Sex: U
Vaccine: COVID19
Symptoms: C-reactive protein, COVID-19, Cardiovascular function test, Colitis, Death
Clinical narrative: ARRHYTHMIA; CONFIRMED CLINICAL VACCINATION FAILURE; CONFIRMED COVID-19 INFECTION; GASTROENTERITIS; COLITIS; LOWER RESPIRATORY TRACT INFECTION; ANXIETY; MOOD DISORDER; DEATH; This report received from a physician: Oral Nirmatrelvir and Ritonavir in Non-hospitalized Vaccinated Patients with Covid-19; 1-30 concerned a multiple patients (111588) of unspecified age, sex, race and ethnicity. The patients were enrolled in a non-company sponsored study COV19VAC-NONCOMP: Jansen COVID 19 Non Company. The objective of the authors was to conduct a comparative retrospective study using the research network. Patients greater than or equal to18 years of age who were vaccinated and subsequently developed Covid-19 between 01-DEC-2021, and 18-APR-2022, were included. Were developed based on the use of NMV-r (nirmatrelvir plus ritonavir) within five days of diagnosis. The patients height, and weight were not reported. The patients concurrent conditions included: hypertension, hyperlipidemia, diabetes mellitus, chronic lower respiratory disease, chronic kidney disease, atrial fibrillation/atrial flutter, ischemic heart disease, heart failure, ischemic stroke, malignancy, demyelinating disease, and systematic connective tissue disorder. The patients initiated treatment with covid-19 vaccine ad26.cov2.s (suspension for injection, route of admin, and batch number were not reported, expiry: unknown) 1 in total, dose, start therapy date were not reported for covid-19 prophylaxis. The batch number was not reported and has been requested. Concomitant medications included acetylsalicylic acid, Beta Blockers, Diuretics, ACE (Angiotensin converting enzyme) inhibitors, Angiotensin Receptor Blocker, Aspirin, Anticoagulants, Statins, Immune Suppressants, Antineoplastics, Antidepressants, Anticonvulsants. On an unspecified date, the patients experienced arrhythmia, gastroenteritis, colitis, confirmed covid-19 infection, confirmed clinical vaccination failure, lower respiratory tract infection, anxiety and mood disorder, and was hospitalized (date unspecified). The number of days of hospitalization was not reported and it was unsure if the patients was discharged from the hospital.  The patients were treated with Non-company suspect drugs included: nirmatrelvir/ritonavir (form of admin, route of admin, and batch number were not reported) dose, frequency, and therapy dates were not reported for covid-19 treatment.  A comparative retrospective study was conducted, including non-hospitalized patients greater than or equal to 18 years of age who were vaccinated and subsequently developed Covid-19 and tested positive for SARS-Cov-2 at least one month after vaccination and between 01-DEC-2021, and 18-APR-2022. Key exclusion criteria were treatment with a monoclonal antibody, convalescent plasma, or molnupiravir for the index case of Covid-19. Patients were further categorized based use of NMV-r within five days of diagnosis. Validated diagnostic, procedure, and laboratory codes were utilized to define the vaccination status and Covid-19 diagnosis. Were matched using propensity score matching (PSM), a technique that attempts to adjust for confounding by selecting a control sample from the untreated population as similar as possible to the treatment group. Primary and secondary outcomes were analyzed 30-days after the index diagnosis of Covid-19 in the control or after initiation of NMV-r in the treatment. The primary composite endpoint of this study was all-cause emergency room (ER) visits, hospitalization, or death at a 30-days follow-up. Secondary endpoints included individual components of composite primary endpoints: all-cause ER visits, hospitalization, and death. Additionally, pre-specified secondary outcomes included the 1 prevalence of various systemic and nonspecific symptoms (constitutional, cardio-respiratory, gastrointestinal, nervous system and musculoskeletal symptoms, smell-taste alteration), systemic complications (cardiovascular, respiratory, gastrointestinal, mood disorders), and diagnostic testing utilization (radiologic diagnostic tests, cardiovascular diagnostic tests (echocardiogram and heart rhythm monitor)) within 