Virus World

Abstract

SARS-CoV-2 has been shown to cause wide-ranging ocular abnormalities and vision impairment in COVID-19 patients. However, there is limited understanding of SARS-CoV-2 in ocular transmission, tropism, and associated pathologies. The presence of viral RNA in corneal/conjunctival tissue and tears, along with the evidence of viral entry receptors on the ocular surface, has led to speculation that the eye may serve as a potential route of SARS-CoV-2 transmission. Here, we investigated the interaction of SARS-CoV-2 with cells lining the blood-retinal barrier (BRB) and the role of the eye in its transmission and tropism. The results from our study suggest that SARS-CoV-2 ocular exposure does not cause lung infection and moribund illness in K18-hACE2 mice despite the extended presence of viral remnants in various ocular tissues. In contrast, intranasal exposure not only resulted in SARS-CoV-2 spike (S) protein in different ocular tissues but also induces a hyperinflammatory immune response in the retina.

Additionally, the long-term exposure to viral S-protein caused microaneurysm, retinal pigmented epithelium (RPE) mottling, retinal atrophy, and vein occlusion in mouse eyes. Notably, cells lining the BRB, the outer barrier, RPE, and the inner barrier, retinal vascular endothelium, were highly permissive to SARS-CoV-2 replication. Unexpectedly, primary human corneal epithelial cells were comparatively resistant to SARS-CoV-2 infection. The cells lining the BRB showed induced expression of viral entry receptors and increased susceptibility towards SARS-CoV-2-induced cell death. Furthermore, hyperglycemic conditions enhanced the viral entry receptor expression, infectivity, and susceptibility of SARS-CoV-2-induced cell death in the BRB cells, confirming the reported heightened pathological manifestations in comorbid populations. Collectively, our study provides the first evidence of SARS-CoV-2 ocular tropism via cells lining the BRB and that the virus can infect the retina via systemic permeation and induce retinal inflammation.

Author summary

SARS-CoV-2 is known to cause several ocular manifestations in COVID-19 patients; however, the role of eyes in viral transmission and ocular tissue tropism remains elusive. The presence of viral remnants in various ocular tissues and fluids from COVID-19 patients has led to an assumption that SARS-CoV-2 may be transmitted through the eyes. Here, we show that SARS-CoV-2 ocular tropism is through cells lining the BRB. SARS-CoV-2 not only infects the various parts of the eye via systemic exposure but also induces a hyperinflammatory immune and antiviral response in the retina. Unexpectedly, the corneal epithelium was found to be resistant to SARS-CoV-2 infection, and ocular exposure of SARS-CoV-2 failed to cause lung pathology and moribund illness. Cells lining the BRB showed induced expression of viral entry receptors and enhanced susceptibility towards SARS-CoV-2-induced cell death, which is further potentiated with comorbidities such as hyperglycemia. Our findings from this study shed light on the role of BRB in SARS-CoV-2 ocular tropism and the role of eyes in viral transmission.

Published in PLOS Pathogen (April 10, 2024):

https://doi.org/10.1371/journal.ppat.1012156

A common variant in an immune-system gene is linked with a much higher chance of dodging symptoms after SARS-CoV-2 infection. At least 20% of people who become infected with the SARS-CoV-2 coronavirus never feel sick. Now scientists have identified a genetic mutation that is linked to a higher likelihood of avoiding symptoms during infection1. This mutation might give an advantage to the immune cells of people who have previously been exposed to ‘seasonal’ coronaviruses, which cause the common cold. That extra boost means the immune system can quickly track down and destroy SARS-CoV-2 before it goes haywire trying to defend against the pathogen, says Jill Hollenbach, an immunogeneticist at the University of California, San Francisco, who co-authored the report. It was published on 19 July in Nature. The study “deserves a round of applause”, says Jean-Laurent Casanova, a paediatric immunologist at the Rockefeller University in New York City. The researchers show a “modest” link, but it’s “stronger than any other association for a common gene published” on COVID-19, he says.

Original study in Nature (July 19, 2023):

https://doi.org/10.1038/s41586-023-06331-x 

Babies develop risk of cancer in womb, but will not go on to develop it without second ‘hit’ from an infection, scientists believe. Childhood leukaemia is driven by common childhood infections meeting pre-cancerous cells in the blood, scientists believe. Experts at the Institute of Cancer Research (ICR) in London have found babies develop the risk for leukaemia in the womb, but will not go on to develop the disease without a second ‘hit’ from a viral or bacterial infection, such as flu. The research highlights the importance of allowing infants to socialise with other children early in their lives, to prime their immune systems against infections. The discovery came by studying pairs of twins, where only one initially developed acute lymphoblastic leukaemia (ALL) - the most common type of the cancer in children. Identical twins are around 15-25 per cent more likely to go on to develop ALL if their sibling already has the disease, while less than one per cent of non-identical twins or other siblings go on to develop the disease. Researchers followed the twins for up to 15 years and found the high risk only applies if the identical twins shared a single placenta before birth - which only happens in around 60 per cent of identical twin pairs.

Findings 'confirm disease can be traced back to womb'

It confirms that the conditions needed to trigger leukaemia first arise in the womb, and even the healthy twin will carry "pre-leukaemia" cells in the blood, which have occurred through a spontaneous developmental error, and passed between the two. But clinically silent cells will not develop into cancer without a post-birth "hit", probably from common childhood infections. Prof Sir Mel Greaves, the founding director of the Centre for Evolution and Cancer and Professor of Cell Biology at The Institute of Cancer Research, London, said: “Our study provides new insights into the origins of childhood acute lymphoblastic leukaemia. “These new findings confirm that the disease can be traced back to the womb when pre-leukaemia cells spread via the twins’ shared blood supply. "What remained a mystery until now was why sometimes only one twin is diagnosed with leukaemia. “We still do not know for certain what leads to the first ‘hit’ of genetic changes in the womb, but we think that the second ‘hit’ of genetic changes is probably triggered by common childhood infections – opening up the possibility of ‘priming’ the immune system in infancy to avoid the development of the disease later on in life.” Acute lymphoblastic leukaemia is the most common type of childhood cancer, accounting for 80 per cent of leukaemia cases in children. The team are now focussed on finding the the second infection-driven hit after birth.

Boosting the gut could protect children against disease

They believe that the gut microbiome may be playing a key role in protecting children against developing leukaemia even if they have pre-cancerous cells. Although vaccines have little impact on preventing ALL, boosting the gut in early life may help. Prof Greaves added: “Risk of ALL is elevated by C-section birth, lack of breast feeding and paucity of social contacts in infancy. “Conversely, attendance at play groups in infancy is protective. So, to some extent , risk can be modified without medical intervention.” The findings will also allow doctors to assess the risk of ALL for twins,  firstly by determining whether the twins are identical and sharing a placenta and then by regularly tracking the levels of pre-leukaemia cells in their blood. Sarah McDonald, the deputy director of research at Blood Cancer UK, who funded the work said: “Understanding the mechanism as to how the cancer develops in identical twins, and why often only one develops leukaemia is an important question to answer. “It helps us understand both the risk of the other sibling developing leukaemia and provides insight into how leukaemia develops in all children. “This research shows that in cases where one twin develops leukaemia, and both twins both share a placenta during pregnancy, two events are needed to determine whether the other sibling develops the disease - one before birth and the other after.”

