COVID-19 is, on average, substantially less dangerous for most people than it was in 2020 or 2021. Widespread immunity from vaccination, prior infection, or both has dramatically reduced the likelihood that any single infection leads to hospitalization or death. But “less severe on average” is doing heavy lifting in that sentence, because the risks that remain are not evenly distributed, and some of them are not about the acute illness at all. Immunocompromised people, older adults, pregnant women, and those catching the virus for a second or third time still face outsized danger, while emerging evidence on organ damage, cognitive effects, and economic fallout suggests the full cost of COVID extends well beyond the initial infection.
Why the Average Infection Feels Milder
Two forces have converged to make the typical COVID case less threatening. The first is the virus itself. The Omicron lineage, which has dominated globally since late 2021, tends to replicate more readily in the upper airways and less aggressively in the deep lung tissue, producing fewer cases of the devastating pneumonia that defined earlier waves. The second, and probably larger, factor is population immunity. By now, the vast majority of adults have encountered SARS-CoV-2 through vaccination, infection, or both. This “hybrid immunity” offers powerful protection against severe outcomes. A large Canadian cohort study of about five million residents found that three vaccine doses provided roughly 93-94% protection against Omicron-associated hospitalization, and that adding a prior infection on top of vaccination pushed protection even higher, to around 97-99%.1PubMed Central. Protection of prior SARS-CoV-2 infection, COVID-19 boosters, and hybrid immunity against Omicron severe illness: A population-based cohort study of five million residents in Canada
Among healthcare workers studied during an Omicron wave, those with hybrid immunity had a reinfection rate under 10%, compared with about 44-46% in colleagues who relied on vaccination alone.2PubMed Central. Protection of vaccination versus hybrid immunity against infection with COVID-19 Omicron variants among Health-Care Workers None of those healthcare workers, regardless of immunity type, were hospitalized or died, underscoring how far the baseline has shifted for healthy, immunized adults. For this group, COVID in 2024 or 2025 often resembles a bad cold or a moderate flu, not the life-threatening emergency it once was.
Immunocompromised People Face a Different Reality
The improvement in average outcomes does not extend equally to people whose immune systems are weakened by disease or medication. A systematic review and meta-analysis covering the Omicron era found that people with immunocompromising conditions had a substantially higher risk of death and hospitalization from COVID compared with the general population. Organ transplant recipients were the hardest hit, with a pooled risk of death nearly seven times higher than people without those conditions, and a risk of hospitalization about seven times higher as well.3PubMed. Risk of Severe Outcomes From COVID-19 in Immunocompromised People During the Omicron Era: A Systematic Review and Meta-Analysis That gap is enormous by any medical standard.
Data from a large U.S. commercial insurance population tells a similar story. Immunocompromised individuals had a hospitalization rate of about 15% upon their first COVID diagnosis, compared with roughly 4% in the general insured population, and their average hospitalization cost about $42,700 versus $28,800 for non-immunocompromised patients. Overall, immunocompromised people faced between 4 and 23 times the risk of hospitalization depending on the specific condition.4PubMed Central. Assessing the Burden and Cost of COVID-19 Across Variants in Commercially Insured Immunocompromised Populations in the United States: Updated Results and Trends from the Ongoing EPOCH-US Study This group includes people on immunosuppressive drugs for autoimmune diseases, cancer patients undergoing chemotherapy, and anyone living with HIV that is not well controlled. For them, COVID remains a genuinely dangerous illness even in the Omicron era, partly because their immune systems mount weaker vaccine responses.5PubMed Central. The Impact of the COVID-19 Omicron Variant on Immunocompromised Patients: ICU Admissions and Increased Mortality
Older adults remain vulnerable too, though the picture is more nuanced than in 2020. A study of over 1,200 elderly patients at a Thai hospital found that about 24% required hospitalization and 3.7% died, numbers that are far lower than the fatality rates seen in the first waves but still high enough to warrant real caution.6Open Forum Infectious Diseases. P-1641. Risk Factors for COVID-19 Hospitalization in the Elderly Population at Maharaj Nakorn Chiang Mai Hospital Advanced age plus chronic conditions like diabetes, kidney disease, or heart failure creates the kind of compounding risk that even widespread immunity cannot fully offset.