30 days of diagnosis of Covid-19. To explore rebound or prolonged Covid symptoms or complications, outcomes between 10 to 30-days following the diagnosis of Covid-19 or initiation of NMV-r was assessed. Non-hospitalized vaccinated patients who subsequently developed Covid-19 were divided into two based on their use of NMV-r within five days of diagnosis: NMV-r and non-NMV-r. A total of 111,588 non-hospitalized vaccinated patients with Covid-19 were identified during the study period. Of the total vaccinated, 1,131 patients received NMV-r within five days of the diagnosis, and 110,457 did not receive NMV-r. Patients treated with NMV-r were older (mean age 57.6 with the deviation of 16.3 vs. 49.3 with deviation of 17.6 years; SD: 0.485). Females comprised 63% of the study population. Were 9.7% in the NMV-r vs. 17.8% in the non-NMV-r group before propensity matching. Patients receiving NMV-r were predominantly Adults (81.9%). Furthermore, patients on NMV-r had a higher prevalence of cardiovascular risk factors, established CVD (and be on medications for CVD), neoplasms, and chronic lower respiratory disease. A primary composite outcome of all-cause ER visits, hospitalization, or death in 30 days occurred in 89 (7.87%) patients in the NMV-r and 163 (14.4%) patients in the non-NMV r (OR 0.5, CI 0.39-0.67; p less than 0.005), consistent with 45% relative risk reduction. Furthermore, patients on NMV-r had a higher probability of event-free survival at 30-days (88.15% vs. 84.16%, HR 0.67 (CI 0.52, 0.87); p equals to 0.002). All-cause ER (Emergency room visits (82 vs. 142, OR 0.55, CI 0.41-0.73, p less than 0.05) and hospitalization (10 vs. 23), 15 OR 0.43, CI 0.2-0.9; p equals 0.02) were significantly lower in Covid-19 patients who received NMV- r. Ten deaths were noted (It was unknown if an autopsy was performed), all in the non-NMV-r, whereas no deaths occurred (p less than 0.05) in the group receiving NMV-r. Patients on NMV-r had fewer constitutional, cardio respiratory, gastrointestinal, nervous, and musculoskeletal symptoms. No significant difference was noted in reported smell-taste alteration between the two. Overall, systemic complications, such as lower respiratory tract infections, arrhythmias, and anxiety/mood disorders, were seen less frequently in the NMV- than in the non-NMV-r. No difference was noted in the occurrence of gastroenteritis, colitis, or diarrhea. Further, patients receiving NMV-r had lower utilization of radiologic diagnostic testing than those who did not receive NMV-r. Cardiovascular diagnostic testing was similar in both. An exploratory secondary analysis of outcomes between 10 to 30-days following the diagnosis of Covid-19 or NMV-r initiation showed that patients in the NMV-r  continued to have overall fewer symptoms and complications. Overall symptom burden was reduced in both  over time and became similar for nervous, musculoskeletal, and constitutional symptoms. However, cardio-respiratory and gastrointestinal symptoms, anxiety/mood disorder, and all-cause ER visits, hospitalization, or death remained lower in the NMV-r at 30 days. In addition, the occurrence of smell-taste alteration, which was similar in both for the entire 30-days follow-up, was significantly less frequent in the NMV-r between 10 to 30-days follow-up. Laboratory data (dates unspecified) included: SARS-CoV-2 test positive, C-reactive protein for subjects with Nirmatrelvir-Ritonavir before propensity matching: 92 (8.1%), with no Nirmatrelvir-Ritonavir:6324 (5.7%) ; after propensity matching with Nirmatrelvir-Ritonavir: 92 (8.1%) and with no Nirmatrelvir- Ritonavir:72 (6.3%), Cardiovascular function test for subjects with Nirmatrelvir-Ritonavir before propensity matching:10 (0.88%) with no Nirmatrelvir-Ritonavir: 14 (1.24%) with the risk difference of -0.004 (-0.012, 0.005) ; with Relative Risk Reduction: 33%, odds ratio:0.712 (0.315, 1.609), P-value: 0.412, Cholesterol total for subjects with Nirmatrelvir-Ritonavir before propensity matching: 183.4 mg/dl with the deviation of 40.9 mg/dl (n equals to 902), with no Nirmatrelvir-Ritonavir: 178.9 mg/dl with the deviation of 42.6 mg/dl (n equals to 65, 344) ; after propensity matching with Nirmatrelvir-Ritonavir: 183.4 mg/dl with the deviation of 40.9 mg/dl (n equal to 