This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for COVID-19 Vaccination of Immunodeficient Persons (COVAXID) (NCT04780659), a na phase 4 study. The primary outcome is Assessment of Seroconversion, Defined as Development of Immunoglobulin G (IgG) Antibodies Against Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) After Vaccination of 2 Doses in Seronegative Individuals..
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT04780659 |
| Phase | Phase 4 |
| Condition | Covid19 |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 539 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Karolinska University Hospital |
| Results posted | Yes |
2. Clinical Question
Population
People with primary or secondary immunosuppressive disorders and immunocompetent individuals. The primary endpoint specifically concerns seronegative individuals at the start of the assessment.
Intervention
Two doses of the Comirnaty mRNA vaccine, administered according to current approval and standard of care.
Comparator
The study included immunocompetent controls as well as immunocompromised participants, but allocation was not randomized. The groups therefore are not a like-for-like randomized comparison.
Primary question
Among seronegative individuals, what proportion developed IgG antibodies against SARS-CoV-2 after two vaccine doses, assessed 2 weeks after the second dose?
The study was designed to investigate immune responses following vaccination, including humoral and cellular responses assessed using blood and saliva. Its primary endpoint focuses on seroconversion: a change to a positive SARS-CoV-2 IgG serology result after vaccination. This is an immunological outcome, rather than a direct measure of prevention of infection or severe disease.
The registry also lists vaccine adverse events, local and systemic reactions, and SARS-CoV-2 infection documented by PCR testing among its secondary outcomes. The record does not report results for the primary endpoint or these secondary outcomes. It therefore does not establish from the posted results how frequently seroconversion occurred or how the immune responses differed between participant groups.
3. Trial Design
COVAXID is registered as a completed, open, non-randomized phase IV multicenter cohort study. The registry lists an enrollment of 539 and identifies Karolinska University Hospital as the sponsor. The study started on 2021-02-23, and primary completion was recorded as 2021-10-15.
Participants received Comirnaty according to current approval, with two vaccine doses described in the study summary. The record identifies people with primary or secondary immunosuppressive disorders and immunocompetent people as the populations of interest. It also lists groups called All Immunocompromised Patients and Controls in its adverse-event information.
There was no random allocation, and masking was listed as none. The registry identifies the model as single group, while also reporting immunocompromised and control groups for safety outcomes. Those labels do not make the groups randomized treatment arms. Differences between them could reflect differences in the people included, and the registry record does not describe a randomized comparison that would balance such differences.
The study aimed to assess immune responses using blood and saliva, including humoral and cellular responses. The primary endpoint was seroconversion to a positive SARS-CoV-2 IgG serology result among seronegative individuals, measured 2 weeks after the second dose. The record also lists reactogenicity, adverse events, and PCR-documented SARS-CoV-2 infection as secondary outcomes. Although the study status is completed, results for the primary endpoint are not reported in the registry record.
The registry record does not report details of the statistical analysis plan, eligibility criteria beyond the broad population descriptions, or how participants were assigned to the immunocompromised and control categories. It also does not report a rationale for the enrollment target. These omissions limit how fully the study’s planned comparisons and analytic decisions can be evaluated.
4. Participant Flow and Accounting
The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.
Before assignment: 781 participants were screened for the study at at Karolinska University Hospital between February 12th and 22nd, 2021 and 539 were included and recived the first vaccin dose. The main reasons for screening failure were previous COVID-19 infection, patient refusal, and that some study subjects already had been vaccinated outside the study.
Overall Study
| Stage | All Immunocompromised Patients | Controls |
|---|---|---|
| STARTED | 449 | 90 |
| COMPLETED | 439 | 90 |
| NOT COMPLETED | 10 | 0 |
Reasons for not completing this period:
| Reason | All Immunocompromised Patients | Controls |
|---|---|---|
| Adverse event, serious fatal | 3 | 0 |
| Withdrawal by Subject | 3 | 0 |
| Physician Decision | 1 | 0 |
| Died in original disease | 2 | 0 |
| Leukemia relapse (more than 6 weeks after dose 2) | 1 | 0 |
5. Baseline Characteristics
The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.
