FEATURES AND THERAPEUTIC OPTIONS
For those of us who witnessed the outbreak of HIV in the early eighties, there are some eerie similarities and sharp differences with the present epidemic. For one, learning as we go then and now means lost lives and fluid guidelines that keep changing. However, we now live in a world where information is swiftly spread and we are faced with an overload of facts, data, making it trying to sift through. Social media is replete with false claims of cure and dubious recipes. There are some reliable repositories of information:
www.coronavirus.jhu.edu This site keeps tab of total count of cases/deaths, country by country.
The 2 previous sites are maintained by Cold Spring Harbor Lab and serve as free online archive and distribution of unpublished preprints as a means to quickly diffuse scientific findings.
www.ndr.de This is a podcast (Das coronavirus) from a foremost virologist from Germany, Christian Drosten, who pioneered the COVID-19 test outside of China and also had discovered SARS. It’s in German but is expected to be translated into English soon.
www.preview.app.goo.gl This is “Corona Virus Daily,” a podcast by NPR that gives an update of the condition in all of its facets.
static01nyt.com This is an e-book prepared by the NY Times about the disease; it’s a collection of articles written since the onset. Good source for laymen and experts.
nejm.org All its articles about Covid-19 are free.
covid.emrap.org Lots of useful podcasts, especially for hospitalists or ER physicians.
The outer shell of the virus contains plenty of spikes; they are proteins that enter the human cell via several receptors. Once inside the human cell, the virus goes on overdrive and replicates itself; it is then released to continue its propagation exponentially. The host cell becomes a factory to produce more viruses and eventually precipitates its apoptosis. Epithelial cells are especially attacked in the respiratory, GI, cardiac tracts. In return the body mounts an immune response that when amplified creates a cytokine overload that creates the complications. This inflammatory process leads to multiorgan failure: ARDS, heart failure, acute kidney injury, septicemia. Therein the high morbidity and mortality.
Primarily from person to person occurs via air droplets; the ports of entry include orifices like the nose, mouth and eyes. Contact with fomites, i.e. surfaces of contaminated sheets, doors, etc. can also propagate the virus once an unwashed hand that touched a contaminated surface reaches the face. The virus’s survival on surfaces can last up to a number of days. First lesson learned the hard way: an infected person who is asymptomatic is a good vector for the disease.
More often than not, symptoms may be mild or can involve the GI or respiratory tract initially. Hence fever, cattarh, cough, dyspnea, diarrhea may be initial symptoms in any order, singly or in combination. Lately we have also learned that a patient may present with just dysgeusia, anosmia or hyposmia. This loss of taste or smell needs to alert the astute clinician the same way that a young person presenting with seborrhea or herpes zoster warrants an HIV titer.
|Transmission is faster/shorter incubation||Mortality is higher|
|Rate of propagation is less||Rate of propagation per person 2-2.5|
|Children are good vectors||Children get infection from adults|
|Percentage of severity is less||15% with severe infection; 5% require ventilation|
|Diagnosis relies on detection of virus RNA from nasal swab; immunosuppressed, elderly, comorbid conditions increase risk of complications. Mortality rate is higher for men than women. For both.|
Diagnosis. With the delay in obtaining the result of the Covid-19 titer, very often, it’s primarily made on clinical grounds once other infections are ruled out such influenza, common bacteria causing pneumonia. Some features include bilateral pneumonia with a pattern of ground glass on CT scan, low oxygen saturation on room air in symptomatic patients, depending on progress of the illness. Toward the end of March, the FDA authorized the use of a rapid test and as it becomes more widespread in its use, one can quickly make diagnosis on patient presenting with even mild symptoms. As it stands now, every patient that comes to the ER gets tested for influenza. One can imagine a time not too far distant that the same will be done for Covid-19.
Therapeutic interventions. Faced with a devastating scourge spreading worldwide and leaving lots of victims in its trail, without any well-defined therapeutic solution, any number of interventions have been tried. As time evolves, more studies are being published. Cao et al did a trial of Lopinavir-Ritonavir on 199 patients and found no benefit1. Remdesivir and Chloroquine were found in vitro to inhibit Covid-19 growth2. Both are being investigated in large scale trials. However, Chloroquine and its derivative Hydroxychloroquine have taken the world by storm when Raoult reported his findings on 20 patients3. Although many have criticized the report, the combination of hydroxychloroquine and azithromycin have become part of mainstream treatment of symptomatic patients in short order even before result of undergoing clinical trials are known. One day of 400mg of hydroxychloroquine BID followed by 200mg BID for 4 days as well as a 3-day course of azithromycin is a regimen widely used due to its simplicity. A recent study from NYU warns about potential QT prolongation that can lead to significant arrhythmia as a side effect to be mindful of 4. Whether it turns out to be a significant clinical problem remains to be seen.
An intervention that’s unheralded but significant is the success of vitamin C as adjuvant treatment. Several meta-analyses are available as solid evidence of the scientific underpinning of the use of vitamin C. The latest one was published last week from Finland about the use of vitamin C and its propensity to reduce duration of mechanical ventilation by Hemilä and Chalker5; the same authors published about patients in the ICU6. Wang et al looked at the published data on the mortality rate of critically ill patients treated with different doses of vitamin C in 20197; in 2018, a meta-analysis about patients with sepsis treated with vitamin C was published by Li8. These are solid scientific documents peering into a therapeutic intervention not used as often as warranted for sick patients. A couple of weeks ago in a video conference, Dr. Enquian Mao, chief of ER at Ruijin Hospital in Shanghai shared his data about 359 patients with Covid-19 treated by the Shanghai Public Health Center who received High dose vitamin C ranging from 10-20gm a day for 7-10 days. No death recorded. He also happens to have been using high dose of vitamin C in acute pancreatitis, sepsis, surgical wound healing for past 10 years with similar good success9. The data are supposed to be published later in a scientific journal.
It’s quite clear that several modalities exist for treatment of a potentially deadly illness. Whereas treatment of serious illnesses like AIDS up to now has relied on expensive medications, the availability and success rate of a low-cost treatment such as vitamin C can be a game changer.
Reynald Altéma, MD
1. Cao, B., et al. A Trial of Lopinavir-Ritonavir in Adults Hospitalized with Severe Covid-19. NEJM, March 18, 2020
2. Wang, M., et al. Remdesevir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res 30, 269-271 (2020).
3. Gautret, P., et al. Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial, International Journal of Antimicrobial Agents (2020).
4. Chorin, E., et al. The QT Interval in Patients with SARS-CoV-2 Infection Treated with Hydroxychloroquine/Azithromycin. medRxiv 2020.04.02.20047050; doi:https://doi.org/10.1101/2020.04.02.20047050
5. Hemilä, H.; Chalker, E. Vitamin C Can Shorten the length of Stay in the ICU: A Meta-Analysis. Nutrients 2019, 11, 708.
6. Hemilä, H.; Chalker, E. Vitamin C may reduce the duration of mechanical ventilation in critically ill patients: a meta-regression analysis. Journal of Intensive Care 2020, 8:15.
7. Wang, Y., et al. Effects of different ascorbic doses on the mortality of critically ill patients: a meta-analysis. Ann. Intensive Care, (2019) 9:58
8. Li, J. Evidence is stonger than you think: a meta-analysis of vitamin C use in patients with sepsis. Critical Care, 2018:22:258
9. Othomolecular Medicine News Release, March 18, 2020. (orthomolecular.org).