Frequently Asked Questions

Trackers

Where can I find up-to-date information on COVID-19 cases and deaths?

Here are some trackers that track cases and deaths:

• Worldometers
• Johns Hopkins University
• STAT News
• HealthMap
• New York Times USA tracker and global tracker

Where can I find information on the status of vaccinations administered?

Here are some trackers that track COVID-19 vaccine doses administered:

• Johns Hopkins University
• Bloomberg
• Our World in Data
• New York Times
• CDC

In addition, the New York Times has a helpful tracker for many vaccine candidates as they move through different stages of development.

Where can I find information about travel restrictions and recommendations?

The WHO provides general information and recommendations on staying safe while traveling. Kayak has aggregated national-level travel restrictions in place due to COVID-19. Within the United States, CNN has aggregated state-level travel restrictions.

It is recommended that if you are planning to travel, you should specifically look for travel restrictions that apply to your origin and your destination.

Prevention

What is the rationale and evidence for mask usage?

The CDC has a useful description of the reasons to believe that mask usage is useful for preventing spread of COVID-19. To briefly summarize, it has been shown that masks (even cloth masks) can block larger respiratory droplets and reduce the spread of smaller aerosol particles, which can result in decreased transmission of the virus. In addition, masks can reduce the number of respiratory particles and droplets inhaled by almost 50%, potentially reducing the amount of virus to which an individual is exposed.

Randomized controlled trials on mask usage are difficult to conduct in the midst of a pandemic, and other trials in the past studying different infections do not well account for the effectiveness of universal community masking as opposed to the effectiveness of an individual wearing a mask. However, per the CDC source above, several lines of epidemiological evidence strongly suggest that universal mask usage results in a marked reduction in infections, even in high-risk exposure situations (e.g. close contact at a hair salon, long-haul flights, close-quarters living). For example, a recently published study from Germany estimates that face masks reduced the number of new infections there by 45%.

What types of masks are most effective?

This study looked at the ability of masks made from fabric to filter ultrafine particles, as compared to N95 masks. While it found that N95 masks were amongst the most effective types of masks, it also found that most common types of fabrics used for masks could block a large proportion of ultrafine particles, and that this proportion was even higher for masks made of layers of fabric. A mask made of cotton and fleece, for example, was roughly as effective as an N95 mask in blocking ultrafine particles. The study also found that a low number of washing cycles did not markedly reduce the effectiveness of masks, but did point out that this could decrease with repeated washing; as such, it may be important to replace masks regularly as they undergo wear-and-tear.

CDC It is important to note that N95’s are the most effective when an individual is suspected to be infected. Given the critical shortage of N95’s, the CDC states that N95’s should be conserved for medical researchers and healthcare workers.

Can wearing a mask make it harder for my child to breathe?

Cloth masks are made from breathable materials that will not block the oxygen your child needs, nor will they lead to carbon dioxide poisoning (known as hypercapnia) from re-breathing the air we normally breathe out. Carbon dioxide molecules are very tiny, even smaller than respiratory droplets. They cannot be trapped by breathable materials like cloth masks. In fact, surgeons wear tight fitting masks all day as part of their jobs, without any harm. Masks will not affect your child's ability to focus or learn in school. The vast majority of children age 2 or older can safely wear a cloth face covering for extended periods of time, such as the school day or at child care. This includes children with many medical conditions.

However, children under 2 years of age should not wear masks since they may not be able to remove them without help. Children with severe breathing problems, cognitive impairments, or another condition leading them to be unable to remove a face covering on their own may also have a hard time tolerating a face mask, and extra precautions may be needed.

Can masks interfere with a child's lung development?

No, wearing a cloth face covering will not affect your child's lungs from developing normally. Face masks blocks the spray of spit and respiratory droplets that may contain the virus, and it does not prevent oxygen from flowing in or around the mask. Keeping your child's lungs healthy is important, which includes preventing infections like COVID-19.

Can masks lead to a weaker immune system by putting the body under stress?

No. Wearing a cloth face covering does not weaken your immune system or increase your chances of getting sick if exposed to the COVID-19 virus. Wearing a cloth face covering, even if you do not have symptoms of COVID-19, helps prevent the virus from spreading.

Should I use a face shield?

Current CDC guidance does not recommend that face shields be used as a replacement for masks if it is avoidable, and it is not clear to what degree a face shield alone will offer protection. In addition, face shields should not be used on newborns or infants. With that said, face shields do offer additional eye protection that masks do not. In situations where mask usage isn’t feasible (for example, as the CDC points out, if you work with the deaf or hard of hearing), it is recommended that you get a face shield that covers as much as possible.

How risky are different activities? Should I be wiping down groceries at home?

Per the Infectious Diseases Society of America, activities can have a broad range of risks in the midst of the pandemic. Activities such as well-distanced outdoor events, going to the grocery store, or going to the doctor’s office are classified as being low-risk, especially when precautions like mask usage are taken. Going to the salon or traveling typically presents a medium risk of infection, and indoor dining or crowded recreation presents the highest risk.

