COVID-19 and SARS-CoV-2 Explained: A Patient's Guide to the 150 Questions Answered by Allergy and Immunology Experts

Table of Contents

• Key Points
• Introduction: The COVID-19 Pandemic and Why This Research Matters
• How This Expert Review Was Conducted
• Key Findings at a Glance
• Section 1: Understanding the Virus (Virology)
• Section 2: How the Immune System Responds to SARS-CoV-2
• What These Findings Mean for Patients
• Limitations of the Current Evidence
• Recommendations for Patients
• Frequently Asked Questions
• Source Information

Key Points

• COVID-19 symptoms range from none to severe pneumonia; 10-20% of patients need hospitalization and 2-4% need ICU care.
• The virus uses ACE2 receptors to enter cells, with help from TMPRSS2 and TMPRSS4 enzymes.
• The virus stays in respiratory samples a median of 18 days, longer in severe cases than mild ones.
• The fecal-oral route is unlikely to spread COVID-19, even though the virus can be found in stool for up to 22 days.
• Antibody responses vary widely, so antibody tests must be interpreted cautiously.

Introduction: The COVID-19 Pandemic and Why This Research Matters

The first cases of coronavirus disease 2019 (COVID-19), caused by a novel virus called severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2), were reported in China in December 2019. Within months, the disease had spread worldwide and was officially declared a pandemic. At the time this review was written, approximately 6.5 to 6.8 million confirmed cases of COVID-19 had been reported globally, with nearly 400,000 related deaths.

These numbers, while staggering, likely undercount the true scale of the pandemic. The authors explain that the actual number of infections is probably higher due to limitations of diagnostic tests, differences in how much each country tests and reports, and the type and timing of community mitigation strategies adopted by different nations.

COVID-19 presents with a wide range of symptoms. Like many viral infections, it can be subclinical (no noticeable symptoms), mild, moderate, or severe.

• Approximately 10-20% of patients require hospitalization
• Approximately 2-4% require intensive care unit (ICU) treatment
• Many patients develop pneumonia, while others do not
• Asymptomatic cases are common, though no clear percentage has been established yet

COVID-19 is considered a zoonosis, meaning it jumped from animals to humans. The authors state that it will be practically impossible to eradicate SARS-CoV-2 without vaccination. The key challenge going forward is learning how to cope with this virus, as COVID-19 is becoming a major cause of illness and death in many countries. The main goal of this review is to provide short, evidence-based answers to pressing questions about virology, immunology, diagnostics, epidemiology, and treatment, with particular attention to managing allergic diseases during the pandemic.

How This Expert Review Was Conducted

This review was not a single laboratory study but rather a compendium, or collection, of answers to over 140 (described as 150 in the title) pressing questions formulated by young clinicians and scientists. These questions were answered by a group of expert scientists and physicians, mainly from the European Academy of Allergy and Clinical Immunology (EAACI), representing institutions across Europe, North America, Asia, and Australia.

The answers are organized into nine major sections:

1. SARS-CoV-2 virology (the virus itself)
2. Immunology of COVID-19 (how the immune system responds)
3. Diagnosis of COVID-19
4. Organization of allergy outpatient clinics and laboratories during the pandemic
5. COVID-19 and allergic disease (including asthma, eczema, and drug allergies)
6. Treatment of COVID-19
7. Clinical trials and drug discovery
8. Vaccine development
9. Epidemiology and environmental factors

The authors note that all information is expected to be updated as new evidence emerges. The COVID-19 situation is evolving rapidly, and basic and clinical research on COVID-19-related topics must be based on more coordinated, high-quality studies.

This patient guide focuses on the detailed sections provided in the original text, specifically the virology of SARS-CoV-2 and the early immunology findings, while summarizing the broader scope of the review.

Key Findings at a Glance

• Symptoms can vary enormously — from no symptoms at all to severe pneumonia requiring intensive care (2-4% of patients)
• The virus uses the ACE2 receptor to enter human cells, with help from enzymes called TMPRSS2 and TMPRSS4
• The virus stays in respiratory samples for a median of 18 days — and significantly longer in severe cases (21 days) than mild ones (14 days)
• Three viral strains (A, B, and C) have been identified, and the virus continues to mutate
• Antibody responses vary widely — some studies show antibodies peaking at 17-19 days, while others report seroconversion taking up to 50 days
• The fecal-oral route is unlikely to spread the disease, even though the virus can be detected in stool for up to 22 days

Section 1: Understanding the Virus (Virology)

Where did SARS-CoV-2 come from?

