Virus World

A new study from the Medical College of Georgia at Augusta University has found that irrigating your nose twice a day with a saline solution after testing positive for Covid-19 can decrease your chances of hospitalization and death in higher-risk patients.  Participants in the study who performed nasal irrigation were more than eight times less likely to be hospitalized than the national rate. Only 1.3% of study participants who used nasal irrigation were hospitalized after testing positive for Covid-19. While 9.47% of Covid patients from a national CDC dataset who did not use nasal irrigation were hospitalized. Irrigating your sinuses is a simple practice anyone can implement at home using a neti pot, sinus rinse bottle, or syringe bulb available at a pharmacy or retailer like Target or Walmart. You can buy pre-made mixes or simply mix a half-teaspoon of salt and a half-teaspoon of baking soda in a cup of boiled and then cooled or distilled water. The water needs to be boiled or distilled to ensure it is sanitary. Many people often use these devices to clear up allergies, colds, or sinus infections.

The study population was aged 55 and older and were enrolled within 24 hours of a postive PCR test between September 24 and December 21, 2020. Among 826 screened, 79 high-risk participants with a medium age of 64 and BMI of 30.1 were enrolled and randomly assigned to add 2.5 mL povidone-iodine 10% or 2.5 mL sodium bicarbonate to 240 mL of isotonic nasal irrigation twice daily for 14 days. To verify irrigation, patients uploaded pictures of used irrigation materials. A researcher called the patient or their designated contact on days 2, 7, 14, and 28 to verify irrigation and hospitalization. Nasal irrigation under pressure has been demonstrated to safely reduce the duration and severity of both Coronaviridae and illnesses like flu with shorter incubation periods. Sodium bicarbonate and povidone-iodine were chosen due to prior research supporting the virucidal activity of povidone-iodine against MERS and SARS-CoV-2 and the possible impact of alkalinization via sodium bicarbonate to reduce SARS-CoV-1 viral cell fusion and entry.

By day 28, there was one emergency department visit and no hospitalizations in the group irrigating with sodium bicarbonate and one hospitalization in the povidone-iodine group. There were no deaths in either group. Eleven particpants reported irrigation-related complaints and four discontinued use. Symptom resolution was more likely for those reporting twice-daily irrigation. While prior research has found that almost half of those 50 and older had continued symptoms 14–21 days after diagnoses, only 13% of participants in the study had symptoms at day 28. The study has limitations in terms of generalizability and risk of bias in the comparison dataset. The CDC national data did not serve as a matched control group. However, the participants in this study were actually at greater risk for severe disease than the general population in the CDC dataset due to age and obesity. Prior studies have also have found that saline can help combat COVID-19. A 2020 study shows that gargling with a saline-based solution can reduce viral load. A 2021 study suggests saline can be used as a “first-line intervention for COVID-19. The results of these studies suggests twice daily nasal irrigation is a safe, over-the-counter measure that can be used reduce disease severity.

Cited study published (August 25, 2022) in Ear Nose and Throat Journal:

https://doi.org/10.1177/01455613221123737

A late-stage trial was halted after strong early results, according to the company, but the data have not yet been published or peer-reviewed.  An experimental drug halved the death rate among critically ill Covid patients who were receiving supplemental oxygen and were at high risk for serious lung disease and death, the drug’s developer announced on Monday. There is a pressing need for new treatments for critically ill patients. Drugs like Paxlovid, made by Pfizer, are aimed primarily at patients who have mild or moderate disease. Other treatments administered to hospitalized patients in serious condition have shown limited effectiveness. The new drug, sabizabulin, reduced deaths among hospitalized Covid-19 patients so drastically in a clinical trial that independent safety monitors recommended stopping it early, officials at Veru Inc., the drug’s maker, said. The trial was halted on Friday. The results of that trial have not been peer-reviewed or published in a medical journal. Veru announced the findings at an early-morning news conference. The company’s stock soared in trading Monday following the announcement. About half of the 52 trial participants given a placebo or dummy pill along with regular care died within 60 days, an indicator of how very sick they were. But the death rate was 20 percent among the 98 participants who received sabizabulin, who were just as ill. The drug was given once a day for up to 21 days.

A clinical trial in older adults with COVID-19 shows that an early dose of blood plasma from recovered people helps to prevent the progression to severe disease. The plasma of people who have recovered from COVID-19 contains antibodies against SARS-CoV-2. But treatment with such plasma has had mixed results, and some scientists have suggested that plasma needs to be given early in the disease course to be effective. Fernando Polack at Fundación INFANT in Buenos Aires and his colleagues conducted a rigorous clinical trial to assess the effect of treatment with plasma within 72 hours of symptom onset. Participants included people over the age of 75 and those between 65 and 74 with at least one pre-existing condition such as diabetes (R. Libster et al. N. Engl. J. Med. https://doi.org/10.1056/NEJMoa2033700; 2021). Severe COVID-19 developed in 16% of the 80 study participants who received plasma and 31% of the 80 participants in the placebo group. The team found that donor plasma containing higher concentrations of antibodies against SARS-CoV-2 was associated with a greater reduction in the risk of developing severe disease — providing evidence that the antibodies themselves are responsible for the therapeutic effect.

The Milken Institute’s COVID-19 Treatment and Vaccine Tracker tracks the development of treatments and vaccines for COVID-19 (coronavirus). Explore the latest updates on the urgent race to develop a COVID-19 vaccine.

FasterCures, a center of the Milken Institute, has curated one of the most detailed and complete databases of treatments and vaccines for COVID-19. The database tracks over 500 therapeutics and prophylactics generated from publicly-available information from validated sources. The database is searchable, and information can be filtered by multiple criteria, including among others the stage of the therapy or vaccine, type of product, developer, and sponsors of clinical trials. Each entry contains important information such as dates and key milestones of each vaccine or therapy, and links to clinical trials and key research publications.

