Challenges And Opportunities As mRNA Manufacturing Spreads Its Wings Beyond COVID-19 Vaccines – In Vivo

Challenges And Opportunities As mRNA Manufacturing Spreads Its Wings Beyond COVID-19 Vaccines – In Vivo

Antiviral drugs in the treatment of COVID-19 | IDR – Dove Medical Press

Antiviral drugs in the treatment of COVID-19 | IDR – Dove Medical Press

August 18, 2022

Introduction

Coronavirus Disease-2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread in many countries and regions around the world since 2019. At present, more than 250 million people have been infected and millions have died. Although vaccination and isolation of patients have been implemented in various countries, more than 100,000 new patients are added daily. Previous studies have shown that about 19% of COVID-19 patients develop into severe or critical diseases,1 and the mortality rate is more than 15%.2 In addition to severe lung injury and functional changes, patients will also lead to complications such as liver, nervous system and gastrointestinal tract. Single drug may not achieve therapeutic effect. At the same time, the combined use of multiple drugs will increase the risk of drug interactions, resulting in reduced or increased drug exposure, affecting the efficacy and safety of treatment. Therefore, drug selection and diagnosis and treatment plan determination have great challenges.3 Treatment of COVID-19 has not yet been defined. Early antiviral therapy is based on the experience of fighting SARS and MARS, and a large number of clinical trials are carried out to verify the efficacy of drugs.4 China National Health Commission has issued eight editions of new coronavirus pneumonia diagnosis and treatment programs. Interferon, lopinavir/ritonavir, ribavirin, chloroch and abidol are among the recommended drugs for the treatment programme.5 Currently, according to various versions of our pneumonia treatment protocols and studies for novel coronavirus infections,6 antiviral drugs such as ribavirin, abirater and lopinavir are included in the treatment of COVID-19 in China. Redsivir is currently in clinical trials and has not been put into use on its own, but only as an adjuvant drug in conjunction with it. NIH guidelines indicate that the antiviral drugs currently available as therapeutic agents in the US are Redsivir, Paxlovid and Monupivir. Meanwhile, after two years of clinical research and practice, more relevant results have been published. Although there are many reviews that have done the same work we have done, searching for and summarising the effectiveness and safety of antiviral drugs, the main drugs analysed and the focus of each review varies and does not provide a detailed summary of the effectiveness and safety of all drugs, and over time, new characteristics of the physicochemical properties of some drugs are identified. In order to obtain a more comprehensive and higher level of research evidence, this article systematically evaluates the efficacy and safety of antiviral drugs for the treatment of COVID-19 based on published clinical findings. This review adds to certain aspects of drugs and medications not summarised in other reviews and is helpful in how antiviral drugs are used to treat neocrown pneumonia.

All the research literatures on antiviral drug treatment COVID-19 from December 2019 to December 2021 in CNKI, PubMed, Embase, Wanfang and VIP databases were searched by computer. Chinese search terms include: novel coronavirus, novel coronavirus pneumonia, novel coronavirus, novel coronavirus pneumonia, COVID-19, antiviral, antiviral therapy, treatment, research, trials, clinical trials. Keywords: COVID-19 (Mesh), 2019-nCo V, SARS-CoV-2, treatment, treatment, clinical observation, antiviral therapy, antiviral.

Inclusion criteria: (1) Confirmed cases according to the ninth edition of the Guidelines for the Diagnosis and Treatment of New Coronavirus Pneumonia: suspected cases also have one of the following etiological or serological basis: 1) positive nucleic acid detection of new coronavirus; 2) positive specific IgM antibody and IgG antibody of new coronavirus in those who are not vaccinated with new coronavirus vaccine.

(2) Use antiviral therapy, and describe the clinical outcome; (3) A complete description of the treatment plan with major efficacy or safety outcomes; (4) It is a prospective or retrospective Chinese or English study published in public. The research types include randomized controlled trials (RCT), non-randomized controlled trials (N-RCT), case-control studies, and cohort studies.

Exclusion criteria: (1) Traditional Chinese medicine, immunotherapy as the main treatment; (2) Summary, case report; (3) Patients are diagnosed as suspected cases; (4) Selective reporting results; (5) Studies describing clinical features.

The literature retrieved by two researchers independently read and evaluated, and the literature was screened according to the inclusion and exclusion criteria, such as the controversial introduction of the third researcher to discuss and decide.

Extract the final information included in the literature. The contents included: (1) Basic information: research area, time, author; (2) Baseline special diagnosis of the subjects: age, disease type, number of cases, number of shedding cases; (3) Research program: research type, research program, course of treatment; (4) Outcome indicators: treatment efficacy, death, adverse reactions.

A total of 1508 articles were retrieved, 273 articles with similar contents were excluded, 1059 articles were excluded after reading topics and abstracts, and 155 articles were excluded after further reading. A total of 21 articles were included.725 The results of literature retrieval included 12 Chinese and 9 English, including 5 randomized controlled studies (RCT), 5 non-randomized controlled studies (N-RCT), 3 retrospective cohort studies, 6 retrospective case series studies, 2 observational studies, and a total of 2118 cases. The results are shown in Table 1.

Table 1 Characteristics of the Included Studies

Two RCTs evaluated the efficacy of lopinavir/ritonavir on COVID-19 with inconsistent results.7,8 Both lopinavir/ritonavir and control were administered at 400mg/100mg, po, bid. Lopinavir/ritonavir did not show obvious advantages in severe patients, and the median clinical improvement time was similar to that in the conventional treatment group (16d vs 16d, P>0.05). The 28d mortality rate was 5.8% lower than that in the conventional treatment group.7 However, RCTs conducted in ordinary patients showed that the addition of Lopinavir/ritonavir on the basis of interferon- and lianhuaqingwen capsule could improve the treatment efficiency (76.67% vs 46.67%, P< 0.05), but the sample size of this study was small.8 Another N-RCT compared the efficacy of lopinavir/ritonavir versus fapiravir in the treatment of mild and common COVID-19. There were 35 patients in the FPV group and 45 patients in the control group, and the drug was administered as falopir 1600 mg, po, bid on day 1, 600 mg, po, bid on day 214, and lopinavir/ritonavir 400 mg/100 mg, po, bid. Changes in chest computed tomography (CT), viral clearance and drug safety were compared between the two groups, with 32 in the FPV group and 28 in the control group. Fapiravir was superior to lopinavir/ritonavir in median virus clearance time (4d vs 11d, P<0.001) and lung CT improvement at 14d (91.43% vs 62.22%, P=0.004).9 Lopinavir/ritonavir was used in four case series studies.1012 There were 83 cases in total. No patient died, only 1 case developed into severe disease, and 3 cases were transferred to hospital.

In one RCT, subjects were treated with 1200 mg/d for 1 to 3 days followed by 800 mg/d for 23 weeks. The RCT showed that there was no significant difference in virus negative conversion rate between hydroxychloroquine group and standard nursing group on day 28 (85.4% vs 81.30%, P=0.314), but the use of hydroxychloroquine could significantly improve clinical symptoms such as fever and cough.13 The efficacy of hydroxychloroquine for COVID-19 in a small sample of N-RCT at 400 mg, po, qd, was similar to that in the conventional treatment group, and the median time of virus negative conversion was longer than that in the control group (4d vs 2d, P>0.05). One case in the hydroxychloroquine group developed into severe disease.12 Another N-RCT compared the clinical outcomes of patients with COVID-19 who were treated with hydroxychloroquine plus azithromycin, hydroxychloroquine alone and untreated. Hydroxychloroquine is administered as 200 mg, po, bid, with azithromycin added as clinically indicated, 500 mg on day 1 and 250 mg daily for the next 4 days, with virus negative conversion rates of the three groups on the sixth day were 100%, 57.1% and 12.5%, respectively (P<0.001). The use of azithromycin could significantly improve the clearance effect of hydroxychloroquine on viruses, and the two had synergistic effects.12 In view of the results of this study, another retrospective cohort study based on the data of the U.S. Veterans Health Management Center included 368 patients with COVID-19, and also compared the mortality and mechanical ventilation ratio of patients with COVID-19 who were treated with azithromycin, with or without hydroxychloroquine. The results showed that hydroxychloroquine did not reduce the mechanical ventilation ratio (6.9% vs 13.3% vs 14.10%, P=0.547), but increased the mortality (22.1% vs 27.8% vs 11.40%, P=0.03).14 The use of azithromycin can reduce the proportion of mechanical ventilation and mortality.

