Putting Science to Work: Cuba’s COVID-19 Pandemic Experience
Ileana Morales Suárez MD MS
July–October 2022, Vol 24, No 3–4

It was just before New Year’s Eve, 2019 when an emerging virus in China caught the attention of Dr Ileana Morales, director of Science and Technological Innovation in Cuba’s Ministry of Public Health. She had already participated in implementing Cuban protocols to prevent Ebola and address diseases such as Zika and dengue. But this was […]

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Polyserositis as a Post–Covid-19 Complication
Polyserositis as a Post–Covid-19 Complication

INTRODUCTION Polyserositis is described as inflammation with effusion of more than one serous membrane. There is very little published literature linking it to COVID-19 as a late complication.

OBJECTIVES Present and describe a case of post–COVID-19 polyserositis.

METHODS Data were collected from the medical record of a female patient admitted for fainting spells and marked weakness. The patient underwent a clinical evaluation, additional hematology, imaging and histopathology tests, and a surgical procedure.

The new index, called the abdominal adipose deposit index, was obtained by multiplying the subcutaneous fat thickness by visceral fat thickness, both measured by ultrasound. A cutoff point was established that facilitated discernment of an unhealthy phenotype: normal weight but metabolically obese, a cardiometabolic risk factor.

RESULTS We present the case of a 57-year-old female patient admitted to hospital for fainting spells and marked weakness, four months after COVID-19 infection. She also had a history of obesity, asthma, type 2 diabetes mellitus and a cholecystectomy in December 1992 for gallstones. Clinical assessment revealed pericardial effusion and bilateral pleural effusion, in addition to a tumor-like lesion outside the pericardium, proximal to the right ventricular wall. A surgical procedure and findings from additional tests led to diagnoses of thymic remnants and polyserositis.

CONCLUSIONS This is a case of polyserositis in a post–COVID-19 patient. After other causes of polyserositis were ruled out, and since there is a likely physiological and pathogenic mechanism operating between the two diseases, the polyserositis was determined to be a late complication of COVID-19. To date, it is the second case reported in the world and the first reported in Cuba.

KEYWORDS COVID-19, SARS-CoV-2, colchicine, pericardial effusion, pleural effusion, pericarditis, thoracoscopy, Cuba

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Global COVID-19 Scorecard: Science 1, Science Diplomacy and Equity 0
July–October 2022, Vol 24, No 3–4

Wherever you may be reading this: thank science. As you dress your children for school, commute, commune, worship or workout: thank science. As you plan a wedding, year-end celebrations, a trip, surgery, or dental cleaning: thank science. Our very survival is thanks to collaborative research and science that delivered safe, effective COVID-19 vaccines in record […]

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Special Abstracts Section COVID-19
Special Abstracts Section COVID-19

Cuban Abdala vaccine: Effectiveness in preventing severe disease and death from COVID-19 in Havana, Cuba; A cohort study. Más-Bermejo PI, Dickinson-Meneses FO, Almenares-Rodríguez K, Sánchez-Valdés L, Guinovart-Díaz R, Vidal-Ledo M, et al. Lancet Reg Health Am. 2022 Dec;16:100366. Epub 2022 Sep 24. https://doi.org/10.1016/j.lana.2022.100366 Background COVID-19 vaccines have proven safe and efficacious in reducing severe illness and […]

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Epidemiological Characterization of Patients in the First Eight Weeks Following Detection of SARS-CoV-2 B.1.1.529 (omicron)
Variant in Cuba
July–October 2022, Vol 24, No 3–4

INTRODUCTION In November 2021, omicron—a new SARS-CoV-2 variant—was identified in South Africa and almost immediately, WHO declared it a ‘variant of concern’. In view of its rapid worldwide spread and its imminent introduction in Cuba, genomic surveillance was strengthened.

OBJECTIVES Describe cases during the first eight epidemiological weeks (epiweeks) of SARS-CoV-2 infection attributable to omicron variant in Cuba by clinical and epidemiological variables.

METHODS From epiweek 48, 2021 to epiweek 4, 2022, 288 nasopharyngeal swabs were processed for sequencing of a 1836 bp fragment of the S gene. Variants were identified according to GISAID database and confirmed by phylogenetic analysis. Variants’ association with clinical and epidemiological outcomes was assessed.

