Covid19mathblog.com

Beyond vaccine is treatment. Good news there are still studies evaluating treatment. This one uses various cells to evaluate efficacy. HCQ is in the study – I am sure many will pull the takeaway it was not effective on the lung cells – but other cells it did a decent job. This actually highlights that it is not a preventer but a mitigator of spread. If money was not an issue for sure remdesivir did very well – but looks like the winner is cyclosporine.

https://www.cell.com/cell-reports/fulltext/S2211-1247(21)00273-4?

“To identify new candidates, we screen a repurposing library of ∼3,000 drugs. Screening in Vero cells finds few antivirals, while screening in human Huh7.5 cells validates 23 diverse antiviral drugs. Extending our studies to lung epithelial cells, we find that there are major differences in drug sensitivity and entry pathways used by SARS-CoV-2 in these cells. Entry in lung epithelial Calu-3 cells is pH independent and requires TMPRSS2, while entry in Vero and Huh7.5 cells requires low pH and triggering by acid-dependent endosomal proteases. Moreover, we find nine drugs are antiviral in respiratory cells, seven of which have been used in humans, and three are US Food and Drug Administration (FDA) approved, including cyclosporine. We find that the antiviral activity of cyclosporine is targeting Cyclophilin rather than calcineurin, revealing essential host targets that have the potential for rapid clinical implementation.”

“Respiratory epithelial cells are the major cellular target for SARS-CoV-2 in vivo and have been used to explore the role of TMPRSS2 in infection. Perhaps surprisingly, although we found remdesivir was antiviral in respiratory Calu-3 cells, hydroxychloroquine was not.”

“we found that hydroxychloroquine and remdesivir were active in Vero cells with IC50s (concentration of a drug that is required for 50% inhibition) and CC50s (concetration of a drug that is required for 50% cell killing), demonstrating little cytotoxicity at the active doses (Figure 1B) (Wang et al., 2020).”

“Because Vero cells are derived from African green monkeys, we set out to identify a human cell line permissive to infection. To this end, we infected a panel of human cell lines with SARS-CoV-2 and monitored infection by microscopy.”

“Remdesivir and hydroxychloroquine were active against SARS-CoV-2 in Huh7.5 cells with IC50s that were more than 10-fold lower than those observed in Vero cells (Figure 2B).”

“We next focused on respiratory epithelial models because these are the most relevant to human SARS-CoV-2 infections. We found that a number of lung-derived epithelial cell lines were refractory to infection (e.g., A549, Calu-1, NCI-H292, CFBE41o). However, we found that Calu-3 cells, which have been shown to be permissive for many coronaviruses, including SARS-CoV-2, were readily infected (Figure 3A) (Hoffmann et al., 2020; Sheahan et al., 2020; Shen et al., 1994). We optimized assays using Calu-3 cells and tested their sensitivity to remdesivir and hydroxychloroquine. As expected, we found that the direct-acting antiviral remdesivir was active; however, hydroxychloroquine had little or no activity in Calu-3 cells (Figure 3B).”

“Cyclosporine is an FDA-approved generic drug that is readily available and showed a micromolar IC50 with high selectivity in both Huh7.5 and Calu-3 cells (Figures 3 and 4; Figure S4). Cyclosporine binds Cyclophilin A and prevents activation of the phosphatase calcineurin, which is required for the nuclear translocation of the nuclear factor of activated T cells (NFAT) (Friedman and Weissman, 1991; Hogan et al., 2003; Liu et al., 1991). Inhibition of this pathway in T cells is used as an immunosuppressant (Matsuda and Koyasu, 2000). Cyclosporins have been shown to have antiviral activity against a wide variety of viruses, including other coronaviruses (“

I think its very important to always look back. Initial reports were asymptomatic people could be the cause of large spreads – this seems to not be the case – Asymptomatic transmission of covid-19 | The BMJ

“Earlier estimates that 80% of infections are asymptomatic were too high and have since been revised down to between 17% and 20% of people with infections.12 Studies estimating this proportion are limited by heterogeneity in case definitions, incomplete symptom assessment, and inadequate retrospective and prospective follow-up of symptoms, however.3 Around 49% of people initially defined as asymptomatic go on to develop symptoms.”

“It’s also unclear to what extent people with no symptoms transmit SARS-CoV-2. The only test for live virus is viral culture. PCR and lateral flow tests do not distinguish live virus. No test of infection or infectiousness is currently available for routine use.678 As things stand, a person who tests positive with any kind of test may or may not have an active infection with live virus, and may or may not be infectious.9

The relations between viral load, viral shedding, infection, infectiousness, and duration of infectiousness are not well understood. In a recent systematic review, no study was able to culture live virus from symptomatic participants after the ninth day of illness, despite persistently high viral loads in quantitative PCR diagnostic tests. However, cycle threshold (Ct) values from PCR tests are not direct measures of viral load and are subject to error”

“The transmission rates to contacts within a specific group (secondary attack rate) may be 3-25 times lower for people who are asymptomatic than for those with symptoms.1121415 A city-wide prevalence study of almost 10 million people in Wuhan found no evidence of asymptomatic transmission.16 Coughing, which is a prominent symptom of covid-19, may result in far more viral particles being shed than talking and breathing, so people with symptomatic infections are more contagious, irrespective of close contact.17 On the other hand, asymptomatic and presymptomatic people may have more contacts than symptomatic people (who are isolating), underlining the importance of hand washing and social distancing measures for everyone.”

Ready to style in the modern day mask world – onsale today – Will.i.am and Honeywell make bet on fashionable high-tech face masks (cnbc.com)

Its super bad in Brazil 4195 deaths

Brazil and India need to be resolved or inevitable more variants.

MI certainly has a spread problem. Ohio leads death perhaps another reporting change.

Miami dade leads all counties for confirm. Postive news only 2 counties showed up on my death screen. Might need to lower the threshold.