The coronavirus family has caused other zoonotic diseases in the past, including Middle East Respiratory Syndrome (MERS). While a direct animal ancestor of SARS-CoV-2 has not been identified, the virus is closely related to β-coronaviruses found in bats and pangolins, which are likely its original reservoir. The virus may have developed through selection in the animal host, followed by transfer to humans (zoonotic transfer) and further mutations as it spread from person to person.

During undetected human-to-human transmission, the virus likely mutated to optimize the binding of its spike protein to human ACE2 receptors — the "doorway" the virus uses to enter cells. Importantly, the authors stress that available genetic data on SARS-CoV-2 do not show evidence of intentional human manipulation of the virus. In other words, the virus was not engineered in a laboratory.

What are the strains of SARS-CoV-2?

Three SARS-CoV-2 variants have been identified — named types A, B, and C — which differ slightly in their amino acid sequences. The ancestral type A and the mutated type C are found in significant proportions outside East Asia, mainly in Europe and the United States. Type B, which has mutated and spread widely, is the most common strain in East Asia. The authors emphasize that continuous genome sequencing of virus mutations is needed to monitor the pandemic and watch for new, potentially more dangerous variants.

How does SARS-CoV-2 enter human cells?

SARS-CoV-2 enters human cells by binding its spike protein to the ACE2 receptor (angiotensin-converting enzyme 2). This receptor is highly expressed in the lungs, small intestine, kidney, and heart. Interestingly, ACE2 is not found on innate and adaptive immune cells.

Cell entry is facilitated by a host enzyme called TMPRSS2, a serine protease that cleaves the spike protein into two fragments (S1 and S2), enabling the viral membrane to fuse with the human cell membrane. The virus also binds to other molecules:

• CD147 (also called basigin or extracellular matrix metalloproteinase inducer) — found in human airway and kidney epithelium, as well as in innate immune cells and lymphocytes
• TMPRSS4 — highly expressed in intestinal epithelial cells

The authors also note that antibody-dependent enhancement — a process where antibodies actually help the virus enter cells instead of neutralizing it — may contribute to infection, as was reported for the original SARS-CoV.

Are there other molecules the virus might use to enter cells?

SARS-CoV-2 may use receptors that have been reported for other coronaviruses, including CD26, aminopeptidase N, and glutamyl aminopeptidase. Among these, CD26 (encoded by the DPP4 gene) has emerged as a possible receptor for SARS-CoV-2 because structural analyses predict that the spike protein of the virus can bind to it. CD26 is expressed in human epithelium and immune cells.

Do genetic variations in ACE2 affect COVID-19 severity?

There is limited evidence about specific gene variations (polymorphisms) that influence COVID-19 severity. ACE2 has been suggested as a candidate gene that influenced pneumonia progression in the original SARS outbreak. The "D allele" variant of ACE may influence the renin-angiotensin system by raising ACE levels in the blood or tissues, potentially damaging the endothelium or epithelium of the lungs.

However, the authors caution that the variance in COVID-19 prevalence and mortality cannot be explained by any single gene variation alone. Instead, variations in genes involved in the immune response — including toll-like receptors, the inflammasome (a protein complex that triggers inflammation), intracellular molecular sensors, interferons (IFNs), and interleukins (ILs) — may all contribute.

What parts of the virus trigger the immune response?

The structural proteins of SARS-CoV-2 — the spike glycoprotein, envelope, membrane, and nucleocapsid — are the main molecules that the immune system recognizes and responds to. The adaptive immune response (the "learned" immune response that remembers past infections) develops mainly against the spike protein, and immunodominant T cell and B cell epitopes (the specific parts of the virus that immune cells target) have been identified.

Inside infected cells, the viral RNA replicase complex and other non-structural and translated proteins activate innate immune pathways. This leads to a type I interferon response, activation of NF-kB (a protein complex that controls inflammation) in epithelial cells, and activation of NLRP3 and other inflammasomes in macrophages and dendritic cells — all part of the body's first-line defense.

How does SARS-CoV-2 differ from the original SARS-CoV-1?