RESULTS The first cases of omicron variant were imported, mostly from African countries and the United States. During the period studied, omicron was detected in 83.0% (239/288) of cases processed, while the delta variant was found in 17.0% (49/288). Most persons infected with omicron were symptomatic (63.2%; 151/239) and fully vaccinated (65.3%; 156/239); severe cases and deaths occurred mainly among patients aged ≥65 years (92.9%; 13/14), and 12 of these deaths occurred in fully vaccinated persons (92.3%; 12/13). Omicron spread rapidly throughout the country (from 10% of cases in epiweek 48, 2021, to 100% by epiweek 4, 2022), displacing the formerly predominant delta variant.

CONCLUSIONS Omicron’s rapid expansion in Cuba was associated with increased incidence but not with a higher case fatality rate. The relatively milder disease in those infected with this variant could be influenced by the high vaccination coverage, along with the natural immunity acquired as a consequence of previous virus infection.

KEYWORDS Pandemics, epidemiology, epidemiological monitoring, COVID-19 testing, COVID-19, SARS-CoV-2, COVID-19 vaccines, Cuba

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A Shift in SARS-CoV-2 Omicron Variant’s Entry Pathway
Might Explain Different Clinical Outcomes
July–October 2022, Vol 24, No 3–4

Globally, SARS CoV-2 omicron variant has led to a notable increase of COVID-19 diagnoses, although with less severe clinical manifestations and decreased hospitalizations. The omicron wave swelled faster than previous waves, completely displacing the delta variant within weeks, and creating worldwide concern about final, successful pandemic control. Some authors contend that symptoms associated to omicron differ from ‘traditional’ symptoms and more closely resemble those of the common cold.

One major COVID-19 symptom frequent with other variants—loss of taste and smell—is rarely present with omicron. This may be of interest, since it has also been suggested that direct SARS-CoV-2 invasion into the brainstem through the olfactory nerves by transsynaptic pathways could provide one explanation for the acute respiratory distress syndrome refractory to treatment. Brainstem infection by SARS-CoV-2 can severely damage the respiratory center, triggering functional deviations that affect involuntary respiration, leading to acute respiratory distress syndrome refractory to treatment, the main cause of death in COVID-19 patients. A shift in the omicron SARS-CoV-2 entry pathway from cell-surface fusion, triggered by TMPRSS2, to cathepsin-dependent fusion within the endosome, may affect transmission, cellular tropism and pathogenesis. Therefore, we can hypothesize that this entrance modification may impact transmission from the olfactory nerve to the brainstem through transsynaptic pathways. A decrement of the virus’s direct invasion into the brainstem could diminish respiratory center dysfunction, reducing acute respiratory distress syndrome and the need for mechanical ventilation.

KEYWORDS SARS-CoV-2, COVID-19, olfactory nerve, COVID-19 pandemics, respiratory center, smell, anosmia, taste, ageusia, brain stem, cathepsins, endosomes

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High Levels of Serum Bile Acids in COVID-19 Patients on
Hospital Admission
July–October 2022, Vol 24, No 3–4

INTRODUCTION Bile acids are signaling molecules with immune, metabolic and intestinal microbiota control actions. In high serum concentrations they increase inflammatory response from the liver-gut axis, until causing multiorgan failure and death; therefore, they may be associated with COVID-19’s clinical progression, as a consequence of tissue and metabolic damage caused by SARS-CoV-2. While this topic is of considerable clinical interest, to our knowledge, it has not been studied in Cuba.

OBJECTIVES Study and preliminarily characterize patients admitted with a diagnosis of COVID-19 and high levels of serum bile acids.

METHODS A preliminary exploratory study was carried out with descriptive statistical techniques in 28 COVID-19 patients (17 women, 11 men; aged 19–92 years) who exhibited high levels of serum bile acids (≥10.1 µmol/L) on admission to the Dr. Luis Díaz Soto Central Military Hospital in Havana, Cuba, from September through November 2021.

