Most Americans have already had COVID-19 at least once with infections lasting a few weeks. But roughly 10 percent of patients have never fully recovered.
Ziyad Al-Aly is a global expert in long COVID, a condition that has left 65 million people worldwide reeling with fatigue, cardiovascular problems, shortness of breath, cognitive impairments, and chronic pain even months or years after infection.
At first, Al-Aly didnt believe what the data and patient accounts told him: that COVID-19 could wreak havoc on multiple organ systems long after the acute infection phase.
From all my education, we're not trained to think that viruses, especially respiratory viruses, have these myriad effects in all these organ systems. So I doubted it for the longest time, but the results came back exactly consistent every single time, Al-Aly said on the "Ground Truths" podcast in September. He directs the Clinical Epidemiology Center and is chief of the Research and Development Service at the U.S. Department of Veterans Affairs St. Louis Health Care System.
Al-Aly will explain his latest findings during a public presentation titled Long COVID: The Lasting Legacy of the COVID-19 Pandemic, at 5:30 p.m. Thursday, Jan. 25, at the Fralin Biomedical Research Institute at VTC in Roanoke.
Dr. Al-Aly is a world-class physician-scientist and an emerging thought leader examining the hidden population health consequences of the pandemic, said Michael Friedlander, executive director of the Fralin Biomedical Research Institute (FBRI) and Virginia Techs vice president for health sciences and technology. We are especially excited to hear from him and share ideas as many of our researchers here at the FBRI are carrying out research on some of the key systems that are impacted by COVID-19 including the brain and the heart and vascular systems. Moreover, our molecular diagnostics COVID-19 testing team is very connected to his work. We expect to learn a great deal from his lecture and are honored to host such an eminent thought leader with our community, particularly as we see Centers for Disease Control data on COVID-19 severity indicators trending up yet again.
Over the past three years, Al-Aly has analyzed health data from millions of veterans nationwide. He has published evidence in top-tier journals that the virus leads to an increased risk of diabetes onset, long-term neurological symptoms, dyslipidemia, cardiovascular disorders, and a wide range of gastrointestinal disorders.
Al-Alys pioneering research also involves one of the worlds largest longitudinal studies to evaluate COVID-19s long-term impacts. His team found that even patients with mild infections remained at higher risk of developing post-acute symptoms and health conditions.
But if youve already had a mild infection, whats the harm in getting COVID-19 again? Al-Alys research published in Nature last year demonstrated how reinfection increases risks of death, hospitalization, and disease.
The results are very, very clear that a second infection or reinfection is consequential, Al-Aly said. I think the best interpretation for this is for people to think that two infections are worse than one and three are worse than two.
Before the pandemic, Al-Alys research focused on the impact of various health conditions, including kidney diseases, on a population level. He analyzed veterans health and satellite air quality data from NASA in a series of studies to define a link between air pollution and chronic kidney disease, obesity, interstitial lung disease, and rheumatoid arthritis.
He also has evaluated the efficacy and long-term side effect profile of a variety of commonly prescribed therapeutics, ranging from metformin for diabetes and proton pump inhibitors for acid reflux to newer drugs marketed to treat diabetes and weight loss, such as GLP-1 receptor agonists like Ozempic.
Al-Alys research program is funded by the National Institutes of Health to conduct randomized trials comparing the impacts of these various drug classes on cardiovascular and kidney health.
Most clinical trials for these things track them for 30 days or at the most for a few months. The long-term risk profiles of these medications have not been characterized previously, Al-Aly said.
Raised in Lebanon, Al-Aly completed his medical degree at the American University of Beirut and his residency and fellowship at Saint Louis University. He has authored over 112 peer-reviewed scientific papers, amassing over 108,000 citations. He holds a faculty appointment at the Washington University School of Medicine in St. Louis and is a member of the American Society of Nephrology.
The institutes free public lecture series is made possible by Maury Strauss, a longtime Roanoke businessman and benefactor who recognizes the importance of bringing leading biomedical research scientists to the community.
The public is welcome to attend the lecture, including a 5 p.m. reception with refreshments in the Fralin Biomedical Research Institute at 2 Riverside Circle in Roanoke. Al-Alys talk will be streamed live via Zoom and archived on the institutes website.
