Non-specific protection against severe COVID-19 associated to typhoid fever and DTP vaccination.

Trained immunity (TRAIM) or the enhanced non-specific immune response after primary stimulation by infection or vaccination is a recent but well-recognized concept. To verify its predictions, our objective was to determine the effects of two bacterial vaccines, typhoid fever (TFV) and diphtheria-tetanus-pertussis (DTP) on the infection, hospitalization and death frequencies associated to COVID-19 in a retrospective study on subjects vaccinated or not with TFV and DTP in the 4 years prior to the start of COVID-19 pandemia in the Basque Country (Spain). The studied outcome records were split into two periods according to COVID-19 vaccination, the pre-vaccination (ACV) from March to December 2020 and the post-vaccination (PCV) from September 2021 to June 2022). In total, 13,673 subjects were vaccinated against TFV and 42,997 against DTP. A total of 2,005,084 individual records were studied in the ACV period and 1,436,693 in the PCV period. The proportion of infection, hospitalization and death associated to COVID-19 among controls in ACV was 4.97 %, 7.14 % and 3.54 %, respectively vs. 7.20 %, 2.24 % and 0.10 % among TFV subjects. Regarding DTP, the proportions were 4.97 %, 7.12 % and 3.58 % for controls and 5.79 %, 5.79 % and 0.80 % for vaccinees. In the PCV period, the proportion of infection, hospitalization and death among controls was 21.89 %, 2.62 % and 0.92 %, respectively vs. 31.19 %, 0.76 %, 0.00 % among TFV. For DTP, infection, hospitalization and death proportions were 21.89 %, 2.62 % and 0.92 %, respectively, among controls vs. 32.03 %, 1.85 % and 0.24 % among vaccinated subjects. The corresponding combined ACV and PCV odds ratios (OR) for SARS-CoV2 infection were 1.505 (95%CI 1.455-1.558; p < 0.0001; reduction -41.85 %) and 1.633 (95%CI 1.603-1.662; p < 0.0001; reduction -51.74 %), for TFV and DTP, respectively. Regarding COVID-19 associated hospitalization, the OR were 0.295 (95%CI 0.220-0.396; p = 0.0001; reduction 69.74 %) and 0.667 (95%CI 0.601-0.741; p = 0.0001; reduction 32.44 %), for TFV and DTP, respectively). COVID-19 associated death OR were 0.016 (95%CI 0.002-0.113, p < 0.0001; reduction 98.38 %) and 0.212 (95%CI 0.161-0.280; p = 0.0001; reduction 78.52 %), for TFV and DTP, respectively. We conclude that TRAIM effects by TFV and DTP vaccination in the four years prior to the pandemic SARS-CoV2 were supported by slightly increased infection rates, but strongly reduced COVID-19 associated hospitalization and death rates.

Analysis of SARS-CoV-2 reverse transcription-quantitative polymerase chain reaction cycle threshold values vis-à-vis anti-SARS-CoV-2 antibodies from a high incidence region.

OBJECTIVES: To examine the relationship between antibody status and cycle threshold (Ct) values, the prognostic value of the latter for COVID-19 patients, and the inter-assay comparability of SARS-CoV-2 Ct values. METHODS: In 347 COVID-19 inpatients, SARS-CoV-2 Ct values (via reverse transcription-quantitative polymerase chain reaction) on admission were compared between 2 assays and correlated with the antibody response (in the course of the disease), the clinical course and the time since onset of symptoms. RESULTS: Ct values for 2 of 3 target genes showed significant differences between the 2 assays used (P=0.012 and P<0.0001). Ct values were significantly higher for antibody positive patients (P<0.0001) and positively correlated with the amount of time since onset of symptoms (R: 0.332-0.363; P<0.001). Patients with fatal outcomes showed higher viral loads than survivors (P<0.0001). CONCLUSIONS: Ct values depend strongly on assay used and target gene examined and should not be used as quantitative values to guide therapeutic or diagnostic decisions. The inverse association between antibody status and viral load suggests that antibodies contribute to the elimination of the virus, independent of the outcome, which is influenced by the viral load on admission and might depend more strongly on other parts of the immune response.

Clinical correlates of anti-SARS-CoV-2 antibody profiles in Spanish COVID-19 patients from a high incidence region.

Laboratory testing for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) consists of two pillars: the detection of viral RNA via rt-PCR as the diagnostic gold standard in acute cases, and the detection of antibodies against SARS-CoV-2. However, concerning the latter, questions remain about their diagnostic and prognostic value and it is not clear whether all patients develop detectable antibodies. We examined sera from 347 Spanish COVID-19 patients, collected during the peak of the epidemic outbreak in Spain, for the presence of IgA and IgG antibodies against SARS-CoV-2 and evaluated possible associations with age, sex and disease severity (as measured by duration of hospitalization, kind of respiratory support, treatment in ICU and death). The presence and to some degree the levels of anti-SARS-CoV-2 antibodies depended mainly on the amount of time between onset of symptoms and the collection of serum. A subgroup of patients did not develop antibodies at the time of sample collection. Compared to the patients that did, no differences were found. The presence and level of antibodies was not associated with age, sex, duration of hospitalization, treatment in the ICU or death. The case-fatality rate increased exponentially with older age. Neither the presence, nor the levels of anti-SARS-CoV-2 antibodies served as prognostic markers in our cohort. This is discussed as a possible consequence of the timing of the sample collection. Age is the most important risk factor for an adverse outcome in our cohort. Some patients appear not to develop antibodies within a reasonable time frame. It is unclear, however, why that is, as these patients differ in no respect examined by us from those who developed antibodies.

Cytomegalovirus hepatitis and myopericarditis.

Cytomegalovirus (CMV) infection in inmunocompetent hosts generally is asymptomatic or may present as a mononucleosis syndrome but rarely can lead to severe organ complications. We report a case of simultaneous hepatic and pericardic CMV infection in a 36-year old immunocompetent man. He was admitted to coronary unit with fever, chest pain radiated to shoulders, changes on electrocardiogram with diffuse ST elevation and modest laboratory elevations in the MB fraction of creatine kinase (CK-MB) of 33.77 microg/L (0.1-6.73), serum cardiac troponin T of 0.904 ng/mL (0-0.4), creatine kinase of 454 U/L (20-195) and myoglobin of 480.4 microg/L (28-72). Routine laboratory test detected an elevation of aminotransferase level: alanine aminotransferase 1445 U/L, aspartate aminotransferase 601 U/L. We ruled out other causes of hepatitis with normal results except IgM CMV. The patient was diagnosed with myopericarditis and hepatitis caused by cytomegalovirus and started symptomatic treatment with salicylic acid. In few days the laboratory findings became normal and the patient was discharged.