Severe Coronavirus Disease 2019 Pneumonia Research Articles

HOW CAN WE TELL? A CHALLENGING CASE OF COVID-19 REINFECTION VS POST-ACUTE COVID SYNDROME

TOPIC: Chest Infections TYPE: Medical Student/Resident Case Reports INTRODUCTION: Coronavirus Disease 2019 (COVID-19) has affected over 140 million with over 3 million deaths worldwide. As the virus continues, we face a new challenge;to discern between post COVID syndromes or COVID reinfection. We present a case with this medical dilemma. CASE PRESENTATION: 64 y/o F with Diabetes, Hypertension & history of asymptomatic COVID infection eight weeks prior to presentation with follow-up negative testing, presented with fever & SOB. She initially developed progressive dyspnea on exertion for which bronchodilators were initiated as an outpatient. She then presented to our hospital with fevers & progressive SOB. Her initial workup revealed normal blood work & inflammatory markers, however her COVID RNA test was positive with seronegative COVID antibodies. Imaging revealed increased bilateral ground-glass opacities & inter-septal thickening when compared to imaging one month prior. Her positive COVID tests were attributed to viral shedding & COVID therapy was not initiated. On hospital day 6 she began to decompensate requiring rapid escalation of oxygen supplementation to high flow nasal cannula. At this time high dose steroids were initiated as post COVID syndrome was thought to be the disease pathology. On hospital day 12 retesting revealed seroconversion of COVID antibodies. Her hospital course was complicated by severe hypoxia requiring prolonged steroid taper & oxygen supplementation. She was ultimately discharged on home oxygen with outpatient management. DISCUSSION: Complications of COVID-19 disease include reinfection & post-COVID syndrome. Reinfection was considered in this patient due to repeated negative tests & an asymptomatic period. This remains a rare phenomenon. There are only 5 reported known cases thus far. It was ruled out according to WHO guidelines, since there were 3 months after infection & despite neutralizing antibodies. We believe she developed severe ARDS due to COVID pneumonitis with possible progression to ILD. Typical disease course is still unclear. There is increasing evidence of fibrotic-like changes in the lung in high rate of patients for up to 6 months. Reversibility of these findings is unknown. Post-mortem evaluation of lung tissue reveals diffuse alveolar damage from chronic inflammation. Obesity, ARDS, prolonged hospitalization & NIMV are reported risk factors. CONCLUSIONS: This case shows the importance of considering COVID reinfection in patients with atypical presentation. It is imperative that we differentiate between viral shedding & reinfection in patients with post-acute COVID symptoms. Both presentations may be similar, therefore it is pivotal that we continue to investigate these two-potentially fatal COVID related processes. REFERENCE #1: Pan American Health Organization / World Health Organization. Interim guidelines for detecting cases of reinfection by SARS-CoV-2. 29 October 2020, Washington, D.C.: PAHO/WHO;2020 REFERENCE #2: Qian Li, Xiao-Shuang Zheng, Xu-Rui Shen, Hao-Rui Si, Xi Wang, Qi Wang, Bei Li, Wei Zhang, Yan Zhu, Ren-Di Jiang, Kai Zhao, Hui Wang, Zheng-Li Shi, HuiLan Zhang, Rong-Hui Du & Peng Zhou (2020): Prolonged shedding of severe acute respiratory syndrome coronavirus 2 in patients with COVID-19, Emerging Microbes & Infections, DOI: 10.1080/22221751.2020.1852058 REFERENCE #3: Han X, Fan Y, Alwalid O, et al. Six-month Follow-up Chest CT Findings after Severe COVID-19 Pneumonia. Radiology. 2021;299(1):E177-E186. doi:10.1148/radiol.2021203153 DISCLOSURES: No relevant relationships by Angelica Medina-Pena, source=Web Response No relevant relationships by Anna-Belle Robertson, source=Web Response No relevant relationships by Noura Semreen, source=Web Response no disclosure on file for David Shiu;No relevant relationships by Ro-Kaye Simmonds, source=Web Re ponse No relevant relationships by Jodi-Ann Smith, source=Web Response

SPONTANEOUS SUBCUTANEOUS EMPHYSEMA AND PNEUMOMEDIASTINUM WITH PROGRESSION TO PNEUMORETROPERITONEUM AS A RARE COMPLICATION OF COVID-19 PNEUMONIA

