Just when we thought it was safe to go back in the water, and as if we didn’t have enough scary words to contend with, a new one making the rounds is “tripledemic”, involving simultaneous infection with COVID, the flu, and RSV. Yikes…more viral spikes! The proverb “all good things come in threes” certainly doesn’t apply here. Neither does “third time’s a charm” unless it’s irony you’re after. To lend a realistic and real-world perspective and to lessen the post-Halloween scare factor we share some hopefully useful tidbits and pearls gleaned from our experience as virologists, researchers, and clinicians that work with viruses every day. At the end, we put your (newfound?) knowledge to the test with a short, just-for-fun quiz.
How are viruses transmitted?
Three main ways.
- direct contact between an infector and an infectee as in through contaminated hands
- indirect contact with objects and surfaces also known as fomites that are contaminated with infected respiratory droplets
- airborne via large droplets or fine particles (aerosols) from talking, sneezing, or coughing
What are the signs and symptoms that these viruses cause?
We present the answer in the form of a table and a diagram of the respiratory tract courtesy of Wikipedia that lists out some common infections of the respiratory system.
Table 1 and Figure 1. Table and diagram of the respiratory tract, divided by respiratory syndromes and with some examples of the most implicated viral agents. (Adapted from Wikipedia)
| Type of Disease | Signs and Symptoms | Main Causes | Treatment Options |
| Upper respiratory infection (URI) or common cold | Nasal congestion, runny nose, cough | Rhinoviruses | Avoid antibiotics. Over the counter analgesics, decongestants with or without antihistamine, and zinc |
| Pharyngitis (sore throat) | Painful swallowing, fever, fatigue, hoarseness, possibly conjunctivitis, inflammation of the throat | Adenoviruses but may need to consider mononucleosis and strep throat | Acetaminophen and ibuprofen. Antibiotics only if strep throat caused by group A beta-hemolytic streptococci. These bacteria are very unlikely to cause respiratory symptoms |
| Laryngitis | Hoarse voice, dry cough | All major respiratory viruses | Voice rest |
| Croup | Primarily in young children. Seal-like cough and inspiratory stridor, which is a high-pitched sound during inspiration from a narrowed airway | Parainfluenza types 1 and 3 | Nebulizers and oxygen if indicated |
| Acute bronchitis (infection of the air tubes or bronchi) | Painful cough usually with production of sputum | Several viruses, with <10% caused by bacteria such as Mycoplasma pneumoniae, Chlamydia pneumoniaeand Bordetella pertussis | Antibiotics should not be used unless bacterial cause is suspected. Possibly cough suppressants |
| Bronchiolitis (infection of and mucus buildup in the tiny air tubes or bronchioles) | Cough, and difficulty to breathe | Respiratory syncytial virus (RSV) | Prevention with monoclonal antibody, palivizumab (Synagis), by intramuscular injection. Treatment with nasal suctioning and possibly oxygen |
| Pneumonia (infection of the lung(s)) | Generalized illness with fever, headaches, body aches, diarrhea, runny nose, cough, sputum production, and possibly difficulty to breathe | Influenza, RSV, human metapneumovirus, adenoviruses and human coronaviruses as well as bacterial pneumonia from Staphylococcus aureus or Streptococcus pneumoniae | Ibuprofen and acetaminophen for fever and body aches. If influenza virus is the cause, possible treatment with prescription antivirals such as oseltamivir (Tamiflu), zanamivir (Relenza), or peramivir (Rapivab). If RSV is the cause possible treatment with prescription ribavirin (Virazole) |
What’s the latest coronavirus (COVID) variant?
As of October 2022, BA.5 is the most recent and most dominant omicron subvariant because of how highly transmissible it is. Bad news: current vaccines, including new boosters, may only offer limited protection because of mutations on the Spike protein. Good news: hospitalizations and deaths from BA.5 are low. Treatment with the antiviral Paxlovid is a potential option as well as bebtelovimab, a monoclonal antibody with activity against all circulating Omicron subvariants for which the Food and Drug Administration (FDA) has issued an Emergency Use Authorization (EUA).