In an RCT comparing the efficacy of abirater and lopinavir/ritonavir in the treatment of mild to moderate COVID-19, lopinavir/ritonavir was administered at 400mg/100mg, po, bid and abirater at 0.2g, po, tid. The RCT showed no significant difference in viral clearance time and viral clearance rates on days 7 and 14.15 A small sample retrospective cohort study showed that the virus clearance rate on the 7 th and 14 th day and chest CT performance on the 7 th day were significantly improved in the combination of Abidol and Lopinavir/Litonavir compared with Lopinavir or Litonavir alone (P<0.05).16 Another RCT compared the efficacy of abidol with that of fapravi. A total of 240 patients were randomly assigned in a 1:1 ratio to receive treatment. In the trial, fapravi was administered at 1600 mg, po, bid on day 1 and 600 mg, po, bid on day 210, while abidol was administered at 0.2 g, po, tid. There was no difference in the recovery rate and time to viral regression in the Arbidol group, with 71 recoveries out of 116 in the Favipiravir group and 62 recoveries out of 120 in the Arbidol group, but fapravi had obvious advantages in relieving clinical symptoms such as fever and cough, and the improvement time was 1.7 days shorter than that of abidol (P<0.001).17

A retrospective analysis of 224 patients with COVID-19 showed that there were no significant differences in the negative conversion time of viral nucleic acids in respiratory tract specimens, the negative conversion rate of viral nucleic acids within 14 days, the proportion of progression to severe disease after admission and the overall incidence of adverse reactions between multiple treatment regimens (interferon- alone, interferon- + lopinavir/ritonavir, interferon- + ribavirin, interferon- + lopinavir/ritonavir + ribavirin, other solutions) (P>0.05).18 A N-RCT study included 62 patients with COVID-19, and the results showed that there was no significant difference in fever clearance time, symptom relief time, nucleic acid negative conversion time and hospitalization time between the treatment group and the control group (P>0.05). In the severe group, the nucleic acid negative conversion time in the treatment group was significantly longer than that in the control group [(23.62 2.12)d vs (9.25 0.95)d], and the difference was statistically significant (P<0.05).19

A retrospective analysis examined the efficacy of favipiravir (FPV) in the treatment of COVID-19.20 Experimental group was famipiravir at 1600 mg, twice a day, then 600 mg, twice a day, for 9 days and control group was herbal medicine, nutrition and oxygenation. The results showed that there was no significant difference in hospitalization time between the treatment group (29 (24, 39)d) and the control group (32 (22, 44)d)(=0.575). The median time of novel coronavirus nucleic acid negative conversion was 25 (18, 33) d in the treatment group and 25 (13, 40) d in the control group (P=0.982). The incidence of severe disease in the treatment group was significantly lower than that in the control group (6.12% vs 21.77%), and the difference was statistically significant (P=0.000). The chest CT remission time of the treatment group (9.38 4.94) d was shorter than that of the control group (13.44 4.67)d, and the difference between the two groups was statistically significant (P= 0.033).

An observational study that included only 11 patients with COVID-19 common type showed that the combination of danorrvir and ritonavir had better curative effect.21 The median time of virus negative conversion was 2 days, and the median time of lung CT obvious absorption was 3 days. All 11 patients were cured and discharged.

In a national multicentre randomised double-blind placebo-controlled trial, patients were randomly allocated in a 2:1 ratio to either intravenous raltegravir (200 mg on day 1, followed by 100 mg on days 210 as a single daily infusion) or the same volume of placebo for 10 days. A total of 237 patients were enrolled, 158 receiving raltegravir and 79 receiving placebo. The results showed that there was no significant difference in the clinical improvement time of patients with severe diseases between Redsivir and placebo, which were 21 d and 23 d, respectively. The mortality rates of the two groups were also close, which were 14% and 13%,22 respectively. Another observational study of international multicenter patients with severe COVID-19 sympathizing with the use of Redsivir showed that 68% of 53 patients had clinical improvements, 57% had extubation, 47% were discharged and 13% died.23

Thirteen studies described adverse events.7,1113,1519,2224 Among the three RCTs, the incidence of adverse events in the lopinavir/ritonavir group was 35.3%, 48.4% and 55.56%,6,15,24 respectively, mainly gastrointestinal reactions. Another retrospective cohort study using lopinavir/ritonavir also reported gastrointestinal dysfunction in 43.7% of patients.16 Severe gastrointestinal adverse reactions caused by lopinavir/ritonavir led to withdrawal of 13% of patients in one study. In a case series of only 10 patients, 30% of patients stopped taking lopinavir because of gastrointestinal discomfort.11

There was no significant difference in the overall incidence of adverse reactions among different antiviral regimens in the comparison of one antiviral treatment for COVID-19 (P=0.080), but there was significant difference in the incidence of nausea/vomiting, diarrhea and dyslipidemia among different regimens (P < 0.05).18 The incidence of gastrointestinal adverse reactions and dyslipidemia in patients receiving three antiviral drugs were significantly higher than those receiving 12 antiviral drugs (P<0.05). Another study also showed that Lopinavir/Rituximab combined with interferon- antiviral therapy could cause higher incidence of diarrhea.19

In addition to Lopinavir/Ritalinavir, the safety of Redsivir needs to be paid attention to. The total incidence of adverse events in the two studies was 66% and 60%, respectively, and the incidence of severe adverse events was 18% and 12%, respectively, including multiple organ dysfunction, septic shock, acute kidney injury and hypotension, which led to the withdrawal of 18 patients (12%) and 4 patients (7.5%),22,23 respectively. Other reported adverse events included nausea caused by light chlorine chirp (one patient was discontinued), diarrhea, and elevation of transaminase, elevation of serum uric acid caused by fapravi, and elevation of bilirubin caused by abidol.

At present, the epidemic of COVID-19 is globalized, but there is no evidence-based medical evidence to support antiviral drugs for new coronaviruses. Therefore, it is extremely important to explore effective treatment regimens as soon as possible to control the epidemic.

Lopinavir/ritonavir is one of the earliest recommended antiviral drugs. Multiple controlled trials showed that the clinical efficacy of lopinavir/ritonavir on COVID-19 was poor, but it caused serious gastrointestinal adverse reactions, so the proportion of withdrawal could reach 13%. The adverse reactions of lopinavir/ritonavir mostly occurred in the early stage of medication, and the recommended course of treatment for COVID-19 was 10 days. The risk of adverse reactions at this stage was high, and medication safety should be closely monitored. Ritonavir is a potent CYP3A4 inhibitor and also inhibits P-glycoprotein transporters. Lopinavir is also a substrate of CYP3A and P-glycoprotein, which can interact with many drugs and cause adverse reactions.9 For COVID-19 patients with more complications, drug interactions should be examined before starting the use of lopinavir/ritonavir to avoid serious adverse reactions.

Chloroquine is also used in the treatment of COVID-19 as an old antimalarial drug. In addition to the recommended treatment plan in China, the FDA also approved that chloroquine and hydroxychloroquine can be used in adult and adolescent COVID-19 inpatients with body weight greater than 50 kg in emergency situations.25 Based on published research data, whether chloroquine or light chloroquine has curative effect on COVID-19 and whether use increases mortality remains unclear. The synergistic effect of azithromycin and hydroxychloroquine also needs further clinical trials to verify. The American Society of Infectious Diseases recommended the application of chloroquine and hydroxychloroquine in clinical trials in the COVID-19 Guidelines for Treatment and Management, while the addition of azithromycin can only be used in clinical trials, and it is not recommended as a conventional treatment.26 The safety of chloroquine and hydroxychloroquine in clinical use is also concerned, which can often cause gastrointestinal reactions, skin allergy, and serious liver and kidney function and cardiac dysfunction. Conditional medical institutions can monitor the plasma concentration. When the plasma trough concentration is greater than 0.8 g/mL, the risk of adverse reactions increases, and it is recommended to reduce the dose. Clinical trial data showed that hydroxychloroquine 600 mg daily, taken three times, the plasma concentration was (0.46 0.2) g/mL, the dose was relatively safe.12

The rapid recovery of the first confirmed patient in the United States was benefited from the treatment of adefovir, making adefovir one of the most concerned drugs that may have special effects on COVID-19. However, the randomized double-blind placebo-controlled trial in critically ill patients in China did not find that Ridzevir had a stronger scavenging effect on SARS-CoV-2 than placebo.22 The curative effect was more obvious after taking adefovir within 10 days of diagnosis, and the average clearance time of the virus was 5 days shorter than that of the placebo group. The results suggested that adefovir was suitable for early viral infection. If the diagnosis had been confirmed for more than 10 days, it would not only benefit little, but also face the high risk of serious adverse reactions and further aggravate the disease. Due to the effective control of the epidemic in China, the study failed to include the target number of subjects, reducing the statistical effectiveness of the data to some extent. The existing evidence can be supplemented when the results of randomized controlled trials (RCTs) ofvir abroad are published.