The spike protein of SARS-CoV-2 has a receptor-binding domain that binds to ACE2 with higher affinity than the original SARS-CoV-1. This stronger binding may explain why SARS-CoV-2 spreads more easily.

In addition, the SARS-CoV-2 spike protein contains a polybasic furin cleavage site (with the amino acid sequence PRRAR), which includes an insertion of 4 amino acid residues not found in SARS-CoV-1 or other SARS-like viruses. This site allows the virus to be cleaved effectively by furin and other proteases, which determines how infectious the virus is and which animal species it can infect.

Is COVID-19 similar to HIV infection?

There are some interesting parallels between COVID-19 and HIV (human immunodeficiency virus), the virus that causes AIDS. The severe lymphopenia (abnormally low levels of lymphocytes, a type of white blood cell) seen in COVID-19 is similar to what is observed in HIV infection. However, there is a key difference: HIV causes CD4+ T cell lymphopenia specifically, whereas COVID-19 causes general lymphopenia affecting all types of lymphocytes.

Another important difference is timing. Severe lymphopenia in COVID-19 develops within weeks, whereas HIV-induced lymphopenia takes years to develop. Both HIV and SARS-CoV-2 are RNA viruses and share some similarities in how they replicate, which means certain RNA replication drugs may potentially work for both diseases.

Could more dangerous mutant strains of SARS-CoV-2 emerge?

Two strains of SARS-CoV-2 are clinically relevant, and genome analysis shows high rates of mutation and deletion in several viral genes, including the spike glycoprotein gene. The authors explain that COVID-19 treatments and future vaccination may drive the genetic evolution of the virus, affecting its virulence (how severe the disease it causes is) and pathogenicity (its ability to cause disease).

For example, a report on a 382-nucleotide deletion in the ORF8 gene of SARS-CoV-2 isolated from patients in Singapore suggested that mutations may arise as a result of human adaptation and could be associated with attenuation (weakening) of the virus. However, the authors warn that the emergence of a "SARS-CoV-3" is possible as long as there is close contact between humans and living animals that harbor coronaviruses.

How long is SARS-CoV-2 detected in respiratory and oral secretions?

This is one of the most practically important questions for infection control. Data from 96 COVID-19 patients in China showed that SARS-CoV-2 was detected in respiratory samples for a median of 18 days (range 13-29 days). In this study, sputum and saliva were not analyzed separately.

Viral shedding (the period during which the virus can be detected and potentially spread) was significantly longer in patients with severe disease:

• Severe disease: median of 21 days (range 14-30 days)
• Mild disease: median of 14 days (range 10-21 days)

The study also found that treatment with glucocorticoids (steroid medications) for longer than 10 days significantly extended the duration of viral shedding — an important consideration for patients and doctors.

Viral load (the amount of virus in the body) differed significantly by sample type. Respiratory samples had the highest viral load, followed by stool samples, with serum samples showing the lowest. Another study of 78 patients (33 asymptomatic and 42 symptomatic) estimated the duration of viral shedding from nasopharynx swabs to be:

• Asymptomatic patients: 8 days (range 3-12 days)
• Symptomatic patients: 19 days (range 16-24 days)

In terms of viral load, sputum from patients who died contained up to 1.34 × 10¹¹ copies per milliliter, while sputum from patients who survived contained up to 7.52 × 10⁵ copies per milliliter — a dramatic difference of several orders of magnitude.

Can the virus spread through the fecal-oral route?

The enzymes TMPRSS2 and TMPRSS4 promote SARS-CoV-2 infection of ACE-expressing human enterocytes (intestinal lining cells), which can cause diarrhea in both adults and children. SARS-CoV-2 has been detected in stool samples by reverse transcription polymerase chain reaction (RT-PCR), the standard diagnostic test.

The median duration of the virus in stool samples was 22 days (interquartile range 17-31 days), which is significantly longer than in respiratory samples (18 days, range 13-29 days). However — and this is reassuring — the virus released into the intestinal lumen was inactivated by simulated human colonic fluid, and infectious virus was not recovered from stool specimens of COVID-19 patients.

The authors conclude that the intestine is a potential site of SARS-CoV-2 replication that may contribute to local and systemic illness and overall disease progression, but it is unlikely to contribute significantly to the spread of COVID-19 through the fecal-oral route.

Section 2: How the Immune System Responds to SARS-CoV-2

B cell and antibody responses: What is the timing of seroconversion?

