ABSTRACT
Background. During the early Covid-19 pandemic, we observed a close-to-full disappearance of the activity of 4 respiratory viruses (RSV, hMPV, influenza, and parainfluenza), followed by an off-season sequential re-emergence in 2021. Surprisingly, a striking similarity between the dynamics of pneumococcus-associated disease (PAD;namely community-acquired alveolar pneumonia [CAAP;often considered pneumococcal] and bacteremic-pneumococcal pneumonia [IPD-Pneumonia]), was also observed. In contrast, adenovirus and rhinovirus activities did not change during COVID-19. We examined the association between PAD and RSV, hMPV, influenza, and parainfluenza (PAD-viruses). Methods. Surveillance of CAAP and IPD-Pneumonia incidences and viral activity in children < 5 years was described in detail previously [Danino D. et al. Clin Infect Dis. 2022, https://doi.org/10.1093/cid/ciab1014]. We extended the observations until December 2021, to capture the sequential re-emergence of the 4 PAD-viruses. A hierarchical linear regression model was used to quantify the association between PAD-viruses (each virus individually and combined), adenovirus and PAD. After fitting the models, the contribution of each virus was estimated. Results. The Figure shows striking similarities in the dynamics of CAAP, IPD-Pneumonia, and PAD-viruses both before and during the COVID-19 pandemic. During the expected peak season (Oct 2020 - Apr 2021) PAD episodes were extremely low. However, off-season peaks were seen during May - Dec 2021. Overall, 78% and 25% of all CAAP and IPD-Pneumonia episodes, respectively, were attributable to these viruses in children < 5 (Table). In CAAP, cases were attributable to each of the 4 PAD-viruses individually throughout the first 5 years of life: RSV and hMPV combined contributed 80%, 63%, and 42% of all CAAP episodes in children aged < 1, 1, and 2-4 years, respectively. The respective figures for influenza and parainfluenza combined were 13%, 21%, and 22%. Only RSV significantly contributed to IPD-Pneumonia (19%). Adenovirus did not contribute to PAD episodes. Conclusion. Our model suggests an important causative association between RSV, hMPV, influenza, and parainfluenza viruses and CAAP, and between RSV and IPD-Pneumonia. (Figure Presented).
ABSTRACT
Background. Respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) and to a lesser extent, parainfluenza and influenza viruses have been associated with pneumonia in young children. In contrast, adenovirus (AdV) and rhinovirus (RhV) are usually not associated with pneumonia. We aimed to evaluate the involvement of the four pneumonia associated viruses (grouped as PAV) in pediatric CAAP, before and during the COVID-19 pandemic. Methods. CAAP incidence and viral activity surveillance in southern Israel in children < 5y and virological detection methods were described previously (Danino. CID 2022, https://doi.org/10.1093/cid/ciab1014). We reviewed the period of Jan 2016 - Mar 2022. Most cases of COVID-19 in children < 5y occurred during Dec 2021 - Mar 2022 (Figure 1);Over 95% of children admitted for respiratory disease were tested for COVID-19 (PCR). Since AdV and RhV activity was previously not associated with CAAP and tended to be equally involved in mixed and single infections, the current analysis was done for the four PAV only. Results. CAAP incidence dynamics closely resembled the four PAV (grouped) activity dynamics (Figure 2A, 2B) with very low activity during the expected peak in winter 2020-2021, but with an off-season resurgence from spring 2021. Even though most CAAP episodes during the pandemic coincided with peak COVID-19 rates, only 9 CAAP episodes were COVID-19 positive (7 in 2022, of which 5 were RSV positive). Out of 3,430 CAAP episodes 55% were tested for PAV, of which 61% were positive, with similar rates before and during the pandemic. RSV was the most common involved virus, followed by hMPV. The virus distribution in CAAP during the entire period reflected their activity in the community (Figure 2C). Unlike pre-pandemic years where all four PAV appeared almost simultaneously, in 2021 PAV resurged sequentially, resulting in successive involvement in CAAP episodes, suggesting a causative association. Conclusion. 1. SARS-CoV-2 was only rarely involved in CAAP in young children. 2. PAV were involved in 61% of CAAP episodes in children < 5y with predominance of RSV and hMPV. 3. The atypical dynamics imposed by the COVID-19 pandemic suggests a causative association between PAV and CAAP. (Figure Presented).
