More than 4.1 million new coronavirus infections were detected in the United States during this period, an increase of more than 85 per cent. In the country with 330 million residents, more than 61.5 million people are known to have been infected with the coronavirus so far. More than 839,000 infected people have died. Some 62.6 per cent of the population is considered vaccinated, and 36.5 per cent have received a booster vaccination so far.
Major US companies are now pulling back on plans to return to in-person work in light of the Omicron variants rapid spread across America. Employers planning to call remote workers back into the office in the new year are now pausing those efforts, and they are wary of setting new return dates only to push them back once again in the face of continued uncertainty and risks from the pandemic. Biden warns of winter of severe illness and death for those unvaccinated against Covid The pandemic is also driving changes in how in-person employees work, with a renewed push for strikes and unionization across several industries where workers have frequently faced long hours and unsafe conditions.
Alphabets Google, Meta, Apple, Uber, Lyft, Ford, DoorDash, DocuSign and Fidelity are among the companies that have delayed returns to the office.
Its warranted, given the uptick that weve seen in cases, Bradford Bell, director of the Center for Advanced Human Resource Studies at Cornell Universitys ILR School, said. The delays also depend on where the offices are located, he said. Theyre very much looking at this on a location-by-location basis. Apple CEO Tim Cook told employees in a memo on Wednesday that the partial return to offices, planned for 1 February, was now pushed to a date yet to be determined, after several other delays over the past two years. Cook offered employees a $1,000 bonus to help improve their home offices. Apples offices remain open and employees are still going into work in countries with lower Covid rates, he said. But he specifically pointed to the global rise in cases and the emergence of the Omicron variant as a cause for concern.NN: Let me intrude you to MR Shutdown. The dare i say normal. This is a major factor in our trade calculations……
(Reuters) – United Airlines Holdings Inc’s Chief Executive Scott Kirby said on Tuesday that the company had about 3,000 employees who have currently tested positive for COVID-19. In a note sent to employees, Kirby added that the company is reducing its near-term flight schedule. NN: what ever they are doing its not working. Their is no way airline filtration systems and mask are stopping the Omicron mutation
Jan 11 (Reuters) – The United States reported 1.35 million new coronavirus infections on Monday, according to a Reuters tally, the highest daily total for any country in the world as the spread of the highly contagious Omicron variant showed no signs of slowing. The previous record was 1.03 million cases on Jan. 3. A large number of cases are reported each Monday due to many states not reporting over the weekend. The seven-day average for new cases has tripled in two weeks to over 700,000 new infections a day. The record in new cases came the same day as the nation saw the number of hospitalized COVID-19 patients also hit an all-time high, having doubled in three weeks, according to a Reuters tally. There were more than 136,604 people hospitalized with COVID-19, surpassing the record of 132,051 set in January last year. While the Omicron variant is potentially less severe, health officials have warned that the sheer number of infections could strain hospital systems, some of which have already suspended elective procedures as they struggle to handle the increase in patients and staff shortages. The surge in cases has disrupted schools, which are struggling with absences of staff, teachers and bus drivers. Chicago canceled classes for a fourth day as the district and teachers failed to agree on how to deal with increased infections. New York City suspended service on three subway lines as a large number of workers were out sick, according to its Twitter account. Companies’ plans for workers to return to office have also been derailed.
Deaths are averaging 1,700 per day, up from about 1,400 in recent days but within levels seen earlier this winter.
A redesigned COVID-19 vaccine that specifically targets the Omicron variant is likely needed, Pfizer Inc’s PFE.N CEO said on Monday, adding his company could have one ready to launch by March. U.S. breaks COVID-19 hospitalization record at over 132,000 as Omicron surges Pfizer CEO says Omicron-targeted vaccine is most likely outcome. NN: DO not be fooled the Omicron mutation is a beast. And the hospitalizations which lag behind infections are climbing. The next shoe to drop will be the death rate which is a lagging indicator. Because it is so infectious and people are so resistant to masking up and isolating and vaccines a dangerous decision has been made. Do nothing and let the chips fall where they may. By the fact one is a leader the assumptions is your smarter then the average bear AND you are willing to make the hard decisions no matter how unpopular they may be. unfortunately clueless spinless leadership is the order of the day. And the masses will pay a extreme price. You might notice how the smart money is in shutdown mode. AS we long predicted their will be no government imposed lockdowns. But instead VOLUNTARY shut downs.