Research published (Dec. 20, 2022) in the journal Leukaemia:

https://doi.org/10.1038/s41375-022-01756-1 

They remain susceptible to the virus for longer after the first vaccination, but achieve a mostly normal response after the second, a study says.  Pregnant and breastfeeding women respond to the first dose of the coronavirus vaccines more slowly than other women, and mount a less potent defense against the virus, according to a new study. After the second dose, however, their response looks almost normal. The results, published this month in the journal Science Translational Medicine, suggest that pregnant and breastfeeding women remain susceptible to the virus for longer after vaccination. The study underscores the importance of giving these women the second dose in time, and monitoring them closely in the meantime for signs of infection. During pregnancy, the immune system is modified to tolerate the fetus — effectively a foreign entity — leaving pregnant women particularly susceptible to pathogens like the coronavirus. Because of this, pregnant women are more likely to become severely ill and to die from Covid than other women of the same age.

Associations between vaccine breakthrough cases and infection by SARS coronavirus 2 (SARS-CoV-2) variants have remained largely unexplored. Here we analyzed SARS-CoV-2 whole-genome sequences and viral loads from 1,373 persons with COVID-19 from the San Francisco Bay Area from February 1 to June 30, 2021, of which 125 (9.1%) were vaccine breakthrough infections. Fully vaccinated were more likely than unvaccinated persons to be infected by variants carrying mutations associated with decreased antibody neutralization (L452R, L452Q, E484K, and/or F490S) (78% versus 48%, p = 1.96e-08), but not by those associated with increased infectivity (L452R and/or N501Y) (85% versus 77%, p = 0.092). Differences in viral loads were non-significant between unvaccinated and fully vaccinated persons overall (p = 0.99) and according to lineage (p = 0.09 – 0.78). Viral loads were significantly higher in symptomatic as compared to asymptomatic vaccine breakthrough cases (p < 0.0001), and symptomatic vaccine breakthrough infections had similar viral loads to unvaccinated infections (p = 0.64).

In 5 cases with available longitudinal samples for serologic analyses, vaccine breakthrough infections were found to be associated with low or undetectable neutralizing antibody levels attributable to immunocompromised state or infection by an antibody-resistant lineage. These findings suggest that vaccine breakthrough cases are preferentially caused by circulating antibody-resistant SARS-CoV-2 variants, and that symptomatic breakthrough infections may potentially transmit COVID-19 as efficiently as unvaccinated infections, regardless of the infecting lineage.

Preprint available in medRxiv (August 25, 2021):

https://doi.org/10.1101/2021.08.19.21262139 

Vaccines have weakened the link between surging cases and serious illness, but in vaccine-deprived parts of the world, the deadly pattern remains.  Two hundred million is an enormous number. But as the world recorded the 200 millionth detected case of coronavirus infection, that daunting figure — more than the populations of Germany, France and Spain combined — also fails to capture how far the virus has embedded itself within humanity. While always an imperfect measure of a virus that causes no symptoms in many of the people it infects, with many infections going unreported, case counts have provided a useful tool for much of the pandemic — like a flashing red light in the cockpit of a jetliner warning of imminent danger. A surge in case numbers has too often been followed by a crush of people crowding emergency rooms. And then, several weeks later, fatality counts have typically spiked. It took more than a year for the pandemic to reach its 100 millionth case, and little more than six months to double that, with the world surpassing the 200 million figure on Wednesday, according to the Center for Systems Science and Engineering at Johns Hopkins University.  The number of those killed by the virus is also staggering. The official tallies stand at more than 614,000 deaths in the United States, 558,000 in Brazil and 425,00 in India. Mexico has recorded more than 240,000 fatalities, and Peru nearly 200,000. Britain, Colombia, France, Italy and Russia have each recorded well over 100,000 deaths. The global toll as of Wednesday was about 4.25 million — a serious underestimate, experts say, given the discrepancies in the way nations record Covid deaths.

As the coronavirus continues to find new hosts across the planet at a rapid rate, the emergence of the Delta variant — thought to be about twice as infectious as the original version first detected in Wuhan, China — is adding fuel to a fire that has never stopped raging. In one week alone, from July 19 to 25, nearly four million cases were recorded by the World Health Organization — a jump of 8 percent from the previous week. With many of the new infections occurring in countries lacking vaccines or among the unvaccinated, 69,000 Covid deaths were recorded that week.  Despite lockdowns, travel restrictions, mask mandates, business closures, social distancing and radical shifts in individual behaviors, the virus continues to find a way to spread.  Some countries, like Australia, had success keeping case counts low thanks to geographic isolation and strict lockdown measures. But that may not be possible given the rise of the Delta variant. And governments are facing increasingly angry protests while trying to enforce lockdowns on weary populations and struggling businesses. Over the last six months, however, the calculus for measuring the danger of the moment has become more complicated. A rise in case counts alone, in many places, may not presage a flood of very sick people. For countries where vaccines are scarce, the math of the pandemic remains unchanged. Indonesian authorities reported nearly 57,000 new cases on one day in mid-July, seven times as many as a month earlier, the highest figure since the pandemic began. Twelve days later, more than 2,000 died in a single day, and the country now is nearing 100,000 dead from Covid-19......

Researchers in Belgium report on the case of a 90-year-old woman who was simultaneously infected with two different variants of concern (VOCs) of COVID-19, in a Case Report being presented at the European Congress of Clinical Microbiology & Infectious Diseases (ECCMID) held online this year.  On March 3 2021, the woman, whose medical history was unremarkable, was admitted to the OLV Hospital in the Belgian city of Aalst after a spate of falls. She tested positive for COVID-19 on the same day. She lived alone and received nursing care at home, and had not been vaccinated against COVID-19. Initially, there were no signs of respiratory distress and the patient had good oxygen saturation. However, she developed rapidly worsening respiratory symptoms, and died five days later. When the patient's respiratory sample was tested for VOCs with PCR, they discovered that she had been infected by two different strains of the virus—one which originated in the UK, known as B.1.1.7 (Alpha), and another that was first detected in South Africa (B.1.351; Beta). The presence of both strains was confirmed by PCR on a second respiratory sample, by sequencing of the S-gene and by whole genome sequencing.

"This is one of the first documented cases of co-infection with two SARS-CoV-2 variants of concern", says lead author and molecular biologist Dr. Anne Vankeerberghen from the OLV Hospital in Aalst, Belgium. "Both these variants were circulating in Belgium at the time, so it is likely that the lady was co-infected with different viruses from two different people. Unfortunately, we don't know how she became infected." On December 14, 2020, the UK authorities informed WHO that a variant (B.1.1.7; Alpha) had been detected in the south east of England (Kent). Within a few weeks, this variant took over from the viral strains circulating in this region, and has since spread to more than 50 countries, including Belgium. On December 18, 2020, the South African authorities reported that a variant (B.1.351; Beta) had been detected and was spreading rapidly throughout three provinces of South Africa, and has now been identified in at least 40 countries, including Belgium. In January 2021, scientists in Brazil reported that two people had been simultaneously infected with two different strains of the coronavirus—the Brazilian variant known as B.1.1.28 (E484K) and a novel variant VUI-NP13L, which had previously been discovered in Rio Grande do Sul. But the study has yet to be published in a scientific journal [1]. Previous research has reported people infected with different influenza strains [2]. "Whether the co-infection of the two variants of concern played a role in the fast deterioration of the patient is difficult to say", says Vankeerberghen.