| Characteristic | Unit | All Immunocompromised Patients | Controls | Total |
|---|---|---|---|---|
| Participants analysed | 449 | 90 | 539 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 181 | 27 | 208 |
| Age, Categorical: >=65 years | Participants | 268 | 63 | 331 |
| Sex: Female, Male: Female | Participants | 242 | 51 | 293 |
| Sex: Female, Male: Male | Participants | 207 | 39 | 246 |
| Race and Ethnicity Not Collected | Participants | — | — | 0 |
| Region of Enrollment: Sweden | participants | 449 | 90 | 539 |
| Ongoing immunosuppression at baseline: Corticosteroids | Participants | 26 | 0 | 26 |
| Ongoing immunosuppression at baseline: Other immunosuppressive agents | Participants | 159 | 0 | 159 |
| Ongoing immunosuppression at baseline: No ongoing immunosuppression at baseline | Participants | 264 | 90 | 354 |
| Immunogloublin G (IgG) level at baseline | Immunglobulin G, IgG (g/L) | 9.9 (1.0 to 34.4) | 11.0 (7.2 to 21.2) | 10.1 (1.0 to 34.4) |
| Absolute lymphocyte count(10^9 cells/L) at baseline | Absolute lymphocyte count (10^9 cells/L) | 1.6 (0.2 to 112.6) | 1.8 (1.0 to 4.1) | 1.6 (0.2 to 112.6) |
6. Primary Endpoint
The registry lists the primary outcome as Assessment of Seroconversion, Defined as Development of Immunoglobulin G (IgG) Antibodies Against Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) After Vaccination of 2 Doses in Seronegative Individuals., measured over 2 weeks after second dose of vaccine..
| Element | Registry entry |
|---|---|
| Result type | Count Of Participants |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is the proportion of seronegative individuals who developed IgG antibodies against SARS-CoV-2 after two vaccine doses. Seroconversion is defined in the registry as development of a positive response on an SARS-CoV-2 IgG serology test. The assessment was scheduled for 2 weeks after the second dose.
This endpoint describes a measured immune response. It is useful for characterizing whether participants who were seronegative at the relevant starting point later had a positive antibody test. The registry specifies that the proportion and its 95% confidence interval were to be assessed. A confidence interval communicates statistical uncertainty around an estimated proportion; it does not guarantee that the true value lies within the interval.
Seroconversion is not itself a clinical outcome such as symptomatic infection, hospitalization, or death. The registry lists PCR-documented SARS-CoV-2 infection separately as a secondary outcome, but does not report its result. Nor does the primary endpoint, as described, give a direct measure of cellular immunity, even though the study summary says cellular responses were among the planned investigations.
The primary endpoint result, including the proportion seroconverting and its confidence interval, is not reported in the registry record. Without that result, the endpoint’s observed frequency and precision cannot be evaluated from this record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record describes the question the study intended to address, but it does not report the primary endpoint result. In particular, it gives no observed proportion of seronegative individuals who developed a positive SARS-CoV-2 IgG result after two doses, and no confidence interval for that proportion. The central immunological result therefore cannot be interpreted from the registry record.
The record reports safety counts for two labeled groups. Among All Immunocompromised Patients, 23 serious adverse events were recorded among 449 at risk; among Controls, 0 were recorded among 90 at risk. Other adverse events were recorded for 173 among 449 in the immunocompromised group and 11 among 90 in the control group. The record lists 5 deaths in the immunocompromised group and 0 in the control group. These are descriptive counts in a non-randomized study; they do not, by themselves, establish that vaccination caused any event or that event risks differed because of vaccination.
The group labels indicate different populations, not randomized arms. Immunocompromised participants may differ from controls in characteristics relevant to adverse events and infection outcomes. The record does not provide an adjusted comparison or enough analytic detail to judge whether such differences were accounted for. A numerical contrast between the groups would therefore need cautious interpretation even if calculated from the posted counts.
The registry’s list of serious adverse event terms includes COVID-19 at 0.7%, Heart failure at 0.4%, Syncope at 0.4%, Urinary tract obstruction at 0.4%, Sepsis at 0.4%, and Increased CRP at 0.2%. These percentages describe terms in the registry’s serious-event listing; the record does not explain the calculation basis or provide event-level context for each term.
The study summary says immune responses, reactogenicity, and adverse events were to be assessed. A completed status does not mean that those outcomes are reported in the registry. The listed results support a limited description of recorded safety counts and serious-event terms, but they do not provide the primary immunological result or a basis for attributing events to the vaccine.
