Does COVID-19 infect peripheral blood cells?

The emergence of the novel coronavirus outbreak in December 2019 was followed by its spread on a global scale unparalleled in the last 100 years. At present, it has claimed over 322,000 lives the world over, with over 4.88 million cases having tested positive.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequence was first uploaded in early 2020, but as of now, over 17,000 genomes have been sequenced from viral strains isolated all over the world. This allows for rapid RNA screening in human tissues as well as environmental samples.

Detection of Virus in Human Blood or Blood Cells

The current study by researchers in Cairo, Egypt, and published on the preprint server medRxiv* was designed to test for the presence of the virus in human blood or any blood cells, which could allow the virus to hide from the immune system or to be trafficked to other organs. It is especially relevant given some (doubtful) reports that the virus could infect lymphocytes.

Other scientists have claimed that the virus perhaps attacks hemoglobin, or that it is to be found in the blood of infected patients, or the peripheral blood mononuclear cells (PMBCs), as is the case with other infectious viruses like hepatitis B, hepatitis C or HIV.

The current study, therefore, used computational analysis on three genome sequences from PBMCs from active COVID-19 patients, three from healthy donor PBMCs, and two from bronchoalveolar lavage fluid (BAL) from patients. They found that traces and large amounts of SARS-CoV-2 RNA were found in the PMBCs and BAL, respectively.

Viral RNA in Blood Cells

The results showed that the BAL and PBMC samples were widely separated, as expected, while the PBMCs from healthy and patient samples were slightly separated for the most part. Viral RNA was present in all the BALF sequences at 2.15% of the total reads (median). The PBMC of one patient also showed two reads that matched the SAR-CoV-2 protein and surface glycoprotein.

Earlier studies showed that with the use of RT-PCR, CoV-RNA was found in plasma samples from COVID-19 patients, but they did not confirm the presence of infectious viral particles in the blood. For this reason, they called their finding ‘RNAemia’ rather than viremia.

The current report is, however, the first to show the presence of viral RNA in PBMC. In fact, a prior study that examined RNA isolated from PBMC made it clear that no viral sequences were found.
The researchers used high-throughput sequencing, which has been demonstrated to be effective in identifying and measuring the number of viral particles in the blood. For this reason, they used this method to do a comprehensive search for viral RNA sequences within the only public dataset now available. They found that viral RNA was present within all BAL samples, at a concentration of 2.15% of the total RNA. Two RNA reads corresponded to the SARS-CoV-2 genome. However, as expected, the PBMC from the controls did not contain any RNA.

Implications

Though the amount of viral RNA is small, it is undoubtedly that of the SARS-CoV-2. One of the reads encodes a polyprotein, which takes part in viral transcription and replication, and which is the largest of the coronavirus proteins. Another encoded the spike protein, which is responsible for the viral entry into human cells that carry the ACE2 molecule receptor.

The possibility is always alive that the viral RNA reads are the result of cross-contamination or one barcode bleeding into another. However, this is a rare chance because none of the control samples showed similar correspondence. Again, they could be the result of virus sampling by antigen-presenting cells, especially dendritic cells, or virus presentation to T cells, which form part of the PBMC population.

There is a third possibility, which can be analyzed only with a much larger number of samples. This is that the virus may have been engulfed either on purpose or by accident by one of the PBMCs. This occurrence could be one mechanism for chronic SARS-CoV-2 infection, but the theory must be tested rigorously.

One hypothesis that is not supported by the current experiment is T cell targeting by the virus in vivo, which arose from an earlier cell culture experiment using pseudotyped viruses.

The current experiment will help to take the present understanding of the progress and replication of the SARS-CoV-2 infection in humans.

 

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Going through cancer treatment and surviving cancer is an arduous journey.

With the evolution of medicine, researchers and scientists have been able to find several ways to deter cancer cells from spreading. But, across the world scientists are still struggling to find foolproof ways of prevention and medication that can cure the fatal disease.

While the disease in itself is fatal, treatment for cancer is painful as well. Harsh drugs, radiation and chemotherapy often leave patients' health in a fragile state. And as newer ways of battling cancer are being introduced, on World Cancer Day, we look at what researchers suggest are promising treatments for the disease:

Representational image.

Adoptive T-cell Therapy: Thymocyte cells or T-lymphocytes are a type of lymphocyte play a key role in immunity. And researchers at the UW School of Medicine say that, "Adoptive T-cell therapy (helps) achieve greater number of T cells than what could be obtained by vaccination alone. The tumor specific T cells are then infused into patients with cancer in an attempt to give their immune system the ability to overwhelm remaining tumor."
According to the researchers, there are several types of T-cell therapy that are being developed that include engineering cells that identify and attack tumours.
Nature says that while T-cell engineering is a cause for optimism, development of more potent T-cells have been stopped by safety concerns.
Immune checkpoint inhibitors: It is when our immune system cannot distinguish between cancer and normal cells is when cancer cells grow. And one way to stop the growth of cancer cells is to use drugs that hide from the "checkpoints" the immune system uses to separate normal cells from foreign cells.
According to cancer.org, antibodies like Pembrolizumab, Nivolumab and Ipilimumab help treat certain types of cancers. The research states that such therapy has shown to have helped cancers like melanoma and non-small cell lung cancer.
Targeted therapy: It targets the changes in cancer cells, the way the divide and spread. According to cancer.gov there are two types of targeted therapy that are done with the use of small-molecule drugs and monoclonal antibodies. The first one is used for targets that are inside cells while the second one attaches itself on the outside of the target.
According to research, this treatment helps destroy cancer cells, stop them from growing, kills them and starve them of hormones that they need to grow.
Hormone therapy with Goserlin: breastcancercare.org states that this drug can be used to treat "women whose breast cancer is sensitive to the female hormone oestrogen – known as oestrogen receptor positive or ER+ breast cancer." It is administered through subcutaneous injections and the frequency depends on the severity of the cancer.
Goserlin uses ovarian suppression or the switching off of production of Oestrogen, since some cancer cells use Oestrogen to grow.