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Jan. 16, 2024 | LITTLE ROCK Researchers at the University of Arkansas for Medical Sciences (UAMS) found significant declines in WIC participation during and after the COVID-19 pandemic, according to a study published in the American Journal of Public Health.
The researchers led by student-researcher and UAMS College of Medicine student Savannah Busch measured changes in participation in the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) among more than 10 million Medicaid-covered births across the United States between 2016 and 2022. During this time period, researchers found that participation in WIC went from 66.6% to 57.9%.
In addition to significant declines in WIC participation during and after the pandemic, researchers discovered even greater reductions in the programs participation among individuals of minority race/ethnicity.
WIC services have been consistently shown to improve infant outcomes at birth, as well as throughout infancy, while providing other maternal health benefits, said researcher Clare Brown, Ph.D., MPH, an assistant professor in the UAMS Fay W. Boozman College of Public Health. Anything that suggests reduced utilization of WIC for those who may need WIC services is a bad thing, and we found that the COVID-19 pandemic reduced the use of WIC services overall, and there were even larger reductions for individuals of minority races or ethnicities.
According to the U.S. Department of Agricultures Food and Nutrition Services, WIC provides supplemental foods, health care referrals, and nutrition education for low-income pregnant, breastfeeding, and non-breastfeeding postpartum women, and to infants and children up to age 5 who are found to be at a nutritional risk.
To apply for WIC, women must visit a health professional to determine whether they are at a nutritional risk. The availability of such processes and other eligibility screenings, Brown said, was greatly impacted during the pandemic, as many clinics and agencies had reduced or limited hours and many populations faced new transportation challenges, particularly in areas that more commonly use public transportation. Additionally, for individuals who speak limited or no English, or who work during daytime hours, applying for WIC can be even more challenging, she said.
When we see that the use of WIC declines for a community whos already at increased risk of bad infant and maternal health outcomes, those bad health outcomes might get even worse, Brown said. Many public health programs have strict eligibility requirements. Understanding what those requirements are and finding ways to create flexibilities in those requirements is really important, particularly for reducing health disparities.
For the WIC program, those flexibilities could include increased hours of clinics and agencies that facilitate the WIC application process, providing non-English applications and resources, allowing various proofs of residency, increasing the number of stores that participate in the WIC program, and increasing WIC-eligible food products.
Brown added that Native Hawaiian and other Pacific Islander groups saw one of the greatest relative declines in WIC participation over the studys six-year period. This is a critical finding for mothers in Arkansas a state that was recently ranked worst in the nation for maternal mortality and given the states large population of Marshallese mothers.
The study, Association of the COVID-19 Pandemic With Women, Infants and Children (WIC) Receipt Among Pregnant Individuals: United States, 2016-2022, can be viewed at https://ajph.aphapublications.org/doi/10.2105/AJPH.2023.307525. For more information about WIC, visit fns.usda.gov/wic.
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Study design
The purpose of the study was to examine the antibody response in RA patients vaccinated against COVID-19 and to identify clinical factors affecting the antibody response in a real-world setting. In this study, the type of vaccination and the intervals between vaccinations were heterogeneous among the patients; this is because COVID-19 vaccinations were administered as part of routine clinical practice. The primary analysis involved measurement of antibody titers from RA patients that received the BNT162b2, mRNA-1273, ChAdOx1, or Ad26.COV2.S vaccines. All vaccines were monovalent as no bivalent vaccines were available at the time. A patient was censored if he/she was infected with COVID-19 during follow-up. Antibody response curves were constructed after the 1st, 2nd, 3rd, and 4th vaccinations; these were based on the anti-RBD antibody titers measured after each vaccination. To identify factors that contribute to a peak response, the antibody response for each patient was modeled based on their individual clinical factors.
The study was carried out in accordance with the Declaration of Helsinki, and was approved by the Institutional Review Boards of Seoul National University Hospital (IRB No. 2205-060-1322).
