While COVID-19 affects people differently, there are symptoms to watch out for in a certain order that help identify if you have the virus. Signs of COVID range from shortness of breath, coughing, sneezing, vomiting, headache and more and Eat This, Not That! Health talked to Dr. J. Wes Ulm, MD, Ph.D., who explains COVID symptoms and patterns to be aware of. Read on—and to ensure your health and the health of others, don’t miss these Sure Signs You’ve Already Had COVID.

“While there are patterns in the order in which COVID symptoms appear, there is no canonical ‘typical sequence’ that unmistakably identifies a COVID-19 infection,” says Dr. Ulm. “The first pearl of wisdom to bear in mind here, regarding the ‘typical sequence’ of COVID signs and symptoms, is that there isn’t any single well-defined order of symptomatic manifestation — every patient is different! We often conceive of COVID-19 as a respiratory disease, and the lungs and respiratory tract more generally do indeed represent one of the most common and hard-hit organ systems in both mild and severe COVID. However, it’s also a gastrointestinal disease, a neurological illness, and a systemic malady that can affect an astonishing variety of human tissues, and it’s instructive to dive a bit into why this is.”

Here’s why: “SARS-CoV-2 — the coronavirus responsible for the disease — is able to infect cells through its spike protein, which docks onto a cellular receptor called ACE2. The ACE2 molecule is actually an enzyme — angiotensin-converting enzyme 2 — which is fairly ubiquitous throughout the body. It resides on the surface of many different cell types to help regulate blood pressure, including the gallbladder, heart, kidney, thyroid, liver, testis, intestines, and particularly the cells lining our blood vessels (endothelial cells). Unfortunately, this ubiquity also means that a slew of different cells and tissues can take a hit if a virus figures out a way to latch onto ACE2 (as a result of both direct viral replication damage and the immune response), and coronaviruses like SARS-CoV-2 have figured out how to do just that. At a clinical level, the practical result of this is that initial patient presentations for COVID-19 are quite heterogeneous, and clinicians must maintain a high index of suspicion and commence testing given a wide array of presenting symptoms.” Keep reading to see which of these symptoms may come first.

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According to Dr. Ulm, “Both large cohort studies and case reports describe a variety of initial presentations, often ‘flu-like’ but commonly manifesting a different symptom cluster. COVID’s presenting symptomatology is often described as “‘flu-like’ and there is some truth to this, but there are some salient differences in the ‘flu-ish’ presentations, and many patients demonstrate a widely divergent constellation of symptoms with little resemblance to the flu. While influenza infection is classically associated with an early manifestation of cough (often in association with muscle aches and malaise) and some COVID-19 cases will also begin this way, COVID patients with a flu-like onset will more frequently begin spiking fevers as the first conspicuous symptom, often in conjunction with fatigue and/or malaise. This in fact is one of the reasons that public venues and clinics often use a digital body temperature reader as a quick-screen for potential COVID in an undiagnosed patient. After the initial fever spike, muscle aches as in the flu are common, frequently followed by gastrointestinal symptoms like nausea and diarrhea — perhaps the closest we have to a ‘canonical sequence of events’ for a COVID presentation dating back to the first major waves in the US in March of 2020.

However for many patients, chronic or severe fatigue— described as being crippling or debilitating, making daily tasks challenging — will be the first noticeable symptom, often followed by fever or the other flu-like manifestations. And then there are patients who don’t seem at all ‘flu-ish’ or have any respiratory symptoms or fever, but still demonstrate a positive RT-PCR test for COVID-19. Such patients may report broadly constitutional symptoms such as malaise, headache, exhaustion, irritability, and dizziness in some combination. Many may present with cutaneous (skin) symptoms, often involving discoloration — including the ‘COVID toes’ often reported — due to vascular effects of the virus. Or they may have strictly gastrointestinal symptoms like nausea, vomiting, or diarrhea, but without preceding fever or muscle aches, or even report only chest pain or vague muscle aches. Interestingly, rhinorrhea (runny nose or nasal discharge) was not reported commonly for COVID patients in 2020, but with the advent of the delta variant as the dominant viral strain infecting patients, it’s become significantly more prominent, perhaps owing to greater coronaviral replication and tissue invasion in the upper respiratory tract. With all this said, there is one symptom complex that can be especially distinctive of a COVID presentation.”

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Many people with COVID report a lack of taste and smell. Dr. Ulm says, “anosmia and dysgeusia — the loss of smell and distortion in the sense of taste, respectively — are strongly suggestive of COVID-19. These two symptoms are not strictly pathognomonic for COVID-19 —that is, they aren’t uniquely associated with SARS-CoV-2 so as to essentially nail a COVID diagnosis. Loss or alteration of sense or smell can occur in principle with any so-called neurotropic virus that can infect the neurons of the nervous system, including many encephalitis viruses, measles, and even influenza. However, anosmia and/or dysgeusia do appear to crop up more commonly and conspicuously in a distinct subset of COVID-19 patients, and frequently as the first presenting symptom. They can be quite unsettling to patients by altering their basic perception and enjoyment of meals, and should immediately arouse suspicion of COVID especially if there was a possibility of a recent sick contact exposure or large indoor event.”

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Dr. Ulm explains, “symptom progression from these diverse initial presentations can vary significantly, but long COVID syndrome can be seen even in the wake of mild cases. Most COVID-19 cases are mild, even for unvaccinated or immune-naive patients (without natural immunity from a prior infection), but unfortunately a significant fraction do develop severe enough symptoms to require hospitalization, which occurs statistically more frequently and with greater severity in the absence of a vaccination within the prior six months. The progression can vary but, in general, entails significant difficulty in maintaining oxygen saturation, alongside increasing stress on the heart and, frequently, severe neurological symptoms, possibly associated with viral breaches of the blood-brain barrier as well as damage from a robust immune response and so-called cytokine storm. In its severe form, COVID-19 in many ways takes on the form of a vascular disease — due in part to the high concentration of ACE2 receptor on the endothelial lining of blood vessels — which explains much of the danger it poses to the respiratory system. With that said, even mild cases that don’t require hospitalization can progress to involve substantial discomfort and exhaustion, as well as brain fog, difficulty breathing, and chest pain. Moreover, both mild and severe cases can progress to long COVID syndrome.”

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When children get COVID, their symptoms are similar to adults, Dr. Ulm says. “Children initially appeared to be less affected by COVID-19 during the 2020 outbreaks, but the delta variant appears to pose significantly greater hazards even to pediatric patients. There has been an increase, for instance, in the eventration of multisystem inflammatory syndrome in children (MIS-C), a kind of inflammatory vascular illness similar to the better-characterized Kawasaki disease. Most kids still have mild cases and hospitalizations are comparatively rare, but more and more pediatric wards are reporting severe cases in children. The symptom clusters do not appear to differ significantly from adults, but kids may more commonly report severe fatigue and malaise as a presenting symptom.”

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Follow the public health fundamentals and help end this pandemic, no matter where you live—get vaccinated ASAP; if you live in an area with low vaccination rates, wear an N95 face mask, don’t travel, social distance, avoid large crowds, don’t go indoors with people you’re not sheltering with (especially in bars), practice good hand hygiene, and to protect your life and the lives of others, don’t visit any of these 35 Places You’re Most Likely to Catch COVID.

J. Wes Ulm, MD, Ph.D., is a physician-researcher, musician (J. Wes Ulm and Kant’s Konundrum), and novelist, and earned a dual MD/Ph.D. degree from Harvard Medical School and MIT. He is part of the Heroes of the COVID Crisis series in relation to his ongoing efforts in the drug discovery and public health arena.