooled frequency of 43.5% (I 2 =94%; 95% PI: 5.9%, 90.4%). This also applied to single non-fibrotic changes, including ground glass opacity, consolidations, nodules/masses, parenchymal bands, and reticulations. The prevalence range of fibrotic traction bronchiectasis/bronchiolectasis was 1.6-25.7% (I 2 =93%; 95% PI: 0.0%, 98.6%;); honeycombing was unremarkable (0-1.1%; I 2 =58%; 95% PI: 0%, 60%). Lung sequelae were unrelated to any characteristics of interest. Conclusion The prevalence of COVID-19 lung sequelae at 1-year chest CT is highly heterogeneous among studies. Heterogeneity determinants remain unknown suggesting caution in data interpretation with no convincing evidence. PROSPERO (CRD42022341258) Keywords: COVID-19 pneumonia, pulmonary fibrosis, chest CT, long-COVID, systematic review, metaanalysis See also the editorial by Parraga and Svenningsen in this issue.

Objectives: High flow nasal cannula (HFNC) is frequently used in patients with acute respiratory failure, but there is limited evidence regarding predictors of therapeutic failure. The objective of this study was to assess diaphragmatic ultrasound criteria as predictors of failure to HFNC, defined as the need for orotracheal intubation or death., Methods: Prospective cohort study including adult patients consecutively admitted to the critical care unit, from July 24 to October 20, 2020, with respiratory failure secondary to SARS-CoV-2 pneumonia who required HFNC. After 12 hours of HFNC initiation we measured ROX index (ratio of SpO 2 /FiO 2 to respiratory rate), excursion and diaphragmatic contraction speed (diaphragmatic excursion/inspiratory time) by ultrasound, both in supine and prone position., Results: In total, 41 patients were analyzed, 25 succeeded and 16 failed HFNC therapy. At 12 hours, patients who succeeded HFNC therapy presented higher ROX index in supine position (9.8 [9.1-15.6] versus 5.4 [3.9-6.8], P < .01), and higher PaO 2 /FiO 2 ratio (186 [135-236] versus 117 [103-162] mmHg, P = .03). To predict therapeutic failure, the supine diaphragmatic contraction speed presented sensitivity of 89% and a specificity of 57%, while the ROX index presented a sensitivity of 92.8% and a specificity of 75%., Conclusions: Diaphragmatic contraction speed by ultrasound emerges as a diagnostic complement to clinical tools to predict HFNC success. Future studies should confirm these results., (© 2022 American Institute of Ultrasound in Medicine.)