South Korea experienced two major peaks of COVID-19 infection: Feb 2022 and Sep 2022. Two groups of RA patients attending Seoul National University Hospital (SNUH), a nationwide tertiary referral center in South Korea, were enrolled before the COVID-19 peaks occurred. Group 1 comprised RA patients enrolled in an influenza vaccination study between October 6 and November 3, 2021 (IRB No. 2109-020-1252). The original study was a randomized controlled trial to evaluate the vaccination response by comparing a 1-week versus 2-week temporary discontinuation of MTX after influenza vaccination. According to the enrollment criteria, all RA patients in Group 1 had taken stable dose of methotrexate over the preceding 6weeks of influenza vaccination. Serial serum samples were obtained at 0, 4, and 16weeks after the influenza vaccination. Group 2 comprised patients who participated in the SNUH RA cohort study between January 1 and June 3, 2022 (IRB No. 2105-085-1219). The study was a cohort study to monitor disease activity and treatment response. For these patients, sera were obtained once at the start of participation. The samples analyzed in the study were all archived samples, not additional blood draws. Informed consent was obtained from all participants to use their samples for further study at the time of the enrollment.
Among the enrolled patients, only those with an available vaccination history and who were nave to COVID-19 infection were included in data analysis. The exclusion criteria were as follows: (1) self-reported or a Korea Disease Control and Prevention Agency (KDCA) record of COVID-19 infection before sampling; (2) positive for anti-nucleocapsid (anti-N) antibodies; (3) did not receive a COVID-19 vaccination before sampling.
Patient demographics, comorbidities, and concurrent immunosuppressive medications were obtained from electronic medical records. Comorbidities included diabetes mellitus, hypertension, chronic liver disease, chronic kidney disease, and history of tuberculosis. Concomitant medications were defined as those prescribed within 3months of blood sampling. These included glucocorticoids (GCs), methotrexate (MTX), hydroxychloroquine, sulfasalazine (SSZ), leflunomide, tacrolimus, tumor necrosis factor alpha inhibitors (TNFi), tocilizumab, abatacept (ABA), Janus kinase inhibitors (JAKi), and rituximab (RTX).
Since February, 2021 in South Korea, COVID-19 vaccinations have been mandatory in accordance with the national guidelines. The type of vaccine and intervals between vaccinations were decided by the government. The first approved vaccines were BNT162b2, mRNA-1273, ChAdOx1, and Ad26.COV2.S. With the exception of Ad26.COV2.S, all primary vaccinations required a follow-up 2nd dose after 312weeks. Cross-vaccination was allowed. In December 2021, the 3rd dose of vaccine was administered (i.e., an interval of 23months after the previous vaccination). In April 2022, a 4th dose was recommended (i.e., an interval of 4months from the previous vaccination). The vaccination history of each patient was listed by the KDCA. Any PCR-proved COVID-19 infection should be reported to the KDCA through the regional infection center or a local clinic.
Information on the dose, date and the type of COVID-19 vaccination, was obtained from the patients and cross-checked with the data from KDCA. Previous COVID-19 infection was reported by the patients, and confirmed by an infection certificate from KDCA and a positive anti-nucleocapsid (anti-N) antibody test. When the patient tested positive in the self-antigen test but did not undergo a formal diagnostic test for any reason, the patient was considered as a positive infection case and excluded.
The titer of IgG antibodies specific for the SARS-CoV-2 receptor binding domain of spike 1 protein (anti-RBD) was measured in stored serum samples using a chemiluminescence microparticle immunoassay (Abbott, USA). The anti-RBD ranged from 21 to 40,000AU/mL. A value<21 or>40,000AU/mL was documented as 20 or 44,000AU/mL, respectively. Anti-RBD antibodies represent the humoral response to COVID-19 vaccination10.
In addition, the titer of anti-N antibodies was measured using an electrochemiluminescence immunoassay (Roche, Germany). Anti-N antibody titers above the cut-off value of 1.00AU/mL denoted a previous natural COVID-19 infection11.
Since the two studies (influenza vaccination study and SNUH RA cohort study) used in this model were not specifically designed for modeling of antibody response to COVID-19 vaccination, vaccination and sampling schedules were heterogenous among individuals. Therefore, we performed several sensitivity analyses to reconfirm our results.
First, we estimated the change of the log anti-RBD titer over time for the subjects who received the same type of vaccination. Second, the group 1 (influenza vaccination study) and group 2 (SNUH RA cohort study) were separately analyzed to investigate the clinical factors affecting anti-RBD titer and to reveal time-course of anti-RBD antibodies following vaccination.