TOPIC: Chest Infections TYPE: Medical Student/Resident Case Reports INTRODUCTION: Spontaneous pneumothorax, pneumomediastinum, and subcutaneous emphysema have been described as rare life-threatening complications of COVID-19. Reports of pneumoperitoneum or pneumoretroperitoneum are extremely rare. We present a patient with COVID-19 pneumonia who developed spontaneous pneumomediastinum and subcutaneous emphysema with subsequent progression to pneumoretroperitoneum, without evidence of pneumothorax. CASE PRESENTATION: A 61 year old man with HIV and Addison's disease presented to the emergency department with worsening dyspnea, cough, and diarrhea. On admission, his oxygen saturation was 80% on room air, and he had diffuse bilateral lung rhonchi. Nasopharyngeal swab was positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Chest x-ray showed bilateral interstitial opacities. He was treated with dexamethasone, remdesivir, enoxaparin and supplemental oxygen. On hospital day three, he developed worsening hypoxia with pO2 of 41mmHg on 15L non-rebreather oxygen. He was transferred to the intensive care unit (ICU) and placed on non-invasive positive pressure ventilation but was quickly weaned to high-flow oxygen. On hospital day 17, he developed worsening hypoxia and reported neck swelling and tenderness. Computed tomography (CT) of the neck and chest confirmed extensive subcutaneous emphysema and pneumomediastinum and diffuse granular lung opacities without any normally aerated lung parenchyma, without evidence of pneumothorax. He was placed on mechanical ventilation after failing non-invasive positive pressure ventilation. Despite supportive care and lung protective ventilation, he remained hypoxic with worsening subcutaneous emphysema. CT of the chest, abdomen and pelvis showed development of pneumoperitoneum and pneumoretroperitoneum. Due to the patient's refractory hypoxia with progression to multi-system organ failure, his family opted for compassionate extubation and he expired on hospital day 34. DISCUSSION: Common causes of pneumoretroperitoneum include perforated viscous or iatrogenic introduction of air. As this patient had neither surgical procedures or evidence of perforation, his pneumoretroperitoneum was likely due to prolonged positive end expiratory pressure (PEEP) in setting of acute respiratory distress syndrome due to COVID-19. Mechanical ventilation likely acted as a shearing force intensifying air leak into the mediastinum which tracked inferiorly into the retroperitoneum. CONCLUSIONS: In conclusion, pneumomediastinum is a possible complication of COVID-19 pneumonia that can progress to pneumoretroperitoneum despite lung protective ventilation causing acute decompensation that can worsen patient prognosis. REFERENCE #1: Salehi, S., Abedi, A., Balakrishnan, S., & Gholamrezanezhad, A. (2020). Coronavirus Disease 2019 (COVID-19): A Systematic Review of Imaging Findings in 919 Patients. AJR. American journal of roentgenology, 215(1), 87–93. https://doi.org/10.2214/AJR.20.23034Zhou, C., Gao, C., Xie, Y., & Xu, M. (2020). COVID-19 with spontaneous pneumomediastinum. The Lancet. Infectious diseases, 20(4), 510. https://doi.org/10.1016/S1473-3099(20)30156-0 REFERENCE #2: Ahmed, A., Mohamed, M., & Ahmed, K. (2021). Severe COVID-19 Pneumonia Complicated by Pneumothorax, Pneumomediastinum, and Pneumoperitoneum. The American journal of tropical medicine and hygiene, tpmd210092. Advance online publication. https://doi.org/10.4269/ajtmh.21-0092Hillman K. M. (1983). Pneumoretroperitoneum. Anaesthesia, 38(2), 136–139. https://doi.org/10.1111/j.1365-2044.1983.tb13932. REFERENCE #3: Okamoto, A., Nakao, A., Matsuda, K., Yamada, T., Osako, T., Sakata, H., Yamaguchi, Y., Terashima, M., Iwano, J., & Kotani, J. (2014). Non-surgical pneumoperitoneum associated with mechanical ventilation. Acute medicine & surgery, 1(4), 254–255. https://doi.org/10.1002/ams2.52 DISCLOSURES: No relevant relationships by Christopher Ignatz, source=Web Response No relevant relationships by Bao Nhi Nguyen, source=Web Res onse No relevant relationships by Navitha Ramesh, source=Web Response

Comparison of High-Flow Nasal Cannula and Noninvasive Ventilation in Acute Hypoxemic Respiratory Failure Due to Severe COVID-19 Pneumonia.

Efficacy of high-flow nasal cannula (HFNC) over noninvasive ventilation (NIV) in severe coronavirus disease 2019 (COVID-19) pneumonia is not known. We aimed to assess the incidence of invasive mechanical ventilation in patients with acute hypoxemic respiratory failure due to COVID-19 treated with either HFNC or NIV. This was a single-center randomized controlled trial performed in the COVID-19 ICU of a tertiary care teaching hospital in New Delhi, India. One hundred and nine subjects with severe COVID-19 pneumonia presenting with acute hypoxemic respiratory failure were recruited and allocated to either HFNC (n = 55) or NIV (n = 54) arm. Primary outcome was intubation by 48 h. Secondary outcomes were improvement in oxygenation by 48 h, intubation rate at day 7, and in-hospital mortality. Baseline characteristics and [Formula: see text]/[Formula: see text] ratio were similar in both the groups. Intubation rate at 48 h was similar between the groups (33% NIV vs 20% HFNC, relative risk 0.6, 95% CI 0.31-1.15, P = .12). Intubation rate at day 7 was lower in the HFNC (27.27%) compared to the NIV group (46.29%) (relative risk 0.59, 95% CI 0.35-0.99, P = .045), and this difference remained significant after adjustment for the incidence of chronic kidney disease and the arterial pH (adjusted OR 0.40, 95% CI 0.17-0.93, P = .03). Hospital mortality was similar between HFNC (29.1%) and NIV (46.2%) group (relative risk 0.6, 95% CI 0.38-1.04, P = .06). We were not able to demonstrate a statistically significant improvement of oxygenation parameters nor of the intubation rate at 48 h between NIV and HFNC. These findings should be further tested in a larger randomized controlled trial. The study was registered at the Clinical Trials Registry of India (www.ctri.nic.in; reference number: CTRI/2020/07/026835) on July 27, 2020.

