Today more than six months since COVID began spreading throughout the United States, we still unfortunately have a long way to go before we can let our guard down. There are some positive developments if you look close enough, but they are overshadowed by over 1,000 new fatalities in our country on a daily basis recently. As usual I will focus on the State and local level more than national and I will take a bit of a deeper dive into some medications being studied in treatment.
Texas has seen a downward trend in daily reported cases but the downward trajectory I would not characterize as a steep downward curve. Our seven day average of new cases is still over 7,000 which is an improvement from a month ago when we were averaging over 10,000 new cases daily. The downward trend started approximately 2 1/2 weeks after Governor Abbott mandated masks state wide. Statewide, the percentage of tests performed which are positive has been above 10% every day going back to July 23rd. At the State level this is a metric that is closely watched. The most recent data I have seen shows August 14th finally dipping below 15% positive. A few days prior it approached 25%. The state has set as a benchmark 10% positive as what they consider to be a “red flag”. Previously I discussed an alarming number of “hot spots” throughout the state of Texas. Right now that does not seem to be the case as much as it was previously, with the Rio Grande Valley being an exception. The situation in that area is alarming to say the least.
Day to day fluctuations in the number of tests being performed seems to fluctuate significantly and I am not sure why that is the case but likely numerous reasons.
The PCR test remains the “gold standard” for diagnosis of COVID-19. It is by far the most accurate/reliable test available. Early on it was extremely difficult to get a PCR test if not sick enough to be admitted to the hospital. Supplies were so limited my practice was only allowed three specimen kits at a time. This has largely improved locally. On a state wide level I cannot comment with any more details but I can tell you locally in DFW, if you want or need a PCR test you should be able to get one and I am seeing turnaround times even from the large labs which were inundated early on and taking sometimes ten days to result, now they are in the 2-3 day range from what I am observing (reviewing lab results and seeing when they were received/resulted).
The rapid test has some usefulness depending on details clinically. The rapid test attempts to identify surface antigens (surface markers specific to COVID) and if present in large enough quantity to detect, a positive result is reliable. The one issue is the false negative rate is relatively high. Some studies have shown the false negative rate to be as high as 20-40%. Currently the rapid test is being performed in some local clinics, often times accompanied by the PCR test being sent off (particular important if rapid test is negative). Rapid test positive: No need for PCR. Rapid test negative: PCR test should be done at the same time. For the time being in our practice we have chosen not to offer the rapid test as we are getting remarkably fast turnaround times with the lab we are using for PCR tests. If done early AM we likely will have a result by end of day (late evening typically which many of my patients will testify I will text them as late as 9:30 if they want to be notified ASAP).
New rapid tests are also being developed which may be (hopefully will be) large scale and could potentially even be done at home, and even if in a clinic or hospital environment they will likely be cheaper than current options: https://news.yale.edu/2020/08/15/yales-rapid-covid-19-saliva-test-receives-fda-emergency-use-authorization
Remdesivir is the drug that seems to be getting the most attention recently due to its demonstrated reduction in duration of illness in trials. Currently Remdesivir is only available as an Intravenous medication, and supply is limited. It is also costly, with a five day course costing $3,120. Studies have shown a five day course to achieve similar outcomes as lengthier courses of treatment. The obvious down sides in addition to supply limitations are cost and requiring IV administration. An inhalational form of Remdesivir is currently in the early stages of trials (Stage 1 trial to evaluate for safety). It it far too soon to know if and when the inhalational form will be available if ever and if so how costly it will be and how widely available. Likely if it comes to market it will be expensive and only recommended for those with respiratory symptoms and those deemed to be high risk.
