By Carol A. Kemper, MD, FACP

Clinical Associate Professor of Medicine, Stanford University, Division of Infectious Diseases, Santa Clara Valley Medical Center

Dr. Kemper reports no financial relationships relevant to this field of study.

Sex in the Time of COVID-19

SOURCE: De Miguel Buckley R, Trigo E, de la Calle-Prieto F, et al. Social distancing to combat COVID-19 led to a marked decrease in food-borne infections and sexually transmitted disease in Spain. J Travel Med 2020; Aug, 25. doi: 10.1093/jtm/taaa134. [Online ahead of print].

Since the first case of COVID-19 in Madrid, Spain, occurred Feb. 25, 2020, the Spanish government has enacted a series of restrictive measures on communal gatherings and travel. Beginning March 15, the citizens of Madrid effectively went into lockdown; public gatherings of more than six people are not allowed, and entry and exit from cities with higher burdens of COVID still is permitted only for work, education, or medical purposes. United States citizens are still barred from travel to Spain. These measures have resulted in a significant drop in local and national travel and activity.

Comparing the first six months of 2020 to the previous semester in 2019, epidemiologic surveillance data for Madrid demonstrate a dramatic reduction in foodborne infections and sexually transmitted diseases (STDs). Cases of Campylobacter and Salmonella have dropped 74% to 76.4% from pre-COVID levels. Cases of gonorrhea, chlamydia, and syphilis have dropped 81%, 76%, and 73%, respectively, since 2019.

If this drop in STDs is any reflection of the reduction in circulating SARS-CoV-2 virus in the community, then shelter-in-place and travel restrictions really work. While concern has been raised that this drop in STD cases is the result of under-diagnosis during COVID, when public health personnel and dollars have been diverted to COVID, and outpatient STD services have been reduced, I imagine these data are real. The simple fear of acquiring COVID, along with restrictions in gatherings, nightclubs, and parties, have limited both desire and opportunity. I’ve heard from several patients that popular gay bars and bathhouses in our area have literally gone out of business during the extended months of closure, unable to pay their bills.

The reduction in foodborne illness during COVID is an interesting “side effect” of COVID — and may be the result of the reliance on more home-cooked meals, limited access to prepared deli foods, and closure of restaurants and bars. Smaller and fewer group gatherings also may have reduced transmission of foodborne illness.

One hates to think it took an epidemic to put a dent in people’s sexual activity, or at least their number of partners. Prior to COVID in 2019, STD rates in the United States were at a record high, with up to 115,000 cases of syphilis, 580,000 cases of gonorrhea, and 1.7 million cases of chlamydia. Among newborns, syphilis cases increased 40%. One can hope that the lessons learned from COVID might rub off on other aspects of life, with attention to hand washing and a better understanding of disease transmission and risk.

Serum SARS-CoV-2 and Disease Severity

SOURCE: Hagman K, Hedenstierna M, Gille-Johnson P, et al. SARS-CoV-2 RNA in serum as predictor of severe outcome in COVID-19: A retrospective cohort study. Clin Infect Dis 2020; Aug. 28:ciaa1285.

Detection of SARS-CoV-2 ribonucleic acid (RNA) in serum has been postulated as an early marker of COVID-19 disease severity. Higher viral loads may suggest an inability to control viral replication with dissemination to other organs and higher organ burden, possibly leading to greater levels of inflammation and disease severity.

These authors at the Danderyd Hospital in Stockholm, Sweden, examined the relationship between SARS-CoV-2 RNA in serum on presentation to hospital and clinical outcome, as defined by disease progression to critical care and mortality. From April 10 to June 30, 2020, serum samples were collected within three days of hospitalization on 167 patients, and patients were followed for 28 days. The median date of sampling was one day after hospitalization, which corresponded to a median of 10 days after the onset of symptoms. No antivirals or chloroquine derivatives were used in these patients, although some of the patients were enrolled in a clinical trial of convalescent plasma. Disease progression was a composite of intensive care unit (ICU) care and mortality.