9. Statistical Methods Explained
What does the primary endpoint measure?
The primary endpoint is binary at the participant level: an individual either meets the registry’s definition of seroconversion or does not. The planned summary is a proportion, with a 95% confidence interval. A proportion expresses the frequency of an outcome relative to the relevant assessment group. The confidence interval describes uncertainty in that estimate under the statistical method used. It is not a guarantee about the true value, and its interpretation depends on the design and assumptions used to construct it.
The endpoint is restricted to seronegative individuals and is assessed 2 weeks after the second dose. That definition matters: a positive antibody test at the endpoint is the stated outcome, not a measure of the amount, durability, or protective effect of the antibody response. The registry record does not report the observed proportion, interval, analysis denominator, or handling of participants without an endpoint test.
Why does the study design matter?
In a randomized comparison, random assignment is intended to make groups comparable, on average, with respect to both measured and unmeasured characteristics. COVAXID is described as open and non-randomized, with allocation listed as not applicable. Its immunocompromised and control groups therefore should not be read as randomized treatment groups. Differences in outcomes across these groups could reflect the populations’ underlying characteristics, follow-up, or other factors, rather than a difference attributable to vaccination.
All participants were described as receiving Comirnaty according to current approval. The design can describe responses and events observed after vaccination, but a record without an unvaccinated randomized comparison cannot on its own establish what would have occurred to the same participants without vaccination. This is a general limitation of interpreting observational comparisons, not a claim about any particular unreported analysis in this study.
How should counts and proportions be read?
The safety information gives counts and the number at risk for each listed group. Such counts are descriptive. The number at risk identifies the stated group denominator for the event category, but the registry record does not explain whether every participant had the same duration of observation or complete event ascertainment. A count does not show when an event occurred, how long it lasted, its severity beyond the event category, or whether investigators judged it related to vaccination.
When an outcome is binary, a proportion is often a straightforward summary, but its precision depends on the number of observations and the number of events. A confidence interval conveys some of this sampling uncertainty. It does not correct for selection, missing outcome data, misclassification, or confounding. Those issues require design information and analytic details that are not reported in the registry record.
What can be learned from a serious-event listing?
The registry lists selected serious adverse event terms with percentages. These terms can indicate which categories appear in the reported listing, but interpretation depends on the denominator and the way terms were coded. The record does not report the derivation of each percentage, whether participants could contribute more than one event, or how the listed terms were selected. Thus the percentages should not be treated as directly comparable rates without further information.
In general, serious adverse event reporting is a safety description, not automatically evidence of causality. Events occurring during a study may arise for many reasons. Establishing whether an event was caused by an intervention requires clinical assessment and a comparison strategy appropriate to the question. The available record does not provide such a causal analysis.
What does a planning illustration mean?
Sample-size calculations are planning tools that explore how many participants might be needed under stated assumptions. They are not observed evidence and do not show whether a study had a particular probability of detecting an effect after the results are known. The registry record says its planning illustration is based on a fraction of an observed effect, assumes equal allocation, uses a two-sided significance level of 0.05 and a normal approximation, and distinguishes participants per arm from total events for time-to-event calculations. It also says that the illustration is not the trial’s own design. These assumptions describe the illustration, not a reported protocol plan or a result of the trial.
The registry record does not report an original sample-size justification, a statistical analysis plan, or the methods used for the primary endpoint analysis. It is therefore not possible to establish from the record whether the analysis followed a prespecified plan, how uncertainty was calculated, or how any departures from the plan were handled.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists multiple outcomes, including seroconversion, adverse events, local and systemic reactions, and PCR-documented SARS-CoV-2 infection. When investigators assess multiple outcomes or conduct multiple statistical tests, the chance of at least one apparently notable finding can increase. Statistical approaches to address this issue may include prespecified outcome hierarchies or adjustments to significance thresholds. The registry record does not report whether any such approach was planned or used.
The primary endpoint is identified, but the record does not report a complete analysis plan, the number of hypothesis tests conducted, or how secondary outcomes were analyzed. It also does not report whether subgroup analyses were prespecified. Without these details, the role of multiplicity in interpreting any unreported analyses cannot be assessed.
