Critical COVID-19 is associated with distinct leukocyte phenotypes and transcriptome patterns.

BACKGROUND: Prognostic markers for disease severity and identification of therapeutic targets in COVID-19 are urgently needed. We have studied innate and adaptive immunity on protein and transcriptomic level in COVID-19 patients with different disease severity at admission and longitudinally during hospitalization. METHODS: Peripheral blood mononuclear cells (PBMCs) were collected at three time points from 31 patients included in the Norwegian SARS-CoV-2 cohort study and analysed by flow cytometry and RNA sequencing. Patients were grouped as either mild/moderate (n = 14), severe (n = 11) or critical (n = 6) disease in accordance with WHO guidelines and compared with patients with SARS-CoV-2-negative bacterial sepsis (n = 5) and healthy controls (n = 10). RESULTS: COVID-19 severity was characterized by decreased interleukin 7 receptor alpha chain (CD127) expression in naïve CD4 and CD8 T cells. Activation (CD25 and HLA-DR) and exhaustion (PD-1) markers on T cells were increased compared with controls, but comparable between COVID-19 severity groups. Non-classical monocytes and monocytic HLA-DR expression decreased whereas monocytic PD-L1 and CD142 expression increased with COVID-19 severity. RNA sequencing exhibited increased plasma B-cell activity in critical COVID-19 and yet predominantly reduced transcripts related to immune response pathways compared with milder disease. CONCLUSION: Critical COVID-19 seems to be characterized by an immune profile of activated and exhausted T cells and monocytes. This immune phenotype may influence the capacity to mount an efficient T-cell immune response. Plasma B-cell activity and calprotectin were higher in critical COVID-19 while most transcripts related to immune functions were reduced, in particular affecting B cells. The potential of these cells as therapeutic targets in COVID-19 should be further explored.

Seasonal variations in Schistosoma haematobium egg excretion in school-age girls in rural KwaZulu-Natal Province, South Africa.

BACKGROUND: A predominant feature of Schistosoma haematobium infection is urinary egg excretion, and microscopic egg detection remains the accepted standard field diagnostic tool. Praziquantel is the drug of choice for schistosomiasis, and the World Health Organization recommends that it should be administered to all children >4 years of age living in schistosomiasis-endemic areas. The frequency of mass drug administration depends on the prevalence rate in the community. Urinary schistosome egg output has a day-to-day and hour-to-hour intrasubject variation. Therefore, it is important to assess possible seasonal variations in egg excretion to improve the planning of drug treatment. OBJECTIVES: To assess the influence of seasonality on urinary schistosome egg excretion in South Africa (SA). METHODS: We performed a prospective cohort study, exploring seasonal variations of S. haematobium egg excretion in 184 girls aged 10 - 12 years from randomly selected schools in a rural area of KwaZulu-Natal Province, SA. The area has a subtropical climate characterised by a cool dry season and a hot humid season. For children, water contact is higher in the latter season. At baseline, 108 girls were examined in the hot season, and 76 in the cold season. In the next year's cold season the untreated patients were re-investigated before treatment. RESULTS: There was a decrease in infection in the group initially tested in the hot season compared with the group tested in the cold season at both time points when adjusted for age and water contact (adjusted odds ratio 3.61 (95% confidence interval 1.14 - 11.44); p=0.03). CONCLUSIONS: This unique study shows that schistosomiasis prevalence determined by microscopy exhibits seasonal variation, with a higher prevalence in the hot rainy season. Precise community prevalence estimations are key in decisions to treat communities. There was significantly lower egg output in the cold season, and sampling in that season may therefore underestimate the prevalence of urinary schistosomiasis. The study indicates that sampling in SA should be done in the hot season.

Initial roentgenographic manifestations of pulmonary Mycobacterium tuberculosis, M kansasii, and M intracellularis infections.

