No abstract

With the emergence of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) variants that may increase transmissibility and/or cause escape from immune responses, there is an urgent need for the targeted surveillance of circulating lineages. It was found that the B.1.1.7 (also 501Y.V1) variant, first detected in the United Kingdom, could be serendipitously detected by the Thermo Fisher TaqPath Coronavirus Disease 2019 (COVID-19) PCR assay because a key deletion in these viruses, spike Δ69–70, would cause a “spike gene target failure” (SGTF) result. However, a SGTF result is not definitive for B.1.1.7, and this assay cannot detect other variants of concern (VOC) that lack spike Δ69–70, such as B.1.351 (also 501Y.V2), detected in South Africa, and P.1 (also 501Y.V3), recently detected in Brazil. We identified a deletion in the ORF1a gene (ORF1a Δ3675–3677) in all 3 variants, which has not yet been widely detected in other SARS-CoV-2 lineages. Using ORF1a Δ3675–3677 as the primary target and spike Δ69–70 to differentiate, we designed and validated an open-source PCR assay to detect SARS-CoV-2 VOC. Our assay can be rapidly deployed in laboratories around the world to enhance surveillance for the local emergence and spread of B.1.1.7, B.1.351, and P.1.

The emergence and spread of SARS-CoV-2 lineage B.1.1.7, first detected in the United Kingdom, has become a global public health concern because of its increased transmissibility. Over 2,500 COVID-19 cases associated with this variant have been detected in the United States (US) since December 2020, but the extent of establishment is relatively unknown. Using travel, genomic, and diagnostic data, we highlight that the primary ports of entry for B.1.1.7 in the US were in New York, California, and Florida. Furthermore, we found evidence for many independent B.1.1.7 establishments starting in early December 2020, followed by interstate spread by the end of the month. Finally, we project that B.1.1.7 will be the dominant lineage in many states by mid- to late March. Thus, genomic surveillance for B.1.1.7 and other variants urgently needs to be enhanced to better inform the public health response.

To test whether acute infection with B.1.1.7 is associated with higher or more sustained nasopharyngeal viral concentrations, we assessed longitudinal PCR tests performed in a cohort of 65 individuals infected with SARS-CoV-2 undergoing daily surveillance testing, including seven infected with B.1.1.7. For individuals infected with B.1.1.7, the mean duration of the proliferation phase was 5.3 days (90% credible interval [2.7, 7.8]), the mean duration of the clearance phase was 8.0 days [6.1, 9.9], and the mean overall duration of infection (proliferation plus clearance) was 13.3 days [10.1, 16.5]. These compare to a mean proliferation phase of 2.0 days [0.7, 3.3], a mean clearance phase of 6.2 days [5.1, 7.1], and a mean duration of infection of 8.2 days [6.5, 9.7] for non-B.1.1.7 virus. The peak viral concentration for B.1.1.7 was 19.0 Ct [15.8, 22.0] compared to 20.2 Ct [19.0, 21.4] for non-B.1.1.7. This converts to 8.5 log10 RNA copies/ml [7.6, 9.4] for B.1.1.7 and 8.2 log10 RNA copies/ml [7.8, 8.5] for non-B.1.1.7. These data offer evidence that SARS-CoV-2 variant B.1.1.7 may cause longer infections with similar peak viral concentration compared to non-B.1.1.7 SARS-CoV-2. This extended duration may contribute to B.1.1.7 SARS-CoV-2's increased transmissibility.

Background: The combined impact of immunity and SARS-CoV-2 variants on viral kinetics during infections has been unclear.Methods: We characterized 1,280 infections from the National Basketball Association occupational health cohort identified between June 2020 and January 2022 using serial RT-qPCR testing. Logistic regression and semi-mechanistic viral RNA kinetics models were used to quantify the effect of age, variant, symptom status, infection history, vaccination status and antibody titer to the founder SARS-CoV-2 strain on the duration of potential infectiousness and overall viral kinetics. The frequency of viral rebounds was quantified under multiple cycle threshold (Ct) value-based definitions.Results: Among individuals detected partway through their infection, 51.0% (95% credible interval [CrI]: 48.3-53.6%) remained potentially infectious (Ct<30) five days post detection, with small differences across variants and vaccination status. Only seven viral rebounds (0.7%; N=999) were observed, with rebound defined as 3+ days with Ct<30 following an initial clearance of 3+ days with Ct≥30. High antibody titers against the founder SARS-CoV-2 strain predicted lower peak viral loads and shorter durations of infection. Among Omicron BA.1 infections, boosted individuals had lower pre-booster antibody titers and longer clearance times than non-boosted individuals.Conclusions: SARS-CoV-2 viral kinetics are partly determined by immunity and variant but dominated by individual-level variation. Since booster vaccination protects against infection, longer clearance times for BA.1-infected, boosted individuals may reflect a less effective immune response, more common in older individuals, that increases infection risk and reduces viral RNA clearance rate. The shifting landscape of viral kinetics underscores the need for continued monitoring to optimize isolation policies and to contextualize the health impacts of therapeutics and vaccines.Funding: Supported in part by CDC contract #200-2016-91779, a sponsored research agreement to Yale University from the National Basketball Association contract #21-003529, and the National Basketball Players Association.