"Up to now, there have been no other published cases. However, the global occurrence of this phenomenon is probably underestimated due to limited testing for variants of concern and the lack of a simple way to identify co-infections with whole genome sequencing." She continues, "Since co-infections with variants of concern can only be detected by VOC-analysis of positive samples, we would encourage scientists to perform fast, easy and cheap VOC-analysis by PCR on a large proportion of their positive samples, rather than just whole genome sequencing on a small proportion. Independent of the technique used, being alert to co-infections remains crucial."

See also abstract of the research cited (July 10, 2021):

https://www.olvz.be/sites/default/files/2021-07/04978-90_year_old_double_infection.pdf 

About 5,800 people out of tens of millions who have been vaccinated against coronavirus have become infected anyway, the CDC tells CNN. Some became seriously ill and 74 people died, the CDC said. It said 396 -- 7% -- of those who got infected after they were vaccinated required hospitalization.  This is the CDC's first public accounting of breakthrough cases, and the agency is searching for patterns based on patient age and gender, location, type of vaccine, variants and other factors. "So far, about 5,800 breakthrough cases have been reported to CDC. To date, no unexpected patterns have been identified in case demographics or vaccine characteristics," the CDC told CNN via email.  About 77 million people in the US are fully vaccinated against coronavirus, according to a CNN analysis of CDC data. The CDC's reports on breakthrough cases will lag day-to-day reports of vaccines given, so many, if not most, of those breakthrough cases will have happened weeks ago. Nonetheless, the total represents a very small percentage of those who have been vaccinated. Breakthrough cases are expected. The vaccines are not 100% effective in preventing infections and as tens of millions of people are vaccinated, more and more such cases will be reported.

Despite signs of infection—including taste loss, dry mouth and mucosal lesions such as ulcerations, enanthema and macules—the involvement of the oral cavity in coronavirus disease 2019 (COVID-19) is poorly understood. To address this, we generated and analyzed two single-cell RNA sequencing datasets of the human minor salivary glands and gingiva (9 samples, 13,824 cells), identifying 50 cell clusters. Using integrated cell normalization and annotation, we classified 34 unique cell subpopulations between glands and gingiva. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral entry factors such as ACE2 and TMPRSS members were broadly enriched in epithelial cells of the glands and oral mucosae.

Using orthogonal RNA and protein expression assessments, we confirmed SARS-CoV-2 infection in the glands and mucosae. Saliva from SARS-CoV-2-infected individuals harbored epithelial cells exhibiting ACE2 and TMPRSS expression and sustained SARS-CoV-2 infection. Acellular and cellular salivary fractions from asymptomatic individuals were found to transmit SARS-CoV-2 ex vivo. Matched nasopharyngeal and saliva samples displayed distinct viral shedding dynamics, and salivary viral burden correlated with COVID-19 symptoms, including taste loss. Upon recovery, this asymptomatic cohort exhibited sustained salivary IgG antibodies against SARS-CoV-2. Collectively, these data show that the oral cavity is an important site for SARS-CoV-2 infection and implicate saliva as a potential route of SARS-CoV-2 transmission. 

Published in Nature Medicine (March 25, 2021):

https://doi.org/10.1038/s41591-021-01296-8 

A new study in the American Journal of Preventive Medicine presents new data that address important questions pertaining to the containment of the coronavirus pandemic: When should COVID-19 quarantine really end and which continuing symptoms may be more indicative of a positive test in recovered patients? The study was conducted by the Fondazione Policlinico Universitario "Agostino Gemelli" IRCCS, Rome, Italy, where a multidisciplinary healthcare service was established for all patients who have recovered from COVID-19 to study what happens to them after recovery and to assess the impact of the virus on their bodies. Investigators report that close to 17 percent of patients considered fully recovered from COVID-19 tested positive for the virus in follow-up screening. Patients who continued to have respiratory symptoms, especially sore throat and rhinitis, were more likely to have a new positive test result. This suggests the persistence of these two symptoms should not be underestimated and should be adequately assessed in all patients considered recovered from COVID-19. 

"Clinicians and researchers have focused on the acute phase of COVID-19, but continued monitoring after discharge for long-lasting effects is needed," explained lead investigator Francesco Landi, MD, Ph.D., Fondazione Policlinico Universitario "Agostino Gemelli" IRCCS, and Catholic University of the Sacred Heart, Rome, Italy.

The study included 131 patients who met the World Health Organization (WHO) criteria for discontinuation of quarantine at least two weeks prior to the follow-up visit. The WHO criteria specify that the patient should be fever-free without fever-reducing medications for three days, show improvement in any symptoms related to COVID-19, be more than seven days past symptom onset, and test negative for the SARS-CoV-2 virus twice, at least 24 hours apart, with reverse transcription PCR (RT-PCR) testing. A new RT-PCR test was administered at the time of post-acute care admission. Demographic, medical, and clinical information was collected, with an emphasis on the persistence of symptoms and signs related to COVID-19 such as cough, fatigue, diarrhea, headache, smelling disorders, loss of appetite, sore throat, and rhinitis.  Twenty-two (16.7 percent) of the patients tested positive again. There was no significant difference between patients with positive and negative test results in terms of age or sex. None of the patients had fever and all reported improvement in their overall clinical condition. Time since onset of disease, number of days hospitalized, and treatments received while hospitalized were not significant. However, some symptoms such as fatigue (51 percent), labored breathing (44 percent) and coughing (17 percent) were still present in a significant percentage of the patients studied, although there were no significant differences between individuals with a positive or negative test. The only two symptoms that were higher and significantly prevalent in patients with a positive test were sore throat (18 percent vs. 4 percent) and signs of rhinitis (27 percent vs. 2 percent). 

Our findings indicate that a noteworthy rate of recovered patients with COVID-19 could still be asymptomatic carriers of the virus," Dr. Landi observed. "The main question for the containment of SARS-CoV-2 pandemic infection that still needs to be answered is whether persistent presence of virus fragments means the patients is still contagious. The RT-PCR test looks for small fragments of viral RNA. A positive swab test can reveal if patients are still shedding viral fragments, but it is not able to discern whether they are or aren't infectious." Importantly, the investigators recommend that for patients who continue to have symptoms potentially related to COVID-19, it is reasonable to be cautious and avoid close contact with others, wear a face mask, and possibly undergo an additional nasopharyngeal swab.

Original study in JAMA (Sept. 18, 2020):

https://doi.org/10.1016/j.amepre.2020.08.014

This case study compares a patient previously infected with coronavirus disease 2019 with a control participant in assessment of nucleocapsid protein antigens on the cells of the conjunctiva, iris, and trabecular meshwork. Coronavirus disease 2019 (COVID-19) has been recognized as a pandemic by the World Health Organization. Whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can also infect tissues besides the respiratory system, such as the ocular tissues, remains unclear.