Missing data are also relevant to a proportion endpoint. The record does not report how many eligible seronegative participants had an evaluable antibody test at the endpoint, how missing tests were handled, or whether any participants were excluded from the primary analysis. It does not describe an analysis population such as all enrolled participants or participants with a measured endpoint. The planned time point is 2 weeks after the second dose, but the registry does not say how deviations from that timing were treated.
These omissions do not establish that data were missing or that analyses were inappropriate. They mean that the registry record does not provide enough information to evaluate completeness, analysis populations, or multiplicity handling. The completed study status does not resolve these reporting gaps.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| All Immunocompromised Patients | 23 | 449 | 5.1% |
| Controls | 0 | 90 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| All Immunocompromised Patients | 5 of 449 |
| Controls | 0 of 90 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| All Immunocompromised Patients | 173 of 449 |
| Controls | 11 of 90 |
Most frequent serious adverse event terms
| Event term | Organ system | All Immunocompromised Patients | Controls |
|---|---|---|---|
| COVID-19 | Infections and infestations | 3 of 449 | 0 of 90 |
| Heart failure | Cardiac disorders | 2 of 449 | 0 of 90 |
| Syncope | Nervous system disorders | 2 of 449 | 0 of 90 |
| Urinary tract obstruction | Renal and urinary disorders | 2 of 449 | 0 of 90 |
| Sepsis | Infections and infestations | 2 of 449 | 0 of 90 |
| Increased CRP | Investigations | 1 of 449 | 0 of 90 |
| Myocardial infarction | Cardiac disorders | 1 of 449 | 0 of 90 |
| Atrial fibrillation | Cardiac disorders | 1 of 449 | 0 of 90 |
| Surgery for colon carcinoma | Surgical and medical procedures | 1 of 449 | 0 of 90 |
| Organ rejection | General disorders | 1 of 449 | 0 of 90 |
Most frequent non-serious adverse event terms
| Event term | Organ system | All Immunocompromised Patients | Controls |
|---|---|---|---|
| Upper respiratory infection | Infections and infestations | 21 of 449 | 0 of 90 |
| Creatinine increased | Investigations | 17 of 449 | 2 of 90 |
| Platelet count decreased | Investigations | 17 of 449 | 0 of 90 |
| Hypertension | Vascular disorders | 13 of 449 | 0 of 90 |
| Fatigue | General disorders | 10 of 449 | 3 of 90 |
| Increased AST/ALT | Hepatobiliary disorders | 11 of 449 | 0 of 90 |
| Increased LFTs | Hepatobiliary disorders | 9 of 449 | 0 of 90 |
| Vaccination site lymphadenopathy | General disorders | 6 of 449 | 1 of 90 |
| Anemia | Blood and lymphatic system disorders | 7 of 449 | 0 of 90 |
| Tachypnea | Respiratory, thoracic and mediastinal disorders | 6 of 449 | 0 of 90 |
Serious events with the highest arm-level rate: covid-19 (0.7%), heart failure (0.4%), syncope (0.4%), urinary tract obstruction (0.4%), sepsis (0.4%).
The registry reports serious adverse events for All Immunocompromised Patients and Controls. The immunocompromised group has 23 serious adverse events among 449 at risk, while the control group has 0 among 90 at risk. Other adverse events are listed as 173 among 449 and 11 among 90, respectively. The death counts are 5 and 0, respectively. These figures are descriptive counts for the groups identified in the record.
The serious-event term listing includes COVID-19 at 0.7%, Heart failure at 0.4%, Syncope at 0.4%, Urinary tract obstruction at 0.4%, Sepsis at 0.4%, and Increased CRP at 0.2%. The record does not explain how the percentages were calculated or give the underlying number of events for each term in that list.
Because the study was non-randomized and the groups were not assigned by chance, their safety counts are not a randomized comparison. The record also does not report event timing, exposure duration, adjudication, or whether events were judged related to vaccination. The counts therefore describe what was recorded, but do not establish that Comirnaty caused an event, nor do they establish comparative safety between the groups.
12. What the Result Does, and Does Not, Mean
The registry record documents a completed phase IV study designed to examine immune responses after Comirnaty vaccination in immunosuppressed and immunocompetent individuals. It specifies seroconversion among seronegative individuals as the primary endpoint, assessed 2 weeks after the second dose. However, the primary outcome result is not reported in the registry record. The record consequently does not answer, in numerical terms, how often seroconversion occurred or how precise that estimate was.