Based on the limited clinical trial results, the efficacy of fapravi, abidol and danorrvir on COVID-19 is not clear, and it needs to be further verified by high-quality, large-sample randomized controlled trials. In addition, when the three antiviral drugs are used in combination, they are most prominent in nausea, vomiting, diarrhea and other aspects. Considering that they are related to the combination of the three antiviral drugs, according to the new coronavirus pneumonia diagnosis and treatment plan (eighth edition) promulgated by the National Health and Health Commission of China, it is not recommended to use the three drugs in combination, and the more drugs are, the heavier the gastrointestinal burden is. The proportion of dyslipidemia in patients with interferon- + lopinavir/ritonavir treatment was higher, which was considered to be related to the adverse reactions of lopinavir/ritonavir.24 It is worth noting that there are many drugs in the treatment of (critically) severe patients, so the adverse reactions need to be considered due to other drugs except antiviral drugs, and the incidence of adverse reactions may be higher. However, some studies have found that compared with Mild and Moderate patients, the incidence of adverse reactions in (critically) severe patients has no significant increase, indicating that most of the adverse reactions may come from antiviral drugs.18 Fortunately, most patients had mild clinical manifestations of adverse reactions.

The drugs discussed in this paper, such as abidol, pitavir, chloroquine, lopinavir/ritonavir, and interferon, have been marketed in China and approved for the treatment of new coronary pneumonia, and the currently carried out clinical trial for the treatment of COVID-19 is its new indication.26 Abidol has currently registered five clinical trials of Abidol for the treatment of COVID-19 in five hospitals including the Second Affiliated Hospital of Chongqing Medical University.27 The trial status of efaprevir is that the Clinical Study on the Safety and Efficacy of Faprevir in the Treatment of Patients with CO V1D-19 currently cooperated by the National Emergency Prevention and Control Drug Engineering Technology Research Center and the Third Peoples Hospital of Shenzhen has been completed, and Hisun Pharmaceutical has obtained the marketing approval letter of efaprevir tablets approved by the China Food and Drug Administration based on the results of this clinical trial. A Phase II clinical study to explore the dose of fapiravir tablets in patients with usual COVID- 1 9 has been completed, but results have not been published.26 Hydroxychloroquine At present, 19 clinical trials of chloroquine/hydroxychloroquine for the treatment of COVID-19 have been registered in 14 hospitals including Peking University First Hospital and the Second Affiliated Hospital of Chongqing Medical University. Lopinavir/ritonavir has been registered in 11 clinical trials using lopinavir/ritonavir for the treatment of COVID-19 in 9 hospitals including the Second Affiliated Hospital of Chongqing Medical University and the Fifth Affiliated Hospital, Sun Yat-sen University. At present, West China Hospital of Sichuan University and Wuhan Jinyintan Hospital have registered two clinical trials of interferon-alpha for the treatment of COVID-19 in the Chinese Clinical Trial Registry.27 Ruidexivir has been marketed and used in the United States, European Union, Japan and other places, but in China, it is still in clinical trials. At present, Wuhan Jinyintan Hospital and China-Japan Friendship Hospital have registered two clinical trials on the use of repaglinide for the treatment of COVID-19.27 Danorevir is mainly used for the treatment of hepatitis C. The highest study phase of the trial of danorevir in the treatment of new crowns is now the fourth phase,28 and the Department of Infectious Diseases of the Ninth Hospital of Nanchang published a clinical study on the medRxiv preprint platform to investigate the therapeutic effect of danorevir combined with ritonavir in the treatment of COVID-19 pneumonia.29

In summary, there is no specific drug for COVID-19. Patients with mild and common types have greater benefits in treatment, and antiviral drugs combined with Chinese patent medicine have better curative effect and prognosis. The treatment of severe patients is difficult, and lopinavir/ritonavir may be ineffective. Ridzevir shows initial effect in the early stage of infection, but it still needs higher quality clinical trials to provide evidence. Fapiravir can significantly improve the clinical symptoms of mild to moderate patients such as fever and cough, which can further investigate the curative effect of severe patients.

All data generated or analyzed during this study are included in this published article.

An ethics statement was not required for this study type, no human or animal subjects or materials were used.

Zhenwang Nie and Tao Sun are co-first authors of this article.

There is no funding to report.

All of the authors had no any personal, financial, commercial, or academic conflicts of interest separately.

1. Wu ZY, McGoogan JM. Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72 314 cases from the Chinese Center for Disease Control and Prevention. JAMA. 2020;323(13):12391242. doi:10.1001/jama.2020.2648

2. Baud D, Qi X, Nielsen-Saines K, Musso D, Pomar L, Favre G. Real estimates of mortality following COVID-19 infection. Lancet Infect Dis. 2020;20(7):773. doi:10.1016/S1473-3099(20)30195-X

3. Wang D, Hu B, Hu C, et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA. 2020;323(11):10611069. doi:10.1001/jama.2020.1585

4. Zhang Q, Wang Y, Qi C, Shen L, Li J. Clinical trial analysis of 2019-nCoV therapy registered in China. J Med Virol. 2020;92(6):540545. doi:10.1002/jmv.25733

5. Medical Administration and Hospital Authority. Notice on printing and distributing the novel coronavirus pneumonia diagnosis and treatment plan (Trial Version 8 Revised Edition). National Health Office Medical Letter [2021] No. 191; 2021. Available from: http://www.nhc.gov.cn/yzygj/s7653p/202104/7de0b3837c8b4606a0594aeb0105232b.shtml. Accessed August 8, 2022.

6. Brown AJ, Won JJ, Graham RL, et al. Broad spectrum antiviral remdesivir inhibits human endemic and zoonotic deltacoronaviruses with a highly divergent RNA dependent RNA polymerase. Antiviral Res. 2019;169:104541. doi:10.1016/j.antiviral.2019.104541

7. Cao B, Wang Y, Wen D, et al. A trial of lopinavir-ritonavir in adults hospitalized with severe Covid-19. N Engl J Med. 2020;382(19):17871799. doi:10.1056/NEJMoa2001282

8. Wang SZ, Wang HJ, Chen HM, et al. Lianhua Qingwen capsule and interferon- combined with lopinavir/ritonavir for the treatment of 30 COVID-19 patients. J Bengbu Med Coll. 2020;45:154155.

9. Cai Q, Yang M, Liu D, et al. Experimental treatment with favipiravir for COVID-19: an open-label control study. Engineering. 2020;6(10):11921198.

10. Xu XW, Wu XX, Jiang XG, et al. Clinical findings in a group of patients infected with the 2019 novel coronavirus (SARS-Cov-2) outside of Wuhan, China: retrospective case series. BMJ. 2020;19(368):m606. doi:10.1136/bmj.m606

11. Liu F, Xu A, Zhang Y, et al. Patients of COVID-19 may benefit from sustained Lopinavir-combined regimen and the increase of Eosinophil may predict the outcome of COVID-19 progression. Int J Infect Dis. 2020;95:183191. doi:10.1016/j.ijid.2020.03.013

12. Chen Y, Li XP, Jiang YH, Wang YP, Yu WJ. Clinical features and treatment of 11 cases of COVID-19. Mod Pract Med. 2020;32(2):5.

13. Tang W, Cao Z, Han M, et al. Hydroxychloroquine in patients with mainly mild to moderate coronavirus disease 2019: open label, randomised controlled trial. BMJ. 2020;14(369):m1849. doi:10.1136/bmj.m1849

14. Gautret P, Lagier JC, Parola P, et al. Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. Int J Antimicrob Agents. 2020;56(1):105949. doi:10.1016/j.ijantimicag.2020.105949

15. Magagnoli J, Narendran S, Pereira F, et al. Outcomes of hydroxychloroquine usage in United States veterans hospitalized with Covid-19. medRxiv. 2020;1:114127.

