Tag Archives: SARS

COVID-19 antibodies last as long as 8 months

Illustration of antibodies (red and blue) responding to an infection with the new coronavirus SARS-CoV-2 (purple). The virus emerged in Wuhan, China, in December 2019, and causes a mild respiratory illness (COVID-19) that can develop into pneumonia and be fatal in some cases.

Our current understanding of SARS-CoV-2 immunity is mainly based on previous experiences with SARS-CoV (2003) and recent studies in patients infected with and recovered from SARS-CoV-2 (2020). 

Similar to the SARS-CoV infection, the main antibody targets in SARS-CoV-2 are the spike and nucleocapsid proteins (NCP) — and this is where the vaccines also strike. However, it’s not clear if lasting immunity against the novel coronavirus can be achieved because serum antibodies seem to decline. Since this pandemic is still relatively new, we haven’t had much time to explore just how long antibodies and immunity lasts — but new results are coming in.

Two new studies published recently demonstrate that COVID-19 antibodies last as long as 8 months, or potentially even more, giving some good news for a mass vaccination campaign.

A study published in Science Immunology followed a small cohort of Australians from day 4 to day 242 after infection. All patients demonstrated the presence of memory B cells — immune cells that “remember” viral proteins and can trigger rapid production of antibodies when re-exposed to the virus — as long as 8 months after the initial infection.

Researchers took blood samples from 25 confirmed COVID-19 patients with a range of disease severities and 36 healthy control patients from March to September, evaluating each patient’s antibody status and levels of virus-specific immune cells. The study showed that by day 6 post-infection, all patients showed immunoglobulin G (IgG) antibodies for the viral receptor-binding domain (a protein on the viral surface that binds to cell receptors, allowing entry and infection) and the nucleocapsid protein. The immunoglobulin G levels began declining 20 days after symptom onset. However, memory B cell levels continued to rise up to 150 days post-infection and remained detectable 240 days post-symptom onset, suggesting that patient immune systems were primed to respond to reinfection.

According to the authors, cellular immunity could explain why there are few documented cases of reinfection with SARS-CoV-2 and why immunity can last longer than the antibody levels would suggest it.

Another study investigated antibody responses in 58 confirmed COVID-19 patients in South Korea 8 months after asymptomatic or mild SARS-CoV-2 infection.

The team used 4 commercially-available immunoassays:

Except for the anti-N IgG ELISA, all of these immunoassays have been granted Emergency Use Authorization by the US Food and Drug Administration.

For 3 of 4 immunoassays used, seropositivity rates were high (69% to 91.4%; < 0.01). These results, published in Emerging Infectious Diseases, are contradictory to both the first study’s antibody data and previous research that showed antibodies waning after 20 days, but the authors suggest that variations in immunoassay test characteristics and manufacturing may be responsible for the difference.

Increasingly, the scientific evidence seems to suggest

People with blood type O may face lower risk of coronavirus infection or have milder symptoms

Two retrospective studies in Blood Advances add evidence for an association between blood type and COVID-19 risk, indicating that people with blood type O could be less susceptible to infection and experience milder disease. But this does not necessarily confirm causation. Further investigations on the mechanism of the different susceptibility to COVID-19 between blood group A and O individuals are needed and regardless of your blood type, you need to follow public health recommendations.

The first study from Denmark compared data from around 473,000 COVID-19–positive individuals with a control group of 2.2 million people in the general population, finding fewer infected people with blood type O and more people with A, B, and AB types. No associations were found between non-O blood groups and comorbidities that might explain infection rate differences.

The authors hypothesize that the presence of virus-neutralizing anti-A and anti-B antibodies on mucosal surfaces of some type O individuals may explain the relative protection for this blood type.

The second study from Vancouver, Canada on 95 critically ill COVID-19 patients in a hospital found that—after adjusting for sex, age, and comorbidities—patients with blood types A or AB were more likely to require mechanical ventilation than patients with types O or B (84% vs 61%, P = 0.02), indicating higher rates of lung damage.