901) and with no Nirmatrelvir- Ritonavir: 181.3 mg/dl with the deviation of 43.4 mg/dl (n equal to 908), Creatinine for subjects with Nirmatrelvir-Ritonavir before propensity matching: 0.88 mg/dl with the deviation of 0.2 (n-number of subjects, equal to1068), with no Nirmatrelvir-Ritonavir: 0.98 mg/dl with the deviation of 1.9 (n equals to 75, 270) ; after propensity matching with Nirmatrelvir-Ritonavir: 0.88 mg/dl with the deviation of 0.2 (n equal to 1, 068) and with no Nirmatrelvir-Ritonavir: 0.92mg/dl with the deviation of 0.5 (n equal to 1018), Ferritin for subjects with Nirmatrelvir-Ritonavir before propensity matching: 181.5 micrograms/L with the deviation of 427.8 micrograms/L (n equal to 283), with no Nirmatrelvir-Ritonavir: 218.4 micrograms/L with the deviation of 676.6 micrograms/L (n equals to 21, 899) ; after propensity matching with Nirmatrelvir-Ritonavir: 181.5 micrograms/L with the deviation of 427.8 micrograms/L (n equal to 283) ) and with no Nirmatrelvir- Ritonavir: 172.3 micrograms/L with the deviation of 274.9 micrograms/L (n equal to 273), Glycosylated haemoglobin for subjects with Nirmatrelvir-Ritonavir before propensity matching: 6.1 with the deviation of 1.7 (n equal to 799), with no Nirmatrelvir-Ritonavir :6.1 with the deviation of 1.6 (n equals to 51, 351) ; after propensity matching with Nirmatrelvir-Ritonavir: 6.1 with the deviation of 1.7 (n equal to 798) and with no Nirmatrelvir- Ritonavir: 6.0 with the deviation of 1.4 (n equal to 779), Hemoglobin for subjects with Nirmatrelvir-Ritonavir before propensity matching: 13.6 g/dl with the deviation of 1.5 (n equal to1023) (n-number of subjects, equal 1023), with no Nirmatrelvir-Ritonavir: 13.3 g/dl with the deviation of 1.8 (n equals to 85, 080) ; after propensity matching with Nirmatrelvir-Ritonavir: 13.6 g/dl with the deviation of 1.5 (n equal to 1022) ) and with no Nirmatrelvir-Ritonavir:13.6 g/dl with the deviation of 1.7 (n equal to 1005), Investigation for subjects with Nirmatrelvir-Ritonavir before propensity matching:48 (4.24%), with no Nirmatrelvir-Ritonavir: 71 (6.23%) with the risk difference of -0.020 (-0.039, -0.002) ; with Relative Risk Reduction: 32%, odds ratio: 0.662 (0.454, 0.964), P-value: 0.03, LDL for subjects with Nirmatrelvir-Ritonavir before propensity matching: 103.5 mg/dl with the deviation of 34.1 mg/dl (n equal to 941), with no Nirmatrelvir-Ritonavir:102.7 mg/dl with the deviation of 35.6 mg/dl (n equals to 67, 443) ; after propensity matching with Nirmatrelvir-Ritonavir: 103.5 mg/dl with the deviation of 34.1 mg/dl (n equal to 940) and with no Nirmatrelvir- Ritonavir: 103.6 mg/dl with the deviation of 36.2 mg/dl (n equal to 939), Left ventricular ejection fraction for subjects with Nirmatrelvir-Ritonavir before propensity matching: 61.3 % with the deviation of 10.7 % (n equal to 167), with no Nirmatrelvir-Ritonavir :58.9 % with the deviation of 11.9% (n equals to 7, 178) ; after propensity matching with Nirmatrelvir-Ritonavir: 61.3 % with the deviation of 10.8 % (n equal to 166) and with no Nirmatrelvir- Ritonavir: 60.5 % with the deviation of 9.5 % (n equal to 143), Lymphocytes for subjects with Nirmatrelvir-Ritonavir before propensity matching: 28.0 with the deviation of 10.4 (n equal to 938) ) (n-number of subjects, equal 938) ), with no Nirmatrelvir-Ritonavir: 27.3 with the deviation of 10.6 (n equals to74, 697 ) ; after propensity matching with Nirmatrelvir-Ritonavir: 28.0 with the deviation of 10.4 (n equal to 937) ) and with no Nirmatrelvir-Ritonavir:27.1 with the deviation of 10.4 (n equal to 897), and Platelet count for subjects with Nirmatrelvir-Ritonavir before propensity matching:253.8 with the deviation of 76.2 (n equal to 1, 023) (n-number of subjects, equal 938) ), with no Nirmatrelvir-Ritonavir: 257.8with the deviation of 77.3 (n equals to 84, 769) ; after propensity matching with Nirmatrelvir-Ritonavir: 253.8 with the deviation of 76.2 (n equal to 1022) and with no Nirmatrelvir- Ritonavir:250.6 with the deviation of 70.7 (n equal to 1005). The patients reported symptoms included: Constitutional symptoms, Cardio-respiratory symptoms, Gastrointestinal symptoms, Nervous system and musculoskeletal symptoms, Smell-taste alteration. The complications included: Lower respiratory tract infection (with Paxlovid: 