16. Li Y, Xie Z, Lin W, et al. Efficacy and safety of lopinavir/ritonavir or arbidol in adult patients with mild/moderate COVID-19: an exploratory randomized controlled trial. Med. 2020;1(1):105113.e4. doi:10.1016/j.medj.2020.04.001

17. Deng L, Li C, Zeng Q, et al. Arbidol combined with LPV/r versus LPV/r alone against Corona Virus Disease 2019: a retrospective cohort study. J Infect. 2020;81(1):e1e5. doi:10.1016/j.jinf.2020.03.002

18. Chen C, Zhang Y, Huang J, et al. Favipiravir versus arbidol for clinical recovery rate in moderate and severe adult COVID-19 patients: a prospective, multicenter, open-label, randomized controlled clinical trial. Front Pharmacol. 2021;12:683296. doi:10.3389/fphar.2021.683296

19. Yuan J, Yan XF, Zhang W, et al. Retrospective analysis of antiviral efficacy of 224 cases of novel coronavirus pneumonia. Chin J Infect Chemother. 2021;21(04):406410.

20. Zhao L, Zhao P, Zhang DW, et al. The efficacy of lopinavir/ritonavir combined with interferon in the treatment of new coronavirus pneumonia. Infect Dis Info. 2021;34(01):1519.

21. Tiandi GZ, Qian F, Zhang TY, et al. Clinical observation on the incidence of severe cases of new coronavirus pneumonia treated with favelavir. Chin J Pharmacov. 2021;18(10):901904 + 909.

22. Chen H, Zhang Z, Wang L, et al. First clinical study using HCV protease inhibitor danoprevir to treat COVID-19 patients. Medicine. 2020;99(48):e23357. doi:10.1097/MD.0000000000023357

23. Wang Y, Zhang D, Du G, et al. Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial. Lancet. 2020;395(10236):15691578. doi:10.1016/S0140-6736(20)31022-9

24. Grein J, Ohmagari N, Shin D, et al. Compassionate use of remdesivir for patients with severe Covid-19. N Engl J Med. 2020;382(24):23272336. doi:10.1056/NEJMoa2007016

25. Puech R, Gagnieu MC, Planus C, et al. Extreme bradycardia due to multiple drug-drug interactions in a patient with HIV post-exposure prophylaxis containing lopinavir-ritonavir. Br J Clin Pharmacol. 2011;71(4):621623. doi:10.1111/j.1365-2125.2010.03849.x

26. Ning L, Xiaohong H. Research progress in clinical trials of COVID-19. Chin J New Drugs. 2020;15:17381745.

27. Sicong L, Xiaoyan N, Sheng H, Luwen S. Advances in researches of anti novel coronavirus drugs. Drug Eval. 2020;17(4):1924.

28. Xiaoxu W, Xinyi W, Hao L, Cheng C, Dongyang L. Progress in drug development for treatment of coronavirus disease 2019(COVID-19). Chin J Pharmacol Toxicol. 2021;35(08):561574.

29. Hui L, Xinwei W, Chaohui B. Current research status of antiviral drugs in the treatment of novel coronavirus pneumonia[J]. Clin J Med Officer. 2020;48(09):11081110.


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Antiviral drugs in the treatment of COVID-19 | IDR - Dove Medical Press
Monkey pox, Afraid? Fear Less & Care More! – Healthieyoo

Monkey pox, Afraid? Fear Less & Care More! – Healthieyoo

August 18, 2022

Different methods of diagnosis include medical history, including any prior travel experiences that may assist your doctor to assess your risk.

The most effective and sensitive laboratory test is the polymerase chain reaction (PCR). The better diagnostic samples for monkey pox come from skin lesions, specifically the fluid that comes from vesicles and pustules as well as dry crusts. Monkey pox virus is particularly detected using a hybridization assay using an MGB Eclipse TM (Epoch Biosciences) probe that targets the B6R envelope protein gene (MPXV).

Lesion samples from five confirmed US cases of monkey pox were utilized to evaluate the assays, which were validated using coded orthopoxvirus DNA samples. Other orthopoxviruses cannot be detected with the B6R assay, only MPXV detected. With other rash illness-causing viruses or bacteria, neither assay produced false positive results.

West African/US MPXV has one SNP within the B6R probe, and the Congo Basin MPXV was the target of the B6R assays design. The detection of MPXV DNA in human samples was unaffected by the lack of complete similarity to the US monkey pox isolates, demonstrating the diagnostic efficacy of the B6R assay for both known MPXV clades (6, 7).

One possibility is a biopsy. Lesion samples must be maintained cool and stored in a dry, sterile tube without a viral transport medium. Due to the short period of viremia (presence of virus in the blood) in relation to the date of specimen collection after symptoms begin, PCR blood tests are typically inconclusive and should not be regularly obtained from patients.


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Monkey pox, Afraid? Fear Less & Care More! - Healthieyoo
Second dose of monkeypox vaccine now available in Los Angeles – Los Angeles Times

Second dose of monkeypox vaccine now available in Los Angeles – Los Angeles Times

August 18, 2022

With a new shipment of monkeypox vaccines expected Wednesday, Los Angeles County public health officials will begin administering second doses for the first time and again open registration for first shots to those considered high risk.

L.A. County Department of Public Health officials said in a statement that the latest shipment will allow them to increase vaccine distribution, but the 5,600 new Jynneos vaccines fall short of what federal officials had promised and still well below the amount needed to inoculate everyone considered high risk.

The county also increased vaccine eligibility to some children after federal officials last week authorized, under emergency use, the shots for those under 18.

The 5,600 vaccine vials about a third of what L.A. officials had expected to receive this week could be used to vaccinate about 28,000 people, following the Food and Drug Administrations recommendation to use only one-fifth of a full dose in order to expand supplies.

Many cities this week expressed frustration with changes to their vaccine distribution allotments after the federal government shifted its strategy.

With this latest shipment, L.A. public health officials plan to provide 8,000 second doses to people who received their first shot before July 20, or four or more weeks ago. The Jynneos vaccine is a two-dose series, taken four weeks apart.

The county had previously aligned with guidance from the state that instructed health departments to prioritize first doses while supplies were limited, but it did say second doses can be offered as more doses of Jynneos become available.

It wasnt immediately clear whether that guidance had changed, but last week, California Public Health Director Dr. Toms Aragn said the emergency use authorization provides more flexibility in how many doses are available.

We still expect demand to outpace supply and are assessing the impact of this authorization on our allocation and distribution strategy, Aragn said.

The L.A. public health department said all additional vaccines will be administered in the new smaller-dose intradermal technique which is given shallower and between layers of skin as opposed to under the skin and into the underlying fat. However, the earlier dosing technique will be used for those under 18 or with a history of keloid scars, health officials said, following federal guidelines.

There are almost 1,000 monkeypox cases confirmed or suspected in L.A. County as of Wednesday, following a week of almost daily double-digit increases, according to county data. Across the state, more than 2,300 cases have been confirmed or suspected more than double the tally from two weeks ago.

Monkeypox continues to spread primarily among men or transgender people who have sex with other men, according to public health officials, though anyone can catch the virus, regardless of gender or sexuality. Most transmission has come from intimate, prolonged skin-to-skin contact, but the virus can be spread through towels or bedsheets or shared respiratory secretions, such as kissing or other close face-to-face contact.

The countys online registration for a monkeypox vaccine had been closed the last few days but it opened Wednesday afternoon. Those interested in a vaccine also can call the Public Health Call Center from 8 a.m. to 8:30 p.m. at (833) 540-0473. The county said 19,000 of the smaller doses will be distributed to community providers and county vaccine sites.

To get a shot, people must meet the countys eligibility requirements, which prioritize gay and bisexual men or transgender people who have had multiple sex partners in the last two weeks or meet other criteria, such as having a sexually transmitted disease.

The county is requiring a consent form for children to receive the vaccine, and they also must meet the countys eligibility requirements.

For those eligible for a second Jynneos dose, county officials said they should contact their healthcare provider if thats where they received their first dose, or wait for a text message from the health department for further instructions.

Public Health has received assurances from the federal leadership that additional doses will be available in the coming weeks, the department said in a statement.


Original post:
Second dose of monkeypox vaccine now available in Los Angeles - Los Angeles Times
Who should get the monkeypox vaccine? Here’s what experts say. – Yahoo Life

Who should get the monkeypox vaccine? Here’s what experts say. – Yahoo Life

August 18, 2022

Who is eligible to get the monkeypox vaccine, which is in limited supply? Experts weigh in. (Mario Tama/Getty Images)

With cases of monkeypox continuing to rise there are nearly 12,000 confirmed cases of monkeypox in the U.S., according to the Centers for Disease Control and Prevention (CDC) the contagious virus doesnt seem to be going anywhere any time soon.

