Viewpoint: Here’s Why COVID-19 Is Much Worse Than Flu


Unlike influenza, SARS-CoV-2 uses ACE2 receptors to infiltrate cells. Similar to HIV, SARS-CoV-2 can silently spread throughout the host’s body and attack almost every organ.

Medicine appears to have largely bought into the SARS-CoV-2 seasonal influenza analogy. Everything appears to be focused on pulmonary disease. Fringe coronavirus deniers started the narrative that COVID-19 was like the flu. This disinformation narrative has taken hold and has even affected decision making of prominent scientific committees, where disease severity is increasingly defined as a hospitalization (most commonly due to pulmonary distress), rather than the potential chronic and long-term disabling sequelae. This unfortunately, appeared to be the focus of some of the members on the Center for Disease Control and Prevention’s Advisory Committee on Immunization Practices (ACIP) which failed to approve boosters for those at high risk of occupational exposure, a decision which the CDC’s director promptly reversed.

COVID-19 has a number of presentations and pulmonary is just one. More than anything else, the receptor used for attachment determines the behavior of any virus, along with what organs and even species it can infect.

Kevin Kavanagh, MD

Kevin Kavanagh, MD

Human rhinoviruses, the most common cause of a cold, uses the ICAM-1 (intercellular adhesion molecule-1) receptor to enter cells. This receptor allows the virus to replicate in sinus tissues but not to a variety of other tissues. The influenza virus attaches to cells via sialic acid receptors, which are sugar-protein and sugar-fat complexes. There are a number of modifications of this receptor across species, which require differing viral mutations to enable cellular attachment and entry. The influenza virus primarily targets a patient’s lungs, but then the patient’s immune response can also produce a myriad of system symptoms from loss of appetite and myalgias. HIV uses the CD4 receptor residing on Lymphocytes. HIV is initially asymptomatic, and the initial stages of disease can easily be classified as “mild”, a disease which, if left untreated, almost uniformly turns aggressive and fatal over the course of 8 to 10 years.

In the case of SARS-CoV-2, the virus which causes COVID-19, the ACE2 receptor is used for viral entry into the cells. The ACE2 receptor is entirely different to that used by the rhinovirus and seasonal flu. It is composed of amino acids along with a zinc ligand. This receptor is present throughout the body, not just the lungs.

Clinically, SARS-CoV-2 combines some of the properties of the seasonal flu plus HIV. Similar to the seasonal flu, SARS-CoV-2 can primarily attack the lungs. But ACE2 receptors are everywhere. Similar to HIV, the virus can also enter a stealth mode, silently spreading throughout the host’s body and attacking almost every organ, especially those with a high ACE2 receptor concentration. And similar to HIV, SARS-CoV-2 also frequently causes asymptomatic spread. In full stealth mode, SARS-CoV-2 can asymptomatically attack the vasculature and heart. Myocarditis can occur and the patient is totally unaware of the damage, until an arrhythmia or symptomatic myocarditis develops. In young asymptomatic patients, this is not an uncommon sequela.

SARS-CoV-2 targeting the cardiovascular system of the body should be a given. It has been known for a long time that ACE receptors are involved in cardiovascular regulation. ACE inhibitors and ACE II blockers have long been used to treat high blood pressure. This is the same pathway the virus infects.

Thus, there are multiple presentations of SARS-CoV-2 including pulmonary, cardiac, gastrointestinal (GI), and central nervous system (CNS).

Recently, there has been mounting evidence regarding the CNS effects of SARS-CoV-2. As early as July 2020, scientists were sounding the alarm regarding COVID-19 brain damage: Including temporary brain dysfunction, strokes, nerve damage and brain inflammation. At that time, these conditions were still considered relatively uncommon. An article published in Lancet Psychology found 1 in 3 COVID-19 survivors were diagnosed with brain or mental health disorders, but separating out what is due to the stressors of the illness versus direct effects of the virus was problematic.

Sandra Lopez-Leon, et al. performed a system review and meta-analysis of long COVID-19 and found the 3 most common long COVID symptoms were “fatigue (58%), headache (44%), and attention disorder (27%)”, all of which can affect concentration.

Ritchie, et al, noted that cognitive dysfunction has been commonly reported with COVID-19, but the true incidence is unknown, and notes that: “The hippocampus appears to be particularly vulnerable to coronavirus infections, thus increasing the probability of post-infection memory impairment…” and that the virus may enter the CNS through the olfactory bulb. Finally, in August of 2021, research by Gwenaëlle Douaud, et al. documented with brain imaging “abnormalities in limbic cortical areas with direct neuronal connectivity to the primary olfactory system.” In addition, there was “a marked reduction of grey matter thickness in fronto-parietal and temporal regions.” “The 401 SARS-CoV-2 infected participants also showed larger cognitive decline between the two timepoints in the Trail Making Test (visual attention and task switching) compared with the controls…”

Again, none of this should come as a surprise, since anosmia or lack of smell, is one of the most common presenting symptoms of COVID-19. The olfactory nerve is not actually a nerve but a projection of the brain itself.

Thus, COVID-19 has a myriad of different presentations, all of which can result in severe and long-term sequelae.Just because COVID-19 is asymptomatic or does not produce “severe” pulmonary disease does not mean the patient does not have a serious infection.It is of utmost importance for public health officials to implement strategies to prevent the occurrence of long-term COVID-19 related disabilities and not just focus on acute pulmonary symptoms.

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