SARS-COV-2 Infects T Cells

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Ranger222
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Published yesterday -- I'll try and hit the highlights

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Some studies reported that lymphocytopenia might be related to mortality, especially in patients with low levels of CD3+, CD4+, and CD8+ T lymphocytes. Lymphocytopenia was also found in the Middle East respiratory syndrome (MERS) cases. MERS-CoV can directly infect human primary T lymphocytes and induce T-cell apoptosis through extrinsic and intrinsic apoptosis pathways, but it cannot replicate in T lymphocytes. However, it is unclear whether SARS-CoV-2 can also infect T cells, resulting in lymphocytopenia.

Lymphocytopenia -- low level of lymphocytes (white blood cells) in the blood. It has been discussed in other threads about the NLR ratio that is being used in the Columbia medical system and others -- Neutrophils / Lymphocytes Ratio. An NLR < 3 is a mild case that would not require hospitalization. NLR > 6 is most likely an ICU case with increased oxygenation needed. NLR > 10-12 is ventilator and NLR > 20 is a most likely fatal outcome.

One apparent reason for this high ratio is loss of the lymphocytes via cell lysis. These cells should start appearing during the second week of infection (second week of symptom onset) as your body begins making antibodies against the virus.

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To address this question, we evaluated the susceptibility of T lymphocytes to SARS-CoV-2 infection.

We used pseudovirus with equal infectivity to 293T/ACE2 cells (Fig. 1c) to infect two T lymphocyte cell lines, MT-2 and A3.01, with very low, or close to negative, expression level of hACE2 mRNA (Fig. 1b). Surprisingly, over several replicates, we saw that the T-cell lines were significantly more sensitive to SARS-CoV-2 infection when compared with SARS-CoV (Fig. 1c). In other words, these results tell us that T lymphocytes may be more permissive to SARS-CoV-2 infection and less permissive for SARS-CoV infection, similar to the findings in a previous study. Therefore, it is plausible that the S protein of SARS-CoV-2 might mediate potent infectivity, even on cells expressing low hACE2, which would, in turn, explain why the transmission rate of SARS-CoV-2 is so high.

It has well established that the S protein of the virus binds ACE2 more efficiently than the original SARS

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To further determine the susceptibility of MT-2 cells to live virus, we used SARS-CoV-2 to infect MT-2 cells and detected the SARS-CoV-2 nucleoprotein (NP) in the cells as reported previously.6 Notably, several MT-2 cells were infected with SARS-CoV-2 (Fig. 1f). Quantitatively, the percentage of SARS-CoV-2 NP-positive MT-2 cells was 23.11% higher than that of uninfected cells at 24 h post infection, which is about 4.6-fold of the portion at 1 h (Fig. 1f). This result means that the virus penetrated MT-2 cells at 24 h and infected them.

MT-2 cells are just a cell line for lymphocytes

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Similar to MERS-CoV, SARS-CoV-2 failed to replicate in MT-2 cells (Fig. 1g). The number of viral genome copies at 6 h was significantly higher than other time points in the cell lysate, but always remained steady at all time points in the supernatants. These results suggest that SARS-CoV-2 may enter MT-2 cells at 6 h post infection, but does not replicate, and then the viral RNA degrade.

So you can get viral infections of these cells, but not replication of the virus.

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the questions of SARS-CoV-2 infection and replication in primary T cells and whether the infection induces apoptosis in T cells still need further research, potentially evoking new ideas about pathogenic mechanisms and therapeutic interventions.

Unfortunately they leave open the question about whether the virus infecting these cells is causing them to die (lyse), ultimately increasing the NLR ratio mentioned above.

If it is shown that the virus is infecting these cells and causing them to die, it would open new strategies towards therapeutic interventions and the cause of the most serious symptoms.

https://www.nature.com/articles/s41423-020-0424-9?fbclid=IwAR2nERxnjNn8HhT0MffTi6iOtpSDFd8RpqMc6l4hHooP9tDKyiSjP9MaHJw
BullSprig07
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