Although the majority of cases have been in men who have sex with men, at least eight children across the U.S. have reportedly tested positive for monkeypox, and recently a day care worker in Illinois was diagnosed with the virus. In addition, children under the age of 8 are at a higher risk of severe complications from monkeypox, the CDC says.

That may leave some people, including parents of young children, wondering whether they need to get the monkeypox vaccine for either themselves or their kids. Adding to the challenge is the fact that the vaccine Jynneos is in limited supply and not widely available to the general public.

Heres what experts have to say about who should get the monkeypox vaccine.

Monkeypox can spread to anyone through prolonged, close, personal, often skin-to-skin contact, as well as through contact with objects, fabrics clothing, bedding, or towels and surfaces that have been used by someone with monkeypox, or contact with respiratory secretions, through kissing and other face-to-face contact, internal medicine specialist Dr. Henry Ng, director of the transgender surgery and medicine program and director of the Center for LGBTQ+ Care at Cleveland Clinic, tells Yahoo Life.

Although monkeypox is not considered an STI (sexually transmitted infection), its predominantly spreading from sexual exposure, Dr. Brandi Manning, an infectious diseases physician at the Ohio State University Wexner Medical Center, tells Yahoo Life. However, it can be contracted from any sort of prolonged direct contact, she says.

Experts say that, given the current limited supply of the Jynneos vaccine, we are prioritizing those at highest risk of exposure to be vaccinated first, says Manning.

Story continues

Its worth pointing out that there is another vaccine, ACAM2000, thats approved for smallpox and was made available for use against monkeypox under an Expanded Access Investigational New Drug protocol, says Ng. Although the single-dose vaccine is more widely available, it comes with more side effects and contraindications, with the CDC stating that many adverse events were more common in young children who received the vaccine. Jynneos, on the other hand, has been administered in the U.S. without any adverse events to date, according to the CDC.

Dr. Prathit Kulkarni, assistant professor of medicine in infectious diseases at Baylor College of Medicine, tells Yahoo Life that people who should consider getting the monkeypox vaccine include men who have sex with men (MSM) who have recently had multiple or anonymous sex partners, along with certain health care professionals, such as laboratorians who are performing monkeypox virus testing.

Others, including children and adolescents, should consider getting the vaccine if theyve had an unprotected exposure to another person with active monkeypox disease, says Kulkarni, adding: Such a recommendation would be guided by public health professionals depending upon the individual circumstances of the exposure.

On Aug. 9, the Food and Drug Administration issued an emergency use authorization for the Jynneos vaccine that includes allowing health care providers to administer the vaccine to those younger than age 18 if theyre at high risk of monkeypox infection.

As students return to school or are in day care, there is some concern about monkeypox spreading in those close-contact conditions. But experts say the current risk is low. At the present time, the risk of monkeypox spread within day cares is believed to be quite low, says Kulkarni. There is no broad recommendation for vaccination of kids in day care or of parents of kids in day care.

Ng explains that, currently, there is no monkeypox vaccine available for administration to all children. However, there is a vaccine available to children under 18 years who have been exposed to monkeypox, Ng says.

If monkeypox infections continue to spread to other groups, then, yes, say experts. Manning anticipates that, as the U.S. vaccine supply increases and once those at the highest risk for monkeypox are vaccinated, we will then be able to expand vaccinations to other groups as well, including children.

Kulkarni agrees, saying its possible that going forward, the number of people recommended for prophylactic monkeypox vaccination will increase. This will depend upon the trajectory of the ongoing outbreak in the United States and globally.

The Jynneos vaccine series requires two doses, given four weeks apart. Similar to other vaccines, people are considered fully vaccinated with the Jynneos vaccine two weeks after receiving their second dose, says Ng. But how long the protection lasts is unknown, Ng notes.

Manning says the Jynneos vaccine was created for smallpox, in the event that we would need it. But she says that it wasnt widely used because fortunately, smallpox was eradicated in the past by a successful mass vaccination effort.

Since the smallpox and monkeypox viruses are similar they belong to the same group of viruses known as orthopoxvirus we are able to use Jynneos to vaccinate against monkeypox, but it takes time to increase production, Manning explains. The move to switch from subcutaneous injection [into the fat layer] to intradermal injection [between the layers of skin] will allow us to increase available doses substantially without sacrificing effectiveness.

The U.S. Department of Health and Human Services announced on Monday that its making up to 442,000 doses of the Jynneos vaccine available to states to further combat the monkeypox outbreak.

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Go here to read the rest: Who should get the monkeypox vaccine? Here's what experts say. - Yahoo Life
Monkeypox cases jumped 20% in the last week to 35,000 across 92 countries, WHO says – CNBC

Monkeypox cases jumped 20% in the last week to 35,000 across 92 countries, WHO says – CNBC

August 18, 2022

Monkeypox continues to spread across the globe with cases jumping by 20% over the last week, according to the World Health Organization.

Infections increased by nearly 7,500 to more than 35,000 cases total across 92 countries, but nearly all reported cases are in Europe and the Americas, according to WHO data. Twelve deaths have been reported so far.

The overwhelming majority of patients continue to be men who have sex with men, WHO Director-General Tedros Adhanom Ghebreyesus said. The global supply of the monkeypox vaccine, called Jynneos in the U.S., remains limited and data on its effectiveness in the current outbreak is sparse, Tedros said. Jynneos is manufactured by Danish biotech company Bavarian Nordic.

"We remain concerned that the inequitable access to vaccines we saw during the Covid-19 pandemic will be repeated and that the poorest will continue to be left behind," Tedros said during a news conference in Geneva on Wednesday.

Though data on the vaccine's effectiveness is limited, there are reports of breakthrough cases in which people who received the shots after exposure to the virus are still falling ill as well as individuals becoming infected after receiving the vaccine as a preventative measure, according to Dr. Rosamund Lewis, the WHO's monkeypox technical lead.

The monkeypox vaccine can be administered after exposure to reduce the risk of severe disease or before exposure to reduce the risk of infection.

"We have known from the beginning that this vaccine would not be a silver bullet, that it would not meet all the expectations that are being put on it, and that we don't have firm efficacy data or effectiveness data in this context," Lewis told reporters.

These reports are not surprising, Lewis said, but highlight the importance of individuals taking other precautions such as reducing their number of sexual partners and avoiding group or casual sex during the current outbreak. It's also important for people to know that their immune system does not reach its peak response until two weeks after the second dose, she said.

"People do need to wait until the vaccine can generate a maximum immune response, but we don't yet know what the effectiveness will be overall," Lewis said. A small study from the 1980s found that the smallpox vaccines available at the time were 85% effective at preventing monkeypox. Jynneos was approved in the U.S. in 2019 to treat both smallpox and monkeypox, which are in the same virus family.

"The fact that we're beginning to see some breakthrough cases is also really important information, because it tells us that the vaccine is not 100% effective in any given circumstance," she said.

The WHO has observed some mutations in the monkeypox virus though it's not year clear what these changes mean for the behavior of the pathogen and how it impacts the human immune response, Lewis said.

The first known instance of an animal catching monkeypox from humans in the current outbreak was recently reported in Paris. A pet dog became infected by a couple who fell ill from the virus. The couple reported sharing their bed with the dog. Public health officials have advised people who are ill with monkeypox to isolate from their pets.

A pet becoming infected is not unusual or unexpected, said Dr. Mike Ryan, head of the WHO's health emergencies program. Dr. Sylvie Briand, head of pandemic preparedness at the WHO, said this does not mean that dogs can transmit the virus to people.

Lewis said there's a theoretical risk of rodents rummaging through garbage catching the virus, and it's important to manage waste properly to avoid infecting animals outside human households. Historically, monkeypox has jumped from rodents and other small mammals to people in West and Central Africa.

"What we don't want to see happen is disease moving from one species to the next and then remaining in that species," Ryan said. In this scenario, the virus could rapidly evolve, which would create a dangerous public health risk.

"I don't expect the virus to evolve any more quickly in one single dog than in one single human," he said.


Continue reading here:
Monkeypox cases jumped 20% in the last week to 35,000 across 92 countries, WHO says - CNBC
How to Get a Monkeypox Vaccine in N.Y.C. – The New York Times
‘Another kind of homophobia:’ Critics say King County’s monkeypox vaccine criteria are intrusive – KUOW News and Information

‘Another kind of homophobia:’ Critics say King County’s monkeypox vaccine criteria are intrusive – KUOW News and Information

August 18, 2022

On Friday morning, Oscar and Darrick were among the first early-birds waiting in line outside King Countys sexual health clinic at Harborview to try to get the monkeypox vaccine.

