COVID-19 is caused by SARS-CoV-2 and can cause moderate to severe symptoms such as respiratory distress. Current treatments include remdesivir, oxygen therapy, and monoclonal antibodies. The virus decreases CD4 and CD8 T cell counts and increases inflammatory cytokines. Researchers are exploring therapies such as T cell immunotherapy targeting SARS-CoV-2, convalescent plasma, monoclonal antibodies targeting IL-6 and IL-1, and mesenchymal stem cells to reduce inflammation and repair lung damage. Vaccine research includes viral vectors expressing the SARS-CoV-2 spike protein and engineering T cells to target the virus.

1. By Dharm Desai
(Int. MSc. Biotechnology)

2.  COVID19 caused by Severe Acute Respiratory Syndrome
Coronavirus 2 (SARS-COV2).
 Over 85% patients show moderate symptoms but
approximately 15% develop ARDS (acute respiratory
distress syndrome), pneumonia, multiple organ failure due
to systematic inflammation response syndrome
(SIRS).(Huang C et al.,2020; Xu et al.,2020)
 Currently used therapies and medications
 Remdesivir
 Vencomycin
 Oxygen therapy with ventilation
 Serum therapy (typical vaccine concept )

3. fever
diarrhoea
nausea
Runn
y nose
Sore
throat
Lose of
taste/smell
headache
Muscle or
body ache
Breathing
difficulty
fatigue
Cough

4.  CD 4 and CD8 cell count decrease; B cell count
increase especially CD19+ B cell (antibody producing
cells), B effecter cell (antibody secreting cell) count
increase, increase levels of PD-1 T cells were
detected.(Diao b et al.,2020)
 Levels of IL-6, IL-10, TNF-alpha are increased in ICU
patients as compared to non-ICU patients (Diao b et
al.,2020)

5. T cells and cytokines levels in ICU and non ICU patients (Diao b et al.,2020)
Increased PD1 T cells levels in ICU
patients

8.  HSV-1 based vectors for vaccine preparation
 Combination of CAR-T cell therapy with anti-viral
drugs
 Recovered patients plasma containing neutralizing
antibodies
 Tocilizumab (anti IL-6r antibody)
 Anti complement antibodies
 Mesenchymal Stem cells

10.  HSV d106S
 Can express viral, bacterial, cancer gene product
 Used for induction of HIV and SIV in rhesus monkey,
proved to be stable and able to provide prolonged
antigenic memory
 Low toxic because of its non replicating behaviour
 In mice model as compared to adenoviral vectors; it
expressed 10 fold transgene of HSV

11.  Viral vector with S protein antigen of SARS-COV2
 Parent strain will be eliminated by guide RNA;
resulting pure and non-toxic viral vectors
 Injection into affected patient
 Provides long time antigenic memory
Intellectual Property Status: Patent(s) Pending
Harvard MIT & Stanford University covid19
collaboration,2020

12.  Patients who developed ARDS advanced from
COVID19, were treated with plasma containing
neutralizing antibodies, identification of B-cells
producing anti-spike antibodies is under investigation.
 All five patients showed improvement.
(Shen C et al,2020)

13.  According to a clinical trial, IL-6 receptor targated monoclonal
antibodies (Tocilizumab) were used on patients with pneumonia
and ARDS advanced from COVID19 and respiratory function
improvement was seen in 21 patients
 Large population study is needed with more numbers of similar
clinical trials
 Potential Targeted cytokine receptors for Monoclonal antibodies
production for COVID19 are IL-1, IL-17.
 Anti complement antibodies can also be used and is under
development
(ChiCTR2000029765)

14.  The engineering of specific virus targeted receptors onto
patient’s own T cells can be a way to fight COVID19.
 T cells can be redirected to target coronavirus with T cell
immunotherapy
 It has been used in hepatitis B and cancer treatment;
reengineered T cells including (CAR-T) chimeric antigenic
receptor T cell and (TCR) T-cell receptors were applied.
 This criteria was suggested by Professor Antonio Bertoletii from
Duke-NUS, the research is under development.
Duke-NUS R & D

15.  Anti-inflammatory; anti-apoptotic
 Can repair pulmonary epithelial cell damage, promote
alveolar fluid clearance
 Passed through preclinical and clinical trials
 Assured safety and efficacy
 In china, MSC based therapy is undergoing through
two clinical trials
(Cao X., 2020)

16.  SARS Cov-2 RT inhibitor
 Ultrasound killing (India!)
 EMF sanitization
 UVC sanitization (Taiwan)

17.  Cao, X. COVID-19: immunopathology and its implications
for therapy. Nat Rev Immunol 20, 269–270 (2020).
 Huang, C. et al. Clinical features of patients infected with
2019 novel coronavirus in Wuhan, China. Lancet 395, 497–
506 (2020).
 Shen, C. et al. Treatment of 5 critically ill patients with
COVID-19 with convalescent plasma (2020).
 Diao, Bo et al. “Reduction and Functional Exhaustion of T
Cells in Patients With Coronavirus Disease 2019 (COVID-
19).” Frontiers in immunology vol. 11 827. 1 May. 2020,
doi:10.3389/fimmu.2020.00827
 Xu, Z. et al. Pathological findings of COVID-19 associated
with acute respiratory distress syndrome. Lancet Respir.
Med. 8, 420–422 (2020).

18.  https://www.drugtargetreview.com/news/60482/could
-t-cell-immunotherapy-be-the-answer-to-covid-19/
 https://otd.harvard.edu/explore-
innovation/technologies/utilizing-the-herpes-
simplex-virus-based-vaccine-vectors-to-develop-a-
covid
 https://microbenotes.com/transmission-
pathogenesis-replication-of-sars-cov-2/

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