Alveolar type II (ATII) pneumocytes as defenders of the alveolus are critical to repairing lung injury. We investigated the ATII reparative response in coronavirus disease 2019 (COVID-19) pneumonia, because the initial proliferation of ATII cells in this reparative process should provide large numbers of target cells to amplify severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus production and cytopathological effects to compromise lung repair. We show that both infected and uninfected ATII cells succumb to tumor necrosis factor-α (TNF)-induced necroptosis, Bruton tyrosine kinase (BTK)-induced pyroptosis, and a new PANoptotic hybrid form of inflammatory cell death mediated by a PANoptosomal latticework that generates distinctive COVID-19 pathologies in contiguous ATII cells. Identifying TNF and BTK as the initiators of programmed cell death and SARS-CoV-2 cytopathic effects provides a rationale for early antiviral treatment combined with inhibitors of TNF and BTK to preserve ATII cell populations, reduce programmed cell death and associated hyperinflammation, and restore functioning alveoli in COVID-19 pneumonia., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: The optimal time to intubate patients with SARS-CoV-2 pneumonia has not been adequately determined. While the use of non-invasive respiratory support before invasive mechanical ventilation might cause patient-self-induced lung injury and worsen the prognosis, non-invasive ventilation (NIV) is frequently used to avoid intubation of patients with acute respiratory failure (ARF). We hypothesized that delayed intubation is associated with a high risk of mortality in COVID-19 patients., Methods: This is a secondary analysis of prospectively collected data from adult patients with ARF due to COVID-19 admitted to 73 intensive care units (ICUs) between February 2020 and March 2021. Intubation was classified according to the timing of intubation. To assess the relationship between early versus late intubation and mortality, we excluded patients with ICU length of stay (LOS) < 7 days to avoid the immortal time bias and we did a propensity score and a cox regression analysis., Results: We included 4,198 patients [median age, 63 (54‒71) years; 71% male; median SOFA (Sequential Organ Failure Assessment) score, 4 (3‒7); median APACHE (Acute Physiology and Chronic Health Evaluation) score, 13 (10‒18)], and median PaO 2 /FiO 2 (arterial oxygen pressure/ inspired oxygen fraction), 131 (100‒190)]; intubation was considered very early in 2024 (48%) patients, early in 928 (22%), and late in 441 (10%). ICU mortality was 30% and median ICU stay was 14 (7‒28) days. Mortality was higher in the "late group" than in the "early group" (37 vs. 32%, p < 0.05). The implementation of an early intubation approach was found to be an independent protective risk factor for mortality (HR 0.6; 95%CI 0.5‒0.7)., Conclusions: Early intubation within the first 24 h of ICU admission in patients with COVID-19 pneumonia was found to be an independent protective risk factor of mortality., Trial Registration: The study was registered at Clinical-Trials.gov (NCT04948242) (01/07/2021)., (© 2023. The Author(s).)

Introduction: whilst many studies have focused on acute and chronic complications of COVID-19, few studies have been performed on the immediate post-acute COVID-19 phase complications. The objective of the study was to describe computed tomography (CT) imaging findings in patients from a South African (SA) cohort during the post-acute COVID-19 phase. To describe the findings using existing CT description systems and, if present, pulmonary imaging findings unique to our cohort., Methods: a review of CT chest examinations performed over the second wave of COVID-19 in SA for post-acute COVID-19 cardiorespiratory complaints at Worcester Hospital. The CT findings were described using a modified semi-quantitative tabulation method., Results: eight males and 12 females met the inclusion criteria with a mean age of 56 years. Half had hypertension, 11 had diabetes, two had human immunodeficiency virus (HIV), half had raised D-dimers and six had pre-existing lung disease. The predominant parenchymal pattern was mixed ground glass and reticular changes in a diffuse/peripheral multilobar distribution with relative sparing of the left upper lobe. Four cases demonstrated pulmonary emboli, 50% pulmonary hypertension, three pleural effusions and nine lymphadenopathy. None of the cases had evidence of active pulmonary tuberculosis., Conclusion: CT lung findings appear to mirror global findings with expected evolutionary differences. An interesting observation was the relative sparing of the left upper lobe. Reporting using the modified table proved efficient. Real-world extrapolation of our findings is limited by low-case numbers., Competing Interests: The authors declare no competing interests., (Copyright: Pieter Barend Kotzé et al.)

COVID-19 is often associated with long-lasting pulmonary symptoms. Data are scarce about interstitial lung disease (ILD) in patients following COVID-19 hospitalization with persistent symptoms. We retrospectively reviewed all cases sent to pulmonary post-COVID evaluation due to persistent symptoms between February 2021 and February 2022 (N = 318). All patients with suspected ILD (N = 44) were reviewed at the multidisciplinary discussion. Patient characteristics, symptoms, time since hospitalization, detailed lung function measurements and 6-min walk test (6MWT) were evaluated. The post-COVID ILD suspected group included more men (68.2 vs. 31.8%) with significantly older age compared to the control group (64.0 ± 12.3 vs. 51.3 ± 14.9 years). Most patient needed hospital care for COVID-19 pneumonia (68.6% of all patients and 84.1% of ILD suspected group) and average time since hospitalization was 2.4 ± 2.3 months. Persisting symptoms included fatigue (34%), dyspnoea (25.2%), cough (22.6%), and sleep disorders (insomnia 13.2%; sleepiness 8.2%). Post-COVID ILD presented more often with new symptoms of cough and sleepiness. Functional impairment, especially decreased walking distance and desaturation during 6-min walk test (6MWT) were detected in the ILD-suspected group. Respiratory function test in the post-COVID ILD group showed slight restrictive ventilatory pattern (FVC: 76.7 ± 18.1%, FEV1: 83.5 ± 19.1%, TLC: 85.6 ± 28.1%) and desaturation during 6MWT were detected in 41% of patients. LDCT changes were mainly ground glass opacities (GGO) and/or reticular abnormalities in most cases affecting < 10% of the lungs. Our data indicate that suspected post-COVID ILD is affecting 13.8% of symptomatic patients. High resolution chest CT changes were mainly low extent GGO/reticulation, while long-term lung structural changes need further evaluation., (© 2023. The Author(s).)