The CDC suggests that food packaging does not present a high risk of COVID-19 transmission; nonetheless, it’s still recommended to wash your hands and disinfect your table and counter after unpacking groceries, especially if coming from a grocery store trip.

What can I use to clean and disinfect surfaces?

The CDC maintains a list of specific recommendations on how to clean different types of surfaces to prevent COVID-19. The EPA also maintains a list of cleaning supplies and general instructions for cleaning and sanitizing.

Vaccines

How can I find resources to help me find and schedule a vaccine appointment?

We have listed several resources for finding resources for a wide range of countries and states here!

Where can I find information about the mechanism and progress of vaccines?

The New York Times runs a vaccine tracker with brief descriptions of the mechanism of action of each of the vaccine candidates and where they are in the testing and approval process.

For a more detailed and more technical description of how the different vaccine candidates work, In the Pipeline has a good description of what each vaccine candidate does. (This particular page is not updated regularly, but the descriptions are nonetheless useful.)

How is it possible to create a safe vaccine in such a short period of time?

Several factors enabled rapid development and testing of vaccines without compromising safety or efficacy.

First, previous research has enabled us to reduce the time necessary to begin developing and testing a vaccine candidate. Advances in vaccine technology have allowed researchers to develop vaccines based only on the genomic sequence of the virus in question (released on Jan 10th). As such, vaccine scientists were able to begin development of vaccine candidates in mid-January, even though the virus was still difficult to obtain at that time.That said, due to global spread of the virus in the following months, laboratories around the world have independently isolated and generated stocks of virus that then could be used to test vaccine efficacy.

In addition, we have considerable existing research on other human coronaviruses, including SARS-CoV and MERS-CoV, that we were able to use to gain rapid insight into SARS-CoV-2. Ordinarily, pharmaceutical companies would wait for more basic research into the novel virus to develop a vaccine with best chances at high efficacy, in no small part due to the high cost of running clinical trials and bringing a vaccine to market. In this case, however, governments around the world were willing to underwrite significant portions of the costs of clinical trials, reducing the financial risk for pharmaceutical companies to develop and produce a vaccine without preliminary data, but heavily leveraging existing research into coronaviruses. These two factors likely reduced the timeline required for vaccine development by months to years.

Second, administrative delays in the vaccine-development timeline were mitigated or outright eliminated during the development of the COVID-19 vaccine candidates. One of the most important such delay is the processing of data and applications between phases of trials or after a trial is complete. For example, just for the formal new drug application stage alone, the United States Food and Drug Administration (FDA) has a target of 8 months to process and review priority applications, with a target of 12 months for regular applications; delays beyond this timeframe are not uncommon, and the new drug application is only one of several intermediate applications that are needed to progress through different phases of clinical trials. By contrast, the applications to progress through clinical trials for the COVID-19 vaccine candidates are being processed and analyzed in a more timely manner by regulatory agencies -- again, shaving unnecessary months to years off the approval timeline.

Third, the nature of the pandemic makes the clinical trials easier to conduct. One of the most difficult and time-consuming tasks for a vaccine or drug candidate is to show superiority over existing drugs or vaccines that are on the market already; however, there were no existing vaccines against COVID-19, so the vaccines simply needed to be tested for superiority over a placebo. In addition, clinical trials often have difficulty enrolling subjects; it normally takes months to years to fully enroll a clinical trial. However, with the number of individuals that wanted to join each of the vaccine trials, enrollment was completed with unprecedented speed. Finally, trials for vaccine candidates often take a long time to complete even after enrollment because many of the pathogens they seek to prevent are relatively rare or regional; as a result, it takes considerably longer for enough infection events to occur, and accordingly longer to be able to determine whether the vaccine is effective. However, in the midst of a global pandemic, infection events are in no short supply, and by sheer numbers, people are infected rapidly in the trials and statistical significance can be reached much more quickly. Again, collectively, these factors reduce the needed timeline by months to years without sacrificing rigor.

Despite this speed, we are still able to effectively judge whether these vaccine candidates will be safe. We have considerable knowledge of the fundamental biology underlying many of these vaccine candidates that allow us to better judge their safety, and after confirmation of their safety, human studies using RNA as therapeutic, both for vaccines, and in other ways to treat diseases are underway since years. Although mRNA vaccine are yet to be approved by the FDA for use in humans (in large part due to low cost-benefit to companies), the molecular biology of mRNA has been studied extensively for decades, and knowledge of the biological pathways involved with mRNA processing and degradation allows us to state with a high degree of confidence that the active component of the vaccine will be degraded quickly and poses no increased risk of causing genetic aberration. (Of note: an infection with the real virus or withany other common cold RNA virus, will generate vastly more viral mRNA in the body's cells than the vaccine carries.) This was borne out in the animal studies of the Pfizer and Moderna vaccines, which found their vaccines did not cause toxicity in animals and conferred immunity against the virus. In addition, the most prominent vaccine candidates (mRNA and adenovirus vectors) do not contain the whole genomic sequence of the SARS-CoV-2 virus or even an attenuated/inactivated version of the SARS-CoV-2 virus, meaning that they present no risk of actually causing COVID-19.