People around us are getting sick, Oscar said. We are hearing that friends of friends or Hey, yeah, my friend just got the monkeypox. So when it starts hitting close to home, you kind of want to get the vaccine.

Its gross-looking; I hear theyre very painful; they hurt; they can get infected, said Darrick, Oscar's husband. And so I just want to protect myself against that.

The couple, who asked to only use their first names for privacy reasons, said they got to the clinic early so they could avoid long lines, and so Darrick could get to work almost on time.

Anyone can contract monkeypox, but the current outbreak is spreading primarily among gay men.

The supply of monkeypox vaccines from the federal government is limited: So far, King County has received 9,160 doses of the monkeypox vaccine, which is only 11% of the 80,000 doses county officials say are needed to vaccinate everyone at highest risk.

To try to make sure those scarce doses are reaching those most at risk of contracting the virus, King County put detailed eligibility requirements in place. But critics of the countys approach say its not working as intended and might actually be doing harm.

In King County, those currently eligible for the vaccine include a subset of men or transgender people who have sex with men: such as those whove had more than 10 sexual partners in the past three months, those whove used meth in the past month, or who meet certain other criteria. People whove had sexual or close contact with someone who tested positive for monkeypox can also get the vaccine.

The way those eligibility requirements are being rolled out might actually be creating problems, said Bekah Telew, the co-executive director of Seattles LGBTQ+ Center.

Thats because, when folks come in for a vaccine, the provider asks them to sign paperwork verifying their eligibility that theyve had 10 sexual partners in the past three months, for example, or that theyve had syphilis or gonorrhea in the past year.

It seems like something that would just create another barrier for folks who may identify in the eligible categories, but wouldnt be comfortable putting that on paper, Telew said.

Keletso Makofane, a social network epidemiologist at Harvard, agrees that the countys approach is inadvisable.

It is intrusive, and it also reveals a kind of callousness with respect to the meaning of sex, the meanings that people attach to sex, he said. To act as if you can just get this information as if these folks are robots who have no shame and no fear, who do not have a desire to keep some things private to not accommodate that humanity that gay men have around our lives is another kind of homophobia.

County officials said the goal of the eligibility requirements is to ensure that the people who most need the vaccine get it first, instead of the people with the most privilege. They said a first-come, first-served approach would mean that people with, say, flexible work schedules and a pre-existing relationship with a primary care provider would get the vaccine first.

Just as in the rollout of the Covid vaccine, the stringent eligibility criteria are only expected to be in place for a short time.

Were trying to be a little bit more targeted in who were giving it to in this initial phase, said Dr. Matthew Golden, the director of the sexual health clinic as well as the countys HIV/STD program. Golden is helping lead the countys monkeypox response. As we get more vaccine, we expect to change what those criteria will be.

Telew said she agrees with the countys aims but that the approach isnt working as officials intended.

Unfortunately, I think what were seeing is that folks who are more comfortable navigating systems because of the many privileges that folks may hold are going to get the vaccines regardless, she said.

Telew and Makofane agree that instead of writing and trying to enforce stringent eligibility requirements, a community-based approach would work better: setting up pop-up clinics at places where gay, bisexual, and transgender men already gather and feel comfortable.

A spokesperson said King Countys public health agency has used a number of strategies to reach the people at highest risk for exposure to the monkeypox virus and who might have limited access to the vaccine, including distributing the vaccine to community-based organizations and businesses and doing targeted outreach through UW Medicine.

The county has also held two pop-up vaccine events on weekends, where 1,200 people were vaccinated, and it plans to hold more pop-up clinics as soon as it has more vaccines on hand.

Also, the county's vaccine supply might stretch slightly further than anticipated, because some providers have started using a new vaccine administration technique that allows each vial to vaccinate three to four people instead of just one.

As people wait for vaccines, Makofane said there are steps they can take to reduce their risk of contracting monkeypox. They can reduce their number of sexual partners, choose a couple of stable partners and only have sex with them for the time being, and talk to them about what risks theyre taking and how many people theyre having sex with.

Also, he said, people who are going to be out in tight, crowded spaces, rubbing against other people, can reduce their risk of contracting the virus by wearing long sleeves.

He said using a condom can reduce the risk of transmission during sex, although monkeypox can also be transmitted through kissing and skin-to-skin contact.

Makofane also expressed frustration over the current state of vaccine access. He said it didnt have to be this way, with people waiting weeks or months for the vaccine as the outbreak continues to grow. He said it was a failure of the federal government.

The reason that people are scrambling for vaccine or are lining up very early in the morning for vaccine is not that there is some kind of global shortage, he said. Its that the people in charge of bringing vaccine over [to the US] did not decide to bring in as much vaccine as we needed.

All that can be done at the local level is set up systems that afford us a little dignity, he said. And theyve failed to do that, by and large.


See more here: 'Another kind of homophobia:' Critics say King County's monkeypox vaccine criteria are intrusive - KUOW News and Information
7 Monkeypox Vaccine Stocks to Buy Before They Shoot Higher – InvestorPlace

7 Monkeypox Vaccine Stocks to Buy Before They Shoot Higher – InvestorPlace

August 18, 2022

Monkeypox stocks, our topic for today, have had a mostly mixed performance so far in 2022. It is likely, however, that they could benefit from the similar tailwinds enjoyed by companies, such as Pfizer (NYSE:PFE), BioNTech (NASDAQ:BNTX), and Moderna (NASDAQ:MRNA), which have developed the Covid-19 vaccines that have now become household names.

Monkeypox is a smallpox-like disease caused by the monkeypox virus. Both viruses share the same genus: Orthopoxvirus.Originally relegated to certain central and western African countries, the disease has spread to some 31,000 people globally. There are around 10,000 cases stateside. Yet, the majority of monkeypox cases are relatively mild.

The diseases relative mildness aside, fears of a possible Covid-like monkeypox pandemic have alleviated some of the recent woes afflicting the biotech industry. Not entirely of course, as the NASDAQ Biotechnology Index, for example, is still down around 10% year to date (YTD). Meanwhile, the broader NASDAQ Composite has fallen almost 16% over the same period.

With governments worldwide stockpiling vaccines and treatments, monkeypox researchers and vaccine manufacturers could see a sharp increase in share prices. With that information, here are seven monkeypox stocks to buy in August.

Source: ktsdesign / Shutterstock.com

52-week range: $0.62 $7.35

Our first on this list of monkeypox stocks is a testing play, Applied DNA Sciences (NASDAQ:APDN) offers DNA-based biotechnology solutions. The company operates in three primary business markets: the manufacture of DNA for use in nucleic acid-based therapeutics; the detection of DNA in molecular diagnostics testing services; and the manufacture and detection of DNA for industrial supply chain security services.

Management released third quarter FY22 results on Aug. 11. Revenue came in at $4.3 million, compared with $1.7 million for the same period last year. Net loss per share was 13 cents compared to 48 cents for the same period last year.

Recently, APDN announced that its wholly-owned clinical laboratory subsidiary, Applied DNA Clinical Labs (ADCL), has developed a PCR-based test to detect the monkeypox virus through its genetic signature. If approved by various health authorities, the test will be used to power ADCLs monkeypox testing services.

APDN stock is down about 17% year-to-date (YTD) and 45% over a 12-month period. Shares trade at 1.68 times sales. Meanwhile, the 12-month median price forecast for APDN stands at $7.00.

Source: angellodeco / Shutterstock.com

52-week range: $5.85 $19.31

Bavarian Nordic (OTCMKTS:BVNRY) is a Danish biotechnology and pharmaceutical company. The company manufactures the only two vaccines approved in the U.S. for monkeypox: Imvanex and Jynneos. This alone makes it a top pick as far as monkeypox stocks go.

In early May, Bavarian Nordic reported Q1 financials. Revenue was 320 million Danish Kroner (DKK), decreasing from 535 million DKK the year before. Cash and equivalents totaled 2.95 billion DKK.

The company recently announced an additional contract to provide 350,000 doses of its Jynneos smallpox/monkeypox vaccine to an undisclosed Asia/Pacific Region country. The company already has contracts with governments in the U.S., Canada, and others. For instance, Jynneos is part of the Strategic National Stockpile, which contains enough vaccines to vaccinate every person stateside.

As a result of these positive developments, BVNRY stock has jumped up 11.7% YTD. Shares are trading at 13.1 times sales.

