Coronavirus COVID-19 Webinar Video

How to Navigate the Coronavirus Infodemic:

Nelson Vergel

March 23, 2020

COVID-19 Webinar Agenda

  • What We Know About COVID-19
  • Difference in Symptoms from Cold, Flu and Allergies
  • Virus Shedding Before and After Symptoms
  • Risk Factors
  • Death Rate by Age
  • Clinical Presentation
  • Italian Data
  • Testing Advances- Where to Get Tested
  • Best Global Data Site
  • Are You Still Infectious After Recovering?
  • Can You Catch it a Second Time?
  • What is the Recovery Rate?
  • When Will it Peak?
  • Potential Treatments- Research and Repurposed
  • How Many Vaccines Are in Research?
  • Controversy Around Blood Pressure Meds and Ibuprofen
  • Zinc as  a Potential Preventative
  • Resources You Can Use

What We Know About Covid-19

  • The current COVID-19 epidemic began in Wuhan, China, in December 2019.
  • The COVID-19 pandemic is caused by a novel coronavirus now named SARS-CoV-2 (a note on terminology: SARS-CoV-2 is the official name for the coronavirus that causes the disease COVID-19)
  • This coronavirus is closely related to, but distinct from, the coronavirus that caused an epidemic of severe acute respiratory syndrome (SARS) in 2002-2003.
  • Coronaviruses are widespread in nature and account for up to 25% of “common colds.”
  • Various species of bats serve as the natural host for coronaviruses, which periodically break out into human populations as zoonotic epidemics.

https://bit.ly/3di0i09

What We Know About Covid-19 (cont.)

  • COVID-19 appears to be far more contagious than the flu and has a case fatality rate that may be up to 10 times higher than that of influenza.
  • Actual death rates vary enormously, from 7.3% in Italy to 0.9% in South Korea. Although the reasons for these wide disparities in case fatality rates are unclear
  • What is clear is that older age (particularly patients older than 70 years of age) and underlying medical conditions, such as hypertension and cardiovascular and pulmonary diseases, substantially increase the risk of death.
  • In contrast to the H1N1 swine flu epidemic of 2009, rates of symptomatic infection and serious illness among children and adolescents are significantly lower with COVID-19 than for older adults.

What We Know About Covid-19 (cont.)

  • Traditional measures for epidemic control of respiratory illness such as influenza are effective, including social distancing, frequent hand washing, and avoiding touching your eyes, nose, and mouth.
  • Those who have had close contact with a person with confirmed COVID-19 should self-quarantine for 14 days (the average incubation period is 5-7 days, but some cases have occurred as long as 12-14 days after exposure).

Covid-19 Risk Factors

  • People age 50 and older are around 2-and-a-half times more likely to progress to a severe case of COVID-19.
  • Cases were considered to be severe if they had symptoms such as shortness of breath requiring 30 or more breaths per minutes (12 to 20 breaths a minute is considered normal for an adult); dangerously low levels of oxygen in the blood; and radiographic evidence of lung damage that had grown by 50% or more within a 24 to 48 hour period.
  • Being male increased the odds of progressing to severe illness by 1.3 times, while smoking made it a little over 1 to 2-and-a-half times more likely. Overall, patients with underlying medical conditions including hypertension, diabetes and cardiovascular disease were 2 to 3 times more likely to progress to severe illness.
  • Certain conditions raised those odds further: People with chronic obstructive pulmonary disorder were anywhere from 2-and-a-half to nearly 11 times more likely to get severely ill. Kidney disease is also likely a big risk factor. While the research didn’t pinpoint exactly how big that risk is, it suggested it’s somewhere between 2- and 16-fold.

CLINICAL PRESENTATION OF COVID-19

  • Common symptoms: cough, fever, and fatigue; however, sputum, shortness of breath, myalgias, sore throat, headache, nasal congestion, and nausea/vomiting/diarrhea have also been reported.
  • The elderly and those with comorbid conditions (most clearly cardiovascular disease, respiratory conditions, and cancer) are at higher risk for a more severe disease course and death.
  • Common lab findings: ↓lymphocytes, ↓platelets, ↑CRP. Higher inflammatory markers seen in more severe disease.
  • Common chest CT findings: bilateral ground glass opacities, consolidations, and “crazy paving” patterns.