To determine whether SARS-CoV-2 exists intracellularly in the ocular tissues of a patient previously infected with COVID-19. This case study analyzed a patient previously infected with COVID-19 who had an acute glaucoma attack during her rehabilitation. Plasma samples and tissue specimens, including ones from the conjunctiva, anterior lens capsular, trabecular meshwork, and iris, were collected during phacoemulsification and trabeculectomy surgery. Specimens from another patient who had glaucoma but not COVID-19 were used as a negative control. Specimens were analyzed using hematoxylin-eosin staining. The nucleocapsid protein antigen of SARS-CoV-2 was measured in the conjunctiva, trabecular meshwork, and iris using immunofluorescence and immunohistochemistry. The expression of angiotensin-converting enzyme 2 receptor on the conjunctiva was measured using immunohistochemistry.

The patient with a previous COVID-19 infection was female and 64 years old, and the control patient without a COVID-19 infection history was male and 61 years old. The nucleocapsid protein antigen of SARS-CoV-2 was detected on the cells of the conjunctiva, trabecular, and iris of the patient infected with COVID-19 but not in the control participant, while angiotensin-converting enzyme 2 receptor proteins were detected on the conjunctiva of both patients. The nucleocapsid protein antigen of SARS-CoV-2 existed intracellularly in the ocular tissues of a patient previously infected with COVID-19. Thus, SARS-CoV-2 can also infect ocular tissues in addition to the respiratory system.

Published in JAMA Ophtalmology (Oct. 8, 2020)

https://doi.org/10.1001/jamaophthalmol.2020.3962

Human Papilloma Virus or HPV has been known to be transmitted between humans via sexual contact and HPV has been known to be a sexually transmitted disease or STD. The Centers for Disease Control and Prevention (CDC) states that HPV is one of the commonest STDs among humans. It affects around 79 million individuals in the United States. In most cases the infection may pass unnoticed and may resolve on its own. However HPV has been associated with the later development of cervival cancers in women and oral and throat cancers among men and women.

A new study however reveals that rabbit and mice papilloma viruses are capable of spreading via contaminated blood from one to another. The study from Pennsylvania State researchers titled, “Papillomavirus can be transmitted through the blood and produce infections in blood recipients: Evidence from two animal models” was published in the recent issue of the journal Emerging Microbes & Infections. The researchers warned that this study could be a basis for the hypothesis that HPV could also be transmitted between humans via blood.

Study leader Jiafen Hu, assistant professor of pathology and laboratory medicine at Penn State College of Medicine called for more research to confirm that papilloma viruses are capable of transmission via blood especially blood transfusions. He said that the blood prepared for receive blood transfusions may require a screening for HPV if this is proven to be true. Hu said, “People who are receiving blood transfusions typically have immune systems that aren't working optimally, so their systems are more vulnerable. We might want to think about adding HPV to the list of viruses for which blood donations are screened, as well as researching whether the typical viral load of HPV in human blood would be sufficient to cause infection.”

Hu explained that the team came across a case in 2005 where a similar transmission was seen. He said, “Some years ago, researchers were looking at blood samples from a group of HIV-positive children, and as they were testing those samples, they found that some of them were also positive for HPV. Because these children were so young, it prompted the question of whether the virus could have come from blood transfusions, which some of the children had undergone.”

Since it is difficult to check for HPV on animal models, the team decided to perform their experiments on other forms of papilloma viruses. “HPV is strictly species-specific,” they wrote, “and thus, cannot be studied directly in animals. Our laboratory has two preclinical animal models with their own naturally occurring papillomaviruses.”

The team used Cottontail Rabbit Papillomavirus which is commonly used for researching HPV infections in humans because of its similarity with HPV. For their experiments the team first injected the rabbit papilloma virus into the bloodstreams of the lab rabbits. The rabbits were then monitored for four weeks when they were found to develop tumours. This proved that the virus had travelled via the blood stream to cause the tumours in the rabbits said Hu. The team found that several genetic expressions were lower in these rabbit tumours similar to actual sexually transmitted tumours. They wrote, “The rabbit skin tumours induced via blood infection displayed decreased expression of SLN, TAC1, MYH8, PGAM2, and APOBEC2 and increased expression of SDRC7, KRT16, S100A9, IL36G, and FABP9, as seen in tumours induced by local infections.”

Hu explained that in this experiment they had used a large amount of the virus to be injected into the rabbits. This infection due to the injection of the viruses could be due to the heavy viral load, he added. In a normal case of blood borne infection, the dose of the virus could be significantly lower. Thereafter the team reduced the viral load injected by five times. This time the tumours were still seen in 18 out of the 32 animals. Hu said, “We were able to show that the virus in the blood caused tumors, but what about blood transfusions? People receiving a transfusion may only get a very small amount of the virus. To simulate this, we injected the virus into one animal, took 10 millilitres of blood and transfused it into a second animal. We still saw tumors.”

The next question the researchers addressed was if the blood borne infection could cause tumours and cancerous changes in the cervix as the sexually transmitted infection was capable of. Now they repeated their experiment using mice model. When injected with the papilloma virus into lab mice, the team found that the virus and viral warts and tumours were found in the tongue and genital mucosa of the mice. They also found the virus in the stomach mucosa of the mice. This proved that the virus was capable of travelling from the blood stream into oral and genital mucosa as well as into the gastric mucosal surfaces.

Findings published in the Journal of Emerging Microbes and Infections:

https://doi.org/10.1080/22221751.2019.1637072

People living with HIV are more likely to develop certain other health conditions over the course of their lives. A comprehensive international analysis of more than 3,000 studies on the subject of HIV, in which MedUni Vienna participated, has identified several outcomes as being HIV-related, eight of these being clearly attributable to infection with the pathogen that causes AIDS: COPD (Chronic Obstructive Pulmonary Disease), dyspnoea, cough, anemia, maternal sepsis, pregnancy-related mortality, as well as bone fractures and ischaemic heart disease.

An international study group including MedUni Vienna has conducted a so-called umbrella review. This relatively new statistical tool is an analysis of meta-analyses representing the highest level of evidence. The umbrella review analyzed the results of 20 meta-analyses, which in turn include a total of 3,200 studies on the subject of health outcomes associated with HIV. The results were published in the specialist journal "Clinical Infectious Diseases".

While the meta-analyses identified a total of 55 outcomes that are associated with HIV infection, the superordinate umbrella review identified 37 of these health outcomes as having significant associations and 8 of them a having suggestive and highly suggestive evidence of associations with HIV. These are COPD (Chronic Obstructive Pulmonary Disease), dyspnoea, cough, anemia, maternal sepsis, pregnancy -related mortality, as well as bone fractures and ischaemic heart disease. 

The study was a collaboration between MedUni Vienna and researchers from Austria, Italy, Spain, Canada and the UK. In Austria, around 98% of people living with HIV have their condition managed by drugs. Despite their good life expectancy, they have more chronic diseases than people without HIV. "Further research is needed to find out why people living with HIV also have additional health problems," explains Igor Grabovac, "possible reasons are the side-effects of the drugs, lifestyle factors or the virus itself, which causes faster cell aging due to chronic infection within the body."