Introduction: Severe acute respiratory distress syndrome coronavirus disease-2 (SARS-CoV-2) can lead to acute hypoxemic respiratory failure (AHRF) with possible multisystemic involvement. Ventilation/perfusion mismatch and shunt increase are critical determinants of hypoxemia. Understanding hypoxemia and the mechanisms involved in its genesis is essential to determine the optimal therapeutic strategy. High flow nasal oxygen (HFNO) and awake prone positioning (APP) in patients with COVID-19 AHRF showed promising benefits. The aim of this systematic review was to depict current situation around the combined use of HFNO and APP in patients with COVID-19 AHRF. Particularly, to investigate and report the pathophysiological rationale for adopting this strategy and to evaluate the (1) criteria for initiation, (2) timing, monitoring and discontinuation, and to assess the (3) impact of HFNO/ APP on outcome., Methods: We performed a systematic search collecting the articles present in PubMed, Scopus, EMBASE, and Cochrane databases with the following keywords: COVID-19 pneumonia, high flow nasal oxygen, awake prone position ventilation., Results: Thirteen studies displayed inclusion criteria and were included, accounting for 1242 patients who received HFNO/ APP. The combination of HFNO/ APP has an encouraging pathophysiological rationale for implementing this technique. The recognition of patients who can benefit from HFNO/ APP is difficult and there are no validated protocols to start, monitoring, and discontinue HFNO/ APP therapy. The most used method to monitor the efficacy and failure of this combined technique are oxygenation indexes, but discontinuation techniques are inconsistently and poorly described limiting possible generatability. Finally, this technique provided no clear benefits on outcome., Conclusions: Our systematic search provided positive feedbacks for improving the utilization of this combination technique, although we still need further investigation about methods to guide timing, management, and discontinuation, and to assess the intervention effect on outcome., Competing Interests: Conflicts of interest None., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objective: Patients hospitalized with COVID-19 and hyperglycemia require frequent glucose monitoring, usually performed with glucometers. Continuous glucose monitors (CGMs) are common in the outpatient setting but not yet approved for hospital use. We evaluated CGM accuracy, safety for insulin dosing, and CGM clinical reliability in 20 adult patients hospitalized with COVID-19 and hyperglycemia., Methods: Study patients were fitted with a remotely monitored CGM. CGM values were evaluated against glucometer readings. The CGM sensor calibration was performed if necessary. CGM values were used to dose insulin, without glucometer confirmation., Results: CGM accuracy against glucometer, expressed as mean absolute relative difference (MARD), was calculated using 812 paired glucometer-CGM values. The aggregate MARD was 10.4%. For time in range and grades 1 and 2 hyperglycemia, MARD was 11.4%, 9.4%, and 9.1%, respectively, with a small variation between medical floors and intensive care units. There was no MARD correlation with mean arterial blood pressure levels, oxygen saturation, daily hemoglobin levels, and glomerular filtration rates. CGM clinical reliability was high, with 99.7% of the CGM values falling within the "safe" zones of Clarke error grid. After CGM placement, the frequency of glucometer measurements decreased from 5 to 3 and then 2 per day, reducing nurse presence in patient rooms and limiting viral exposure., Conclusion: With twice daily, on-demand calibration, the inpatient CGM use was safe for insulin dosing, decreasing the frequency of glucometer fingersticks. For glucose levels >70 mg/dL, CGMs showed adequate accuracy, without interference from vital and laboratory values., Competing Interests: Disclosure A.D. holds shares in Dexcom, Sensionics, Tandem, and Insulet. M.P. holds shares in Dexcom and Insulet. A.M. holds shares in Medtronics. The other authors have no multiplicity of interest to disclose., (Copyright © 2022 AACE. Published by Elsevier Inc. All rights reserved.)