Good News About Testing In The Us

  • The Food and Drug Administration (FDA) has approved the first coronavirus diagnostic test that can be conducted entirely at the point of care.
  • The test from California-based Cepheid will deliver results in about 45 minutes — much faster than current tests that require a sample to be sent to a centralized lab, where results can take days.
  • To be rolled out by March 30.

Am I still Infectious After Recovering?

  • Probably to some extent, though the first batch of studies is far from conclusive as to how long virus shedding lasts. • Provisional research from Germany has suggested that COVID-19 infectiousness – in contrast to the 2003 SARS outbreak – peaks early and that recovering patients with mild symptoms become low-risk around 10 days after they first fall ill.
  • But another study, following four medical professionals treated at a Wuhan hospital, revealed that traces of the virus could persist in the body for up to two weeks after symptoms had vanished; as the patients were no longer coughing or sneezing, the potential means of transmission were albeit much reduced.
  • Less optimistic was a study published last week in The Lancet medical journal that showed the virus survived in one Chinese patient’s respiratory tract for 37 days – well above the average of 24 days for those with critical disease status.

https://bit.ly/3aeQvpJ

Can I Catch COVID-19 a Second Time?

  • Catching a coronavirus generally means that person is immune, at least for a time, to repeat infection. But doubts arose regarding COVID-19 in late February when a woman in her late 40s who had been discharged from hospital in Osaka, Japan tested positive a second time. There also a similar case with one of the Diamond Princess passengers, and another in South Korea. These were isolated cases, but more worrying was research from Guangdong province, China reporting that 14% of recovering patients had also retested positive.
  • However, it is too early to jump to conclusions. These cases have not been fully confirmed, with many possible explanations, including faulty, over-sensitive or over-diligent testing; or that the virus had become dormant for a time and then re-emerged. •The Centers for Disease Control and Prevention (CDC) stress that our immune response to this particular disease is not yet clearly understood: “Patients with MERS-CoV infection are unlikely to be reinfected shortly after they recover, but it is not yet known whether similar immune protection will be observed for patients with COVID-19.”

https://bit.ly/3aeQvpJ

What Is The Recovery Rate?

  • At the time of writing, on 20 March, the mortality rate among confirmed cases was 4%.
  • Though the good news is the true figure is likely to be lower, because of large numbers of unreported people with mild symptoms. The UK’s chief medical officer, Chris Whitty, has disputed the WHO’s global figure of 3.4%, saying he believes the eventual toll will be around 1%.
  • One reassuring tipping point to bear in mind is that around one month after the initial outbreak in China, with strict containment measures in place, the number of recoveries began to outstrip the number of new cases. This is the point the West’s containment measures are hoping to reach.

Covid-19 Potential Treatments

  • In vitro data and animal models (based on MERS) suggest that the investigational RNA polymerase inhibitor remdesivir may have activity against SARS-CoV-2 and prevent serious pulmonary complications; several clinical trials are currently underway.
  • Likewise, in vitro data suggest that chloroquine or hydroxychloroquine may have antiviral activity by blocking egress of SARS-CoV-2 from endocytic vesicles.
  • A randomized clinical trial of the HIV drug combination lopinavir/ritonavir (Kaletra) conducted in China found no difference in time to clinical improvement, viral shedding, or 28-day mortality.
  • Tocilizumab and other IL-6 receptor antagonists may have a role in modulating the inflammatory state (cytokine storm) engendered by COVID-19 but remain investigational.

Remdesivir

  • Two phase 3 studies intended to begin in March are set to conclude in May 2020.  Both studies have similar designs and will compare remdesivir 200 mg IV loading dose followed by 100 mg IV daily to standard of care therapy.
  • Both studies have 5-day and 10-day treatment durations that are being evaluated. Additionally, the U.S. Army Medical Research and Development Command is operating an expanded access program.

https://bit.ly/3di0i09

Gilead Just Stopped Emergency Access to Remdesivir Outside of Clinical Trials

“Due to overwhelming demand over the last several days, during this transition period we are unable to accept new individual compassionate use requests, with the exception of requests for pregnant women and children less than 18 years of age with confirmed COVID-19 and severe manifestations of disease. We are focused now on processing previously approved requests and anticipate the expanded access programs will initiate in a similar expected timeframe that any new requests for compassionate use would have been processed.”