RESULTS On admission patients presented hypocholesterolemia (13/28; 46.4%), hyperglycemia (12/28; 43.0%) and hyper gamma-glutamyl transpeptidase (23/28; 84.2%). Median blood glucose (5.8 mmol/L) and cholesterol (4.1 mmol/L) were within normal ranges (3.2‒6.2 mmol/L and 3.9‒5.2 mmol/L, respectively). Severe or critical stage was the most frequent (13/28) and median serum bile acids (31.6 µmol/L) and gamma-glutamyl transferase (108.6 U/L) averaged well above their respective normal ranges (serum bile acids: 0‒10 µmol/L; GGT: 9‒36 U/L). Arterial hypertension was the most frequent comorbidity (19/28; 67.9%).

CONCLUSIONS Severe or critical stage predominated, with serum bile acids and gamma-glutamyl transferase blood levels above normal ranges. The study suggests that serum bile acid is toxic at levels ≥10.1 µmol/L, and at such levels is involved in the inflammatory process and in progression to severe and critical clinical stages of the disease. In turn, this indicates the importance of monitoring bile acid homeostasis in hospitalized COVID-19 patients and including control of its toxicity in treatment protocols.

KEYWORDS COVID-19, SARS-CoV-2, bile acids and salts, gamma-glutamyl transferase, pregnant women, postpartum, Cuba

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Families in Grief:
Need for Psychological Care and Support for Those Who Lost Loved Ones to COVID-19
July–October 2022, Vol 24, No 3–4

The COVID-19 pandemic has caused notable changes in all areas of our lives. Pandemic-coping strategies include attention and care at various levels, for different people and in various scenarios. Death is one of the most feared consequences of COVID-19 for both patients and their families; for the latter, the grief and adaptation processes to loss require that care for grievers be an important part of the public health response to the COVID-19 pandemic.

Grief from losses due to COVID-19 has distinctive features: it is not anticipatory (with virtually no time or progressive stages to facilitate adaptation to loss); closure or goodbyes are not possible (in-person social support decreases due to distancing to minimize risk of infection); it may affect various close relationships (a relevant predictor of complicated grief); it may imply stigmatization by peers, friends and neighbors; it is preceded by a period of absence of fluid and in-person communication between family members and the hospitalized patient; and those who break the news of the death are often professionals in red zones who are stressed and do not always have the skills or the ability to properly communicate bad news.

The death of a family member from COVID-19 generally causes an unexpected crisis in the family, which is already affected by the pandemic and its daily consequences. This has prompted an analysis of COVID-19 loss on family life and how best to mitigate its consequences.

During the COVID-19 pandemic, care and monitoring of the grief of family members and those who were close to the deceased require psychological action within a framework of comprehensive care, which demands preparation of healthcare professionals. Experiences described are taken from some actions developed in Cuba.

KEYWORDS Grief, psychology, death, attitude to death, COVID-19, SARS-CoV-2, Cuba

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Politics, Profits & Pandemics: Earth’s Worst-Case Scenario
April 2022, Vol 24, No 2

The year 2020 was one for the record books: an estimated 90 million people were driven into extreme poverty; it tied for the hottest year on record, with soaring global temperatures and heat waves resulting in thousands of fatalities; and in any given month, 19% of our planet’s land area was stricken by severe drought, […]

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Evaluation of SARS-CoV-2 Rapid Antigen Tests in Use
on the Isle of Youth, Cuba
April 2022, Vol 24, No 2

INTRODUCTION The use of various diagnostic techniques is increasingly common in pandemic scenarios. It is important to update evaluations of their metric properties in different times and settings.

OBJECTIVE Evaluate metric properties of a SARS-CoV-2 rapid antigen test relative to a reference standard.

METHODS We carried out a prospective evaluation study of the SARS-CoV-2 rapid antigen test as compared to the RT-PCR test, which is considered the reference standard. Our sample was comprised of 778 individuals, and we calculated sensitivity, specificity, predictive values, prevalence and validity indices.

RESULTS Of the total 778 samples, 70 were true positives, 658 were true negatives, and 27 were false negatives when compared to RT-PCR test results. We obtained a sensitivity of 75.3% (95% CI = 65.96–84.50); a specificity of 96.1% (95% CI = 94.53–97.59); 72.2% for positive predictive value, and 96.6% for negative predictive value. The estimated prevalence was 11.9% and the validity index was 93.6%.

CONCLUSIONS The index values validate use of the SARS- CoV-2 rapid antigen test until prevalence falls below 2.5%, since as SARS-CoV-2 infection prevalence decreases, so does the predictive value of the PCR result.