Low-Density Lipoprotein Cholesterol Levels and Disease Severity in COVID-19 Pneumonia

Objective: Pneumonia and acute respiratory distress syndrome are observed as major complications in Coronavirus disease-2019 (COVID-19). Cholesterol is a principal lipid component of the cell membranes. Lipoproteins have a fundamental role as the first line of defense against microbes. Lipoprotein levels are altered during viral infections. This study aimed to investigate the association between low-density lipoprotein cholesterol (LDL-C) levels and disease severity of patients hospitalized with COVID-19 pneumonia. Methods: This is a retrospective and observational study of 817 patients with Severe Acute Respiratory syndrome-Coronavirus-2 (SARS-CoV-2), who are diagnosed with COVID-19 using the real-time polymerase chain reaction and are hospitalized due to moderate and severe COVID-19 pneumonia. Results: Among 817 patients with COVID-19 pneumonia, 347 (42.5%) were moderate and 470 (57.5%) were severe. Total cholesterol (TC) and LDL-C levels reduced in patients who have severe condition than those with moderate condition (p=0.02, p=0.03, respectively). TC and LDL-C were negatively correlated with the hospitalization duration (r=-0.163, p=0.02, r=-0.154, p=0.03, respectively). Conclusion: Our results suggest a decreased LDL-C levels in patients with COVID-19 in relation to disease severity. Therefore, a strong link was found between lipid metabolism and SARS-CoV-2, which allow us to suggest LDL as a marker indicating COVID-19 severity in the near future.

Cytokine profile in Egyptian children and adolescents with COVID‐19 pneumonia: A multicenter study

BackgroundTo date, the cytokine profile in children and adolescent with novel coronavirus disease 2019 (COVID‐19) has not been reported.ObjectivesWe investigated serum levels of a panel of key cytokines in children and adolescent with COVID‐19 pneumonia with a primary focus on “cytokine storm” cytokines such as interleukin (IL)‐1β, IL‐6, IL‐17, IL‐2, IL‐4, IL‐10, interferon (IFN‐γ), tumor necrosis factor (TNF)‐α, and two chemokines interferon‐inducible protein‐10 (IP‐10) and IL‐8. We also studied whether these cytokines could be potential markers for illness severity in COVID‐19 pneumonia.MethodsNinety‐two symptomatic patients aged less than 18 years with confirmed COVID‐19 pneumonia and 100 well‐matched healthy controls were included in this multi‐center study. For all patients, the presence of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) in respiratory fluid specimens was detected by real‐time reverse‐transcriptase polymerase chain reaction. We measured serum concentrations of studied cytokines by using flow cytometry.ResultsPatients with COVID‐19 had significantly higher median IL‐1β, IL‐6, IL‐8, IL‐10, IL‐17, TNF‐α, and IP‐10 serum levels than did control children (all p < 0.01). Patients with severe COVID‐19 pneumonia had significantly higher median IL‐1β, IL‐6, and IP‐10 serum levels as compared with those with moderate COVID‐19 pneumonia; all p < 0.01. ROC analysis revealed that three of the studied markers (IL‐6, IL‐1β, and IP‐10) could predict severe COVID‐19 pneumonia cases with the largest AUC for IL‐6 of 0.893 (95% confidence interval: 0.84–0.98; p < 0.01).ConclusionOur study shows that pediatric patients with COVID‐19 pneumonia have markedly elevated serum IL‐1β, IL‐6, IL‐8, IL‐10, IL‐17, TNF‐α, and IP‐10 levels at the initial phase of the illness indicating a cytokine storm following SARS‐CoV‐2 infection. Moreover, serum IL‐6, IL‐1β, and IP‐10 concentrations were independent predictors for severe COVID‐19 pneumonia.