SYDNEY (Reuters) – Major share markets made cautious gains on Monday as investors counted down to another U.S. inflation reading that could well set the seal on an early rate hike from the Federal Reserve, lifting bond yields yet further. The explosion in coronavirus cases globally also threatens to crimp consumer spending and growth just as the Fed is considering turning off the liquidity spigots, tough timing for markets addicted to endless cheap money. That made for wary trading with S&P 500 futures adding 0.1% and Nasdaq futures 0.2%. EUROSTOXX 50 futures and FTSE futures both edged up 0.2%. MSCI’s broadest index of Asia-Pacific shares outside Japan added 0.3%, while South Korea lost 1.0%. Chinese blue chips were a fraction firmer as recent policy easing was balanced by lingering concerns over the property sector. Analysts fear the U.S. consumer price report on Wednesday will show core inflation climbing to its highest in decades at 5.4% and usher in a rate rise as soon as March. While the December payrolls number did miss forecasts, the drop in the jobless rate to just 3.9% and strength in wages suggested the economy was running short of workers. “It was consistent with the Fed’s evolving view that the labour market is getting close to or is already at maximum employment with wage pressures building,” said analysts at NatWest Markets. “This should add to speculation about a March hike, and we have pulled our expectation for the Fed’s lift-off to occur in March instead of June.” A raft of Fed officials will be out to offer their latest thinking this week, including Chair Jerome Powell and Governor Lael Brainard who face confirmation hearings. Markets quickly shifted to reflect the risks with futures implying a greater than 70% chance of a rise to 0.25% in March and at least two more hikes by year end.
Technology and growth stocks tumbled as investors switched to banks and energy firms, while bonds took a beating.
Yields on 10-year U.S. Treasury notes were near highs last seen in early 2020 at 1.765%, having shot up 25 basis points last week in their biggest move since late 2019. The next chart target is the 1.95/1.97% area. [U/S] “We think that the increase in long-dated Treasury yields has further to run,” said Nicholas Farr, an economist at Capital Economics. “Markets may still be underestimating how far the federal funds rate will rise in the next few years, so our forecast is for the 10-year yield to rise by around another 50bp, to 2.25%, by the end of 2023.” The Fed’s hawkish shift has tended to benefit the U.S. dollar, though it ran into profit taking on Friday after the payrolls report failed to meet the market’s lofty expectations. The dollar index edged up to 95.900, after falling 0.5% on Friday only to find support at 95.700. The euro stood at $1.1336, leaving it near the top of the recent $1.1184/1.1382 trading range. The Japanese yen got a brief break from its recent bear run to stand at 115.74, as the dollar faded from last week’s 116.34 peak. NN: We need to wait and see how the markets sort all this out.
“Well, today’s jobs report ends 2020 on a sour note. We saw payrolls slow well below expectations and in fact even more sluggish payroll growth than what we saw in November, which we were hoping to see, was a bit of a fluke. On top of that, even though we’ve actually seen a pretty significant slowdown in jobs growth in the last two months as the Delta and Omicron variants have took their toll. We have actually seen over six million jobs added over the course of 2021, which is a record high and I think really speaks to the fact that we’ve actually seen significant job growth over the year, despite the conversations and discussions we’ve been having about how difficult it is for employers to hire.” NN: We have two key events. The omicron mutation that is ripping through society. It is obvious the powers that be do not want to provuide tests. And the game they are playing is let the virus rip through society. As often pointed out no more lock downs. As you are seeing its shut down time again. The unemployment numbers picked up the fact that the smart people are staying at home and not working. The other element to this is the run away inflation. The Fed really fucked up by waiting a year to put out the fire. The twin curse of the FED pulling stimulus and raising rates along with an economy that could suck shut again because of the Omicron spread will devastate the markets
WASHINGTON, Jan 7 (Reuters) – COVID-19 hospitalizations in the United States are poised to hit a new high as early as Friday, according to a Reuters tally, surpassing the record set in January of last year as the highly contagious Omicron variant fuels a surge in infections. Hospitalizations have increased steadily since late December as Omicron quickly overtook Delta as the dominant coronavirus variant in the United States, although experts say Omicron will likely prove less deadly than prior iterations. While potentially less severe, health officials have warned that the sheer number of infections caused by Omicron could strain hospital systems, some of which have already shown signs of distress, partly due to staffing shortages.