The initial radiographic features of 188 patients with pulmonary infections due to Mycobacterium tuberculosis were compared to 184 patients with M kansasii and 100 patients with M intracellularis infections. The patients were all from the University of Texas Health Center at Tyler, all had at least two positive sputum cultures and no other potential pathogen, and none had a past medical history of any type of tuberculosis. The comparison showed that all three organisms have a strong tendency to produce cavitary infiltrates in the posterior portions of the upper lobes. No distinctive or pathognomonic feature could be found. The atypical organisms were more likely to produce thin-walled cavities and far advanced unilateral disease, but both of these patterns also occurred with M tuberculosis. Endobronchial spread and volume loss were common in all three diseases. The only definite difference seems to be the absence of a primary or juvenile form of atypical tuberculosis and a much greater incidence of empyema and postprimary pleural effusions with M tuberculosis. In an individual case, the roentgenographic manifestations of the three diseases are indistinguishable.

The effect of search time on perception.

A group of 100 carefully selected chest radiographs was read by ten observers, five experienced and five inexperienced. The radiographs were chosen to present the readers with a disproportionately large number of both subtle abnormalities and nonpulmonary lesions. Each reader was allowed to search the radiographs for as long as appropriate, up to a maximum of four minutes. The length of time taken for each observation was recorded to the nearest second. The time-perception data were plotted on both linear and semilogarithmic graphs. The results showed that experienced readers concluded their visual search while positive detection rate was higher than the rate for false-positives. For lesions in the central phasic, with both a rapid and a slow component of perception. If these data are plotted on a semilogarithmic scale, each of the two components plots as a straight line. For lesions in the periphery of the radiograph (chest wall and upper abdomen), the time-perception curve is monophasic, showing only a slow component.

Visible muscle of the diaphragm: sign of extraperitoneal air.

Epiphrenic air collections may be difficult to compartmentalize. The air may be in the peritoneal cavity, extraperitoneal or extrapleural spaces, or in a pleural cavity. Extraperitoneal and extrapleural air usually comes from a pneumomediastinum, but it may arise from an intraabdominal source, such as a ruptured second part of the duodenum. Pneumoperitoneum is frequently the only radiographic sign of a perforated hollow viscus. The radiologist is confronted with an important differentiation. A pneumoperitoneum may indicate a need for abdominal surgery and a pneumothorax may require surgical aspiration; but extraperitoneal and extrapleural air require no specific treatment, assuming that the source of the air can be ascertained and the quantity does not compromise respiration. A new sign is described to assist in the recognition of extraperitoneal and extrapleural air. When the muscle bundles of the diaphragm are outlined by air, the air must be between the parietal peritoneum and parietal pleura and thus be extraperitoneal and/or extrapleural in location. This sign was observed in five patients.

Hepatic and thoracic amaebiasis.

Sonographic and radiographic fidings were reviewed in 27 patients with hepatic amebiasis. Sonography usually demonstrated nonspecific, peripheral, hypoechoic lesions. The only diagnostic sonographic appearance was a combination of a hypoechoic lesion and diaphragmatic disruption, which was found in four patients. About 50% of the patients had accompanying radiographic abnormalities that were nondiagnostic. These included elvation of the right hemidiaphragm, basilar pulmonary infiltrates, and pleural effusions. Liver abscesses occasionally grew during the first 2 weeks of treatment even though the patients were responding well to medical therapy. Lesions frequently became more anechoic and better defined on follow-up examinations. Successfully treated abscesses may calcify rather than diminish.

Anaerobic pleural and pulmonary infections.

Radiographic findings are reviewed for 69 patients with bacteriologically proven anaerobic infections in the thorax. On the initial films, the disease was confined to the lung parenchyma in 50%, and to the pleura in 30% of patients. The other 20% had combined pleural and parenchymal disease. Over 50% of cases had lung necrosis on the initial films, and many patients who began with a noncavitary pneumonia developed necrosis during hospitalization despite antimicrobial therapy. Once necrosis developed, resolution was slow with an average closure of 65 days for lung abscesses. Parenthymal disease was usually confined to one anatomic site. This site was almost always in a basal or posterior part of the lungs. Pleural effusions tended to progress very rapidly and always proved to be empyemas. Many empyemas occurred without recognizable pneumonic disease. A few were nosocomial, occurring as a complication of surgery, penetrating chest wounds, or subphrenic abscesses. Many patients developed empyemas as a complication of parenchymal disease, frequently while on antimicrobial therapy. Almost all empyemas required surgical drainage with either a rib resection or decortication.

