No abstract

SARS-CoV-2 is the novel coronavirus responsible for the current COVID-19 pandemic. Severe complications are observed only in a small proportion of infected patients but the cellular mechanisms underlying this progression are still unknown. Comprehensive flow cytometry of whole blood samples from 54 COVID-19 patients reveals a dramatic increase in the number of immature neutrophils. This increase strongly correlates with disease severity and is associated with elevated IL-6 and IP-10 levels, two key players in the cytokine storm. The most pronounced decrease in cell counts is observed for CD8 T-cells and VD2 γδ T-cells, which both exhibit increased differentiation and activation. ROC analysis reveals that the count ratio of immature neutrophils to VD2 (or CD8) T-cells predicts pneumonia onset (0.9071) as well as hypoxia onset (0.8908) with high sensitivity and specificity. It would thus be a useful prognostic marker for preventive patient management and improved healthcare resource management.

No abstract

No abstract

Highlights Platypnea-orthodeoxia syndrome (POS) is observed in COVID-19 acute respiratory distress syndrome (ARDS) survivors. POS is associated with older age, lower body mass index and varying degrees of dyspnea. Arterial to end-tidal carbon dioxide and alveolar to arterial oxygen partial pressure differences were persistently elevated. POS is likely a gravitational exacerbation of intrapulmonary shunt in ARDS due to COVID-19 specific changes. POS may cause alarm and requires adjustment in the rehabilitation approach during the recovery period.

We describe a COVID-19 patient with acute hyperhidrosis and symptomatic orthostatic tachycardia. We encountered 3 other patients with ophthalmic dysautonomia. We posit COVID-19 as a cause of acute, limited, possibly dysimmune, autonomic dysfunction.A 39-year-old man, a construction worker with no medical history, was diagnosed with COVID-19 from nasopharyngeal swab reverse transcription polymerase chain reaction (rt-PCR) when he presented with 8 days of acute respiratory symptoms, diarrhea, abdominal discomfort and pneumonia. Within 2 days‚ he required supplemental oxygen and prone-positioning, and was placed on a remdesivir trial. He recovered without ventilatory support. His blood pressure at admission was 165/92 mmHg. In hospital‚ it ranged from 130 to 170/80-110 mmHg. He was started on amlodipine 2.5 mg. His blood glucose ranged from 9 to 13 mmol/L and HbA1c was 8.8%. He was diagnosed with diabetes mellitus (DM) and given insulin and metformin.At day 13 of illness, as he was recuperating in the general ward with stable blood pressure and parameters, he developed right leg ischemia. Computed tomography (CT) aortogram showed a mural thrombus at the suprarenal aorta.

Singapore had 96 COVID-19 cases confirmed by real time reverse transcriptase-polymerase chain reaction (RT-PCR) for SARS-CoV-2. We examined the peripheral blood films of 32 patients and found reactive lymphocytes as shown in the top images in 23 cases (72%). This is in stark contrast to the pattern with coronavirus responsible for the 2003 SARS outbreak where reactive lymphocytes of this type were not present in a review of 185 SARS cases in Singapore and were present in only 15Á2% of 138 cases in Hong Kong. 1,2 Reactive lymphocytes are commonly seen in other viral diseases such as dengue fever and infectious mononucleosis. They have varied morphological features. The most common subtype seen in our COVID-19 patients displayed a distinctive abundant pale blue cytoplasm that often abuts adjacent red blood cells (top left and right). Strikingly, lymphoplasmacytoid lymphocytes were present in 16 out of 23 patients (bottom images: left, right and centre). These are small mature lymphocytes with condensed chromatin and an eccentric nucleus, occasionally with a paranuclear hof. Lymphoplasmacytoid lymphocytes are also seen in dengue fever and in several B-cell non-Hodgkin lymphomas. Reactive lymphocytes of both types can coexist in a single peripheral blood film in COVID-19 patients.

Patients with COVID-19 are known to be at risk of developing both venous, arterial and microvascular thrombosis, due to an excessive immuno-thrombogenic response to the SARS-CoV-2 infection. Overlapping syndromes of COVID-19 associated coagulopathy with consumptive coagulopathy and microangiopathy can be seen in critically ill patients as well. Blood was collected from 12 Intensive Care Unit (ICU) patients with severe COVID-19 who were on either mechanical ventilation or on high flow oxygen with a PaO2/FiO2 ratio of <300 mmHg. Laboratory tests were performed for parameters of haemostasis, clot waveform analysis and anti-phospholipid antibodies. CWA parameters were raised with elevated aPTT median Min1 (clot velocity) 9.3%/s (IQR 7.1–9.9%/s), elevated PT median Min1 10.3%/s (IQR 7.1–11.1%/s), elevated aPTT median Min2 (clot acceleration) 1.5%/s 2 (IQR 1.0–1.6%/s 2 ), elevated PT median Min2 5.2%/s 2 (3.6–5.7%/s 2 ), elevated aPTT median Max2 (clot deceleration) 1.3%/s 2 (IQR 0.8–1.4%/s 2 ) elevated PT median Max2 3.8%/s 2 (IQR 2.6–4.2%/s 2 ), increased aPTT median Delta change (decreased light transmission due to increased clot formation) 87.8% (IQR 70.2–91.8%) and PT median Delta change 33.0%. This together with raised median Factor VIII levels of 262.5%, hyperfibrinogenemia (median fibrinogen levels 7.5 g/L), increased median von Willebrand factor antigen levels 320% and elevated median D-dimer levels 1.7 μg/dl support the diagnosis of COVID-19 associated coagulopathy. A lupus anticoagulant was present in 50% of patients. Our laboratory findings further support the view that severe SARS-CoV-2 infection is associated with a state of hypercoagulability.