A small study in Spain has shown some evidence that certain HIV medications may reduce the incidence and severity of COVID. These drugs have been demonstrated in a laboratory environment to inhibit one enzyme specific to COVID-19. How that translates clinically is yet to be determined but trials are underway to evaluate these drugs as prophylaxis. Hydroxychloroquine, despite many randomized double blinded placebo controlled trials showing no benefit (and one study showing potential harm) is still being evaluated as well in at least one new trial comparing the HIV medications as well as Hydroxychloroquine as prophylaxis for those who work in a healthcare environment. At this point in time until we have more data none of these are recommended for prophylaxis but that could potentially change, though not likely in the short term. While many studies have demonstrated no benefit for treating symptomatic patients with Hydroxychloroquine (of various disease severity) diagnosed with COVID, its role in prophylaxis is still being investigated by at least one study underway. We do have one recent study published within the past few weeks which showed no benefit using Hydroxychloroquine as prophylaxis post exposure: https://www.nejm.org/doi/full/10.1056/NEJMoa2016638
Other trials are underway to evaluate additional medications which are immunomodulators, interfering in the “Cytokine Storm” that is often seen in patients with severe illness. Laboratory markers as well as clinical indicators both can be used to determine when patients are entering a phase of critical illness often caused by the body’s own immune system making the disease process far worse. A good article in relatively simple language regarding explains what this involves from a pathophysiology standpoint: https://www.knowablemagazine.org/article/health-disease/2020/what-cytokine-storm?gclid=Cj0KCQjwsuP5BRCoARIsAPtX_wF8ZXsiDa2Zx_A1EnGIdLTWo_5d2VjNh45so7D-i6F6nDdzgZ6lJ0kaAhtsEALw_wcB. One drug called Actemra recently was investigated in a trial and unfortunately did not show any clinical benefit in the benchmarks being evaluated (mortality rate being one of them) but will likely be studied in more detail. Another drug called Olumiant is also being studied in similar fashion. These medications will likely—-if shown in studies to be beneficial—-mostly be indicated for use in patients ill enough to require hospitalization.
Convalescent Plasma also is being researched. Small studies from Wuhan conducted early on in the outbreak showed improved outcomes in critically ill patients. These were observational studies involving small numbers of patients. Studies conducted in the United States have demonstrated benefit from a safety standpoint (not making people worse) and this is being used as an intervention largely as investigational standpoint. One recent study in the United States has reportedly shown reduction in mortality but has not yet been peer reviewed and was not placebo controlled. I am in the early stages of diving in to the details of this study and will likely have more info at a later time. This was a nation wide study with a large number of patients involved at a number of different institutions, spearheaded by the Mayo Clinic.
Numerous vaccines are being investigated and I am following peripherally. My interest will perk up when we see something likely to be widely available with good data to support its use.
When can we stop wearing these masks and get back to normalcy?
I understand your frustration. Believe me, I do not enjoy wearing masks any more than you do. But for now they are necessary and important and I believe that will be the case likely through the fall, unless we see a sudden significant shift in our case rate. We have some early encouraging signs in terms of some of the numbers depending on which metrics you are looking at but we are nowhere near being ready to stop wearing masks and resume normal day to day life. In order for that to take place we need our case rate to drop from the point of community spread to isolated clusters of cases which can quickly identified/contact traced and hopefully eliminated. I will be very surprised if this happens in the next few months. It would be speculative for me to be any more specific than that.
At this point in time numerous drugs are being investigated for treatment of moderate/severe cases of COVID. While we still have a lot to learn, hopefully these drugs will offer some promise in terms of decreased mortality rate. This is of course priority number one in terms of treating COVID. Other medications are being researched as post exposure prophylaxis, and at least one medication which may be available as an inhalational preparation depending on how the studies go. Rapid tests are available and we should soon have more of them and cheaper ones more readily available/accessible. If and when that happens, PCR will remain the best test available particularly when the rapid test is negative but the rapid test will be a valuable tool as part of our armamentarium.
My hope: Even if no vaccine available, the best case scenario from a treatment and diagnosis standpoint would be the following:
- Proven medications for prophylaxis post exposure and/or for high risk individuals
- Given #1, for those symptomatic: ubiquitous inexpensive rapid tests, with medications for those with respiratory symptoms (inhaled Remdesivir perhaps depending on study results) to limit duration of illness
- Multiple options in terms of pharmacologic intervention to lower the mortality rate for those with severe disease, based on randomized double blinded placebo controlled trials showing mortality benefit
- Even better but not likely to materialize any time soon: Genetic testing available for those at risk for developing severe disease from Cytokine Storm, with those with the genetic markers being given priority for vaccination if available and prophylaxis if proven effective
Even better would be to have a combination of all of the above plus a widely available vaccine.
Until several of the above things occur—-wearing a mask, social distancing, and good hand hygiene remain the most effective interventions we have and will likely be necessary for a few more months at a minimum.