The characteristics of the subjects were expressed as mean (standard deviation) for continuous variables and numbers (percentage) for categorical variables. The anti-RBD titer was log-transformed to improve normality. The second-degree fractional polynomials which covers wide range of curve shapes were applied since the pattern of change in the log anti-RBD titer over time is unknown and may not be linear12. The change of the log anti-RBD titer over time was determined in the fractional polynomial regression while adjusting the vaccination dose. Robustness of the curve was confirmed with adjustment of clinical factors affecting log anti-RBD titer: age, ABA use JAKi use, SSZ use, and the vaccination dose. Then clinical variables related to humoral responses to COVID-19 vaccination were determined. A regression model using a generalized estimating equation was applied to account for the correlation among anti-RBD titers among the subjects. Since only 22% subjects (120 out of 550) have two or three antibody responses, we chose the population average model, instead of a subject specific estimate. The exchangeable variance structure was applied because the interval between repeated measurements were various from subject to subject, and only 20% of the subjects had three anti-RBD titer. However, the mixed effect model was used to estimate the change of the log anti-RBD for Group1 subjects (from whom serial samples were obtained). The time and vaccination dose were fixed effects and the subject was a random effect. The linear assumption of continuous variables was checked using scatter plot and locally weighted scatterplot smoothing with clinical knowledge of relationship with log anti-RBD titer. The significant variables at 0.1 significance levels in the univariable analysis were considered for the multivariable model. The forward variable selection method was used to detect significant clinical variables affecting the log anti-RBD titer. The all two-way interaction terms were tested in the multivariable model one by one at 0.01 level of significance. The goodness of fit for the multivariable model was measured using R-square.
Statistical analysis was performed using R (version 4.3.1; R Foundation for Statistical Computing) and SAS software (version 9.4; SAS Institute).
Representational Image
Monday, January 15: After five consecutive weeks of rising COVID-19 cases and anxieties, India finally witnessed a 25% dip in the viral infection during the week ending on January 13. And this encouraging trend was accompanied by a decline in deaths, with 22 reported compared to 31 the previous week.
As of Sunday, India logged 375 new cases of COVID-19, while the number of active infections has dropped to 3,075, the Health Ministry said. Although a new variant and colder weather conditions initially drove the surge, the situation now seems to be stabilising. The good news is widespread too, with most major states registering a drop in reported infections.
Kerala led the pack with a nearly 60% reduction, from 1,109 cases last week to 452 this week. Even Karnataka and Maharashtra, which were previously witnessing a surge, saw a gratifying decline. Karnataka, still with the highest case count at 1,583, had dropped from 1,856 previously, while Maharashtra reported a dip from 915 to 709.
Bengal remains a concern as it continues to see a rise in infections. But experts are closely monitoring the situation and urging strict adherence to safety protocols to prevent further spread.
While the recent developments offer a glimmer of hope amidst concerns about the new JN.1 sub-variant, a new INSACOG report indicates that we cannot let our guards down just yet.
According to INSACOG data, the JN.1 sub-variant has crossed the 1,000 mark nationwide. Karnataka has been revealed to be the leading hotspot with 214 cases, followed by Andhra Pradesh (189) and Maharashtra (170). Even as concerns remain about JN.1, official sources assure there's no evidence of it triggering an exponential increase in cases or a surge in hospitalisations and deaths.
Given the decrease in active COVID-19 cases, we do have reason for some cautious optimism. However, the JN.1 variant requires close monitoring, and continued vaccination efforts remain essential to bolster population immunity. Continued vigilance, coupled with responsible social distancing and adherence to safety protocols, can help solidify this downward trend and prevent future surges.
(With inputs from TOI)
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The curves on some Covid graphs are looking quite steep, again.
Reported levels of the virus in U.S. wastewater are higher than they have been since the first Omicron wave, according to data from the Centers for Disease Control and Prevention, though severe outcomes still remain rarer than in earlier pandemic winters.
We are seeing rates are going up across the country, said Amy Kirby, program lead for the C.D.C.s National Wastewater Surveillance System. The program now categorizes every state with available data at high or very high viral activity.
The surge might reach its peak this week or soon after, modelers predict, with high levels of transmission expected for at least another month beyond that.
Hospitalizations and deaths have remained far lower than in previous years. There were around 35,000 hospitalizations reported in the last week of December down from 44,000 a year earlier and 1,600 weekly deaths as of early December, down from 3,000. (At the same time in 2020, there were around 100,000 hospitalizations and 20,000 deaths each week.)
