ABSTRACT
The SARS-CoV-2 is the betacoronavirus responsible for the coronavirus disease 2019 (COVID-19) pandemic. Severe COVID-19 affects approximately 10-15% of patients and results in prolonged morbidity and mortality. Little is known about the immunophenotypic changes of the lung parenchyma driven by the viral infection in patients who die of severe COVID-19. Ultrasound-guided lung biopsies (LB) were collected (IRB approval#1561/21) within few hours from death in 15 severe COVID-19 patients between November 2020 and January 2021, in two patients who underwent lung transplantation after COVID-19 and in one patient who had surgery for bacterial superinfection during COVID-19 disease. All samples underwent histologic and immunohistochemistry evaluation and molecular profiling using the nCounter Host Response and Coronavirus Panel plus. As controls, lungs from end-stage usual interstitial pneumonia (UIP;n=9) and from lobectomy for lung cancer (Norm;n=5) were used. Eleven lungs (61%) were positive for SARS-CoV-2 RNA. Signs of diffuse alveolar damage (DAD) were observed in 6 patients (30%). COVID-19 lungs showed a marked macrophage infiltration with M2 polarization compared with controls. Globally, COVID-19 lungs showed distinct molecular profiles from UIP or Norm lungs. Specifically, a marked upregulation of interferon-genes that was directly correlated with SARS-CoV-2 genes was seen in COVID-19 lungs. COVID-19-specific genes signatures (Log2FC >1.5;adj p<0.05) obtained using VENN diagram showed impairment of the STAT3-pathway accompanied by the upregulation of the NFkB signaling. Results herein provide new insights into lung alterations induced by severe COVID-19 and suggest novel potential targets for therapeutic intervention.
ABSTRACT
Background: On March 13, 2020, the United States declared a national emergency to combat coronavirus disease 2019 (COVID-19). Many states and localities issued shelter-in-place or stay-at-home orders to reduce the spread of COVID-19, limiting movement outside the home to essential activities. Since that time the pandemic has been associated with documented disruptions in routine preventive and other nonemergency care. Screening for HIV infection as well as HIV-1 viral load monitoring for persons living with HIV have likely been affected by the pandemic. Laboratory data from the National Syndromic Surveillance Program provide one way to assess the impact of the COVID-19 pandemic on HIV screening, HIV diagnoses and HIV-1 viral load monitoring. Methods: Using data reported daily to CDC from a large commercial laboratory, we identified lab test reports for HIV screening or HIV-1 viral load testing. For reports with HIV screening test results, we assessed how often the final HIV test algorithm result was confirmed positive. We plotted daily counts of each of the three HIV test types and 7-day moving averages. We also calculated the difference in the number of each type of test performed between March 13, 2019 and September 30, 2019 from those performed during the same time period in 2020. Results: Compared with number of tests performed in 2019, there were 669,847 fewer HIV screening tests, 4,910 fewer confirmed HIV-1 diagnoses, and 67,694 fewer HIV-1 viral load tests performed during March 13 to September 30, 2020. The 7-day average number of HIV tests performed dropped dramatically after March 13, 2020 and did not recover to 2019 levels by September 30, 2020 (Figure). Conclusion: During the national COVID-19 emergency, routine screening for HIV and HIV-1 viral load monitoring may have been delayed or foregone by many patients and clinicians. Undiagnosed HIV infection and higher viral loads could have led to increased morbidity and transmission. Although the number of tests being performed has partially recovered from a nadir this spring, testing at this commercial lab has not yet rebounded to make up what was lost. Healthcare system adaptations including home testing, home sample collection, and telemedicine visits for HIV care can help to address this shortfall as the COVID-19 pandemic persists in the US.