Mechanical ventilation in COVID‐19: A physiological perspective

New Findings What is the topic of this review? This review presents the fundamental concepts of respiratory physiology and pathophysiology, with particular reference to lung mechanics and the pulmonary phenotype associated with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection and subsequent coronavirus disease 2019 (COVID‐19) pneumonia. What advances does it highlight? The review provides a critical summary of the main physiological aspects to be considered for safe and effective mechanical ventilation in patients with severe COVID‐19 in the intensive care unit. Severe respiratory failure from coronavirus disease 2019 (COVID‐19) pneumonia not responding to non‐invasive respiratory support requires mechanical ventilation. Although ventilation can be a life‐saving therapy, it can cause further lung injury if airway pressure and flow and their timing are not tailored to the respiratory system mechanics of the individual patient. The pathophysiology of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection can lead to a pattern of lung injury in patients with severe COVID‐19 pneumonia typically associated with two distinct phenotypes, along a temporal and pathophysiological continuum, characterized by different levels of elastance, ventilation‐to‐perfusion ratio, right‐to‐left shunt, lung weight and recruitability. Understanding the underlying pathophysiology, duration of symptoms, radiological characteristics and lung mechanics at the individual patient level is crucial for the appropriate choice of mechanical ventilation settings to optimize gas exchange and prevent further lung injury. By critical analysis of the literature, we propose fundamental physiological and mechanical criteria for the selection of ventilation settings for COVID‐19 patients in intensive care units. In particular, the choice of tidal volume should be based on obtaining a driving pressure < 14 cmH2O, ensuring the avoidance of hypoventilation in patients with preserved compliance and of excessive strain in patients with smaller lung volumes and lower lung compliance. The level of positive end‐expiratory pressure (PEEP) should be informed by the measurement of the potential for lung recruitability, where patients with greater recruitability potential may benefit from higher PEEP levels. Prone positioning is often beneficial and should be considered early. The rationale for the proposed mechanical ventilation settings criteria is presented and discussed.

Morphological and functional sequelae after COVID-19 pneumonia

HintergrundNach einer Coronavirus-Krankheit-2019 (COVID-19) berichtet ein Teil der Patienten über länger andauernde oder sich verschlechternde Symptome und Beeinträchtigungen. Diese anhaltenden Symptome werden mit dem Begriff „Long-COVID“-Syndrom zusammengefasst. Sie können mit radiologischen Veränderungen in der Computertomographie (CT) und einer Verschlechterung der Lungenfunktion einhergehen.Ziel der ArbeitDie Rolle der langfristigen Verlaufskontrollen von COVID-19-Patienten wird erörtert, um festzustellen, welche Patienten davon profitieren können.Material und MethodenIn diesem Artikel werden die aktuellen Ergebnisse der klinischen, radiologischen und lungenfunktionellen Nachsorgenuntersuchungen nach COVID-19-Pneumonie präsentiert.ErgebnisseChronische Müdigkeit und Dyspnoe sind die häufigsten anhaltenden Symptome nach COVID-19. Außerdem zeigen viele dieser Patienten eine Beeinträchtigung der körperlichen Leistungsfähigkeit. In der CT sind Milchglasareale und strangförmige Verdichtungen die häufigsten residualen Veränderungen nach einer COVID-19-Pneumonie, die histologisch einer organisierenden Pneumonie entsprechen. Ein Teil der Patienten kann nach einer schweren COVID-19-Pneumonie im Verlauf fibroseähnliche Veränderungen aufweisen. Patienten mit einem vormals schwereren Verlauf können ein restriktives Syndrom mit niedriger Kohlenmonoxid-Diffusionskapazität (DLCO) und Gesamt-Lungenkapazität (TLC) zeigen. Im längerfristigen Verlauf zeigen die meisten Patienten eine deutliche und kontinuierliche Verbesserung aller Symptome sowie einen Rückgang der radiologisch-morphologischen und funktionellen Veränderungen.DiskussionPatienten mit persistierenden Symptomen nach COVID-19 sollten in spezialisierten Post-COVID-19-Ambulanzen multidisziplinär abgeklärt und behandelt werden.

Pulmonary function and six-minute-walk test in patients after recovery from COVID-19: A prospective cohort study.

To study abnormality of spirometry, six-minute walk distance, and chest radiograph among patients recovered from Coronavirus Disease 2019 (COVID-19). A prospective cohort study was conducted in 87 COVID-19 confirmed cases who recovered and discharged from a medical school hospital in Thailand. At the follow-up visit on day 60 after onset of symptoms, patients underwent an evaluation by spirometry (FVC, FEV1, FEV1/FVC, FEF25-75, and PEF), a six-minute-walk test (6MWT), and a chest radiograph. There were 35 men and 52 women, with a mean age of 39.6±11.8 years and the mean body mass index (BMI) was 23.8±4.3 kg/m2. Of all, 45 cases had mild symptoms; 35 had non-severe pneumonia, and 7 had severe pneumonia. Abnormality in spirometry was observed in 15 cases (17.2%), with 8% of restrictive defect and 9.2% of obstructive defect. Among the patients with an abnormal spirometry, the majority of the cases were in the severe pneumonia group (71.4%), compared with 15.6% in the non-severe pneumonia group, and 10.2% in the mild symptom group (p = 0.001). The mean six-minute-walk distance (6MWD) in the mild symptom and non-severe pneumonia groups was 538±56.8 and 527.5±53.5 meters, respectively. Although the severe pneumonia group tended to have a shorter mean 6-min walking distance, but this was not statistically significant (p = 0.118). Twelve patients (13.8%) had abnormal chest radiographs that showed residual fibrosis. This abnormality was more common in the severe pneumonia group (85.7%) and in others (7.5%) (p<0.001). Abnormal spirometry was noted in 17.2% of COVID-19 survivors with both restrictive and obstructive defects. Severe COVID-19 pneumonia patients had higher prevalence rates of abnormal spirometry and residual fibrosis on the chest radiographs when compared to patients in the mild symptom and non-severe pneumonia groups.