Published in Clinical Infectious Diseases:

https://doi.org/10.1093/cid/ciz539

A study found that the floor and walls around the toilet could still get contaminated with viruses from the toilet bowl even when the lid is down during flushing. Will shutting the toilet lid when you flush really keep nasty microbes from leaving the bowl and spraying all over the place? Well, it’s not exactly an open and shut case, according to a new study published in the American Journal of Infection Control. The study found that the floor and walls around the toilet could still go quite viral, so to speak, even when the lid stays down during the flush. Yes, even the walls around the toilet ended up getting contaminated with viruses from the toilet bowl. For the study, a team of researchers from the University of Arizona (Madison P. Goforth, BS Stephanie A. Boone, PhD Justin Clark, MS Priscilla B. Valenzuela, MS, FRSPH, and Charles P. Gerba, PhD) and Reckitt Benckiser, LLC, the makers of Lysol (Julie McKinney, PhD, and M. Khalid Ijaz, DVM, PhD) dumped some bacteriophage MS2 into two different types of toilets...

This report describes the effectiveness of hybrid immunity among people aged 16 years and older from a blood donor cohort. 

What is already known about this topic?

SARS-CoV-2 hybrid immunity (immunity derived from both previous infection and vaccination) has been reported to provide better protection than that from infection or vaccination alone.

What is added by this report?

By the third quarter of 2022, an estimated 96.4% of persons aged ≥16 years in a longitudinal blood donor cohort had SARS-CoV-2 antibodies from previous infection or vaccination, including 22.6% from infection alone and 26.1% from vaccination alone; 47.7% had hybrid immunity. Hybrid immunity prevalence was lowest among adults aged ≥65 years.

What are the implications for public health practice?

Low prevalence of infection-induced and hybrid immunity among older adults, who are at increased risk for severe disease if infected, reflects the success of public health infection prevention efforts while also highlighting the importance of this group staying up to date with recommended COVID-19 vaccination, including at least 1 bivalent dose.

Published in MMWR (June 2, 2023):

 http://dx.doi.org/10.15585/mmwr.mm7222a3 

Background. The purpose of this study was to evaluate whether boosting healthcare personnel, already reasonably protected by prior infection or vaccination, with a vaccine developed for an earlier variant of COVID-19 protects against the Omicron variant. 

Methods. Employees of Cleveland Clinic who were previously infected with or vaccinated against COVID-19, and were working in Ohio the day the Omicron variant was declared a variant of concern, were included. The cumulative incidence of COVID-19 was examined over two months during an Omicron variant surge. Protection provided by boosting (analyzed as a time-dependent covariate) was evaluated using Cox proportional hazards regression. Analyses were adjusted for time since proximate overt immunologic challenge (POIC) as a time-dependent covariate. 

Results. Among 39 766 employees, 8037 (20%) previously infected and the remaining previously vaccinated, COVID-19 occurred in 6230 (16%) during the study. Risk of COVID-19 increased with time since POIC. In multivariable analysis, boosting was independently associated with lower risk of COVID-19 among those with vaccine-induced immunity (HR, .43; 95% CI, .41-.46) as well as those with natural immunity (HR, .66; 95% CI, .58-.76). Among those with natural immunity, receiving 2 compared to 1 dose of vaccine was associated with higher risk of COVID-19 (HR, 1.54; 95% CI, 1.21-1.97). 

Conclusions. Administering a COVID-19 vaccine not designed for the Omicron variant, 6 months or more after prior infection or vaccination, protects against Omicron variant infection in both previously infected and previously vaccinated individuals. There is no evidence of an advantage to administering more than 1 dose of vaccine to previously infected persons.

Preprint available at medRxiv (Feb. 13, 2022):

https://doi.org/10.1101/2022.02.10.22270744

Hope for a future without fear of COVID-19 comes down to circulating antibodies and memory B cells. Unlike circulating antibodies, which peak soon after vaccination or infection only to fade a few months later, memory B cells can stick around to prevent severe disease for decades. And they evolve over time, learning to produce successively more potent "memory antibodies" that are better at neutralizing the virus and more capable of adapting to variants. Vaccination produces greater amounts of circulating antibodies than natural infection. But a new study suggests that not all memory B cells are created equal. While vaccination gives rise to memory B cells that evolve over a few weeks, natural infection births memory B cells that continue to evolve over several months, producing highly potent antibodies adept at eliminating even viral variants.  The findings highlight an advantage bestowed by natural infection rather than vaccination, but the authors caution that the benefits of stronger memory B cells do not outweigh the risk of disability and death from COVID-19. "While a natural infection may induce maturation of antibodies with broader activity than a vaccine does—a natural infection can also kill you," says Michel C. Nussenzweig, the Zanvil A. Cohn and Ralph M. Steinman professor and head of Rockefeller's Laboratory of Molecular Immunology. "A vaccine won't do that and, in fact, protects against the risk of serious illness or death from infection."

Your body on COVID-19

When any virus enters the body, immune cells immediately churn out hordes of circulating antibodies. Foot soldiers of the immune system, these antibodies burn bright but decay at variable rates depending on the vaccine or infection—they may protect us for months or years but then dwindle in number, allowing possible reinfection. The immune system has a backup plan: an elite cadre of memory B cells that outlive circulating antibodies to produce so-called memory antibodies that provide long-term protection. Studies suggest that memory B cells for smallpox last at least 60 years after vaccination; those for Spanish flu, nearly a century. And while memory B cells don't necessarily block reinfection, they can prevent severe disease. Recent studies have suggested that within five months of receiving a vaccine or recovering from a natural infection, some of us no longer retain sufficient circulating antibodies to keep the novel coronavirus at bay, but our memory B cells stand vigilant. Until now, however, scientists did not know whether the vaccines could be expected to provide the sort of robust memory B cell response seen after natural infection.

The convalescent advantage

Nussenzweig and colleagues resolved to tease out any differences in memory B cell evolution by comparing blood samples from convalescent COVID-19 patients to those from mRNA-vaccinated individuals who had never suffered natural infection. Vaccination and natural infection elicited similar numbers of memory B cells. Memory B cells rapidly evolved between the first and second dose of the Pfizer and Moderna vaccines, producing increasingly potent memory antibodies. But after two months, progress stalled. The memory B cells were present in large numbers and expressed potent antibodies, but the antibodies were not getting any stronger. Also, although some of these antibodies were able to neutralize Delta and other variants, there was no overall improvement in breadth. With convalescent patients, on the other hand, memory B cells continued to evolve and improve up to one year after infection. More potent and more broadly neutralizing memory antibodies were coming out with every memory B cell update.