The trials are also sufficiently long (even with all this streamlining) to be able to catch adverse events that would occur with any significant frequency. Indeed, the vast, overwhelming majority of adverse events after vaccination present within days to weeks of vaccination. For example, the very rare, but one of the most severe possible side-effects, Guillane-Barre syndrome (GBS) almost always arises within 6 weeks of receiving the influenza vaccine; other adverse reactions due to vaccines present similarly quickly or even sooner. This timeframe for adverse events to appear is markedly shorter than the time for evaluation of the vaccine candidates. The FDA, for example, mandated that the subjects in the trial had to be monitored for a median of at least two months before an emergency use authorization application would be considered. This enables regulatory agencies to adequately assess the safety profile of the vaccines. In clear contrast, the viral infection carries significant side-/chronic effects for a large number of people, and without vaccine immunity, at least 50-70% of individuals would be infected without indefinite public health measures.

In addition, to monitor for any safety events that may occur, the United States has a long-standing robust vaccine safety monitoring system that has been operating for decades. In particular, for the COVID-19 vaccines, there will be expanded safety monitoring, including a new smartphone-based health checker for people who receive the COVID-19 vaccines. In this way, in the extremely unlikely event that problems caused by the vaccine occur in any significant numbers, it will be detected quickly.

It's also important to remember that unlike many drugs, which are taken at regular intervals for long periods of time, vaccines are only administered at infrequent intervals and only once or twice for a given vaccine. This is why many drugs need to be tested for years to establish side effect profiles; the consistent concentrations of the drugs over a long period of time can cause harm, which can present years after first starting the medication. Vaccines, on the other hand, are rapidly cleared, meaning that they do not stay in the body for long periods of time and are thus highly unlikely to cause issues that present after more than a few weeks.

To summarize, the development of these vaccines has not been this rapid because we have cut corners or sacrificed rigor. Moreso, these trials have progressed at a rapid pace because of pre-existing research and technology that could be leveraged to develop a vaccine candidate quickly, policy decisions to mitigate usual administrative delays, and the impact that rapid spread of a novel pathogen has on the logistics of a clinical trial. Collectively, these factors have comfortably reduced the development timeline by years while still allowing for sufficient assessment of efficacy and safety.

Why are existing vaccine testing paradigms useful for testing safety of mRNA vaccines?

In general, we can think of vaccine-related side effects as being either directly due to the components themselves or as the result of the body’s reaction to the vaccine components.

The first one is going to be a fear of a side effect from direct action of the mRNA molecules itself (or the lipid nanoparticles, but liposomal formulations of drugs are not uncommon, so that's not particularly new). That is unlikely to happen as a direct result of the mRNA after any significant period of time; as we know from decades of mRNA research, mRNA is so unstable that it doesn’t survive for a long time at physiological conditions. Rather, it is rapidly degraded and cleared and poses little risk of having some sort of side effect "pop up" later on. As such, the mRNA itself is overwhelmingly unlikely to cause issues that don't show up immediately.

The second question is on delayed issues that occur because of the body's reaction to the mRNA; essentially, we're thinking about autoimmune reactions here. As noted above, the vast majority of those cases will present within weeks of immunization, if they occur at all; the likelihood that we see an unforeseen autoimmune reaction in any significant numbers long after the vaccine is given out is very small. It's also worth remembering that these mRNA molecules encode for a protein already encoded by SARS-CoV-2, and to date, we haven't seen a massive rise in autoimmune reactions from that virus beyond that which we would expect for a widespread viral infection. To that end, if this vaccine causes a widespread problem in the future (which, again, is very unlikely), it would be reasonable to suspect this hypothetical adverse event would occur from natural infection as well.

In summary, the delivery system may be relatively new (although it's been used before in investigational drugs and has decades of underlying research, as noted in the post body), but the underlying biology of adverse effects is pretty similar to that of other vaccines.

Can/Should those who have had a previous SARS-CoV-2 infection wait to get vaccinated?

It is expected that all persons in the phased risk categories, regardless of prior infection, will be eligible for vaccine. It is also anticipated that vaccination will be recommended regardless of prior infection. While vaccine supplies are constrained, vaccination of persons with recent prior infection may be delayed; however, the duration of protection after infection is unknown.

What immediate reactions can present after getting a vaccine, and what is anaphylaxis?