Seroconversion is the period during which the body develops detectable antibodies against a virus. Understanding this timing is crucial for interpreting antibody tests and for understanding how long immunity might last.

From previous SARS studies, researchers know that the median seroconversion time for detectable IgG antibodies (the long-term antibodies that provide lasting immunity) was 17 days after infection. Detectable levels of SARS-specific IgG and neutralizing antibodies persisted for up to 720 days (about 2 years). This suggests that antibody-mediated protection from recurrent SARS-CoV infection may last up to 2 years.

However, reports on the antibody response to SARS-CoV-2 are inconsistent. One study of 285 COVID-19 patients reported that SARS-CoV-2-specific IgG and IgM antibodies peaked at 17-19 days and 20-22 days after symptom onset, respectively. On the other hand, another study of 26 hospitalized COVID-19 patients showed that seroconversion could take up to 50 days.

The authors explain that these discrepancies may be related to when the patients were diagnosed with SARS-CoV-2 or the clinical characteristics of each patient group. Additional studies are needed to resolve these differences and to give patients and doctors a clearer picture of immunity after infection.

What is the role of IgA antibodies in SARS-CoV-2 infection?

Systemic IgA responses — antibodies found mainly in mucous membranes, saliva, and blood — may play a relevant role in the development of COVID-19. Mucosal IgA likely exerts a protective role by preventing SARS-CoV-2 from adhering to the respiratory tract epithelium, the thin layer of cells lining the airways. This suggests that IgA antibodies at mucosal surfaces could be an important part of the body's defense against the virus, though more research is needed to fully understand their protective capacity.

What These Findings Mean for Patients

Several findings from this review have direct relevance for patients and their families.

First, the duration of viral shedding matters for isolation guidance. The finding that the virus remains detectable in respiratory samples for a median of 18 days — and up to 30 days in severe cases — suggests that patients should prepare for potentially extended isolation periods. The fact that asymptomatic patients shed virus for only about 8 days on average is reassuring, but the wide range means individual variation is significant.

Second, patients taking glucocorticoids should be aware of potential effects on viral clearance. The study showing that glucocorticoid treatment longer than 10 days significantly extended viral shedding (to a median of 21 days in severe disease) is an important consideration. Patients should not stop prescribed steroid medications without consulting their doctor, but this information can help guide discussions about treatment plans.

Third, the fecal-oral transmission risk appears low. While the virus can be detected in stool for longer periods than in respiratory samples (22 days vs. 18 days), the fact that infectious virus was not recovered from stool specimens and that simulated colonic fluid inactivated the virus is reassuring for household and sanitation concerns.

Fourth, immunity after infection is complex and variable. The wide range of seroconversion times (17-19 days in one study, up to 50 days in another) means that antibody tests must be interpreted cautiously. A negative antibody test soon after infection does not necessarily mean the patient has no immunity, and a positive test does not guarantee protection.

Limitations of the Current Evidence

The authors are transparent about the limitations of the evidence available at the time of writing. First, the reported number of COVID-19 cases and deaths likely underestimates the true cumulative incidence due to limitations of diagnostic tests, the extent of population testing and reporting, and the different mitigation strategies adopted by each country.

Second, there is a lack of epidemiological surveys that provide a clear percentage of asymptomatic cases, making it difficult to understand the full spectrum of disease.

Third, there is limited evidence about COVID-19-associated genetic polymorphisms. The variance in COVID-19 prevalence and mortality cannot be explained by an ACE insertion/deletion polymorphism alone or by any single gene variation.

Fourth, reports on the humoral (antibody) response to SARS-CoV-2 are inconsistent, with seroconversion times varying widely between studies. These discrepancies may reflect differences in when patients were diagnosed or their clinical characteristics, and they warrant additional research.

Finally, the authors emphasize that while vaccine and drug development studies are growing at unprecedented speed, basic and clinical research on COVID-19-related topics must be based on more coordinated, high-quality studies to produce reliable and actionable evidence.