Injuries of the first costovertebral articulation.

The costovertebral articulations consist of two gliding type synovial joints, the costocentral and the costotransverse. When subjected to severe trauma, these joints may be subluxed or dislocated. The costotransverse joint is the more likely of the two to be injured. The first costotransverse joint is especially vulnerable because of its unique position at the top of the rib cage. Three cases are presented to show various injuries to this joint.

Radiographic techniques for balloon-occlusion pulmonary angiography.

Pulmonary angiography was performed in 125 patients with suspected pulmonary embolism. Standard angiographic techniques were combined with balloon occlusion of pulmonary arterial branches using a double lumen catheter and contrast material injection distal to the occlusion. Vessel opacification was fluoroscopically monitored and images obtained with either a conventional cut-film camera, a spot-film camera, or cineangiography. Balloon-occlusion angiography improved image quality and contributed substantially to the radiographic diagnosis of pulmonary embolism in most patients. The technique is useful in patients too ill to undergo conventional angiography and may be performed at the bedside.

Pulmonary manifestations of Mycobacterium intracellularis.

Pulmonary manifestations in 114 patients with at least two sputum cultures positive for M. intracellularis, no history of any kind of tuberculosis, and not other potential pathogen are described. Even with these stringent diagnostic criteria, seven patients had normal chest radiographs and another seven had reticulonodular-appearing disease without a definite focus of infection. In the other 100 patients, 92% had infiltrates in the apical and/or posterior segments of the upper lobes, and 88% had cavitary disease. The cavities were usually multiple and frequently measured over 4 cm. Scarring and volume loss were common, occurring to some degree in 70% of upper lobe foci. Pleural effusions were uncommon (5%) and usually small. Adenopathy was less common (4%) and usually occurred with upper lobe disease in younger patients. Most patients had some degree of endobronchial spread (81%). The radiographic characteristics of Mycobacterium intracellularis are not believed distinctive enought to differentiate it from Mycobacterium tuberculosis.

Radiographic manifestations of pulmonary Mycobacterium kansasii infections.

The radiographic characteristics of 187 pristine cases of pulmonary Mycobacterium kansasii infection are reviewed. The cases were selected from a total of 309 patients with two positive sputum cultures. All but three of the 187 patients had pulmonary disease. The progenitive focus of disease almost always involved the upper lobes, the right side (72%) more often than the left (50%). Upper lobe disease began posterior to the trachea in every case. Only one patient had disease that originated in an atypical location, that is, in the superior segment of the right lower lobe. The most frequent radiographic abnormality was cavitation (96% of diseased patients). The classical description of a thin walled cavity (or cavities) occurred in 33% of patients. A cicatricial reaction was common (two-thirds of cases). About 63% of patients had endobronchial spread. The likelihood of endobronchial disease decreased as the distance from the progenitive focus increased. Pleural effusions and adenopathy were rare. In an individual case, it is not possible to differentiate between pulmonary M. tuberculosis and M. kansasii infections.

Pulmonary manifestations of acute aspiration of gastric contents.

Radiographic manifestations of aspiration of gastric contents were reviewed in 60 patients. The findings were extremely variable, and there was no typical or characteristic appearance. Confluent and acinar infiltrates, as well as infiltrates composed of small irregular shadows, occurred singly or in a variety of combinations; the third pattern predominated in the majority of cases. Distribution was most commonly bilateral and multicentric and usually favored perihilar or basal regions, but localized or atypical densities were also observed. Patients with the most extensive radiographic abnormalities on initial studies tended to have the worst prognosis; however, mild early pulmonary infiltrates occasionally progressed to life-threatening abnormalities, and extensive initial involvement was frequently followed by a benign clinical and radiographic course. Radiographic changes often worsened for several days in uncomplicated cases, but improvement was generally manifested within the first week after aspiration. Worsening of infiltrates after initial improvement was associated with the development of bacterial pneumonia, the adult respiratory distress syndrome, and pulmonary embolism. In the appropriate clinical setting, aspiration of gastric contents should be an important diagnostic consideration in the presence of a wide variety of radiographic changes.

