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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Study finds chronic fatigue clues in overactive immune response

Scientists exploring what may trigger a complex disorder known as chronic fatigue syndrome (CFS) have found clues in the way some people’s immune systems respond more actively to a health attack.
A severe illness characterised by long-term physical and mental fatigue, CFS is thought to affect up to 17 million people worldwide and around 250,000 people in Britain.

Sufferers are often bed-bound and unable to carry out basic daily activities like washing and feeding themselves.

The researchers used a drug known as interferon alpha to create a model of the syndrome and found that patients whose immune response to treatment was hyperactive or exaggerated were more likely to then develop severe fatigue.

“For the first time, we have shown that people who are prone to develop a CFS-like illness have an overactive immune system, both before and during a challenge to the immune system,” said one of  the researchers.

The condition, as well as research into it, is highly contentious, in part because its possible causes and range of debilitating symptoms are poorly understood.

Interferon alpha is used as a treatment for hepatitis C infection, and activates the immune system in the same way as a powerful infection.

Many patients who receive interferon alpha experience extreme fatigue during treatment, and some continue to feel chronic fatigue for many months after the drug course is completed.

The team used this knowledge and measured fatigue and immune system markers in 55 patients before, during and after treatment with interferon alpha.

They found that the 18 of those 55 who went on to develop a CFS-like illness had a hyperactive immune system before treatment, and an highly overactive response during treatment.

“(This suggests) people who have an exaggerated immune response to a trigger may be more at risk of developing CFS,” the author told reporters at a briefing about the findings.

 A Prof. stressed that while the study’s main finding is a useful addition to scant scientific knowledge about CFS - also known as myalgic encephalopathy (ME) - it offers few clues on how to treat, cure or prevent it.

“It’s a light in the fog,” he told reporters.

“But a better understanding of the biology underlying the development of CFS is needed to help patients.”

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Ultrasound, blood test together may boost liver cancer detection

Earlier detection is important to improving survival of patients with liver cancer, and combining an ultrasound imaging with a blood test can help achieve that, say researchers.

Using ultrasound and a blood test for high alpha fetoprotein (AFP) levels together improves detection of early-stage liver cancer significantly, said the study published in a journal .

AFP is a plasma protein that is produced in abundance by the liver cells in the foetus. In adults, AFP levels are normally low, but liver cancer can cause AFP levels to rise.

"Liver cancer screening in patients with chronic liver disease has traditionally been performed using an abdominal ultrasound. While ultrasound is readily available and noninvasive, it misses many cancers when they are small," said an associate professor.

Risk factors for liver cancer -- also known as hepatocellular carcinoma (HCC) -- include hepatitis C infection, chronic heavy alcohol consumption, and nonalcoholic fatty liver disease related to diabetes and obesity.

Symptoms can include upper abdominal pain or swelling, loss of weight or appetite, white chalky stools, and general fatigue, the researchers said.

"Our study found that adding the blood biomarker alpha fetoprotein increased detection of early-stage hepatocellular carcinoma from 45 per cent with ultrasound alone to 63 per cent using the two tests in combination," a researcher. said. 

Liver cancer screening guidelines for patients with cirrhosis vary, with some guidelines calling for just imaging and other guidelines calling for both imaging and AFP measurement.

"Our results support a change in clinical practice and the routine use of ultrasound and biomarkers together for liver cancer screening," a researcher said. 

The results were based on a meta-analysis of 32 previous studies. Meta-analysis refers to a technique of combining the results of multiple scientific studies.

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Expanding waistline linked to increased liver cancer risk

High body mass index (BMI), increased waist circumference and type 2 diabetes mellitus may increase the risk of liver cancer, a new study has found.

A team of researchers from the National Cancer Institute in the US and the American Cancer Society, studied whether obesity, and type 2 diabetes mellitus are associated with liver cancer risk.

Peter Campbell from the American Cancer Society and colleagues pooled data from 1.57 million adults enrolled in 14 different US-based prospective studies.

At enrolment, participants completed questionnaires related to their height, weight, alcohol intake, tobacco use and other factors potentially related to cancer risk. None of them had cancer at enrolment.

Type 2 diabetes mellitus was diagnosed in 6.5 per cent of the study participants. Over time, 2,162 developed liver cancer, which the researchers had verified.

They compared the rates of liver cancer among participants with and without obesity and diabetes to determine the relative risks of liver cancer.

Researchers found that for every five kg/m2 increase in BMI, there was a 38 and 25 per cent increase in the risk for liver cancer in men and women, respectively.

