An interesting study, examining the association of BCG vaccination and risk of COVID-19 deaths using country level data. Authors make a compelling case that there is an association using data from a large number of countries.
Such studies have potential for ecological fallacy – however, there is underlying biological plausibility and further, as we are collecting data on these cases, knowing about patients who had BCG vaccination versus those who did not may help to solidify the evidence in support of BCG. In other words, the evidence in not solid but need further study.
Indeed, clinical trial examining the role of BCG in stimulating immunity and generating resistance is ongoing Australia where they are planning to enroll approximately 4,000 healthcare workers at hospitals across Australia.
Sunday, March 29, 2020
Friday, March 27, 2020
Plasma From Recovered Patients Can Help Critically-sick COVID-19 Patients
Interesting case series of 5 patients who received transfusion with plasms from patients who had recovered from COVID-19 infection and had high titers of immunoglobulins against COVID-19. All 5 patients were on ventilator, critically sick, and febrile. With days of receiving plasma, their condition improved. Three of the five have now been discharged while the other two are doing better.
Sunday, March 08, 2020
Myocarditis in Novel Coronavirus (COVID-19) Infected Patients
Due to significant similarities between SARS-CoV and COVID-19 virus (also called SARS-CoV-2), ACE2 has been proposed as a possible mechanism of entry and possible lung injury.
ACE2 is also expressed in heart and some studies have shown the ACE2 may play a role in the size of ischemic injury. Hence, one can propose that there may be myocardial injury in patients infected with novel corona virus (COVID-19).
A recently reported study found that the cardiac troponin levels were elevated in many patients, markedly elevated in patients who died, and that some of the patients died due to myocardial damage related to myocarditis. Further, patients with prior cardiovascular disease did poorly. In other words, while majority of patients have lung disease, a significant number of patients may also develop cardiac inflammation.
ACE2 May be a Receptor for COVID-19 Virus Entry into the Cells
Because SARS-COV virus has significant similarities to the COVID-19 virus (also called SARS-CoV-2), it is worth comparing the two viruses for similarities to learn about COVID-19.
SARS-CoV has surface spikes that bind to Angiotensin Converting Enzyme 2 (ACE2) and gain entry into human cells. Once inside the human cell, virus downregulates the further expression of ACE2 on cell surface. Importantly, ACE2 surface expression is important to keep inflammatory response in check and low levels of ACE2 results in increased inflammatory response.
It is quite likely that COVID-19 (SARS-CoV-2) also binds to ACE2 receptors. In fact, there is significant homology in the amino acid and gene sequence of virus spikes. Further, the computer-generated 3-D models show similar structure and maintenance of the binding site.
Thus, one can propose a model similar to SARS-CoV where COVID-19 binds to the ACE2 on surface of pulmonary epithelial cells, downregulates these receptors, worsens local inflammatory responses and leads to the lung disease that we see on lung imaging (particularly on CT scans) that is so prevalent in these patients.
Of note, ACE2 is present on the intestinal epithelial cells luminal surface giving another portal of entry for these patients and presence of diarrhea in some patients with COVID-19. Other places where ACE2 expression is particularly high include heart, kidneys, and testes.
While there are several inhibitors of ACE1 in the market and are one of the most commonly prescribed medications for hypertension, these inhibitors don’t work on ACE2. Further, inhibition of ACE2 might potentially lead to worsening of the disease in these patients.
Other methods that can be tested include vaccinations against the viral spike proteins, inhibition of ACE2 downstream pathways such as TMPRSS2, and delivering excessive amounts of ACE2 (or homologues) to saturate viral surface receptors.
The role of ACE2 as potential anti-inflammatory agent in human body makes developing any vaccine or therapeutic drugs challenging as it is difficult to predict the responses inside our bodies. Because ACE2 pathways are not fully discovered yet, the development of effective treatments with minimal adverse effects likely will be challenging.
SARS-CoV has surface spikes that bind to Angiotensin Converting Enzyme 2 (ACE2) and gain entry into human cells. Once inside the human cell, virus downregulates the further expression of ACE2 on cell surface. Importantly, ACE2 surface expression is important to keep inflammatory response in check and low levels of ACE2 results in increased inflammatory response.
It is quite likely that COVID-19 (SARS-CoV-2) also binds to ACE2 receptors. In fact, there is significant homology in the amino acid and gene sequence of virus spikes. Further, the computer-generated 3-D models show similar structure and maintenance of the binding site.
Thus, one can propose a model similar to SARS-CoV where COVID-19 binds to the ACE2 on surface of pulmonary epithelial cells, downregulates these receptors, worsens local inflammatory responses and leads to the lung disease that we see on lung imaging (particularly on CT scans) that is so prevalent in these patients.
Of note, ACE2 is present on the intestinal epithelial cells luminal surface giving another portal of entry for these patients and presence of diarrhea in some patients with COVID-19. Other places where ACE2 expression is particularly high include heart, kidneys, and testes.
While there are several inhibitors of ACE1 in the market and are one of the most commonly prescribed medications for hypertension, these inhibitors don’t work on ACE2. Further, inhibition of ACE2 might potentially lead to worsening of the disease in these patients.
Other methods that can be tested include vaccinations against the viral spike proteins, inhibition of ACE2 downstream pathways such as TMPRSS2, and delivering excessive amounts of ACE2 (or homologues) to saturate viral surface receptors.
The role of ACE2 as potential anti-inflammatory agent in human body makes developing any vaccine or therapeutic drugs challenging as it is difficult to predict the responses inside our bodies. Because ACE2 pathways are not fully discovered yet, the development of effective treatments with minimal adverse effects likely will be challenging.
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