In this study, we present an 18-month serological follow-up of 294 patients with COVID-19 pneumonia. The aim was to assess the dynamics of serological response and its correlation with clinical worsening, as well as to describe clinical worsening determinants. Results of the study showed an early immunoglobulin M response, which clearly diminished starting at 4 months, but nonetheless, a small group of patients remained positive. As for immunoglobulin G, levels were higher up to 6 months in patients who presented clinical worsening during hospitalization. High titers of the immunoglobulin were maintained in all patients during follow-up, which would indicate that humoral immunity due to infection is long-lasting. Male sex, presence of myalgias and extensive radiological affectation were significantly correlated with clinical worsening., (© 2022. The Author(s), under exclusive licence to Società Italiana di Medicina Interna (SIMI).)

Objectives: To compare the radiological findings of immune checkpoint inhibitor-related pneumonitis (IRP) and COVID-19 pneumonia, evaluating the potential of the CO-RADS score to differentiate between them., Methods: Two readers blindly reviewed chest CTs from age- and sex-matched groups of 33 patients with IRP and 33 patients with COVID-19 pneumonia. Each examiner evaluated the presence of 13 CT features, semiquantitatively scored lung involvement, and assigned a CO-RADS score. Inter-reader reliability in the assessment of CT features and CO-RADS categories was evaluated with Cohen's κ. Distribution differences between groups were evaluated with the χ 2 , Fisher's, and Mann-Whitney U tests., Results: Substantial or higher inter-reader reliability was found in CO-RADS assignments (κ = 0.664) and in the evaluation of CT features (κ ≥ 0.638), among which the sole feature found to significantly differentiate IRP from COVID-19 pneumonia was unilateral presentation (p < 0.001). Lung involvement semiquantitative scores and CO-RADS scores were significantly higher (p < 0.001) in COVID patients (median involvement score 4, IQR 4-6; median CO-RADS score 5, IQR 4-5) than in IRP patients (median involvement score 2.5, IQR 2-4; median CO-RADS score 3, IQR 3-4) but exploratory analysis of CO-RADS specificity revealed comparatively low values, ranging between 51.5% (Reader 1) and 54.6% (Reader 2)., Conclusions: CT features of IRP and COVID-19 pneumonia frequently overlap, save for the extent of lung involvement and bilaterality. In the current SARS-CoV-2 pandemic, the low specificity of the CO-RADS score for the differential diagnosis of COVID-19 pneumonia and IRP may prompt to reconsider the role of imaging in IRP work-up., (© 2023. Italian Society of Medical Radiology.)