Reinfection Carries Cumulative Risk
One of the most important and least appreciated findings from the past few years is that repeat infections are not harmless reruns. A large study using U.S. Veterans Affairs health records found that, compared with a single infection, reinfection more than doubled the risk of death and tripled the risk of hospitalization. Beyond those headline outcomes, reinfection also added risks across multiple organ systems, including the lungs, heart, kidneys, and brain. Those risks were present regardless of vaccination status and persisted into the six-month post-acute phase.7PubMed Central. Acute and postacute sequelae associated with SARS-CoV-2 reinfection
This matters because, with COVID now circulating year-round and new immune-evasive subvariants appearing regularly, many people will catch it more than once. The popular assumption that “I already had it, so I’m fine” is only partially correct. Prior infection does confer some protection against reinfection and severe illness, but that protection wanes, and each additional infection appears to add incremental health risk rather than simply repeating the same gamble. The cumulative burden across heart disease, kidney disorders, and other conditions grows with each infection.8PubMed Central. The risks from covid-19 reinfection
Long COVID and Cognitive Effects
The Omicron variants do appear to cause long COVID less frequently than their predecessors. One study comparing long-term symptoms across variant waves found that Omicron infection was associated with about 70% lower odds of developing persistent symptoms compared with the Alpha variant.9PubMed Central. COVID-19 long-term sequelae: Omicron versus Alpha and Delta variants That is a meaningful improvement, but a 70% reduction from a large baseline still leaves a substantial number of people affected when hundreds of millions of infections are occurring globally.
Cognitive difficulties are among the most unsettling long-term complaints. A large community-based study published in the New England Journal of Medicine found measurable cognitive deficits even in people whose acute symptoms had resolved quickly, averaging about a quarter of a standard deviation below uninfected controls in global cognition. For those with persistent unresolved symptoms, the deficit was larger, roughly 0.42 standard deviations below uninfected peers, with memory, reasoning, and executive function hit the hardest. People infected during earlier variant waves showed bigger deficits than those infected during Omicron, and hospitalized patients fared worse than those who stayed home.10PubMed Central. Cognition and Memory after Covid-19 in a Large Community Sample The practical meaning of a quarter-standard-deviation drop in cognition for any individual is debatable, but across a population of billions of infections, it represents a significant public health concern.
Cardiovascular and Metabolic Aftershocks
COVID’s reach extends beyond the lungs and brain. A study tracking outcomes over a full year post-infection found elevated risks of heart failure in women who had tested positive for SARS-CoV-2, and elevated risks of arrhythmias and blood clots in men, with those increased risks persisting from four to twelve months after the acute illness.11PubMed Central. Increased risk of arrhythmias, heart failure, and thrombosis in SARS-CoV-2 positive individuals persists at one year post-infection These are not rare, exotic complications; arrhythmias and blood clots are common cardiovascular problems, and even a modest increase in their incidence across a population translates into a lot of additional cases.
There has also been concern about COVID triggering new-onset diabetes. A Swedish population-based cohort study did find a 12% increase in type 2 diabetes risk following SARS-CoV-2 infection, but the increase was concentrated among people who had been hospitalized or admitted to intensive care. The researchers concluded that the elevated diabetes rates likely reflected increased detection of pre-existing, undiagnosed diabetes during hospitalization rather than the virus itself causing the disease.12PubMed. SARS-CoV-2 infection as a trigger of type 2 diabetes in adults: a population-based cohort study in Sweden using a double negative control design Other reviews have been less definitive, noting that the evidence suggests COVID increases diabetes risk but that the true size of that risk remains uncertain because of how quickly the pandemic landscape has changed.13PubMed Central. New-Onset Diabetes After COVID-19 The honest answer is that the metabolic picture is still being sorted out, and blanket claims in either direction outrun the data.
Lung abnormalities also persist in some people. Research has linked elevated levels of a specific protein, MMP-7, in post-COVID patients with ongoing problems in gas exchange and subtle structural changes in chest imaging suggestive of fibrosis.14PubMed Central. Matrix metalloprotease-7 is associated with post-COVID-19 persistent lung abnormalities This does not mean everyone who gets COVID develops lung scarring, but it does mean that subclinical damage can linger in ways that are not obvious from symptoms alone.