Many of the metrics used early in the pandemic have become much less useful indicators of how widely the virus is spreading, especially since federal officials stopped more comprehensive data tracking efforts when they declared an end to the public health emergency last spring. Higher population-wide immunity has meant fewer hospitalizations even with high virus spread, and the sharp decline of Covid test results reported to authorities has made case counts far less relevant.
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Dr. Eric Topol:
Well, a lot more than it's doing.
In the first year of the pandemic, we saw that Operation Warp Speed, and we took this virus as an existential threat and pulled out all the stops.
But, right now, John, we need oral or nasal vaccines to stop infections, to stop spread, to be variant-proof, whatever this virus mutates to in the times ahead. And we have a small amount of funding towards that end, but not enough.
And the messaging has been poor. That is, even the people at highest risk, about 35 percent of them have had the updated booster that's been available since September. That's the highest-risk people of advanced age. We had 90, 95 percent of those same high-risk people getting the initial primary series of the vaccine.
So we're not doing enough. We have known this was coming. We have seen countries in Europe that had wastewater levels of the virus that were unprecedented, even exceeding Omicron. And it isn't like they stay the virus is going to stay there. We knew it was coming since September, October, and only in recent weeks have health systems started to get masking back as a policy.
We're just not doing enough to prepare or manage this big surge.
WTOP anchors Shawn Anderson and Kyle Cooper spoke with CBS News medical contributor Dr. Celine Gounder on what to know about JN.1, the latest COVID-19 variant.
The Centers for Disease Control and Prevention said health departments across the country are seeing an increase in respiratory illnesses, including the flu, RSV and a fast-growing new COVID-19 variant called JN.1.
WTOP anchors Shawn Anderson and Kyle Cooper spoke with CBS News medical contributor Dr. Celine Gounder on the trend and what to know about the latest variant.
CBS News medical contributor Dr. Celine Gounder speaks with WTOP's Shawn Anderson and Kyle Cooper
Read the interview transcript below, which has been lightly edited for clarity.
Shawn Anderson: So lets first talk about this latest COVID variant. Is it showing the same symptoms as other variants for those who get infected?
Dr. Celine Gounder: The kind of COVID you get with JN.1, this current variant, the symptoms are the same. So its going to be that typical fever, cough, perhaps in some people shortness of breath, sore throat, but the symptoms are the same. And its really important for people to understand that youre going to hear about variant after variant after variant emerging. And its not necessarily really big news, unless that variant is seen to be escaping your immunity, if its transmitting from person-to-person a lot more efficiently. And if its leading to more people ending up in the hospital than with prior variants, and were just not seeing that with this current one. Its behaving like other recent COVID variants.
Kyle Cooper: Of course, weve been reporting that flu and RSV cases are also up. But theres also some anecdotal reporting out there that some urgent care doctors are seeing lots and lots of people with some type of virus that doesnt necessarily test positive for COVID or anything else. Is that just a run-of-the mill kind of winter virus that so many people are getting these days?
Celine Gounder: There are hundreds of respiratory viruses; we dont test for all of them. Currently, the ones we test for most frequently are the flu, COVID and RSV, because those are the three that get people the sickest, that are most likely to land you in the hospital and to kill you. But there are many, many others. And we just dont always test for them. So sometimes its a little bit hard to know which of those others it might be.
Shawn Anderson: Curious about this, did anything happen with the average immune system during the pandemic that now makes it maybe harder to fight off a cold or some other virus?
Celine Gounder: Well, we were social distancing, we were wearing masks. And so for people who were doing that they were less exposed to other viruses. Its not that your immune system was made weaker per se, but just that it wasnt seeing those typical seasonal viruses during the period of the pandemic as much as it might have. And so now youre getting exposed to things that you hadnt been exposed to before. And you are perhaps getting sick all at once. Kind of like when you send a kid to preschool. They come home with cold after cold after cold. Its kind of like that what youre seeing now and in adults.
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The JN.1 version of the omicron covid-19 variant was first detected in Luxembourg in August and spread to numerous countries over the following months
JUN LI/Getty Images
Some of the recent news stories about covid-19 have felt reminiscent of the first two years of the pandemic. Due to a variant called JN.1 sometimes called Juno infection rates have been rising in many countries, with some initial claims that it could cause more serious illness.