Buckling of the innominate artery simulating a right apical lung mass.

A tortuous retroflexed innominate artery can simulate a right apical mass. Four cases are presented to illustrate the four fairly distinct appearances which can result. When the innominate artery buckles posteriorly and laterally, it occasionally impresses deeply into the lung and becomes almost completely surrounded by air. The artery will then look like a pulmonary mass on frontal radiographs. The lower margin of the mass is always more crisply defined than the upper margin, and the appearance on the lateral film is fairly characteristic. Aortography is recommended when the radiographic picture is equivocal. In a survey of 200 randomly selected patients over 50 years old, only one had an innominate artery that presented as an apparent pulmonary mass.

The effect of fatigue on resident performance.

Fourteen rested and fatigued residents read a set of 25 test radiographs on two separate occasions approximately one month apart. The radiographs were made with partial chest phantom using pulmonary nodules as test objects. Seven rested and 7 fatigued residents read the radiographs, and a month later the order of fatigue was reversed. Fatigued residents had worked a minimum of 15 consecutive hours before their interpretations. Performance did not deteriorate with fatigue, and the nodule detection rate was almost identical on both occasions.

Grid versus non-grid techniques for the detection of pulmonary nodules in a chest phantom.

A partial chest phantom was constructed to compare two commonly employed radiographic techniques, 70 kVp without a grid and 120 kVp with a grid, for the detection of pulmonary nodules. The phantom consisted of human ribs embedded in paraffin, the lungs of a dog injected with silicone rubber, a tissue equivalent wax heart and beeswax nodules. The nodules ranged in size from 3-7 mm. A series of 120 films was exposed, half with each technique, and the films were interpreted by three senior residents and seven staff radiologists. More nodules of all sizes except 3 mm were detected with the 120 kVp technique. The 3 mm nodules were rarely detected with either technique. The disadvantages of the 120 kVp technique were an approximate 50 percent increase in patient exposures and almost twice as many false-positive nodule detections.

Effect of kilovoltage on detectability of pulmonary nodules in a chest phantom.

A partial chest phantom was constructed to examine the effect of kilovoltage on the detectability of pulmonary nodules. Four different energies were studied: 100, 150, 200, and 300 kVp. Nodule detectability improved with increasing energies up to 200 kVp, but improvement was relatively small and was accompanied by an almost equal rise in the number of false positive readings. Patient exposures were least at 200 kVp. There seems to be no advantage in a 300 kVp technique, since nodule detectability decreased and patient exposures increased at this energy.

Normal "Cupid's bow" contour of the lower lumbar vertebrae.

The inferior end plates of the 3d, 4th, and 5th lumbar vertebral bodies frequently have paired parasagittal concavities when viewed in the frontal projection. When viewed in the lateral projection, the concavities superimpose, lying in the posterior portion of the vertebral body. This normal contour of the end plate should not be confused with other vertebral body anomalies having clinical importance. The incidence and degree of end plate depression are discussed.

Subpulmonic pneumothorax in patients with chronic obstructive pulmonary disease.

A spontaneous pneumothorax is occasionally seen under the lung on upright views, apparently due to subpulmonic trapping of pleural air by adhesions. This is most likely to occur in patients with chronic obstructive pulmonary disease (COPD), especially if they have extensive parenchymal scarring from previous tuberculosis. The authors describe 4 patients who had subpulmonic pneumothorax, severe COPD, and parenchymal scarring and presented in respiratory failure. None had other clinical symptoms suggesting pneumothorax. Radiologists should be aware of this condition, since it is potentially lethal.