Pregnancy and Children
Pregnant women caught a break with Omicron compared with Delta, but COVID during pregnancy is still not trivial. A multi-country World Health Organization cohort study found that during the Omicron era, the only outcome that remained at significantly elevated risk compared with uninfected pregnant women was very early preterm birth (before 34 weeks), whereas pre-Omicron infections had carried elevated risks across a much wider range of outcomes including emergency cesarean delivery, NICU admission, and preterm birth at multiple gestational thresholds.15PubMed Central. Maternal, perinatal, neonatal, and postpartum outcomes following Severe Acute Respiratory Syndrome – Coronavirus-2 infection in pregnancy: a World Health Organization multi-country prospective cohort study A broader review of maternal outcomes across all variants confirmed that Omicron was associated with lower rates of severe maternal morbidity (about 2.9%) compared with Delta (about 10.3%), while maternal death remained rare across all variants at under 1%.16PubMed Central. Maternal and Perinatal Outcomes of SARS-CoV-2 and Variants in Pregnancy
The worst-case scenario for pregnant women, though, is severe COVID requiring intensive care. Among pregnant patients admitted to ICUs, nearly 95% delivered by cesarean, about 79% of their newborns needed NICU care, and there were five intrauterine fetal deaths and one neonatal death among 19 births studied.17PubMed Central. Severe COVID-19 in Pregnant Versus Nonpregnant Women: Intensive Care Unit Outcomes and Perinatal Risks These are small numbers, but the severity of outcomes when pregnancy and critical COVID collide underscores why vaccination before or during pregnancy continues to be recommended.
For children, the acute illness has generally been mild throughout the pandemic. The rarer concern is multisystem inflammatory syndrome in children (MIS-C), a delayed autoimmune reaction that typically appears two to six weeks after COVID infection, most commonly in children aged 6 to 11. MIS-C carries a mortality rate of about 1-3%.18PubMed Central. Multisystem inflammatory syndrome in children: A dysregulated autoimmune disorder following COVID-19 Cases of MIS-C have declined substantially since the early pandemic, likely because of both widespread immunity in children and the shift to Omicron, but it has not disappeared entirely.
Antivirals Make a Measurable Difference
One genuine bright spot is the availability of antiviral treatments, particularly nirmatrelvir-ritonavir (Paxlovid). A systematic review and meta-analysis of observational studies in the post-vaccine Omicron era found that Paxlovid was associated with about a 30-40% reduction in hospitalization and an even larger reduction in mortality.19PubMed Central. Evaluating the Effectiveness of Antivirals for COVID-19 in the Post-vaccine, Omicron Era: A Systematic Review and Meta-analysis A separate large observational study confirmed similar numbers: a roughly 40% reduction in hospitalization odds among treated patients compared with untreated patients after adjusting for risk level.20PubMed Central. A Retrospective Observational Study on COVID-19 Patients Receiving Treatment with Nirmatrelvir/Ritonavir (PAXLOVID)
There are caveats. One electronic health record-based study estimated that you would need to treat about 111 people with Paxlovid to prevent one hospitalization, which reflects the already-low absolute risk of hospitalization for most vaccinated adults.21PubMed Central. Effect of nirmatrelvir/ritonavir (Paxlovid) on hospitalization among adults with COVID-19: An electronic health record-based target trial emulation from N3C That number-needed-to-treat gets much smaller in high-risk groups like the immunocompromised and elderly, where the baseline risk of hospitalization is higher. Molnupiravir, the other widely available oral antiviral, has shown weaker and less consistent results, with the same meta-analysis finding no statistically significant reduction in hospitalization from its use.19PubMed Central. Evaluating the Effectiveness of Antivirals for COVID-19 in the Post-vaccine, Omicron Era: A Systematic Review and Meta-analysis
Disparities That Have Not Gone Away
COVID-19’s burden has never been distributed equally across racial and socioeconomic lines, and there is little evidence that the shift to milder variants has closed those gaps. A systematic review of studies on racial and socioeconomic disparities found that racial and ethnic minority groups consistently had higher risks of infection, hospitalization, and death, with contributing factors including poverty, crowded housing, lower educational attainment, and language barriers.22PubMed Central. A systematic review of racial/ethnic and socioeconomic disparities in COVID-19 Even after adjusting for neighborhood deprivation, Black and Hispanic individuals in the U.S. were about twice as likely to test positive compared with White individuals.23PubMed Central. Disparities in COVID-19 Outcomes by Race, Ethnicity, and Socioeconomic Status
Machine learning analyses of real-world data have confirmed that Black patients tend to be younger at the time of severe outcomes, carry a higher burden of chronic conditions, and are more likely to be uninsured, all of which compound the direct infectious risk.24PubMed Central. Identifying Potential Factors Associated With Racial Disparities in COVID-19 Outcomes: Retrospective Cohort Study Using Machine Learning on Real-World Data The underlying drivers of these disparities, including unequal access to healthcare, higher exposure in essential jobs, and the compounding effects of chronic underfunding in certain communities, are structural problems that a milder virus variant does not fix.