27 (2.38%), with no paxlovid: 92 (8.14%), Arrhythmia (with paxlovid: 22 (1.9%), with no paxlovid: 43 (3.8%), Gastroenteritis/Colitis/Diarrhea (with paxlovid: 12 (1%), with no paxlovid: 13 (1.1%), Anxiety/mood disorder (with paxlovid: 64 (5.6%), with no paxlovid: 114 (10%). The action taken with covid-19 vaccine ad26.cov2.s was not applicable; and action taken with nirmatrelvir/ritonavir was not reported. The patients died of an unspecified cause on an unspecified date, and the outcome of confirmed covid-19 infection, confirmed clinical vaccination failure, lower respiratory tract infection, arrhythmia, gastroenteritis, colitis, anxiety and mood disorder was not reported. The reporter provided no causality assessment. Company causality between covid-19 vaccine ad26.cov2.s, and death, arrhythmia, gastroenteritis, colitis, confirmed covid-19 infection, confirmed clinical vaccination failure, lower respiratory tract infection, anxiety and mood disorder was not related.  The authors concluded that in vaccinated non-hospitalized patients with Covid-19, real-world data demonstrated a strong association between treatment with nirmatrelvir with ritonavir (NMV-r) and improved outcomes. The study shows that when NMV-r was administered within five days of Covid-19 diagnosis, there was a 45% relative risk reduction in the occurrence of subsequent emergency room (ER) visits, hospitalizations, or deaths compared to a group receiving no treatment. Also reported reduced symptom burden (constitutional, cardio-respiratory, gastrointestinal, nervous system, and musculoskeletal symptoms) and complications such as lower respiratory tract infection or cardiac arrhythmia. While a virologic rebound is known to occur in some treated patients, findings demonstrate that, even if a rebound did occur in some, it did not negate the benefit of NMV-r treatment and found no late increase in complications among those with treatment compared to no treatment, although study likely would have missed cases of transient or mild rebound occurring between 10 and 30 days after diagnosis. These are further reflected in our secondary outcomes, with a 72% relative risk reduction in the subsequent development of pneumonia and 50% reduction in arrhythmia in patients treated with NMV-r. Furthermore, treatment was associated with fewer clinical complaints at 30-days, specifically cardio-respiratory, gastrointestinal, nervous system, and musculoskeletal and constitutional symptoms. With lower rates of these complications, not surprisingly, we also observed additional evidence of reduced resource utilization, with a significant relative reduction in diagnostic radiology testing (45%) in NMV-r treated patients. This report was serious (Death, and Hospitalization Caused / Prolonged). This report was associated with a product quality complaint, and reference number requested.; Sender's Comments: V0: 20230374394- Death, Gastroenteritis, Colitis, Anxiety, Mood disorder .The event has an unknown/unclear temporal relationship, is unlabeled, and has unknown scientific plausibility. There is no information on any other factors potentially associated with the event. Therefore, the WHO Causality is considered indeterminate. The company causality is considered not related. 20230374394-Arrhythmia, Lower respiratory tract infection. The event has an unknown/unclear temporal relationship, is unlabeled, and has unknown scientific plausibility. There are other factors more likely to be associated with the event. Specifically: MEDICAL HISTORY. Therefore, this event is considered inconsistent with vaccine administration. 20230374394-Confirmed covid-19 infection. The event is deemed to be scientifically implausible, i.e., there is scientific evidence against a drug/event relationship; AND there is no known class effect. Therefore, this event is considered inconsistent with vaccine administration. 20230374394-Confirmed clinical vaccination failure. The event has an unknown/unclear temporal relationship, is unlabeled, and has unknown scientific plausibility. There are other factors more likely to be associated with the event. Specifically: SPECIAL SITUATIONS. Therefore, this event is considered inconsistent with vaccine administration.; Reported Cause(s) of Death: UNKNOWN CAUSE OF DEATH