ABSTRACT
To examine innate immune responses in early SARS-CoV-2 infection that may change clinical outcomes, we compared nasopharyngeal swab data from 20 virus-positive and 20 virus-negative individuals. Multiple innate immune-related and ACE-2 transcripts increased with infection and were strongly associated with increasing viral load. We found widespread discrepancies between transcription and translation. Interferon proteins were unchanged or decreased in infected samples suggesting virally-induced shut-off of host anti-viral protein responses. However, IP-10 and several interferon-stimulated gene proteins increased with viral load. Older age was associated with modifications of some effects. Our findings may characterize the disrupted immune landscape of early disease.
ABSTRACT
COVID-19 causes severe disease with poor outcomes. We tested the hypothesis that early SARS-CoV-2 viral infection disrupts innate immune responses. These changes may be important for understanding subsequent clinical outcomes. We obtained residual nasopharyngeal swab samples from individuals who requested COVID-19 testing for symptoms at drive-through COVID-19 clinical testing sites operated by the University of Utah. We applied multiplex immunoassays, real-time polymerase chain reaction assays and quantitative proteomics to 20 virus-positive and 20 virus-negative samples. ACE-2 transcripts increased with infection (OR =17.4, 95% CI [CI] =4.78-63.8) and increasing viral N1 protein transcript load (OR =1.16, CI =1.10-1.23). Transcripts for two interferons (IFN) were elevated, IFN-λ1 (OR =71, CI =7.07-713) and IFN-λ2 (OR =40.2, CI =3.86-419), and closely associated with viral N1 transcripts (OR =1.35, CI =1.23-1.49 and OR =1.33 CI =1.20-1.47, respectively). Only transcripts for IP-10 were increased among systemic inflammatory cytokines that we examined (OR =131, CI =1.01-2620). We found widespread discrepancies between transcription and translation. IFN proteins were unchanged or decreased in infected samples (IFN-γ OR =0.90 CI =0.33-0.79, IFN-λ2,3 OR =0.60 CI =0.48-0.74) suggesting viral-induced shut-off of host antiviral protein responses. However, proteins for IP-10 (OR =3.74 CI =2.07-6.77) and several interferon-stimulated genes (ISG) increased with viral load (BST-1 OR =25.1, CI =3.33-188; IFIT1 OR =19.5, CI =4.25-89.2; IFIT3 OR =245, CI =15-4020; MX-1 OR =3.33, CI =1.44-7.70). Older age was associated with substantial modifications of some effects. Ambulatory symptomatic patients had an innate immune response with SARS-CoV-2 infection characterized by elevated IFN, proinflammatory cytokine and ISG transcripts, but there is evidence of a viral-induced host shut-off of antiviral responses. Our findings may characterize the disrupted immune landscape common in patients with early disease.
Subject(s)
COVID-19/immunology , Immunity, Innate/immunology , Nasopharyngeal Diseases/virology , SARS-CoV-2/immunology , Viral Load/immunology , Adolescent , Adult , Age Factors , Aged , Aged, 80 and over , COVID-19/virology , Child , Cytokines/blood , Enzyme-Linked Immunosorbent Assay , Female , Humans , Male , Middle Aged , Nasopharyngeal Diseases/immunology , RNA, Messenger/genetics , Real-Time Polymerase Chain Reaction , SARS-CoV-2/genetics , Sex Factors , Young AdultSubject(s)
COVID-19 , Pneumonia , Respiratory Distress Syndrome , Adrenal Cortex Hormones , China , Humans , Risk Factors , SARS-CoV-2ABSTRACT
OBJECTIVE: Vertical transmission from SARS CoV-2-infected women is uncommon and coronavirus has not been detected in amniotic fluid. Human amniotic products have a broad immune-mediating profile. Observing that many COVID-19 patients have a profound inflammatory response to the virus, we sought to determine the influence of human amniotic fluid (hAF) on hospitalized patients with COVID-19. RESULTS: A 10-patient case series was IRB-approved to study the impact of hAF on hospitalized patients with documented COVID-19. Nine of the 10 patients survived to discharge, with one patient succumbing to the disease when enrolled on maximal ventilatory support and severe hypoxia. The study design was altered by the IRB such that the last 6 patients received higher dose of intravenous hAF. In this latter group, patients that had observed reductions in C-reactive protein were associated with improved clinical outcomes. No hAF-related adverse events were noted. Acknowledging some of the inherent limitations of this case series, these results inform and catalyze a larger scaled randomized prospective trial to further investigate hAF as a therapy for COVID-19. Trial Registration ClinicalTrials.gov: NCT04319731; March 23, 2020.