The Economic Weight of Ongoing COVID
Even setting aside the direct health risks, the economic toll of COVID continues to accumulate. Long COVID alone, defined as symptoms persisting at least three months after infection, is estimated to carry an average annual global burden of about $1 trillion. In the United States, lost earnings attributable to long COVID run to roughly $170 billion per year, with individual patients facing an average cost burden of about $9,000 annually. Long COVID has been associated with increased unemployment, financial distress, and work impairment lasting up to three years after infection.25PubMed Central. Economic burden of long COVID: macroeconomic, cost-of-illness and microeconomic impacts These numbers are not abstractions; they represent people who cannot return to full-time work, who drain savings on medical appointments and therapies, and who fall out of the labor force in ways that ripple through households and communities.
Why the Virus Remains Unpredictable
The relative mildness of current COVID variants is not guaranteed to last. SARS-CoV-2 continues to mutate, and the mutations that accumulate in its spike protein can reshape how well existing antibodies neutralize it.26PubMed Central. Immune Evasion of SARS-CoV-2 Emerging Variants: What Have We Learnt So Far? Research on multiple variants has shown that antibodies with similar binding strength can have very different neutralization effects depending on the structural changes a new variant introduces to the spike, meaning that immune evasion is not simply a matter of the virus “outrunning” antibodies but of subtly reshaping the lock they are trying to fit.27PubMed Central. Defining neutralization and allostery by antibodies against COVID-19 variants
There is also the animal reservoir question. SARS-CoV-2 has spilled over from humans into multiple animal species, where it can mutate in ways it would not in a human host. The concern is that the virus could spill back into humans carrying mutations that are unfamiliar to our immune systems, potentially creating a variant that sidesteps existing immunity more dramatically than the incremental changes we see in human-circulating lineages.28PubMed Central. Role of Spillover and Spillback in SARS-CoV-2 Transmission and the Importance of One Health in Understanding the Dynamics of the COVID-19 Pandemic This is not science fiction; white-tailed deer in North America, for example, have been found to harbor diverse SARS-CoV-2 lineages. Modeling work has suggested that this cycle of human-to-animal-to-human transmission could eventually produce variants that render current vaccines less effective.29PubMed. Predicting potential SARS-CoV-2 spillover and spillback in animals
The Risk Perception Gap
Perhaps the most practical risk that remains is psychological. Research on how people perceive COVID risk has shown a predictable pattern: as case counts fall and restrictions ease, people’s sense of personal risk drops, their trust in public health messaging weakens, and their willingness to take protective measures declines.30PubMed Central. Worldviews, trust, and risk perceptions shape public acceptance of COVID-19 public health measures This is human nature, not a character flaw, but it creates a gap between actual residual risk and perceived risk that can leave vulnerable people unprotected. Wastewater surveillance, which tracks viral levels in sewage and has been shown to reliably correlate with case trends while picking up signals days before clinical reporting catches up, continues to detect substantial ongoing circulation of SARS-CoV-2 even during periods when few people are testing or reporting illness.31PubMed Central. Tracking the temporal variation of COVID-19 surges through wastewater-based epidemiology during the peak of the pandemic: A six-month long study in Charlotte, North Carolina The virus has not become rare; it has become less visible because fewer people are looking for it.
For the average healthy, vaccinated adult, COVID in its current form is a manageable illness most of the time. That is real progress. But treating “less severe on average” as “no longer a concern” misreads the landscape. The people who pay the highest price for that misreading are those whose biology or social circumstances put them on the wrong side of the average.