Background
Key knowledge gaps remain in the understanding of viral dynamics and immune response of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection.
Methods
We evaluated these characteristics and established their association with clinical severity in a prospective observational cohort study of 100 patients with PCR-confirmed SARS-CoV-2 infection (mean age, 46 years; 56% male; 38% with comorbidities). Respiratory samples (n = 74) were collected for viral culture, serum samples for measurement of IgM/IgG levels (n = 30), and plasma samples for levels of inflammatory cytokines and chemokines (n = 81). Disease severity was correlated with results from viral culture, serologic testing, and immune markers.
Results
Fifty-seven (57%) patients developed viral pneumonia, of whom 20 (20%) required supplemental oxygen, including 12 (12%) with invasive mechanical ventilation. Viral culture from respiratory samples was positive for 19 of 74 patients (26%). No virus was isolated when the PCR cycle threshold (Ct) value was >30 or >14 days after symptom onset. Seroconversion occurred at a median (IQR) of 12.5 (9–18) days for IgM and 15.0 (12–20) days for IgG; 54/62 patients (87.1%) sampled at day 14 or later seroconverted. Severe infections were associated with earlier seroconversion and higher peak IgM and IgG levels. Levels of IP-10, HGF, IL-6, MCP-1, MIP-1α, IL-12p70, IL-18, VEGF-A, PDGF-BB, and IL-1RA significantly correlated with disease severity.
Conclusions
We found virus viability was associated with lower PCR Ct value in early illness. A stronger antibody response was associated with disease severity. The overactive proinflammatory immune signatures offer targets for host-directed immunotherapy, which should be evaluated in randomized controlled trials.
Oxygenation failure recalcitrant to increasing positive end-expiratory pressure is a feature of severe coronavirus disease 2019 (COVID-19) pneumonia [1]. A Chinese group used prone positioning to improve oxygenation for intubated patients with severe COVID-19 pneumonia [2]. However, prone positioning in unconscious patients is labour-intensive and is associated with various complications [3, 4]. As the incidence of severe COVID-19 pneumonia worldwide increases rapidly, many countries are also facing the problem of diminishing intensive care resources. Prone positioning ventilation is most used today in intensive care units (ICU) for patients with acute respiratory distress syndrome (ARDS) [5-7] and for prevention of ventilator-induced lung injury [8, 9]. Many mechanisms have been proposed, including relieving the dependent lung regions from the compressive force of the heart's weight [10] or increasing aeration in the originally dorsal lung regions [11]. The overall lung ventilation from dorsal to ventral areas is more homogeneous in the prone position than in the supine position. Prone positioning thus improves oxygenation whilst the other variable, perfusion, remains almost constant in both postures.
Objectives
A wide range of duration of viral RNA shedding in patients infected with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS‐CoV‐2) has been observed. We aimed to investigate factors associated with prolonged and intermittent viral RNA shedding in a retrospective cohort of symptomatic COVID‐19 patients.
Methods
Demographic, clinical and laboratory data from hospitalised COVID‐19 patients from a single centre with two consecutive negative respiratory reverse transcription‐polymerase chain reaction (RT‐PCR) results were extracted from electronic medical records. Kaplan–Meier survival curve analysis was used to assess the effect of clinical characteristics on the duration and pattern of shedding. Plasma levels of immune mediators were measured using Luminex multiplex microbead‐based immunoassay.
Results
There were 201 symptomatic patients included. Median age was 49 years (interquartile range 16–61), and 52.2% were male. Median RNA shedding was 14 days (IQR 9–18). Intermittent shedding was observed in 77 (38.3%). We did not identify any factor associated with prolonged or intermittent viral RNA shedding. Duration of shedding was inversely correlated with plasma levels of T‐cell cytokines IL‐1β and IL‐17A at the initial phase of infection, and patients had lower levels of pro‐inflammatory cytokines during intermittent shedding.
Conclusions
Less active T‐cell responses at the initial phase of infection were associated with prolonged viral RNA shedding, suggesting that early immune responses are beneficial to control viral load and prevent viral RNA shedding. Intermittent shedding is common and may explain re‐detection of viral RNA in recovered patients.
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