“I don’t believe we’ve seen the peak yet here in the United States,” Centers for Disease Control and Prevention (CDC) Director Rochelle Walensky told NBC News’ “Today” program on Friday, as schools and businesses also struggle with rising caseloads.
The United States reported 662,000 new COVID-19 cases on Thursday, the fourth highest daily U.S. total coming just three days after a record of nearly 1 million cases was reported, according to the Reuters tally. The seven-day average for new cases set a record for a 10th consecutive day at 597,000, while COVID hospitalizations reached nearly 123,000 and appeared poised to top the record of over 132,000 set last year. Deaths, an indicator that lags hospitalizations, remain fairly steady at a still high 1,400 a day, according to the tally, well below last year’s record numbers. New York Governor Kathy Hochul and the head of one of the largest U.S. hospitals both said they were cautiously optimistic that cases and hospitalizations would soon plateau in the state. “We think with our modeling that the peak will happen next week,” said Steven Corwin, chief executive of New York-Presbyterian Hospital, during Hochul’s daily briefing.
Delaware, Illinois, Maryland, Pennsylvania, Ohio, Vermont and Washington, D.C., all reported record levels of hospitalized COVID patients in recent days, according to the Reuters analysis.
Hospitalization data, however, does not differentiate between people admitted for COVID-19 and so-called incidental positives. Those are patients who were admitted and treated for issues other than COVID-19 and contracted the virus while in the hospital and are counted in coronavirus hospitalization numbers. Incidental infections have occurred throughout the pandemic but might be significantly higher now due to the staggering pace of Omicron’s spread – a phenomenon that has prompted state health departments to consider altering their disclosures. Starting next week, Massachusetts hospitals will report whether admissions are primary or incidental to COVID-19, said Kathleen Conti, a spokesperson for the state’s department of health. Rising cases have forced hospital systems in nearly half of U.S. states to postpone elective surgeries. While many school systems have vowed to continue in-person instruction, some have faced ad hoc closures as cases rise. Chicago Public Schools, the third-largest U.S. school system, were closed for a third day on Friday amid a teacher walkout over COVID-19 protections. U.S. and other officials have said schools can be safely opened, especially with widely available vaccines and boosters, and the CDC on Thursday issued new isolation policy guidelines for schools. Officials continue to press vaccinations as the best protection against serious illness, although federal mandates requiring them have become politically contentious. U.S. Supreme Court justices on Friday grilled Republican state officials and business groups seeking to block President Joe Biden’s vaccine-or-testing mandate for large businesses and pressed the administration to justify the policy at a time of surging COVID-19 cases nationwide.] The U.S. Food and Drug Administration on Friday shortened the interval between the primary series of the Moderna MRNA.O COVID-19 vaccine and a booster dose from six months to five for people aged 18 or older. The regulatory decision comes days after the agency made a similar move for getting a booster shot of the Pfizer PFE.N and BioNTech BNTX.O COVID-19 vaccine. The Pfizer booster has also been authorized for use in children aged 12 to 15. Overwhelmed by Omicron surge, U.S. hospitals delay surgeries. NN: this show the complete lack of leadership. The system is crushed. Of course they are not gong to admit to their failures. As they disclose record hospitalizations they are quick to tell us the Omicron mutation is less infectious and less deadly. I am sure you feel the same way as i do… their claims are not comforting to me.. REALLY less deadly well reality is something is shutting down the economy as we predicted and filling covid isolation ward of the hospitals with a lot of very very sick people. So for me its time for the booster shot, vitamin up, mask up, test test test andlive for now in self imposed isolation. And ill let the stupid money be the lab rats as this sorts itself out.