Coronavirus disease 2019 (COVID-19) is associated with pneumonia and has various pulmonary manifestations on computed tomography (CT). Although COVID-19 pneumonia is usually seen as bilateral predominantly peripheral ground-glass opacities with or without consolidation, it can present with atypical radiological findings and resemble the imaging findings of other lung diseases. Diagnosis of COVID-19 pneumonia is much more challenging for both clinicians and radiologists in the presence of pre-existing lung disease. The imaging features of COVID-19 and underlying lung disease can overlap and obscure the findings of each other. Knowledge of the radiological findings of both diseases and possible complications, correct diagnosis, and multidisciplinary consensus play key roles in the appropriate management of diseases. In this pictorial review, the chest CT findings are presented of patients with underlying lung diseases and overlapping COVID-19 pneumonia and the various reasons for radiological lung abnormalities in these patients are discussed., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Introduction: COVID-19 pneumonia is a manifestation of SARS-CoV-2 infection and in most cases involves hospital admission. There are recommendations according to which these patients can be discharged without hospital admission, but there is no evidence regarding the revisit and the most appropriate type of follow-up. The objective of the RESALSEVID study was to investigate the variables associated with the 30-day revisit (Rev30d) in a group of patients discharged directly from 4 emergency departments (ED) with COVID-19 pneumonia, and analyze whether there were differences based on 4 different tracking devices., Method: Analysis of a prospective cohort of patients discharged directly from the ED with COVID-19 pneumonia in 4 hospital with different models of follow-up at discharge (primary care, hospitalization at home [HaH] phone and in person, HaH phone, hospital phone)., Results: Five hundred twenty patients were included, with a mean age of 50.1 years and 51% men. Rev30d was 18.3% and was related only to immunosuppression, odds ratio 4.49 (95% confidence interval 1.10-18.24); p=0.022. There was no difference in Rev30d based on the follow-up model used at discharge from the ED., Conclusions: There are some recommendations that allow the safe discharge of patients with COVID-19 pneumonia, with no differences in Rev30d depending on the type of follow-up., (Copyright © 2022 FECA. Publicado por Elsevier España, S.L.U. All rights reserved.)

Background: Coronavirus-19 Disease (COVID-19) may cause persistent symptoms and functional respiratory impairment, known as long COVID. Determinants of long COVID are unclear. Although males experience more severe acute illness, the impact of sex on the occurrence of long-term sequelae is unknown. The aim of this study was to establish whether sex affects pulmonary function, exercise capacity, and clinical outcomes in patients recovered from COVID-19 pneumonia. Materials and Methods: We performed a retrospective analysis on patients evaluated in our "Post-COVID Clinic" after a median follow-up of 128 days from the acute disease. Tests performed included standard spirometry, diffusion capacity of the lung for carbon monoxide (DLCO), and 6-minute walk test (6-MWT). Results: A total of 157 patients (mean age 59.9 ± 12, 91 males) recovered from mild to severe pneumonia, without previous respiratory disease, were included. No differences in demographic data and in the severity of the acute illness were observed between the two study groups, males and females. Abnormal alveolar diffusion was more common and severe among females (DLCO <80% in 31% of males vs. 53% of females, p  < 0.01; DLCO <70%, in 20% of males vs. 40% of females, p  < 0.01). Severe reduction in 6-MWT was observed in 20% of males versus 46% of females ( p  < 0.01). Multiple logistic regression showed that female sex was an independent predictor of abnormal DLCO and 6-MWT. The prevalence of symptoms and radiological abnormalities was similar in the two groups. Conclusions: These data show that at 4 months follow-up women recovered from COVID-19 pneumonia are more likely to exhibit a reduced alveolar diffusion capacity and exercise tolerance than men, although a similar severity of the acute disease.