Patients with blood types A and AB also had higher rates of dialysis for kidney failure, suggesting increased organ dysfunction or failure due to COVID-19 (32% vs 95%, P = 0.004). Patients with blood types A and AB did not have longer hospital stays than those with types O or B, but they did experience longer intensive care unit stays, which may signal greater COVID-19 severity.

A study in June looking at patients in Italy and Spain found that blood type O had a 50 percent reduced risk of severe coronavirus infection (i.e. needing intubation or supplemental oxygen) compared to patients with other blood types. A study published in July looking at patients in five major hospitals in the state of Massachusetts found that people with blood type O were less likely to test positive for COVID-19 than those with other blood types. Another study in April (pre-print and awaiting peer-review) found that among 1,559 coronavirus patients in New York City, a lower proportion than would be expected had Type O blood. Earlier in March, a study of over 2,100 coronavirus patients in Wuhan and Shenzhen (also not peer-reviewed) found that people with Type O blood had a lower risk of infection.

Past research analyzing a hospital outbreak in Hong Kong suggested that people with Type O blood were less susceptible to (the original, not the pandemic) SARS, which shares ~80 percent of its genetic code with the new coronavirus, SARS-CoV-2. A 2005 Clinical Microbiology Review also found that most individuals infected with SARS had non-O blood types. 

It’s important to emphasize that the type of reduction in risk achieved with appropriate physical distancing, wearing a mask, and hand hygiene are significantly better than depending on your blood group for protection, so people with blood type O should not be complacent about public health advice.

Risk of death from COVID-19 is 2.4 times higher in men

For many infectious diseases, women are at higher risk and experience a more severe course of illness than men. In some southern African countries, for example, young women are up to eight times more likely to have HIV than men of the same age, which is thought to be due, in part, to gender inequity, gender-based violence, age-disparate relationships, and not simply because of biological differences.

But in the case of COVID-19, that’s not the case — in this case, it’s men that seem to bear the brunt of the damage.

Men are more likely than women to die of the coronavirus. This is particularly pronounced in Italy, where men represent nearly 70% of the country’s deceased patients. Scientists suspect unhealthy habits like smoking and underlying health issues among men could be influencing this trend. 

According to a study in Frontiers in Public Health, men are 2.4 times as likely to die from COVID-19 than women, regardless of age. Moreover, older men with underlying medical conditions are much more likely than their female counterparts to have poor outcomes from COVID-19 infection, according to a small retrospective study published in PLOS Pathogens.

Investigators in the Frontiers study extracted data from a case series of 43 COVID-19 patients hospitalized in Wuhan, China; a public data set from the first 37 patients who died of the virus and 1,019 survivors in China; and information from 524 SARS (severe acute respiratory syndrome) patients, including 139 who died, in 29 Beijing hospitals in early 2003 to compare the two diseases.

In the case series, 37.2% of patients had one or more underlying conditions, such as high blood pressure, diabetes, cardiovascular diseases, and chronic lung disorders. Male COVID-19 patients had elevated levels of serum creatinine (indicating kidney damage), white blood cells (indicating immune response), and neutrophils (indicating inflammation). Of the 43 patients in the case series, 13 (30.2%) had mild or moderate pneumonia, while 14 (32.6%) had severe pneumonia, 16 (37.2%) had critical pneumonia. Chi-square (χ2) test for trend showed that men tended to have more serious illnesses than women (P = 0.035).

Advanced age and a high number of underlying diseases were linked to more severe disease and death in patients who had either COVID-19 or SARS. In the case series, men tended to have more serious disease than women (P = 0.035), while the public data set revealed that men were 2.4 times more likely than women to die of COVID-19 (70.3% versus 29.7%; P = 0.016).

Of the 37 non-survivors in the public data set, 70.3% were men, 29.7% were women, and 64.9% had one or more underlying conditions. These patients were significantly older, at 65 to 81 years, with 83.8% of them age 65 and older, versus survivors, who were 35 to 57 years old, with 13.2% 65 and older.