Two types of reactions are most likely to present immediately after getting a vaccine. The first are anxiety-related reactions, including fainting (i.e. vasovagal syncope), hyperventilation, and breath-holding. These are by far the most common types of immediate reactions to vaccines and virtually always resolves uneventfully with little additional medical support. The second are true allergic reactions, including anaphylaxis or other immediate hypersensitivity reactions to the vaccine components or its container. These are much rarer than anxiety-related reactions.

Anaphylaxis is a rare but serious allergic reaction to foreign antigens. This reaction occurs with an estimated frequency of 1.3 episodes per million vaccine doses administered. Notably, in many cases, anaphylaxis is preventable; in all cases, it is treatable.

Signs and symptoms of anaphylaxis can include:

• Sudden skin rashes, redness, hives, and itching
• Breathing difficulty, swollen lips and tongue, runny nose, cough
• Low blood pressure (hypotension), dizziness, fainting
• Sweating, paleness, nausea, vomiting, abdominal pain
• Uneasiness, sleepiness, altered mental status including loss of consciousness (less common)

Pre-vaccination screening includes screening for a history of anaphylaxis and identification of potential risk factors such as allergies to food, medicines, or prior vaccines. Questions about possible allergy to any component or container of the scheduled vaccines help identify if the vaccine should not be given to the individual. If you have questions about your risk of anaphylaxis or other allergic reactions when receiving the vaccine, please contact a qualified and licensed medical provider in your area. Most episodes of anaphylaxis begin within minutes after vaccination. Therefore, a person getting the vaccine is typically asked to stay on the premises for 10-15 minutes after getting the vaccine. If the person develops the signs and symptoms of an allergic reaction, immediate treatment can be given if they are already on the premises. If medical care is not available at hand, call for emergency medical assistance immediately. Someone should stay with the affected individual at all times until medical professionals can provide care. Trained medical practitioners can medically assess the patient, identify if the patient is experiencing a true anaphylaxis episode, and administer medications as appropriate.

What do we know about the ability of the vaccines to prevent transmission of the virus?

Transmissibility of the virus was not one of the endpoints of the Phase 3 clinical trials for the vaccines. In other words, the trials were set up to determine whether the vaccine prevented infection or symptomatic infection (depending on the trial), not whether the infected individuals could transmit the virus to others -- in no small part because such an endpoint would be challenging to rigorously test in the context of a Phase 3 clinical trial.

As such, we do not have definitive evidence one way or another to suggest that the vaccine confers protection against transmission of the virus, and to that end, the pharmaceutical companies are not yet able to legally say that their vaccines prevent transmission. Further research is needed to reach a conclusion. However, experience from past vaccinations would suggest that it is more likely than not that a vaccinated individual will at least show a reduction in viral transmission.

What do we know about the use of the vaccines in pregnant women?

Pregnant women were not explicitly studied in the Phase 3 clinical trials and, as such, we do not definitively have positive or negative evidence on the safety and effectiveness of the vaccine in pregnancy. These studies will be conducted with dedicated trials and post-marketing studies. This does not mean that we know or even believe the vaccine will be unsafe or ineffective in pregnant women; we simply don’t have any evidence yet. There is no reason to believe that the vaccine will impact fertility.

Are there any data from volunteers who happened to get pregnant or who were breastfeeding during vaccine trials? Any effects of COVID vaccine on pregnancy, the developing fetus, or infants?

No pregnancy related data have yet been released. Typically, in large trials, there are some inadvertent pregnancies. They will be followed for birth outcomes. Especially because the vaccines candidates are not live-virus vaccines, pregnancy and breastfeeding will probably not be contraindications to receiving COVID-19 vaccine; however, there is no safety data in the pregnant woman, her fetus or infants at this time. While these vaccines were not specifically tested in breastfeeding women, it is not likely (based on the mechanisms of action of the vaccines in US trials) that there would be any risk to the child.

What is the current status of COVID-19 vaccine research in children and adolescents?

To date, Pfizer has enrolled children down to age 12 and submitted its EUA for vaccination indications down to age 16. Moderna is about to start a similar study, as is Janssen. Astra Zeneca has approval to enroll children in the UK, ages 5-12, but has not yet enrolled any children in the US. We anticipate that studies including younger children will begin soon (perhaps over the next couple of months).

The president of the American Academy of Pediatrics (AAP), Dr. Sally Goza, issued a letter to federal health officials in October urging them to include children in vaccine safety and efficacy trials. Until these data are available as a result of the trials, there will be a significant delay in when children are able to access the COVID-19 vaccines.

Children are much less likely than adults to have severe disease from COVID-19, so why do they need to be vaccinated?

COVID-19 can cause significant illness in children. In children for whom COVID-19 caused serious illness, half had an underlying condition, and half did not. This is similar to influenza. We need to vaccinate children because we do not know which children may be at higher risk of serious, possibly life-threatening illness. Children can also transmit the virus, including to more vulnerable adults who are in their family or in their school, so it is important that children be included in the vaccine distribution in order to reduce community spread.