But in fact, the latest figures show that in Englands current wave, people who get infected are substantially less likely
The U.S. is currently in the midst of a Covid wave, fueled by the JN.1 variant thats driving up hospitalizations and deaths across the country. For most people, however, the new variant doesnt seem to be causing worse symptoms.
Thats left many wondering whether we need to keep swabbing our nasal passages with Covid tests at the first sign of congestion or achiness? How well do at-home rapid tests work against the new variant?
Heres what to know:
Influenza and some cold viruses are circulating along with Covid. So there are good reasons to know which virus youve got, particularly if you are at higher risk of getting really sick.
Its important to know if you have Covid versus the flu versus something thats not viral at all like strep throat because they have different treatments, said Dr. Abraar Karan, an infectious disease physician at Stanford Medicine. They have different treatments, and the sooner you get treated the better outcome youll have.
For a healthy 25-year-old, there is still some utility in getting tested. If somebody in the home has a weak immune system or is fighting cancer, for example, its important to isolate if its Covid.
Remember for all these viruses or bacterial infections, contagiousness is different and how sick you may get is different. Karan said.
Joseph Petrosino, a chair of molecular biology and microbiology at Baylor College of Medicine, acknowledged that while it may not be as necessaryfor young, healthy people to take an at-home test, it can be helpful to know if its Covid in case someone ends up with lingering symptoms.
There are healthy people, runners or people who work out, who do get long Covid as well, he said. You just really never know its hard to predict just based on comorbidity factors alone.
Otherwise, for someone who is low-risk, getting a positive Covid test wont change much about treatment. Whether its Covid, a cold or flu, get plenty of rest, hydration and stay away from others.
There is no data that the JN.1 variant should have any effect on the results of an at-home rapid test, experts say.
I have not seen anything to suggest that the newer variants have evaded detection on tests, said Karan. Certainly this has happened in the past with other diagnostics earlier in the pandemic, but at this point the tests should pick up these variants.
Susan Butler-Wu, a clinical pathologist at Keck School of Medicine at the University of Southern California, said that while she hasnt seen data for this specific variant, if its anything like other variants, it wont be an issue.Rapid tests actually look for a part of the virus that is less likely to mutate and dodge the tests.
Theres always this fear that were going to have some mutation thats now going to make the tests not work, but so far thats not really the case, said Butler-Wu.
In the early days of the pandemic, before most people had some kind of immunity either after infection or from the vaccines, an individuals viral load would be highest when symptoms first appeared.
Now, the levels of virus may actually be highest a few days into the illness, according to a study published last fall in the journal Clinical Infectious Diseases from researchers at Harvard Medical School. They found that in those with pre-existing immunity, the level of virus peaks around the fourth day of symptoms.
This means that if someone tests too early in the illness, it may show up negative.
Their symptoms could be caused by their immune response, Karan said. So youre getting some inflammation and thats causing symptoms, and thats also preventing the virus from building up quite as fast, and so your initial test could be negative.
The Centers for Disease Control and Prevention still recommends testing immediately if you believe youve been exposed to Covid and are showing symptoms such as congestion, cough or body aches.
If youve been exposed but dont have any symptoms, the CDC says to wait five days.
There is a misconception that rapid tests are one and done, says Butler-Wu.
If youre symptomatic and the first one is negative, you need to repeat it, she said.
The official guidance from the CDC is that if you have symptoms, take a rapid test, and if its negative repeat it 48 hours later.
At-home rapid tests are a good way to know if someone is contagious.
Simply put, rapid tests require a higher level of virus to turn positive, and higher levels of virus typically mean somebody is more contagious.
There are some limitations to the tests, however.
Karan said that while early on in the course of the illness they can be good proxies for contagiousness, they arent as reliable at the end of an illness.
There is data where rapid tests were positive, but when they got peoples samples, the virus couldn't be cultured meaning that those people were unlikely to be contagious, Karan said.
A 2022 study from researchers at Harvard Medical School suggested that only half of people who test positive after five days are actually contagious.
After that time period, if your rapid test is positive its not a guarantee youre still contagious.
