Effectiveness of a nation-wide COVID-19 vaccination program in Mexico (preprint)

ABSTRACT BACKGROUND Vaccination has been effective in ameliorating the impact of COVID-19. However, estimation of vaccine effectiveness (VE) is still unavailable for some widely used vaccines and underrepresented groups. Here, we report on the effectiveness of a nation-wide COVID-19 vaccination program in Mexico. METHODS We used a test-negative design within a national COVID-19 surveillance system to assess VE of the BNT162b2, mRNA-12732, Gam-COVID-Vac, Ad5-nCoV, Ad26.COV2.S, ChAdOx1 and CoronaVac vaccines, against SARS-CoV-2 infection, COVID-19 related hospitalization and death for adults ≥18 years in Mexico. VE was estimated using Cox proportional hazard models considering time-varying vaccination status in partial and fully vaccinated individuals compared to unvaccinated adults, adjusted by age, sex, comorbidities and municipality. We also estimated VE for adults ≥60 years, for cases with diabetes and comparing periods with predominance of variants B.1.1.519 and B.1.617.2. RESULTS We assessed 793,487 vaccinated compared to 4,792,338 unvaccinated adults between December 24 th , 2020, and September 27 th , 2021. VE against SARS-CoV-2 infection was highest for fully vaccinated individuals with mRNA-12732 (91.5%, 95%CI 90.3-92.4) and Ad26.COV2.S (82.2%, 95%CI 81.4-82.9), whereas for COVID-19 related hospitalization were BNT162b2 (84.3%, 95%CI 83.6-84.9) and Gam-COVID-Vac (81.4% 95%CI 79.5-83.1) and for mortality BNT162b2 (89.8%, 95%CI 89.2-90.2) and mRNA-12732 (93.5%, 95%CI 86.0-97.0). VE for all evaluated vaccines was reduced for adults ≥60 years, people with diabetes, and in periods of Delta variant predominance. CONCLUSIONS All evaluated vaccines were effective against SARS-CoV-2 infection and COVID-19 related hospitalization and death. Mass vaccination campaigns with multiple vaccine products are feasible and effective to maximize vaccination coverage.

Antibody and memory B-cell immunity in a heterogeneously SARS-CoV-2 infected and vaccinated population (preprint)

Global population immunity to SARS-CoV-2 is accumulating through heterogenous combinations of infection and vaccination. Vaccine distribution in low- and middle-income countries has been variable and reliant on diverse vaccine platforms. We studied B-cell immunity in Mexico, a middle-income country where five different vaccines have been deployed to populations with high SARS-CoV-2 incidence. Levels of antibodies that bound a stabilized prefusion spike trimer, neutralizing antibody titers and memory B-cell expansion correlated with each other across vaccine platforms. Nevertheless, the vaccines elicited variable levels of B-cell immunity, and the majority of recipients had undetectable neutralizing activity against the recently emergent omicron variant. SARS-CoV-2 infection, experienced prior to or after vaccination potentiated B-cell immune responses and enabled the generation of neutralizing activity against omicron and SARS-CoV for all vaccines in nearly all individuals. These findings suggest that broad population immunity to SARS-CoV-2 will eventually be achieved, but by heterogenous paths

Inexpensive workflow for simultaneous monitoring of HIV viral load and detection of SARS-CoV-2 infection (preprint)

BackgroundCOVID-19 pandemic interrupted routine care for individuals living with HIV, putting them at risk of becoming virologically unsuppressed and ill. Often they are at high risk for exposure to SARS-CoV-2 infection and severe disease once infected. For this population, it is urgent to closely monitor HIV plasma viral load (VL) and screen for SARS-COV-2 infection. MethodWe have developed a non-proprietary method to isolate RNA from plasma, nasal secretions (NS), or both. HIV, SARS-CoV-2, and human RP targets in extracted RNA are then RT-qPCR to estimate the VL and classify HIV/SARS-CoV-2 status (i.e., HIV as VL failure or suppressed; SARS-CoV-2 as positive, presumptive positive, negative, or indeterminate). We evaluated this workflow on 133 clinical specimens: 40 plasma specimens (30 HIV-seropositive), 67 NS specimens (31 SARS-CoV-2-positive), and 26 pooled plasma/NS specimens (26 HIV-positive with 10 SARS-CoV-2-positive), and compared the results obtained using the in-house extraction to those using a commercial extraction kit. ResultsIn-house extraction had a detection limit of 200-copies/mL for HIV and 100-copies/mL for SARS-CoV-2. In-house and commercial methods yielded positively correlated HIV VL (R2: 0.98 for contrived samples; 0.81 for seropositive plasma). SARS-CoV-2 detection had 100% concordant classifications in contrived samples, and in clinical NS extracted by in-house method, excluding indeterminate results, was 95% concordant (25 positives, 6 presumptive positives, and 31 negatives) to those using the commercial method. Analysis of pooled plasma/NS showed R2 of 0.91 (contrived samples) and 0.71 (clinical specimens) for HIV VL correlations obtained by both extraction methods, while SARS-CoV-2 detection showed 100% concordance in contrived and clinical specimens. InterpretationOur low-cost workflow for molecular testing of HIV and SARS-CoV-2 could serve as an alternative to current standard assays for laboratories in low-resource settings.