Complete Heart Block as a Clinical Feature in Critically Ill Coronavirus Disease 2019 (COVID-19) Patients: A Case Series of Three Cases

Background. Novel coronavirus-19 disease (COVID-19) is associated with significant cardiovascular morbidity and mortality. However, there have been very few reports on complete heart block (CHB) associated with COVID-19. This case series describes clinical characteristics, potential mechanisms, and short-term outcomes of critically ill COVID-19 patients complicated by CHB. Case Summary. We present three cases of new-onset CHB in critically ill COVID-19 patients. Patient 1 is a 41-year-old male with well-documented history of Familial Mediterranean Fever (FMF) who required mechanical ventilator support for acute hypoxic respiratory failure from severe COVID-19 pneumonia. He developed new-onset CHB without a hemodynamic derangement but subsequently had acute coronary syndrome complicated by cardiogenic shock. Patient 2 is a 77-year-old male with no past medical history who required intubation for severe COVID-19 pneumonia acute hypoxic respiratory failure. He developed CHB with sinus pause requiring temporary pacing but subsequently developed multiorgan failure. Patient 3 is 36-year-old lady 38 + 2 weeks pregnant, gravida 2 para 1 with no other medical history, who had an emergency Lower Section Caesarean Section (LSCS) as she required intubation for acute hypoxic respiratory failure. She exhibited new-onset CHB without hemodynamic compromise. The CHB resolved spontaneously after 24 hours. Discussion. COVID-19-associated CHB is a very rare clinical manifestation. The potential mechanisms for CHB in patients with COVID-19 include myocardial inflammation or direct viral infiltration as well as other causes such as metabolic derangements or use of sedatives. Patients diagnosed with COVID-19 should be monitored closely for the development of bradyarrhythmia and hemodynamic instability.

The Crazy-Paving Pattern in Chest CT Imaging of COVID-19 Patients: An Alarming Sign for Hospitalization

Background: The outbreak of coronavirus disease 2019 (COVID-19) has become a major threat to all humans. Objectives: To assess the association between the patients’ clinical and laboratory records, computed tomography (CT) findings, and epidemiological features of COVID-19 with the severity of the disease. Patients and Methods: In this retrospective case-control study conducted on the medical records of confirmed COVID-19 pneumonia patients on admission, we investigated the CT manifestations and clinical and laboratory risk factors for progression to severe COVID-19 pneumonia. The medical records and radiological CT features of confirmed COVID-19 patients were reviewed in one public hospital and one respiratory clinic in Qom, Iran, from August 1 to September 30, 2020. Results: Of 236 confirmed COVID-19 cases, 62 were infected with moderate to severe COVID-19 and required hospital admission, and 174 were followed-up on an outpatient basis. A significant difference was found in the mean age of the outpatient and hospitalized groups. The incidence of bilateral lung involvement, consolidations, linear opacities, crazy-paving pattern, air bronchogram, and number of lobes involved were significantly higher in the hospitalized group compared to the outpatient group. However, the crazy-paving pattern was only significantly associated with an oxygen saturation (SpO2) level &lt; 90% and, coughing. Our findings indicated that the crazy-paving pattern was significantly associated with the inflammatory phase. The presence of this pattern on admission, SpO2 &lt; 90%, older age, and diabetes were independent risk factors for progression to severe COVID-19. Conclusion: The crazy-paving pattern can predict the severity of COVID-19, which is of great importance in the management and follow-up of COVID-19 pneumonia patients. Clinical factors, such as aging, male gender, and diabetes, may be risk factors for the crazy-paving pattern. Severe cough is the most important clinical sign related to this pattern, along with an SpO2 &lt; 90%, which is an important sign of COVID-19 severity.

Silent Hypoxemia in Patients with COVID-19 Pneumonia: A Review

During the coronavirus disease 2019 (COVID-19) pandemic due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, patients presented with COVID-19 pneumonia of varying severity. The phenomenon of severe hypoxemia without signs of respiratory distress is also known as silent or hidden hypoxemia. Although silent hypoxemia is not unique to pneumonia due to SARS-CoV-2 infection, this phenomenon is now recognized to be associated with severe COVID-19 pneumonia. Proper management of critically ill patients is the key to reducing mortality. Herein, we summarize the possible and rare factors contributing to silent hypoxemia in patients with COVID-19. Microvascular thrombosis causes dead space ventilation in the lungs, and the flow of pulmonary capillaries is reduced, which leads to an imbalance in the V/Q ratio. The dissociation curve of oxyhemoglobin shifts to the left and limits the release of oxygen to the tissue. SARS-CoV-2 interferes with the synthesis of hemoglobin and reduces the ability to carry oxygen. The accumulation of endogenous carbon monoxide and carboxyhemoglobin will reduce the total oxygen carrying capacity and interfere with pulse oxygen saturation readings. There are also some non-specific factors that cause the difference between pulse oximetry and oxygen partial pressure. We propose some potentially more effective clinical alternatives and recommendations for optimizing the clinical management processes of patients with COVID-19. This review aims to describe the prevalence of silent hypoxemia in COVID-19 pneumonia, to provide an update on what is known of the pathophysiology, and to highlight the importance of diagnosing silent hypoxemia in patients with COVID-19 pneumonia.