Background: Lung ultrasound (LUS) scanning is useful to diagnose and assess the severity of pulmonary lesions during COVID-19-related ARDS (CoARDS). A conventional LUS score is proposed to measure the loss of aeration during CoARDS. However, this score was validated during the pre-COVID-19 era in patients with ARDS in the ICU and does not consider the differences with CoARDS. An alternative LUS method is based on grading the percentage of extension of the typical signs of COVID-19 pneumonia on the lung surface (LUSext)., Research Question: Is LUSext feasible in patients with COVID-19 at the onset of disease, and does it correlate with the volumetric measure of severity of COVID-19 pneumonia lesions at CT scan (CTvol)?, Study Design and Methods: This observational study enrolled a convenience sampling of patients in the ED with confirmed COVID-19 whose condition demonstrated pneumonia at bedside LUS and CT scan. LUSext was visually quantified. All CT scan studies were analyzed retrospectively by a specifically designed software to calculate the CTvol. The correlation between LUSext and CTvol, and the correlations of each score with Pao 2 /Fio 2 ratio were calculated., Results: We analyzed data from 179 patients. Feasibility of LUSext was 100%. Time to perform LUS scan was 5 ± 1.5 mins. LUSext and CTvol were correlated positively (R = 0.67; P < .0001). Both LUSext and CTvol showed negative correlation with Pao 2 /Fio 2 ratio (R = -0.66 and R = -0.54; P < .0001, respectively)., Interpretation: LUSext is a valid measure of the severity of the lesions when compared with the CT scan. Not only are LUSext and CTvol correlated, but they also have similar inverse correlation with the severity of respiratory failure. LUSext is a practical and simple bedside measure of the severity of pneumonia in CoARDS, whose clinical and prognostic impact need to be investigated further., (Copyright © 2022 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Objective: To investigate whether physicians with short-term training can use a modified lung ultrasound scoring system for coronavirus disease 2019 (COVID-19) pneumonia to assess lung damage in pregnant women., Methods: Sixteen consecutively hospitalized third-trimester pregnant women with pregnancy-induced hypertension, preeclampsia, rheumatoid arthritis or connective tissue disease were selected as the study subjects for the simulation of COVID-19 pneumonia. Two physicians (imaging and internal medicine) without ultrasonic experience performed lung examinations on pregnant women after six days of lung ultrasound training, and their consistency with examinations by the expert was assessed. In addition, 54 healthy third-trimester pregnant women and 54 healthy nonpregnant women of the same age who were continuously treated in the outpatient clinic of this hospital were selected for comparisons of abnormalities on lung ultrasound., Results: (1) Third trimester pregnant women with pregnancy-induced hypertension, preeclampsia, rheumatoid arthritis or connective tissue disease had the same lung ultrasound patterns as those associated with COVID-19 pneumonia. (2) There was no statistically significant difference between the scores of the two trained doctors and the expert when the modified ultrasound scoring system was used ( p  > .05). (3) The evaluations of the two trained doctors and the expert showed good consistency (kappa value = 0.833-0.957). (4) The incidence of abnormal ultrasound manifestations of the pleura and lung parenchyma was higher among healthy third-trimester pregnant women than among healthy women of the same age ( p  < .001)., Conclusions: After receiving short-term training, imaging and internal medicine physicians can use the modified lung ultrasound scoring system to evaluate pregnant women's pulmonary damage, but caution is needed to avoid false-positive results among pregnant women with suspected COVID-19 pneumonia.

Objective: To identify the type of the non-invasive ventilatory treatment for patients diagnosed with chronic obstructive pulmonary disease (COPD), with respiratory status deteriorated by COVID-19 pneumonia, and in need of treatment in the Intensive Care Unit (ICU)., Materials and Methods: This cross-sectional study was conducted over a one-year period in the medical intensive care units of two hospitals. As the patients' clinical condition deteriorated and the parameters of the arterial blood gas (ABG) analysis worsened, oxygen support was applied via a high flow nasal cannula (HFNC) or by non-invasive positive pressure ventilation (NPPV). According to the control values of the arterial oxygen saturation (SaO2) and the parameters of ABG, the patients were enabled to be transferred between the two types of non-invasive ventilatory support. The primary outcome was the length of hospital stay, while secondary outcomes were the rate of intubation, the mortality rate, and respiratory supportfree days., Results: Out of 21 critical patients with COPD and COVID-19, 11 (52.4%) were initially treated with NPPV and 10 (47.6%) with HFNC. The ages (67±9.79 in NPPV group vs. 70.10±10.25 in HFNC group) and severity of illness (SOFA score 5 (3.5) in NPPV group vs. 5 (2.8) in HFNC group) were similar between the two groups. Switching the mode of respiratory support was more common in NPPV (58.3% in survivor group vs. 41.7% in non-survivor group). Patients treated with NPPV compared to HFNC had a nominally longer length of stay (15 (11) vs. 11.5 (4.25)), and higher risk of intubation (66.7% vs. 33.3%) and mortality (66.7% vs. 33.3%), but the comparisons did not reach statistical significance. Survivors had significantly longer Medical Intensive Care Unit and hospital stays, but significantly lower FiO2 (0.60 vs.1) and higher values of PaO2/FiO2 (78(32.4) vs. 56.3(17.8)) than non-survivors. All patients were treated with corticosteroids, and the duration of treatment was similar between groups., Conclusion: In critically ill patients with COPD and COVID-19, both HFNC and NPPV were commonly used as the initial mode of ventilation. Switching to a different mode and adverse patient outcomes were more frequent in patients initially treated with NPPV. Survivors had higher values of PaO2/FiO2 than non-survivors., (Copyright © 2022 by Academy of Sciences and Arts of Bosnia and Herzegovina.)