The use of the SARS-CoV-2 rapid antigen test on the Isle of Youth, Cuba, was decisive in the pandemic’s clinical– epidemiological management.

KEYWORDS SARS-CoV-2, COVID-19, antigens, validation study, sensitivity and specificity, Cuba

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Hematological Alterations in Patients Recovered from
SARS-CoV-2 Infection in Havana, Cuba
April 2022, Vol 24, No 2

INTRODUCTION COVID-19 sequelae, or the short-, medium-, and long-term manifestations of the disease are under continuous study. There are currently few reports on the evolution of hematological variables following a demonstrated absence of SARS-CoV-2 after infection.

OBJECTIVE Identify hematological alterations in Cuban adults recovered from SARS-CoV-2 infection, and their relation with disease severity.

METHODS We selected 348 persons recovered from COVID-19 residing in Havana, Cuba with an RT-PCR study negative for SARS-CoV-2 performed two weeks after hospital discharge; a structured survey was administered to obtain clinical–epidemiological data. Three groups were established according to COVID-19 clinical criteria: asymptomatic, mild/moderately symptomatic, and severely symptomatic, which, in turn, were divided according to hospital discharge date and blood sample collection date. We performed hemograms with differential leukocyte counts and compared results among groups. We then measured the associations between hematological variables, personal medical history, and relevant lifestyle habits (smoking).

RESULTS All hematological variables were within normal reference limits, although men from the group of severely ill patients had increased total leukocytes, neutrophils and lymphocytes, and decreased hemoglobin and eosinophils, which was also evident in those with a recovery time of 31–90 days.

CONCLUSIONS The relation between hematological variables and degree of clinical severity offers evidence as to persistence of systemic alterations (possibly inflammatory) associated with viral infection. Their identification and characterization can facilitate personalized patient followup and rehabilitation.

KEYWORDS COVID-19, SARS-CoV-2, hematology, leukocytosis, neutrophils, eosinophils, Cuba

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Cuban COVID-19 Vaccines for Children:
January 2022, Vol 24, No 1

Cuba’s decision in September 2021 to launch a massive vaccination campaign against COVID-19 for children as young as two years old turned heads around the world—of clinicians, immunologists, public health experts, governments and regulatory authorities alike. Since then—and just as pediatric COVID-19 hospitalizations reached record numbers globally—some two million Cuban children and adolescents have received the Cuban Soberana vaccines (1.7 million, or 81.3% of that population through December 16, 2021).[1]

Why did Cuban health authorities decide to vaccinate children? What clinical trials provided the evidence for such a course of action, especially for the youngest? And what have been the results thus far?

To answer these and other questions, MEDICC Review spoke with Dr Rinaldo Puga, principal investigator for the completed phase 1/2 clinical trials of the Finlay Vaccine Institute’s Soberana 02 and Soberana Plus vaccines in pediatric ages. Dr Puga’s 30 years as a practicing pediatrician have been accompanied by teaching and research, the latter earning him awards from the Cuban Academy of Sciences, among others. He is currently chief of pediatrics and chair of the Scientific Council at the Cira García Clinic in Havana, which granted him leave to lead the pediatric vaccine trials.

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Vaccines and Public Trust: Containing COVID-19 in Cuba
January 2022, Vol 24, No 1

As 2021 drew to a close, Cuba struggled to contain the highly transmissible omicron variant of SARS-CoV-2, braced for a new wave of infections and kept a close eye on other variants of concern popping up around the world—a common experience to countries everywhere as we head into the second year of the pandemic. In Cuba, however, there is one marked difference making all the difference: by early January, 87% of the population was fully vaccinated using a three-dose schedule of vaccines developed and produced on the island.[1] This massive vaccination campaign is complemented by a rapid booster rollout—also using Cuban vaccines—that began in December 2021 and was ongoing as we finalized this issue.

The island nation was able to achieve the third highest COVID-19 vaccination rate in the world[2] after decades of scientific investment, research, discovery and innovation; regulatory oversight and compliance; professional training; and increased production capacity. But a vaccine is only as effective as the health system charged with administering it—in a safe and timely manner, to as many people as possible. Here too, Cuba has decades of experience, including a national pediatric immunization program where 98% of children under 5 are immunized against 13 diseases,[3] an annual polio vaccination campaign (both launched in 1962 and uninterrupted since) and campaigns to contain epidemics such as H1N1.