Source: Pavel Kapysh / Shutterstock.com

52-week range: $1.27 $7.42

Biopharma play Chimerix (NASDAQ:CMRX) is known for TEMBEXA, an oral antiviral in tablet and oral suspension formulations used for the treatment of smallpox disease. It was approved bythe Food and Drug Administration (FDA) in June 2021.

Management released Q2 results on Aug. 8. Revenue came in at $0.4 million. Net loss per share was 27 cents compared with 21 cents for the year-ago quarter.

In Late June, Chimerix announced that the Public Health Agency of Canada awarded a contract up to $25.3 million to procure TEMBEXA. Long-term CMRX shareholders would know that earlier in the year, the company agreed with Emergent BioSolutions (NYSE:EBS) for Emergent to sell Chimerixs exclusive worldwide rights to TEMBEXA. Therefore, the exact amount of royalties for Chimerix needs to be finalized.

CMRX stock is down about 58% YTD and 56% over a 12-month period. Wall Streets 12-month median price forecast for CMRX is $6.00.

Source: Flabygasted / Shutterstock.com

52-week range: $0.55 $7.50

Next on our list of monkeypox stocks is GeoVax Labs (NASDAQ:GOVX). GeoVax is a clinical-stage, pre-revenue pharma company with a focus on vaccines and immunotherapies. Its current research programs center around Covid-19, various hemorrhagic fever viruses, Zika virus, malaria, and various forms of cancer. The company utilizes recombinant-DNA-based genetic engineering to develop its drugs.

In early August, GeoVax provided Q2 earnings. Loss per share was 18 cents, compared to a loss per share of 21 cents the prior year. Cash and equivalents totaled $30.9 million.

Recently, the company announced that its GEO-CM04S1 vaccine was being evaluated for effectiveness against monkeypox. GeoVax also revealed that its hemorrhagic fever virus vaccine will also be assessed as a possible candidate for monkeypox. GeoVax anticipates both vaccines will show effectiveness against the virus.

Yet, despite the potential, GOVX stock has lost close to a third of its value since January. Shares are trading at 80.4 times sales.

52-Week Range: $24.77-$55.55

Dividend Yield: 1.15%

Expense Ratio: 0.47% per year

Recent metrics suggest that the global biotechnology market can hit $3.9 trillion by 2030, expanding at a compound annual growth rate (CAGR) of 13.9% between 2022 and 2030. Thus, our next choice is an exchange-traded fund (ETF) that focuses on global biopharmaceutical and healthcare companies.

The iShares Genomics Immunology and Healthcare ETF (NYSEARCA:IDNA) invests in businesses that could benefit from the long-term growth and innovation in genomics, immunology, as well as bioengineering. Many of these stocks are involved in critical research and development (R&D). The fund was first listed in June 2019.

IDNA, which tracks the NYSE FactSet Global Genomics and Immuno Biopharma Index, currently holds a basket of 41 holdings. The top 10 stocks comprise more than 40% of $217.2 million in net assets. More than two-thirds of the companies come from the U.S. Next in line are businesses from Germany (7.6%), Japan (6.4%), China (4.5%), and Denmark (3.9%).

Leading names include biotechnology company Beam Therapeutics (NASDAQ:BEAM); clinical-stage genome editing firm Intellia Therapeutics (NASDAQ:NTLA); Cayman Islands-based biotech name Beigene (NASDAQ:BGNE); clinical-stage biopharmaceutical company Fate Therapeutics (NASDAQ:FATE); and Moderna.

IDNA has dropped nearly 22% since January and 35.5% over the past 12 months. Trailing price-to-earnings (P/E) and price-to-book (P/B) ratios stand at 12.36x and 2.19x, respectively. Interested readers whose long-term portfolios can handle short-term choppiness could invest in the promising prospects of the biotech sector through IDNA.

Source: Dmitry Kalinovsky / Shutterstock.com

52-week range: $5.49 $25.54

SIGA Technologies (NASDAQ:SIGA) is a commercial-stage pharmaceutical company. It offers, TPOXX, an antiviral medication used to treat smallpox and other pox viruses, including monkeypox. It is also available through the Strategic National Stockpile.

In early August, SIGA posted Q2 metrics. Revenue totaled $16.7 million, compared to $8.7 million the previous year. Diluted income per share was 3 cents. Cash and equivalents totaled $114.5 million.

The company recently announced its TPOXX antiviral medication will be used in an experimental treatment protocol in the Central African Republic, CAR. The company will provide up to 500 doses to the study, sponsored by Oxford University in the U.K.

SIGA stock has skyrocketed almost 230% since the beginning of the year. Shares are trading at 12.6 times sales.

Source: Sisacorn / Shutterstock.com

52-week range: $1.19 $24.89

Last on our list of monkeypox stocks is the clinical-stage biopharmaceutical company Tonix Pharmaceuticals (NASDAQ:TNXP). Its portfolio comprises of candidates for the central nervous system (CNS), immunology and infectious diseases.

Management reported Q2 results on Aug. 8. The pharma play has not recorded any revenues, yet. However, loss per share went down to $1.22 compared to $2.25 for the prior-year quarter.

Recently, TNXP announced a collaboration with the Kenya Medical Research Institute (KEMRI) to seek regulatory approval for conducting a Phase 1 clinical study in Kenya. The study aims to develop TNX-8011 as a vaccine to protect against monkeypox and smallpox and is expected to start in the first half of 2023.

TNXP stock is down 86% YTD struggling to stay above $1 per share to stay listed on the stock exchange. Therefore, it is a risky biotech and smallpox play, not suitable for most portfolios.

On Penny Stocks and Low-Volume Stocks:With only the rarest exceptions, InvestorPlace does not publish commentary about companies that have a market cap of less than $100 million or trade less than 100,000 shares each day. Thats because these penny stocks are frequently the playground for scam artists and market manipulators. If we ever do publish commentary on a low-volume stock that may be affected by our commentary, we demand thatInvestorPlace.coms writers disclose this fact and warn readers of the risks.

Read More:Penny Stocks How to Profit Without Getting Scammed

On the date of publication, Tezcan Gecgil, Ph.D., is both long and short BNTX. The opinions expressed in this article are those of the writer, subject to the InvestorPlace.comPublishing Guidelines.

Tezcan Gecgil has worked in investment management for over two decades in the U.S. and U.K. In addition to formal higher education in the field, she has also completed all 3 levels of the Chartered Market Technician (CMT) examination. Her passion is for options trading based on technical analysis of fundamentally strong companies. She especially enjoys setting up weekly covered calls for income generation.


Original post: 7 Monkeypox Vaccine Stocks to Buy Before They Shoot Higher - InvestorPlace
When COVID-19 or flu viruses kill, they often have an accomplice  bacterial infections – The Conversation

When COVID-19 or flu viruses kill, they often have an accomplice bacterial infections – The Conversation

August 18, 2022

The 1918 influenza pandemic resulted in the loss of over 3% of the worlds population at least 50 million people. But it wasnt the flu virus that caused the majority of these deaths.

An analysis of lung samples collected during that flu pandemic indicated that most of the deaths were likely due to bacterial pneumonia, which ran rampant in the absence of antibiotics. Even in more recent history, like the 1957 H2N2 and 2009 H1N1 flu pandemics, nearly 18% of patients with viral pneumonia had additional bacterial infections that increased their risk of death. And the COVID-19 pandemic is no different.

With yet another flu season fast approaching in the midst of the ongoing COVID-19 pandemic, lessening the harm caused by these viruses is important to prevent deaths and reduce infections. However, many deaths associated with the flu and COVID-19 dont occur at the hand of the virus alone. Instead, its a secondary bacterial infection that is often at the root of the devastating consequences attributed to an initial viral infection.

I am an immunologist who studies why and how cells die during bacterial and viral infections. Understanding the synergy between these microbes is critical not only for effective diagnosis and treatment, but also for managing current pandemics and preventing future ones. My colleagues and I published a study showing how an immune system protein crucial to fighting against viruses also plays an indispensable role in fighting bacteria.

Multiple pathogens can cause multiple infections in different ways. Scientists distinguish each type based on the timing of when each infection occurs. Coinfection refers to two or more different pathogens causing infections at the same time. Secondary or superinfections, on the other hand, refer to sequential infections that occur after an initial infection. Theyre often caused by pathogens resistant to antibiotics used to treat the primary infection.

How viral and bacterial infections interact with each other increases the potential harm they can cause. Viral respiratory infections can increase the likelihood of bacterial infections and lead to worse disease. The reason why this happens is often multifaceted.