ABSTRACT
SESSION TITLE: Late-breaking Abstract Posters SESSION TYPE: Original Investigation Posters PRESENTED ON: October 18-21, 2020 PURPOSE: Nitric oxide (NO) is a small endogenous messenger molecule with free radical characteristics that plays a key role in the pathophysiological processes in the lung, including host defense against airway pathogens. NO donors have been reported to inhibit replication of severe acute respiratory syndrome coronavirus (SARS-CoV-1) in vitro, and exogenous gaseous NO (gNO) at concentrations = 150ppm has been shown to act as a potent antimicrobial agent. In multiple clinical trials, administration of high dose (150 to 250ppm) intermittent gNO (30-40 min cycles, 2-5 cycles a day) was safe and well-tolerated, with promising antimicrobial efficacy potential. Beyond Air™ has developed the LungFit™ platform system, which produces and delivers up to 400 ppm gNO from ambient air to the human lung, eliminating the need for cylinders. Given its safety and antimicrobial activity, inhaled gNO is a potential treatment for patients with COVID-19. The objective of this in vitro study is to evaluate the use of gNO as a method of treating human coronavirus infection as a proof of concept for the treatment of SARS-CoV-2. METHODS: OC43 human coronavirus was exposed to 150-250ppm gNO, for up to 8 hours intermittently (1-hour alternating) both before and after infection of human HCT-8 cells. Host cell viability was assessed by an XTT cell proliferation-based assay 3-7 days post exposure to NO. The coronavirus viability was assessed by TCID50 (Median Tissue Culture Infectious Dose) 3-7 days post exposure. RESULTS: When coronavirus was exposed to 250ppm NO prior to infection, a significant reduction in infectivity was achieved as viral load was reduced by 24-fold compared to untreated sample and host cell viability was higher by more than 85% (p<0.05). Post infection exposure of OC43 coronavirus to 250ppm NO resulted in 45% increase in host cell viability (p<0.05). Upon exposure of coronavirus infected cells to 150ppm NO. While coronavirus lost 50% of its infectivity after 4 hours of treatment with 150ppm NO, complete inhibition of infectivity was achieved after 8 hours of treatment. CONCLUSIONS: These results indicate the potential of inhaled gNO as a novel treatment for COVID-19. According to our data, 150-250ppm gaseous NO shows anti-coronavirus properties against OC43 human coronavirus in vitro, when administered either prior to or post infection. CLINICAL IMPLICATIONS: The data presented shows that the use of NO and the LungFit™ system may be effective for usage in both prevention and treatment of the SARS-CoV-2 infection. DISCLOSURES: No relevant relationships by Amir Avniel, source=Web Response No relevant relationships Added 07/15/2020 by Hila Confino, source=Web Response, value=Salary Removed 07/15/2020 by Hila Confino, source=Web Response No relevant relationships Added 07/15/2020 by Hila Confino, source=Web Response, value=Salary Removed 07/16/2020 by Hila Confino, source=Web Response No relevant relationships Added 07/15/2020 by Elya Dekel, source=Web Response, value=Salary Removed 07/16/2020 by Elya Dekel, source=Web Response No relevant relationships by Pam Golden, source=Web Response No relevant relationships Added 07/15/2020 by Matan Goldshtein, source=Web Response, value=Salary Removed 07/16/2020 by Matan Goldshtein, source=Web Response Owner/Founder relationship with Beyond air company Please note: $20001 - $100000 Added 06/11/2020 by David Greenberg, source=Web Response, value=Consulting fee No relevant relationships Added 05/26/2020 by Rinat Kalaora, source=Web Response, value=Salary Removed 07/16/2020 by Rinat Kalaora, source=Web Response No relevant relationships Added 05/26/2020 by Rinat Kalaora, source=Web Response, value=stocks Removed 07/16/2020 by Rinat Kalaora, source=Web Response No relevant relationships Added 07/16/2020 by Rinat Kalaora, source=Web Response, value=Salary Removed 07/16/2020 by Rinat Kalaora, source=Web Response No relevant relationships Added 07/16/2020 by Rinat Kalaora, source=Web Response, value=Shares Removed 07/16/2020 by Rinat Kalaora, source=Web Response No relevant relationships Added 07/15/2020 by Omer Lerner, source=Web Response, value=Salary Removed 07/16/2020 by Omer Lerner, source=Web Response No relevant relationships by Steve Lisi, source=Web Response No relevant relationships by Yonat Shemer-Avni, source=Web Response No relevant relationships Added 07/16/2020 by Shay Yarkoni, source=Web Response, value=Salary Removed 07/16/2020 by Shay Yarkoni, source=Web Response No relevant relationships Added 07/16/2020 by Shay Yarkoni, source=Web Response, value=Shares Removed 07/16/2020 by Shay Yarkoni, source=Web Response