Citation: Ajayi AAL. Drugs Shown to Inhibit SARS-CoV-2 in COVID-19 Disease: Comparative Basic and Clinical Pharmacology of Molnupiravir and Ivermectin. Austin J Pharmacol Ther. 2021; 9(5).1149.Austin J Pharmacol Ther – Volume 9 Issue 5 – 2021ISSN: 2373-6208 | www.austinpublishinggroup.com Ajayi. © All rights are reservedAustin Journal of Pharmacology and TherapeuticsOpen AccessAbstractThe pharmacology of anti-SARS-CoV-2 drugs, Molnupiravir (M) and repurposed Ivermectin (IV) were compared. The IC50 for the inhibition of viral replication were 0.3μM for M and 2.8μM for IV. Both drugs have good oral absorption, with M achieving peak plasma concentrations by 2 hours and IV by 5 hours. The plasma half life were 7 hours for M and 81-91 hours for IV. M inhibits viral replication inducing viral mutagenesis in RdRp, causing viral error catastrophe and viral extinction. IV affects viral cell entry, nuclear transport and inhibits replication via RdRp. IV has additional effect to suppress cytokine production through STAT-3 inhibition. M is a more potent antiviral drug and IV has a longer residence in the body. Their effects on RdRp and cytokine inhibition are potentially complimentary for anti-COVID-19 activity. Both IV and M should be compared in randomized controlled clinical trials, and the possibility of their combination for anti-SARS-CoV-2 antiviral actions, explored further. Keywords: COVID-19; Antiviral therapeutics; Molnupiravir; Ivermectin; CombinationIntroductionThe COVID-19 pandemic caused by SARS-CoV-2, has affected more than 120 million people and resulted in nearly 3 million deaths worldwide. Although vaccine roll out is mitigating the community transmission and enabling a reopening of global economy piecemeal, there are still many nations where vaccines are not yet widely available, and new viral variants are emerging. There is a gradual shift in focus, to antiviral drugs, both for possible adjunctive chemoprophylaxis, as well as for active treatment of patients with new SARS-CoV-2 infections, or post -vaccination breakthrough COVID-19 cases. There have been purposive efforts, to develop novel and specific antiviral drugs for SARS-CoV-2, and to repurpose existing FDA -approved drugs to treat COVID-19. Molnupiravir is the most advanced of the novel antiviral drugs undergoing clinical development and trials, whilst Ivermectin is the most studied “repurposed” medication globally, in randomized clinical trials, retrospective studies and meta-analyses. This mini- review examines and compares their basic and clinical pharmacology and the possible utility of their combination, in treating COVID-19 and future corona virus diseases.Molnupiravir and Ivermectin Anti-SARS-CoV-2 Mechanisms, Pharmacokinetics and PharmacodynamicsMolnupiravir (EIDD2801/MK-4482) is a pro-drug of the novel active antiviral nucleoside analogue β-d-N4-hydroxycytidine (NHC, EIDD1931) [1]. It’s a broad spectrum antiviral agent against SARS-CoV-2, SARS-CoV,seasonal or pandemic influenza and MERS corona virus [1]. The basic and clinical pharmacological properties are shown on Table 1. Ivermectin is an FDA-approved, WHO essential drug used as broad spectrum antiparasitic, antibiotic and Ajayi AAL*Department of Medicine, Division of Hypertension and Clinical Pharmacology, Baylor College of Medicine, USA*Corresponding author: Ajayi AAL, Department of Medicine, Division of Hypertension and Clinical Pharmacology, Baylor College of Medicine, Houston TX 77030, USAReceived: July 10, 2021; Accepted: August 03, 2021; Published: August 10, 2021Mini ReviewDrugs Shown to Inhibit SARS-CoV-2 in COVID-19 Disease: Comparative Basic and Clinical Pharmacology of Molnupiravir and Ivermectinwhich has demonstrated broad spectrum antiviral activity against RNA viruses, including HIV, Zika, MERS corona virus. It is being repurposed as a therapeutic agent for COVID-19, after in vitro studies in Vero/hSLAM cells, showed that it caused a 5000-fold inhibition of SARS-CoV-2, (99.98% at 48 hours) with an