Waning of SARS-CoV-2 booster viral-load reduction effectiveness

The BNT162b2 COVID-19 vaccine has been shown to reduce viral load of breakthrough infections (BTIs), an important factor affecting infectiousness. This viral-load protective effect has been waning with time post the second vaccine and later restored with a booster shot. It is currently unclear though for how long this regained effectiveness lasts. Analyzing Ct values of SARS-CoV-2 qRT-PCR tests of over 22,000 infections during a Delta-variant-dominant period in Israel, we found that this viral-load reduction effectiveness significantly declines within months post the booster dose. Adjusting for age, sex and calendric date, Ct values of RdRp gene initially increased by 2.7 [CI: 2.3-3.0] relative to unvaccinated in the first month post the booster dose, yet then decayed to a difference of 1.3 [CI: 0.7-1.9] in the second month and became small and insignificant in the third to fourth months. The rate and magnitude of this post-booster decline in viral-load reduction effectiveness mirror those observed post the second vaccine. These results suggest rapid waning of the booster's effectiveness in reducing infectiousness, possibly affecting community-level spread of the virus.

504. Case SEries: Nasal Antimicrobial Photodisinfection (APDT) as Treatment Protocol for Asymptomatic and Early Stage COVID-19 Patients

Background Targeted reduction of SARS-CoV-2 viral load in the nose may mitigate the severity of lower tract respiratory disease as well as reduce hospitalization and mortality rates. Nasal Photodisinfection has been deployed for 10 years in Canadian hospitals reducing post-surgical infections. The objective of thiswork was to demonstrate effectiveness of APDT in early stage COVID-19 and asymptomatic carriers. Methods A cohort of 40 COVID-19 positive patients were treated with nasal photodisinfection (Steriwave) at a private clinic. All patients were previously identified by PCR as SARS-CoV-2 positive and admitted into the treatment cohort. BD rapid antigen nares testing was used before and after Photodisinfection treatment. Of the 40 patients, 13 were female and 27 were male. Age range was 9- 56 years of age. Treatment involved 3-4 applications of photosensitizer and 16-24 minutes per patient of treatment time. Patients were followed up within 24 hours, 48 hours as well as day 5 and 6 and day 10/11. Patients filled out a COVID-19 score card. Results Results demonstrated APDT was capable of significant and rapid viral load reduction in COVID-19 carriers. 100% of patients were converted from positive rapid antigen test to negative. 60% of patients reported fever resolution within 24 hours. Fever resolution occurred in 100% of patients within 48hours. Moreover, results demonstrated accelerated resolution of COVID-19 symptoms and significantly improved mental health benefits from reduction of COVID-19 related stress and anxiety. None of the patients experienced severe symptoms and no patients were hospitalized. Safety outcomes demonstrated no patient safety issues with only minor transient side effects (rhinorrhea, sneezing) observed. Moreover, the treatment procedure was pain-free and well tolerated by all patients. Conclusion Photodisinfection-based nasal decolonization anti-viral efficacy was demonstrated with improved outcomes for all patients treated in this case series. Significant rapid viral load reduction was confirmed by rapid antigen tests in all patients. More clinical studies are warranted in support of Photodisinfection based therapy for upper respiratory infections such as COVID-19. Disclosures All Authors: No reported disclosures

Development and verification of a test rig for inactivation of bacteria and (corona-) viruses by UVC air disinfection systems

The ongoing coronavirus pandemic spreads through airborne transmission and is therefore difficult to contain. However, coronaviruses are highly sensitive to UVC, so UVC air disinfection systems should be able to inactivate the virus. Unfortunately, so far there are only few possibilities to test the reduction of airborne viruses or other pathogens. A special test rig, which mainly consisted of a nebulizer and an airflow system, was developed to determine the antiviral and antibacterial efficiency of UVC air disinfection systems. In the assessment of such an UVC air disinfection system with nebulized Staphylococcus carnosus and a sampling period of 30 minutes, a mean bactericidal reduction of 3.70 log10 (99.98 %) was determined. For antiviral irradiation of the coronavirus surrogate phi6 a mean viral load reduction of 1.18 log10 (93.40 %) was observed after a sampling period of 10 minutes. Therefore, mobile UVC air disinfection systems could be applied in hospitals, retirement and nursing homes.

COVID-19: Azelastine nasal spray Reduces Virus-load In Nasal swabs (CARVIN). Early intervention with azelastine nasal sprays reduces viral load in SARS-CoV-2 infected patients. First report on a double-blind placebo-controlled phase II clinical trial.