Seroepidemiology of SARS-CoV-2 in Healthcare Personnel Working at the Largest Tertiary COVID-19 Referral Hospitals in Mexico City (preprint)

Background: We performed a longitudinal SARS-CoV-2 seroepidemiologic study in healthcare personnel of the two largest tertiary referral hospitals in Mexico City. Methods: Participants answered a computer-assisted self-administered interview and donated blood samples for antibody testing every three weeks from October 2020 to June 2021. Findings: 290/883 participants had a positive result in any of the antibody tests, yielding an overall adjusted prevalence in the study period of 33·5%. 235 positive tests were identified at baseline (prevalent cases), the remaining 55 positive tests were incident cases. Prevalent cases showed associations with both occupational (institution 2 vs. 1: adjusted odds ratio [aOR]=2·24, 95% confidence interval [CI]: 1·54, 3·25; laboratory technician vs. medical doctor: aOR=4·38, 95% CI: 1·75, 10·93) and community risk (municipality of residence Xochimilco vs. Tlalpan: aOR=2·03, 95% CI: 1·09, 3·79). The incidence rate was 3·0 cases per 100 person-months. Incident cases were mainly associated with community-acquired risk, due to contact with suspect/confirmed COVID-19 cases (HR=2·45, 95% CI: 1·21, 5·00).Interpretation: We observed similar level of exposure to SARS-CoV-2 in healthcare workers of the two largest tertiary COVID-19 referral centers in Mexico City to the general population. Most variables associated with exposure in this setting pointed toward community rather than occupational risk.Funding: Consejo Nacional de Ciencia y Tecnología (CONACyT) (Fondo FORDECYT-PRONACES) and the Mexican Government (Programa Presupuestal P016; Anexo 13 del Decreto del Presupuesto de Egresos de la Federación).Declaration of Interest: None to declare. Ethical Approval: The study was reviewed and approved by the Institutional Review Boards of both participating institutions.

EVALUATION OF A RAPID ANTIGEN TEST FOR SARS-COV-2 IN SYMPTOMATIC PATIENTS AND THEIR CONTACTS: A MULTICENTER STUDY (preprint)

BACKGROUND Point-of-care rapid tests to identify SARS-CoV-2 can be of great help because, in principle, they allow decisions to be made at the site of care for treatment, or for the separation of cohorts avoiding cross-infection, especially in emergency situations. METHODS A cross sectional study in adults requesting care in Emergency Rooms (ER), or the outpatient clinics of referral hospitals for COVID-19, to define the diagnostic characteristics of a rapid antigen test for SARS-CoV-2 (the Abbott PanbioTM) having as a gold standard the RT-PCR for SARS-CoV-2. Health personnel in a routine situation within an active pandemic in several cities of Mexico performed the tests. RESULTS A total of 1,069 participants with a mean age of 47 years (SD 16 years), 47% with a self-reported comorbidity, and an overall prevalence of a positive RT-PCR test of 45%, were recruited from eight hospitals in Mexico. Overall sensitivity of the Panbio test was 54.4% (95%CI 51-57) with a positive likelihood ratio of 35.7, a negative likelihood ratio of 0.46 and a Receiver-Operating Characteristics curve area of 0.77. Positivity for the rapid test depended strongly on an estimate of the viral load (Cycle threshold of RT-PCR, Ct), and the days of symptoms. With a Ct 25, sensitivity of the rapid test was 0.82 (95%CI, 0.76-0.87). For patients during the first week of symptoms sensitivity was 69.6% (95%CI 66-73). On the other hand, specificity of the rapid test was above 97.8% in all groups. CONCLUSIONS The PanbioTM rapid antigen test for SARS-CoV-2 has a good specificity, but due to low and heterogeneous sensitivity in real life, a negative test in a person with suggestive symptoms at a time of community transmission of SARS-CoV-2 requires confirmation with RT-PCR, and after the first week of symptoms, sensitivity decreases considerably.

