Prolonged virus shedding even after seroconversion in a patient 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...

Experimental Models for the Study of Central Nervous System Infection by SARS-CoV-2

“…Vero E6 cells have therefore already been used in studies with SARS-CoV and MERS-CoV ( 30 , 33 – 36 ) and also in the development of live-attenuated and inactivated vaccines for human use ( 37 , 38 ). More recently, they have been used in research into the viral infection mechanism in COVID-19 ( 23 , 39 , 40 ), the effects of the virus on cells, confirmation of viral infection ( 41 – 43 ) and pharmacological research ( 44 – 48 ).…”

SARS-CoV-2 RNA shedding in recovered COVID-19 cases and the presence of antibodies against SARS-CoV-2 in recovered COVID-19 cases and close contacts

“…Chirathaworn C et al 16 and individuals who traveled with COVID-19 cases had a high risk of infection [28]. Meanwhile, Guo et al showed that the median duration of antibody detection was 5 days for IgM and IgG and 14 days for IgG.…”

“…Viral RNA has been shown to be detectable in recovered patients, although the duration of viral RNA shedding reported varied among infected patients. Viral RNA shedding can last at least 6 weeks [12][13][14][15][16]. Liu et al reported that patients with severe symptoms had a higher viral load and a longer viral shedding period than patients with mild symptoms (<10 days for the group with mild symptoms and >10 days for the group with severe symptoms).…”

Characterization of Rhamnolipids for the Inactivation of Enveloped Viruses

“…Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, China, in late 2019, is now causing a pandemic COVID-19. It was estimated that 104-107 genome copies/ml were present in nasal and pharyngeal swab specimens from COVID-19 patients (Liu et al, 2020a). In a similar study, 104-105 genome copies /ml SARS-CoV2 were detectable in sputum from severe infected COVID 19 patients (Huang et al, 2020;Liu et al, 2020b).…”

“…Respiratory viruses are common in humans and are transmitted mostly via droplets or aerosols, or body secretions, such as tears, nasal or oral discharges. The amount of viruses shed in the nasal or oral secretion can range from 104 to 107 genome copies/ml depending on the severity of the infection and the types of viruses (Finberg et al, 2019;Liu et al, 2020a). For example, Middle East respiratory syndrome coronavirus (MERS-CoV) is a highly pathogenic coronavirus, can cause 34% mortality in infected humans (Ogimi et al, 2020).…”