To boost or not to boost

There are several potential reasons that memory B cells produced by natural infection might be expected to outperform those produced by mRNA vaccines, the researchers say. It is possible that the body responds differently to viruses that enter through the respiratory tract than those that are injected into our upper arms. Or perhaps an intact virus goads the immune system in a way that the lone spike protein represented by the vaccines simply cannot. Then again, maybe it's that the virus persists in the naturally infected for weeks, giving the body more time to mount a robust response. The vaccine, on the other hand, is flushed out of the body mere days after triggering the desired immune response. Regardless of the cause, the implications are clear. We can expect memory B cells to undergo limited volleys of evolution in response to mRNA vaccines, a finding that may have significant implications for the design and rollout of booster shots. A booster with the currently available mRNA vaccine would be expected to engage memory cells to produce circulating antibodies that are strongly protective against the original virus and somewhat less so against the variants, Nussenzweig says. "When to administer the booster depends on the object of boosting," he says. "If the goal is to prevent infection, then boosting will need to be done after 6 to 18 months depending on the immune status of the individual. If the goal is to prevent serious disease boosting may not be necessary for years."

See findings published in Nature (October 7, 2021):

https://doi.org/10.1038/s41586-021-04060-7

Israelis who had an infection were more protected against the Delta coronavirus variant than those who had an already highly effective COVID-19 vaccine. The natural immune protection that develops after a SARS-CoV-2 infection offers considerably more of a shield against the Delta variant of the pandemic coronavirus than two doses of the Pfizer-BioNTech vaccine, according to a large Israeli study that some scientists wish came with a “Don’t try this at home” label. The newly released data show people who once had a SARS-CoV-2 infection were much less likely than vaccinated people to get Delta, develop symptoms from it, or become hospitalized with serious COVID-19.  The study demonstrates the power of the human immune system, but infectious disease experts emphasized that this vaccine and others for COVID-19 nonetheless remain highly protective against severe disease and death. And they caution that intentional infection among unvaccinated people would be extremely risky. “What we don’t want people to say is: ‘All right, I should go out and get infected, I should have an infection party.’” says Michel Nussenzweig, an immunologist at Rockefeller University who researches the immune response to SARS-CoV-2 and was not involved in the study. “Because somebody could die.” The researchers also found that people who had SARS-CoV-2 previously and then received one dose of the Pfizer-BioNTech messenger RNA (mRNA) vaccine were more highly protected against reinfection than those who once had the virus and were still unvaccinated. The study, conducted in one of the most highly COVID-19–vaccinated countries in the world, examined medical records of tens of thousands of Israelis, charting their infections, symptoms, and hospitalizations between 1 June and 14 August, when the Delta variant predominated in Israel. It’s the largest real-world observational study so far to compare natural and vaccine-induced immunity to SARS-CoV-2, according to its leaders.

The research impresses Nussenzweig and other scientists who have reviewed a preprint of the results, posted yesterday on medRxiv. “It’s a textbook example of how natural immunity is really better than vaccination,” says Charlotte Thålin, a physician and immunology researcher at Danderyd Hospital and the Karolinska Institute who studies the immune responses to SARS-CoV-2 . “To my knowledge, it’s the first time [this] has really been shown in the context of COVID-19.” Still, Thålin and other researchers stress that deliberate infection among unvaccinated people would put them at significant risk of severe disease and death, or the lingering, significant symptoms of what has been dubbed Long Covid. The study shows the benefits of natural immunity, but “doesn’t take into account what this virus does to the body to get to that point,” says Marion Pepper, an immunologist at the University of Washington, Seattle. COVID-19 has already killed more than 4 million people worldwide and there are concerns that Delta and other SARS-CoV-2 variants are deadlier than the original virus. The new analysis relies on the database of Maccabi Healthcare Services, which enrolls about 2.5 million Israelis. The study, led by Tal Patalon and Sivan Gazit at KSM, the system’s research and innovation arm, found in two analyses that people who were vaccinated in January and February were, in June, July, and the first half of August, six to 13 times more likely to get infected than unvaccinated people who were previously infected with the coronavirus. In one analysis, comparing more than 32,000 people in the health system, the risk of developing symptomatic COVID-19 was 27 times higher among the vaccinated, and the risk of hospitalization eight times higher. “The differences are huge,” says Thålin, although she cautions that the numbers for infections and other events analyzed for the comparisons were “small.” For instance, the higher hospitalization rate in the 32,000-person analysis was based on just eight hospitalizations in a vaccinated group and one in a previously infected group. And the 13-fold increased risk of infection in the same analysis was based on just 238 infections in the vaccinated population, less than 1.5% of the more than 16,000 people, versus 19 reinfections among a similar number of people who once had SARS-CoV-2. No one in the study who got a new SARS-CoV-2 infection died—which prevented a comparison of death rates but is a clear sign that vaccines still offer a formidable shield against serious disease, even if not as good as natural immunity. Moreover, natural immunity is far from perfect. Although reinfections with SARS-CoV-2 are rare, and often asymptomatic or mild, they can be severe.

In another analysis, the researchers compared more than 14,000 people who had a confirmed SARS-CoV-2 infection and were still unvaccinated with an equivalent number of previously infected people who subsequently received one dose of the Pfizer-BioNTech vaccine. (In Israel, it’s recommended that people who have been previously infected get just one dose.) The team found that the unvaccinated group was twice as likely to be reinfected as the singly vaccinated. “We continue to underestimate the importance of natural infection immunity … especially when [infection] is recent,” says Eric Topol, a physician-scientist at Scripps Research. “And when you bolster that with one dose of vaccine, you take it to levels you can’t possibly match with any vaccine in the world right now.” Nussenzweig says the results in previously infected, vaccinated people confirm laboratory findings from a series of papers in Nature and Immunity by his group, his Rockefeller University colleague Paul Bieniasz and others—and from a preprint posted this month by Bieniasz and his team. They show, Nussenzweig says, that the immune systems of people who develop natural immunity to SARS-CoV-2 and then get vaccinated produce exceptionally broad and potent antibodies against the coronavirus. The preprint, for example, reported that people who were previously infected and then vaccinated with an mRNA vaccine had antibodies in their blood that neutralized the infectivity of another virus, harmless to humans, that was engineered to express a version of the coronavirus spike protein that contains 20 concerning mutations. Sera from vaccinated and naturally infected people could not do so. As for the Israel medical records study, Topol and others point out several limitations, such as the inherent weakness of a retrospective analysis compared with a prospective study that regularly tests all participants as it tracks new infections, symptomatic infections, hospitalizations, and deaths going forward in time. “It will be important to see these findings replicated or refuted,” says Natalie Dean, a biostatistician at Emory University. She adds: “The biggest limitation in the study is that testing [for SARS-CoV-2 infection] is still a voluntary thing—it’s not part of the study design.” That means, she says, that comparisons could be confounded if, for example, previously infected people who developed mild symptoms were less likely to get tested than vaccinated people, perhaps because they think they are immune. Nussenzweig’s group has published data showing people who recover from a SARS-CoV-2 infection continue to develop increasing numbers and types of coronavirus-targeting antibodies for up to 1 year. By contrast, he says, twice-vaccinated people stop seeing increases “in the potency or breadth of the overall memory antibody compartment” a few months after their second dose. For many infectious diseases, naturally acquired immunity is known to be more powerful than vaccine-induced immunity and it often lasts a lifetime. Other coronaviruses that cause the serious human diseases severe acute respiratory syndrome and Middle East respiratory syndrome trigger robust and persistent immune responses. At the same time, several other human coronaviruses, which usually cause little more than colds, are known to reinfect people regularly.