Background:The current COVID-19 pandemic has had a major influence on our daily lives. The most frequent early symptoms associated with SARS-CoV-2 infection are coughing, fever, rhinitis, and loss of smell and taste. If the infection progresses to the lower respiratory tract, it can cause massive inflammation of the pulmonary system, which can be life threatening. There is urgent need for a broadly available and effective therapy for the treatment of early infections with SARS-CoV-2 in order to prevent progression to severe disease. Methodology:CARVIN is a phase II proof of concept, randomized, parallel, double-blind, placebo-controlled, interventional clinical trial. 90 SARS-CoV-2 positive volunteers were randomized into three groups to receive either placebo, azelastine 0.02% or azelastine 0.1% nasal spray for a period of 11 days. Seven nasopharyngeal swabs were taken during this period for quantitative PCR measurements assessing the viral load via the ORF 1a/b and E genes. Investigators also assessed patients’ status continuously throughout the trial, and the intensity of individual symptoms were reported by the patients using an electronic diary. Two safety follow-ups were performed at days 16 and 60 of study participation. Results:Since the data of the primary outcome did not show a normal distribution, all statistical tests presented here were done non-parametrically and all p-values are descriptive and without adjustment for multiple testing. A broader descriptive analysis will be performed at a later date on all variables and it will be published in a peer-reviewed publication. A wide range of initial viral loads in the nasopharyngeal swabs of the study population was observed with an overall median/mean + SD Ct value of approximately 21.9 / 23.6 + 5.8, corresponding to log10 6.6 + 1.8 copies per /ml. Out of the 90 enrolled subjects, at least 54 carried the Alpha (B.1.1.7, UK) variant.Treatment with azelastine nasal sprays resulted in a greater but non-significant decrease in mean viral load compared to that measured in the placebo group at all 6 timepoints after initiation of treatment. This tendency was stable and most pronounced on day 8 (after 7 days treatment), when in the 0.1% and 0.02% azelastine nasal spray groups, an approximately 8- and 29-fold greater clinically meaningful reduction of the baseline viral load, respectively, compared to placebo was observed (based on the ORF1a/b gene). On days 4 and 11, approximately 4-fold greater mean viral load reduction was seen in the 0.1% azelastine group.Differences in mean viral load compared to baseline values were seen starting on the second day (after one day of treatment) in the azelastine 0.1% and azelastine 0.02% group for ORF 1a/b gene, and with azelastine 0.1% for the E gene, while this reduction was less pronounced in the placebo group.The effects of 0.1% azelastine nasal spray treatment to accelerate viral load reduction were even more pronounced in patients with initial high viral load (subgroup analyses in patients exhibiting initial Ct values below 25 and below 20, respectively). Of note, by day 8 the PCR-test had turned negative in more patients in the 0.1% azelastine group (n=6, p= 0.01 for the ORF 1a/b gene and n = 3, p= 0.08 for the E gene) and in the 0.02% azelastine group (n=8, p< 0.01 for the ORF 1a/b gene and n = 5, p= 0.02 for the E gene) than in the placebo group (n=0 for the ORF 1a/b gene and n = 0, for the E gene).Discussion:This study provides the first clinical hints of the effects of an azelastine nasal spray in SARS-CoV-2 positive patients. Subgroup analyses performed in patients exhibiting high initial viral loads are further suggestive of azelastine’s potential as an antiviral treatment.

Risk versus Benefit of Using Hydroxychloroquine to Treat Patients with COVID-19

Hydroxychloroquine (HCQ), also known by its trade name Plaquenil®, has been used for over 50 years as a treatment for malaria, systemic lupus erythematosus, and rheumatoid arthritis. As the COVID-19 pandemic emerged in the United States and globally in early 2020, HCQ began to garner attention as a potential treatment and as prophylaxis against COVID-19. Preliminary data indicated that HCQ as well as chloroquine (CQ) possessed in vitro antiviral activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Early clinical data from China and France reported that HCQ and CQ were associated with viral load reduction and clinical improvement in patients with COVID-19 compared to control groups; however, an overwhelming number of randomized controlled trials, meta-analyses, and systematic reviews have since concluded that HCQ used alone, or in combination with azithromycin (AZ), provides no mortality or time-to-recovery benefit in hospitalized patients with COVID-19. Additionally, these same trials reported adverse events including cardiac, neuropsychiatric, hematologic, and hepatobiliary manifestations in patients with COVID-19 whom had been treated with HCQ. This review article summarizes the available data pertaining to the adverse events associated with HCQ use, alone or in combination with azithromycin, in patients with COVID-19 in order to fully assess the risk versus benefit of treating COVID-19 patients with these agents. The results of this review lead us to conclude that the risks of adverse events associated with HCQ use (with or without AZ) outweigh the potential clinical benefits and thus recommend against its use in the treatment or prevention of COVID-19.