In patients with SARS, the proportion of males in the group who died was higher than that of the surviving group (P = 0.015). In this group, 57.0% of patients had one or more underlying conditions. Median age of non-survivors was much higher than that of survivors (57 versus 32; P < 0.001), and non-survivors were also more likely than survivors to have underlying disease (57.0% versus 17.9%; P < 0.001). The percentage of men was higher in the non-surviving group (53.2%) than in the surviving group (42.3%) (χ2 test; P = 0.027). Men were also significantly more likely to die than women (31.2% vs 22.6%; hazard ratio, 1.47; 95% confidence interval [CI], 1.05 to 2.06; P = 0.026).

In the PLOS Pathogens case series, researchers studied the data of 168 patients with the novel coronavirus admitted consecutively to Tongji Hospital in Wuhan, China, from Jan 16 to Feb 4. Overall, 17 patients (8.9%) died, while 136 (81%) were released from the hospital. Eleven (12.8%) of the 86 male patients died, while 65 (75.6%) were released from the hospital. Six (7.3%) of the 82 female patients died, while 71 (86.6%) were released. Fifty-seven patients had underlying conditions (33.7%). Median time from illness onset to hospital admission was 9 days for males and 7 days for females.

Of male patients, 36.0% had a chronic underlying illness, especially diabetes and cardiovascular and cerebrovascular diseases. After adjusted logistic regression analysis, males with underlying illnesses were more vulnerable to critical illness than those without comorbidities.

This was not the case for females. After adjustment for confounding factors, males 80 years and older were more likely to become critically ill than those younger than 59. But this wasn’t true for females.

Men and women differ in both innate and adaptive immune responses. These disparities may be attributed to steroids and X-linked gene activity, which both regulate the immune response to viruses. The authors said that future studies are needed to identify the different pathways and cellular responses between the two sexes.

A compound against SARS shows promise against the COVID-19 virus

Commonalities between the coronavirus responsible for the current outbreak and the SARS virus could point the way towards a treatment option, a new paper reports.

Graphical abstract of the study.
Image credits Hoffman et al., (2020), Cell.

SARS (severe acute respiratory syndrome) was capturing headlines and causing panic around the world back in 2003. The virus responsible for SARS — SARS-CoV — is a coronavirus related to the current SARS-CoV-2 virus that is at the root of the current global outbreak. SARS eventually resulted in more than 8,000 cases and 800 deaths, but was contained through a combination of “surveillance, prompt isolation of patients, strict enforcement of quarantine of all contacts, and in some areas top-down enforcement of community quarantine,” according to a study (A. Wilder-Smith, J. Chiew, J. Lee, 2020) published last week in The Lancet.

“By interrupting all human-to-human transmission, SARS was effectively eradicated. By contrast, by Feb 28, 2020, within a matter of 2 months since the beginning of the outbreak of coronavirus disease 2019 (COVID-19), more than 82,000 confirmed cases of COVID-19 have been reported with more than 2,800 deaths,” the study adds.

“Although there are striking similarities between SARS and COVID-19, the differences in the virus characteristics will ultimately determine whether the same measures for SARS will also be successful for COVID-19.”

The “striking similarities” the authors note here may, however, point us to a viable treatment option for the COVID-19 disease caused by the SARS-CoV-2 virus.

Birds of a feather get shot together

Published in the journal Cell, the new study explains that structural similarities between the two viruses allow for a substance already approved for clinical use against SARS to engage the COVID-19 virus and that natural antibodies against SARS “may offer some protection” against the current outbreak.

“A TMPRSS2 inhibitor approved for clinical use blocked entry and might constitute a treatment option,” the authors explain. “Finally, we show that the sera from convalescent SARS patients cross-neutralized SARS-2-S-driven entry. Our results reveal important commonalities between [the two viruses] and identify a potential target for antiviral intervention.”

TMPRSS2, or transmembrane protease serine 2, is an enzyme (protein) in the serine protease family that “is associated with […] processes such as digestion, tissue remodeling, blood coagulation, fertility, inflammatory responses, tumor cell invasion, and apoptosis [cellular death],” according to Sciencedirect. According to the findings, the COVID-19 virus relies on this enzyme to reproduce (by multiplying its genes inside infected cells). The authors further report that the virus enters human cells by using ACE2 (angiotensin converting enzyme 2) receptors on its viral casing.

