The Many Faces of Covid-19 at a Glance: A University Hospital Multidisciplinary Account From Milan, Italy

Abstract

In March 2020, northern Italy became the second country worldwide most affected by Covid-19 and the death toll overtook that in China. Hospital staff soon realized that Covid-19 was far more severe than expected from the few data available at that time. The Covid-19 pandemic forced hospitals to adjust to rapidly changing circumstances. We report our experience in a general teaching hospital in Milan, the capital of Lombardy, the most affected area in Italy. First, we briefly describe Lombardy's regional Covid-19-related health organizational changes as well as general hospital reorganization. We also provide a multidisciplinary report of the main clinical, radiological and pathological Covid-19 findings we observed in our patients.

Keywords: COVID-19; gynecology; infectious diseases respiratory medicine; internal medicine; neurology; pathology; psychology.

Figure 1

(A) Numbers of patients at ASST Santi Paolo e Carlo University Hospital in Milan (from March 1, 2020 to April 16, 2020) during the Covid-19 epidemic. (B) Nurses celebrating a patient's birthday at the bedside. (C) A representative case of Covid-related conjunctivitis. (D) Cycle for positioning a patient in the prone position in the intensive care unit.

Figure 2

(A) Electrocardiogram (ECG) showing a prolonged QTc interval in a Covid-19 patient treated with hydroxychloroquine and azithromycin. These two drugs combined may prolong the QT interval by more than 500 ms and induce arrhythmias. (B) Sustained ventricular tachycardia in a Covid-19 patient. The ECG showed frequent malignant ventricular arrhythmias. (C) A further Covid-19 related complication was myocarditis probably due to a direct heart muscle infection. This 4D echocardiographic image shows a ventricular dilatation and a concomitant apical thrombus (yellow arrow). (D) Coronary thrombosis in a Covid-19 patient with an acute coronary syndrome. In Covid-19 patients, we frequently found coronary vessel thrombosis obstructing the coronary artery. In this patient, the ECG clearly shows a blood clot obstructing the interventricular coronary artery (yellow arrow). (E) Interventricular septum rupture (yellow arrow, basal septum rupture with shunt) in a Covid-19 patient who arrived late in the coronary unit during S-T elevation myocardial infarction.

Figure 3

(A) An “alternative” pathophysiological hypothesis for Covid-19 pandemia developed at the department of internal medicine. Amusing moments helped staff to face the disaster (modified from https://www.news-medical.net/health/Blood-Plasma-Components-and-Function-(Italian).aspx). (B) (a) Some Covid-19 patients had myoclonus with a typical electroencephalographic (EEG) pattern showing both periodic lateralized epileptiform discharges (PLEDs) and bilateral PLEDs (bi-PLEDs), predominantly involving the left hemisphere, mainly recorded in the parasagittal and midline regions. (b,c) Black arrows indicate myoclonic jerks, without any correlation with periodic lateralized discharges, nor with a prominent proximal-to-distal gradient of appearance (surface electromyography recorded from the right sternocleidomastoid, extensor carpi radialis longus, and tibialis anterior muscles). (C) The virus as seen by an autistic child aged 8. In children with psychiatric disorders, Covid-19 remarkably influenced their thought and mood. (D) The algorithm for ventilation used in our patients (PEEP, positive end-expiratory pressure; SpO₂, pulse oximetry; FiO₂, fractional inspiration of oxygen; NiV, non-invasive ventilation; CPAP, continuous positive airway pressure).