Association between coronary artery calcifications and 6-month mortality in hospitalized patients with COVID-19

PurposeThe purpose of this study was to evaluate the association between coronary artery calcium (CAC) visual score and 6-month mortality in patients with coronavirus disease 2019 (COVID-19). Material and methodsA single-center prospective observational cohort was conducted in 169 COVID-19 consecutive hospitalized patients between March 13 and April 1, 2020, and follow-up for 6-months. A four-level visual CAC scoring was assessed by analyzing images obtained after the first routine non-ECG-gated CT performed to detect COVID-19 pneumonia. ResultsAmong 169 confirmed COVID-19 patients (118 men, 51 women; mean age, 65.6 ± 18.8 [SD] years; age range: 30–95 years) 63 (37%) presented with either moderate (n = 26, 15.3%) or heavy (n = 37, 21.8%) CAC detected by CT and 20 (11.8%) had history of cardiovascular disease requiring specific preventive treatment. At six months, mortality rate (45/169; 26.6%) increased with magnitude of CAC and was 7/64 (10.9%), 11/42 (26.2%), 10/26 (38.5%), 17/37 (45.9%) for no-CAC, mild-CAC, moderate-CAC and heavy-CAC groups, respectively (P = 0.001). Compared to the no CAC group, risk of death increased after adjustment with magnitude of CAC (HR: 2.23, 95% CI: 0.73–6.87, P = 0.16; HR: 2.78, 95% CI: 0.85–9.07, P0.09; HR: 5.38, 95% CI: 1.57–18.40, P = 0.007; in mild CAC, moderate and heavy CAC groups, respectively). In patients without previous coronary artery disease (154/169; 91%), mortality increased from 10.9% to 45.8% (P = 0.001) according to the magnitude of CAC categories. After adjustment, presence of moderate or heavy CAC was associated with higher mortality (HR: 2.26, 95% CI: 1.09–4.69, P = 0.03). ConclusionBy using non-ECG-gated CT during the initial pulmonary assessment of COVID-19, heavy CAC is independently associated with 6-month mortality in patients hospitalized for severe COVID-19 pneumonia.

Dissociation between the clinical course and chest imaging in severe COVID-19 pneumonia: A series of five cases

BackgroundAlthough an RT-PCR test is the “gold standard” tool for diagnosing an infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), chest imaging can be used to support a diagnosis of coronavirus disease 2019 (COVID-19) – albeit with fairly low specificity. However, if the chest imaging findings do not faithfully reflect the patient's clinical course, one can question the rationale for relying on these imaging data in the diagnosis of COVID-19. AimsTo compare clinical courses with changes over time in chest imaging findings among patients admitted to an ICU for severe COVID-19 pneumonia. MethodsWe retrospectively reviewed the medical charts of all adult patients admitted to our intensive care unit (ICU) between March 1, 2020, and April 15, 2020, for a severe COVID-19 lung infection and who had a positive RT-PCR test. Changes in clinical, laboratory and radiological variables were compared, and patients with discordant changes over time (e.g. a clinical improvement with stable or worse radiological findings) were analyzed further. ResultsOf the 46 included patients, 5 showed an improvement in their clinical status but not in their chest imaging findings. On admission to the ICU, three of the five were mechanically ventilated and the two others received high-flow oxygen therapy or a non-rebreather mask. Even though the five patients’ radiological findings worsened or remained stable, the mean ± standard deviation partial pressure of arterial oxygen to the fraction of inspired oxygen (PaO2:FiO2) ratio increased significantly in all cases (from 113.2 ± 59.7 mmHg at admission to 259.8 ± 59.7 mmHg at a follow-up evaluation; p=0.043). InterpretationOur results suggest that in cases of clinical improvement with worsened or stable chest imaging variables, the PaO2:FiO2 ratio might be a good marker of the resolution of COVID-19-specific pulmonary vascular insult.

Acute pancreatitis disease in the patient with COVID-19 infection: A systematic review

The coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a major outbreak in the world. Few reports have associated COVID-19 with pancreatitis. Angiotensin-converting enzyme-2, the functional virus host cell receptor expressed by organs and tissues, seems to have an important role in the pathophysiology and presentation of this disease. In pancreas, this receptor is expressed in both exocrine glands and islets, being a potential target for the virus and subsequent pancreatic injury. The aim of this study is to determine the relationship between COVID-19 and acute pancreatitis. Data obtained from secondary data on 21 articles journal evaluated by searching in PubMed, EMBASE, and the Cochrane Library database that have been carried out in the last 5 years (2016-2020). The severe COVID-19 pneumonia can lead to pancreatitis. Elevated pancreatic enzymes levels and computed tomography findings led to the diagnosis of acute pancreatitis due to COVID-19. Other research shows that, two of the three family members were diagnosed with acute pancreatitis associated with SARS-CoV-2. Other causes of acute pancreatitis were excluded for both patients (including alcohol, biliary obstruction/gall stones, drugs, trauma, hypertriglyceridemia, hypercalcemia, and hypotension). However, SARS-CoV-2-mediated pancreatic injury had been evident but COVID-19 induced established acute pancreatitis case has seldomly been reported till date globally. It can be concluded that in acute pancreatitis can occur in some COVID-19 patients. Diagnosing acute pancreatitis secondary to SARS-CoV-2 infection is challenging due to the need to rule out other etiologies as well the notable heterogeneous presentations.