When visiting the site ensure you click on the spreadsheet link to access the searchable and filter options of the database tracker

Available at https://covid-19tracker.milkeninstitute.org/

As the current crisis phase of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic winds down—and the world nervously awaits potentially dangerous new variants—research into the nature and treatment of so-called long coronavirus disease (COVID) is beginning to ramp up. The White House has promised funding and a federal research roadmap, and dedicated clinics have started cropping up at academic medical centers across the country.  But attempts to understand and treat long COVID have been underway almost since the pandemic began. For more than 2 years, clinicians have been coping—mostly on their own—with streams of patients complaining of persistent symptoms or mysterious new ones after a bout with COVID-19 had seemingly resolved ( 1 ). And collectively, doctors and researchers have already made headway toward identifying some of the mechanisms underlying the condition—formally known as post-acute sequelae of COVID (PASC). That’s not to say that it’s been easy; estimates of the proportion of COVID-19 patients who will report symptoms 12–24 weeks after their infection range from about 30% to 70% ( 2 – 4 ). Some 200 different symptoms have been ascribed to long COVID, and the syndrome is yet to be fully defined. The most common complaints include fatigue, shortness of breath, and a dysfunctional sense of smell ( 5 ). For many, symptoms clear up on their own within 6 months. But one large study in China found that 55% of patients infected early in the pandemic were still struggling with at least one symptom 2 years after infection ( 6 ).

Published in PNAS (September 1, 2022):

https://doi.org/10.1073/pnas.2213524119

The Drug Controller General of India (DCGI) on Friday granted emergency use approval for pharma major Zydus Cadila’s antiviral drug ‘Virafin’, to treat moderate COVID-19 disease in adults, company press release said. “A single dose subcutaneous regimen of the antiviral Virafin [a pegylated interferon alpha-2b (PegIFN)] will make the treatment more convenient for the patients. When administered early on during COVID, Virafin will help patients recover faster and avoid much of the complications. Virafin will be available on the prescription of a medical specialist for use in hospital/institutional setup,” the release added.  The drug’s safety profile is already well known as it is used in treating people with chronic hepatitis B and C. The drug has been repurposed for treating moderate COVID-19 disease. According to Dr. Sharvil Patel, Managing Director, Cadila Healthcare Limited, the therapy “significantly reduces viral load when given early on and can help in better disease management”.

In a multi-centre trial in 20-25 centres across India, the company found the drug reduced the need for supplemental oxygen. This clearly “indicates that the antiviral was able to control respiratory distress and failure which has been one of the major challenges in treating COVID-19”, the company said. In the phase-3 trials, the drug was able to achieve “better clinical improvement in the patients suffering from COVID-19”. A “higher proportion (91.15%) of patients administered the drug were RT-PCR negative by day seven as it ensures faster viral clearance”. According to an April 5 company press release, the drug reduced the duration for supplemental oxygen to 56 hours from 84 hours in moderate COVID-19 patients. The results of the phase-2 trial using the drug published in the International Journal of Infectious Diseases found that of the 20 participants who received the drug and standard of care, 19 (95%) achieved clinical improvement on day 15 compared to 13 of the 20 (68.42%) participants who were in the control arm and received only standard of care. The trial found that 80% and 95% of participants who received the therapy plus standard of care were RT-PCR negative on day seven and 14, respectively, compared to 63% and 68% in the control arm.

The significant improvement in clinical status on day 15 is likely due to faster viral reduction compared to the control arm. Participants with moderate disease showed a difference as early as day seven, which became significant by day 14, the authors say in the paper. Mild adverse events were reported in 11 participants in the phase-2 trial compared with eight in the control arm. According to the release, type I interferons are the body’s first line of defence against many viral infections. In old people, the ability to produce interferon alpha in response to viral infections gets reduced, which might be the reason for higher mortality. The drug when administered early during the disease can replace this deficiency and help in the recovery process.

BACKGROUND

Convalescent plasma is frequently administered to patients with Covid-19 and has been reported, largely on the basis of observational data, to improve clinical outcomes. Minimal data are available from adequately powered randomized, controlled trials.

METHODS

We randomly assigned hospitalized adult patients with severe Covid-19 pneumonia in a 2:1 ratio to receive convalescent plasma or placebo. The primary outcome was the patient’s clinical status 30 days after the intervention, as measured on a six-point ordinal scale ranging from total recovery to death.

RESULTS

A total of 228 patients were assigned to receive convalescent plasma and 105 to receive placebo. The median time from the onset of symptoms to enrollment in the trial was 8 days (interquartile range, 5 to 10), and hypoxemia was the most frequent severity criterion for enrollment. The infused convalescent plasma had a median titer of 1:3200 of total SARS-CoV-2 antibodies (interquartile range, 1:800 to 1:3200]. No patients were lost to follow-up. At day 30 day, no significant difference was noted between the convalescent plasma group and the placebo group in the distribution of clinical outcomes according to the ordinal scale (odds ratio, 0.83 (95% confidence interval [CI], 0.52 to 1.35; P=0.46). Overall mortality was 10.96% in the convalescent plasma group and 11.43% in the placebo group, for a risk difference of −0.46 percentage points (95% CI, −7.8 to 6.8). Total SARS-CoV-2 antibody titers tended to be higher in the convalescent plasma group at day 2 after the intervention. Adverse events and serious adverse events were similar in the two groups.

CONCLUSIONS

No significant differences were observed in clinical status or overall mortality between patients treated with convalescent plasma and those who received placebo. (PlasmAr ClinicalTrials.gov number, NCT04383535. opens in new tab.)

Published in NEJM (November 24, 2020):

https://doi.org/10.1056/NEJMoa2031304