IC50 of 2.8μM [2]. The corresponding in vitro IC50 of molnupiravir for SARS-CoV-2 is 0.3μM in Vero cells and 0.08μM in Calu-3 Cells [3]. The IC50 of Molnupiravir shows it to be a more potent anti-SARS-CoV-2 agent, compared to Ivermectin in vitro. Both molnupiravir and ivermectin are well absorbed after oral dosing, the Tmax of molnupiravir being 1-1.75 hours , with a half life of 7 hours, 1 whilst the Tmax of ivermectin is 4-6 hours, and a very long half life of 81-91 hours [4]. Ivermectin, being lipophilic has a large volume of distribution (Vd) and the ability to accumulate in the lungs [5], the major target organ of COVID-19. Molnupiravir is given twice daily, and doses of 400 and 800 mg showed viral clearance by RT-PCR [1]. By contrast, the dosing regimen of ivermectin in randomized clinical trials with RCT-PCR SARS-CoV-2 clearance, varied from 12mg daily [6], to 12mg twice a week [7]. The anti-SARS-CoV-2 actions, both of molnupiravir and ivermectin, are dose and concentration dependent [1,7]. Pharmacodynamically, the mechanisms of anti-SARS-CoV-2 action, both of molnupiravir and ivermectin are overlapping and complimentary (Table 1). Molnupiravir active metabolite (NHC-5’ Triphosphate), acts as a competitive alternative substrate for the viral RNA dependent RNA polymerase (RdRp), causing viral mutagenesis or transition mutations, which leads to viral error catastrophe and extinction of replication [8]. There is some concern about the safety of NHC -nucleoside triphosphate, which is also mutagenic to mammalian cells [9]. Ivermectin (Table 1) exhibits multifarious actions, ranging from binding to SARS-CoV-2 spike protein S, reducing cell entry via human ACE2 receptors, inhibition of the
Austin J Pharmacol Ther 9(5): id1149 (2021) – Page – 02Ajayi AALAustin Publishing GroupSubmit your Manuscript | www.austinpublishinggroup.comnuclear transport of viral proteins, which prevents interference with replication, to binding to RdRP, reducing the activity of the viral transcription -replication complex [10]. Ivermectin has additional effects on Signal Transduction Activation of Transcription (STAT-3) and inhibition of cytokine production and inflammation, which has not yet been shown for molnupiravir.As most but not all double blind studies, and meta-analyses, have shown benefits of ivermectin in COVID19 including 56% mortality reduction [11], and given the complimentary pharmacokinetics and pharmacodynamics of the drugs, direct head -to -head comparison of molnupiravir and ivermectin, in blinded randomized clinical trials are needed. A combination of molnupiravir with Ivermectin putatively, may be at least additive or synergistic in effects on RdRP or cytokine release. This should be further investigated in anti-SARS-CoV-2 antiviral combination therapy.References1.Painter WP, Holman W, Bush JA, Almazedi F, Malik H, Eraut CJEN, et al. Human safety, tolerability, and pharmacokinetics of Molnupiravir, A novel broad- spectrum oral antiviral agent with activity against SARS-CoV-2. Antimicrob Angents Chemother. 2021; 65: e02428-e02520.2.Caly L, Druce JD, Catton MG, Jans DA, Wagstaff KM. The FDA -approved MolnupiravirIvermectinChemical structure/NameRiboNucleoside analogue. Pro-drug of β-d-N4 Hydroxycytidine (NHC), EIDD 280122,23 dihydroavermectin B1a + B1b (80:20) mixturePharmacokineticsAbsorption and F Distribution (Vd) Metabolism Excretion routes T ½ (hours) Mean Residence Time (hours) Tmax (hours)Daily dosesSARS-CoV2 IC50RapidProdrug > EIDD1931 (plasma esterases) > active 5’ATP EIDD (tissue kinases).7 hours?1-1.75 hours20.3μM (Vero cells) 0.08μM (Calu cells)414.6 nM (Syrian Hamster)Good 9-12L/KgHepatic CYP3A4 mainly, 3A5, 2C9, 2D6Fecal >99%81-91 hours84 hours5 hours12.5-2-8 μM (E, RdRP cell associated virus genes)Vero-h/SLABPharmacodynamicsAntiviral mechanisms•Cell viral entry-hACE2 receptor. •Nuclear transport -importin α/β1•RNA dependent, RNA polymerase (RdRp)*Viral mutagenesisDose/Concentration-anti SARS-CoV-2 response??Competitive alternative