Study Cited Available in medRxiv (August 25, 2021):

https://doi.org/10.1101/2021.08.24.21262415 

Infections in vaccinated Americans are rare, compared with those in unvaccinated people, the document said. But when they occur, vaccinated people may spread the virus just as easily.  The Delta variant is much more contagious, more likely to break through protections afforded by the vaccines and may cause more severe disease than all other known versions of the virus, according to an internal presentation circulated within the Centers for Disease Control and Prevention. Dr. Rochelle P. Walensky, the director of the agency, acknowledged on Tuesday that vaccinated people with so-called breakthrough infections of the Delta variant carry just as much virus in the nose and throat as unvaccinated people, and may spread it just as readily, if less often. But the internal document lays out a broader and even grimmer view of the variant. The Delta variant is more transmissible than the viruses that cause MERS, SARS, Ebola, the common cold, the seasonal flu and smallpox, and it is as contagious as chickenpox, according to the document, a copy of which was obtained by The New York Times. The immediate next step for the agency is to “acknowledge the war has changed,” the document said. Its contents were first reported by The Washington Post on Thursday evening.

Long-haul COVID-19 patients face many health threats -- including a higher chance of dying -- up to 6 months after they catch the virus, according to a massive study published in the journal Nature. A second study, released by the CDC on Friday, also found lingering symptoms months later among COVID-19 patients who originally had mild symptoms.  For the Nature study, researchers examined more than 87,000 COVID-19 patients and nearly 5 million control patients in a federal database. They found COVID-19 patients had a 59% higher risk of death up to 6 months after infection, compared to non-infected people. Those findings translate into about eight extra deaths per 1,000 patients over 6 months, because many deaths caused by long-term COVID complications are not recorded as COVID-19 deaths, the researchers said. Among patients who were hospitalized and died after more than 30 days, there were 29 excess deaths per 1,000 patients over 6 months. “As far as total pandemic death toll, these numbers suggest that the deaths we’re counting due to the immediate viral infection are only the tip of the iceberg,” Ziyad Al-Aly, MD, the senior author of the study and a director of the Clinical Epidemiology Center at the Veterans Affairs St. Louis Health Care System, said in a news release from the University of Washington Medical School in St. Louis. Johns Hopkins University says more than 3 million people worldwide and about 570,000 people in the United States have died of coronavirus-related reasons. Long-haul COVID patients also had a much higher chance of getting sick, and not just in the respiratory system, according to the study.

The BNT162b2 vaccine was shown to have 95% efficacy against coronavirus disease 2019 (Covid-19).1 To date, the two-dose vaccine protocol has not been approved in Israel for persons previously infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); however, administration of a single dose is now being considered. In addition to the original virus first identified in Wuhan, China, SARS-CoV-2 variants first identified in the United Kingdom (B.1.1.7), South Africa (B.1.351), and Brazil (P.1) have been detected in recent months.2 Samples from persons who had been vaccinated or previously infected with the original virus or the B.1.1.7 variant were shown to have significantly less neutralizing activity against the B.1.351 variant than against the other variants.3,4 In this study, we investigated whether one dose of the BNT162b2 vaccine would increase neutralizing activity against the B.1.1.7, B.1.351, and P.1 variants in persons previously infected with SARS-CoV-2. 

A microneutralization assay with isolates of the original virus (sublineage B.1) and the B.1.1.7, B.1.351, and P.1 variants was performed on 18 serum samples from six health care workers previously infected with SARS-CoV-2, with a sample obtained from each patient at three time points: 1 to 12 weeks after natural infection, immediately before vaccination, and 1 to 2 weeks after vaccination (Table S1 in the Supplementary Appendix, available with the full text of this letter at NEJM.org). All six health care workers were women (32 to 67 years of age) and had been infected with the original virus (sublineage B.1), as determined by sequencing of SARS-CoV-2 performed at the time of diagnosis. Samples obtained at the first time point had neutralizing activity against the original virus and the B.1.1.7 and P.1 variants, with geometric mean titers of 456, 256, and 71, respectively, but had little or no neutralizing activity against the B.1.351 variant, with a geometric mean titer of 8. At the second time point, geometric mean titers were 81, 40, 36, and 7 for the original virus and the B.1.1.7, P.1, and B.1.351 variants, respectively. Of note, at the third time point, geometric mean titers were 9195, 8192, 2896, and 1625 for the original virus and the B.1.1.7, P.1, and B.1.351 variants, respectively — that is, the titers after vaccination were 114, 203, 81, and 228 times as high as the titers immediately before vaccination (Figure 1 and Table S2).

This study showed that, in our small cohort, one vaccine dose substantially increased neutralizing activity against all variants tested, with similar titers detected across patients for each variant. This highlights the importance of vaccination even in previously infected patients, given the added benefit of an increased antibody response to the variants tested. Limitations of the study include the small cohort of only women and the lack of evaluation of T-cell response. However, we think the fact that all six patients responded similarly to vaccination supports our conclusions. Further studies could investigate the effects of a second vaccine dose on neutralizing activity against variants of concern in persons who have and persons who have not been previously infected.

Published in New England J. Medicine (April 7, 2021):

https://10.1056/NEJMc2104036 

Three-quarters of people who died of COVID-19 harbored the SARS-CoV-2 virus in their hearts, according to the most detailed study of cardiac tissue to date. Those people were also more likely than patients without cardiac invasion to experience abnormal heart rhythms before they died. The study offers insight into how the disease may damage the heart—and how certain treatments may help. The finding “paints a really nice picture” of the connection between the virus and heart problems, says Joseph Maleszewski, a cardiovascular pathologist at the Mayo Clinic who was not involved with the study.  Scientists have ample evidence of heart damage in COVID-19 patients. Some people, for example, show elevated levels of troponins, molecules released in the blood when the heart is injured. Others have experienced inflammation of the sac surrounding the heart—and inflammation of the heart itself. But it’s been unclear whether these problems were caused by the SARS-CoV-2 virus attacking the heart directly, or the damage is due to an overactive immune response. Part of the problem is that previous studies are mixed about whether SARS-CoV-2 can invade heart tissue. Many that haven’t found the virus use real-time polymerase chain reaction (RT-PCR), says James Stone, a cardiovascular pathologist at Massachusetts General Hospital. RT-PCR works by detecting viral RNA in tissue, then making many DNA copies of it. Once there’s enough DNA, a molecule called a fluorescent tag can stick to it and shine to reveal its presence. But Stone says that heart tissue is often processed and preserved using chemicals like paraffin, which can break down the RNA and prevent detection to begin with. So he and his team used another approach: in situ hybridization and NanoString transcriptomic profiling. Like RT-PCR, these techniques use special molecules to attach to and detect pieces of viral RNA, but they do so without having to make DNA copies first. The approach can identify viral RNA even after it’s broken into smaller pieces. The scientists also analyzed about 1000 pieces of heart tissue—more than 20 samples from each of the 41 patients they looked at. That’s double the number of samples per patient in most studies, Stone says. 