Akshay Syal, M.D.,is a medical fellow with the NBC News Health and Medical Unit.
Updated 16 January 2024
Image source, Getty Images
Nicola Sturgeon led Scotland's response to the Covid pandemic
The UK Covid inquiry is sitting in Edinburgh over the next three weeks as it focuses on pandemic decision-making in Scotland.
Key witnesses are expected to include former first minister Nicola Sturgeon.
Former health minister Jeane Freeman and national clinical director Prof Jason Leitch are also expected to give evidence.
It is the first time the hearings have taken place outside of London since it began in August 2022.
A total of 12 sessions will be held at the Edinburgh International Conference Centre (EICC) between 16 January and 1 February.
It is now almost four years since 20 March 2020, the day that schools shut down, and pubs and restaurants were ordered to close because of the risk of spreading the Covid virus.
Having questioned UK ministers and officials, Baroness Hallett and the UK Covid Inquiry team will turn their attention to the decisions made in Scotland and their impact on people here.
At the time of the first lockdown, there was a generally collaborative 'four nations' approach, but as the pandemic progressed, there was a divergence in strategy.
Nicola Sturgeon was widely praised for her clarity and holding daily briefings to update the public but she herself would often talk of Scotland taking a 'more cautious approach' to opening up again after virus restrictions.
Lawyer Aamer Anwar and Covid Bereaved relatives at the opening of the UK Covid Inquiry hearings in Edinburgh
During the London hearings we heard evidence from UK government ministers of tensions between Westminster and the devolved administrations.
Former prime minister Boris Johnston told the inquiry he feared a 'mini-EU of four nations', sending Michael Gove to lead meetings with the nations.
The former UK health secretary, Matt Hancock told Lady Hallett he did not think it logical to have devolved powers handling communicable diseases.
Prof Jason Leitch, Scotland's national clinical director, is expected to give evidence to the inquiry
And constitution expert Prof Ailsa Henderson told the inquiry that politics, and not public health, influenced some positions taken by the UK government.
In her testimony, the Edinburgh University professor said there was a "fear of leaks" from the devolved administration and the UK government perceived a "self-serving nature" to their motives.
She said the UK government never expressed the opinion that it might improve decision-making if more voices from across the UK were included.
Scotland's ability to go its own way during Covid was limited. For example, mass testing and vaccination as well as the furlough scheme, were funded and co-ordinated by the UK government.
But ministers in Scotland set rules on how many people were allowed to gather together, whether schools and businesses could open up, and where face masks were required.
So the inquiry may also probe whether political motives contributed to differing approaches in those areas, or whether distinctive Scottish decisions were based purely on alternative scientific advice.
It will likely also address the question of whether leadership was strong as it should have been at such a crucial time.
Image source, Getty Images
Scotland's chief medical officer Catherine Calderwood resigned two weeks into the lockdown in a row over visiting her second home
Rule-breaking in Downing Street and Whitehall during the pandemic is well-documented but in Scotland too, there were human failures.
Dr Calderwood has been excused from giving evidence for the foreseeable future for health reasons.
Also among the many issues the inquiry will tackle in the coming weeks will be the thorny topic of WhatsApp messages.
After some delays the Scottish government has sent 19,000 documents and 28,000 Whatsapps to UK inquiry.
In Scotland to date, more than 18,000 people have died with Covid and Office for National Statistics (ONS) analysis suggests death rates were very similar in Scotland and England and slightly better in Wales and Northern Ireland.
The ONS compared death rates during the pandemic with those seen in the five years before it.
The question the UK Covid inquiry will ask is did the different decisions in Scotland have any real impact on the virus, for better or worse?
Over the next three weeks the focus will be on key decision-making, with Ms Sturgeon expected to be called towards the end of proceedings.
Lady Hallett's inquiry will then do the same in Wales and Northern Ireland, before turning its attention to the impact of the pandemic on healthcare across the UK.
Separately, a Scottish Covid Inquiry, commissioned by the Scottish government, will continue to consider evidence after a short break.
Under its chairman, Lord Brailsford, it has started from a very different point, with the first phase of hearings taking evidence from dozens of ordinary members of the public for whom the consequences were the most devastating.
Political decision-making will instead come at the end of its schedule.
But both inquiries have a long way to go before making recommendations to ensure we are better equipped for any such event in future.