Within your respiratory tract, the epithelial cells lining your airways and lungs serve as the first line of defense against inhaled pathogens and debris. However, viruses can kill these cells and disrupt this protective barrier, allowing inhaled bacteria to invade. They can also change the surface of epithelial cells to make them easier for bacteria to attach to.

Viruses can also alter the surface of epithelial and immune cells by reducing the number of receptors that help these cells recognize and mount a response against pathogens. This reduction means fewer immune cells report to the viral infection site, giving bacteria an opening to launch another infection.

Patients who have a bacterial infection at the same time theyre battling the seasonal flu are more likely to wind up in a hospital. Nearly a quarter of patients admitted to the ICU with severe influenza also have a bacterial infection. One study on the 2010 to 2018 flu seasons found that nearly 20% of patients admitted to the hospital with flu-associated pneumonia had acquired bacterial infections.

Another study of patients hospitalized with viral or bacterial infections found that nearly half had a coinfection with another pathogen. These patients also had nearly double the risk of dying within 30 days compared to those with only a single infection.

Interestingly, the two bacteria species most commonly involved in coinfections with the influenza virus are Streptococcus pneumoniae and Staphylococcus aureus, which normally exist in the respiratory tract without causing disease. However, the influenza virus can damage the cell barrier of the lungs and disrupt immune function enough to make patients susceptible to infection by these otherwise benign bacteria.

Secondary bacterial infections are also exacerbating the COVID-19 pandemic. A 2021 review estimated that 16% to 28% of adults hospitalized for COVID-19 also had a bacterial infection. These patients stayed in the hospital for twice as long, were four times more likely to need mechanical ventilation and had three times greater odds of dying compared to patients with only COVID-19.

The immune system responds differently to viruses and bacteria. Antivirals dont work on bacteria, and antibiotics dont work on viruses. A better understanding of what pathways the body uses to regulate both antiviral and antibacterial infections is critical to addressing secondary and coinfections.

Recent work by my colleagues and me may provide a clue. We sequenced the RNA of one type of immune cell, macrophages, in mice to identify what molecules were present in cells that were either protected from or died due to bacterial infection.

We identified Z-DNA binding protein (ZBP1), a molecule already known to play a regulatory role in how the immune system responds to influenza. Specifically, ZBP1 detects influenza viruses within the lungs and signals infected epithelial and immune cells to self-destruct. This induced cell death eliminates the virus and promotes recruitment of additional immune cells to the infection site.

Building off this finding that ZBP1 is important for fighting viral infection, we found that macrophages infected with Yersinia pseudotuberculosis, a type of bacteria that causes foodborne illness, also use this protein to initiate cell death. This limits bacterial replication while also sending inflammatory signals that help clear bacteria.

These findings raise the possibility that ZBP1 may play a dual role in how the body responds to viral and bacterial infections. Its possible that treatments that increase ZBP1 in certain types of cells may be useful in managing bacterial and viral coinfections.


Link: When COVID-19 or flu viruses kill, they often have an accomplice bacterial infections - The Conversation
It’s going to be a complicated fall for Covid and flu vaccinations – STAT – STAT

It’s going to be a complicated fall for Covid and flu vaccinations – STAT – STAT

August 18, 2022

For the health officials who steer vaccination campaigns, its going to be a complicated fall.

The U.S. plan to roll out updated Covid-19 boosters will not only coincide with the logistical tangle of the regular flu shot drive, but will also face questions about when people should get the new shots to provide themselves with the best protection through our third Covid winter.

Its a balancing act that health officials run into every year with flu. Vaccinating tens of millions of people takes weeks. People also need a few weeks after their shot for their immune systems to be fully primed. And yet, vaccinators dont want to put shots in arms too early, either. The power of the flu shot wanes over months, so the concern is that someone who gets a shot in say, September, may lose a chunk of their protection if the peak of the season is going to be in February.

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The power of the Covid vaccines also wanes, with their ability to block infection fading over the months though, crucially, the protection they generate against severe outcomes is maintained for much longer. But part of the reason the country is rolling out an updated shot is to better match the forms of the SARS-CoV-2 virus that are circulating now to prevent more infections and to act as a drag on transmission during what could be another cold-season surge.

When that comes out and weve got this extra coverage for the Omicron variants, thatll be great, said Sterling Ransone, a physician in Deltaville, Va., and the president of the American Academy of Family Physicians. The question is the timing. I want my patients to have the best protection they can.

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Complicating the process is that scientists dont have a sense yet after only two winters with SARS-2 about just when the virus might peak, and how strong the seasonal factors are. The virus has been spreading incredibly effectively throughout this summer, but many experts do anticipate even more elevated transmission at some point this fall and winter, at least in colder parts of the country.

Even with flu, its still a bit of a guessing game as to which month the virus will peak, particularly as Covid-mitigation efforts have thrown off the regular behavior of other viruses. And while the past two flu seasons have been tamed by the efforts to slow Covid, Australia is in the midst of a severe flu season, which can often portend what the U.S. season will look like.

Weve got a narrow window, Patsy Stinchfield, a pediatric nurse practitioner and the president of the National Foundation for Infectious Diseases, said about the annual flu shots. We want to make sure were not vaccinating too early, because then you risk a late season outbreak.

Stinchfield said people should generally receive their flu shots by Halloween.

Ed Belongia, the director of the Center for Clinical Epidemiology and Population Health at the Marshfield Clinic Research Institute, said that flu vaccines lose about 8% of their effectiveness each month. But there is an important balance, too. While October might be a better time to get a flu shot than September, September is better than never a lesson that should be applied to the Covid campaign as well.

Theres a potential tradeoff between giving the vaccine too early versus missing opportunities to vaccinate people who then never get the vaccine at all, Belongia said.

Running the two vaccine campaigns simultaneously could also stretch clinics and public health departments even further, though there is the advantage of people being able to get both their Covid booster and flu shot at one time if they choose to do so.

With annual flu shots, there is a well-choreographed system in place to have the shots ready by fall. Health officials typically pick which strains will go into that seasons shot early in the year, giving manufacturers months to mass produce the vaccine. From filling and shipping vials, to purchasing syringes, to getting health care workers and residents of long-term care facilities vaccinated, it is in itself a big lift every year.

With the updated Covid shots, it seems to be even more of a sprint. The Biden administration has signaled the boosters could be available in September, presuming the Food and Drug Administration and Centers for Disease Control and Prevention sign off on them. But it was only in late June that the FDA said the new boosters should target the original form of the virus as well as the spike protein of the BA.5 Omicron subvariant, the dominant lineage in the United States as of now.

I used to think that flu was really challenging, said Claire Hannan, the executive director of the Association of Immunization Managers. There was never a year that was the same as the previous year. And I think the challenges around supply and trying to plan and optimal planning, theyre very difficult. And just when you think youve solved that, you havent. And throwing Covid boosters into the mix, it just makes it more complicated.

Hannan said there wasnt guidance yet from the federal government about how much of and when exactly the new Covid shots will be available. She also noted that public health departments are also fighting an unprecedented monkeypox outbreak, complete with a convoluted vaccine delivery process.

While the Biden administration hasnt yet laid out its vision for the Covid booster campaign, its expected that it will be similar to when the original Covid boosters were authorized last fall, with more reliance on pharmacies and doctors offices and less on mass vaccination sites.

And in many ways, the sites are well practiced for another go-round with another Covid shot: theyve dealt with different shots from different manufacturers, different booster doses, kids shots, and, already, extra boosters for older adults and people with certain health issues. One wrinkle, however, is that the updated shots are expected to be authorized only as boosters, whereas the primary series of shots will still use the original formulation.

Tinglong Dai, a health care operations expert at Johns Hopkins University, said that hospitals and clinics should be able to handle delivering the updated boosters. But he also pointed out that health officials need to embark on a crucial messaging campaign. Only about half those eligible for a first booster have received one, and people may wonder why they need an updated shot. Its like someone with an iPhone 10 debating if they really need to upgrade to a newer model, Dai said.

Dai also said that the campaign needs to ensure easy access to both Covid and flu shots no matter where people live.

The logistics aspects have been mostly resolved, Dai said. The challenge is now really to connect the supply and demand to access issues.

With all the uncertainties around what the Covid winter might look like when will the virus spike and just how high? what variant is going to be dominant? Belongia said people shouldnt try to time when they get their boosters to try to make sure their protection is maximized through whatever surge might come. Instead, people should just get the Covid shots when they can.

Forecasting is a futile effort right now, Belongia said. If its available and authorized, the best thing is to not wait but to get it.

Helen Branswell contributed reporting.


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