Lymphocyte subset (CD4+, CD8+) counts reflect the severity of infection and predict the clinical outcomes in patients with COVID-19

Abstract

Coronavirus, uses the Angiotensin Converting Enzyme-2 Receptor to enter airway cells. Viral endocytosis is mediated by several factors, including clathrin, the adaptor protein-2 complex (AP2) and the adaptor-associated kinase-1 (AAK1). 2 According to a recent report, 3 COVID-19, the disease caused by SARS-CoV-2, is characterized by three clinical patterns: no symptoms, mild to moderate disease, severe pneumonia requiring admission to Intensive Care Unit (ICU) in up to 31% of the patients. 3 Thus far, there is no specific therapy for COVID-19 infection. No benefit of lopinavir-ritonavir treatment resulted in a recent trial. 4 Hydroxychloroquine, currently used in view of its "in vitro" observed effect of reduction of viral replication, seems unsatisfactory. 5 Elevated proinflammatory cytokine/chemokine responses seem associated with respiratory failure. 3 Recently, tocilizumab, an interleukin-6 inhibitor, was reported as effective in patients with severe COVID-19 pneumonia. 6 Baricitinib, another inhibitor of cytokine-release, seems an interesting anti-inflammatory drug. It is a Janus kinase inhibitor (anti-JAK) licensed for the treatment of rheumatoid arthritis (RA) with good efficacy and safety records. 7 Moreover it seems to have anti-viral effects by its affinity for AP2-associated protein AAK1, reducing SARS-CoV-2 endocytosis. 8 On this basis, we assessed the safety of baricitinib therapy combined with lopinavir-ritonavir in moderate COVID-19 pneumonia patients and we evaluated its clinical impact.All consecutive hospitalized patients (March 16th −30th) with moderate COVID-19 pneumonia, older than 18 years, were treated for 2 weeks with baricitinib tablets 4 mg/day added to ritonavir-lopinavir therapy. The last consecutive patients with moderate COVID-19 pneumonia receiving standard of care therapy (lopinavir/ritonavir tablets 250 mg/bid and hydroxychloroquine 400 mg/day/orally for 2 weeks) admitted before the date of the first baricitinib-treated patient served as controls. Antibiotics were scheduled only in the case of suspected bacterial infection.Inclusion criteria were: a. SARS-Co-V2 positivity in the nasal/oral swabs; b. presence of at least 3 of the following symptoms: fever, cough, myalgia, fatigue; c. evidence of radiological pneumonia . After discharge, patients treated with baricitinib were planned to be followed for additional 6 weeks. Exclusion criteria: history of thrombophlebitis (TP), latent tuberculosis infection (QuantiFERON Plus-test positivity, Qiagen, Germany 9 ), pregnancy and lactation.Mild to moderate COVID-19 disease definition: presence of bilateral pneumonia with or without ground glass opacity and in absence of consolidation, not requiring intubation at enrollment; arterial oxygen saturation (SpO2) > 92% at room-air, and ratio arterial oxygen partial pressure/fractional inspired oxygen (PaO2/FiO2) 10 0-30 0 mmHg. Parameters daily accessed were: fever, pulmonary function, Modified Early Warning Score (MEWS), 10 pulse rate, blood pressure. After the initial execution, r...

American College of Rheumatology Guidance for the Management of Rheumatic Disease in Adult Patients During the COVID‐19 Pandemic: Version 1

“…In addition to older age and comorbidity, a number of laboratory measures have been preliminarily associated with poor outcomes from COVID-19 (11,12). Examined in retrospective cohorts of hospitalized patients, biomarkers predictive of poor outcomes have included lymphopenia (particularly, low CD4+ T cell numbers) and elevations in circulating levels of lactate dehydrogenase, C-reactive protein, IL-6, and d-dimer, among others (19)(20)(21)(22). Whether lymphopenia portends "preexisting" risk or is a conse-quence of more severe infection in hospitalized patients is unclear.…”

Lymphocyte Subset Counts in COVID‐19 Patients: A Meta‐Analysis

“…CD4+ and/or CD8+ T‐cell counts from COVID‐19 patients with different disease severity status were reported in all 20 publications, and 10 of them also included CD19+ B cell and CD16 + CD56+ NK cell counts. These 20 peer‐reviewed publications were selected for meta‐analysis in this brief report (6‐25).…”

American College of Rheumatology Guidance for the Management of Rheumatic Disease in Adult Patients During the COVID‐19 Pandemic: Version 2

“…outcomes from COVID-19 (11,12). Examined in retrospective cohorts of hospitalized patients, biomarkers predictive of poor outcomes have included lymphopenia (particularly, low CD4+ T cell numbers) and elevations in circulating levels of lactate dehydrogenase, C-reactive protein, IL-6, and d-dimer, among others (19)(20)(21)(22). Whether lymphopenia portends "preexisting" risk or is a consequence of more severe infection in hospitalized patients is unclear.…”