substrate for SARS-CoV-2 RdRP viral genome >excessive mutations > viral error catastrophe > viral extinction.YesDose -Dependent Viral RNA clearance in human phase 2A study.Binds to active sites of spike protein S. Inhibits human cell entrance of virus via h-ACE2.Binds Importin α to prevent link with β1 and nuclear transport of viral and host proteins.Binds to and inhibits viral RdRp replication and transcription complex with -9.7Kcal/mol energyNoSignificant dose and concentration dependent virucidal response seen in humans.Effects on Cytokines & interleukins (IL)?Inhibits Janus Kinase (JAK) Signal transduction Activator of Transcription (STAT-3) and IL-6/10Clinical Trials and Real World EfficacyRT-PCR CasesPhase 2A shows dose dependent high anti-SARS-CoV-2 efficacy in COVID-19.Mixed outcomes. Meta-analyses show clinical and laboratory benefits and mortality reduction. Adverse effects and Drug-Drug InteractionsNo Serious Adverse effects compared to placebo.No Serious Adverse Effects. Dizziness Table 1: Comparison of Anti-SARS-CoV-2 pharmacology of Molnupiravir and Ivermectin.drug ivermectin inhibits the replication of SARS-CoV-2 in vitro. Antiviral Res. 2020.3.Sheahan TP, Sims AC, Zhou S, Graham RL, Pruijsssers AJ, Agostini ML et al. An orally bioavailable broad-spectrum antiviral inhibits SARS-CoV-2 in human airway epithelial cell cultures and multiple corona viruses in mice. Sci Trans Med. 2020; 12: eabb5883.4.Munoz J, Ballester MR, Antonijoan RM, Gich I, Rodriguez M, Colli E, et al. Safety and pharmacokinetic profile of fixed dose ivermectin with an innovative 18 mg tablet in healthy adult volunteers. PLoS Negl Trop Dis. 2018; 12: e0006020.5.Duthaler U, Suenderhauf C, Karlsson MO, Hussner J, Schwabedissen HMZ, Krahenbull S, et al. Population pharmacokinetics of oral ivermectin in venous plasma and dried blood spots in healthy volunteers. Br J Clin Pharmacol. 2019; 85: 626-633.6.Elgazzar A, Hany B, Yousef SA, Hafez M, Moussa H. Efficacy and safety of ivermectin for treatment and prophylaxis of COVID-19 pandemic in Egypt. 2020.7.Babalola OE, Bode CO, Ajayi AA, Alakaloko FM, Akase IE, Otrofanowei E, et al. Ivermectin shows clinical benefits in mild to moderate COVID-19: A randomized controlled, double blind, dose response study in Lagos. QJM An international Journal of Medicine. 2021.8.Wahl A, Gralinski LE, Johnson CE, Yao W, Kavarova M, Dinnon 3rd KH, et al. SARS-CoV-2 is effectively treated and prevented by EIDD-2801. Nature. 2021; 591: 451-457.
Today, the U.S. Food and Drug Administration amended the emergency use authorization (EUA) for the Moderna COVID-19 Vaccine to shorten the time between the completion of a primary series of the vaccine and a booster dose to at least five months for individuals 18 years of age and older.
“The country is in the middle of a wave of the highly contagious omicron variant, which spreads more rapidly than the original SARS-CoV-2 virus and other variants that have emerged,” said Peter Marks, M.D., Ph.D., director of the FDA’s Center for Biologics Evaluation and Research. “Vaccination is our best defense against COVID-19, including the circulating variants, and shortening the length of time between completion of a primary series and a booster dose may help reduce waning immunity. Today’s action also brings consistency in the timing for administration of a booster dose among the available mRNA vaccines. We encourage everyone to get vaccinated—it’s never too late to get your COVID-19 vaccine or booster.”
The most commonly reported side effects by individuals who received a booster dose of the Moderna COVID-19 Vaccine after completion of a two-dose primary series were pain, redness and swelling at the injection site, as well as fatigue, headache, muscle or joint pain and chills. The fact sheets for recipients and caregivers and for healthcare providers include information about the potential side effects, as well as the risks of myocarditis and pericarditis.
The amendment to the EUA was granted to ModernaTx Inc.