C9orf72 Intermediate Repeats Confer Genetic Risk for Severe COVID-19 Pneumonia Independently of Age

A cytokine storm, autoimmune features and dysfunctions of myeloid cells significantly contribute to severe coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Genetic background of the host seems to be partly responsible for severe phenotype and genes related to innate immune response seem critical host determinants. The C9orf72 gene has a role in vesicular trafficking, autophagy regulation and lysosome functions, is highly expressed in myeloid cells and is involved in immune functions, regulating the lysosomal degradation of mediators of innate immunity. A large non-coding hexanucleotide repeat expansion (HRE) in this gene is the main genetic cause of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS), both characterized by neuroinflammation and high systemic levels of proinflammatory cytokines, while HREs of intermediate length, although rare, are more frequent in autoimmune disorders. C9orf72 full mutation results in haploinsufficiency and intermediate HREs seem to modulate gene expression as well and impair autophagy. Herein, we sought to explore whether intermediate HREs in C9orf72 may be a risk factor for severe COVID-19. Although we found intermediate HREs in only a small portion of 240 patients with severe COVID-19 pneumonia, the magnitude of risk for requiring non-invasive or mechanical ventilation conferred by harboring intermediate repeats >10 units in at least one C9orf72 allele was more than twice respect to having shorter expansions, when adjusted for age (odds ratio (OR) 2.36; 95% confidence interval (CI) 1.04–5.37, p = 0.040). The association between intermediate repeats >10 units and more severe clinical outcome (p = 0.025) was also validated in an independent cohort of 201 SARS-CoV-2 infected patients. These data suggest that C9orf72 HREs >10 units may influence the pathogenic process driving more severe COVID-19 phenotypes.

Diabetes Mellitus as the Major Factor of Prolonged Hospitalisation in Mild or Moderate COVID-19 Pneumonia.

Coronavirus Disease 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has been declared by the World Health Organization (WHO) as a pandemic [1]. Diabetes mellitus (DM) belongs to the comorbidities increasing the risk of severe COVID-19 pneumonia [2]. Notably, in our department among those who died from severe pneumonia, 71% had DM [3].

Intravenous methylprednisolone with or without tocilizumab in patients with severe COVID-19 pneumonia requiring oxygen support: A prospective comparison

BackgroundCytokine storm is a marker of severity and severe mortality in patients with coronavirus disease 2019 (COVID-19) pneumonia. Immunomodulatory treatments may reduce morbidity and mortality. ObjectivesTo determine whether a 7-day course of methylprednisolone (MP) administered with and without tocilizumab improves outcomes in patients with severe COVID-19 (SARS-CoV-2) pneumonia requiring oxygen therapy, relative to historical controls. Study design and methodIn this randomized controlled study, patients hospitalized with severe COVID-19 at Rashid Hospital, Dubai, in June 2020 were randomized 1:1 to receive intravenous MP (40 mg twice daily for 7 days) with or without a single dose of intravenous tocilizumab (400 mg). While data from the control arm, consisting of patients administered usual care, were obtained through retrospective review of their electronic medical records. The patients in the three arms were matched by disease severity and inclusion and exclusion criteria. The primary outcomes were day 45 all-cause mortality after randomization, rate of admission to the intensive care unit (ICU), length of ICU stay, days on ventilators, and length of hospital stay. ResultsIn total, 76 patients were recruited, including 23 treated with MP, 26 with MP plus tocilizumab, and 27 historical controls. The rates of admission to the ICU and invasive mechanical ventilation were lowest in patients treated with MP alone, with the rates in this group being significantly lower than the rates in the control group (p = 0.04). Time on a ventilator was lowest in the MP group (1.09 ± 3.68 days) and highest in the control group (7.93 ± 14.86 days). The number of days in the ICU was significantly lower in the MP group than in the control and MP plus tocilizumab groups (p = 0.043). One patient (4.3%) in the MP group and five (18.5%) in the control arm died within 45 days. Survival was highest in patients treated with MP alone, with the addition of tocilizumab not improving survival or any of the other outcomes significantly. Interpretation/conclusionIn patients with severe COVID-19 pneumonia on oxygen support, administration of MP daily for 7 days had reduced mortality at 45 days and was associated with significantly lower ICU admission and ventilation rates compared with usual. Adding tocilizumab to MP did not improve any of the studied outcomes significantly.

COVID-19 pneumonia in kidney transplant recipients: A promising treatment algorithm in the absence of a disease-specific drug.