SARS-CoV-2 was present in 30 of the hearts, the team reports today in Modern Pathology. And only those patients experienced new atrial fibrillations, fast and irregular heart rhythms, or early or extra heartbeats, compared with the other patients in the study—a correlation Stone calls “pretty phenomenal.” Still, it’s unclear whether the virus attacked the heart directly in these cases. Most of the infected cardiac cells were immune cells, which SARS-CoV-2 could have invaded elsewhere in the body before they traveled to the heart. It’s also unclear whether the virus—rather than the immune cells themselves—is causing the problems. Regardless, the study may help explain why the steroid dexamethasone is so helpful to some patients. The drug was one of the first found to prevent deaths from severe COVID-19. It reduces inflammation, so it may have curbed the presence of SARS-CoV-2–harboring immune cells in the heart, Stone says. Only 50% of the patients treated with dexamethasone had the virus in their hearts, compared with 90% of patients who were not on the drug. But compared with large clinical trials, the number of patients in this new study is small, making it impossible to say that one drug protects the heart better than another, says Nicholas Hendren, a cardiology fellow at the University of Texas Southwestern Medical Center. Still, Maleszewski says the new findings are a call to action. Scientists need to probe more cardiac tissue, he argues, not just to see how COVID-19 kills patients, but to figure out how it hurts the hearts of those that survive. The disease may, for example, create scar tissue that can cause cardiac problems down the line. We’re starting to understand what COVID-19 does to patients when they have it, he says. “What’s not clear is what happens later on.”

Research Cited Published in Modern Pathology (March 17, 2021):

https://doi.org/10.1038/s41379-021-00790-1 

Data on the characteristics of COVID-19 patients disaggregated by race/ethnicity remain limited. We evaluated the sociodemographic and clinical characteristics of patients across the major racial/ethnic groups and assessed their associations with COVID-19 outcomes. This retrospective cohort study analyzed patients who were tested for SARS-CoV-2 in a large, integrated health system spanning California, Oregon, and Washington between March 1 and August 30, 2020. Sociodemographic and clinical characteristics were obtained from electronic health records. Odds of SARS-CoV-2 infection, COVID-19 hospitalization, and in-hospital death were assessed with multivariate logistic regression. 

289,294 patients with known race/ethnicity were tested for SARS-CoV-2 by PCR, of whom 27.5% were non-White minorities. 15,605 persons tested positive, with minorities representing 58.0%. Disparities were widest among Hispanics, who represented 40.5% of infections but 12.8% of those tested. Hispanics were generally younger and had fewer comorbidities except diabetes than White patients. Of the 3,197 patients hospitalized, 58.9% were non-White. 459 patients died, of whom 49.8% were minorities. Racial/ethnic distributions of outcomes across the health system tracked with state-level statistics. Increase odds of testing positive and hospitalization were associated with all minority races/ethnicities except American Indian/Alaska Native. Highest odds of testing SARS-CoV-2 positive was for Hispanic patients (OR [95% CI]: 3.68 [3.52-3.84]) and highest odds of COVID-19 hospitalization was for Native Hawaiian/Pacific Islander patients (2.13 [1.48 - 3.06]). Hispanic patients also exhibited increased morbidity including need for mechanical ventilation. In multivariate modeling, Hispanic race/ethnicity was associated with increased odds of hospital mortality (1.75 [1.15-2.67]) among patients over age 70, but hospital mortality was not increased for any race/ethnicity sub-population in the multivariate model. 

Major healthcare disparities were evident, especially among Hispanics who tested positive at a higher rate, and despite younger in age, required excess hospitalization and need for mechanical ventilation compared to their expected demographic proportions. As characteristics of patients varying between race/ethnicity, targeted, culturally-responsive interventions are needed to address the increased risk of poor outcomes among minority populations with COVID-19

Preprint available at medRxiv (Oct. 15, 2020):

https://doi.org/10.1101/2020.10.14.20212803

Cats and dogs are just as likely to be infected with SARS-CoV-2 as people are, according to a survey in northern Italy that is the largest study of pets so far. Nicola Decaro at the University of Bari and his colleagues took nose, throat or rectal swabs of 540 dogs and 277 cats in northern Italy between March and May (E. I. Patterson et al. Preprint at bioRxiv http://doi.org/d4r7; 2020). The animals lived in homes with infected people, or in regions severely affected by COVID-19.

Nicola Decaro at the University of Bari and his colleagues took nose, throat or rectal swabs of 540 dogs and 277 cats in northern Italy between March and May (E. I. Patterson et al. Preprint at bioRxiv http://doi.org/d4r7; 2020). The animals lived in homes with infected people, or in regions severely affected by COVID-19. Infection rates among cats and dogs were comparable with those among people in Europe at the time of testing, suggesting that it is not unusual for pets to be infected. The findings have not yet been peer reviewed.

Preprint available at bioRxiv (July 23, 2020):

https://doi.org/10.1101/2020.07.21.214346

Zika virus attracted worldwide attention in recent years due to the devastating consequences of infection for pregnant women and their fetuses, many of which were born with microcephaly and other severe neurological malformations. Although ZIKV infection has historically been associated to relatively mild symptoms, a number of serious neurological complications were described in adult patients during the 2015 outbreak in America. Despite these clinical observations, how ZIKV is toxic to the adult brain and how neurological problems are caused in infected adults have remained unknown.

Researchers led by neuroscientists Sergio T. Ferreira e Claudia Figueiredo and virologist Andrea Da Poian at the Federal University of Rio de Janeiro (Brazil) have now come up with answers to these questions. First, they exposed small fragments of adult human brain tissue to ZIKV isolated from the blood of an infected Brazilian patient. Contrary to the previous belief that ZIKV only infects neuronal progenitor cells or neurons that are still immature in the developing brain, they found that the virus infected and replicated in adult human tissue, producing new viral particles capable of infecting more cells.

But what are the consequences of this infection? To address this question, they injected Zika virus directly into the brains of mice. As lead author Claudia P. Figueiredo and Ferreira explains: "Infected mice exhibited marked memory impairment that persisted even after infection had been fought off by the organism. Moreover, this was consistent with the fact that brain regions responsible for learning and memory processing were the main sites of viral replication in their brains." 

The work further showed that infection by ZIKV causes a strong inflammatory response in the mouse brain, and this includes activation of brain resident immune cells called microglia. Fernanda Barros-Aragão, a PhD student and author of the study, explains that this exaggerated inflammatory response is ultimately responsible for memory loss: "Neurons communicate through highly specialized regions called synapses. Surprisingly, we found that microglia that become aberrantly activated upon infection by ZIKV attack and engulf synapses. This impairs communication between neurons and, therefore, the formation of new memories." Interestingly, when animals were treated for about one week with anti-inflammatory drugs capable of blocking microglial activation, they recovered memory. Results from this study indicate that the adult brain is damaged by infection by ZIKV, and point to the need to carefully evaluate learning and memory performance in follow-up assessments of infected adults. Although no specific treatments for ZIKV infection are yet available, these findings further reveal the possibility that neurological symptoms caused to infection by controlling brain inflammation.

Findings published September 5 in Nature Communications:

https://www.nature.com/articles/s41467-019-11866-7