Using standard reverse-transcriptase polymerase chain reaction (PCR), SARS-CoV-2 RNA was detected in 61 patients (36.5%) at entry to the study. The median age of those with RNA-positive serum was significantly higher than for those with RNA-negative serum specimens (63 years vs. 53 years, respectively), and the proportion of those with positive RNA PCR in serum increased with age. Three patients with RNA-negative serum (2.8%) and 15 of those with RNA-positive serum (24.6%) died. Disease progression occurred in seven patients with RNA-negative serum (7%) compared with 34 of those with detectable SARS-CoV-2 RNA (44%). Multivariate analysis factoring in age, heart disease, hypertension, C-reactive protein level, and RNA positivity showed that only age and PCR positivity significantly correlated with disease severity and death. The hazard ratios for progression to critical care and all-cause mortality at day 28 were 7.2 (95% confidence interval [CI], 3.0-17) and 8.6 (95% CI, 2.4-30), respectively, for patients with positive serum PCR results compared with those with negative serum PCR.

The use of convalescent plasma did not appear to affect 28-day outcomes. Twenty-eight of 61 PCR-positive patients received convalescent plasma. The proportion of these who died among PCR-positive patients receiving convalescent plasma or not was 21.4 % vs. 27% (P = NS).

Natural History of Untreated Tuberculosis

SOURCE: Ragonnet R, Flegg JA, Brilleman SL, et al. Revising the natural history of pulmonary tuberculosis: A Bayesian estimation of natural recovery and mortality rates. Clin Infect Dis 2020; Aug. 7:ciaa602. [Online ahead of print].

Characterizing the natural history of tuberculosis (TB), including the possibility of spontaneous recovery, disease chronicity and mortality, is important to the determination of worldwide TB disease burden. Several modeling studies have been published, estimating the rates of these outcomes, largely based on historical pre-treatment data. True natural history studies are impossible to perform now, when all patients should receive treatment. One of the best studies of the natural history of untreated TB comes from a 2011 publication, which included 10-year case fatality rates for smear-positive (SP) and smear-negative (SN) pulmonary TB patients (70% and 20% mortality, respectively). However, the interpretation of these data, and their use in mathematical models, has been complicated by the inability to distinguish TB mortality from other causes of death.

These authors examined published literature for the natural history of TB before the advent of anti-tuberculous chemotherapy, identifying 64 cohorts of patients with pulmonary TB, many containing data on mortality. The size of the cohorts varied from as few as eight patients to 2,382 patients, with a median of 379 patients. All of the studies were from Western Europe, patients were followed for up to 31 years, and included six surveys of patients from sanitoriums, six officially notified patient cohorts, and three groups of hospitalized patients. There were 41 cohorts with SP patients and 23 cohorts with SN patients, although four of these latter cohorts reported incomplete data. Forty-seven of 64 cohorts (73%) included patients from sanitoriums and hospitals, with complete follow-up data for almost all of the patients. TB-driven mortality was separated out when possible from non-TB mortality.

The median estimates of TB-specific mortality rates for SP-pulmonary TB and SN-pulmonary TB patients were 0.389 year-1 and 0.025 year-1. The estimates for self-recovery were 0.231 year-1 and 0.130 year-1, respectively. With an estimated non-TB mortality rate of 0.014 year-1, these rates correspond to an average duration of survival for untreated SP-TB of 1.57 years and for SN-TB of 5.35 years. There was considerable variation in the estimates of TB mortality among the cohorts, and hospitalized patients had the lowest rates of mortality.

An important finding from this newer analysis was the difference in outcomes between SP-TB patients and SN-TB patients, demonstrating the more acute and aggressive nature of SP pulmonary disease in the years before treatment. In contrast, patients with SN pulmonary disease lived four times longer, with a more indolent course. Earlier models underestimated the difference between these two groups. This also means that SN patients probably contributed as much to transmission risk as those with SP disease, since they lived longer with their infection.

Of course, earlier TB data were based on the detection of acid-fast organisms on smear, since cultures were not invented until the 1930s. Both groups of SP and SN participants may have included patients with other diseases. As I recall from my earlier nontuberculous mycobacteria (NTM) reading, some of the SP patients may have had M. avium or M. kansasii, which would have been recognized only with appropriate in vitro animal studies demonstrating non-virulence, which were seldom performed. SN patients would have been detected clinically or radiographically, and may have had lung problems other than TB. A potential drawback from these earlier studies is the lack of data on sputum smear conversion, since patients may shift back and forth between being SP and SN. An important consideration when modeling disease burden is that the duration of survival in these studies was assessed from the time of diagnosis and not from the onset of symptoms.