The reported safety information provides counts of serious and other adverse events, deaths, and a list of serious-event terms. These figures describe events recorded in the listed groups. They do not show whether an event was caused by vaccination. The non-randomized design and differences between the immunocompromised and control populations also prevent the group counts from serving as a like-for-like randomized comparison.
The study summary describes plans to examine humoral and cellular responses using blood and saliva, as well as reactogenicity and adverse events. The registry’s outcome listings alone do not provide results for all of those measures. In particular, an antibody seroconversion outcome does not summarize all cellular or humoral responses, and it is not the same as a clinical outcome such as PCR-documented infection.
Accordingly, the record offers information about the study design, intended measurements, and some safety counts, but not the principal numerical immune-response result. It should not be read as proof that vaccination did or did not produce a particular level of seroconversion, or as a causal estimate of vaccine effects. The missing endpoint results and limited analytic detail constrain what can be concluded from the registry record.
13. Why This Trial Matters Statistically
This study addresses a statistical challenge in evaluating immune responses across populations that may differ in immune status. A seroconversion proportion can describe how often a defined antibody response is observed in a specified population and at a specified time point. In COVAXID, the registry defines that time point as 2 weeks after the second dose and focuses on participants who were seronegative.
That focused outcome is only one part of the broader question. The study summary describes humoral and cellular vaccine responses, while the registry also lists reactogenicity, adverse events, and PCR-documented infection. Keeping these outcomes distinct is important: an antibody test result is not interchangeable with a cellular immune measure, a reported symptom, or a clinical infection outcome.
The study’s non-randomized design also makes transparent interpretation important. Immunocompromised participants and controls are not randomized arms, so differences between them could arise from differences between the groups themselves. Clear reporting of endpoint definitions, denominators, uncertainty, missing data, and analysis methods would help readers judge what the observed data support.
The registry record identifies the intended primary endpoint and provides some safety counts, but does not report the primary result or detailed analysis methods. This makes the study statistically relevant as an example of why a stated endpoint and completed status are not substitutes for outcome reporting. It also illustrates why descriptive safety counts should not be treated as causal evidence in the absence of a suitable comparison and supporting analysis.
14. Limitations
- The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
- Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.
The primary limitation for interpreting the study is that the seroconversion result is not reported in the registry record. The planned proportion and 95% confidence interval are described, but no estimate, interval, or analysis denominator is given. The central endpoint therefore cannot be assessed for magnitude or precision.
The registry record also does not report details of the statistical analysis plan, sample-size justification, missing-data handling, analysis populations, or methods for addressing multiple outcomes. It does not explain how the primary endpoint’s seronegative population was defined in practice or how participants without a measured endpoint were handled. These are reporting gaps; they do not prove that the study lacked those procedures.
The open, non-randomized design means the immunocompromised and control groups are not randomized comparators. The record does not describe adjustment for differences between the groups, so safety counts should not be interpreted as causal comparisons. The record also lacks event-level details such as timing, duration, adjudication, and attribution to vaccination.
Although the study summary says blood and saliva were used to investigate humoral and cellular responses, the registry record does not report numerical results for those measures. The safety listing gives selected serious-event terms and percentages, but does not specify how the percentages were derived or whether events could be counted more than once. These constraints limit interpretation of both the immune-response aims and the reported safety information.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: COVID-19 Vaccination of Immunodeficient Persons (COVAXID) — NCT04780659.
- Registry record last updated 2025-12-04; status last verified 2025-11.
- Results first posted 2025-12-04.
- Data retrieved from ClinicalTrials.gov on 2026-11-09.
- Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.
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18. Record Summary
COVAXID (NCT04780659) is a completed, open, non-randomized phase IV multicenter cohort study sponsored by Karolinska University Hospital. The registry lists enrollment of 539, a start date of 2021-02-23, and primary completion on 2021-10-15.
Participants received two doses of Comirnaty according to current approval. The study included people with primary or secondary immunosuppressive disorders and immunocompetent individuals. Its primary endpoint was seroconversion to a positive SARS-CoV-2 IgG result among seronegative individuals, assessed 2 weeks after the second dose.
The primary endpoint result and its confidence interval are not reported in the registry record. Safety counts are reported for immunocompromised patients and controls, but the groups were not randomized comparators. The registry record does not report a detailed statistical analysis plan or missing-data methods.