Will the COVID-19 vaccine be required for school entry?

When a vaccine is shown to be safe and effective in children, health authorities, including the CDC and the AAP, will make recommendations on when and how children should receive the vaccine. However, it is a state government decision which vaccines are required for school entry. Those decisions could vary by state.

Do we need to worry about an increase in MIS-C in kids receiving COVID-19 vaccine?

One of the reasons to perform vaccine trials in children is to make sure that they do not have any side effects that are pediatric-specific. Since there are also cases of MIS-A, in young adults, if MIS were to be a problem, we may see it in the larger adult trials. We have not, to date. There is no known biomarker to predict an immune response that leads to MIS-C. It is also possible that protection from COVID-19 by vaccination will also protect against its sequelae, including MIS-C.

Would you still recommend continuing full precautions after vaccination until community immunity is reached?

Yes! We will need to continue to practice physical distancing, wearing cloth face coverings and masks, and using PPE during medical encounters for some time after the vaccine is introduced. It will be some time before there is evidence that the vaccines not only prevent illness in the person who is vaccinated, but also prevent them from transmitting the virus. Even more pressingly, it will be a significant amount of time until large proportions of the population are vaccinated against COVID-19. Until then, we will need to practice these public health measures.

Do the vaccines contain animal products?

The Pfizer, Moderna, and AstraZeneca COVID-19 vaccines do not contain animal products, including pork.

Virology

Where are the best places to look for data about the virus?

LitCovid, NIH National Library of Medicine’s “curated literature hub for tracking up-to-date scientific information about the 2019 novel Coronavirus”.

Vincent Racaniello’s virology blog and accompanying podcast.

The Program for Monitoring Emerging Diseases, (ProMED), an internet service from the International Society for Infectious Diseases (ISID) to identify unusual health events related to emerging and re-emerging infectious diseases.

ViralZone, a Swiss Institute of Bioinformatics (SIB) web-resource for all viral genus and families, providing general molecular and epidemiological information, along with virion and genome figures.

COVID-19 Resource Center from the Center for Infectious Disease Research and Policy (CIDRAP).

How closely related is SARS-CoV-2 to other pathogenic coronaviruses?

Bats are reservoirs for a diverse range of coronaviruses, including but not limited to predecessors of MERS, SARS-CoV, and SARS-CoV-2, all of which are pathogenic and have caused outbreaks in humans. The immune systems of bats, unlike those of humans, are not geared towards clearance but rather tolerance of viruses. This allows them to live in concert with a number of viruses at once without experiencing negative health outcomes. Because of this, they are a frequent source of virus spillover from non-human animals to humans, typically through an intermediate host like palm civets as seen in SARS-CoV. The intermediate host of SARS-CoV-2 is still being sought out at the time of this writing, but investigations in wild bats to identify closely related coronaviruses in bats is ongoing. So far, candidates for this bat progenitor virus have been identified in both Japan and Cambodia

What is currently known about the SARS-CoV-2 variant that was recently described in the United Kingdom?

This section described a relatively recent finding and will be updated as more data is available.

This variant, termed the B1.1.7 variant of SARS-CoV-2 was found to be rapidly spreading across the United Kingdom as of late November and December. Though much more study is needed to definitively determine the effect of this variant on the course of the outbreak, there are some tentative and early findings. Per the government of the United Kingdom, it is believed that this new variant is markedly more transmissible than the other forms of SARS-CoV-2 in circulation, with some estimates suggesting an increase in transmissibility of roughly 70%. Though further study is needed, it is currently not believed that this variant causes more clinically severe COVID-19 than do other forms of the virus. In addition, though data largely does not exist to this point, there is no evidence suggesting that the variant is less susceptible to current vaccines and vaccine candidates than are the other forms of the circulating virus, and it is highly unlikely that this variant would render the vaccines largely ineffective.

Disease

What are the symptoms of COVID-19?

Per the CDC and the Mayo Clinic, and work in the Lancet, a person infected with COVID-19 typically begins to show symptoms around 5-7 days after infection, although symptoms presentation can range from 2-14 days post exposure. Patients with COVID-19 typically first experience a viral-type illness known as a “prodrome” with symptoms similar to the influenza. These symptoms include respiratory tract infection (eg, sore throat, runny nose, cough), lost of taste or smell, fevers, chills, headaches, muscles aches (e.g. fever, chills, headache, myalgias), or gastroenteritis (eg, nausea, vomiting, diarrhea). Recovery depends on infection severity and several other factors. Most people recover ranges from after several days to several weeks.

When should I seek medical attention?

We cannot provide medical advice or provide a full list of situations in which you should seek medical attention; in general, if you are concerned about your symptoms, you should speak with a qualified and licensed medical provider to seek their opinion.