When the first COVID-19 cases were detected on the island in March 2020, Cuba harnessed this vaccine experience, making a hard tack towards developing its own vaccines. Two of the main protagonists in the country’s biotechnology development, the Finlay Vaccine Institute (IFV) and the Genetic Engineering and Biotechnology Center (CIGB), both with several groundbreaking preventive and therapeutic vaccines in their portfolios, led the search for a vaccine. Today, Cuba has three vaccines authorized for emergency use—Soberana 02 and Soberana Plus developed by IFV, and Abdala, developed by CIGB. Schedules with these vaccines have demonstrated more than 90% efficacy in clinical trials,[4] and after regulatory approval for emergency use, became the backbone of Cuban COVID-19 vaccination efforts. A fourth vaccine, Mambisa (CIGB), administered nasally, and a fifth, Soberana 01 (IFV) are still in clinical trials.

For this installment in MEDICC Review’s series spotlighting leading women of Cuban science, we sat down with Dr Verena Muzio, Director of Clinical Research at CIGB. A pioneer of Cuba’s biotechnology sector, she is an immunologist with a doctorate in biological sciences. Her professional trajectory began researching the genetically engineered hepatitis B surface antigen that led to the development of Cuba’s recombinant hepatitis B vaccine in 1989. The same technological platform used in this vaccine was used to develop CIGB’s Abdala vaccine against SARS-CoV-2—part of the reason Cuba was able to secure a vaccine so quickly. A phase 3 clinical trial determined a 92.28% efficacy rate for Abdala, with results to appear in forthcoming publications.

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Innate Immune Stimulation Should not be Overlooked in Post-exposure Prophylaxis and Early Therapy for Coronavirus Infections
January 2022, Vol 24, No 1

We discuss the suitability of innate immune stimulation in acute respiratory infection post-exposure prophylaxis. The induction of innate immunity can be used to reduce susceptibility to immune-evasive pathogens (coronavirus, influenza virus, respiratory syncytial virus and rhinovirus). After the emergence of multiple SARS-CoV-2 variants, scientists are debating whether new variants could affect vaccine efficacy and how antigens could be redesigned to compensate. In addition, there is insufficient vaccine production to cover universal demand, and equitable vaccine distribution is a global challenge. Given these factors, non-specific immune stimulators may be suitable for a quick first response in the case of a suspected or early respiratory infection. Our group completed several HeberNasvac studies in healthy volunteers and patients with respiratory infections, and is currently starting large clinical trials in patients with early SARS-CoV-2 infections. This nasal formulation of hepatitis B vaccine has demonstrated its capacity to stimulate innate immunity markers (TLR3, TLR7 and TLR8 in tonsils) at the virus’ entry site, in systemic compartments (HLA class II in monocytes and lymphocytes) and in the activation of dendritic cells, lymphocytes and other cell lines in vitro and ex vivo. In addition, research generated by the current pandemic may obtain results useful for treating other acute respiratory infections, which have long been main drivers of mortality among older adults and in early childhood.

KEYWORDS Immunity, innate; toll-like-receptors; SARS-CoV-2; COVID-19; respiratory tract infections; Cuba

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Cerebral Hemodynamic Reserve Abnormalities Detected Via Transcranial Doppler Ultrasound in Recovered COVID-19 Patients
January 2022, Vol 24, No 1

ABSTRACT
INTRODUCTION
SARS-CoV-2 infection can produce endothelial injury and microvascular damage, one cause of the multiorgan failure associated with COVID-19. Cerebrovascular endothelial damage increases the risk of stroke in COVID-19 patients, which makes prompt diagnosis important. Endothelial dysfunction can be evaluated by using transcranial Doppler ultrasound to study cerebral hemodynamic reserve, but there are few of these studies in patients with COVID-19, and the technique is not included in COVID-19 action and follow-up guidelines nationally or internationally.

OBJECTIVE Estimate baseline cerebral hemodynamic patterns, cerebral hemodynamic reserve, and breath-holding index in recovered COVID-19 patients.