Pigoń, Katarzyna, Ryszard Grzanka, Ewa Nowalany-Kozielska, and Andrzej Tomasik. Severe respiratory failure developing in the course of high-altitude pulmonary edema in an alpinist with COVID-19 pneumonia: a case report. High Alt Med Biol . 23:372-376, 2022.-The case of a 38-year-old Polish alpinist, evacuated from base camp (4,200 m) under Lenin's Peak due to severe high-altitude pulmonary edema (HAPE) and symptoms of acute mountain sickness/high-altitude cerebral edema (HACE), is presented. Starting the expedition, the man was asymptomatic and had a negative COVID-19 molecular test. After a few days of trekking, he developed typical HAPE and HACE. After evacuation to the hospital in Bishkek, a diagnosis of acute bronchopneumonia was made by computed tomography (CT) imaging. A COVID-19 test was not performed at that time. After returning to Poland, a complete noninvasive cardiac and pulmonary assessment disclosed no pathology. The initial chest CT reassessment was read as demonstrating the densities typical for COVID-19 pneumonia, and a SARS-CoV-2 antibody test corroborated the diagnosis. Pre-existing lung disease increases the risk of developing HAPE. In the era of the COVID-19 pandemic, people traveling at a high altitude and unaware of the infection are at particular risk.

Background & Aims: l-Arginine (l-Arg) has been shown to help reduce respiratory support requirements in coronavirus disease 2019 (COVID-19), in an Italian study. We investigated the effect of l-Arg supplementation on the reduction in respiratory support for patients with severe COVID-19 pneumonia in an Indian population., Methods: A parallel-group, triple-blinded, randomized controlled trial (RCT) was conducted on patients with severe COVID-19 pneumonia on oxygen (O 2 ) support. Patients received either 3 g of oral l-Arg or placebo, daily under supervision, until they were off O 2 support, or for a maximum of 10 days, whichever was earlier. The primary outcome was cessation in O 2 support. Other outcomes were time to cessation of O 2 support, duration of hospitalization, and incidence of adverse thrombotic events., Results: We did an intention-to-treat analysis on 74 patients who were randomized into l-Arg (n = 38) or placebo group (n = 36). There were no significant differences between the two groups in the outcomes. At end of the study, 28 patients (73.6%) in l-Arg and 26 patients (72.2%) in the placebo group were weaned off oxygen support. The median number of days to the cessation of O 2 support estimated using Kaplan Meir survival analysis, was 3 days in the l-Arg group (95% confidence interval [CI]: 1.2, 4.7) and 5 days in the placebo group (95% CI, 4.1,5.8); P = 0.27., Conclusion: In this group of patients with severe COVID-19 pneumonia, l-Arg supplementation did not show any significant difference in outcomes when compared to placebo supplementation., Competing Interests: Declaration of competing interest No conflict of interest to declare., (Copyright © 2022 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)