The increase in risk was eight per cent for every five cm increase in waist circumference.

When adjusted for alcohol intake, smoking, race and BMI, participants with type 2 diabetes mellitus were 2.61 times more likely to be diagnosed with liver cancer and the risk increased with increase in BMI.

“We found that each of these three factors was associated, robustly, with liver cancer risk. All three relate to metabolic dysfunction. This adds substantial support to liver cancer being on the list of obesity-associated cancers,” Campbell said.

The findings also add further evidence to support public health efforts aimed at curbing obesity, Campbell added.

“This is yet another reason to maintain a body weight in the ‘normal’ range for your height,” he said.

“Liver cancer is not simply related to excess alcohol intake and viral hepatitis infection,” he said.

“From a public health perspective, these results are very important because obesity and diabetes, unfortunately, are common conditions in the population,” said Katherine A McGlynn, from the National Cancer Institute.

“While some other well-described risk factors, such as hepatitis B virus or hepatitis C virus, are associated with increased risks of liver cancer, these factors are much less common than are obesity and diabetes,” McGlynn added.

The study was published in the journal Cancer Research. 

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Hepatitis C ups risk of head, neck cancers

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 Individuals infected with Hepatitis C virus (HCV) may be prone to certain head and neck cancers, a new study has found, pressing the need for screening and treatment for the most common blood-borne virus infection.
The findings showed that people with hepatitis C are two to five times more likely to develop certain head and neck cancers.
The risk increased 2.4 times for oral cavity cancers, 2.04 times for oropharynx cancers, and 4.96 times for larynx cancers.
"The findings tell us that the association between hepatitis C and oropharyngeal and nonoropharyngeal cancers is as high as its link to non-Hodgkin's lymphoma," said Harrys A Torres, associate professor, University of Texas in US.
HCV was long associated with liver cancers and non-Hodgkin's lymphoma and additional cancers, but there was no known association with a significant number of head and neck cancer.
For the study, published in the Journal of the National Cancer Institute, the researchers identified 34,545 patients who were tested for HCV between 2004 and 2014.

The team included 409 head and neck cancer patients as case subjects (164 with oropharyngeal and 245 with nonoropharyngeal).
Also paramount to the research, said Torres, was to control for smoking, a major risk factor for head and neck cancers. Therefore, they identified 694 control subjects, all with a diagnosis of smoking-related cancers (378 with lung, 168 with esophageal and 148 with bladder).

 The study revealed that 14 percent of patients with oropharyngeal cancers tested positive for HCV antibodies, compared to just 6.5 percent in the control group.
In those with nonoropharyngeal cancer, 20 percent tested positive for HCV antibodies.

It is important to screen for HCV because treatment with antiviral drugs may possibly prevent cancer from ever developing, as reported for liver cancers and non-Hodgkin's lymphoma, the authors suggested.

HOW HEPATITIS C GETS TRANSMITTED

THE HEPATITIS C VIRUS CAUSES CHRONIC LIVER DISEASES. MOST PEOPLE ARE UNAWARE  THAT THEY'RE INFECTED. HEPATITIS C, TAKES ITS TIME IN CHIPPING AWAY AT THE LIVER & DECADES PASS WITHOUT ANY NOTICEABLE SYMPTOMS. DURING THAT TIME, AN INFECTED PERSON MAY UNKNOWINGLY  PASS THE INFECTION TO OTHERS THROUGH CONTACT WITH INFECTED BLOOD ( SHARING A NEEDLE, TOOTH-BRUSH OR RAZOR) OR SEXUAL ACTIVITY. THE NEWLY INFECTED PERSON MAY THEN UNKNOWINGLY PASS IT ALONG. AND THAT CAN REPEAT AGAIN AND AGAIN. HEPATITIS-C CAUSES LIVER DISEASE & CAN TRIGGER CIRRHOSIS OR LIVER CANCER.

BUT THE GOOD NEWS IS THAT WITH TREATMENT, 75% OF CASES CAN BE CURED. sO, GO TO THE DOCTOR FOR A SIMPLE ONE-TIME BLOOD TEST. IT CHECKS FOR ANTI-BODIES TO THE HEPATITIS-C VIRUS. IF YOU'VE GOT THE BUT, YOU NEED TO KNOW WHAT SUBTYPE OF THE INFECTION YOU'VE; IT CHANGES TREATMENT CHOICES & EFFECTIVENESS.