Background. The Omicron SARS-CoV-2 variant is responsible for a major wave of COVID-19, with record case counts reflecting high transmissibility and escape from prior immunity. Defining the time course of Omicron viral proliferation and clearance is crucial to inform isolation protocols aiming to minimize disease spread. Methods. We obtained longitudinal, quantitative RT-qPCR test results using combined anterior nares and oropharyngeal samples (n = 10,324) collected between July 5th, 2021 and January 10th, 2022 from the National Basketball Association's (NBA) occupational health program. We quantified the fraction of tests with PCR cycle threshold (Ct) values <30, chosen as a proxy for potential infectivity and antigen test positivity, on each day after first detection of suspected and confirmed Omicron infections, stratified by individuals detected under frequent testing protocols and those detected due to symptom onset or concern for contact with an infected individual. We quantified the duration of viral proliferation, clearance rate, and peak viral concentration for individuals with acute Omicron and Delta variant SARS-CoV-2 infections. Results. A total of 97 infections were confirmed or suspected to be from the Omicron variant and 107 from the Delta variant. Of 27 Omicron-infected individuals testing positive ≤1 day after a previous negative or inconclusive test, 52.0% (13/25) were PCR positive with Ct values <30 at day 5, 25.0% (6/24) at day 6, and 13.0% (3/23) on day 7 post detection. Of 70 Omicron-infected individuals detected ≥2 days after a previous negative or inconclusive test, 39.1% (25/64) were PCR positive with Ct values <30 at day 5, 33.3% (21/63) at day 6, and 22.2% (14/63) on day 7 post detection. Overall, Omicron infections featured a mean duration of 9.87 days (95% CI 8.83-10.9) relative to 10.9 days (95% CI 9.41-12.4) for Delta infections. The peak viral RNA based on Ct values was lower for Omicron infections than for Delta infections (Ct 23.3, 95% CI 22.4-24.3 for Omicron; Ct 20.5, 95% CI 19.2-21.8 for Delta) and the clearance phase was shorter for Omicron infections (5.35 days, 95% CI 4.78-6.00 for Omicron; 6.23 days, 95% CI 5.43-7.17 for Delta), though the rate of clearance was similar (3.13 Ct/day, 95% CI 2.75-3.54 for Omicron; 3.15 Ct/day, 95% CI 2.69-3.64 for Delta). Conclusions. While Omicron infections feature lower peak viral RNA and a shorter clearance phase than Delta infections on average, it is unclear to what extent these differences are attributable to more immunity in this largely vaccinated population or intrinsic characteristics of the Omicron variant. Further, these results suggest that Omicron's infectiousness may not be explained by higher viral load measured in the nose and mouth by RT-PCR. The substantial fraction of individuals with Ct values <30 at days 5 of infection, particularly in those detected due to symptom onset or concern for contact with an infected individual, underscores the heterogeneity of the infectious period, with implications for isolation policies.

Highlights d Tumor organoid cultures from >1,000 patients reveal genomic/transcriptomic fidelity d Establishment of chemically defined minimal medias for each solid tumor type d Pan-cancer neural network predicts drug response from label-free light microscopy

To date, the leading causes of mortality and morbidity worldwide include viral infections, such as Ebola, influenza virus, acquired immunodeficiency syndrome (AIDS), severe acute respiratory syndrome (SARS) and recently COVID-19 disease, caused by the SARS-CoV-2 virus. Currently, we can count on a narrow range of antiviral drugs, especially older generation ones like ribavirin and interferon which are effective against viruses in vitro but can often be ineffective in patients. In addition to these, we have antiviral agents for the treatment of herpes virus, influenza virus, HIV and hepatitis virus. Recently, drugs used in the past especially against ebolavirus, such as remdesivir and favipiravir, have been considered for the treatment of COVID-19 disease. However, even if these drugs represent important tools against viral diseases, they are certainly not sufficient to defend us from the multitude of viruses present in the environment. This represents a huge problem, especially considering the unprecedented global threat due to the advancement of COVID-19, which represents a potential risk to the health and life of millions of people. The demand, therefore, for new and effective antiviral drugs is very high. This review focuses on three fundamental points: (1) presents the main threats to human health, reviewing the most widespread viral diseases in the world, thus describing the scenario caused by the disease in question each time and evaluating the specific therapeutic remedies currently available. (2) It comprehensively describes main phytochemical classes, in particular from plant foods, with proven antiviral activities, the viruses potentially treated with the described phytochemicals. (3) Consideration of the various applications of drug delivery systems in order to improve the bioavailability of these compounds or extracts. A PRISMA flow diagram was used for the inclusion of the works. Taking into consideration the recent dramatic events caused by COVID-19 pandemic, the cry of alarm that denounces critical need for new antiviral drugs is extremely strong. For these reasons, a continuous systematic exploration of plant foods and their phytochemicals is necessary for the development of new antiviral agents capable of saving lives and improving their well-being.