Chloroquine: An Old Malaria Drug That Shows Promise

  • Chloroquine is a medication used to prevent and to treat malaria in areas where malaria is known to be sensitive to its effects.  Occasionally it is used for amebiasis that is occurring outside the intestines, rheumatoid arthritis, and lupus erythematosus. It is taken by mouth.  It is also being used experimentally to treat COVID-19 as of 2020.
  • All Europeans visiting malaria-endemic geographic areas for decades received chloroquine prophylaxis and continued it for 2 months after their return. In addition, local residents took chloroquine continuously, and treatment of malaria has long been based on this drug.
  • Common side effects include muscle problems, loss of appetite, diarrhea, and skin rash. Serious side effects include problems with vision, muscle damage, seizures, and low blood cell levels.
  • An early clinical trial conducted in COVID-19 Chinese patients (in print as of March 2020), showed that chloroquine had a significant effect, both in terms of clinical outcome and viral clearance, when comparing to controls groups .
  • A better tolerated drug, hydroxychloroquine,  was approved for medical use in the United States in 1955.
  • Hydroxychloroquine has been used for decades at much higher doses (up to 600 mg/day) to treat autoimmune disease.

 https://bit.ly/3dnXpLl

Hydroxychloroquine: Hype or Reality?

  • This article included just 36 patients (20 hydroxychloroquine and 16 controls)
  • Six of the 20 hydroxychloroquine patients got azithromycin and these patients appeared to have more rapid microbiological eradication of the virus as compared to monotherapy or the control group.  No blood samples.
  • These data should be taken with caution as amongst other things, it is a small sample and not a finding that was anticipated when designing this analysis.
  • “A treatment with the hydroxychloroquine combination (200 mg x 3 per day for 10 days) + Azithromycin (500 mg on the 1st day then 250 mg per day for 5 more days), plus precautions for use of this association (including an electrocardiogram on D0 and D2)”
  • This is not considered a study but a “white paper” with a small sample size. Non-randomized and no placebo arm. 
  • It started with 26 patients on treatment but only 20 were included in the analysis.

Gautret et al. (2020) Hydroxychloroquine and azithromycin as a treatment of COVID‐19: results of an open‐label non‐randomized clinical trial. International Journal of Antimicrobial Agents – In Press 17 March 2020 – DOI : 10.1016/j.ijantimicag.2020.105949

Hydroxychloroquine Studies Currently Enrolling

  • A Chinese clinical study evaluating 5 daily doses of 400 mg in adults who developed pneumonia from the viral infection is scheduled to conclude in the latter half of 2020. The study is sponsored by the Shanghai Public Health Clinical Center, and it is unknown how long after study conclusion the information may be shared with other stakeholders.
  • A large ongoing study is comparing hydroxychloroquine’s clinical outcomes to carrimycin, lopinavir/ritonavir, and umifenovir, but the study is not anticipated to conclude before February 2021. The most recent Chinese guidelines on COVID-19 recommend chloroquine phosphate 500 mg twice a day for up to 10 days.
  • On 17 March 2020, the AIFA Scientific Technical Commission of the Italian Medicines Agency expressed a favorable opinion on including the off-label use of chloroquine and hydroxychloroquine for the treatment of COVID-19.
  • It is currently out of stock in most  US pharmacies, but compounding pharmacies are starting to make it available.
  • The University of Minnesota is starting a placebo-controlled study to see if hydroxychloroquine can prevent infection in health-care workers.

Dong L, Hu S, Gao J. Discovering drugs to treat coronavirus disease 2019 (COVID-19). Drug Discov Ther.2020;14:58-60

Ibuprofen (Advil) and Covid-19: Yes or No?

  • Experts say there’s no clear evidence that ibuprofen makes COVID-19 worse.
  • One thing specific to COVID-19 is that some lab experiments are showing that ibuprofen may boost the amount of ACE2 receptors that the virus uses to infect cells and could make the virus spread faster. But that’s just theoretical.
  • The World Health Organization (WHO) has changed its stance on taking ibuprofen if you have COVID-19, but people are still scratching their heads over what they should take if or when they contract the virus.
  • Acetominophen (Tylenol) is better than ibuprofen for fever management. But it needs to be used with caution in people with liver issues.