What are the most common symptoms of BA.5?
Fever, runny nose, cough, very painful sore throat, headache, muscle aches and fatigue. Loss of taste and/or smell are possible but less likely to occur with omicron.
When is COVID-19 no longer contagious?
No one knows for sure, but a good rule of thumb is probably 5 full days if fever-free without the use of Tylenol or ibuprofen and symptoms improve. The exception to this may be those that receive the antiviral drug, Paxlovid (nirmatrelvir-ritonavir), and experience a rebound phenomenon in which symptoms seem to resolve only to reappear a few days later.
Is co-infection with COVID, flu, RSV, enterovirus, and adenovirus possible?
Yes. Several studies have reported coinfection with (coexistence of) several viruses including COVID-19 and even bacteria, which have the potential to significantly worsen illness severity.[1],[2] This makes it important to screen for the presence of other viruses (and even bacteria) with COVID-19 infections, given the current surge of influenza, RSV, enteroviruses, and adenoviruses. In September the CDC issued an advisory about EV-D68, an enterovirus that is responsible for respiratory symptoms like cough, wheezing, and shortness of breath and as well as more rarely for acute flaccid myelitis (AFM), a rare polio-like condition that can cause muscle pain and weakness.[3]
Is a vaccine based on Spike the best strategy?
Data suggests it’s not. Spike is a protein that mutates over and over, which makes it less and less likely that future variants will respond to vaccines. Data has shown a better protein than Spike may be Nucleocapsid, a protein, which is common to all coronaviruses, since it envelops the RNA of the virus, and which is less likely to mutate.
Is a nucleocapsid COVID-19 vaccine on the horizon?
EpicentRx has developed a vaccine called N-finity based on the Nucleocapsid protein. N-finity may not only be variant-proof but also may serve as a universal vaccine against other as-yet-to-appear coronaviruses.
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- A friend is complaining of nasal congestion, runny nose, and dry cough for the last 3 days without fever. What does he probably have?
- a) Pharyngitis
- b) Common cold
- c) Croup
- d) Bronchitis
- e) Laryngitis
- Which is the least likely cause of a respiratory symptoms?
- a) Enterovirus
- b) Adenovirus
- c) Influenza
- d) Rhinovirus
- e) Group A beta-hemolytic streptococci
- True or false. Respiratory viral infections always require antibiotics
- a) True
- b) False
- Which of the treatments below is applicable for Omicron?
- a) Z-pack
- b) Tamiflu
- c) Relenza
- d) Paxlovid
- e) Rapivab
- Which of these clinical syndromes is associated with a seal-like, barking cough?
- a) Croup
- b) Pneumonia
- c) Laryngitis
- d) Bronchitis
- e) Pharyngitis
- Which isn’t responsible for the spread of viruses?
- a) Fomites
- b) Respiratory droplets
- c) Rubbing eyes
- d) Direct person-to-person contact
- e) Vaccines
- Which protein is the EpicentRx vaccine, N-finity, directed against?
- a) Spike
- b) Nucleocapsid
- c) Envelope
- d) Membrane
- e) GP36
- A friend is complaining of nasal congestion, runny nose, and dry cough for the last 3 days without fever. What does he probably have?
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Answer key: 1.b 2.e 3.b 4.d 5.a 6.e 7.b
[1] Kim D, Quinn J, Pinsky B, Shah NH, Brown I. Rates of co-infection between SARS-CoV-2 and other respiratory pathogens. JAMA. 2020;323(20):2085–6. 5.
[2] Zhu X, Ge Y, Wu T, Zhao K, Chen Y, Wu B, Zhu F, Zhu B, Cui L. Co-infection with respiratory pathogens among COVID-2019 cases. Virus Res. 2020;285:198005.
[3] https://www.medpagetoday.com/infectiousdisease/generalinfectiousdisease/100632