The CDC recommends that you should seek emergency medical attention at once if you develop any of the items on the following (non-exhaustive) list of symptoms:

• Trouble breathing
• Persistent chest pain or pressure
• New onset of altered mental status, including confusion or loss of consciousness
• Inability to wake up or stay awake
• Bluish lips or face

What are the different types of COVID-19 tests, and how do they work?

There are three types of commonly used COVID-19 tests: nucleic acid tests (NATs), antigen tests, and antibody tests.

NATs are diagnostic tests that specifically detect SARS-CoV-2 genetic material in the sample, which acts like a fingerprint for any organism. The most commonly used NAT is the polymerase chain reaction test (RT-qPCR), which uses a highly specific reaction (real-time PCR using TaqMan probes) to measure whether genetic material (if any) is amplified in the PCR reaction, resulting in a quantitative measurement of viral genome copies in the sample. This test is highly specific, meaning that they have a very low rate of false positives, although they cannot differentiate between infectious or “dead” virus. Other NATs include isothermal amplification tests (“LAMP”), or direct nucleic acid detection using CRISPR/Cas13 systems (“Sherlock”). These tests are also amongst the most sensitive tests for COVID-19, meaning that typically have the fewest false negatives. However, this is very dependent on when the test is taken (see below: “When is the best time to get a test for accurate results?”).

Antigen tests are diagnostic tests that work by detecting the proteins that the virus produces, much like rapid strep tests. These tests tend to be less sensitive than NATs, particularly for asymptomatic individuals or individuals with lower viral loads. As such, a negative antigen test should not be taken as a definitive negative diagnosis. However, these tests have the advantage of being faster to run than NAATs, and do not trigger as often on “lingering” viral debris.

Antibody tests are serological tests that determine whether you have antibodies against SARS-CoV-2 in your blood serum. These are not typically used as diagnostic tests; because of the delay in generation of detectable levels of antibodies in the body during infection, their clinical usage is very limited. In addition, the sensitivity and specificity of serological antibody tests can vary widely depending on the test used and the timing of testing. Notably, antibody tests themselves do not indicate immunity or a lack thereof ; cross-reactivity (which does not necessarily imply cross-protection) with related viruses is rather common, so a positive antibody test could very reasonably represent a false positive, and a negative antibody test does not inherently rule out immunity at levels not detectable by that particular test (or other forms of immunity).

When is the best time to get a test for accurate results?

The sensitivity of COVID-19 NATs appears to be the highest 5-8 days following exposure. The same study suggested that onset of symptoms roughly corresponded with this timeframe, which may indicate that testing will be most sensitive after symptom onset. Antigen tests typically are most accurate after symptom onset and may fail to detect the virus in asymptomatic or presymptomatic individuals.

When is an infected individual most infectious?

Per recent work in the Lancet Microbe, individuals with COVID-19 are most infectious in the first week following infection (including while presymptomatic), with infectiousness peaking at approximately the fifth day of illness, near the onset of symptoms. None of the studies analyzed in this meta-analysis were able to find patients with live virus after 9 days of illness, even though the NAAT viral loads would often remain high after that time.

How long should I isolate following a positive test and/or onset of symptoms?

Per CDC guidelines, individuals that test positive for COVID-19 and never develop symptoms may discontinue isolation 10 days after the first positive test.

Individuals that test positive for COVID-19 and develop symptoms may discontinue isolation once all of the following criteria are met:

• At least 10 days have passed since symptom onset
• At least 24 hours have passed without a fever WITHOUT use of fever-reducing medications (such as NSAIDs or acetaminophen)
• Other symptoms of COVID-19 have improved.

Most individuals are no longer required to receive a negative test to discontinue isolation so long as the above criteria are met; however, in some situations, the treating physician may recommend waiting for a negative test result.

What is CFR and IFR?

The case fatality rate (CFR) is the proportion of deaths amongst diagnosed cases of the disease (which generally primarily includes symptomatic infections), whereas the infection fatality rate (IFR) is the proportion of deaths amongst all people infected with the disease (including non-diagnosed and asymptomatic infections). The CFR is highly dependent on the prevalence of testing and will thus by definition be higher than the IFR; the IFR, on the other hand, has to estimate the proportion of asymptomatic infections or total number of infections in order to compute the mortality across all infections.

What is the IFR of COVID-19?

A recent meta-analysis of several studies on the IFR of COVID-19 suggested a mean IFR of 0.68%. However, it is important to note that the IFR of COVID-19 is highly age-dependent another meta-analysis ranging from 0.01% or lower for the <24 years old to >1% for >65 years old.This IFR appears to be from 3x (for 30 years olds) to >10x higher (for 54+ year olds) than for seasonal influenza (source).

Who is most at risk of severe COVID-19 infection?