Figure 4

LEFT. Autopsy findings in Covid-19 positive patients. Patients who died underwent autopsy 2–3 h after death, ascertained by a continuous 20-min electrocardiographic recording. (A–C) Lung findings at autopsy. Gross autopsy examination shows that the lungs have increased consistency but reduced volume. The lung parenchyma on the cut surface appears dry: squeezing produces scarce aerated blood. The lung parenchyma varies in color from bright red to grayish, with hemorrhagic areas of various sizes [(A) right lung, outer surface. (B) Left lung: external surface. (C) Left lung: cut surface of the parenchyma]. (D) Histologically, the lung alveolar cavities display abundant cellularity and fibrin aggregates (one in the yellow circle). The red arrows indicate in areas surrounding the bronchiolar walls amorphous material suggesting hyaline pulmonary membranes (E-E; 11.5x magnification; Hamamatsu NanoZoomer digital slide). (E,F) Left cerebral hemisphere without macroscopically evident pathological alterations. (G) Liver. The image highlights a portal septum with marked inflammatory infiltration. Inflammatory cells attack the adjacent hepatocyte plate and can also be seen within the sinusoidal spaces. The liver image also shows changes indicating biliary stasis (E-E; 19.3x magnification; Hamamatsu NanoZoomer digital slide). (H) Left ventricular myocardium. The gap between the myocytes contains mild but widespread inflammatory infiltration (E-E; 33.5x; Hamamatsu NanoZoomer digital slide). Right: Involvement of the nervous system in SARS-CoV-2 infection on transmission electronic microscopy. Ultrastructure in the medulla oblongata (A–C); gyrus rectus (D,E); and olfactory nerve (F). (A) Marked axonal damage involving the medulla oblongata, with irregular axonal swelling and disordered myelin sheath. The damage appears widespread. (B) A viral particle (red box) is observed in the periaxonal matrix near the outer surface of a myelin sheath. (C) Magnification of the red box area in (B) the spherical particle (~98 nm) has a crown shape with a dense inner core and electron-dense periphery with small external projections. The center of the particle contains a small roundish electron-dense structure compatible with that of SARS-CoV-2. (D) The image shows a neuron in the gyrus rectus, as demonstrated also by a nucleolus in the center of the euchromatic nucleus; autophagy phenomena in the cytoplasm (arrows) suggest cell damage. (E) Magnification of the red box area in (D), showing a viral-like particle measuring 160 nm (arrowhead). Black arrows indicate two well preserved mitochondria; the red arrows show the neuron's typical double nuclear envelope. The well-preserved ultrastructural features of these organelles demonstrate adequate collection and fixation methods and suggest that the tissue damage is related to the viral infection. (F) Severe tissue damage in the olfactory nerve: the oval structure is difficult to identify and is characterized by extensive autophagy phenomena with markedly electron-dense peripheral aggregates (arrows) (Images by Unitech NO LIMITS).

Figure 5

Immunohistochemical positivity for SARS-CoV-2 in autoptical tissues. Immunohistochemistry examination was performed using an automated immunostainer (DAKO OMNIS). (A) Brain. The red granule in the cytoplasm of neurons (arrows) and glial cells (arrowheads) indicates the positivity for nuclear protein (NP) of the virus. (B) Lung. Widespread cellular positivity (brown granulia) for viral spike protein. Positive cells are largely macrophages and pneumocytes. [A: SARS-CoV-2 (2019-nCoV) Nucleoprotein/NP Antibody, Rabbit MAb; Sino Biological; 1:800, antigen retrieval low; detection with DAB. B: SARS-CoV / SARS-CoV-2 (COVID-19) spike antibody [1A9] Cat No. GTX632604; GeneTex; 1:100, antigen retrieval high; detection with Magenta].

Figure 6

A 55-year-old man admitted to our emergency department with signs and symptoms of respiratory infection underwent chest ultrasound (US) (A), showing white lung areas, then confirmed at computed tomography (CT) examination (B) which showed multiple bilateral subpleural areas of ground glass opacity (GGO) in the upper lobes. CT scans obtained 48 h after admission showed the multiple GGO areas increased in number and extension (C) and the development of pulmonary consolidations in the basal posterior and lateral segments of both lower lobes (D). Chest x-ray obtained 9 days after admission (E) showed multiple coalescent pulmonary consolidations involving both lungs, mainly in the periphery. CT scans obtained 13 days after admission showed the GGOs in the upper lobes now partly regressed (F). CT scan in a 75-year-old man, with severe lung involvement, secondary to SARS-CoV-2 infection, showing pulmonary thromboembolic disease involving segmental arteries in the left (G) and right (H) lower lobes with triangular shaped subpleural consolidations (pulmonary infarcts). A 68-year-old man admitted to our emergency department with signs and symptoms of respiratory infection then resulted Covid+. Chest US showed an interstitial syndrome, characterized by more than three B lines per longitudinal field (I).