METHOD We conducted an exploratory study in 51 people; 27 men and 24 women 20–78 years of age, divided into two groups. One group comprised 25 recovered COVID-19 patients, following clinical and epidemiological discharge, who suffered differing degrees of disease severity, and who had no neurological symptoms or disease at the time they were incorporated into the study. The second group comprised 26 people who had not been diagnosed with COVID-19 and who tested negative by RT-PCR at the time of study enrollment. Recovered patients were further divided into two groups: those who had been asymptomatic or had mild disease, and those who had severe or critical disease. We performed transcranial Doppler ultrasounds to obtain baseline and post-apnea tests of cerebral hemodynamic patterns to evaluate cerebral hemodynamic reserve and breath-holding indices. We characterized the recovered patient group and the control group through simple descriptive statistics (means and standard deviations).

RESULTS There were no measurable differences in baseline cerebral hemodynamics between the groups. However, cerebral hemodynamic reserve and breath-holding index were lower in those who had COVID-19 than among control participants (19.9% vs. 36.8% and 0.7 vs. 1.2 respectively). These variables were similar for patients who had asymptomatic or mild disease (19.9% vs.19.8%) and for those who had severe or critical disease (0.7 vs. 0.7).

CONCLUSIONS Patients recovered from SARS-CoV-2 infection showed decreased cerebral hemodynamic reserve and breath-holding index regardless of the disease’s clinical severity or presence of neurological symptoms. These abnormalities may be associated with endothelial damage caused by COVID-19. It would be useful to include transcranial Doppler ultrasound in evaluation and follow-up protocols for patients with COVID-19.

Keywords: SARS-CoV-2; COVID-19; breath holding; ultrasonography, Doppler, transcranial; endothelium, vascular; cerebrovascular circulation; Cuba

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Asymptomatic SARS-CoV-2 Infection in Havana, Cuba, March–June 2020: Epidemiological Implications
January 2022, Vol 24, No 1

INTRODUCTION The percentage of asymptomatic COVID-19 cases worldwide is estimated at 18–50%; 53% in Cuba specifically, and 58% in Havana, the Cuban capital and the 2020 epicenter of the country’s COVID-19 epidemic. These figures, however, do not represent the transmission capacity or behavior of asymptomatic cases. Understanding asymptomatic transmission’s contribution to SARS-CoV-2 spread is of great importance to disease control and prevention.

OBJECTIVE Identify the epidemiological implications of asymptomatic SARS-CoV-2 infection in Havana, Cuba, during the first wave of the epidemic in 2020.

METHODS We carried out a cross-sectional study of all confirmed COVID-19 cases diagnosed in Havana, Cuba, from March 16 through June 30, 2020. The information was obtained through review of the standardized form for investigation of suspected and confirmed cases. Examined variables included age, sex, occupation, case type and source of infection. Cases were divided into asymptomatic and symptomatic groups, and transmission was characterized through the creation of a contact matrix. Analysis was carried out in Epidat and R.

RESULTS We studied 1287 confirmed cases, of which 57.7% (743) were asymptomatic, and 42.3% (544) were symptomatic. Symptomatic presentation was the most common for both imported and introduced cases, while asymptomatic presentation was more common in autochthonic cases and infections from an undetermined source. Asymptomatic infection was more common in groups aged <20 and 20–59 years, while symptomatic infection was more common in those aged >60 years. In the contact matrix, 34.6% of cases (445/1287) were not tied to other cases, and 65.4% (842/1287) were infectious–infected dyads, with symptomatic–symptomatic being the most common combination. The majority of primary cases (78.5%; 1002/1276) did not generate secondary cases, and 85.6% (658/743) of asymptomatic cases did not lead to other cases (although one asymptomatic superspreader led to 90 cases in a single event). However, 63.2% (344/544) of symptomatic primary cases generated secondary cases, and 11 symptomatic superspreaders spawned 100 secondary cases in different events.

CONCLUSIONS Asymptomatic SARS-CoV-2 infection was the most common form of COVID-19 in Havana during the study period, but its capacity for contagion was lower than that of symptomatic individuals. Superspreader events under specific conditions played an important role in sustaining the epidemic.

KEYWORDS COVID-19, SARS-CoV-2, pandemics, asymptomatic infection, Cuba

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