This process is the same one used by the SARS virus. A more exciting finding was that a TMPRSS2-inhibiting compound already approved for use against SARS successfully prevented the COVID-19 virus from infecting human cells. In addition, the team found that serum derived from the blood of former SARS patients — which contains natural antibodies against it — is “moderately effective” in protecting individuals from infection with the COVID-19 virus.

“Although confirmation with infectious virus is pending, our results indicate that neutralizing antibody responses raised against SARS-S could offer some protection against SARS-CoV-2 infection, which may have implications for outbreak control,” they explain.

While the findings are definitely encouraging, there are still unknowns left to sort out. For example, the higher infection rates seen in COVID-19 compared to SARS could mean that the new coronavirus is better able to bind to the ACE2 receptors in cells in the upper respiratory tract. More research is needed, and fast, to elucidate these issues, the team explains, but they are hopeful that their findings lay the groundwork for such efforts in the future.

The paper “SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor” has been published in the journal Cell.

New SARS-like virus can jump directly to humans from bats

A virus similar to SARS has been identified in Chinese horseshoe bats that may be able to infect humans without prior adaptation. Overcoming this genetic barrier could be the first step for an outbreak, according to a study at the University of North Carolina at Chapel Hill.

The newly identified virus, known as WIV1-CoV, could bind to the same receptors as SARS-CoV.
Image credits CDC/Dr. Fred Murphy

In the wake of the recent Zika and Ebola outbreaks which claimed thousands of lives and cost billions in forgone economic development, a team led by Ralph Baric, Ph.D., professor of epidemiology at UNC’s Gillings School of Global Public Health warns of a new, and just as dangerous, virus.

“The capacity of this group of viruses to jump into humans is greater than we originally thought,” said Vineet Menachery, Ph.D., the study’s first author.

“While other adaptations may be required to produce an epidemic, several viral strains circulating in bat populations have already overcome the barrier of replication in human cells and suggest reemergence as a distinct possibility.”

Baric and Menachery used coronavirus sequences obtained from Chinese horeshoe bats, in which SARS also originated. From them, they reconstructed the virus and tested it to see its potential to infect human and mouse cells. The newly discovered virus, which the team dubbed WIV1-CoV, could bind to the same receptors as SARS-CoV; in essence, allowing it to infect the same types of cells. The virus also replicated quickly and efficiently in cultured human airway tissue cells, suggesting it can jump directly to humans from bats.

“To be clear, this virus may never jump to humans, but if it does, WIV1-CoV has the potential to seed a new outbreak with significant consequences for both public health and the global economy,” said Vineet.

Due to a slightly different genetic make-up, SARS vaccines don’t provide protection against it. The good news however is that the antibodies we’ve developed to fight SARS were really good at killing WIV1-CoV in both human and animal tissue samples — giving us a powerful treatment option in case of an outbreak. The only limiting factor when using antibodies, as Ebola treatment ZMapp showed, is quantity; producing antibodies takes time and resources, and if the number of infected runs out of check there won’t be enough to go around.

When SARS (severe acute respiratory syndrome) was first seen in an outbreak in 2002 it spread to nearly 8,000 people, causing almost 800 deaths. It can spread through airborne contact, and in the early stages its symptoms resemble a dry-cough flu; but it can develop rapidly, causing pneumonia, filling of the lungs with fluid and wreaking havoc on the immune system. Baric and his team believe that WIV1-CoV has the potential to induce similar results with proper adaptation to humans.

“This type of work generates information about novel viruses circulating in animal populations and develops resources to help define the threat these pathogens may pose to human populations,” Baric said.

“It’s important to note that it’s not an approach that’s limited to SARS or SARS-like viruses. It can be applied to other emerging pathogens to helping us prepare for the next emergent virus, whether it be MERS, the Zika virus or something we haven’t even heard of yet.”

According to the Centers for Disease Control and Prevention, SARS’ mortality rate can range from less than one percent in patients below 24 years old to more than 50 percent in patients aged 60 and older.

The full paper, titled “SARS-like WIV1-CoV poised for human emergence” has been published online in the journal PNAS and can be read here.