This is a blood collection and retrospective data collection study. The investigators plan to assess whether the sedative drug, isoflurane, can treat COVID-19 patients relatively better compared to other sedative drugs given during routine treatment to patients on mechanical ventilation. The investigators will also use nanoneedle biosensors to quickly detect blood IgM/IgG ratio in those patients, and (3) to establish a pre-clinical system to determine the effects of inhalational anesthetics on amounts of SARS-CoV-2 and other viruses, and pneumoniae.
There are neither effective treatments nor fast detection for COVID-19. Here the
investigators propose a medical records and excess clinical material study to determine
whether anesthetic isoflurane can treat COVID-19. Specifically, inhalation anesthetics,
including isoflurane, inhibit the replication of an RNA virus. In addition, anesthesia
machines have been used to provide mechanical ventilation for COVID-19 patients at MGH and at
other hospitals. Finally, due to the shortage of intravenous anesthetic propofol, inhalation
anesthetics including isoflurane, delivered by the anesthesia machine, are currently used to
sedate COVID-19 patients during mechanic ventilation. Moreover, isoflurane is very
economical, e.g. $6 (isoflurane) versus $1200 (propofol) per patient per day in sedating
COVID-19 patients. As such, the investigators propose to use this already established system
in COVID-19 patients to determine whether isoflurane, delivered to lungs, can treat COVID-19
and especially COVID-19 pneumonia. In summary, the proposed study is a low risk observation
research using the already established clinical care system of COVID-19 patients and the
investigators will NOT have any additional procedures required for research purpose. The
investigators will also collect the left-over clinical sample and then use nanotechnology to
achieve fast detection of IgM/IgG ratio as the biomarker of the progress of COVID-19
following the isoflurane or propofol sedation.
Specifically, inhalation anesthetics, including isoflurane, inhibit replication of the
measles virus and other RNA virus 1,2. Severe COVID-19 patients need mechanical ventilation
to support lung function. The anesthesia machine can be used to ventilate lungs in these
patients in addition to regular ventilators which has already been started at MGH and other
hospitals as regular ventilators are extremely limited. Clinicians have already determined
the settings of these machines, including humidification, for treating COVID-19 patients and
the investigators will use these predetermined settings in this study. Additionally, there is
a shortage of the intravenous anesthetic propofol. As a result, inhalation anesthetics
including isoflurane, delivered by the anesthesia machine, are currently used to sedate
COVID-19 patients during mechanic ventilation. Moreover, isoflurane is very economical, e.g.
$6 (isoflurane) versus $1200 (propofol) per patient per day in sedating COVID-19 patients. As
such, the investigators propose to use this already established system in COVID-19 patients
to determine whether isoflurane, delivered to lungs, can treat COVID-19 and especially
COVID-19 pneumonia better than other sedatives in this retrospective data collection study.
Moreover, in pre-clinical studies, the investigators propose to establish a system to
determine whether inhalation anesthetics can treat virus-induced pneumonia by reducing the
amount of virus, e.g., SARS-CoV-2 and influenza.
Sensitive, cost-effective and fast detection of SARS-CoV-2 is extremely critical. Currently,
a real-time polymerase chain reaction (PCR) test detects the genetic material of SARS-CoV-2.
However, the test has large false negatives, poses risks during specimen collection and
sample handling, and takes a long time (~ 8 hours). However, in response to SARS-CoV-2, IgG
is the most abundant immunoglobulin to be produced and is maintained in the body after
initial exposure for a long-term response. IgM is the first immunoglobulin to be produced but
is primarily detected during the early onset of disease. Therefore, SARS-CoV-2 specific
IgM/IgG ratio in blood could be used as biomarker for COVID-19 prognostics (Fatma et al,
medRxiv, 2020), and could also be used as a measure of drug response 3. The nanoneedle
technology developed at a startup-company from Harvard University (NanoMosaic LLC) provides
pg/ml-level sensitivity and 10 uL sample volume for quantification of a panel of biomarkers
including SARS-CoV-2 specific IgG and IgMs in a single assay. The technology uses nanoneedle
biosensors densely integrated on a silicon chip and manufactured with CMOS-compatible
nanofabrication processes 4. Each nanoneedle is a label-free biosensor and changes its
scattering spectrum when an antigen binds to its surface. Each analyte-specific sensing area
consists of a total of ~24k nanoneedles divided into a digital region (~20k nanoneedles), an
analog region (~3k nanoneedles) and a fabrication QC region (~1k nanoneedles), thus providing
a wider dynamic range beyond the digital counting concentration ranges. Each single analyte
area, including both digital and analog sensors, is less than 500 um. With further
development, the entire assay can be finished in a half-hour on a table-top instrument with
less than 10 ul blood samples, which will facilitate therapeutic development and decision
making for COVID-19 and other virus-induced pneumoniae.
Inclusion Criteria:
- Over the age of 18 years old
- Tested positive for COVID-19
- Documented SARS-CoV-2 carriage in the nasopharyngeal sample by PCR
- Intubated for mechanical ventilation with an anesthesia machine
Exclusion Criteria:
- Patient or any their family members have any contraindication for inhalation
anesthetics (e.g., malignant hyperthermia).
Massachusetts General Hospital
Boston, Massachusetts, United States