Recommendations for Patients

Based on the findings in this review, patients can take several practical steps:

1. Follow public health guidance on isolation and quarantine. Given that viral shedding can last a median of 18 days in respiratory samples, and up to 30 days in severe cases, patients should follow their local health authority's guidelines for isolation duration.
2. Do not stop prescribed medications without consulting your doctor. This is especially important for patients taking glucocorticoids, who should discuss the risks and benefits with their healthcare provider. The study showing extended viral shedding with glucocorticoid use is important, but stopping these medications suddenly can have serious health consequences.
3. Practice good hygiene, including handwashing. While the fecal-oral route appears unlikely to be a major transmission pathway, the virus can be detected in stool for over 3 weeks. Rigorous hand hygiene after bathroom use remains a sensible precaution.
4. Understand that antibody tests have limitations. A negative antibody test does not necessarily mean you have no immunity, particularly if tested early after infection. Discuss test results with your doctor rather than drawing conclusions on your own.
5. For patients with allergic disease and asthma: The full review contains extensive guidance on managing allergic conditions during the pandemic. Stay in contact with your allergist or specialist to ensure your condition is well controlled, as this may help reduce the risk of complications if you do become infected.
6. Continue to take preventive measures seriously. The authors note that it will be practically impossible to eradicate SARS-CoV-2 without vaccination. Until vaccines are widely available, preventive measures remain the primary defense.

Frequently Asked Questions

How long does the virus stay in your body after COVID-19 infection?

In a study of 96 patients in China, the virus was detected in respiratory samples for a median of 18 days. Severe cases lasted about 21 days, mild cases about 14 days. Another study found asymptomatic patients shed virus for about 8 days. Isolation should follow local health guidelines.

Can COVID-19 spread through feces (fecal-oral route)?

The virus can be detected in stool for a median of 22 days, longer than in respiratory samples. However, infectious virus was not recovered from stool specimens, and simulated intestinal fluid inactivated the virus. So the fecal-oral route is unlikely to be a major way COVID-19 spreads.

I take steroid medication. Does that affect COVID-19?

One study found that treatment with glucocorticoids for longer than 10 days significantly extended viral shedding, to a median of 21 days in severe disease. However, do not stop prescribed steroids suddenly. Discuss risks and benefits with your doctor to make the safest choice.

Do antibody tests tell me if I am immune to COVID-19?

Antibody responses vary widely. One study of 285 patients found IgG and IgM antibodies peaked at 17-19 and 20-22 days after symptoms. Another study of 26 hospitalized patients reported seroconversion could take up to 50 days. So antibody tests have limitations and should be interpreted cautiously.

How does SARS-CoV-2 enter human cells?

The virus uses its spike protein to bind to the ACE2 receptor, found in lungs, intestine, kidney, and heart. Enzymes called TMPRSS2 and TMPRSS4 help the virus fuse with cells. It may also bind to CD147 and CD26. This is how the virus infects the body.

Are there different strains of SARS-CoV-2?

Yes, three variants have been identified: types A, B, and C. Type A and C are found more in Europe and the US, while type B is most common in East Asia. The virus continues to mutate, and genome sequencing is needed to monitor for new variants.

Could a more dangerous mutant strain of SARS-CoV-2 emerge?

Yes, it is possible. The virus mutates, and treatments or vaccines may drive genetic changes. A report from Singapore found a deletion in the ORF8 gene that may weaken the virus. As long as humans have close contact with animals carrying coronaviruses, a 'SARS-CoV-3' could emerge.

I have COVID-19 and was prescribed glucocorticoids. I'm worried they extend viral shedding. When should I get a second opinion?

Glucocorticoid treatment lasting longer than 10 days has been linked to significantly longer viral shedding, with severe cases shedding for a median of 21 days. However, stopping prescribed steroids suddenly can be harmful. A second opinion is reasonable if you or your doctor are uncertain about the risks and benefits of continuing this treatment, especially in severe or prolonged illness. Antibody test results are also variable, so expert interpretation may help. Seek a second opinion when treatment decisions feel unclear or test results are confusing. Diagnostic Detectives Network provides independent expert second opinions.

Source Information

This patient-friendly article is based on the following peer-reviewed research:

Original Title: A compendium answering 150 questions on COVID-19 and SARS-CoV-2

Journal: Allergy (Wiley), accepted article, DOI: 10.1111/ALL.14449

Article Type: Review

Note: This patient-friendly article is based on peer-reviewed research. It is intended for educational purposes and is not a substitute for professional medical advice. Always consult your healthcare provider with questions about your individual health situation. The original review is protected by copyright. This translation preserves the key findings, statistics, and conclusions from the original article while making them accessible to a non-scientific audience.