The science on risk factors predisposing to severe infection is still evolving. However, in general, elderly individuals tend to be at high risk of poor outcomes from COVID-19. Per the CDC, some groups of individuals of any age are at higher risk of severe illness. This includes individuals with:

• Cancer
• Chronic kidney disease
• Lung conditions: COPD, smoking
• Heart conditions
• Immunocompromised states secondary to solid organ transplantation
• Metabolic conditions: Obesity, severe obesity, type 2 diabetes mellitus
• Sickle cell disease
• Pregnancy

In addition, several groups of individuals may be at higher risk of severe COVID-19 illness. This group includes individuals with:

• Lung conditions: Asthma, cystic fibrosis, pulmonary fibrosis
• Cerebrovascular (e.g. stroke, TIA) or neurological conditions
• Hypertension
• Immunocompromised states (not due to solid organ transplantation)
• Metabolic conditions: Overweight, type 1 diabetes mellitus
• Liver disease
• Thalassemia

What are the similarities and differences between COVID-19 and seasonal flu?

The CDC has an excellent summary on similarities and differences between COVID-19 and the seasonal flu. To summarize some of the important points:

• COVID-19 has a higher rate of severe illness than does seasonal flu, especially in older populations.
• Individuals with COVID-19 are contagious for longer than they are with flu (roughly 12 days vs. 7 days, respectively).
• COVID-19 seems to be more contagious and present a greater risk of superspreading events than does flu.

Control of influenza without widespread social distancing is easier for those reasons; influenza appears to be less contagious and presents a lesser risk to individuals than does COVID-19. In addition, vaccines for influenza are widely available, which helps prevent severe disease and reduce spread of the virus to the point that the healthcare system can manage seasonal spread of influenza.

What are some of the treatments available for COVID-19?

This section should not be taken as medical advice; it is not meant to offer advice on what you should do if you are ill or suspect you are ill. If you have questions on your medical regimen, please speak to a qualified and licensed medical professional in your area.

The primary treatment for most cases of COVID-19 is supportive treatment, including fever reduction, hydration, and rest. The use of NSAIDs (e.g. ibuprofen) in COVID-19 was initially controversial, but at this time, it does not appear that NSAIDs worsen COVID-19 outcomes. As such, the U.S. National Institutes of Health, European Medical Agency, and World Health Organization-in-patients-with-covid-19) do not recommend avoiding NSAIDs when appropriately used for management of COVID-19.

Treatments for higher acuity COVID-19 infections are an active area of investigation. Below is a brief summary of some of the different therapies under investigation.

• Remdesivir: Remdesivir has been approved for use in hospitalized individuals with COVID-19 aged 12 years and older. The efficacy of remdesivir is murky and varies between large studies; amongst the biggest randomized trials of remdesivir are the SOLIDARITY trial, which showed no significant benefit from remdesivir, and the ACTT-1 trial, which showed a significantly decreased time to recovery with remdesivir treatment.
• Glucocorticoids: Dexamethasone is currently believed to be effective in treating individuals with COVID-19 on oxygen or ventilator support, as described by the RECOVERY trial. Studies to assess the role of other glucocorticoids, including hydrocortisone and methylprednisolone, are ongoing.
• Immunomodulators: IL-6 receptor antagonist tocilizumab may be effective for treating some COVID-19 cases; though a trial published in the New England Journal of Medicine suggested that tocilizumab is not effective for treating moderately ill patients, a recent press release by the REMAP-CAP trial suggested that it may prevent worsening in critically ill ICU patients. The role of other immunomodulators in COVID-19 remains under investigation.
• Antibody therapies: The FDA has granted emergency use authorization to several monoclonal antibody drugs to treat mild-to-moderate cases of COVID-19 in hospitalized patients. These drugs include banlanivimab, casirivimab, and imdevimab.

What are some of the long-term sequelae of COVID-19, and what is known about “long COVID?”

In a longitudinal study of COVID-19 outcomes after infection in the general population, it was found that more than 85% of individuals recovered fully from COVID-19 within 28 days of symptom onset; only 2.3% of individuals still reported symptoms of COVID-19 after 12 weeks. The degree to which this is unique to COVID-19 as opposed to representing a more stereotyped post-viral syndrome is not yet known, nor is it known how long these symptoms will last in the subset of individuals with “long COVID.”

With regards to long-term sequelae of COVID-19, a study describing the clinical course of hospitalized COVID-19 patients after discharge found that amongst survivors, a relatively large proportion (10-30%) reported some adverse outcome in the 60 days after discharge, be it physical, emotional, or financial, consistent with previous studies on non-COVID-19 patients hospitalized with sepsis or severe respiratory illnesses.

Several studies have suggested that there are some changes seen in imaging or pathology of various tissues in COVID-19; however, the degree to which these laboratory or imaging findings are clinically significant remains unclear. For example, several studies have suggested an association between COVID-19 infection and myocardial inflammation; these studies have collectively indicated that COVID-19 may cause damage to the cardiac tissues. However, myocarditis is not unique to COVID-19, and the frequency with which such heart damage occurs is unclear, as is the clinical significance of these findings -- it isn’t known whether these signs of cardiac damage would persist or present functional impairment to the patient.