There is no consensus on the management of coronavirus disease 2019 (COVID‐19) and modification of immunosuppressive therapy in kidney transplant recipients (KTRs). In this study, we examined the clinical outcome of our KTRs with COVID‐19 disease, who were treated with a broad‐spectrum anti‐inflammatory protocol. This protocol is essentially composed of intravenous immunoglobulin +/‐ tocilizumab in KTRs with severe COVID‐19 pneumonia. Among 809 KTRs, 64 patients diagnosed with COVID‐19 disease between April 2020 and February 2021, were evaluated. Twenty‐nine patients with pneumonia confirmed by chest computed tomography (CCT) were hospitalized. The treatment protocol included high‐dose intravenous methylprednisolone, favipiravir, enoxaparin, and empirical antibiotics. Patients with pneumonic involvement of more than 25% on CCT with or without respiratory failure were given a total of 2 g/kg intravenous immunoglobulin (IVIg) therapy. Nonresponders received tocilizumab, an interleukin‐6 receptor antibody. Of the 29 patients with pneumonia, 6 were treated in other hospitals. These six patients did not receive IVIg and 5 of them deceased. In our center, IVIg treatment was applied to 15 of 23 patients. Seven of them required tocilizumab. Respiratory parameters improved significantly in all but one patient after IVIg ± tocilizumab treatment. The mortality rate was 6.6% in patients who received IVIg therapy and 35.7% in those who did not (p = 0.08). The mortality rate was higher in patients who received treatment in external centers (2.2% vs. 26.3%; p = 0.0073). The treatment of KTRs with severe COVID‐19 pneumonia in organ transplant centers with significant experience yields better results. The administration of broad‐spectrum anti‐inflammatory treatment in this patient group was safe and provided excellent outcomes.

Clinical Characteristics and Early Interventional Responses in Patients with Severe COVID-19 Pneumonia.

Progressive acute respiratory distress syndrome (ARDS) is the most lethal cause in patients with severe COVID-19 pneumonia due to uncontrolled inflammatory reaction, for which we found that early intervention of combined treatment with methylprednisolone and human immunoglobulin is a highly effective therapy to improve the prognosis of COVID-19-induced pneumonia patients. Objective. Herein, we have demonstrated the clinical manifestations, laboratory, and radiological characteristics of patients with severe Coronavirus Disease-2019 (COVID-19) pneumonia, as well as measures to ensure early diagnosis and intervention for improving clinical outcomes of COVID-19 patients. Summary Background Data. The COVID-19 is a new infection caused by a severe acute respiratory syndrome- (SARS-) like coronavirus that emerged in China in December 2019 and has claimed millions of lives. Methods. We included 37 severe COVID-19 pneumonia patients who were hospitalized at Taizhou Public Health Medical Center in Zhejiang province from January 17, 2020, to February 18, 2020. Demographic, clinical, and laboratory features; imaging characteristics; treatment history; and clinical outcomes of all patients were collected from electronic medical records. Results. The patients' mean age was 54 years (interquartile range, 43−64), with a slightly higher male preponderance (57%). The most common clinical features of COVID-19 pneumonia were fever (29 (78%)), dry cough (28 (76%)), dyspnea (9 (24%)), and fatigue (9 (24%)). Serum interleukin (IL)-6 and IL-10 were elevated in 35 (95%) and 19 (51%) patients, respectively. Chest computerized tomography scan revealed bilateral pneumonia in 35 (95%) patients. Early intervention with a combination of methylprednisolone and human immunoglobulin was highly effective in improving the prognosis of these patients. Conclusions. Progressive acute respiratory distress syndrome is the most common cause of death in patients with severe COVID-19 pneumonia owing to an uncontrolled inflammatory response. Early intervention with methylprednisolone and human immunoglobulin was highly effective in improving their prognosis.

Evaluation of long-term radiological findings, pulmonary functions, and health-related quality of life in survivors of severe COVID-19.

ObjectiveIt was aimed to evaluate long‐term radiological changes in severe coronavirus disease 2019 (COVID‐19) patients, to investigate pulmonary function, exercise capacities, and health‐related quality of life results.MethodsSixty‐five patients with severe COVID‐19 pneumonia were evaluated in the sixth month after discharge from the hospital. Spirometry, 6 min walking test (6MWT), and short form of health‐related quality of life scale (SF‐36) were applied in the sixth month. Chest computed tomography (CT) was performed and the findings were grouped according to lung involvement.ResultsForty‐nine male and 16 female patients were included in the study. Forced expiratory volume in 1 s (FEV1)% values of 18 patients (30.5%), forced vital capacity (FVC)% values of 27 patients (45.8%), and 6MWT of 13 patients (23.2%) were found lower than expected in the sixth month. On the SF‐36 scale, physical function, energy‐vitality, social functionality, pain, and general health parameters were found lower than normal. Minimal interstitial changes in chest CT were seen in 26 patients. Nine patients had lung area involvement between 10% and 50% of the surface, there was a correlation between FEV1% and FVC% values in this group. There was severe pulmonary fibrosis in four patients. There was a correlation between pulmonary function and physical function and general perception of health from SF‐36 scale subparameters.ConclusionFunctional and radiological abnormalities were detected in a significant number of patients in the sixth month after severe COVID‐19 pneumonia. A systematic monitoring plan must be established to assess and properly manage the long‐term problems that may arise.