Viral loads of Delta-variant SARS-CoV2 breakthrough infections following vaccination and booster with the BNT162b2 vaccine

The BNT162b2 vaccine showed high real-life effectiveness both at preventing disease and in reducing viral loads of breakthrough infections, but coincidental with the rise of the Delta-variant SARS-CoV2, these protective effects have been decreasing, prompting a third, booster, vaccine inoculation. Here, analyzing viral loads of over 11,000 infections during the current wave in Israel, we find that even though this wave is dominated by the Delta-variant, breakthrough infections in recently vaccinated patients, still within 2 months post their second vaccine inoculation, do have lower viral loads compared to unvaccinated patients, with the extent of viral load reduction similar to pre-Delta breakthrough observations. Yet, this infectiousness protection starts diminishing for patients two months post vaccination and ultimately vanishes for patients 6 months or longer post vaccination. Encouragingly, we find that this diminishing vaccine effectiveness on breakthrough infection viral loads is restored following the booster vaccine. These results suggest that the vaccine is initially effective in reducing infectiousness of breakthrough infections even with the Delta variant, and that while this protectiveness effect declines with time it can be restored, at least temporarily, with a booster vaccine.

Use of an antiviral mouthwash as an additional barrier measure in the SARS-CoV-2 transmission in adults with asymptomatic to mild COVID-19: A multicenter, randomized, double-blind controlled trial

Background The research hypothesis is that commercially available mouthwash with ß-cyclodextrin and citrox (bioflavonoids) could decrease the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) salivary viral load in adults with asymptomatic to mild COVID-19. Methods In this RCT, SARS-CoV-2 PCR-positive patients aged 18-85 years with asymptomatic to mild COVID-19 symptoms <8 days were recruited. A total of 154 eligible patients were randomly assigned (1:1) to antiviral ß-cyclodextrin and citrox mouthwash (CDCM) or placebo. Three rinses daily were performed for 7 days. Saliva sampling was performed on day 1 at 9 a.m. (T1), 1 p.m. (T2) and 6 p.m. (T3). On the following 6 days, one sample was taken at 3 p.m. Quantitative RT-PCR was used to detect SARS-CoV-2. The trial is registered at ClinicalTrials.gov (NCT04349592). Findings CDCM was significantly more effective than placebo 4 hours after the first intake (p<0·001), with a median percentage decrease T1-T2 of -14·25% [95% CI; -32·68% - 0·06%]. In patients with an initial salivary load > 2·95 log10 copies/mL, there was a significant difference in the reduction in viral load at T2. Over the course of one day, the first mouthwash rinse significantly reduced the viral load, and the second dose maintained this low value, compared to placebo. At day 7, there was still a greater decrease in salivary viral load over time in the CDCM group. In individuals with an initial viral SARS-CoV-2 load higher than 4·12 log10 copies/mL or 5·16 log10 copies/mL, CDCM reduced the salivary viral load more quickly than placebo (MLM p-value = 0·03; 0·029). Interpretation This trial supports the relevance of using mouthwash with ß-cyclodextrin and citrox as an additional barrier measure on day 1 to reduce the dissemination of SARS-CoV-2. Over 7 days, the use of this mouthwash showed a benefit of viral load reduction for patients with the highest initial loads.

Broad-Spectrum Host-Based Antivirals Targeting the Interferon and Lipogenesis Pathways as Potential Treatment Options for the Pandemic Coronavirus Disease 2019 (COVID-19)

The ongoing Coronavirus Disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) signals an urgent need for an expansion in treatment options. In this study, we investigated the anti-SARS-CoV-2 activities of 22 antiviral agents with known broad-spectrum antiviral activities against coronaviruses and/or other viruses. They were first evaluated in our primary screening in VeroE6 cells and then the most potent anti-SARS-CoV-2 antiviral agents were further evaluated using viral antigen expression, viral load reduction, and plaque reduction assays. In addition to remdesivir, lopinavir, and chloroquine, our primary screening additionally identified types I and II recombinant interferons, 25-hydroxycholesterol, and AM580 as the most potent anti-SARS-CoV-2 agents among the 22 antiviral agents. Betaferon (interferon-β1b) exhibited the most potent anti-SARS-CoV-2 activity in viral antigen expression, viral load reduction, and plaque reduction assays among the recombinant interferons. The lipogenesis modulators 25-hydroxycholesterol and AM580 exhibited EC50 at low micromolar levels and selectivity indices of >10.0. Combinational use of these host-based antiviral agents with virus-based antivirals to target different processes of the SARS-CoV-2 replication cycle should be evaluated in animal models and/or clinical trials.