To summarize, it appears that much like any other serious infection, COVID-19 can cause adverse effects that persist beyond the acute phase and may present an ongoing morbidity. However, the nature, frequency, and prognosis of these different sequelae remains unclear.

Pregnancy and Breastfeeding

What is the current evidence about newborn risk for COVID-19?

Of the 4,300 newborn cases reported to the Perinatal COVID-19 Registry, approximately 1-3% of infants born to a mother who tested positive for COVID-19 near the time of delivery have tested positive within the first 4 days of life. Vertical transmission from mother to baby leading to symptomatic disease occurs rarely, and those requiring respiratory support were only seen in preterm infants.

Can COVID-19 be passed through breastfeeding?

Active COVID-19 (virus that can cause infection) has not, to date, been detected in the breastmilk of any mother with confirmed/suspected COVID-19. It appears unlikely, therefore, that COVID-19 would be transmitted through breastfeeding or by giving breastmilk that has been expressed by a mother who is confirmed/suspected to have COVID-19.

What are the current recommendations on breastfeeding in the context of the COVID-19 pandemic?

The AAP strongly supports breastfeeding as the best choice for infant feeding. Several published studies have detected SARS-CoV-2 nucleic acid in breast milk. Currently, however, viable infectious virus has not been detected in breast milk. One study demonstrated that pasteurization methods (such as those used to prepare donor milk) inactivate SARS-CoV-2. It is not established whether protective antibody is found in breast milk. Given these findings and uncertainties, as well as established short-term and long-term benefits, direct breastfeeding is encouraged at this time.

Breastfeeding protects infants from infection. Human milk has natural bioactive factors, antibodies, and targeted immunologic mediators; although the effects on SARS-CoV-2 infection are not currently known, breastfed infants are less likely to develop other viral infections. In addition to other maternal and infant health benefits, the release of oxytocin during breastfeeding promotes maternal wellness and relieves stress and anxiety. Breastfeeding is also sustainable, which is particularly important during a time of potential shortages of formula, bottles, and other feeding supplies.

In all socio-economic settings, breastfeeding improves survival and provides lifelong health and development advantages to newborns and infants. Breastfeeding also improves the health of mothers. In contrast, transmission of COVID-19 through breastmilk and breastfeeding has not been detected. Currently, there is no reason to avoid or stop breastfeeding in regards to COVID-19.

What are the guidelines for breastfeeding after a positive maternal COVID-19 test?

Although challenging in the home environment, mothers who test positive for COVID-19 should maintain a reasonable distance from their infants when possible and use a mask and hand hygiene when directly caring for the infant. Safety precautions can be stopped when the following have been noticed:

1. Mother is afebrile for 24 hours without use of antipyretics;
2. At least 10 days have passed since symptoms first appeared, and
3. Other symptoms have improved.

For mothers who want to breastfeed directly:

Encourage proper hand washing with soap and water prior to handling the infant and advise the mother to wear a mask while nursing. Holding the baby skin-to-skin helps with latching and hormonal responses that trigger milk release. When not nursing, the infant can be cared for by a healthy caregiver, if available, and/or maintained in a separate room or at least 6 feet away from the mother. Once the mother has met time and symptom-based criteria for being noncontagious, these precautions can be discontinued.

For mothers who wants to express her milk:

Prior to expressing milk, the mother should put on a mask and thoroughly clean her hands as well as any pump parts, bottles, and artificial nipples. Optimal milk expression is facilitated by use of an efficient electric double pump. She should express milk as often as her baby is eating or at least 6 to 8 times per 24 hours. The mother can use her hands for simultaneous breast massage/compression during pumping to improve milk flow, breast emptying, and likely calorie content of her milk. The expressed milk can be fed to the infant by a healthy caregiver. Support should be provided to the mother to reintroduce direct breastfeeding when she is well.

Pediatrics

What are the current guidelines on return to sports after COVID-19 infection?

Per the CDC and the AAP, re-engaging in sports has both physical and psychological benefits. Physical activity and exercise improve cardiovascular health, strength, overall fitness, and decreases the risk of obesity and diabetes. Socializing with friends and learning a routine schedule is beneficial for development growth and prevention of mental health conditions.

Determining the best approach requires weighing the benefits of sports activity against the risk of infection. Current data indicates that children and adolescents can become infected and are less likely to be symptomatic and less likely to have severe disease resulting from SARS-CoV-2 infection. It appears that children younger than 10 years may be less likely to become infected and less likely to spread infection to others, although further studies are needed. More recent data suggest children older than 10 years may spread SARS-CoV-2 as efficiently as adults. As COVID-19 continues to impact our everyday lives, the data will be updated as more information becomes available.

In summary, deciding on the return of sports activity is complicated by many contributing factors and requires thorough communication among health organizations, youth sports organizations, the school, and most importantly, the family.