Systemic and Neurologic Adverse Events Among 704,003 First-Dose Recipients of the Pfizer-Biontech (BNT162b2) mRNA COVID-19 Vaccine in Mexico (preprint)

​Background: The development of mRNA vaccines to prevent SARS-CoV-2 has been remarkably successful, with highly effective vaccines available less than one year after confirming the first case. Due to the global burden of COVID-19 on health systems, emergency approval was attained after clinical trials with relatively small sample sizes and short follow-up periods. Limited information exists about the incidence of adverse events following immunisation (AEFI), particularly neurologic ones. Here, we describe the neurologic AEFI reported by recipients of the BNT162b2 mRNA COVID-19 vaccine. Methods: We conducted a prospective observational cohort using de-identified information from a database of all systemic and neurologic AEFI reported to the Mexican Ministry of Health throughout a passive Epidemiological Surveillance System by first-dose vaccine recipients, from December 24, 2020 to February 12, 2021. The cut-off date for this data was February 18, 2021. We performed descriptive analyses on demographics, timing from vaccination to AEFI development, event duration, and current outcome.Findings: Nationwide, 704 003 first-doses were administered; 6536 AEFI were reported. Among those, 4258 (65·1%) had at least one neurologic manifestation. Non-serious neurologic AEFI occurred in 99·6%. Headache (62·2%), transient sensory symptoms (3·5%), and weakness (1%) were the most frequent. Thirty-three serious AEFI were reported, of which 17 (2·4/100 000 doses) were neurologic, seven seizures, four functional syndromes, three Guillain-Barré syndrome (GBS) cases, and two of acute transverse myelitis. All GBS cases were related to a gastrointestinal infection before vaccination, 3/7 seizure episodes were related to poor antiepileptic drug compliance, and 2/7 to anaphylactic reactions. At the time of this report, 16/17 cases of serious neurologic AEFI had been discharged with no observed deaths.Interpretation: Our data suggest that the BNT162b2 mRNA vaccine is effective and safe. Their individual and societal benefits outweigh the low-percentage of serious neurologic and non-neurologic AEFI.Funding: Consejo Nacional de Ciencia y Tecnología, México.Declaration of Interest: None to declareEthical Approval: The study was revised and approved by the Ethics and Research Committees of the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán (Ref. NER-3667-2021) and the Mexican Ministry of Health.

A Randomized, Controlled Study on the Safety and Efficacy of Maraviroc and/or Favipiravir Vs Currently Used Therapy in Severe COVID-19 Adults. (COMVIVIR, clinicaltrials.gov NCT04475991) (preprint)

Background: Multiple studies have now established that hyperinflammatory response induced by SARS CoV-2 is a main cause of complications and death in infected subjects. Such dysfunctional immune response has been described as a dysregulated and exacerbated production of cytokines and chemokines that attracts and activates inflammatory cells, which start and sustain pulmonary and systemic damage, thus causing complications that lead to multi organ failure and death. Therefore, we suggest that blocking key inflammation receptors could help to reduce migration and activation of Th17, monocytes/macrophages and neutrophils, thus mitigating the cytokine storm and averting severe complications and death. Importantly, the optimum treatment for COVID-19 severe patients could combine a modulator of the immune response with a direct antiviral drug against SARS-CoV-2, in order to address both the viral load and the hyperinflammatory effects of the immune dysregulation.Methods: Maraviroc (MVC), a CCR5 antagonist, and Favipiravir (FPV), an antiviral, will be evaluated single and combined, added to the treatment currently used at the Hospital General de México for severe non-critical COVID-19 patients. One hundred patients will be allocated in four arms [Current treatment only (CT), CT+MVC, CT+FPV, CT+MVC+FPV]. Percentage of patients free of mechanical ventilation or death at day 28, immunophenotyping and viral load will be compared between groupsDiscussion: New immune focused therapies are targeting strong inflammation mediators such as IL-6 and IL1-B; nevertheless, to our best knowledge, controlling chemotaxis has not been explored. The use of a drug therapy that addresses both the regulation of the immune response and the inhibition of viral replication could at the same time, help to alleviate the hyperinflammatory condition and reduce the time of the viral clearance process, therefore improving treatment outcomesTrial registration: Clinical Trials (www.clinicaltrials.gov) NCT: 04475991.