Viral hepatitis in persons living with HIV in the post-COVID era.

Coinfection with hepatitis viruses A to E is frequent in persons living with HIV (PLWH) and causes significant morbidity and mortality. Oro-fecal transmissible hepatitis A and E mostly produce acute self-limited episodes in poor income regions and in non-vaccinated travelers. In high-income countries, outbreaks of hepatitis A occur in men having sex with men (MSM) and chronic hepatitis E is occasionally reported among PLWH with severe immunodeficiency. Chronic hepatitis B, C, and D are frequent in PLWH in highly endemic regions and globally in persons who inject drugs (PWID) and MSM. Progression to liver cirrhosis and development of hepatocellular carcinoma (HCC) is major clinical complications in coinfected patients. Current estimates for PLWH are of 38 million worldwide. Roughly 12% have chronic viral hepatitis (5 million). Coinfection figures are of 5-10% for HBV (2-4 million), 4% for HCV (1.5 million), and 15% of HBsAg+ for HDV (0.5 million). Oral direct-acting antivirals (DAA) cure almost all treated patients with hepatitis C. However, given that there is no protective HCV immunity, PLWH with high-risk behaviors may experience HCV reinfection episodes. Tenofovir is the drug of choice in PLWH with chronic hepatitis B, given its dual effect on HIV and HBV. Lifelong oral tenofovir suppresses HBV replication and ameliorate liver damage. However, the risk of HCC persists even in the absence of cirrhosis. Finally, HDV causes the worst of viral hepatitis with faster progression to cirrhosis and HCC. An entry inhibitor, bulevirtide, has recently been approved and another drug, lonafarnib, is completing Phase 3 trials. Combination antiviral therapy for hepatitis D could improve dramatically the poor prognosis of HIV-HDV coinfected patients. The resumption of good medical practices in PLWH after the big disruption caused by COVID-19 will reduce the burden of viral hepatitis coinfections. Renewed efforts on HAV and HBV vaccination of susceptible individuals and earlier and wider prescription of antiviral therapy for HBV, HCV, and/or HDV coinfection should be prioritized in PLWH. The benefits of innovative strategies for viral hepatitis, including pre-exposure prophylaxis or use of long-acting antivirals, warrant further consideration in PLWH.

Is SARS-CoV-2 the only cause of long-COVID?

Around 10% of adults infected with SARS-CoV-2 that survive a first episode of COVID-19 appear to experience long-term clinical manifestations. The signs and symptoms of this post-acute COVID-19 syndrome (PACS) include fatigue, dyspnea, joint pain, myalgia, chest pain, cough, anosmia, dysgeusia, headache, depression, anxiety, memory loss, concentration difficulties, and insomnia. These sequelae remind the constellation of clinical manifestations previously recognized as myalgic encephalomyelitis (ME) or chronic fatigue syndrome (CFS). This condition has been described following distinct infectious events, mostly acute viral illnesses. In this way, the pathophysiology of PACS might overlap with mechanisms involved in other post-infectious fatigue syndromes. The risk of PACS is more frequent in women than men. Additional host genetic factors could be involved. There is a dysregulation of multiple body organs and systems, involving the immune system, the coagulation cascade, endocrine organs, autonomic nervous system, microbiota-gut-brain axis, hypothalamic-pituitary-adrenal axis, hypothalamic-pituitary-thyroid axis, etc. Hypothetically, an abnormal response to certain infectious agents could trigger the development of postinfectious fatigue syndromes.

Pre-Exposure Prophylaxis for viral infections other than HIV

SUMMARY The battle against human viral infections has historically relied on two medical strategies, namely vaccines to protect from contagion and antivirals to treat infected patients. In the absence of vaccines, antivirals have occasionally been used as peri-exposure prophylaxis, given either before (pre-exposure prophylaxis) or right after (post-exposure prophylaxis). In an unprecedented way, the use of antiretrovirals as chemoprophylaxis has triumphed in the HIV field. Indeed, oral antiretrovirals given either daily or at demand to HIV-uninfected individuals engaged in high-risk behaviors protect from contagion. More recently, the advent of long-acting formulations has allowed HIV protection following intramuscular injections every three months. Can we envision a similar prophylactic strategy for other human viral infections? The advent of such ‘chemical vaccines’ would fill an unmet need when classical vaccines do not exist, cannot be recommended, immune responses are suboptimal, escape mutants emerge or immunity wanes. In this review, we discuss the opportunities for antiviral chemoprophylaxis for viral hepatitis B and C, retroviruses HTLV-1 and HIV-2, and respiratory viruses influenza and SARS-CoV-2, among others.

Third wave of COVID-19 in Madrid, Spain.

A third wave of COVID-19 occurred after Christmas 2020 in Madrid, one of the European pandemic epicenters. We noticed 6 major differential features to previous waves. First, household contacts were a large proportion of cases. Second, access to rapid antigen tests allowed prompt diagnosis and isolation. Third, clinically severe cases and mortality rates were lower. Fourth, the more transmissible B.1.1.7 strain was increasingly found. Fifth, vaccination benefits were seen in healthcare workers and nursing homes. Lastly, reinfections were more common. By Easter 2021, approximately 25% of the population in Madrid had been infected with SARS-CoV-2. Therefore, massive and accelerated vaccination campaigns are warranted to prevent new COVID-19 waves.

Main differences between the first and second waves of COVID-19 in Madrid, Spain.

BACKGROUND: The emergence and rapid global spread of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) represents a major challenge to health services, and has disrupted social and economic activities worldwide. In Spain, the first pandemic wave started in mid-March 2020 and lasted for 3 months, requiring home confinement and strict lockdown. Following relaxation of the measures during the summer, a second wave commenced in mid-September 2020 and extended until Christmas 2020. METHODS: The two pandemic waves were compared using information collected from rapid diagnostic tests and polymerase chain reaction assays at one university clinic in Madrid, the epicentre of the pandemic in Spain. RESULTS: In total, 1569 individuals (968 during the first wave and 601 during the second wave) were tested for SARS-CoV-2-specific antibodies using fingerprick capillary blood. In addition, during the second wave, 346 individuals were tested for SARS-CoV-2-specific antigen using either oral swabs or saliva. The overall seroprevalence of first-time-tested individuals was 12.6% during the first wave and 7.7% during the second wave (P < 0.01). Seroconversions and seroreversions within 6 months occurred at low rates, both below 5%. During the second wave, 3.5% of tested individuals were SARS-CoV-2 antigen positive, with two cases considered as re-infections. Severe clinical symptoms occurred in a greater proportion of cases during the first wave compared with the second wave (27.8% vs 10.6%, respectively; P = 0.03). CONCLUSION: The cumulative seroprevalence of SARS-CoV-2 antibodies in Madrid at the end of 2020 was approximately 20%. Seroreversions within 6 months occurred in 4% of cases. Seroconversions and re-infections were clinically less severe during the second wave than during the first wave. Hypothetically, a lower viral inoculum as a result of social distancing, increased use of face masks, promotion of outdoor activities and restrictions on gatherings may have contributed to this lower pathogenicity.

Inoculum at the time of SARS-CoV-2 exposure and risk of disease severity.

A relationship between the infecting dose and the risk of disease severity has not been demonstrated for SARS-CoV-2 infection. Here, we report three clusters of individuals that were potentially exposed to distinct inoculum in Madrid. Overall each group developed divergent clinical forms of COVID-19. Our data support that a greater viral inoculum at the time of SARS-CoV-2 exposure might determine a higher risk of severe COVID-19.